J_ID: ZAY Customer A_ID: BKLT2012_Book_Cover Cadmus Art: ANA7 Date: 14-September-12 Stage: Page: 1 2012 Annual Meeting of the American Neurological Association in partnership with Association of British Neurologists October 7вЂ“9, 2012 Marriott Copley Place Boston Poster Listings Poster Session Abstracts Works in Progress Abstracts Career Development Abstracts Author Index Subject Index ID: srinivasanv I Black Lining: [ON] I Time: 00:13 I 1вЂ“31 32вЂ“151 152вЂ“163 164вЂ“179 180вЂ“200 201вЂ“204 Path: N:/3b2/ANA#/Vol00000/120250/APPFile/JW-ANA#120250 J_ID: ANA Customer A_ID: BKLT2012_Poster_Listings Cadmus Art: ANA8 Date: 19-September-12 Stage: Page: 1 Poster Listings Sunday, October 7, 2012 Posters Poster Listing Pages Topic Abstract Pages S101-S161 1вЂ“4 32вЂ“47 Education S201-S209 4 47вЂ“49 Neuro-oncology S301-S309 4 49вЂ“51 Sleep Disorders and Circadian Rhythm S401-S407 5 51вЂ“53 Neurogenetics S501-S521 5вЂ“6 53вЂ“58 Neuroinfectious Disease S601-S608 6 58вЂ“60 Neuro-opthalmology S701-S714 6вЂ“7 60вЂ“63 Pediatric Neurology S801-S806 7 63вЂ“64 Rehabilitation and Regeneration S901-S914 7вЂ“8 64вЂ“68 8 68вЂ“70 Trauma/Injury S1001-S1007 Monday, October 8, 2012 Posters Poster Listing Pages Topic Abstract Pages Dementia and Aging M1101-M1162 8вЂ“11 70вЂ“86 Epilepsy M1201-M1232 11вЂ“13 86вЂ“93 Neurology Critical Care M1301-M1306 13 94вЂ“95 Neuromuscular Disease M1401-M1474 13вЂ“17 95вЂ“113 Tuesday, October 9, 2012 Posters Poster Listing Pages Topic Abstract Pages Behavioral Neurology T1501-T1522 17вЂ“18 113вЂ“118 Headache and Pain/Neuro-otology T1601-T1613 18 118вЂ“122 Movement Disorder T1701-T1780 19вЂ“22 122вЂ“141 Autoimmune Neurology T1801-T1840 22вЂ“24 141вЂ“151 ID: senthilk I Black Lining: [ON] I Time: 15:21 I Path: N:/Wiley/3b2/ANA#/Vol00000/120251/APPFile/JW-ANA#120251 Poster Listings Cerebrovascular Disease J_ID: ZAY Customer A_ID: BKLT2012_Poster_Sessions Cadmus Art: ANS9 Date: 14-September-12 2012 Annual Meeting Sunday, October 7, 2012 Poster Session Stage: Page: 1 S108 Brain and Abdominal Aneurysm Study (BAAS): Interim Analysis Kevin M. Barrett, Sothear M. Luke, Albert G. Hakaim, Rabih G. Tawk, Ricardo A. Hanel, Bradford B. Worrall, William D. Freeman, Thomas G. Brott and James F. Meschia; Jacksonville, FL and Charlottesville, VA Posters will be displayed in Gloucester, located on the 3rd floor in the Back Bay Hall of the Marriott Copley Place from 11:30 am вЂ“ 7:00 pm, with authors present from 5:30 pm вЂ“ 7:00 pm. NOTE: An asterisk designates a resident/fellow travel award winner. Two asterisks designates an abstract selected for oral presentation in the Derek Denny-Brown New Member Symposium. S109 Revising the Model of Vascular Homeostasis: Mechanotransduction Is Opposed by a Novel Electrical Force Darshan P. Trivedi and Peter R. Bergethon; Boston, MA S110 Does the NMDA Receptor Biomarker Predict Impaired Cerebral Vascular Function in Diabetes? Kerstin Bettermann, Julia E. Slocomb, Mary E.J. Lott and Svetlana Dambinova; Hershey, PA and Atlanta, GA Cerebrovascular Disease S101 The Expression of Individual Genes in Acute Stroke Differs across Leukocyte Subsets Mateusz G. Adamski, Erin Wagenr, Yan Li, Hua Yu, Steven A. Soper and Alison E. Baird; Brooklyn, NY; Krakow, Poland and Baton Rouge, LA S111 Neurophysiological Identification of Two Independent Generators Causing Oculofaciopalatal and Lingual Myoclonus Rony Dekermenjian, Nancy Gadallah, Sushanth Bhat, Sumaiya Salim, Liudmila Lysenko, Michael Rosenberg and Sudhansu Chokroverty; Edison, NJ S102 Genetic Risk in Cerebral Small Vessel Disease (SVD): 17q25 Locus Associates with White Matter Lesions but Not Lacunar Stroke Poneh Adib-Samii, The International Stroke Genetics Consortium and METASTROKE Consortium; London, United Kingdom S112 Evaluation of Gender Disparities in Hemicraniectomy Utilization in the United States Mahmoud Rayes, Seemant Chaturvedi and Pratik Bhattacharya; Detroit, MI S103 The Untreated Clinical Course of Cerebral Cavernous Malformations: A Prospective, Population-Based Cohort Study Rustam Al-Shahi Salman, Julie M. Hall, Margaret A. Horne, Fiona A. Moultrie, Colin B. Josephson, Jo J. Bhattacharya, Carl E. Counsell, Gordon Murray, Vakis Papanastassiou, Vaughn Ritchie, Richard C. Roberts, Robin J. Sellar and Charles P. Warlow; Edinburgh, United Kingdom; Newcastleupon-Tyne, United Kingdom; Glasgow, United Kingdom; Aberdeen, United Kingdom; Fauldhouse, United Kingdom and Dundee, United Kingdom S113 Functional Weakness in tPA Candidates: Challenges and NIHSS-Minus Ilya Bragin, Mirret M. El-Hagrassy and Adham Kamel; Syracuse, NY S114 Cognitive Outcomes of Acute Ischemic Stroke Patients: Association with Concentrations of Thyroid Axis Hormones and C-Reactive Protein Adomas Bunevicius, Henrikas Kazlauskas, Nijole Raskauskiene, Rima Radziuviene, Audra Anskoliene, Vinsas Janusonis and Robertas Bunevicius; Palanga, Lithuania; Klaipeda, Lithuania and Chapel Hill, NC S104 Characteristic Distributions of Intracerebral Hemorrhage-Associated Microinfarcts Eitan Auriel, Mahmut Edip Gurol, Alison Ayers, Andrew Dumas, Kristin Schwab, Anastasia Vashkevich, Sergi Martinez-Ramirez, Jonathan Rosand, Anand Viswanathan and Steven M. Greenberg; Boston, MA S115 Angioplasty and Stenting of Patients with Carotid Artery or Vertebral Artery Stenosis: Experience from Lithuania Adomas Bunevicius, Donatas Cerniauskas, Rytis S. Kaupas and Edvardas Vaicekavicius; Kaunas, Lithuania and Chapel Hill, NC S105 Effect of Leukoaraiosis on Neglect Performance in Acute Stroke Patients Zainab Bahrainwala, Argye E. Hillis, Jennifer Dearborn and Rebecca F. Gottesman; Baltimore, MD S116 Risk Factors for Stroke in South Asians across Two Continents Zhongbo Chen, Muhammad S. Khan, Sunaina Yadav, Ankita Maheshwari, Tharushi Fernando, Ranil de Silva, Ranjani Gamage, Kameshwar Prasad and Pankaj Sharma; London, United Kingdom; New Delhi, India; Nugegoda, Sri Lanka and Colombo, Sri Lanka S106 First Mexican Family with CADASIL: A Novel Mutation in the NOTCH3 Gene Fernando Barinagarrementeria, Antonio Arauz and Manuele Minw; Queretaro, Mexico; Mexico City, Mexico and Paris, France S107 Prolyl 4-Hydroxylase Inhibition (GSK360A) Increases Hypoxia Inducible Factor (HIF)-Regulated Transcripts and Improves Post-Stroke Sensory-Motor and Cognitive Functions Frank C. Barone, Jin Zhou, Jie Lie, Robert N. Willette, John Lapore, Erding Hu and Daniel M. Rosenbaum; Brooklyn, NY and King of Prussia, PA S117 Withdrawn. S118 A Fulminant Case of Atypical Posterior Reversible Encephalopathy Syndrome Associated with Status Epilepticus Bhavpreet Dham, Usman Moghal, Yadira Velazquez, Tapan Kavi, Luis Zayas and Akbar Umer; Camden, NJ 1 ID: srinivasanv I Black Lining: [ON] I Time: 00:34 I Path: N:/3b2/ANA#/Vol00000/120252/APPFile/JW-ANA#120252 J_ID: ZAY Customer A_ID: BKLT2012_Poster_Sessions Cadmus Art: ANS9 Date: 14-September-12 S119 Quality of Life after Lacunar Stroke: The Secondary Prevention of Small Subcortical Strokes (SPS3) Mandip S. Dhamoon, Leslie A. McClure, Carole L. White, Oscar Benavente and Mitchell S.V. Elkind; New York, NY; Birmingham, AL; San Antonio, TX and Vancouver, BC, Canada Stage: Page: 2 S130 No Significant Association of Aspirin Use with Cerebral Microbleeds in the Asymptomatic Elderly Chi Kyung Kim, Hyuk Tae Kwon, Jong-Ho Park and Hyung-Min Kwon; Seoul, Korea and Koyang, Korea S131 A Population-Based Study of Pre-Morbid Blood Pressure in Patients with Small Vessel TIA and Stroke Linxin Li, Nicola L.M. Paul, Linda Bull, Ziyah Mehta and Peter M. Rothwell; Oxford, United Kingdom S120 Primary/Familial CAA and Maeda-Type Cerebral Small-Vessel Disease: Clinicopathological Diferential Diagnosis and Role of Amyloid Deposition Diseases A.N. Viswanathan, S.M. Greenberg and Sabino Guillermo Echebarria; Boston, MA and Las Arenas, Bizkaia, Spain S132 Is the Susceptibility to Carotid Atherosclerosis Reduced in Small Vessel Disease? Evidence from a Population-Based Study Linxin Li, Ziyah Mehta, Ursula Schulz and Peter M. Rothwell; Oxford, United Kingdom S121 TIA with New Ischemic Lesion: Clinical Features and Stroke Risk for Patients with Different TIA Subtypes Olena Y. Fartushna; Kiev, Ukraine S133 The Secondary Degeneration in Red Nuclei Following Striatum Infarction Revealed by Diffusion Tensor Imaging Zijun Wang, Chao Qin, Zhijian Liang, Xuean Mo, Daobin Cheng, Yajuan Chen, Wei Ye and Yi Dai; Nanning, Guangxi, China S122 Risk Factors for Intracranial Haemorrhage in Acute Ischaemic Stroke Patients Treated with rtPA William N. Whiteley, Karsten Bruins-Slot, Peter M. Fernandes, Peter A.G. Sandercock and Joanna Wardlaw; Edinburgh, United Kingdom and Oslo, Norway S134 Early Plasma Biomarkers of Ischemic Penumbra in Acute Stroke Svetlana Lorenzano, Natalia S. Rost, Hens B. Brouwers, Alfredo J. Caceres, Matthew S. Siket, Octavio M. Pontes Neto, Hua Li, Rebecca E. Green, Tijy Thankachan, Allison J. Dipietro, Brenda J. Thornell, Ona Wu, Ken Arai, Sophia Hartdegen, Angel T. Som, Loc-Duyen D. Pham, Peter J. Kelly, Gordon J. Harris, Eng H. Lo, Steven K. Feske and Karen L. Furie; Boston, MA and Dublin, Ireland S123 Reversible Cerebral Vasoconstriction in Pre-Eclampsia Pablo Garcia-Reitboeck, Phil Rich and Ali Al-Memar; London, United Kingdom S124 Endothelial Engulfment of Emboli вЂ�вЂ�AngiophagyвЂ™вЂ™ Is a Fundamental Mechanism of Microvascular Recanalization Jaime Grutzendler; New Haven, CT S135 Elevated Factor IX and XI Activities May Not Be a Risk Factor for Ischemic Stroke Jennifer J. Majersik, George M. Rodgers, Kevin D. Call, Jana J. Wold, Ronda A. Crist, Anna M. Sherr, Elaine J. Skalabrin and Kristi J. Smock; Salt Lake City, UT; Provo, UT and Springfield, OR S125 Chronic Inflammatory Diseases and Stroke: Evidence for Heterogeneous Mechanisms Jose Gutierrez and Mitchell S.V. Elkind; New York, NY S136 Partial to Complete Recanalization in Middle Cerebral Artery Occlusion Following Intra-Arterial tPA and Transcranial Doppler Monitoring Amer M. Malik, Krislynn Barnhart and Yince Loh; Seattle, WA S126 Dabigatran Etexilate: Management in Acute Ischemic Stroke Parisa P. Javedani, B. Zane Horowitz, Wayne M. Clark and Helmi L. Lutsep; Portland, OR S137 Clinical and Radiologic Significance of Dilated Perivascular Spaces in Patients with Cognitive Impairment Sergi Martinez-Ramirez, Amy Halpin, Megan Quimby, Andrew P. Dumas, Mahmut Edip Gurol, Eithan Auriel, Steven M. Greenberg and Anand Viswanathan; Boston, MA S127 High Resolution Magnetic Resonance Imaging (HRMRI) in Intracranial Atherosclerosis Tanya N. Turan, Truman R. Brown, Zoran Rumboldt and Robert J. Adams; Charleston, SC S128 Outcomes of Perfusion Based Endovascular Therapy in Witnessed Onset and Unwitnessed Onset of Stroke Deependra Khanal, Pratik Bhattacharya and Seemant Chaturvedi; Detroit, MI S138 Protective Association between ACE Inhibitors and Lobar Intracerebral Hemorrhage Sharyl R. Martini, Matthew L. Flaherty, William M. Brown, Charles J. Moomaw, Mary E. Comeau, Mary Haverbusch, Dawn O. Kleindorfer, Brett M. Kissela, Joseph P. Broderick, Carl D. Langefeld and Daniel Woo; Cincinnati, OH and Winston-Salem, NC S129 A Retrospective Study of Complications and Discharge Dispositions after Treatment for Acute Ischemic Stroke Based on the Nationwide Inpatient Sample from 2006-2009 Tobias B. Kulik, Kate C. Young, Ann M. Leonhardt, Babak S. Jahromi and Curtis G. Benesch; Rochester, NY S139 Heparin May Not Improve Recanalization of Intraluminal Thrombi in Acute Stroke Patients Haris Kamal, Ping Li, Mohammed Shafie, Max Mokin and Bijal K. Mehta; Buffalo, NY and Torrance, CA 2 ID: srinivasanv I Black Lining: [ON] I Time: 00:34 I Path: N:/3b2/ANA#/Vol00000/120252/APPFile/JW-ANA#120252 J_ID: ZAY Customer A_ID: BKLT2012_Poster_Sessions Cadmus Art: ANS9 Date: 14-September-12 Stage: Page: 3 S140 Cerebral Vasospasm and Anterior Circulation Stroke Secondary to an Exacerbation of Hereditary Corproporphyria вЂ“ First Reported Case Stephen Mullin, Andrew Platts and Kashmir Randhawa; London, United Kingdom S150 Comparative Gene Expression Profiling of Simvastatin Single and Vytorin Combination Therapy in Hypercholesterolemic Subjects Zohara Sternberg, Trevor Chichelli, David Hojnacki, Alison Drake and Frederick Munschauer; Buffalo S141 Physiologic Device-Based Diagnosis of Stroke in Acute Vertigo: Proof-of-Concept Ali S. Saber Tehrani, Georgios Mantokoudis, John H. Pula, Cindy Guede, Kevin A. Kerber, Richard Rothman, Daniel F. Hanley, David S. Zee, Jorge C. Kattah and David E. Newman-Toker; Baltimore, MD; Peoria, IL and Ann Arbor, MI S151 Immune Inflammatory Cross-Talk between Carotid Plaque and Peripheral Circulation Zohara Sternberg, Husam Ghanim, Elad Levy, Adnan Siddiqui and Paresh Dandona; Buffalo, NY S142 Ischemic Burden in Relation to Apolipoprotein B/ AI Ratio in Intracranial Atherosclerotic Stenosis Jong-Ho Park; Goyang, Republic of Korea and Seoul, Republic of Korea S152 A Comparative Study of Immune Cells, and Their Activation State, in the Carotid Plaque and in the Peripheral Circulation Zohara Sternberg, Kristen Glotti, Joseph Tario, Richard Curl, Sonya Noor, Paul Wallace, Frederick Munschauer and Paresh Dandona; Buffalo, NY S143 Lipid Measurements and Risk of Ischemic Vascular Events: Framingham Study Aleksandra Pikula, Alexa S. Beiser, Jayandra J. Himali, Margaret Kelly-Hayes, Carlos S. Kase, Sudha Seshadri and Philip A. Wolf; Boston, MA and Framingham, MA S153 Dissection in the VeteransвЂ™ Administration (DIVA): Re-Examining Spinal Manipulation and Cervical Artery Dissection David E. Thaler, Xuemei Cai, Ali Razmara, Karen Switkowski, Sergey D. Goryachev, Leonard DвЂ™Avolio, Pari J. Fariborz and Edward Feldmann; Boston, MA S144 Transient Aura Attacks in Cerebral Amyloid Angiopathy Respond to Migraine Prophylactics Patrick Pullicino, Ross W. Paterson and Ken Uchino; Canterbury, Kent, United Kingdom and Cleveland, OH S154 Lobar Microbleeds without Intracerebral Hemorrhage: A Clinical, Genetic and Neuroimaging Analysis Ellis S. van Etten, Eitan Auriel, Alison M. Ayers, Anastasia Vashkevich, Kristin M. Schwab, Jonathan Rosand, Anand Viswanathan, Steven M. Greenberg and M. Edip Gurol; Boston, MA S145 Superposition of Stents in the Management of Intracranial Aneurysms in Arterial Bifurcations Ricardo A. Rangel-Guerra and Alberto Garcia-de la Fuente; Monterrey, NL, Mexico and Monterrrey, NL, Mexico S146 A Recombinant Human Neuron-Binding IgM Protects the Brain Against Experimental Stroke by Improving Motor Function, Reducing Infarct Volume and Preserving Tissue Integrity Bharath Wootla, Aleksandar Denic, Makoto Eriguchi, Istvan Pirko and Moses Rodriguez; Rochester, MN S155 A New Mouse Model for Central Post-Stroke Pain Simon Gritsch, Rohini Kuner and Daniel Vardeh; Heidelberg, Germany and Boston S147 Acute Ischemic Stroke Caused by Thrombotic Thrombocytopenic Purpura without Significant Hematologic Abnormalities Julio C. Rojas, Fazeel Siddiqui, Bardia Nourbakhsh, Chirantan Banerjee and Craig Powell; Dallas, TX S156 The Third International Stroke Trial (IST-3) of Intravenous rt-PA: Effect of Age and Time among 3035 Patients Randomised Graham Venables, Richard Lindley, Peter Sandercock, Joanna Wardlow and Geoff Cohen; Sheffield, United Kingdom; Sydney, Australia and Edinburgh, United Kingdom S148 Genetic Variants Associated with Severity of Leukoaraiosis Predict Ischemic Stroke Risk Natalia S. Rost, William J. Devan, Jing Wang, Guido Falcone, Poneh Adib-Samii, Matthew Traylor, Alesandro Biffi, Kaitlin M. Fitzpatrick, Valerie Valant, Alexa Beiser, Steven Bevan, Bradford B. Worrall, Christopher Levi, Cathie Sudlow, Peter Rothwell, Giorgio Boncoraglio, Martin Dichgans, James Meschia, Philip A. Wolf, Hugh Markus, Karen L. Furie, Qiong Yang, Sudha Seshadri and Jonathan Rosand; Boston; London, United Kingdom; Charlottsville; Newcastle, Australia; Edinburgh, United Kingdom; Oxford, United Kingdom; Milan, Italy; Munich, Germany and Jacksonville S157 Should We Thrombolyse the Oldest Old? Julio R. Vieira, Shankar Awasthi and Barbara Koppel; New York, NY S158 Early Arrival to Stroke Centers Should Be Most Emphasized in Public Education Concerning Strokes Kuniyasu Wada, Tadashi Terasaki, Yasuhiro Ogata and Yukio Ando; Kumamoto, Japan S159 Recurrent Brain Hemorrhage Caused by Cerebral Vasculitis Due to Ulcerative Colitis: A Case Report and Review Heisuke Mizukami, Toshiyuki Yanagisawa, Hisanao Akiyama, Yuta Hagiwara, Takahiro Shimizu, Makoto Shiraishi and Yasuhiro Hasegawa; Kawasaki, Kanagawa, Japan S149 Body Mass Index and Mortality in Acute Ischemic Stroke Lesli E. Skolarus, Brisa N. Sanchez, Deborah A. Levine, Kevin A. Kerber, Lewis B. Morgenstern, Melinda A. Smith and Lynda D. Lisabeth; Ann Arbor 3 ID: srinivasanv I Black Lining: [ON] I Time: 00:34 I Path: N:/3b2/ANA#/Vol00000/120252/APPFile/JW-ANA#120252 J_ID: ZAY Customer A_ID: BKLT2012_Poster_Sessions Cadmus Art: ANS9 Date: 14-September-12 S160 Genetic Variants on 9p21.3 Are Associated with Brain Arteriovenous Malformations with Associated Flow-Related Arterial Aneurysms Helen Kim, Nasrine Bendjilali, Jeffrey Nelson, Shantel M. Weinsheimer, Mark Segal, Charles E. McCulloch, Ludmila Pawlikowska and William L. Young; San Francisco, CA Stage: Page: 4 S209 ChurgвЂ“Strauss Syndrome in a Patient Previously Diagnosed with Multiple Sclerosis: A Case Report Pamela Sarkar, Richard T. Ibitoye and Douglas A. Promnitz; London, United Kingdom; Preston, United Kingdom and Ipswich, United Kingdom Neuro-oncology S161 Impact of Acute Ischemic Stroke Treatment in Patients over Age 80: The SPOTRIAS Consortium Experience Joshua Z. Willey, Santiago Ortega-Gutierrez, Nils Petersen, Pooja Khatri, Andria L. Ford, Natalia S. Rost, Latisha K. Ali, Nichole R. Gonzales, Jose G. Merino, Brett C. Meyer and Randolph S. Marshall; New York, NY; Cincinnati, OH; St. Louis, MO; Boston, MA; Los Angeles, CA; Houston, TX; Bethesda, MD and San Diego, CA S301 Cerebrospinal Fluid and MRI Analysis in Leptomeningeal Carcinomatosis Ameya Save, Nicholas Blondin and Joachim Baehring; New Haven, CT S302 Emerging Therapeutic Targets in Merlin-Deficient Tumors Clemens O. Hanemann, Sylwia Ammoun and Lu Zhou; Plymouth, United Kingdom Education S303 Ataxia, Ophthalmoplegia and Areflexia: What Would You Think? Nazia Karsan, Phillip Fletcher, Istvan Bodi and Bridget K. Macdonald; London, United Kingdom S201 Competency-Based Curricula in Neuromodulation Device Therapies Bruce Bellande, Zev Winicur, John Huffman, Maged Hamza, David Caraway, Michael Saulino, Michael Turner, David Charles, Bruno Gallo, Kevin Benson, Steven Siegel, Mary Elizabeth Nelson, Susan Bennett, Susan Heath, Gail McGlothlen, Myra Joseph-Gonzales, Glenn Sulley, Cynthia Reese, Suzanne Dawidowicz, Kathleen Cox, Jamie Boche, Andrea Larson and Peter Scott; Carmel, IN; Silver Spring, MD; Richmond, VA; Huntington, WV; Philadelphia, PA; Indianapolis, IN; Nashville, TN; Miami, FL; Sioux Falls, SD; Woodbury, MN; Milwaukee, WI; Buffalo, NY; San Francisco, CA; Napa, CA; San Antonio, TX; Oklahoma City, OK and Minneapolis, MN S304 Use of Rituximab in a Case of Paraneoplastic Sensorimotor Neuropathy with Positive ANNA-1 Antibodies Inhyup Kim, Shyla Kodi and Etta Eskridge; Valhalla, NY S305 Use of Body-CT and PET-CT in the Investigation of Paraneoplastic Neurological Syndromes: Retrospective Audit of Practice in a UK Neuro-Science Unit Deacon Z.J. Lee, Ammar Kheder, Mhairi Forbes, Ian Craven and Marios Hadjivassiliou; Sheffield, South Yorkshire, United Kingdom S202 Improved Timeliness of Neurology Consults in the Emergency Department Marius Birlea*, Charles Braun, Drew Kern, William Jones, Steven P. Ringel and Kenneth L. Tyler; Aurora, CO S306 Widespread Intracerebral Metastases from Prostate Adenocarcinoma Devin D. Mackay, Eli L. Diamond and Joshua P. Klein; Boston, MA and New York, NY S203 What? No Ascending Paralysis? Joseph Khalil and Frank Hrisomalos; Indianapolis, IN S307 Evaluating Corneal Innervation as a Surrogate for Skin-Biopsy Diagnosis of Small-Fiber Polyneuropathy Giulio Ferrari, Nambi Nallassamy, Heather Downs, Reza Dana and Anne Louise Oaklander; Boston, MA S204 A Survey To Identify Neurology Education in Africa Heather Koons and Gretchen Birbeck; Nashville, TN and East Lansing, MI S205 Withdrawn. S308 Neurophysiologic Tests Do Not Correlate Well with Pain Measures and Quality of Life in Taxane Neuropathy Harry Openshaw, Karen Knight, Wei Ye, Gloria Juarez, Paul Frankel and George Somlo; Duarte, CA S206 Neurological Diagnoses among the Uninsured Farrah J. Mateen; Baltimore, MD S207 The Neurology Boot Camp: Tackling the вЂ�July PhenomenonвЂ™ Wazim Mohamed, Maysa M. Basha and Benjamin E. Atkinson; Detroit, MI S309 Leveraging Expression of the GABA-A Receptor, alpha 5 in Medulloblastoma as a Novel Therapeutic Target Soma Sengupta, Shyamal D. Weeraratne, Hongyu Sun, Bela Kosaras, Jillian Phallen, Natalia Teider, Sundari Rallapalli, Mirna Lechpammer, Dimitrios Mathios, Vlad Amani, Jessica Pierre-Francois, Tenley Archer, James Cook, Frances Jensen, Michael Lim, Scott Pomeroy and Yoon-Jae Cho; Boston; Baltimore; Milwaukee and Stanford S208 Who Needs Us Most? вЂ“ Seeking out Those Needing Rapid Neurological Assessment Catriona L. Gribbin, Edward J. Newman, Paul Gallagher and John Paul Leach; Glasgow, United Kingdom 4 ID: srinivasanv I Black Lining: [ON] I Time: 00:34 I Path: N:/3b2/ANA#/Vol00000/120252/APPFile/JW-ANA#120252 J_ID: ZAY Customer A_ID: BKLT2012_Poster_Sessions Cadmus Art: ANS9 Date: 14-September-12 Stage: Page: 5 S503 Subarachnoid Hemorrhage and Acute Hydrocephalus in a Patient with Familial Transthyretin Type Amyloidosis Matthew B. Bevers, Nivedita U. Jerath and Patricia L. Musolino; Boston, MA Sleep Disorders and Circadian Rhythm S401 Polysomnographic and Polymyographic Characteristics of Painful/Painless Limbs Moving Toes Syndrome (PPLMTS) Syndrome Rony Dekermenjian, Nancy Gadallah, Sushanth Bhat, Phillip Hanna, Fouzia Siddiqui and Sudhansu Chokroverty; Edison and Harrisonburg, VA S504 Exome Sequencing Identifies Two Separate Mutations in a Novel Gene as Cause of Autosomal Dominant Cervical Dystonia in Two Families Gavin Charlesworth, Jose M. Bras, Rita Guerreiro, Una M. Sheerin, Kailash Bhatia and Nicholas W. Wood; London, United Kingdom S402 Complex Sleep Behavior with Multiple Etiologies: A Diagnostic Challenge Rony Dekermenjian, Nancy Gadallah, Sushanth Bhat, Sumaiya Salim, Luidmila Lysenko, Disha Patel and Sudhansu Chokroverty; Edison, NJ S505 Withdrawn. S506 Progressive Supranuclear Palsy Genetic Risk Variants Associate with Brain Gene Expression and Neuropathology Endophenotypes Nilufer Ertekin-Taner, Mariet Allen, Melissa Murray, Julia Crook, Daniel Serie, Fanggeng Zou, High Seng Chai, Curtis Younkin, Shane Pankratz, Minerva Carrasquillo, Christopher Rowley, Asha Nair, Sumit Middha, Sooraj Maharjan, Thuy Nguyen, Li Ma, Kimberly Malphrus, Ryan Palusak, Sarah Lincoln, Gina Bisceglio, Constantin Georgescu, Naomi Kouri, Christopher Kolbert, Jin Jen, Gerard Schellenberg, Ronald Petersen, Neill Graff-Radford, Steven Younkin and Dennis Dickson; Jacksonville; Rochester and Philadelphia S403 Sleep and Circadian Rhythm Disruption in Incident ParkinsonвЂ™s Disease вЂ“ A Multimodal Analysis David P. Breen, Romina Vuono, Kate Fisher, Shani Nawarahtna, John M. Shneerson, Akhilesh B. Reddy and Roger A. Barker; Cambridge, United Kingdom S404 The Tuberous Sclerosis Complex-Mammlian Target of Rapamycin (mTOR) Pathway Regulates Mammalian Circadian Rhythms Jonathan Lipton, Elizabeth Yuan, Ashwin Nathan, Jarrett Leech, Juliette Han, Fred Davis and Sahin Mustafa; Boston, MA S405 A Longitudinal Study of 322 Individuals with Narcolepsy Maurice M. Ohayon; Palo Alto, CA S507 Hexanucleotide Repeat Expansion in c9orf72 Is Associated with Increased Risk of Bulbar Amyotrophic Lateral Sclerosis (ALS) Paloma Gonzalez-Perez, Peter Sapp, Zack C. Kennedy, Diane McKenna-Yasek, Ru-Ju Chian, Andrew Fox and Robert H. Brown; Worcester, MA S406 Medical Conditions and Psychiatric Disorders Associated with Narcolepsy Maurice M. Ohayon; Palo Alto, CA S508 Infrequent NaV1.7 Mutation in Insensitivity to Pain, Erythromelalgia and Small Fiber Neuropathy Christopher J. Klein, Dean H. Kilfoyle, Yanhong Wu, Paola Sandroni, Phillip A. Low, Mark D. Davis and Peter J. Dyck; Rochester, MN and Epsom, Aucklund, New Zealand S407 Bmal1 Provides a Molecular Link between Circadian Clock Function, Brain Metabolism, and Neurodegeneration Erik S. Musiek, Miranda M. Lim, Adam Q. Bauer, Guangrui Yang, Jee Hoon Roh, Benoit I. Giasson, David M. Holtzman and Garret A. FitzGerald; St. Louis, MO; Philadelphia, PA and Gainesville, FL S509 Improvement of Learning and Memory in Ts65Dn Mouse Model of Down Syndrome (DS) by GABAB Receptor Antagonists: DS-Specific and Non-Specific Mechanisms Francisco Madamba, Yasaman Pirahanchi, Brett Rasmussen and Alexander Kleschevnikov; La Jolla, CA Neurogenetics S501 Nonsyndromic and Syndromic Polymicrogyria: Illustration of Clinical, Radiological and Genetic Heterogeneity in a Cohort of 50 Patients Dina R. Amrom, Jacques Michaud, Grant Mitchell, Emmanuelle Lemyre, Annapurna Poduri, Jennifer Partlow, Vijay Ganesh, Bernard Dan, Giorgi Kuchukhidze, Ingrid Unterberger, Eugen Trinka, Nicolas Deconinck, Catherine Christophe, BenoД±Л†t Pichon, FrancВёois Dubeau, Donatella Tampieri, Jean-Claude DeВґcarie, William B. Dobyns, Frederick Andermann, Christopher A. Walsh and Eva Andermann; Montreal, QC, Canada; Boston, MA; Brussels, Belgium; Innsbruck, Austria; Salzburg, Austria; Seattle, WA and Montreal, QC S510 PRRT2 Mutations in Japanese PKC Cases Mitsuya Morita and Imaharu Nakano; Shimotsuke, Tochigi, Japan S511 C9ORF72 Hexanucleotide Repeat Expansion Analysis in Multiple System Atrophy and Progressive Supranuclear Palsy Karen E. Morrison, Rachel V. Denyer, Gilbert Bensimon, Albert Ludolph, Yves Agid, P. Nigel Leigh, Ammar Al-Chalabi and on Behalf of NNIPPS Consortium; Birmingham, United Kingdom; Paris, France; Ulm, Germany; Falmer, Brighton, United Kingdom and London, United Kingdom S502 The Phenotypic Spectrum of Subcortical Band Heterotopia in Patients Negative for DCX/LIS1 Gene Mutations Eva Andermann, Dina Amrom, FrancВёois Dubeau, Maria D. DвЂ™Agostino, William B. Dobyns and Frederick Andermann; Montreal, QC, Canada and Seattle, WA S512 No Association of CETP Genotypes with Evolution of Dementia Due to AlzheimerвЂ™s Disease Fabricio F. Oliveira, Paulo H. Bertolucci, Marilia A. Smith and Elizabeth S. Chen; SaЛњo Paulo, SP, Brazil 5 ID: srinivasanv I Black Lining: [ON] I Time: 00:34 I Path: N:/3b2/ANA#/Vol00000/120252/APPFile/JW-ANA#120252 J_ID: ZAY Customer A_ID: BKLT2012_Poster_Sessions Cadmus Art: ANS9 Date: 14-September-12 S513 GLRB Is the 3rd Major Gene-of-Effect in Hyperekplexia Charlotte Hunt, Anna Derrick, Thomas Cushion, Sian Wood, Cheney Drew, Owain W. Howells, Rhys H. Thomas, Seo Kyung Chung and Mark I. Rees; Swansea, Wales, United Kingdom and, Wales, United Kingdom Stage: Page: 6 Neuroinfectious Disease S601 Spiroplasma Biofilm on Stainless Steel Is a Model for Iatrogenic Transmission of CJD Via Surgical Instruments Frank O. Bastian, Xiaochu Wu and Philip H. Elzer; Baton Rouge, LA S514 Neuronal Loss of Tuberous Sclerosis Complex Activity Results in Increased Autophagosome Accumulation Despite mTOR Activation Alessia Di Nardo, Mary H. Wertz, Jarrett Leech, Emily Greene-Colozzi, June Goto, Dennis Wall, David J. Kwiatkowski and Mustafa Sahin; Boston, MA S602 Upstate Eastern Equine Encephalitis: A Case Report Mirret M. El-Hagrassy and Yaman Eksioglu; Syracuse, NY S603 HIV-1 Exposure Affects Neural Progenitor Cell Renewal and Accelerates Astrocyte Differentiation in Human Brain Slices Ricardo Martinez, Rebeca Geffin and Micheline McCarthy; Miami, FL S515 Homozygous Nonsense Mutations of C12orf65 in Patients with Spastic Paraplegia, Optic Atrophy and Neuropathy Haruo Shimazaki; Shimotsuke, Tochigi, Japan S604 Anti-Ganglioside Antibodies Positive Influenza Encephalopathy Hitoshi Mori and Katuro Shindo; Kurashiki, Okayama, Japan S516 Hyperekplexia Phenotypes Associated with GLRB Mutations Rhys H. Thomas*, Cheney J. Drew, Owain W. Howell, Thomas Cushion, Sian E. Wood, Jonathan G. Mullins, SeoKyung Chung and Mark I. Rees; Swansea, United Kingdom S605 A Severe Case of Recurrent Coccidioidal Meningitis Complicated by Hydrocephalus Sarah Nelson and Michal Vytopil; Burlington, MA S517 Increased Cancer Incidence in LRRK2-G2019S Mutation Carriers BjГёrg Johanne WarГё, Krisztina K. Johansen and Jan Olav Aasly; Trondheim, Norway S606 A Mouse Model of Arachnoid Granulation Obstruction by Cryptococcus Jeffrey A. Rumbaugh, Angela Pool, Lindsey Gainey and Yu Hui Wu; Atlanta, GA S518 Detailed Phenotype of a Novel Allelic Form of Spinocerebellar Ataxia Type 13 Michael F. Waters, Kristina Santiago, Alexis K. Harmeling and Richard P. Morse; Gainesville, FL and Lebanon, NH S607 Pathways to Neurodegeneration: The Effects of HIV & Aging on Resting State fcMRI Jewell B. Thomas, Matthew R. Brier, Florin F. Vaida, Abraham Z. Snyder and Beau M. Ances; St. Louis, MO and San Diego, CA S519 A Meta-Analysis of Genome Wide Association Studies To Identify Loci Associated with Brain Atrophy in Multiple Sclerosis Zongqi Xia*, Nikolaos Patsopoulos, Charles Guttmann, PierreAntoine Gourraud, Sergio Baranzini, Jorge Oksenberg, Jeroen Geurts, Bernard Uitdehaag, Raija Lindberg, Yvonne Naegelin, Stephen Hauser, Ludwig Kappos, Chris Polman, Howard Weiner and Philip De Jager; Boston, MA; Cambridge, MA; San Francisco, CA; Amsterdam, Netherlands and Basel, Switzerland S608 Clearance of Low Copy JC Virus from CSF of MS Patients on Natalizumab Gloria von Geldern, Caroline Ryschkewitsch, Peter Jensen, Avindra Nath and Eugene O. Major; Bethesda, MD Neuro-ophthalmology S701 Withdrawn. S702 3-Tesla MRI of the Optic Nerve: A Pilot Study David Bradley, Iqbal Mudassir, Gerard OвЂ™Connor, Lisa Costelloe, Derbhail OвЂ™Driscoll, Andrew Fagan, Jim Meaney and Janice Redmond; Dublin, Ireland S520 Engineering Mouse Chromosomes To Facilitate Genetic Analysis of Down Syndrome Xiaoling Jiang, Chunhong Liu, Li Zhang, Pavel V. Belinchenko, Alexander M. Kleschevnikov, Annie Pao, William C. Mobley and Y. Eugene Yu; Buffalo, NY and La Jolla, CA S703 The Lone Abducting Eye and Laterality of Motor Control: Congresswoman GiffordsвЂ™ вЂ�вЂ�Wrong-Way EyesвЂ™вЂ™ Denotes Crossed Right Hemisphere Syndrome in a Right Hander Iraj Derakhshan; Veckeley, WV and Cleveland, OH S521 Body-Wide Correction of Myotonic Dystrophy Type 1 (DM1) in Transgenic Mice by RNase H-Active Antisense Oligonucleotides (ASOs) Thurman M. Wheeler, Andrew J. Leger, Sanjay K. Pandey, A. Robert MacLeod, Masayuki Nakamori, Seng H. Cheng, Bruce M. Wentworth and C. Frank Bennett; Rochester, NY; Framingham, MA and Carlsbad, CA S704 MOG Antibody Positive Optic Neuritis in Adults Jithin S. George, Joanna Kitley, Mark Woodhall, John Elston, Maria I. Leite, Angela Vincent and Jacqueline Palace; Oxford, Oxfordshire, United Kingdom 6 ID: srinivasanv I Black Lining: [ON] I Time: 00:34 I Path: N:/3b2/ANA#/Vol00000/120252/APPFile/JW-ANA#120252 J_ID: ZAY Customer A_ID: BKLT2012_Poster_Sessions Cadmus Art: ANS9 Date: 14-September-12 S705 Longitudinally Extensive Optic Neuritis in Pediatric Patients Jennifer Graves, Verena Kraus, Bruno Soares, Jonathan Strober and Emmanuelle Waubant; San Francisco and Munich, Germany Stage: Page: 7 S804 Visual Function and Optical Coherence Tomography in Pediatric Demyelinating Diseases Amy T. Waldman, Girish Hiremath, Robert A. Avery, Amy Conger, Michael Loguidice, Lauren S. Talman, Kristin M. Galetta, Michael J. Shumski, James Wilson, EвЂ™tona Ford, Benjamin M. Greenberg, Jonas Ellenberg, Elliot M. Frohman, Laura J. Balcer and Peter A. Calabresi; Philadelphia, PA; Baltimore, MD and Dallas, TX S706 Hypertrophic Perioptic Neuritis (HPN) in Wegener Granulomatosis (WG) Ken Ikeda, Takanori Takazawa, Tetsuro Nagaoka, Takehisa Hirayama, Osamu Kano, Kiyokazu Kawabe and Yasuo Iwasaki; Tokyo, Japan S805 Epidermal Growth Factor Treatment Rescues Neonatal White Matter Injury Joseph Scafidi, Maria Roncal, Tamas L. Horvath, Robert J. McCarter and Vittorio Gallo; Washington, DC and New Haven, CT S707 Is This the Tolosa-Hunt Syndrome? Ulya S. Malik and Odai Jumma; Birmingham, United Kingdom S708 Ethambutol Induced Optic Chiasmopathy Subin Mathew, Raghavendra Seetharam, Ravindra Kamble and Rajani Battu; Bangalore, Karnataka, India S806 Drosophila Peroxisomal Biogenesis Defects Produce Shortened Lifespan and Excess Cystene-String Protein at the Synapse Michael F. Wangler, Lucy Liu, Nikolaos Giagtzoglou, Vafa Bayat, Joseph Faust, James McNew and Hugo J. Bellen; Houston, TX S709 Optic Disc Edema Does Not Always Correlate with Retinal Nerve Fiber Layer (RNFL) Thickening Mark J. Morrow; Torrance, CA S710 Syphilitic Optic Neuritis: Possibly Forgotten but Not Gone Robert K. Shin, Marc A. Malouf, Shalom E. Kelman, Larysa D. Kwintkiewicz and Stephen G. Reich; Baltimore, MD Rehabilitation and Regeneration S901 Time Limited Functional Properties of Transplanted Neural Stem Cells Nina Fainstein, Ofira Einstein, Mikhal Cohen and Tamir Ben-Hur; Jerusalem, Israel S711 Correlation of the Retinal Ganglion Cell Complex and Contrast Sensitivity in Parkinson Disease Eric M. Shrier, Christopher R. Adam, Yin Ding, Sophya Glazman and Ivan Bodis-Wollner; Brooklyn, NY S902 Recovery of Motor Function after Complete Unilateral Injury of the Corticospinal Tract Using Electrical Stimulation of Motor Cortex on the Uninjured Hemisphere in Rats Jason B. Carmel, Hiroki Kimura, Gabriel Felder, Ashley Khalili, Melissa Lopresti, Chelsea Jin and John H. Martin; White Plains, NY and New York, NY S712 Late Diffusion Changes in Optic Radiations Predicted by Early Optic Nerve Structure after Optic Neuritis, Suggesting Trans-Synaptic Effects Olivia Goodkin, Olga Ciccarelli, Daniel Altmann, Camilla Fini, Alessia Mirigliani, Thomas M. Jenkins, Alan J. Thompson and Ahmed T. Toosy; London, United Kingdom S713 Cerebellar Esotropia Misdiagnosed as VI Nerve Paresis: A Case Series Sui H. Wong, Leena Patel and Gordon T. Plant; London, United Kingdom and London, United Kingdom S903 Synergic Effects of Enriched Environment and Mesenchymal Stem Cells in Hypoxic-Ischemic Brain Injury through FGF-2 Dependent Mechanism Jung Hwa Seo, Ji Hea Yu, Yang Hyun Cho and Sung-Rae Cho; Seoul, Republic of Korea S714 Withdrawn. S904 OnabotulinumtoxinA Plus Rehabilitation Improves Functional Outcome in Post-Stroke Upper Limb Spasticity: A Single-Blind, Randomized Trial Deidre J. Devier, JoAnn Harnar, Leandro M. Lopez, Allison Brashear and Glenn D. Graham; New Orleans, LA; Albuquerque, NM; Albuqueruque, NM; Winston Salem, NC and Washington, DC Pediatric Neurology S801 Elevated Immune Response to Gliadin in Autism: Association with Gastrointestinal Symptoms but Not Celiac Disease Nga M. Lau, Peter H. Green, Donald D. Kasarda, Luan To, Abhishek Chandra, Barry E. Kosofsky, Joseph J. Higgins, Anjali M. Rajadhyaksha and Armin Alaedini; New York, NY and Albany, CA S905 Peripheral and Cutaneous Nerve Fiber Regeneration in the Distal Foot of Macaques after Spinal Nerve Ligation (SNL) Gigi J. Ebenezer, Jasenka Borzan, Matthias Ringkamp, Lun Chen, Justin C. McArthur, Peter Hauer, James N. Campbell, Richard A. Meyer, John W. Griffin and Michael Polydefkis; Baltimore S802 Cognitive Assessment in Rett Syndrome: A Pilot Study of Eyetracking Aleksandra Djukic, Maria Valicenti-McDermott, Kathleen Mavrommatis and Cristina Martins; Bronx, NY S803 Asymptomatic Abnormalities in the White Matter of Patients with CMT-X Amy R. Viehoever, Linda Schimmoeller, Tammie Benzinger, Soe Mar and Amy Viehoever; St. Louis, MO S906 Vestibular Rehabilitation and Multiple Sclerosis: Do Patients with Infratentorial Lesions Benefit More? Jeffrey R. Hebert; Aurora, CO 7 ID: srinivasanv I Black Lining: [ON] I Time: 00:34 I Path: N:/3b2/ANA#/Vol00000/120252/APPFile/JW-ANA#120252 J_ID: ZAY Customer A_ID: BKLT2012_Poster_Sessions Cadmus Art: ANS9 Date: 14-September-12 S907 Effects of Vestibular Rehabilitation on Multiple Sclerosis-Related Fatigue and Upright Postural Control: A Randomized Controlled Trial Jeffrey R. Hebert, John R. Corboy, Mark M. Manago and Margaret Schenkman; Aurora, CO Stage: Page: 8 S1003 Widely Used Clinical Predictors Do Not Account for Outcome Variability in Mild Traumatic Brain Injury Paolo Moretti, Stephen McCauley, Elisabeth Wilde and Harvey Levin; Houston S1004 Systematic Review and Meta-Analysis of Glasgow Coma Scale and Simplified Motor Scale in Predicting Traumatic Brain Injury Outcomes Balwinder Singh, M. Hassan Murad, Larry J. Prokop, Patricia J. Erwin, Zhen Wang, Shannon K. Mommer, Sonia S. Mascarenhas and Ajay K. Parsaik; Rochester, MN and London, United Kingdom S908 RTMS in Treatment of Poststroke Aphasia Wolf-Dieter Heiss, Alexander Hartmann, Josef Kessler, Nora Weiduschat, Ilona Rubi-Fessen, Carole Anglade and Alexander Thiel; Cologne, Germany and Montreal, Canada S909 Regulatory Experience with Orphan Disorders of the Nervous System Orest Hurko, Andra E. Miller, Ruth Wolff and James G. Kenimer; Alexandria, VA S1005 Headaches and Cognitive Performance after Combat Mild Traumatic Brain Injury (mTBI) Correlate with Episodes of Loss of Consciousness (LOC), Post-Traumatic Stress Disorder (PTSD) and Impaired Sleep (IS) Ronald G. Riechers, Robert L. Ruff, Xiao-Feng Wang, Suzanne S. Ruff and Traci Piero; Cleveland, OH S910 Examining Driving Ability in Multiple Sclerosis Maria Schultheis, Chelsea Morse, Josh McKeever, Lisa Zhao and Thomas Leist; Philadelphia, PA S1006 Delayed Imaging Findings in Delayed Posthypoxic Leukoencephalopathy Kevin A. Shapiro, Mai Anh Huynh, Riley M. BoveВґ, Stephanie L. Cincotta and Jeffrey M. Ellenbogen; Boston, MA S911 Shefstim: Automated Setup of Functional Electrical Stimulation for Drop Foot Using a 64 Channel Prototype Stimulator and Electrode Array Ben W. Heller, Alison J. Clarke, Timothy R. Good, Jamie Healey, Krishnan P.S. Nair, Emma J. Pratt, Mark L. Reeves, Jill M. van der Meulen and Anthony T. Barker; Sheffield, South Yorkshire, United Kingdom S1007 When Mild Traumatic Brain Injury IsnвЂ™t so Mild Latha G. Stead, Aakash N. Bodhit, Keith R. Peters, Lawrence Lottenberg and Bayard D. Miller, Sr; Gainesville, FL 2012 Annual Meeting Monday, October 8, 2012 Poster Session S912 Deconditioning in Patients with Orthostatic Intolerance Ajay K. Parsaik, Thomas G. Allison, Wolfgang Singer, David M. Sletten, Michael J. Joyner, Eduardo E. Benarroch, Phillip A. Low and Paola Sandroni; Rochester, MN Posters will be displayed in Gloucester, located on the 3rd floor in the Back Bay Hall of the Marriott Copley Place from 11:30 am вЂ“ 6:30 pm, with authors present from 5:30 pm вЂ“ 6:30 pm. NOTE: An asterisk designates a resident/fellow travel award winner. S913 Orthostatic Intolerance with or without Postural Orthostatic Tachycardia Ajay K. Parsaik, Thomas G. Allison, Wolfgang Singer, David M. Sletten, Michael J. Joyner, Eduardo E. Benarroch, Phillip A. Low and Paola Sandroni; Rochester, MN Dementia and Aging M1101 Epigenetics of Induced Neuronal Cells to Model Neurologic Diseases Andy J. Liu, Bradley T. Hyman, Asa Abeliovich, Benjamin S. Bleier and Mark W. Albers; Boston, MA; North Chicago, IL and New York, NY S914 Efficacy of Vitamin E Supplementation in Cisplatin-Induced Neuropathy: A Meta-Analysis of Randomized Controlled Trials Rechilda Rhea P. Reyes, Rechilda Rhea Reyes, Rechilda Rhea Reyes, Rechilda Rhea Reyes and Rechilda Rhea Reyes; Davao City, Davao, Philippines M1102 Family History of Alzheimer Disease Disrupts Functional Connectivity between the Hippocampus and Posterior Cingulate Cortex Liang Wang, Abraham Z. Snyder, Matthew Brier, Jewell Thomas and Beau M. Ances; Saint Louis, MO Trauma/Injury S1001 Preliminary Clinical Utility of Advanced SpinalCord MRI Julien Cohen-Adad, Wei Zhao, Lawrence L. Wald, Bradley Buchbinder and Anne Louise Oaklander; Charlestown, MA and Boston, MA M1103 Interactive Visual Analysis of Diffusion-Tensor MRI Data Using the Expectation Maximization Algorithm Jian Chen, Andrew Maxwell, Haipeng Cai and Alexander P. Auchus; Hattiesburg and Jackson S1002 Neuregulin-1 Effects on Endothelial and Blood-Brain Barrier Permeability after Experimental Injury Josephine Lok, Song Zhao, Wendy Leung, Ji Hae Seo, Deepti Navaratna, Xiaoying Wang and Lo Eng; Boston, MA and Jilin, China M1104 The Hypothalamus in AlzheimerвЂ™s Disease: A Golgi and Electron Microscope Study Stavros J. Baloyannis, Ioannis Mavroudis and Ioannis S. Baloyannis; Thessaloniki, Greece 8 ID: srinivasanv I Black Lining: [ON] I Time: 00:34 I Path: N:/3b2/ANA#/Vol00000/120252/APPFile/JW-ANA#120252 J_ID: ZAY Customer A_ID: BKLT2012_Poster_Sessions Cadmus Art: ANS9 Date: 14-September-12 M1105 Mixed-Risk Vascular Cognitive Impairment: Hypertension Plus Hypoperfusion Decrease Cognition and Gait and Increase Fiber Tract Pathology and Inflammation Frank C. Barone, Jin Zhou, Jie Li, Alison E. Baird, Adamski G. Mateusz, Diana L. Dow-Edwards, Peter J. Bergold, Samah G. Abdel Baki, Howard Crystal and Daniel M. Rosenbaum; Brooklyn, NY Stage: Page: 9 M1114 Cognitive, Functional, and Neuropsychiatric Trajectories before and after an AlzheimerвЂ™s Disease Diagnosis Joseph E. Gaugler, David L. Roth, Robert Kane, Martha Hovater, Joseph Johnston and Khaled Sarsour; Minneapolis, MN; Baltimore and Indianapolis M1115 Hippocampal Volumes Predict Response to Acetylcholinesterase Inhibitors in Patients with Dementia with Lewy Bodies Jonathan Graff-Radford*, Bradley F. Boeve, Otto Pedraza, Tanis J. Ferman, Scott Przybelsk, Timothy Lesnick, Matthew Senjem, Glenn E. Smith, David S. Knopman, Clifford R. Jack, Jr, Ronald C. Petersen and Kejal Kantarci; Rochester and Jacksonville M1106 Excessive Trk-B Signaling in GABAeric Synapses Revealed by Array Tomography in the Ts65Dn Mouse Model of Down Syndrome Rachel L. Nosheny, Pavel V. Belichenko, Brad Busse, Kristina D. Micheva, Stephen J. Smith and William C. Mobley; La Jolla, CA and Stanford, CA M1116 Sustained Cognitive Improvement with Extended-Release Memantine (28 mg, Once Daily) in Moderate to Severe AlzheimerвЂ™s Disease Michael Tocco, Suzanne Hendrix, Michael L. Miller, Vojislav Pejovic and Stephen M. Graham; Jersey City, NJ; Salt Lake City, UT and Chicago, IL M1107 Degeneration of Brainstem Respiratory Nuclei in Dementia with Lewy Bodies Michael F. Presti, Ann M. Schmeichel, Phillip A. Low, Joseph E. Parisi and Eduardo E. Benarroch; Rochester, MN M1108 Pathological Accumulation of a-Synuclein and Ab in Dementia Associated with Parkinson Disease Meghan C. Campbell, Paul T. Kotzbauer, Nigel J. Cairns, Allison W. Willis, Brad A. Racette, Samer D. Tabbal and Joel S. Perlmutter; St. Louis, MO M1117 Response across Multiple Outcome Measures in Patients with Moderate to Severe AlzheimerвЂ™s Disease Taking Extended-Release Memantine (28 mg, Once Daily) Stephen M. Graham, Suzanne Hendrix, Michael L. Miller, Vojislav Pejovic and Michael Tocco; Jersey City, NJ; Salt Lake City, UT and Chicago, IL M1109 Impaired Default Network Functional Connectivity in Autosomal Dominant AlzheimerвЂ™s Disease: Findings from the DIAN Study Jasmeer P. Chhatwal*, Aaron P. Schultz, Keith A. Johnson, Tammie L.S. Benzinger, Clifford R. Jack, Stephen Salloway, John M. Ringman, Robert A. Koeppe, David L. Marcus, Paul M. Thompson, Andrew J. Saykin, Sonia C. Correia, Peter R. Schofield, Christopher C. Rowe, Nick C. Fox, Adam M. Brickman, Richard Mayeux, Miroslava Rimajova, Chester A. Mathis, Eric M. McDade, William E. Klunk, Michael W. Weiner, Randall J. Bateman, Alison M. Goate, Chengjie Xiong, Virginia Buckles, Krista L. Moulder, John C. Morris and Reisa A. Sperling; Boston, MA; St. Louis, MO; Rochester, MN; Providence, RI; Los Angeles, CA; Ann Arbor, MI; New York, NY; Indianapolis, IN; Coimbra, Portugal; Randwick, Australia; Melbourne, Australia; London, United Kingdom; Perth, Australia; Pittsburgh, PA and San Francisco, CA M1118 Retinal Degeneration in FTLD Patients and PGRN-Deficient Mice Preceded by TDP-43 Mislocalization Michael E. Ward*, Alice Taubes, Bruce L. Miller, Jeffrey M. Gelfand, Li Gan and Ari J. Green; San Francisco, CA M1119 Cerebral Amyloid Angiopathy Independently Contributes to Ischemic White Matter Disease: A PET/ MRI Correlative Study Edip M. Gurol, Christopher Gidicsin, Andrew Dumas, Trey Hedden, Alison Ayres, Alex Becker, Anastasia Vashkevich, Sergi R. Martinez, Eitan Auriel, Kristen Schwab, Anand Viswanathan, Jonathan Rosand, Keith A. Johnson and Steven M. Greenberg; Boston, MA M1110 Apples Far from the Tree: Clinical and Electrophysiologic Variability in a Family with c9FTD/ ALS Elizabeth A. Coon, Jasper R. Daube, Mariely DeJesusHernandez, Anahita Adeli, Rodolfo Savica, David S. Knopman, Josephs E. Parisi, Rosa Rademakers and Bradley F. Boeve; Rochester, MN and Jacksonville, FL M1120 Gephyrin Plaques Identified in Frontal Cortex of AlzheimerвЂ™s Disease Brains Chadwick M. Hales, Howard Rees, James J. Lah, Allan I. Levey and Thomas Wingo; Atlanta, GA M1121 Clinical, Imaging and Pathologic Features of C9ORF72 Hexanucleotide Expansion in ALS and FTLD David J. Irwin, Corey T. McMillan, Johannes Brettschneider, David J. Libon, Ashley Boller, John Powers, Keerthi Chandrasekaran, Elisabeth McCarty Wood, Jon B. Toledo, Leslie Shaw, Katya Rascovsky, John H. Woo, David A. Wolk, Steven E. Arnold, Vivianna Van Deerlin, Leo F. McCluskey, Lauren Elman, Virginia M.Y. Lee, John Q. Trojanowski and Murray Grossman; Philadelphia, PA M1111 Withdrawn. M1112 Neural Correlates of Face-Name Encoding Using Simultaneous Eye-Tracking and ERP Ali Ezzati, Meghan B. Mitchel, Steven D. Shirk, Donald G. Mclaren, Brandon A. Ally and Alireza Atri; Boston, MA; Bedford, MA and Nashville, TN M1122 Inflammatory Cerebral Amyloid Angiopathy: An Unrecognized Cause of Reversible Dementia Nivedita Jerath, Aarti Jerath, Keri Oxley, Matt Bevers, Shelley Waite and Steve Greenberg; Boston, MA M1113 Efficacy of a Brain/Cognitive Training Therapeutic Program for Diagnosed Dementia Barbara C. Fisher and Danielle M. Garges; Shelby Township, MI 9 ID: srinivasanv I Black Lining: [ON] I Time: 00:34 I Path: N:/3b2/ANA#/Vol00000/120252/APPFile/JW-ANA#120252 J_ID: ZAY Customer A_ID: BKLT2012_Poster_Sessions Cadmus Art: ANS9 Date: 14-September-12 Stage: Page: 10 M1123 Inclusion of Axial Rigidity May Improve Diagnostic Accuracy for Dementia with Lewy Bodies Fariha Zaheer, John T. Slevin, Erin L. Abner, Peter T. Nelson and Gregory A. Jicha; Lexington, KY M1134 Decreased Life Expectancy When Seizures Develop in AlzheimerвЂ™s Lauren R. Moo and Steven D. Shirk; Bedford, MA and Boston, MA M1124 Quantitative Neurofibrillary Tangle Density and Brain Volumetric MRI Analyses in AlzheimerвЂ™s Disease Presenting as Progressive Fluent Aphasia Keith A. Josephs, Dennis W. Dickson, Melissa E. Murray, Matthew L. Senjem, Joseph E. Parisi, Ronald C. Petersen, Clifford R. Jack and Jennifer L. Whitwell; Rochester, MN and Jacksonville, FL M1135 Comparison of the Impact of AlzheimerвЂ™s Disease on Medicare and Medicaid Lisa Mucha, Amanda Forys, Huai-Che Shih, Joel Bobula, Trent McLaughlin, Kara Suter, Machaeon Bonafede and Robert Fowler; Collegeville, PA; Arlington, VA; Abbott Park, IL and Cambridge, MA M1125 Hippocampal CA1 Apical Neuropil Atrophy and Memory Performance in Alzheimer Disease Geoffrey A. Kerchner, Gayle K. Deutsch, Michael Zeineh, Robert F. Dougherty and Brian K. Rutt; Stanford, CA M1136 Optineurin Immunoreactivity in Neuronal and Glial Intranuclear Inclusions in Adult-Onset Neuronal Intranuclear Inclusion Disease Masataka Nakamura, Melissa E. Murray, Wen-Lang Lin, Hirofumi Kusaka and Dennis W. Dickson; Jacksonville, FL and Moriguchi, Osaka, Japan M1126 Dimensions of Dementia: Item Response Analysis of the AlzheimerвЂ™s Disease Assessment Scale (ADAS-Cog) Christian Yavorsky, Anzalee Khan, Mark Opler, Guillermo DiClemente and Sofija Jovic; New York, NY; Hamilton, NJ and Orangeburg, NY M1137 Redistribution of Memory Load in Temporal Association Tracts in Mild Cognitive Impairment Claudia Metzler-Baddeley, Sarah Hunt, Derek K. Jones, John P. Aggleton and Michael J. OвЂ™Sullivan; Cardiff, United Kingdom and London, United Kingdom M1127 Quantifying Differences in the Shape Complexity of the Cerebral Cortex across the Adult Lifespan Richard D. King, Sourav Kole and Nikhil Singh; Salt Lake City, UT M1138 Cingulum Bundle Microstructure Predicts Cognitive Control in Ageing and Mild Cognitive Impairment Michael J. OвЂ™Sullivan, Claudia Metzler-Baddeley, Derek K. Jones, Jessica Steventon, Laura Westacott and John P. Aggleton; London, United Kingdom and Cardiff, United Kingdom M1128 Treatment of Primary Progressive Aphasia with Rivastigmine Hisatomo Kowa, Tsuneyoshi Seki, Mikiko Yamamoto, Fumio Kanda and Tatsushi Toda; Kobe, Japan M1139 AlzheimerвЂ™s Disease Progression Rates: New Estimates Natalia Olchanski, Pei-Jung Lin, Joshua T. Cohen and Peter J. Neumann; Boston, MA M1129 Rest/Activity Fragmentation and the Risk of AD in Older Adults Andrew S. Lim, Matthew Kowgier, Lei Yu, Aron S. Buchman and David A. Bennett; Toronto, ON, Canada and Chicago, IL M1140 Impact of Cerebrovascular Risk over Age of Onset of Dementia Due to AlzheimerвЂ™s Disease in a Sample of Patients with Low Schooling from Brazil Fabricio F. Oliveira, Paulo H. Bertolucci, Marilia A. Smith and Elizabeth S. Chen; SaЛњo Paulo, SP, Brazil M1130 Does Sporadic Atonia Occur in Alzheimer Disease? Leopold Liss; Columbus, OH M1141 Repurposing Anti-Hypertensive Drugs for AlzheimerвЂ™s Disease Giulio M. Pasinetti and Paul Rosenberg; New York, NY and Baltimore, MD M1131 Diminished Thalamocortical Feedforward Inhibition in an Aging Mouse Model of Chronic Tinnitus: Implications for Deafferentation Syndromes and Aging Daniel A. Llano, Jeremy Turner and Don Caspary; Urbana, IL; Jacksonville, IL and Springfield, IL M1142 Changes in Specific Resting State Brain Networks Correlate with Clinical Measures in PSP and CBD Timothy Rittman, Boyd Ghosh, William R. Shirer, Michael D. Greicius and James B. Rowe; Cambridge, Cambridgeshire, United Kingdom and Stanford, CA M1132 Does Education Slow Functional Decline in AlzheimerвЂ™s Disease? Revisiting the Reserve Hypothesis Meghan B. Mitchell, Steven D. Shirk and Alireza Atri; Boston, MA and Bedford, MA M1143 Patterns of Longitudinal Brain Atrophy in the Logopenic Variant of Primary Progressive Aphasia Jonathan D. Rohrer, Francesca Caso, Colin Mahoney, Maya Henry, Howard Rosen, Martin N. Rossor, Bruce Miller, Jason D. Warren, Gerard R. Ridgway and Maria Luisa Gorno-Tempini; London, United Kingdom and San Francisco M1133 Predictive Value of the MemoryImpairment-Screen Test in Subjects with Subjective Memory Loss Pedro J. Modrego, JoseВґ Gazulla and Pedro J. Modrego; Zaragoza, Spain 10 ID: srinivasanv I Black Lining: [ON] I Time: 00:34 I Path: N:/3b2/ANA#/Vol00000/120252/APPFile/JW-ANA#120252 J_ID: ZAY Customer A_ID: BKLT2012_Poster_Sessions Cadmus Art: ANS9 Date: 14-September-12 M1144 Differential Patterns of White Matter Degeneration as a New Biomarker for Dementia Seyed Ahmad Sajjadi, Julio Acosta-Cabronero and Peter J. Nestor; Cambridge, Cambridgeshire, United Kingdom Stage: Page: 11 M1154 Gait and Balance Dysfunction in Dementia Yutaka Tanaka, Masao Miyazaki and Lisa T. Connor; IkomaGun, Nara, Japan; Ise, Mie, Japan and St. Louis, MO M1145 Souvenaid Improves Memory in Mild AD вЂ“ Results from the Clinical Study Program P. Scheltens, R. Shah, D.A. Bennett, R.L. Wieggers, T. Hartmann, H. Soininen and P.J.G.H. Kamphuis; Amsterdam, Netherlands; Chicago, IL; Wageningen, Netherlands; Homburg, Germany and Kuopio, Finland M1155 Pharmacodynamic and Pharmacokinetic Properties of Novel gamma-Secretase Modulators in Multiple Animal Model Systems Brian S. Bronk, Timonthy D. McKee, Robyn M.B. Louriero, JoAnn Dumin, Vladislav Zarayskiy, Wesley F. Austin, Nathan O. Fuller, Jed L. Hubbs, Ruichao Shen, Paul Pearson, Jeffrey Ives, Jeffrey Jonker and Barbara Tate; Cambridge, MA M1146 Relationship between Гџ-Amyloid Retention and Ischemia in the Patients with Subcortical Vascular Cognitive Impairment Young Noh*, Sang Won Seo, Geon Ha Kim, Seun Jeon, Jong Min Lee, Seung Jun Oh, Jae Seung Kim, Yearn Seong Choe, KyungHan Lee, Jae-hong Lee and Duk L. Na; Seoul, Republic of Korea M1156 Effects of Extended-Release Memantine (28 mg, Once Daily) on Language and Communication Abilities in Patients with Moderate to Severe AlzheimerвЂ™s Disease Michael Tocco, Suzanne Hendrix, Michael L. Miller, Vojislav Pejovic and Stephen M. Graham; Jersey City, NJ; Salt Lake City, UT and Chicago, IL M1147 Prefrontal Cortex: Unilateral Disruption Differentially Affects Verbal Working Memory in Young and Older Adults Jessica A. Shields, Jeffrey Mock and Anne L. Foundas; New Orleans, LA M1157 Ile143Thr Presenilin 1 Mutation in Sporadic Atypical Early-Onset AlzheimerвЂ™s Disease Maria Travasarou, Stella Marousi, Vasiliki Kyrimi and Clementine E. Karageorgiou; Athens, Greece M1158 Brain Imaging and Cognitive Predictors of Incident Stroke, Dementia and AlzheimerвЂ™s Disease (AD) Galit Weinstein, Alexa Beiser, Charles DeCarli, Rhoda Au, Philip A. Wolf and Sudha Seshadri; Boston, MA and Sacramento, CA M1148 Normative Scores and Calculator for the NACC UDS Neuropsychological Test Battery Steven D. Shirk, Meghan B. Mitchell, Joseph J. Locascio, Sandra Weintraub and Alireza Atri; Bedford, MA; Boston, MA and Chicago, IL M1159 Beyond the Myths: Forgetting the Fictions of AlzheimerвЂ™s and Facing the Facts Peter J. Whitehouse; Cleveland, OH M1149 Integrating Human and Fly Genetics To Understand AlzheimerвЂ™s Disease Susceptibility Joshua M. Shulman, Selina Imboywa, Allison E. Diamond, Portia Chipendo, Philip L. De Jager and Mel B. Feany; Boston, MA M1160 Baseline Characteristics of Subjects with Prodromal AlzheimerвЂ™s Disease: The LipiDiDiet Study Y. Freund-Levi, P.J. Visser, M. Kivipelto, R.L. Wieggers, T. Hartmann and H. Soininen; Huddinge, Sweden; Maastricht, Netherlands; Amsterdam, Netherlands; Stockholm, Sweden; Wageningen, Netherlands; Homburg, Germany and Kuopio, Finland M1150 Genetic Susceptibility for Amyloid Pathology in AlzheimerвЂ™s Disease Joshua M. Shulman, Kewei Chen, Brendan T. Keenan, Lori B. Chibnik, Pradeep Thiyyagura, Cristin McCabe, Jason J. Corneveaux, Lei Yu, Matthew J. Huentelman, Denis A. Evans, Julie A. Schneider, Eric M. Reiman, Philip L. De Jager and David A. Bennett; Boston, MA; Phoenix, AZ and Chicago, IL M1161 Pellagra: The Forgotten American Neurological Epidemic Adrian C. Williams; Birmingham, United Kingdom M1151 Impaired Nutritional Status in Patients with Mild AlzheimerвЂ™s Disease Compared to Healthy AgeMatched Controls J.W. Sijben, M.G.M. Olde Rikkert, P. Scheltens, A.M.J. van Hees, M. Groenendijk and P.J.G.H. Kamphuis; Wageningen, Netherlands; Nijmegen, Netherlands and Amsterdam, Netherlands M1162 Induction of Autophagy Protects Against TDP43-Mediated Neurodegeneration Sami Barmada, Aaron Daub, Michael Ando, Andrea Serio, Andrey Tsvetkov, Arpana Arjun, Siddharthan Chandran and Steve Finkbeiner; San Francisco, CA and Edinburgh, United Kingdom M1152 Supporting Synapse Formation and Function in AlzheimerвЂ™s Disease: Mechanism of Action of the Specific Nutrient Combination FortasynTM Connect John W. Sijben, Patrick J. Kamphuis, Martijn C. de Wilde, Robert J. Hageman, Laus M. Broersen and Martine Groenendijk; Wageningen, Netherlands and Utrecht, Netherlands Epilepsy M1153 A Return to Clinical Skills in the Early Diagnosis of AlzheimerвЂ™s Disease Cassandra Szoeke, Kathryn Ellis, Ping Zhang, Christopher Rowe, Ralph Martin, Colin Masters, David Ames and AIBL Research Group; Melbourne, VIC, Australia and Melbourne, Australia M1202 Pharmacokinetics of Extended- and Immediate-Release Topiramate at Steady State and after Formulation Switch Tricia L. Braun, Lawrence J. Lambrecht, Wesley M. Todd and Mark B. Halvorsen; Maple Grove, MN M1201 Extended-Release Topiramate Exhibits Linear and Dose-Proportional Pharmacokinetics Tricia L. Braun, Lawrence J. Lambrecht, Wesley M. Todd, Mark B. Halvorsen and T.L. Braun; Maple Grove, MN 11 ID: srinivasanv I Black Lining: [ON] I Time: 00:34 I Path: N:/3b2/ANA#/Vol00000/120252/APPFile/JW-ANA#120252 J_ID: ZAY Customer A_ID: BKLT2012_Poster_Sessions Cadmus Art: ANS9 Date: 14-September-12 M1203 Magnetic Resonance Volumetry Reveals Focal Brain Atrophy in Transient Epileptic Amnesia Christopher R. Butler, Willemijn van Erp, Amit Bhaduri, Alexander Hammers, Rolf Heckemann and Adam Z. Zeman; Oxford, United Kingdom; Nijmegen, Netherlands; London, United Kingdom; Lyon, France and Exeter, United Kingdom Stage: Page: 12 M1216 Dravet Syndrome Patient-Derived Cells and Mouse Model Suggest SUDEP Mechanisms David Auerbach, Huilin Shi, Yu Liu, Julie M. Jones, Miriam H. Meisler, Lori L. Isom and Jack M. Parent; Ann Arbor, MI M1217 Hypothermia Attenuates Glial Injury and Prevents EEG Progression during Status Epilepticus Sandipan Pati, J.X. Yin, Y. Gan, J. Georges, F.D. Shi, M. Maalouf and D.M. Treiman; Phoenix, AZ M1204 SOS for Seizures in SESA Mirret M. El-Hagrassy and Robert Beach; Syracuse, NY M1205 Reduced GABAA Receptor Endocytosis in a Mouse Model of Absence Epilepsy Chengwen Zhou, Li Ding and Martin J. Gallagher; Nashville, TN M1218 Weight Change Associated with Anti-Epileptic Drugs W.O. Pickrell, A.S. Lacey, R.H. Thomas, M.I. Rees and P.E.M. Smith; Swansea, United Kingdom and Cardiff, United Kingdom M1206 Leucine Has Anticonvulsant Effects in Acute Seizure Tests Adam L. Hartman, Polan Santos and J. Marie Hardwick; Baltimore, MD M1219 Mutations in the Novel Protein PRRT2 Cause Infantile Convulsions with Paroxysmal Kinesigenic Dyskinesia Hsien-Yang Lee, Yong Huang, Nadine Bruneau, Patrice Roll, Elisha D.O. Roberson, Mark Hermann, Emily Quinn, James Maas, Robert Edwards, Tetsuo Ashizawa, Betul Baykan, Kailash Bhatia, Susan Bressman, Michiko K. Bruno, Ewout R. Brunt, Roberto Caraballo, Bernard Echenne, Natalio Fejerman, Steve Fruct, Christina A. Gurnett, Edouard Hirsch, Henry Houlden, Joseph Jankovic, Wei-Ling Lee, David R. Lynch, Shehla Mohammed, Ulrich MuВЁller, Mark P. Nespeca, David Renner, Jacques Rochette, Gabrielle Rudolf, Shinji Saiki, Bing-Wen Soong, Kathryn J. Swoboda, Sam Tucker, Nicholas Wood, Michael Hanna, Anne M. Bowcock, Pierre Szepetowski, Ying-Hui Fu and Louis J. Ptacek; San Francisco, CA; Marseille, France; Saint Louis, MO; Gainesville, FL; Istanbul, Turkey; London, United Kingdom; New York, NY; Honolulu, HI; Groningen, Netherlands; Buenos Aires, Argentina; Montpellier, France; Strasbourg, France; Houston, TX; Novena, Singapore; Philadelphia, PA; Giessen, Germany; San Diego, CA; Salt Lake City, UT; Amiens, France; Ishikawa, Japan and Taipei, Taiwan M1207 Withdrawn. M1208 Antiphospholipid Syndrome Presenting as Epilepsia Partialis Continua Fenella F. Johnstone and Odai Jumma; Birmingham, United Kingdom M1209 Race and Sex Differences in Characteristics of Temporal Lobe Epilepsy Robert Knowlton, Suzanne Miller, Maria Pisu, Lawrence Ver Hoef, Kristen Riley and Nita Limdi; Houston, TX and Birmingham, AL M1210 A Higher Hurdle? Baseline Frequency and Severity of Seizures in Trials of Perampanel, a New AED, Compared with Previously Approved AEDs Gregory L. Krauss, Frank Kerling, Vicente Villanueva, David Squillacote, Haichen Yang, Jin Zhu and Antonio Laurenza; Baltimore, MD; Ulm, Germany; Valencia, Spain and Woodcliff Lake, NJ M1220 Appropriate Drug Treatment for Status Epilepticus Does Not Influence Its Prognosis Andrea O. Rossetti, Vicent Alvarez, Jean-Marie Januel and Bernard Burnand; Lausanne, Switzerland M1211 Optogenetic Treatment Approaches for Focal Neocortical Epilepsy Laura Mantoan, Rob Wykes, Stephanie Schorge, Matthew C. Walker and Dimitri M. Kullmann; London, United Kingdom M1221 Planes Trains and Automobiles: Neurologic Disorders and the Workforce. A Systematic Review Eva Pilcher, Maria Baldwin and Michael J. Schneck; Maywood, IL and Pittsburgh, PA M1212 Effect of Ocimum basilicum Extract Against Pentylenetetrazole-Induced Seizure in Mice Mehrdad Modaresi and Arezoo Pouriyanzadeh; Isfahan, Islamic Republic of Iran M1222 Electroconvulsive Therapy Induced Absence Status Epilepticus Umang Shah, Evren Burakgazi and Usman Mogul; Camden, NJ M1213 MRI Volumetry of the Temporal Lobe in Sudan; Comparative Study between Epileptics and Matching Control Mohamed A. Nurein, Mohamedsalah M. Magzoub, Tahir O. Ali, Abdullah M. Jabir and Abdulrahman M. Fadlalmola; Umdurman, Khartoum, Sudan and Khartoum, Sudan M1223 The Role of RhoA, Filamin and Formin in Cortical Development Gewei Lian, Markus Dettenhofer, Russell Ferland and Volney Sheen; Boston, MA and Albany, NY M1214 Epileptic Aphasia as an Initial Manifestation of Lyme Meningoencephalitis Dipakkumar P. Pandya, Anery Patel, Jennie Luna, Megan McGarry and Sourav Sen; Paterson, NJ M1224 Seizure Etiology & Outcome in HIVГѕ Zambian Adults Omar K. Siddiqi, Melissa Elafros, Izukanji Sikazwe, Chris Bositis, Michael J. Potchen, Igor J. Koralnik, William Theodore and Gretchen L. Birbeck; Boston, MA; Lusaka, Zambia; East Lansing, MI; Baltimore, MD; Lawrence, MA and Bethesda, MD M1215 Synaptic Reporter Labeling of Adult-Born Hippocampal Neurons in Experimental Epilepsy Alison L. Althaus, Helen Zhang, Hisashi Umemori and Jack M. Parent; Ann Arbor, MI 12 ID: srinivasanv I Black Lining: [ON] I Time: 00:34 I Path: N:/3b2/ANA#/Vol00000/120252/APPFile/JW-ANA#120252 J_ID: ZAY Customer A_ID: BKLT2012_Poster_Sessions Cadmus Art: ANS9 Date: 14-September-12 M1225 Ketamine in the Treatment of Refractory Status Epilepticus Andrea S. Synowiec, Deepinder S. Singh, Vamsi Yenugadhati, James P. Valeriano, Carol J. Schramke and Kelly M. Kevin; Pittsburgh, PA and Philadelphia, PA Stage: Page: 13 M1304 Serum Sodium Values and Their Association with Adverse Outcomes in Moderate-Severe Traumatic Brain Injury (TBI) Lucia Rivera-Lara, Raphael Carandang, Wiley Hall, Cynthia Ouillette, Frederick A. Anderson, Robert J. Goldberg and Susanne Muehlschlegel; Worcester, MA M1226 Self Reported Anger and Depression in Patients on Levetiracetam in Mono and Polytherapy Udo C. Wieshmann and Gus Baker; Liverpool, United Kingdom M1305 Impact of Medical and Neurological ICU Complications on Moderate-Severe Traumatic Brain Injury (TBI) Susanne Muehlschlegel, Raphael Carandang, Wiley Hall, Fred A. Anderson and Robert J. Goldberg; Worcester, MA M1227 Intravenous Sodium Valproate for Status Epilepticus Yuan Wu, Xiaofei Liu, ZiBin Chen, MeiGang Ma and Li Su; Nanning, Guangxi, China M1306 Incidence Rates of ICU Complications in Moderate-Severe Traumatic Brain Injury (TBI) Susanne Muehlschlegel, Raphael Carandang, Cynthia Ouillette, Wiley Hall and Robert J. Goldberg; Worcester, MA M1228 Protective Effect of Alpha -Asarone in SombatiвЂ™s Cell-Based Model of Epilepsy Yuan Wu, Xiao-Fei Liu, Yue-Juan Wu, Jie Su and Mei-Gang Ma; Nanning, Guangxi, China Neuromuscular Disease M1401 Novel Choline Kinase Beta Gene Mutation Associated with Exercise Induced Myalgia and Mitochondrial Changes Hena Ahmad, Aleksander Radunovic, Angharad Davis, Sylvia Marino, Heinz Jungbluth, Chieko Aoyama, Steve Abbs and David Moore; London, United Kingdom and Tochigi, Japan M1229 The Syndrome of Transient Epileptic Amnesia (TEA) Adam Zeman and Christopher R. Butler; Exeter, Devon, United Kingdom and Oxford, Oxfordshire, United Kingdom M1402 Might Sodium Phenylbutyrate (PBA) Be a Drug for Sporadic Inclusion-Body Myositis (s-IBM)? Anna Nogalska, Carla DвЂ™Agostino, W. King Engel and Valerie Askanas; Los Angeles, CA M1230 Oxygen-Enhanced MRI: A New Imaging Tool for Localization of Focal Epilepsy and Eloquent Cortex Giridhar P. Kalamangalam, Timothy M. Ellmore, Nelson T. Nelson and Narayana A. Ponnada; Houston, TX M1231 Attenuated and Augmented Emotional Face Processing Networks in Temporal Lobe Epilepsy Brett W. Fling, Jeff Riley and Jack J. Lin; Irvine, CA M1403 Chaperone-Mediated Autophagy (CMA) in Sporadic Inclusion-Body Myositis (s-IBM) Muscle Fibers Mafalda Cacciottolo, Anna Nogalska, Carla DвЂ™Agostino, W. King Engel and Valerie Askanas; Los Angeles, CA M1232 Microelectrodes Produce Unreliable EEG Recordings William Stacey, Spencer Kellis, Christopher Butson, Paras Patil, Trevor Assaf, Temenuzhka Mihaylova and Simon Glynn; Ann Arbor, MI; Pasadena, CA and Milwaukee, WI M1404 Is the Familial Amyotrophic Lateral Sclerosis (ALS) Classification Fit for Purpose? Rubika Balendra and Ammar Al-Chalabi; London, United Kingdom M1405 Putative Mechanisms Involved in Primary Hyperoxaluria Type 1 Polyneuropathy Sarah E. Berini, JaNean K. Engelstad, Jennifer A. Tracy, Dawn S. Milliner, P. James B. Dyck and Peter J. Dyck; Rochester, MN Neurology Critical Care M1301 Fatal Hyperammonemic Brain Injury from Valproic Acid Exposure Danny Bega, Henrikas Vaitkevicius, Torrey Boland, Rebecca Folkerth, Michael Murray, Katia Meirelles and Sherry Chou; Boston, MA M1406 Cachexia in Two Adults with Single Mitochondrial DNA Deletions Is Due to Dysphagia Sergiu C. Blumen, Ron Dabby, Yaron River, Esther Leshinsky-Silver and Itzhak Braverman; Hadera, Israel and Holon, Israel M1302 A Population-Based Study of Aetiology and Outcome in Acute Neuromuscular Respiratory Failure Aisling S. Carr, Anne I. Hoeritzaur, Rachel Kee, Michael Kinney, Aoibhean Hutchinson and Gavin V. McDonnell; Belfast, Northern Ireland, United Kingdom M1407 Slowly Progressing Familial ALS with Bulbar Onset Due to a Novel VCP Mutation Sergiu C. Blumen, Paloma Gonzales-Perez, Vivian E. Drory, Ron Dabby, Diane McKenna-Yasek and Robert H. Brown, Jr; Hadera, Israel; Worcester; Tel Aviv, Israel and Holon, Israel M1303 Rapid High Volume CSF Loss вЂ“ A New Cause of Coma Minjee Kim, Rose Du and Sherry H.-Y. Chou; Boston, MA 13 ID: srinivasanv I Black Lining: [ON] I Time: 00:34 I Path: N:/3b2/ANA#/Vol00000/120252/APPFile/JW-ANA#120252 J_ID: ZAY Customer A_ID: BKLT2012_Poster_Sessions Cadmus Art: ANS9 Date: 14-September-12 Stage: Page: 14 M1416 Withdrawn. M1408 Bulbar Speech-Articulation/Swallowing Rate Changes Measured in Amyotrophic Lateral Sclerosis (ALS) Patients Treated with Dextromethorphan/ Quinidine(Nuedexta) for Pseudobulbar Affect (PBA) вЂ“ Determination of Treatment Effect Size for Future Clinical Trials Benjamin Rix Brooks, Elena Bravver, Urvi G. Desai, K. Amy Wright, Velma L. Langford, Nicole M. Williams, Mohammed S. Sanjak and Richard A. Smith; Charlotte, NC and La Jolla, CA M1417 Often-Treatable вЂ�вЂ�Multi-MicrocrampsвЂ™вЂ™ (MMCs) Are Common and Frequently Overlooked Manifestations of Peripheral Neuropathy W. King Engel; Los Angeles, CA M1418 Q-Fever IgM-Positivity in 3/5 sALS Patients: Any Pathogenic Significance Regarding the XYZ Hypothesis? W. King Engel; Los Angeles, CA M1409 Assessment of Clinical Disease Trajectory [CDT] in Amyotrophic Lateral Sclerosis [ALS] Patients by вЂ�ALS DashboardвЂ™ Containing Cognitive- Behavior (Depression-Pseudobulbar Affect (PBA)-BulbarRespiratory-Arm-Leg Domains вЂ“ Longitudinal Validation over Time and by El Escorial/Awaji Shima Criteria [EEC/ASC] Clinically-Definite [EECD/ASCD] Classification at Diagnosis Benjamin Rix Brooks, Mohammed S. Sanjak, Elena K. Bravver, William L. Bockenek, Urvi G. Desai, Scott S. Lindblom, Thomas J. Paccio, Nicole M. Williams, Mindy S. Nichols, Amber L. Ward, K. Amy Wright, Velma L. Langford, Michael P. Fischer, Kristy L. Walgren, Louise H. Frumkin, Priscilla C. Russo, Anne S. Blythe, Nicole P. Smith, Jessica N. Scrmina, Scott E. Holsten and Heather L. Oplinger; Charlotte, NC M1419 Disruption of Intracellular Redox Homeostasis by Mutant CUG-RNA in Myotonic Dystrophy Type 1 (DM1) Xiang Fang, Rui Gao, Arpita Chatterjee, Tapas K. Hazra, Robert Glen Smith and Partha S. Sarkar; Galveston, TX M1420 Expanded CUG-RNA Suppresses PGC-1a Transcription Via Activating DNA Damage Response ATM Signaling in Myotonic Dystrophy Type 1 (DM1) Xiang Fang, Rui Gao, Arpita Chatterjee, Tapas K. Hazra, Robert Glen Smith and Partha S. Sarkar; Galveston, TX M1421 A Common Link between Three Sporadic Amyotrophic Lateral Sclerosis Cases in Annapolis, MD Nicholas C. Field, Sandra Banack, Tracie A. Caller, James Metcalf, Paul A. Cox and Elijah W. Stommel; Lebanon, NH and Jackson, WY M1410 Peripheral Nerve Function Following Treatment with Tanezumab Mark T. Brown, William J. Litchy, David N. Herrmann, Mark Goldstein, Aimee M. Burr, Michael D. Smith, Christine R. West, Kenneth M. Verburg and Peter J. Dyck; Groton, CT; Rochester, MN; Rochester, NY and Atlantis, FL M1422 Infections in Myasthenia Gravis (MG) Raghav Govindarajan, Dennys Reyes, John Morren, Evelio Velis and Nestor Galvez; Weston, FL and Miami M1411 Evaluation of Neuropathy: Tests and Expenditures by Provider Type Brian C. Callaghan, Ann Rodgers, Kevin Kerber, Ken Langa and Eva L. Feldman; Ann Arbor, MI M1423 Anti Acetylcholine Receptor Antibodies in a Patient with LEMS and Idiopathic Thromobocytopenic Purpura Raghav Govindarajan and Virgilio Salanga; Weston, FL M1412 Clinical, Neurophysiological and Histological Differentiators of Congenital Myasthenic Syndromes from the General Neuromuscular Disease Cohort Aisling S. Carr, Estelle Healy, Brian Herron, Stephen Haffey, Kiang Pang, Jacqueline Palace, David Beeson and John McConville; Belfast, Northern Ireland, United Kingdom and Oxford, United Kingdom M1424 Blockade of Matrix Metalloproteinase-3 after Traumatic Nerve Injury Preserves the Motor End Plate Tom Chao, Derek Frump, Vincent J. Caiozzo, Tahseen Mozaffar and Ranjan Gupta; Orange, CA M1413 High Fat Diet Induces Impaired Glucose Tolerance and Painful Peripheral Neuropathy Hsinlin T. Cheng, Jacqueline R. Dauch, John M. Hayes, Sangsu Oh and Eva L. Feldman; Ann Arbor, MI M1425 Transgenic Mouse Models of FUS/TLS-Mediated ALS Lawrence J. Hayward, Hongru Zhou, Guohong Gao and Robert H. Brown; Worcester, MA M1414 Iatrogenic Mitochondrial Disease Emerging Years after Stopping Anti-HIV Treatment: The Tip of the Iceberg in 2012? Brendan Payne, David A. Price, David Samuels, Ian Wilson, Kris Gardner, Michael Trenell, Mauro Santibanez-Koref and Patrick F. Chinnery**; Newcastle upon Tyne, United Kingdom and Nashville M1426 A Novel Mutation in the CACNA1S Gene in a Japanese Family with Hypokalemic Periodic Paralysis Makito Hirano, Yosuke Kokunai, Yusaku Nakamura, Kazumasa Saigoh, Susumu Kusunoki and Masanori P. Takahashi; Sakai, Osaka, Japan; Suita, Osaka, Japan and Osakasayama, Osaka, Japan M1427 Pathological Involvement of ubiquilin2 in Autophagy in Sporadic Amyotrophic Lateral Sclerosis Makito Hirano, Keiji Shimada, Tatsuki Itoh, Yoshiyuki Mitsui, Kazumasa Saigoh, Hikaru Sakamoto, Shuichi Ueno, Takao Satou, Noboru Konishi, Yusaku Nakamura and Susumu Kusunoki; Sakai, Osaka, Japan; Kashihara, Nara, Japan and Osakasayama, Osaka, Japan M1415 Development of C9orf72 ALS Biomarkers and Therapeutics Christopher J. Donnelly, Lyle W. Ostrow, Ying Li, Svetlana Vidensky, Pingwu Zhang, Alan E. Renton, Rita G. Sattler, Bryan J. Traynor and Jeffery D. Rothstein; Baltimore, MD and Bethesda, MD 14 ID: srinivasanv I Black Lining: [ON] I Time: 00:34 I Path: N:/3b2/ANA#/Vol00000/120252/APPFile/JW-ANA#120252 J_ID: ZAY Customer A_ID: BKLT2012_Poster_Sessions Cadmus Art: ANS9 Date: 14-September-12 M1428 An Unbiased Phenotypic Screen Identifies Ethoxyquin as an hsp90 Activity Modulating Neuroprotective Compound for Peripheral Neuropathies Jing Zhu, Weiran Chen and Ahmet Hoke; Baltimore, MD Stage: Page: 15 M1438 Psoriatic Myopathies: The Mayo Clinic Experience Teerin Liewluck and Jennifer A. Tracy; Rochester, MN M1439 Dynactin Mutations in HMN7B Disrupt Initiation of Retrograde Transport at NMJ Terminal Boutons Thomas E. Lloyd, James Machamer, Sarah H. Collins, Yunpeng Yang and Alex L. Kolodkin; Baltimore, MD M1429 Zonisamide (ZNS) Treatment Attenuates Motor Neuron Degeneration and Astrocytosis in the Wobbler Mouse Ken Ikeda, Yasuhiro Yoshii, Takehisa Hirayama, Kiyokazu Kawabe, Osamu Kano and Yasuo Iwasaki; Tokyo, Japan M1440 Phenotypic Diversity of Mutations in the Ryanodine Receptor (RYR1): A Series of Six Cases Charles Marshall, Hena Ahmad, Nicholas Parkin, Stephen Abbs, Silvia Marino, Sujit Vaidya, Heinz Jungbluth and Aleksandar Radunovic; London, United Kingdom M1430 Serum Lipid, Creatinine, Urate and Ferritin Levels at the First Time Diagnosed with Amyotrophic Lateral Sclerosis (ALS) Contribute to Disease Progression Ken Ikeda, Takehisa Hirayama, Kiyokazu Kawabe, Osamu Kano and Yasuo Iwasaki; Tokyo, Japan M1441 Advanced Neuroimaging Study of Molecularly Defined Hereditary Spastic Paraplegias (HSPs) Andrea Martinuzzi, Domenico Montanaro, Nicola Martino, Hana Hlavata, Giuseppe Rossi, Gabriella Paparella, Francesca Peruch, Maria G. Rossetto, Alessandra T. Baratto and Maria T. Bassi; Conegliano and Bosisio Parini, Italy; Pisa-Massa, Italy and Conegliano, Italy M1431 Protective Effect of Erythropoietin on Glutamate-Mediated and Axotomy Induced Motor Neuron Death Yasuo Iwasaki, Ken Ikeda, Kiyokazu Kawabe and Osamu Kano; Tokyo, Japan M1432 Denervation Causes Lower Expression of Insulin-Like Growth Factor (IGF) mRNA in Regenerating Skeletal Muscle Takahiro Jimi, Yoshiriro Wakayama and Hiroo Ichikawa; Yokohama, Japan M1442 The Use of Non-Invasive Ventilation for Patients with Motor Neurone Disease: Patient and Carer Perceptions of Obstacles and Outcomes Susan K. Baxter, Wendy O. Baird, Sue Thompson, Stephen Bianchi, Stephen Walters, Sam H. Ahmedzai, Alison Proctor, Pamela J. Shaw and Christopher J. McDermott; Sheffield, United Kingdom M1433 Quantitative Image Analysis of Brain Abnormality in Myotonic Dystrophy Nam-Hee Kim, Dong-Eog Kim, Sang-Wuk Jeong, Ho Jin Kim and Kyung Seok Park; Goyangsi, Korea and Bundang, Korea M1443 Steroid Responsive Anti-GAD Antibody Positive Spino-Cerebellar Ataxia Shri K. Mishra, Yama Akbari and Parampreet Singh; Los Angeles, CA; Baltimore, MD and Sylmar, CA M1434 Prolonged High Frequency Electrical Nerve Stimulation Precipitates Motor Axon Degeneration in Presymptomatic SOD1G127X Mutant Mice Susana Alvarez, Alexandru Calin, Stefan Marklund, Karin Graffmo, Mihai Moldovan and Christian Krarup; Copenhagen, Denmark; Bucharest, Rwanda and UmeaЛљ, Sweden M1444 Confocal Microscopy Analysis of Altered TDP-43 Expression in Peripheral Blood Lymphocytes from ALS Patients Jean-Luc C. Mougeot, Sriparna Ghosh, Anne C. Lutin, Andrea E. Price, Richelle A. Hemendinger, Edward J. Armstrong and Benjamin R. Brooks; Charlotte, NC M1435 More MS Patients Remain Free from Disease Activity with Teriflunomide Versus Placebo in TEMSO, a Phase III Trial Marcelo Kremenchutzky, Paul W. OвЂ™Connor, Jerry Wolinsky, Christian Confavreux, Giancarlo Comi, Ludwig Kappos, Tomas P. Olsson, Philippe Truffinet, Deborah Dukovic and Aaron Miller; London, ON, Canada; Toronto, Canada; Houston; Lyon, France; Milan, Italy; Basel, Switzerland; Stockholm, Sweden; Chilly-Mazarin, France; Bridgewater and New York M1445 Myasthenia Gravis Associated with GravesвЂ™ Disease Hiroyuki Murai, Natsumi Yamashita and Jun-ichi Kira; Iizuka, Fukuoka, Japan; Matsuyama, Ehime, Japan and Fukuoka, Japan M1446 Effects of Small-Fiber Polyneuropathy (SFPN) on Bone Mineral Density and Skeletal Microarchitecture Benjamin Z. Leder, Ruchit Khumbani, Erica Siwila-Sackman, Heather Downs and Anne Louise Oaklander; Boston, MA M1436 Anxiety in Benign Fasciculation Syndrome Alexandra LaMela, Stephanie Scala, Ioannis Karakis, James A. Russell and Doreen T. Ho; Biddeford, ME and Burlington, MA M1447 Mononeuropathy of the Lateral Cutaneous Nerve of the Calf (LCNC) in Patients Previously Labeled with вЂ�вЂ�Complex Regional Pain Syndrome-IвЂ™вЂ™ Anne Louise Oaklander and JoseВґ Ochoa; Boston, MA and Portland, OR M1437 Myositis with Autoantibodies to c/d Sarcoglycan: A New Disease Russell Lane, Chiara Marini-Bettolo, Peter Charles and Federico Roncaroli; London, United Kingdom 15 ID: srinivasanv I Black Lining: [ON] I Time: 00:34 I Path: N:/3b2/ANA#/Vol00000/120252/APPFile/JW-ANA#120252 J_ID: ZAY Customer A_ID: BKLT2012_Poster_Sessions Cadmus Art: ANS9 Date: 14-September-12 M1448 The Incidence and Prevalence of CIDP in Iceland Brynhildur Hafsteinsdottir, Elias Olafsson and Sigurjon Stefansson; Reykjavik, Iceland Stage: Page: 16 M1459 Confocal Microscopy Is a Reliable Measure of Corneal Innervation A. Gordon Smith, Gene Kim, Michael Porzio, Blaine Allen, Kathleen Digre, Mark Mifflin and Rob Singleton; Salt Lake City, UT M1449 Abundant FUS-Immunoreactive Pathology in the Skin in Sporadic Amyotrophic Lateral Sclerosis Seiitsu Ono, Takahiko Yamano, Hirotsugu Mikami, Takeshi Watanabe, Tomomi Tsukie, Hiroyuki Fukazawa, Kazuhiro Higashida, Yoshihiko Oketa, Hiroaki Ishikawa, Kanako Yasui, Makoto Nomura and Megumi Suzuki; Ichihara, Chiba, Japan M1460 In Sensory Neuropathy Contact Heat Evoked Potential Stimulation (CHEPS) Small Fiber Conduction Velocity (CV) Is Faster in Peripheral Than in Central Spinothalamic Pathways Benn E. Smith, Mark A. Ross, Brent P. Goodman, E.P. Bosch and Lyell K. Jones, Jr; Scottsdale, AZ and Rochester, MN M1450 Brown Sequard Syndrome as an Initial Manifestation of Idiopathic Spinal Cord Herniation Dipakkumar P. Pandya, Anery Patel, Jennie Luna, Megan McGarry, Sourav Sen and Gaetan Moise; Paterson, NJ M1461 Bortezomib Alters Microtubule Localization and Mitochondrial Dynamics in Rat Dorsal Root Ganglion Neurons Nathan P. Staff, Jewel L. Podratz, Lukas Grassner, Miranda Lange, Justin Paz, Andrew M. Knight, Charles L. Loprinzi, Eugenia Trushina and Anthony J. Windebank; Rochester, MN M1451 Sub-Regional Dual-Energy X-Ray Absorptiometry (DEXA) Analysis: A Potential Endpoint Measure for Therapeutic Trials in Myotonic Dystrophy Type 1 (DM1) Araya Puwanant, Noya Rackovsky, Jeffrey M. Statland, Katy J. Eichinger, Richard T. Moxley, III and Charles A. Thornton; Rochester, NY M1462 Facioscapulohumeral Dystrophy (FSHD): D4Z4 Fragment Size in Patients with CoatвЂ™s Syndrome Jeffrey M. Statland and Rabi Tawil; Rochester, NY M1452 A Recombinant Human Neuron-Binding IgM Promotes Survival and Protects Spinal Cord Anterior Horn Cells in a Transgenic Murine Model of Amyotrophic Lateral Sclerosis Aleksandar Denic, Laurie Zoecklein, Bharath Wootla, Arthur E. Warrington and Moses Rodriguez; Rochester, MN M1463 SMN May Have Multiple Functions Necessitating Widespread Restoration for Maximal Therapeutic Benefit in SMA Tara L. Martinez, Lingling Kong, James P. Van Meerbeke, Rebecca Gibbs, Crystal Davis, Heather L. Plaster, Chien Ping Ko, James R. Rusche, Cathleen M. Lutz, Mark M. Rich and Charlotte J. Sumner; Baltimore, MD; Dayton, OH; Bar Harbor, ME; Waltham, MA and San Diego, CA M1453 A Clinical Study of the Distal Hereditary Motor Neuropathies Alexander M. Rossor, Henry Houlden and Mary M. Reilly; London, United Kingdom M1464 A Multicenter Phase II Open-Label Trial of Valproic Acid and L-Carnitine in Infants with SMA Type I Kathryn J. Swoboda, Kristin Krosschell, Thomas Crawford, Charles Scott, John Kissel, Mary K. Schroth, Gyula Acsadi, Priya Kishnani, Jurgen-Christoph von Kleist-Retzow, Guy DвЂ™Anjou, Edward C. Smith, Bakri Elsheik, Louise R. Simard, Thomas W. Prior and Sandra P. Reyna; Salt Lake City, UT; Chicago, IL; Baltimore, MD; Fort Washington, PN; Columbus, OH; Madison, WI; Detroit, MI; Durham, NC; Cologne, Germany; Montreal, QC, Canada and Winnepeg, MB, Canada M1454 Withdrawn. M1455 Electrical Impedance Alterations in Muscle Induced by Hindlimb Unloading Jia Li, Andrew Spieker, Glenn D. Rosen and Seward B. Rutkove; Boston, MA M1456 SMN Controlled MiR-183 Regulates Neuronal Morphology Via mTOR and Akt1 Min J. Kye, Mary H. Wertz, Bikem Akten, Pierre Neveu, Kenneth S. Kosik and Mustafa Sahin**; Boston, MA; Santa Barbara, CA and Heidelberg, Germany M1465 Fetal Stem Cells in DuchenneвЂ™s Muscular Dystrophy (DMD) Nataliia S. Sych, Mariya O. Klunnyk, Olena V. Ivankova and Iryna G. Matiyaschuk; Kiev, Ukraine M1457 Clinical, Molecular and Muscle Histopathological Features in Myotonic Dystrophy Type 1 (DM1) Associated with Variant CCG Expansions Marcella Masciullo, Massimo Santoro, Giulia Conte, Roberta Pietrobono, Anna Modoni, Maria Laura E. Bianchi, Valentina Rizzo, Maria Grazia Pomponi, Enzo Ricci, Giovanni Neri and Gabriella Silvestri; Rome, Italy M1466 The Survival Motor Neuron (SMN) Gene as a Therapeutic Target in Amyotrophic Lateral Sclerosis Kevin Talbot, Neza Alfazema, Kay E. Davies and Bradley J. Turner; Oxford, United Kingdom and Melbourne, Australia M1458 Metabolic Syndrome Reduces Cutaneous Nerve Regenerative Capacity J. Robinson Singleton, Robin Marcus, Collin J. Arsenault, Michael Porzio, Justin E. Jackson and A. Gordon Smith; Salt Lake City, UT M1467 Quantitative Analysis of FLAIR Images in ALS Has Diagnostic Potential Jez Fabes, Lucy Matthews, Nicola Fillipini, Kevin Talbot, Mark Jenkinson and Martin R. Turner; Oxford, United Kingdom 16 ID: srinivasanv I Black Lining: [ON] I Time: 00:34 I Path: N:/3b2/ANA#/Vol00000/120252/APPFile/JW-ANA#120252 J_ID: ZAY Customer A_ID: BKLT2012_Poster_Sessions Cadmus Art: ANS9 Date: 14-September-12 M1468 Complexity-Based Classification of Resting-State fMRI in Amyotrophic Lateral Sclerosis Tomer Fekete, L. R. Mujica-Parodi and Martin R. Turner; Stony Brook, NY and Oxford, United Kingdom Stage: Page: 17 T1503 From Molecule to Mechanism: How Listening to Synapses Reveals Novel Insights to OCD Pathogenesis Nicole Calakos, Yehong Wan, Meng Chen, Kristen Ade, William Wetsel and Guoping Feng; Durham, NC and Boston, MA M1469 Congenital Amyelinating Neuropathy: A Genetically Heterogeneous Syndrome Jean-Michel Vallat, Pierre-Marie Gonnaud, Philippe Latour, Federico Garcia Bragado and Benoit Funalot; Limoges, France; Pierre Benite, France; Lyon, France and Pamplona, Spain T1504 Brainstem Lesions and Central Auditory Processing Gastone G. Celesia; Chicago, IL T1505 Frequency of Elevated ASO Titer in Children and Adolescents at Onset or Exacerbation of Tic, OCD or Aggression and Symptomatic Effect of Antibiotic Treatment Brittany M. DiVito, Karen D. Ellis and Drake D. Duane; Scottsdale, AZ and Tempe, AZ M1470 Cerebral Metabolic Features of Clinically Heterogenous A3243G Mitochondrial DNA Mutation Carriers: Prognostic Implications Nora Weiduschat, Petra Kaufmann, Xiangling Mao, Kristin Engelstad, Vanessa Battista, Mary Sano, Michio Hirano, Salvatore DiMauro, Darryl C. DeVivo and Dikoma C. Shungu; New York, NY T1506 Modulation and Assessment of the CerebelloCortical Connectivity through Transcranial Magnetic Stimulation (TMS) Combined with Electroencephalography (EEG) Faranak Farzan, Mark A. Halko, Andrea Pousada-Casal, Jeremy D. Schmahmann and Alvaro Pascual-Leone; Boston, MA M1471 The Role for Macrophages in Nerve Repair in an Animal Model of Autoimmune Neuropathy Gang Zhang, Nataliia Bogdanova, Lixia Gao and Kazim A. Sheikh; Houston, TX M1472 Comprehensive Genetic Screening of a Large ALS Cohort Using Pooled-Sample Sequencing Matthew B. Harms, Janet Cady, Peggy Allred, Taha Bali, Ryan T. Libby, Alan Pestronk, John Ravits and Robert H. Baloh; Saint Louis, MO; La Jolla, CA and Los Angeles, CA T1507 Changes in Cortical Functional Connectivity Introduced with Intermittent Theta Burst TMS to the Cerebellum Assessed with fMRI Mark A. Halko, Faranak Farzan, Andrea Pousada-Casal, Jeremy Schmahmann and Alvaro Pascual-Leone; Boston, MA M1473 Optimizing the Total Neuropathy Score for HIV-Associated Distal Symmetric Polyneuropathy Jessica Robinson-Papp, Sandeep Sharma, David M. Simpson and Susan Morgello; New York, NY T1508 PRISM Registry: A Novel Tool To Determine the Prevalence of Pseudobulbar Affect Daniel Kantor, Jonathan Fellus and Randall E. Kaye; Ponte Vedra Beach, FL; Secaucus, NJ and Aliso Viejo, CA M1474 Motor Neuron Disease-Associated Mutations in p150/Glued Disrupt the Initiation of Retrograde Axonal Transport at Synaptic Termini Thomas E. Lloyd, James Machamer, Sarah Collins and Alex L. Kolodkin; Baltimore, MD T1509 Effects of the Dopamine Agonist Rotigotine on Hemispatial Neglect Following Stroke Nikos Gorgoraptis, Yee-Haur Mah, Bjoern Machner, Victoria Singh-Curry, Paresh Malhotra, Maria Hadji-Michael, David Cohen, Robert Simister, Ajoy Nair, Elena Kulinskaya, Nick Ward, Richard Greenwood and Masud Husain; London, United Kingdom; LuВЁbeck, Germany and Norwich, United Kingdom 2012 Annual Meeting Tuesday, October 9, 2012 Poster Session Posters will be displayed in Gloucester, located on the 3rd floor in the Back Bay Hall of the Marriott Copley Place from 11:30 am вЂ“ 7:00 pm, with authors present from 5:30 pm вЂ“ 7:00 pm. NOTE: An asterisk designates a resident/fellow travel award winner. T1510 Sudden Visual Spatial Memory Loss as Presenting Manifestation of CJD Nivedita Jerath, Aarti Jerath, Shelley Waite, Deborah Forst, Shivraj Sohur and Jeremy Schmahmann; Boston, MA T1511 Inflammation and Cognitive Decline in Normal Elderly Joel H. Kramer, Brianne Bettcher, Ralph Green and Josh Miller; San Francisco, CA and Davis, CA Behavioral Neurology T1501 Metabolic Abnormalities in the Caudate in Patients with Mitochondrial Disorders Measured Using Proton Magnetic Resonance Spectroscopy Rebecca Anglin, Patricia Rosebush, Michael Noseworthy, Mark Tarnopolsky and Michael Mazurek; Hamilton, Canada T1512 Acute Impairments of Empathy Richard Leigh and Argye E. Hillis; Baltimore, MD T1513 Evolution of Psychiatric Co-Morbidity in the Transition Phase in a Cohort of Patients with Neurological Perinatal Disability Sara Piccoli, Gianni De Polo and Andrea Martinuzzi; Conegliano, Italy T1502 Antipsychotic Drug Effects at Nicotinic AChRs Studied in a Novel Model System Tai-Xiang Xu, Limin Hao, Bruce M. Cohen and Edgar A. Buttner; Belmont, MA 17 ID: srinivasanv I Black Lining: [ON] I Time: 00:34 I Path: N:/3b2/ANA#/Vol00000/120252/APPFile/JW-ANA#120252 J_ID: ZAY Customer A_ID: BKLT2012_Poster_Sessions Cadmus Art: ANS9 Date: 14-September-12 T1514 fMRI Study of Yogic Meditation Shri K. Mishra, Manbir Singh and Parampreet Singh; Los Angeles, CA and Sylmar, CA Stage: Page: 18 T1602 Analysis of the Development of Allodynia: Correlation between Migraine Duration and Severity Biao Lu, Xiaodong Li, Songyang Zhao, Emilee Connors and Shashidhar Kori; Mountain View, CA T1515 Withdrawn. T1603 Is Lack of Habituation of Somatosensory Evoked Potential (SEP) a Biological Marker of Migraine? Jayantee Kalita, Sanjeev K. Bhoi and Usha K. Misra; Lucknow, UP, India T1516 A Randomised Controlled Trial of Cognitive Behaviour Intervention for Impulse Control Behaviours Affecting ParkinsonвЂ™s Disease Patients and Their Caregivers David Okai, Sally Askey-Jones, Michael Samuel, Sean S. OвЂ™Sullivan, Ray Chaudhuri, Anne Martin, Joel Mack, Richard G. Brown and Anthony David; London, United Kingdom; Ashford, United Kingdom and Portland, OR T1604 Dextromethorphan Plus Quinidine for Headache Prophylaxis: The First Case Report Daniel Kantor; Ponte Vedra, FL T1517 Characteristics of Subjects with Chronic Low Back Pain-Related Neuropathic Pain (CLBP-NeP) in the US: BEAT Neuropathic Pain Observational Study Alesia Sadosky, Caroline Schaefer, Bruce Parsons, Rebecca Baik, Rachael Mann, Felicia Bergstrom, Gergana Zlateva, Brett Stacey, Srivinas Nalamachu, Michael Tuchman and Edward Nieshoff; New York, NY; Gaithersburg, MD; San Diego, CA; Portland, OR; Leawood, KS; Palm Beach Gardens, FL and Detroit, MI T1605 Sustained Pain Relief with Dihydroergotamine in Migraine Is Potentially Due to Persistent Binding to 5-HT1B/5-HT1D Receptors Shashidhar Kori, Jian Zhang, Donald Kellerman, Thomas Armer and Peter J. Goadsby; Mountain View, CA and San Francisco, CA T1606 Valsalva Test Responses in Cough Headache Patients Russell J.M. Lane and Paul T.G. Davies; London, United Kingdom and Oxford, United Kingdom T1518 Characteristics of Subjects with Painful Diabetic Neuropathy (PDN) in the US: BEAT Neuropathic Pain Observational Study Felicia Bergstrom, Rachael Mann, Alesia Sadosky, Bruce Parsons, Caroline Schaefer, Rebecca Baik, Gergana Zlateva, Brett Stacey, Srivinas Nalamachu, Edward Nieshoff and Michael Tuchman; Gaithersburg, MD; San Diego, CA; New York, NY; Portland, OR; Leawood, KS; Detroit, MI and Palm Beach Gardens, FL T1607 Comparative Efficacy of Triptans for the Abortive Treatment of Migraine: A Multiple Treatment Comparison Meta-Analysis (MTC) Edward J. Mills, Kristian Thorlund, Ping Wu and Anjan Chatterjee; Ottawa, ON, Canada; Hamilton, ON, Canada and New York, NY T1519 Increased Phosphorylation of the MAPK/ERK Pathway Is Associated with Social Impairment in BTBR Mice Alireza Faridar, Dorothy M. Jones-Davis, Mu Yang, Adam M. Katz, Michael D. Weber, Eric Rider, Saunak Sen, Jacqueline Crawley and Elliott H. Sherr; San Francisco, CA and Bethesda, MD T1608 Repetitive Transcranial Magnetic Stimulation (rTMS) Results in Elevation of b Endorphin Level and Relief of Migraine Headache Usha K. Misra, Jayantee Kalita, Gyanesh M. Tripathi and Sanjeev K. Bhoi; Lucknow, UP, India T1520 Stepwise Onset of Memory Impairment, Encephalopathy and Hearing Loss Presenting as Susac Syndrome Alvin Shrestha, Tatiana Mihalova, Daniel Burns and Mark Willmot; Birmingham, United Kingdom T1609 Alice in Wonderland Syndrome: Epilepsy, Migraine or Both? W.O. Pickrell, R.H. Thomas, J.A. Johnston, C.P. White and M.I. Rees; Swansea, United Kingdom and Cardiff, United Kingdom T1521 The Effect of a Family History of Major Depression on the Outcome of Electroconvulsive Therapy Ceri A. Smith; Cardiff, Wales, United Kingdom T1610 Analysis of EEG and MRI for Localization of Structures Affected in Temporal Lobe Epilepsy Ildefonso RodrД±Вґguez-Leyva, Ana A. RenterД±Вґa Palomo, Luis Concha-Loyola and Adriana MartД±Вґnez-Mayorga; San Luis Potosi, Mexico T1522 Syphilitic Polyradiculoneuropathy in an Immunocompetent Patient Safaa Zahlane, Nissrine Louhab and Najib Kissani; Marrakesh, Morocco T1611 Direct Conversion of Fibroblasts into Functional Nociceptors Brian J. Wainger, Amy J. Wang, Lee Barrett, Justin Ichida, Qiufu Ma, Lee L. Rubin, Kevin Eggan and Clifford J. Woolf; Boston, MA and Cambridge, MA Headache and Pain/Neuro-otology T1601 Lidocaine Desensitizes TRPA1 Receptors in Human Sural Nerves Anupam Bhattacharjee, Lionel Ginsberg, Richard Orrell, Saqiba Jadoon and Reginald Docherty; London, United Kingdom T1612 The Prevalance of Anxiety and Depression in Migraine Patients Hakan Balibey, Halit Yasar, Nalan Bayar and Hakan Tekeli; Ankara, Turkey and Istanbul, Turkey 18 ID: srinivasanv I Black Lining: [ON] I Time: 00:34 I Path: N:/3b2/ANA#/Vol00000/120252/APPFile/JW-ANA#120252 J_ID: ZAY Customer A_ID: BKLT2012_Poster_Sessions Cadmus Art: ANS9 Date: 14-September-12 Stage: Page: 19 T1713 Identification of Axonal Transport Biomarkers in ParkinsonвЂ™s Disease Christine W. Chadwick, Michael J. Aminoff, Po- Yin A. Wong, Kristofor H. Husted, Shanshan Liu, Victoria M. Liu, Lori A. Kohlstaedt, Johan Protasio, Timothy Riff, Drina Boban, Maudi Killian, Lorrie Epling, Elisabeth Sinclair, Julia Peterson, Richard Price, Marc K. Hellerstein and Patrizia Farnara; San Francisco; Emeryville, CA and Berkeley Movement Disorder T1701 PARK2 Mutant hiPSC-Derived Neural Progenitors Exhibit Altered Sensitivity and Mitochondrial Dysfunction to Neurotoxic Metal Exposure Asad A. Aboud, Andrew M. Tidball, Kevin K. Kumar, M. Diana Neely, Michael Litt, Peter Hedera, Charles C. Hong, Kevin C. Ess and Aaron B. Bowman; Nashville, TN T1714 Predictors of Cognitive Performance Following Bilateral Subthalamic Nucleus Deep Brain Stimulation Lidia Yaguez, Angela Costello, John Moriarty, Natasha Hulse, Richard Selway, Chris Clough, Michael Samuel and Keyoumars Ashkan; London, United Kingdom and Kent, United Kingdom T1702 Amyloid Profiles of Subjects with Lewy Body Disease Rizwan S. Akhtar, Laura Brennan, Daniel Weintraub and Andrew D. Siderowf; Philadelphia, PA T1703 Reversal of Levodopa-Induced Dyskinesia Mathew Alias and Mohamed Hassan; Farmington, CT T1715 What Patient Factors Associate with Inaccuracies in Reporting of Parkinsonian Signs? Nabila Dahodwala, Andrew Siderowf and Jason Karlawish; Philadelphia T1704 L-Dopa Induced Dystonia, Dyskinesia in Juvenile ParkinsonвЂ™s Disease Sarah M. Misbah El-Saadig; Khartoum, Sudan T1716 Previously Unspecified SETX Mutation Producing AOA2 in Two Siblings Neil Datta and Anna Hohler; Boston, MA T1705 Amelioration of Somatic and Autonomic Neuropathy in Patients with Idiopathic ParkinsonвЂ™s Disease Following Cobalamin Therapy Sabrina Apel and Cory Toth; Calgary, AB, Canada T1717 Directional EEG Connectivity Method Demonstrates Complex, Reciprocal Information Flows during Praxis Performance Joshua B. Ewen, Balaji M. Lakshmanan, Stewart H. Mostofsky, Nathan E. Crone and Anna Korzeniewska; Baltimore, MD T1706 Low Frequency DBS in PD Patients with Gait and Speech Problems Diana Apetauerova, Janet W. Zani and Stephanie A. Scala; Burlington, MA T1718 Clinical Assessment of the Effect of Tetrabenazine on Motor Function in Moderate Huntington Disease Robert Fekete, Anthony Davidson and Joseph Jankovic; Valhalla, NY and Houston, TX T1707 Chronic Parkinsonism Associated with Liver Cirrhosis Diana Apetauerova, Peter G. Hildenbrand, Janet W. Zani and Stephanie A. Scala; Burlington, MA T1719 Identification of Individualized Cortical Targets for Focal Brain Stimulation Based on Intrinsic Functional Connectivity Michael D. Fox, Randy L. Buckner and Alvaro Pascual-Leone; Boston, MA T1708 A Genetic Study of Wilson Disease in the UK Oliver Bandmann, Alison Coffey, Magnus Rattray and Ann Dalton; Sheffield, United Kingdom and Cambridge, United Kingdom T1709 Metronidazole-Induced Reversible Ataxia and Numbness Chirantan Banerjee, Fazeel Siddiqui and Jessica Lee; Dallas, TX T1720 Does Iron Play Different Roles in Various Neurodegenerations? Andrzej Friedman and Jolanta Galazka-Friedman; Warsaw, Poland T1710 Striatal Functional Connectivity during Rest in ParkinsonвЂ™s Disease Brian D. Berman, Erika Shelton, Mark Hallett and Tor Wager; Denver, CO; Bethesda, MD and Boulder, CO T1721 Asymmetric Upper Motor Neuron Disease (MillsвЂ™ Syndrome) Presenting as Corticobasal Syndrome Shinsuke Fujioka, Masataka Nakamura, Melissa E. Murray, Zbigniew K. Wszolek and Dennis W. Dickson; Jacksonville, FL T1711 Short Hairpin RNA Targeting Endogenous a-Synuclein Prevents Degeneration of Dopaminergic Neurons in the Rat Rotenone Model of ParkinsonвЂ™s Disease Jason R. Cannon, Qing Bai, Maxx Horowitz, Victor Tapias, J. Timothy Greenamyre and Edward A. Burton; Pittsburgh, PA and West Lafayette, IN T1722 Progressive Ataxia and Palatal Tremor Syndrome (PAPTS): Clinical and Radiological Findings Pablo Garcia-Reitboeck, Marie-Helene Marion and Salah Omer; London, United Kingdom T1712 Effect of Deep Brain Stimulation on Autonomic Function in Early ParkinsonвЂ™s Disease Anna L. Molinari, Fenna T. Phibbs, Lily Wang, Yanna Song, Amanda Currie, Maxim Turchan, Danielle S. Cherdak and David Charles; Nashville, TN T1723 Progressive Bilateral Parkinsonism Secondary to a Unilateral Midbrain Lesion Maiya R. Geddes, A. Jon Stoessl, Alain Dagher, Jean-Paul Soucy and Anne-Louise Lafontaine; Montreal, QC, Canada and Vancouver, BC, Canada 19 ID: srinivasanv I Black Lining: [ON] I Time: 00:34 I Path: N:/3b2/ANA#/Vol00000/120252/APPFile/JW-ANA#120252 J_ID: ZAY Customer A_ID: BKLT2012_Poster_Sessions Cadmus Art: ANS9 Date: 14-September-12 Stage: Page: 20 T1735 Randomized, Double-Blind, Double-Dummy Study of Levodopa-Carbidopa Intestinal Gel in Patients with Advanced ParkinsonвЂ™s Disease: Functional and Quality-of-Life Outcomes K. Kieburtz, A. Antonini, C.W. Olanow, H.H. Fernandez, A.J. Espay, D.G. Standaert, S. Hass, K. L. Widnell, W.Z. Robieson, Y. Pritchett, K. Chatamra and J. Benesh; Rochester, NY; Padua, Italy; New York, NY; Cleveland, OH; Cincinnati, OH; Birmingham, AL and Abbott Park, IL T1724 Rapid Onset Dystonia-Parkinsonism Associated with the I758S ATP1A3 Mutation: A Neuropathologic Study of Three Affected Siblings Bernardino Ghetti, Matthew C. Hagen, Joseph Maldjian, Christopher T. Whitlow, Laurie J. Ozelius, Kathleen J. Sweadner and Allison Brashear; Indianapolis, IN; Cincinnati, OH; Winston-Salem, NC; New York, NY and Boston, MA T1725 Alcoholic Cerebellar Degeneration: Not All Due to Alcohol Marios Hadjivassiliou, Stuart Currie, David Sanders and Nigel Hoggard; Sheffield, United Kingdom T1736 Videotape Assessments of Psychogenic Movement Disorders Subjects Following Immediate Versus Delayed Treatment with Short Term Psychodynamic Psychotherapy: Randomized Parallel Trial Katie Kompoliti, Vanessa K. Hinson, Burgess Wilson and Glen T. Stebbins; Chicago, IL and Charleston, SC T1726 GABA Receptor Changes and Functional Connectivity Abnormalities in Focal Hand Dystonia Cecile Gallea, Priyantha Herath, Valerie Voon, Alicja Lerner and Mark Hallett; Bethesda, MD T1737 Binding of the Alpha-Synuclein Radioligand SIL-23 Reflects the Level of Aggregated Alpha-Synuclein in ParkinsonвЂ™s Disease Brain tissue Paul T. Kotzbauer, Devika Bagchi, Maria Udan, Lihai Yu, Robert H. Mach and Zhude Tu; St. Louis, MO T1727 What Issues Face ParkinsonвЂ™s Patients at Ten Years and beyond? Anhar Hassan, Samuel Wu, Peter Schmidt, Irene A. Malaty, Yun Feng Dai, Janis Miyasaki and Michael S. Okun; Gainesville, FL; Miami, FL and Toronto, Canada T1738 An Unexpected Cause of Altered Mental State in a Presumed Healthy Caucasian Male Tobias B. Kulik and Irene H. Richard; Rochester, NY T1739 Withdrawn. T1728 Dysphagia i Spinocerebellar Ataxia Type 3 and Type 6 Chiharu Isono, Makito Hirano, Hikaru Sakamoto, Shuichi Ueno, Susumu Kusunoki and Yusaku Nakamura; Sakai, Osaka, Japan and Osakasayama, Osaka, Japan T1740 An Unsupported Exploratory Clinical Trial on Tremor Gian L. Lenzi, Laura Troilo and Francesca Puledda; Rome, Italy T1741 4-aminopyridine for Gait Dysfunction in ParkinsonвЂ™s Disease Corneliu C. Luca and Carlos Singer; Miami, FL T1729 Multiple System Atrophy with Inappropriate Secretion of Antidiuretic Hormone Makoto Samukawa, Makito Hirano, Hikaru Sakamoto, Mari Kitada, Susumu Kusunoki and Yusaku Nakamura; OsakaSayama, Osaka, Japan and Sakai, Osaka, Japan T1742 Risk Factors for Cardiac Arrhythmia and Syncope through QTc Prolongation in ParkinsonвЂ™s Disease Naveed Malek, Katherine A. Grosset, David Stewart, Graeme J. Macphee and Donald G. Grosset; Glasgow, United Kingdom T1730 Higher Iron in the Red Nucleus Marks ParkinsonвЂ™s Dyskinesia Mechelle M. Lewis, Guangwei Du, Michal Kidachi, Nisargkumar Patel, Michele L. Shaffer, Richard B. Mailman and Xuemei Huang; Hershey, PA T1743 Effects of Green Tea Extract (GTE) on Haloperidol (HAL) Induced Neuroleptic Anxiety Syndrome (NAS) in Rat Model of Extrapyramidal Syndrome (EPS) Tafheem Malik and Darakhshan J. Haleem; Karachi, Sind, Pakistan T1731 Side of ParkinsonвЂ™s Disease Onset Predicts Gray Matter Loss and Cognitive Impairments Suman Sen, Paul J. Eslinger, Daymond Wagner, Michele L. Shaffer, Mechelle M. Lewis, Guangwei Du and Xuemei Huang; Hershey, PA T1744 Innovative Web-Based Matching Service, Fox Trial Finder, as a Mechanism To Improve Clinical Trial Recruitment Claire C. Meunier, Sohini Chowdhury, Todd Sherer and Deborah W. Brooks; New York, NY T1732 Patient Expectations and Outcome after DBS Nasrin Esnaashari, Jospehine Hwu, Jennifer S. Hui and Daniel Togasaki; Los Angeles, CA T1733 Lewy Body Negative Idiopathic Parkinsonism Fariha Zaheer, John T. Slevin, Erin L. Abner, Peter T. Nelson and Gregory A. Jicha; Lexington, KY T1745 LIVECHART: A System for Recording, Evaluating and Monitoring Botulinum Toxin Treatments for Any Condition Austen P. Moore; Liverpool, Merseyside, United Kingdom T1734 Comparison of In Vivo PET with In Vitro Measures of Pre-Synaptic Nigrostriatal Neurons Morvarid Karimi, LinLin Tian, Christopher A. Brown, Hubert P. Flores, Susan K. Loftin, Tom O. Videen, Steve M. Moerlein and Joel S. Permutter; St. Louis, MO T1746 C9ORF72 Hexanucleotide Repeat Expansion Analysis in Patients with ParkinsonвЂ™s Disease Joanne D. Stockton, Catriona Moorby, Rachel V. Denyer, Caroline Rick, Keith Wheatley, Carl E. Clarke and Karen E. Morrison; Birmingham, United Kingdom 20 ID: srinivasanv I Black Lining: [ON] I Time: 00:34 I Path: N:/3b2/ANA#/Vol00000/120252/APPFile/JW-ANA#120252 J_ID: ZAY Customer A_ID: BKLT2012_Poster_Sessions Cadmus Art: ANS9 Date: 14-September-12 T1747 Cannabinoid CB2 Receptor Gene and Protein Expression Differences in ParkinsonвЂ™s Disease PostMortem Brain Samples and Lymphocytes from Recently Diagnosed and Non-Treated Patients Francisco Navarrete, MarД±Вґa Salud GarcД±Вґa-GutieВґrrez, JoseВґ Antonio Molina, Carlos Leiva and Jorge Manzanares; San Juan de Alicante, Spain; Madrid, Spain and Alicante, Spain Stage: Page: 21 T1754 Role of the Subthalamic Nucleus in Modulating Cognitive Functions. A Viewpoint Based on Recordings from DBS Electrodes Ivan Rektor, Marek BalaВґz, Martina BockovaВґ and Irena Rektorova; Brno, Czech Republic T1755 The AddenbrookeвЂ™s Cognitive Examination in Parkinsonian Disorders at Baseline and 18 Months Timothy Rittman, Boyd C.P. Ghosh, Jonathan R. Evans, Peter McColgan, David P. Breen, Roger A. Barker and James B. Rowe; Cambridge, Cambridgeshire, United Kingdom T1748 Randomized, Double-Blind, Double-Dummy Study of Levodopa-Carbidopa Intestinal Gel in Patients with Advanced ParkinsonвЂ™s Disease: Efficacy and Safety C.W. Olanow, A. Antonini, K. Kieburtz, H.H. Fernandez, A.J. Espay, D.G. Standaert, A. Vanagunas, K. L. Widnell, S. Freeman, W.Z. Robieson, Y. Pritchett, K. Chatamra, J. Benesh and R.A. Lenz; New York, NY; Padua, Italy; Rochester, NY; Cleveland, OH; Cincinnati, OH; Birmingham, AL; Chicago, IL and Abbott Park, IL T1756 Alpha-Synuclein Expression in the Epidermis and Epithelial Tissue in Parkinsonism Ildefonso Rodriguez-Leyva, Ana Laura Calderon-GarciduenЛњas, Ana Arely Renteria-Palomo, Rodrigo Valdez-Rodriguez, Julio Sepulveda and Juan Pablo Castanedo-Cazares; San Luis PotosД±Вґ, Mexico; Jalapa, VER, Mexico and Monterrey, NL, Mexico T1757 Paradigm for Neuroprotection in Presymptomatic HuntingtonвЂ™s Disease H. Diana Rosas, Gheorghe Doros, Sona Gevorkian, David H. Salat, Martin Reuter, Bruce Fischl, Keith Malarick, Wayne R. Matson, Clemens R. Scherzer, Robert J. Ferrante and Steven M. Hersch; Charlestown, MA; Boston, MA; Bedford, MA; Cambridge, MA and Pittsburgh, PA T1749 A Prospective, Observational Trial Evaluating Xeomin (incobotulinumtoxinA) for Cervical Dystonia (CD) or Blepharospasm in the United States вЂ“ Preliminary Baseline Results on the Health Impact of CD on Patients Using the Cervical Dystonia Impact Profile (CDIP) Joseph Jankovic, Madhavi Thomas, Alberto Vasquez, Kapil D. Sethi, Amit Verma, Eric J. Pappert and Hubert H. Fernandez; Houston, TX; St. Petersburg, FL; Greensboro, NC and Cleveland, OH T1758 Withdrawn. T1759 Diagnostic Error in Primary Torsion Dystonia Caroline M. Tanner, Stephen K. Van Den Eeden, Samuel Goldman, Raymond Y. Lo, Connie Marras, Kathleen B. Albers, Amethyst D. Leimpeter, Robin Fross, Kathleen Comyns, Zhuqin Gu, Robin Smit, Annelie de Kleijn, Laurie Ozelius, Susan Bressman, Rachel Saunders-Pullman, Cynthia Comella, Lorene M. Nelson and Jeffrey Klingman; Sunnyvale, CA; Oakland, CA; Taiwan, Taiwan; Toronto, ON, Canada; BeiJing, China; Nijmegen, Netherlands; New York City, NY; Chicago, IL and Palo Alto, CA T1750 A Prospective, Observational Trial Evaluating Xeomin [IncobotulinumtoxinA] for Cervical Dystonia or Blepharospasm in the US вЂ“ Preliminary Baseline Results for Patients with Blepharospasm Mark S. LeDoux, Joseph Jankovic, Kapil D. Sethi, Amit Verma, Eric J. Pappert and Hubert H. Fernandez; Memphis, TN; Houston, TX; Greensboro, NC and Cleveland, OH T1751 A Prospective, Observational Trial Evaluating Xeomin [IncobotulinumtoxinA] for Cervical Dystonia (CD) or Blepharospasm in the United States вЂ“ Preliminary Baseline Results for Patients with CD Daniel D. Truong, Fabio O. Danisi, Kapil D. Sethi, Amit Verma, Eric J. Pappert and Hubert H. Fernandez; Fountain Valley, CA; Kingston, NY; Greensboro, NC and Cleveland, OH T1760 Analysis of Wave III of Brain Stem Auditory Evoked Potential during Microvascular Decompression of Cranial Nerve VII for Hemifacial Spasm Balaji Krishnaiah, Parthasarathy D. Thirumala, Miguel Habeych, Donald Crammond and Jeffrey Balzer; Pittsburgh, PA T1752 Rapid Generation of iPSCs from Lymphoblastoid Cell Lines Using an Episomal Plasmid Containing Multi-Reprogramming Factors in a Single Cassette Sharan Paul, Warunee Dansithong, Karla Figueroa and Stefan M. Pulst; Salt Lake City, UT T1761 Establishing Baseline Values for Brainstem Auditory Evoked Potentials (BAEP) during Microvascular-Decompression for Hemifacial Spasm Santhosh Kumar Mohanraj, Parthasarathy D. Thirumala, Miguel Habeych, Donald Crammond and Jeffrey Balzer; Pittsburgh, PA T1753 Is Psychiatric Disease a Core Phenotype of Myoclonus Dystonia Syndrome Caused by SGCE Mutations? Kathryn J. Peall, Manju A. Kurian, Mark Wardle, Martin Smith, Hardev Pall, Jean-Pierre Lin, Tammy Hedderly, Alan Whone, Cathy White, Andrew Lux, Adrian J. Waite, Michael Samuel, Timothy Lynch, Patrick F. Chinnery, George Kirov, Mary King, Derek J. Blake, Huw R. Morris, Daniel J. Smith and Michael J. Owen; Cardiff, United Kingdom; London, United Kingdom; Birmingham, United Kingdom; Bristol, United Kingdom; Swansea, United Kingdom; Dublin, Ireland and Newcastle, United Kingdom T1762 Proteomic Analysis of Serum Microvesicles in ParkinsonвЂ™s Disease Paul R. Tomlinson, Samuel Evetts, Michele Hu, Chris Gradner, Benedikt Kessler, Kevin Talbot and George K. Tofaris; Oxford, United Kingdom T1763 Examining Memory Subtypes in HuntingtonвЂ™s Disease Using the Montreal Cognitive Assessment Charles P. Van Liew, Shea Gluhm, Daniel Brown, Jody L. Goldstein and Jody Corey-Bloom; San Diego, CA 21 ID: srinivasanv I Black Lining: [ON] I Time: 00:34 I Path: N:/3b2/ANA#/Vol00000/120252/APPFile/JW-ANA#120252 J_ID: ZAY Customer A_ID: BKLT2012_Poster_Sessions Cadmus Art: ANS9 Date: 14-September-12 T1764 Inhibitory Neurons In the Ventral Medial Medulla Modulate Gait and Tone Veronique G. VanderHorst, Brian Ellison and Clifford B. Saper; Boston, MA Stage: Page: 22 T1774 Evaluation of Smelling Function, F-DOPA PET Study and Transcranial Sonography of Substantia Nigra in Asymptomatic Carriers of Common LRRK2 Risk Variants: A Longitudinal Case-Control Study Ruey-Meei Wu, Chin-Yi Yu, Kai-Yuan Tzen and Meng-Ling Chen; Taipei, Taiwan T1765 Genetic Association Studies (Single Nucleotide Polymorphisms) in South Indian ParkinsonвЂ™s Disease Patients and Controls Padmaja M. Vishwanathan, Devaprasad Markandeyan, Meenakshi Jayaraman, Srikumari C.R. Srisailapathy, Bhanu K. Murthy, Srinivasan A. Venkatesan and Ramesh Arabandi; Chennai, Tamilnadu, India and Chennai, Tamil Nadu, India T1775 Modulation of 14-3-3 Proteins in the MPTP ParkinsonвЂ™s Disease Model Huiping Ding, Sunny Slone and Talene Yacoubian; Birmingham, AL T1766 REM Sleep without Atonia and Freezing of Gait in ParkinsonвЂ™s Disease Aleksandar Videnovic, Clare C. Marlin, Joni Planetta, Laila Alibiglou, David E. Villancourt and Colum D. MacKinnon; Chicago, IL and Gainesville, FL T1776 Short Latency Afferent Inhibition: A Biomarker for Mild Cognitive Impairment in ParkinsonвЂ™s Disease? Alison J. Yarnall, Lynn Rochester, Rachel David, Tien K. Khoo, Gordon W. Duncan, Brook Galna, Mark R. Baker and David J. Burn; Newcastle, United Kingdom T1767 Clinical and Immunological Features with Glycine Receptor Antibodies Angela Vincent, M. Isabel Leite, Alexander Carvajal, Patrick Waters and Mark Woodhall; Oxford, United Kingdom T1777 Normal Striatal D1 Dopamine Receptor Binding in Primary Focal Dystonias Morvarid Karimi, Joanne Markham, Hubert Flores, Stephen Moerlein, Tom Videen and Joel S. Perlmutter; St. Louis, MO T1778 Dopaminergic Modulation of Basal Ganglia Connectivity in ParkinsonвЂ™s Disease Kathleen L. Poston, William Shire, Richard Joseph, Vinod Menon and Michael Greicius; Stanford, CA T1768 Short Latency Cortical Activation during Clinically Effective Ventral Intermediate Nucleus Deep Brain Stimulation for Essential Tremor Harrison C. Walker, He Huang, Christopher L. Gonzalez, James E. Bryant, Jeffrey Killen, Robert C. Knowlton, Erwin B. Montgomery, Gary C. Cutter, Abidin Yildirim, Barton L. Guthrie and Ray L. Watts; Birmingham, AL T1779 Alpha Synuclein as a Cutaneous Biomarker of Parkinson Disease Christopher H. Gibbons, Ningshan Wang and Roy Freeman; Boston, MA T1769 Can Proton and Phosphorus MR Spectroscopy Be Used for Early Diagnosis in ParkinsonвЂ™s Disease? Nora Weiduschat, M. Flint Beal, Xiangling Mao, Melissa J. Nirenberg, Dikoma C. Shungu and Claire Henchcliffe; New York, NY T1780 Circadian Rhythm of Melatonin Secretion Is Altered in ParkinsonвЂ™s Disease Aleksandar Videnovic, Angelica Marconi, Charleston Noble, Katherine Reid, Teresa Kuhta, Tanya Simuni, Cindy Zadikoff and Phyllis Zee; Chicago, IL T1770 Structural Abnormalities in the Brain Associated with Rapid Onset Dystonia-Parkinsonism: A Preliminary Investigation Christopher T. Whitlow, Allison Brashear, Bernardino Ghetti, Matthew C. Hagen, Kathleen J. Sweadner and Joseph A. Maldjian; Winston-Salem, NC; Indianapolis, IN; Cincinnati, OH and Boston, MA Autoimmune Neurology T1801 A Case of Bilateral Horizontal Gaze Ophthalmoplegia: The 1Гѕ1 Syndrome Nadeem Akhtar and Sumeet Singhal; Nottingham, United Kingdom T1771 MRI Comparison of Primary Progressive Apraxia of Speech and PSP Jennifer L. Whitwell, Joseph R. Duffy, Edythe A. Strand, Mary M. Machulda, Matthew L. Senjem, Jeffrey L. Gunter, Kejal Kantarci, Scott D. Eggers, Clifford R. Jack and Keith A. Josephs; Rochester, MN T1802 Chronic Microglial Encephalomyelitis (CME) Allen J. Aksamit, Brian G. Weinshenker and Joseph E. Parisi; Rochester, MN T1803 Elevated IFNa Activity in Patients with a History of Lyme Disease and Persistent Symptoms Elzbieta Jacek, Brian Fallon, Mary K. Crow and Armin Alaedini; New York, NY T1772 Subacute Combine Degeneration of the Cord Due to Functional B12 Deficiency Subhashie Wijemanne, Sui Li and Michal Vytopil; Boston, MA T1804 Anti-NMDA Receptor Antibody Encephalitis Presenting as Acute Psychosis Matthew B. Bevers, Isabel C. Arrillaga-Romany and Bradford C. Dickerson; Boston, MA T1773 MRI Signal Intensity in Dystonic Muscle Kathleen V. Woschkolup, Gonzalo J. Revuelta and Kenneth Spicer; Charleston, SC 22 ID: srinivasanv I Black Lining: [ON] I Time: 00:34 I Path: N:/3b2/ANA#/Vol00000/120252/APPFile/JW-ANA#120252 J_ID: ZAY Customer A_ID: BKLT2012_Poster_Sessions Cadmus Art: ANS9 Date: 14-September-12 T1805 Patients Can Adequately Report Their MS Severity Online; Implications for Online Research Platforms Riley Bove, Timothy Vaughan, Brian C. Healy, Elizabeth Secor, Alexander Musallam, Bonnie Glanz, Howard Weiner, Paul Wicks, Tanuja Chitnis and Philip L. De Jager; Boston, MA and Cambridge Stage: Page: 23 T1816 Intrathecal Autologous Mesenchymal Stem Cell Transplantation in Patients with Amyotrophic Lateral Sclerosis: A Four Year Case Control Follow-Up Study Clementine E. Karageorgiou, Ioanna Chatzi, Athanasia Alexoudi, George Gortzolidis, Elissaios Karageorgiou, Helen Papageorgiou, George A. Tagaris, Theofanis Chatzistamatiou, Aikaterini Stavropoulou-Gioka and Aikaterini StavropoulouGioka; Athens, Greece and Minneapolis T1806 Comparison of Disease Activity in SPMS and PPMS in the Context of Multicenter Clinical Trials Diego Cadavid, Rotem Orbach and Zhenming Zhao; Cambridge, MA and Tal Hashomer, Israel T1817 Chronic Pain as a Manifestation of Potassium Channel-Complex Autoimmunity Christopher J. Klein, Vanda A. Lennon, Paula A. Aston, Andrew McKeon and Sean J. Pittock; Rochester, MN T1807 The MS-STAT Trial: A Phase II Trial of High Dose Simvastatin for Secondary Progressive Multiple Sclerosis (SPMS): Initial Results Jeremy S. Chataway, Ali Alsanousi, Dennis Chan, David MacManus, Kelvin Hunter, Jo Foster, Charles Bangham, David Wilkie, Jennifer Nicholas, Virginia Calder, John Greenwood, Chris Frost and Richard Nicholas; London, United Kingdom and Brighton, United Kingdom T1818 Targeting Innate Receptors with MIS416 Reshaped Autoimmune T Cell Responses and Suppressed CNS Inflammation and Disease Anne C. La Flamme, Gill Webster, David OвЂ™Sullivan, Madeleine White and Sarrabeth Stone; Wellington, New Zealand and Auckland, New Zealand T1819 Treatment of MS with ACTHar Gel вЂ“ Clinical Experience and Case Presentation Gerard M. Lehrer; New York, NY T1808 Seasonal Variation of Relapses in Neuromyelitis Optica Peter Chater-Lea, Joanna Kitley, Liene Elsone, Yoshiki Takai, Anu Jacob, Ichiro Nakashima, M. Isabel Leite, Kazuo Fujihara and Jackie Palace; Oxford, United Kingdom; Liverpool, United Kingdom and Sendai, Japan T1820 Blood Brain Barrier Changes Prior to Lesion Formation in a Primate Model of Multiple Sclerosis Pietro Maggi, Emily Leibovitch, Maria I. GaitaВґn, Jillian Wholer, Govind Nair, Luca Massacesi, Steve Jacobson, Afonso Silva and Daniel S. Reich; Bethesda, MD T1809 PK11195-PET Enhancement in Black Holes Correlates with Disability and Outcome in Progressive Multiple Sclerosis Paolo Giannetti, Marios Politis, Paul Su, Federico E. Turkheimer, Omar Malik, Shiva Keihaninejad, Kit Wu, Richard Reynolds, Richard Nicholas and Paola Piccini; London, United Kingdom T1821 Phase Imaging in Marmoset EAE at 7T Demonstrates Heterogeneity within Focal Lesions Pietro Maggi, Pascal Sati, Emily Leibovitch, Maria I. GaitaВґn, Jillian Wholer, Sheila Macri, Luca Massacesi, Susan Westmoreland, Steve Jacobson, Afonso Silva and Daniel S. Reich; Bethesda, MD and Boston, MA T1810 Withdrawn. T1811 Natal Natalizumab Daniel Lashley, Kevin Gormley and Timothy Harrower; Exeter, United Kingdom T1822 Cognitive Function and Visual outcome Measures in Patients with Early MS Amir H. Maghzi, Laura Julian, Jackie Marcus, Jennifer Graves, Ellen M. Mowry, Rebecca Spain, Ari Green, Michelle K. Mass, Daniel Pelletier and Emmanuelle Waubant; San Francisco, CA; Baltimore; Prtland and New Haven T1812 Brain-Infiltrating Inflammatory Monocytes Injure the Hippocampus and Induce Seizures during Acute Picornavirus Infection of the CNS Charles L. Howe; Rochester, MN T1823 Clinical Information of Four Men with Anti-N-Methyl D-Aspartate Receptor Encephalitis Makoto Samukawa, Makito Hirano, Hikaru Sakamoto, Shuichi Ueno, Toshiharu Maekura, Harutoshi Fujimura, Susumu Kusunoki and Yusaku Nakamura; Osaka-Sayama, Osaka, Japan; Sakai, Osaka, Japan and Toyonaka, Osaka, Japan T1813 Faciobrachial Dystonic Seizures Are Immunotherapy-Responsive and Treatment May Prevent Amnesia Sarosh R. Irani*, Susanne A. Schneider, Rosemary Pettingill, Philippa Pettingill, Bethan Lang, Shelagh J.M. Smith, Michael R. Johnson and Angela Vincent; Oxford, United Kingdom and London, United Kingdom T1824 Connexin Astrocytopathy in Multiple Sclerosis, BaloВґвЂ™s Disease and Neuromyelitis Optica Katsuhisa Masaki, Satoshi O. Suzuki, Takuya Matsushita, Takeshi Matsuoka, Toshihiko Suenaga, Takeshi Tabira, Toru Iwaki and Jun-ichi Kira; Fukuoka, Japan; Nara, Japan and Tokyo, Japan T1814 Withdrawn. T1815 Evaluation of Blood Anti-JCVirus Antibodies of Natalizumab Treated Multiple Sclerosis Patients Themistoklis Kalamatas, Nikolaos Protopapas, Ioannis Doumos, Aimilia Lafioniati, Athina Nella, Anastasios Graigos and Klimentini Karageorgiou; Athens, Attiki, Greece 23 ID: srinivasanv I Black Lining: [ON] I Time: 00:34 I Path: N:/3b2/ANA#/Vol00000/120252/APPFile/JW-ANA#120252 J_ID: ZAY Customer A_ID: BKLT2012_Poster_Sessions Cadmus Art: ANS9 Date: 14-September-12 T1825 The Role of Manganese Enhanced MRI (MEMRI) in TheilerвЂ™s Murine Encephalitis Virus (TMEV) Induced CNS Inflammatory Disease Models Istvan Pirko, Jeffrey Gamez, Emily R. Shearier, Mekala Raman, Aaron J. Johnson and Slobodan I. Macura; Rochester, MN Stage: Page: 24 T1833 Profound Alternating Corticospinal Tract Enhancement in Neuro-BehcetвЂ™s Disease April A. Erwin, Carlo Tornatore and Mark Lin; Washington, DC T1834 Anti-CD52 Therapy in Experimental Autoimmune Encephalomyelitis Michael J. Turner, Nathalie Chretien, Evis Havari, Michael LaMorte, Bruce Roberts, Johanne Kaplan and William M. Siders; Framingham, MA T1826 Pilot Clinical Trial of Eculizumab in AQP4-IgG-Positive NMO Sean J. Pittock**, Andrew McKeon, Jay N. Mandrekar, Brian G. Weinshenker, Claudia F. Lucchinetti and Dean M. Wingerchuk; Rochester, MN and Scottsdale, AZ T1835 MOG Antibodies in Adult and Pediatric Demyelinating Diseases Joanna Kitley, Mark Woodhall, Patrick Waters, M. Isabel Leite, Jackie Palace and Angela Vincent; Oxford, United Kingdom T1827 Growth Factors PDGF and FGF-2 Are Required for Human Recombinant IgM-Mediated Stimulation of Oligodendrocyte Proliferation and Survival Jens O. Watzlawik, Arthur E. Warrington and Moses Rodriguez; Rochester, MN T1836 Serum Proteomic Analysis of a Presymptomatic MS Cohort Mitchell Wallin, Unsong Oh, Julius Nyalwidhe, Thomas Kislinger, O. John Semmes, John Kurtzke, Parisa Coffman and Steven Jacobson; Washington, DC; Richmond, VA; Norfolk, VA; Bethesda, MD and Toronto, ON, Canada T1828 Does вЂ�вЂ�FulminantвЂ™вЂ™ Multiple Sclerosis Exist? Loren A. Rolak and Susan Anderson; Marshfield, WI T1829 Demographic and Clinical Features of Participants in a VA Longitudinal Study of MS Walter Royal, Mitchell Wallin, Terry Lee-Wilk, Heidi Maloni, William J. Culpepper, Joseph Finkelstein, Jong-Chaur Shieh, Michael Levin, Micheline McCarthy, William Tyor, Jonathan Leigh, Min Zhan, Robert Kane and Christopher Bever; Baltimore, MD; Washington, DC; Buffalo, NY; Memphis, TN; Miami, FL; Atlanta, GA and Cleveland, OH T1837 Guillain-BarreВґ Syndrome and Its Association with the 1976 вЂ�Swine FluвЂ™ Immunisation Programme James N.R. Wyatt; Liverpool, United Kingdom T1838 Leveraging Electronic Health Records for Studying Multiple Sclerosis Zongqi Xia, Tianxi Cai, Suchun Cheng, Raul N.G. Perez, Vivian S. Gainer, Shwan N. Murphy, Pei J. Chen, Guergana K. Savova, Katherine P. Liao, Elizabeth W. Karlson, Ashwin N. Ananthakrishnan, Peter Szolovitis, Susanne E. Churchill, Issac S. Kohane, Robert M. Plenge and Philip L. De Jager; Boston, MA; Cambridge, MA and Charlestown, MA T1830 Unusual Presentation of Paraneoplastic StiffPerson Syndrome with Underlying Breast Cancer Alvin Shrestha, Tatiana Mihalova, Daniel Burns, Hannah Jennens and Roland Etti; Birmingham, West Midlands, United Kingdom T1831 The Prevalence of Cardiovascular Risk Factors in Multiple Sclerosis Patients Zohara Sternberg, Christopher Leung, Daniel S. Sternberg and Elad Levy; Buffalo T1839 The First Nationwide Survey of Hypertrophic Pachymeningitis in Japan Tomomi Yonekawa, Katsuhisa Masaki, Takuya Matsushita, Shinya Sato and Jun-ichi Kira; Fukuoka, Japan T1832 Akt1, Not Ak2 or Akt3, Regulates Oligodendrocyte Maturation In Vitro Jennifer A. Minarcik, Mary V. Reid, Morris J. Birnbaum, Chen Po, Judith B. Grinspan and Gihan I. Tennekoon; Philadelphia, PA and Baltimore, MD T1840 Caspr2 Autoantibodies Target CNS and PNS Axons Eric Lancaster, Josep Dalmau and Steven S. Scherer; Philadelphia, PA and Barcelona, Spain 24 ID: srinivasanv I Black Lining: [ON] I Time: 00:34 I Path: N:/3b2/ANA#/Vol00000/120252/APPFile/JW-ANA#120252 J_ID: ZAY Customer A_ID: BKLT2012_WIP_Poster_Sess Cadmus Art: ANA10 Date: 18-September-12 Stage: Page: 25 2012 Annual Meeting Works in Progress Poster Session WIP202 Quantifying Neurologist Outpatient Test Utilization and Costs James F. Burke, Brian Callaghan, Lesli E. Skolarus and Kevin A. Kerber; Ann Arbor, MI Posters will be displayed in Arlington, located on the 3rd floor in the Back Bay Hall of the Marriott Copley Place from 11:30 am вЂ“ 7:00 pm. Authors will be present during the following times: WIP100-WIP1001: Sunday, October 7, 5:30 вЂ“ 7:00 pm WIP1100-WIP1409: Monday, October 8, 5:30 вЂ“ 6:30 pm WIP1500-WIP1804: Tuesday, October 9, 5:30 вЂ“ 7:00 pm The Works in Progress category emphasizes ongoing clinical or basic research of an extraordinary nature, which warrants expediated presentation. These abstracts were selected based on scientific merit, timeliness, and anticipated interest to the membership. Key aspects of research must have been conducted after the regular abstract deadline. NOTE: Two asterisks designates an abstract selected for oral presentation in the Derek Denny-Brown New Member Symposium. Neuro-oncology WIP301 Malignant Glioma Genotyping by CSF 2-Hydroxyglutarate Oncometabolite and IDH1 Mutation Analysis Leonora Balaj, Edwin Lok, Kenneth D. Swanson, John M. Asara, Clark C. Chen, Fred Hochberg, Xandra O. Breakefield and Eric T. Wong; Boston, MA and San Diego, CA WIP302 Genetic Modifiers Affecting Neurofibromatosis (GMAN): Cutaneous Tumor Burden in Neurofibromatosis Type 1 Fawn Leigh, Lan Kluwe, Victor Mautner, Douglas R. Stewart, Conxi Lazaro, Neale Benjamin, Bergen Sarah, Scott R. Plotkin, Alexander Pemov, Jennifer Sloan, Lee Kaplan, Maragaret P. Wallace, Meena Upadhyaya, Ludwine Messiaen, Bruce Korf, Andre Bernards and James Gusella; Boston, IL; Hamburg, Germany; Rockville, MD; Barcelona, Spain; Gainesville, FL; Birmingham, AL and Cardiff, United Kingdom Cerebrovascular Disease WIP101 The Detrimental Effect of Aging on Leptomeningeal Collaterals in Ischemic Stroke Atay Vural, Murat E. Arsava, Erhan Akpinar, Rahsan Gocmen, Seray Akcalar, Kader K. Oguz and Akif M. Topcuoglu; Ankara, Turkey Neurogenetics WIP102 The Association between Non-Alcoholic Fatty Liver Disease and Intracranial Atherosclerotic Disease Hyun-Suk Jung, Byung-Su Kim and Yoon Ho Choi; Seoul, Republic of Korea WIP501 Dark Xavier, Zebrafish Model of MADD Seok-Hyung Kim, Robert Carson, Michael J. Bennett, Sarah A. Scott, H. Alex Brown and Kevin C. Ess; Nashville, TN and Philadelphia, TN WIP103 Hydrogen Sulfide Increases Angiogenesis and Improves Functional Outcome after Stroke Mi-Young Oh, Hyunduk Jang, Wi-Sun Ryu, Seung-Hoon Lee and Byung-Woo Yoon; Seoul, Korea WIP502 Driving Selection Against Heteroplasmic Mitochondrial DNA Mutations by Rapamycin Ying Dai, Kangni Zheng, Joanne Clark, Russell H. Swerdlow, Stefan M. Pulst, James P. Sutton, Leslie A. Shinobu and David K. Simon; Boston, MA; Kansas City, KS; Salt Lake City, UT; Oxnard, CA and Fujisawa, Kanagawa, Japan WIP104 Retinal Microvascular Abnormalities Predict Brain Microvascular Disease Progression: An ARIC Study Thomas C. Hanff, A. Richey Sharrett, Tom H. Mosley, Dean Shibata, David S. Knopman, Ronald Klein, Barbara Klein and Rebecca F. Gottesman; Baltimore, MD; Jackson, MS; Seattle, WA; Rochester, MN and Madison, WI WIP503 Voxel Based Morphometry and Voxel Based Relaxometry in Neuroferritinopathy Michael J. Keogh, Andrew M. Blamire and Patrick F. Chinnery; Newcastle upon Tyne, Tyne and Wear, United Kingdom WIP105 Racial and Ethnic Differences in Post-Stroke Depression among Community Dwelling Adults Lesli Skolarus, Lynda Lisabeth, Lewis Morgenstern, Deborah Levine and Devin Brown; Ann Arbor WIP504 Early Neuropsychiatry Features in Neuroferritinopathy Michael J. Keogh, Baldev Singh and Patrick F. Chinnery; Newcastle upon Tyne, Tyne and Wear, United Kingdom WIP106 Association between TBI and Ischemic Stroke James F. Burke, Jessica L. Stulc, Lesli E. Skolarus, Darin B. Zahuranec and Lewis B. Morgenstern; Ann Arbor, MI Pediatric Neurology WIP801 Anti-NMDA Receptor Encephalitis, a Series of 208 Children Maarten J. Titulaer**, Lindsey McCracken, Thais Armangue, Inigo Gabilondo, Eugenia Martinez-Hernandez, Takahiro Iizuka, Lawrence S. Honig, Susanne Benseler, Myrna R. Rosenfeld, Rita Balice-Gordon, Francesc Graus, Carol Glaser and Josep Dalmau; Barcelona, Spain; Philadelphia, PA; Sagamihara, Japan; New York, NY; Toronto, Canada and Richmond, CA Education WIP201 The Association of Non-Clinical Factors with Head CT Use in Emergency Department Dizziness Visits: A Population-Based Study Kevin A. Kerber, James F. Burke, Lesli E. Skolarus, Brian C. Callaghan, Devin L. Brown, William J. Meurer, Lynda D. Lisabeth, A. Mark Fendrick and Lewis B. Morgenstern; Ann Arbor, MI 25 ID: guganp I Black Lining: [ON] I Time: 08:44 I Path: N:/3b2/ANA#/Vol00000/120253/APPFile/JW-ANA#120253 J_ID: ZAY Customer A_ID: BKLT2012_WIP_Poster_Sess Cadmus Art: ANA10 Date: 18-September-12 WIP802 Tolerability and Efficacy of rTMS in Children with ASD Lindsay M. Oberman, Brittany Irish, Lidya Poni, Alvaro Pascual-Leone and Alexander Rotenberg; Boston, MA Stage: Page: 26 Trauma/Injury WIP1404 Completion and Outcomes of a Phase 1 Intraspinal Stem Cell Transplantation Trial for ALS Eva L. Feldman, Nicholas M. Boulis, Karl Johe, Seward B. Rutkove, Thais Federici, Meraida Polak, Crystal Kelly and Jonathan D. Glass; Ann Arbor, MI; Atlanta, GA; Rockville, MD and Boston, MA WIP1001 Predicting Return to Functional-Independence by 12-15 Months after Severe Traumatic Brain Injury on Discharge from Inpatient-Rehabilitation David S. Kushner, Jasmine Martinez-Barrizonte and Myrlynn Delille; Miami, FL WIP1405 Congenital Myasthenic Syndrome (CMS), Autophagic Myopathy, and Cognitive Dysfunction Caused by Mutations in DPAGT1 Duygu Selcen**, XinMing Shen, Ying Li, Eric Wieben and Andrew G. Engel; Rochester, MN and Rochester Dementia and Aging WIP1406 Withdrawn. WIP1101 Dementia Hospital Length-of-Stay and Cost Leslie S. Wilson; San Francisco, CA WIP1407 Withdrawn. WIP1408 DNA Replication, but Not Chromosomal Unequal Exchange, as an Alternative Mechanism That Results in CMT1A Mutation Brett A. Parker, Ryan Alexander, Xingyao Wu, Michael Shy, Nathalie Schnetz-Boutaud, Jonathan Haines, Jun Li and Bryan Burnette; Nashville, TN and Iowa City, IA WIP1102 The Auditory Event-Related Oscillations Are Diminished, and Correlate with Hippocampal Volumetry in Mild Cognitive Impairment Gorsev G. Yener, Pinar Kurt, Berrin Cavusoglu, Derya D. Emek, Gulsah Aktas, Emel Ada, Bahar Guntekin and Erol Basar; Izmir, Turkey and Istanbul, Turkey WIP1409 Prevalence of Small-Fiber Polyneuropathy in Fibromyalgia Anne Louise Oaklander, Daniela Herzog, Heather Downs and Siena Napoleon; Boston, MA WIP1103 Biomarkers of Neuroinflammation in Subcortical Ischemic Vascular Disease Gary A. Rosenberg, Yi Yang, Richard R. Reichard, Jillian Prestopnik and John C. Adair; Albuquerque, NM and Albququerque, NM Behavioral Neurology WIP1501 Cognitive Remediation (CR) Combined with Transcranial Magnetic Stimulation (TMS) in AlzheimerвЂ™s Disease (AD) Lukas Schilberg, Anna-Katharine Brem, Catarina Freitas, Natasha Atkinson, Ilya Vidrin, Leonie Asboth, Daniel Z. Press and Alvaro Pascual-Leone; Boston, MA WIP1104 Behavioral Deficits in APP Transgenic Mice Reversed by mGluR Inhibitor with Pro-Neurogenic, Ab-Reducing, and Anxiolytic Properties Sam Gandy, John W. Steele, Star W. Lee, Dane Clemenson, Reto Gadient, Pam Wedel, Charles Glabe, Carrolee Barlow, Michelle Ehrlich, Fred H. Gage and Soong Ho Kim; New York, NY; La Jolla, CA and Irvine, CA Movement Disorder WIP1701 A Diagnostic Questionnaire Discriminates between Psychogenic and Neurogenic Movement Disorders David S. Glosser, Nathan A. Taylor, Lori Sheehan, Daniel Kremens and Tsao-Wei Liang; Philadelphia, PA WIP1105 Transcranial Magnetic Stimulation of Deep Brain Regions in AlzheimerвЂ™s Disease: A Pilot Study Elissa L. Ash, Veronika Vakhapova, Irena Bova, Ely Simon, Moran Korem, Moran Eldad, Amos D. Korczyn and Avraham Zangen; Tel Aviv, Israel and Beersheva, Israel WIP1702 Resting State Functional Connectivity Pharmaco-MRI of ParkinsonвЂ™s Disease Peter S. Pressman, Darren R. Gitelman and Tanya Simuni; San Francisco, CA and Chicago, IL Neuromuscular Disease WIP1401 Non-Human Primate Model of Amyotrophic Lateral Sclerosis with Cytoplasmic Mislocalization of TDP-43 Takuya Ohkubo, Mio Tajiri, Azusa Uchida, Hiroki Kimura, Nobuyuki Sasaguri, Toshiki Uchihara, Hidehiro Misusawa and Takanori Yokota; Tokyo, Japan and Tsukuba, Japan WIP1703 Distinct Progressive Genotype-Related Neurodegeneration in Spinocerebellar Ataxia Types 1, 3 and 6 вЂ“ A Longitudinal Study Kathrin Reetz, Shahram Mirzazade, Anna Lehmann, Agnes Juzek, Anna Costa, Till K. Hauser, Heike Jacobi, Thomas Klockgether, Jorg B. Schulz and On Behalf of the Ataxia Study Group; Aachen, Germany; TuВЁbingen, Germany and Bonn, Germany WIP1402 Regional Spread of ALS Lesion вЂ“ Multifocal Hits and Local Propagation? Teruhiko Sekiguchi, Tadashi Kanouchi, Kazumoto Shibuya, Yuichi Noto, Masanori Nakagawa, Satoshi Kuwabara, Hidehiro Mizusawa and Takanori Yokota; Tokyo, Japan; Chiba, Japan and Kyoto, Japan WIP1704 Cerebellar Ataxia with Neuronopathy and Bilateral Vestibular Areflexia Syndrome (CANVAS) David J. Szmulewicz, John A. Waterston, Hamish G. MacDougall, Stuart Mossman, Andrew M. Chancellor, Catriona A. McLean, Saumil Merchant, Peter Patrikios, Leslie Roberts, Elsdon Storey and G. Michael Halmagyi; Melbourne, Australia; Sydney, Australia; Wellington, New Zealand; Boston and Brisbane, Australia WIP1403 Miller-Fisher Variant of Guillain-Barre: Is Treatment Cost-Effective? Li Yang, Harrison X. Bai, Li-Ming Tan and Bo Xiao; Changsha, Hunan, China and New Haven, CT 26 ID: guganp I Black Lining: [ON] I Time: 08:44 I Path: N:/3b2/ANA#/Vol00000/120253/APPFile/JW-ANA#120253 J_ID: ZAY Customer A_ID: BKLT2012_WIP_Poster_Sess Cadmus Art: ANA10 Date: 18-September-12 WIP1705 N-Acetylcysteine Increases Cerebral Glutathione as Measured by 7T Magnetic Resonance Spectroscopy in Patients with Gaucher or ParkinsonвЂ™s Disease Mary J. Holmay, Melissa Terpstra, Lisa Coles, Usha Mishra, Matthew Ahlskog, Gulin Oz, James C. Cloyd and Paul J. Tuite; Minneapolis, MN Stage: Page: 27 Autoimmune Neurology WIP1801 Elevated Micro RNAs in Cerebrospinal Fluid of Multiple Sclerosis Patients Contribute to Neuronal Injury Neha Patel, Elliot Choi, Marie Medynets, Scott Newsome, Peter Calabresi, Avindra Nath and Tongguang Wang; Bethesda, MD and Baltimore, MD WIP1706 Changes in D1 Receptor Are Associated with the Potentiation of Response to Levodopa Following Subthalamotomy in Parkinsonian Monkeys Vincent A. Jourdain, Laurent Gregoire, Marc Morissette, Nicolas Morin, Martin Parent and Therese Di Paolo; Quebec, QC, Canada WIP1802 Encephalitis and Antibodies to DPPX, a Regulatory Subunit of Kv4.2 Potassium Channels Anna Boronat, Jeffrey M. Gelfand, Nuria Gresa-Arribas, HyoYoung Jeong, Michael Walsh, Kirk Roberts, Eugenia MartinezHernandez, Myrna R. Rosenfeld, Rita Balice-Gordon, Francesc Graus, Bernardo Rudy and Josep Dalmau; Barcelona, Spain; San Francisco; New York; Brisbane, Australia and Philadelphia WIP1707 A Novel Alpha-Synuclein Missense Mutation in ParkinsonвЂ™s Disease Christos Proukakis, Maria Katsianou, Angelika Hummel, Timothy Brier, Henry Houlden, Jonathan Mark Cooper and Anthony H. Schapira; London, United Kingdom and London, United Kingdom WIP1803 Human Aquaporin 4 281-300 Is the Immunodominant Linear Determinant in the Context of HLA-DRB1*03:01 вЂ“ Relevance for Diagnosing and Monitoring Patients with Neuromyelitis Optica Benjamin Arellano, Rehana Hussain, Tresa Zacharias, Doris Lambracht-Washington and Olaf Stuve; Dallas, TX WIP1708 The Discharge of Striatal Neurons Is Profoundly Altered in Patients with ParkinsonвЂ™s Disease Arun Singh, Lisa F. Potts, Klaus Mewes, Robert Gross, Mahlon R. DeLong and Stella M. Papa; Atlanta, GA WIP1804 Treatment Patterns in Co-Occurring Multiple Sclerosis and Sarcoidosis Dorlan J. Kimbrough, Justin C. McArthur and Carlos A. Pardo; Baltimore, MD 27 ID: guganp I Black Lining: [ON] I Time: 08:44 I Path: N:/3b2/ANA#/Vol00000/120253/APPFile/JW-ANA#120253 J_ID: ZAY Customer A_ID: BKLT2012_CD_Poster_Sessi Cadmus Art: ANA11 Date: 18-September-12 NINDS/ANA Career Development Symposium Poster Session Stage: Page: 28 CD508 Sex Chromosomes Modulate Longevity and Susceptibility to Alzheimer Disease Dena B. Dubal, Nino Devidze, Kurtresha Worden, Daniel Kim, Julie Harris, Gui-Qiu Yu, Jorge Palop, Art Arnold, Bruce Miller and Lennart Mucke; San Francisco, CA and Los Angeles, CA Each year, recipients of K awards are invited to attend the NINDS/ANA Career Development Symposium, designed to provide them with the essential tools to enhance their ability to write successful grant proposals and to obtain grant funding from the NIH and other institutions. The NINDS/ANA Career Development Symposium was set up to foster the success of young members of the faculty who had obtained career development awards (K08, K12, or K23) from the NIH. Career Development posters will be presented during the wine and cheese reception of the Career Development Symposium from 5:00 pm вЂ“ 7:00 pm on Saturday, October 6. The K-awardee participantвЂ™s name is in bold. CD509 Genome-Wide Scan for Copy Number Variation Association with Age at Onset of AlzheimerвЂ™s Disease Kinga Szigeti, Deepika Lal, Yanchun Li, Rachelle S. Doody and Li Yan; Buffalo, NY and Houston, TX CD510 Video-EEG Monitoring of Lithium PilocarpineInduced Status Epilepticus in Postnatal Day 7 Rats Using a Novel Miniature Telemetry System Erika A. Scholl, Andrew Zayachkivsky, Mark J. Lehmkuhle, Fisher H. John, F. E. Dudek and Jeffrey J. Ekstrand; Salt Lake City, UT CD501 Directional EEG Connectivity Method Demonstrates Complex, Reciprocal Information Flows during Praxis Performance Joshua B. Ewen, Anna Korzeniewska, Balaji M. Lakshmanan, Stewart H. Mostofsky and Nathan E. Crone; Baltimore, MD CD511 Leucine Has Anticonvulsant Effects in Acute Seizure Tests Adam L. Hartman, Polan Santos and J. Marie Hardwick; Baltimore, MD CD512 Oxygen-Enhanced MRI: A New Imaging Tool for Localization of Focal Epilepsy and Eloquent Cortex Giridhar P. Kalamangalam, Timothy M. Ellmore, Nelson T. Nelson and Narayana A. Ponnada; Houston, TX CD502 Genetic Variants on 9p21.3 Are Associated with Brain Arteriovenous Malformations with Associated Flow-Related Arterial Aneurysms Helen Kim, Nasrine Bendjilali, Jeffrey Nelson, Shantel M. Weinsheimer, Mark Segal, Charles E. McCulloch, Ludmila Pawlikowska and William L. Young; San Francisco, CA CD513 Attenuated and Augmented Emotional Face Processing Networks in Temporal Lobe Epilepsy Brett W. Fling, Jeff Riley and Jack J. Lin; Irvine, CA CD503 Metabolomics Identifies Alterations in the Tricarboxylic Acid Cycle in Acute Ischemic Stroke W. Taylor Kimberly, Yu Wang, Ly Huong Pham and Robert E. Gerszten; Boston, MA CD514 Seizure Recurrence and Remission after Switching Antiepileptic Drugs Scott Mintzer, Sophia P. Wang, Christopher T. Skidmore, Tingting Zhan, Erika Stuckert, Maromi Nei and Michael R. Sperling; Philadelphia, PA CD504 Perception among African Americans towards Calling 911 for Acute Stroke Lesli E. Skolarus, Jillian S. Murphy, Marc A. Zimmerman, Sarah Bailey, Sophronia Fowlkes and Lewis B. Morgenstern; Ann Arbor and Flint CD515 Combined Therapy with Clonazepam and Tiagabine Is Protective Against Febrile Seizures in a Mouse Model of Dravet Syndrome and Has Reduced Toxicity Compared with Monotherapy John C. Oakley, Christine Cheah, Franck Kalume, Ruth Westenbroek and William Catterall; Seattle, WA CD505 High Resolution Magnetic Resonance Imaging (HRMRI) in Intracranial Atherosclerosis Tanya N. Turan, Truman R. Brown, Zoran Rumboldt and Robert J. Adams; Charleston, SC CD516 Microelectrodes Produce Unreliable EEG Recordings William Stacey, Spencer Kellis, Christopher Butson, Paras Patil, Trevor Assaf, Temenuzhka Mihaylova and Simon Glynn; Ann Arbor, MI; Pasadena, CA and Milwaukee, WI CD506 Impact of Acute Ischemic Stroke Treatment in Patients over Age 80: The SPOTRIAS Consortium Experience Joshua Z. Willey, Santiago Ortega-Gutierrez, Nils Petersen, Pooja Khatri, Andria L. Ford, Natalia S. Rost, Latisha K. Ali, Nichole R. Gonzales, Jose G. Merino, Brett C. Meyer and Randolph S. Marshall; New York, NY; Cincinnati, OH; St. Louis, MO; Boston, MA; Los Angeles, CA; Houston, TX; Bethesda, MD and San Diego, CA CD517 High Fat Diet Induces Impaired Glucose Tolerance and Painful Peripheral Neuropathy Hsinlin T. Cheng, Jacqueline R. Dauch, John M. Hayes, Sangsu Oh and Eva L. Feldman; Ann Arbor, MI CD518 Endogenous l-Opioid System as a Research and Therapeutic Target in Migraine Alexandre F. DaSilva, Thiago D. Nascimento, Tiffany Love, Marcos F. DosSantos, Ilkka K. Martikainen, Misty DeBoer, Chelsea M. Cummiford, Felipe Fregni, Yolanda R. Smith, Eric Maslowski and Jon-Kar Zubieta; Ann Arbor, MI and Boston, MA CD507 Induction of Autophagy Protects Against TDP43-Mediated Neurodegeneration Sami Barmada, Aaron Daub, Michael Ando, Andrea Serio, Andrey Tsvetkov, Arpana Arjun, Siddharthan Chandran and Steve Finkbeiner; San Francisco, CA and Edinburgh, United Kingdom 28 ID: guganp I Black Lining: [ON] I Time: 09:11 I Path: N:/3b2/ANA#/Vol00000/120254/APPFile/JW-ANA#120254 J_ID: ZAY Customer A_ID: BKLT2012_CD_Poster_Sessi Cadmus Art: ANA11 Date: 18-September-12 CD519 Adiponectin (ADP) & ADP Oligomers Are Differentially Modulated by Treatment Response in Episodic Migraineurs B. L. Peterlin, G. E. Tietjen, B. A. Gower, L. W. White, E. Hammond, P. D. Dash, T. N. Ward, S. J. Tepper and J. A. Haythornthwaite; Baltimore, MD; Toledo, OH; Birmingham, AL; Lebanon, NH and Cleveland, OH Stage: Page: 29 CD531 Caspr2 Autoantibodies Target CNS and PNS Axons Eric Lancaster, Josep Dalmau and Steven S. Scherer; Philadelphia, PA and Barcelona, Spain CD532 Vitamin D Levels Are Associated with Disability and Brain Volume in Multiple Sclerosis Ellen M. Mowry, Emmanuelle Waubant, Charles E. McCulloch, Mehul Sampat, Pamela Qualley, Robin Lincoln, Pierre-Antoine Gourraud, Alan Evangelista, Don Brenneman, Azadeh Beheshtian, Sara Llufriu, Stephen Hauser and Daniel Pelletier; San Francisco, CA; Baltimore, MD and New Haven, CT CD520 Obesity Increases Nociceptive Activation of the Trigeminal System Ana Recober, Sang Luu, Jennika DeVilbiss and Heather Rossi; Iowa City, IA CD533 fMRI Findings Using the Immediate Memory Task/Delayed Memory Task and Correlation with Neuropsychological Assessment of Cognitive Function in Multiple Sclerosis Patients Flavia Nelson, Edward Zuniga, Zahra Kamdar, Muhammad Akhtar, Jeffrey Wilken, Jerry Wolinsky, Ponnada Narayana and Joel Steinberg; Houston, TX and Washington, DC CD521 Feasibility of Electrogastrography in Parkinson Disease Samay Jain, Peter J. Gianaros and Max E. Levine; Pittsburgh, PA and Loudonville, NY CD522 Normal Striatal D1 Dopamine Receptor Binding in Primary Focal Dystonias Morvarid Karimi, Joanne Markham, Hubert Flores, Stephen Moerlein, Tom Videen and Joel S. Perlmutter; St. Louis, MO CD534 Decreased Inflammation in Response to sarA-Mediated Biofilm Formation in a Model of CNS Catheter Infection Jessica Snowden; Omaha, NE CD523 The Transcription Factor ATF4 as a Neuroprotective Target in Parkinson Disease Xiaotian Sun, Lloyd A. Greene and Oren A. Levy; New York, NY CD535 Leveraging Electronic Health Records for Research in Multiple Sclerosis Zongqi Xia, Riley Bove, Tianxi Cai, Suchun Cheng, Raul N.G. Perez, Vivian S. Gainer, Shawn N. Murphy, Pei J. Chen, Guergana K. Savova, Katherine Liao, Elizabeth W. Karlson, Stanley Shaw, Ashwin N. Ananthkrishnan, Peter Szolovits, Susanne E. Churchill, Issac S. Kohane, Robert M. Plenge and Philip L. De Jager; Boston, MA; Cambridge, MA and Charlestown, MA CD524 Rab Protein Expression Alters alpha-Synuclein Oligomer Formation and Cytotoxicity Nikolaus R. McFarland and Tomoko Sahara; Gainesville, FL CD525 Dopaminergic Modulation of Basal Ganglia Connectivity in ParkinsonвЂ™s Disease Kathleen L. Poston, William Shire, Richard Joseph, Vinod Menon and Michael Greicius; Stanford, CA CD536 Toxoplasma Co-Opts Host Cells It Does Not Invade Anita A. Koshy, Hans K. Dietrich, Patrick K. House, Robert Sapolsky and John C. Boothroyd; Stanford, CA CD526 Circadian Rhythm of Melatonin Secretion Is Altered in ParkinsonвЂ™s Disease Aleksandar Videnovic, Angelica Marconi, Charleston Noble, Katherine Reid, Teresa Kuhta, Tanya Simuni, Cindy Zadikoff and Phyllis Zee; Chicago, IL CD537 Problematic Initial Shunt Placement and Initial Infection Are Associated with Reinfection Tamara D. Simon, Nicole Mayer Hamblett, Kathryn B. Whitlock, Marcie Langley, John R.W. Kestle, Jay RivaCambrin, Margaret Rosenfeld and Emily A. Thorell; Seattle, WA and Salt Lake City, UT CD527 Modulation of 14-3-3 Proteins in the MPTP ParkinsonвЂ™s Disease Model Huiping Ding and Talene Yacoubian; Birmingham, AL CD538 JC Virus Infection in a Humanized Mouse Model Chen S. Tan, Thomas A. Broge Jr, Edward Seung, Vlad Vrbanac, Raphael Viscidi, Jennifer Gordon, Andrew M. Tager and Igor J. Koralnik; Boston, MA; Baltimore, MD and Philadelphia, PA CD528 Genome-Wide Association Study of Tourette Syndrome Jeremiah M. Scharf and TS GWAS Consortium; Boston, MA and Bayside, NY CD529 Body-Wide Correction of Myotonic Dystrophy Type 1 (DM1) in Transgenic Mice by RNase H-Active Antisense Oligonucleotides (ASOs) Thurman M. Wheeler, Andrew J. Leger, Sanjay K. Pandey, A. Robert MacLeod, Masayuki Nakamori, Seng H. Cheng, Bruce M. Wentworth and C. Frank Bennett; Rochester, NY; Framingham, MA and Carlsbad, CA CD539 Comprehensive Genetic Screening of a Large ALS Cohort Using Pooled-Sample Sequencing Matthew B. Harms, Janet Cady, Peggy Allred, Taha Bali, Ryan T. Libby, Alan Pestronk, John Ravits and Robert H. Baloh; Saint Louis, MO; La Jolla, CA and Los Angeles, CA CD540 Motor Neuron Disease-Associated Mutations in p150/Glued Disrupt the Initiation of Retrograde Axonal Transport at Synaptic Termini Thomas E. Lloyd, James Machamer, Sarah Collins and Alex L. Kolodkin; Baltimore, MD CD530 Timed-25 Foot Walk & The Real World Myla D. Goldman, John Scagnelli, Robert W. Motl, John Pula and Jacob J. Sosnoff; Charlottesville, VA and Urbana, IL 29 ID: guganp I Black Lining: [ON] I Time: 09:11 I Path: N:/3b2/ANA#/Vol00000/120254/APPFile/JW-ANA#120254 J_ID: ZAY Customer A_ID: BKLT2012_CD_Poster_Sessi Cadmus Art: ANA11 Date: 18-September-12 Stage: Page: 30 CD541 Validation of the Pediatric CMT Quality of Life Outcome Measure Sindhu Ramchandren, Richard Finkel, Cathey Boyer, Thomas Templin, Carly Siskind, Mary Reilly and Michael Shy; Detroit, MI; Philadelphia, PA; Palo Alto, CA; London, United Kingdom and Iowa City, IA CD551 Drosophila Peroxisomal Biogenesis Defects Produce Shortened Lifespan and Excess Cystene-String Protein at the Synapse Michael F. Wangler, Lucy Liu, Nikolaos Giagtzoglou, Vafa Bayat, Joseph Faust, James McNew and Hugo J. Bellen; Houston, TX CD542 Optimizing the Total Neuropathy Score for HIV-Associated Distal Symmetric Polyneuropathy Jessica Robinson-Papp, Sandeep Sharma, David M. Simpson and Susan Morgello; New York, NY CD552 Glial Restricted Precursor and Oligodendrocyte Progenitor Cell Transplantation in an Ischemic Perinatal White Matter Injury Model Ali Fatemi, Andre W. Phillips, Michael Porambo, Mary Ann Wilson, Joel Marx, Jeffrey D. Rothstein and Michael V. Johnston; Baltimore CD543 TGF-b Signaling in Glioma Microenvironment Inhibits Engraftment and Differentiation of Oncogenic Neural Stem/Progenitor Cells Sabah O. Ghazi, Laura D. Hover, Michelle Stark, Alex Munden and Ty W. Abel; Nashvill, TN CD553 Epidermal Growth Factor Treatment Rescues Neonatal White Matter Injury Joseph Scafidi, Maria Roncal, Tamas L. Horvath, Robert J. McCarter and Vittorio Gallo; Washington, DC and New Haven, CT CD544 Hexokinase-2-Mediated Aerobic Glycolysis as a Novel Target for Medulloblastoma Therapy Timothy R. Gershon, Andrew Crowther, Andrey Tikunov, Hong Yuan, Jeffrey Macdonald and Mohanish Deshmukh; Chapel Hill, NC CD554 Visual Function and Optical Coherence Tomography in Pediatric Demyelinating Diseases Amy T. Waldman, Girish Hiremath, Robert A. Avery, Amy Conger, Michael Loguidice, Lauren S. Talman, Kristin M. Galetta, Michael J. Shumski, James Wilson, EвЂ™tona Ford, Benjamin M. Greenberg, Jonas Ellenberg, Elliot M. Frohman, Laura J. Balcer and Peter A. Calabresi; Philadelphia, PA; Baltimore, MD and Dallas, TX CD545 Reversible Opening of the Blood-Brain Barrier by Targeted Suppression of Claudin 5 To Enhance Drug Delivery into Brain Tumors Gerald A. Grant, Christy Wilson, Matthew Campbell, Shuqin Li, Peter Humphries, Allan Johnson, Mark Dewhirst and Darell Bigner; Durham, NC and Dublin, Ireland CD555 Impact of Acute Hypoxia on the Developing Mouse EEG Santina A. Zanelli, Samuel Kowalski and Jaideep Kapur; Charlottesville CD546 A New Genetic Model of Sporadic Medulloblastoma Reveals Heterogeneity of the Sonic Hedgehog Tumor Subtype G. Praveen Raju, Giselle A. Suero-Abreu, Diane Pham, Luis Barazza, Brandon Wainwright, Marc K. Rosenblum, Daniel H. Turnbull and Alexandra L. Joyner; New York, NY and Brisbane, Queensland, Australia CD556 Recovery of Motor Function after Complete Unilateral Injury of the Corticospinal Tract Using Electrical Stimulation of Motor Cortex on the Uninjured Hemisphere in Rats Jason B. Carmel, Hiroki Kimura and John H. Martin; White Plains, NY and New York, NY CD547 Regulation and Impact of HSF1 in Malignant Human Cancers Sandro Santagata, Marc L. Mendillo, Rulla M. Tamimi, Tan A. Ince, Chengkai Dai, Luke Whitesell and Susan Lindquist; Cambridge, MA; Boston, MA; Miami, FL and Bar Harbor, ME CD557 Bimanual Dexterity and Interhemispheric Interactions in Musicians Alex R. Carter, Kristi Zinn, Jennifer Rengachary and Maurizio Corbetta; Saint Louis, MO CD548 MicroRNA 218a Acts as a Tumor Suppressor in Medulloblastoma Sujatha Venkataraman, Diane K. Birks, Irina Alimova, Peter Harris and Rajeev Vibhakar; Aurora, CO CD558 Probing for Hemispheric Specialization for Motor Skill Learning: A Transcranial Direct Current Stimulation Study Heidi M. Schambra, Mitsunari Abe, David A. Luckenbaugh, Janine Reis, John W. Krakauer and Leonardo G. Cohen; New York, NY; Bethesda, MD and Baltimore, MD CD549 Alpha Synuclein as a Cutaneous Biomarker of Parkinson Disease Christopher H. Gibbons, Ningshan Wang and Roy Freeman; Boston, MA CD559 Bmal1 Provides a Molecular Link between Circadian Clock Function, Brain Metabolism, and Neurodegeneration Erik S. Musiek, Miranda M. Lim, Adam Q. Bauer, Guangrui Yang, Jee Hoon Roh, Benoit I. Giasson, David M. Holtzman and Garret A. FitzGerald; St. Louis, MO; Philadelphia, PA and Gainesville, FL CD550 Erythropoietin Alters Cell Fate of Subventricular Zone Progenitor Cells at Early and Late Time Points after Neonatal Stroke Fernando Gonzalez, Patrick McQuillen, Amara Larpthaveesarp, Nikita Derugin, Michael Wendland and Donna Ferriero; San Francisco, CA 30 ID: guganp I Black Lining: [ON] I Time: 09:11 I Path: N:/3b2/ANA#/Vol00000/120254/APPFile/JW-ANA#120254 J_ID: ZAY Customer A_ID: BKLT2012_CD_Poster_Sessi Cadmus Art: ANA11 Date: 18-September-12 CD560 Neuregulin-1 Effects on Endothelial and BloodBrain Barrier Permeability after Experimental Injury Josephine Lok, Song Zhao, Wendy Leung, Ji Hae Seo, Deepti Navaratna, Michael J. Whalen, Xiaoying Wang and Eng H. Lo; Boston, MA; Charlestown, MA and Changchun, Jilin, China Stage: Page: 31 CD561 Acetyl-L-Carnitine (ALCAR) Provides Long-Term Neuroprotection after Traumatic Brain Injury in Immature Rats Susanna Scafidi, Su Xu, Shruti V. Kabadi, JayLyn Waddell, Rao Gullapalli, Alan Fadan, Mary C. McKenna and Gary Fiskum; Baltimore, MD 31 ID: guganp I Black Lining: [ON] I Time: 09:11 I Path: N:/3b2/ANA#/Vol00000/120254/APPFile/JW-ANA#120254 J_ID: ZAY Customer A_ID: BKLT2012_Abstracts Cadmus Art: ANA12 Date: 18-September-12 2012 Annual Meeting Sunday, October 7, 2012 Poster Session Abstracts Stage: Page: 32 expect it to associate with lacunar stroke. Therefore, we also tested this hypothesis. Methods: Association between six single nucleotide polymorphisms (SNPs) at 17q25 and WMHV measured in 2504 ischaemic stroke cases was assessed. These SNPs were also investigated for association with lacunar stroke in 1886 SVD strokes and 52277 controls. Results: All six SNPs associated with WMHV (risk alleles concordant with previous reports). The most significant SNP was rs11869977 (p Вј 0.00031) and accounted for 0.5% of WMHV variability. Conditional analysis did not reveal other independent signals within the region. In contrast, no SNPs associated with lacunar stroke. Conclusion: This study further supports the association between 17q25 locus and WMH, but not with lacunar stroke. This suggests that its effects are mediated via brain responses to injury rather than promoting small vessel arteriopathy. Study supported by: The principal funding for this study was provided by the Wellcome Trust, the Intramural Research Program of the National Institute on Aging (NIH), National Institute for Neurological Disorders and Stroke (NINDS), the National Institutes of Health Genes, Environment and Health Initiative (GEI), National Health & Medical Research Council (Australia), Annual Research Funding of the Italian Ministry of Health, National Human Genome Research Institute (NIH), National Heart, Lung, and Blood Institute, Henry Smith Charity, the Medical Research Council (UK) and the British Council (UKIERI). Posters will be displayed in Gloucester, located on the 3rd floor in the Back Bay Hall of the Marriott Copley Place from 11:30 am вЂ“ 7:00 pm, with authors present from 5:30 pm вЂ“ 7:00 pm. NOTE: An asterisk designates a resident/fellow travel award winner. Two asterisks designates an abstract selected for oral presentation in the Derek Denny-Brown New Member Symposium. Cerebrovascular Disease S101. The Expression of Individual Genes in Acute Stroke Differs across Leukocyte Subsets Mateusz G. Adamski, Erin Wagenr, Yan Li, Hua Yu, Steven A. Soper and Alison E. Baird; Brooklyn, NY; Krakow, Poland and Baton Rouge, LA In prior microarray studies overlapping gene expression panels for acute ischemic stroke were developed. In these studies mRNA was isolated either from whole blood or from peripheral blood mononuclear cells (PBMC). We aimed to validate individual genes from these published panels and to determine the cellular sources of alterations in acute stroke patients. Peripheral blood was obtained from 12 acute stroke patients within 48 hours from symptom onset and from 12 age, race and sex matched control subjects. The expression of five genes previously found to be substantially altered in ischemic stroke (IL1R2, S100A9, FDFT1, C3AR1 and RNASE2) was measured in four leukocyte subsets: CD14Гѕ monocytes, CD4Гѕ T, CD20Гѕ B cell lymphocytes and PBMCs. The expression of these five 5 genes was measured using qPCR and compared between stroke patients and control subjects. S100A9 was significantly (p<0.05) overexpressed in CD4Гѕ and CD20Гѕ lymphocytes whereas FDFT1 expression was significantly (p<0.05) decreased in CD20Гѕ lymphocytes. These results show the potential diagnostic value of genes identified in prior microarray studies in stroke patients. They also emphasize the potential and added value of studying gene expression in specific leukocyte subsets. Study supported by: S. A. Soper: Research Grant; NIH funded grant # 1 R01 EB010087-01A1. A. E. Baird: Research Grant; NIH funded grant # 1 R01 EB010087-01A1. S103. The Untreated Clinical Course of Cerebral Cavernous Malformations: A Prospective, Population-Based Cohort Study Rustam Al-Shahi Salman, Julie M. Hall, Margaret A. Horne, Fiona A. Moultrie, Colin B. Josephson, Jo J. Bhattacharya, Carl E. Counsell, Gordon Murray, Vakis Papanastassiou, Vaughn Ritchie, Richard C. Roberts, Robin J. Sellar and Charles P. Warlow; Edinburgh, United Kingdom; Newcastleupon-Tyne, United Kingdom; Glasgow, United Kingdom; Aberdeen, United Kingdom; Fauldhouse, United Kingdom and Dundee, United Kingdom Background: Cerebral cavernous malformations (CCM) are prone to bleeding but the risk of intracranial haemorrhage and other complications, as well as their predictors, are unclear. Methods: We conducted a population-based study using multiple overlapping sources of case ascertainment and prospective follow-up. Findings: During 1,177 person-years of follow-up (completeness 97%), the five-year risk of a first haemorrhage was lower than the risk of recurrent haemorrhage (2ГЃ4% [95% confidence interval (CI) 0-5ГЃ7] versus 29ГЃ5% [95% CI 4ГЃ1-55ГЃ0], p<0ГЃ0001). Considering a composite endpoint of intracranial haemorrhage or focal neurological deficit definitely or possibly related to CCM, the five-year risk of a first event was again lower than the risk of recurrence (9ГЃ3% [95% CI 3ГЃ1-15ГЃ4] versus 42ГЃ4% [95% CI 26ГЃ8-58ГЃ0], p<0ГЃ0001); the annual risk of recurrence declined from 19ГЃ8% (95% CI 6ГЃ1-33ГЃ4) in year one to 5ГЃ0% (95% CI 0ГЃ0-14ГЃ8) in year five, and it was higher for women than men (p Вј 0ГЃ01). Interpretation: The risk of recurrent intracranial haemorrhage or focal neurological deficit from CCM is greater than the risk of a first event, is greater for women than for men, and declines over five years. S102. Genetic Risk in Cerebral Small Vessel Disease (SVD): 17q25 Locus Associates with White Matter Lesions but Not Lacunar Stroke Poneh Adib-Samii, The International Stroke Genetics Consortium and METASTROKE Consortium; London, United Kingdom Background: Recently, CHARGE consortium identified a novel locus at 17q25 associated with white matter hyperintensities (WMH) on MR-imaging in stroke-free individuals. In stroke, WMH are linked to SVD; therefore, we aimed to replicate the association with WMH volume (WMHV) in stroke. If the locus acts by promoting SVD, one might 32 ID: guganp I Black Lining: [ON] I Time: 09:24 I Path: N:/3b2/ANA#/Vol00000/120255/APPFile/JW-ANA#120255 J_ID: ZAY Customer A_ID: BKLT2012_Abstracts Cadmus Art: ANA12 Date: 18-September-12 Study supported by: This study was supported by the UK Medical Research Council, the Chief Scientist Office of the Scottish Government, and the UK Stroke Association. Stage: Page: 33 infarct size. Further studies of the possible mechanism behind this association are needed. Study supported by: NINDS R01 NS047691 S106. First Mexican Family with CADASIL: A Novel Mutation in the NOTCH3 Gene Fernando Barinagarrementeria, Antonio Arauz and Manuele Minw; Queretaro, Mexico; Mexico City, Mexico and Paris, France S104. Characteristic Distributions of Intracerebral Hemorrhage-Associated Microinfarcts Eitan Auriel, Mahmut Edip Gurol, Alison Ayers, Andrew Dumas, Kristin Schwab, Anastasia Vashkevich, Sergi Martinez-Ramirez, Jonathan Rosand, Anand Viswanathan and Steven M. Greenberg; Boston, MA We report the first Mexican family affected with CADASIL. Material and methods: DNA was extracted from whole blood using standard procedures. Results: The family is a native Mexican family settled in Sinaloa, Northwestern part of the Country. The proband is a female seen at age of 48 years with history of migraine. Recently developed depression. An MRI disclosed white matter and periventricular abnormalities as well temporal anterior poles and basal ganglia. Her father died at age 63 after 6 years history of repeated strokes and dementia and two paternal uncles with history of multiple strokes and dementia. She had fourteen siblings. Six of them with history of depression, multiple strokes and dementia. Five of them are alive and with abnormal MRI. One nephew with migraine and and one brother with CADASIL spectrum were evaluated in search of notch 3 mutation.We identified a heterozygous point mutation in exon 3 of NOTCH3 (c .304T>A. This mutation, was detected in all 3 patients. It is a mutation typical of CADASIL. Conclusion: Clinical, imaging and genetic characteristics of the first Mexican Family with CADASIL are similar to other races with the disease. Study supported by: None Clinically silent cerebral microinfarcts have been observed with high incidence on diffusion-weighted imaging of patients with primary intracerebral hemorrhage (ICH). We examined the timing and spatial distribution of cerebral microinfarcts in patients with lobar and deep ICH. We retrospectively analyzed 458 MRI scans from 392 subjects with lobar (n Вј 276) and deep (n Вј 116) ICH (48.7% females; mean age 72.8611.7 years) and identified 103 DWI-hyperintense lesions on 62 MRI scans, located mostly in lobar brain regions (90/103, 87.4%). The lesions were not uniformly distributed throughout the brain lobes and specifically differed between the lobar and deep ICH patients (p Вј 0.002). Although the frequency of DWI lesions tended to be greater on scans performed within 7 days after ICH (39/214, 18.2%), they continued at high frequency in the non-acute (>14 days post-ICH) period as well (23/178, 12.9%, OR 1.5, 95% CI 0.86-2.6 for acute vs. nonacute). The characteristic distributions of incident microinfarcts and their high frequency even outside the acute post-ICH period suggest that they are products of the underlying small vessel disease. These findings also support the possibility that cortical microinfarcts are numerous enough to make important contributions to small vessel-related cognitive impairment. Study supported by: None S107. Prolyl 4-Hydroxylase Inhibition (GSK360A) Increases Hypoxia Inducible Factor (HIF)-Regulated Transcripts and Improves Post-Stroke Sensory-Motor and Cognitive Functions Frank C. Barone, Jin Zhou, Jie Lie, Robert N. Willette, John Lapore, Erding Hu and Daniel M. Rosenbaum; Brooklyn, NY and King of Prussia, PA S105. Effect of Leukoaraiosis on Neglect Performance in Acute Stroke Patients Zainab Bahrainwala, Argye E. Hillis, Jennifer Dearborn and Rebecca F. Gottesman; Baltimore, MD Hypoxia inducible factor (HIF) is upregulated by decreased oxygen tension and ischemic preconditioning. GSK360A is a prolyl 4-hydroxylase (PHD) inhibitor that increases HIF1a. Here we evaluated an optimum, pharmacodynamically determined dose in focal stroke over 3 weeks. Rats received reperfusion stroke. Vehicle (1% Methyl cellulose) or GSK360A (30 mg/kg) was administered by oral gavage at 18 and 5 hr prior to stroke. Measurements were made of circulating and tissue erythropoietin (EPO) mRNA and protein, sensory-motor and cognitive (Active Avoidance; AA) functions, and terminal brain tissue loss due to infarction. GSK360A increased circulating and tissue EPO mRNA and protein up to 80-fold (p<0.01) by 5 hr poststroke. Stroke increased sensory-motor deficits that were reduced (20-31%, p<0.05) by GSK360A. Stroke decreased AA performance that was improved (p<0.01) by GSK360A. GSK360A also reduced terminal brain tissue loss (30%, p<0.05). These data demonstrate GSK360A brain protection and long-term functional improvement in post-stroke function. PHD inhibition can stimulate HIF-induced transcription and might be useful for highstroke-risk situations and/or prior to surgery to reduce post-surgical cognitive decline. Study supported by: GlaxoSmithKline and SUNY Downstate Medical Center Background: Leukoaraiosis is longitudinally associated with cognitive decline and dementia, but how it interacts with the brainвЂ™s response to acute ischemia is less understood. We hypothesized that acute ischemic stroke patients with a higher burden of leukoaraiosis would perform worse on tests of cognitive performance, specifically neglect, when controlling for infarct size. Methods: 261 patients with an acute ischemic right-hemispheric stroke at The Johns Hopkins Hospital underwent brain MRI and cognitive assessment for hemispatial neglect, within 5 days of symptom onset. Acute infarcts were measured volumetrically on DWI images and FLAIR images were reviewed for white matter hyperintensities (WMH), using the Cardiovascular Health Study (CHS) scale (0-9, with 9 being most extensive). Results: Each one-point increase in CHS category was associated with a 1.17-fold increased odds (95% CI 0.991.37) of having any neglect and a 1.19-fold increased odds (95% CI 1.02-1.40) of having severe neglect, after adjusting for DWI volume, age, sex and race. Neglect scores were markedly worse in individuals with both severe WMH and large infarcts (p-interaction<0.05). Conclusion: More severe leukoaraiosis is associated with worse neglect after acute ischemic stroke, independent of 33 ID: guganp I Black Lining: [ON] I Time: 09:24 I Path: N:/3b2/ANA#/Vol00000/120255/APPFile/JW-ANA#120255 J_ID: ZAY Customer A_ID: BKLT2012_Abstracts Cadmus Art: ANA12 Date: 18-September-12 S108. Brain and Abdominal Aneurysm Study (BAAS): Interim Analysis Kevin M. Barrett, Sothear M. Luke, Albert G. Hakaim, Rabih G. Tawk, Ricardo A. Hanel, Bradford B. Worrall, William D. Freeman, Thomas G. Brott and James F. Meschia; Jacksonville, FL and Charlottesville, VA Stage: Page: 34 unknown whether the NR2 peptide, a breakdown product of brain specific NMDA receptors, which is released into the bloodstream during acute cerebral ischemia, is elevated in diabetics and how it may correlate with cerebrovascular function. Methods: NR2 peptide plasma concentrations were measured in 27 diabetics, 14 prediabetics and 9 healthy controls and correlated with cerebrovascular function. Middle cerebral artery (MCA) vasoreactivity was measured using Transcranial Doppler Ultrasound at rest and following inhalation of 5%CO2. Results: NR2 levels were significantly different between all groups (p Вј 0.033). Diabetics had increased NR2 peptide levels (0.24 lg) compared to prediabetics (0.07 lg/l) and healthy controls (0.09lg/l), but prediabetics had no significant peptide elevations compared to controls (p Вј 0.99). Regression analysis showed that increased NR2 peptide levels were significantly associated with increased MCA pulsatility (p< 0.001) and resistance (p< 0.001) indices, and possibly with impaired cerebral vasoreactivity (p Вј 0.056). Conclusion: The NR2 peptide may indicate injury to cerebral vessels in patients with diabetes and may predict risk of cerebrovascular disease. Study supported by: Funding of this study was partially provided by a grant from Pennsylvania Tobacco Settlement Funds, Human Health Services The relationship between intracranial and aortic aneurysms has not been well quantified. Evidence of shared genetic risk factors suggests screening for abdominal aortic aneurysms (AAA) may be warranted in patients with aneurysmal subarachnoid hemorrhage. BAAS (NCT01420991) is a prospective study designed to obtain an estimate of the proportion of patients with aneurysmal subarachnoid hemorrhage who are found to have AAA by screening ultrasonography. Thirty-eight subjects have been screened for eligibility; 18 subjects enrolled as of 3/27/12. One (6%) was excluded from enrollment for pre-existing diagnosis of AAA. Sixteen subjects have completed 30 day follow-up. Mean age was 50.2 yrs (range 33 to 69 yrs); 72% were women. Sixty-seven percent were active cigarette smokers. Five (28%) subjects had more than one intracranial aneurysm. Aneurysm treatment: 13 (72%) endovascular coiling, 5 (28%) clipping. Subjects with mild (<6), moderate (6-13), and severe (>13) baseline NIHSS was 12 (67%), 2 (11%), and 4 (22%). One (6%) had an aortic aneurysm (5.9 cm) detected by ultrasonography. In this population of aneurysmal subarachnoid hemorrhages, 2 (5%) of the 38 subjects had AAA. Updated results will be presented. Study supported by: Mayo Jacksonville Intramural Funds S111. Neurophysiological Identification of Two Independent Generators Causing Oculofaciopalatal and Lingual Myoclonus Rony Dekermenjian, Nancy Gadallah, Sushanth Bhat, Sumaiya Salim, Liudmila Lysenko, Michael Rosenberg and Sudhansu Chokroverty; Edison, NJ S109. Revising the Model of Vascular Homeostasis: Mechanotransduction Is Opposed by a Novel Electrical Force Darshan P. Trivedi and Peter R. Bergethon; Boston, MA Oculofaciopalatal myoclonus, characterized by rhythmic, pendular vertical eye movements with synchronous contraction of the soft palate, is often seen in brainstem infarction or hemorrhage with damage to the Guillian-Mollaret triangle. Lingual myoclonus occurs in an idiopathic fashion, with Arnold-Chiari malformations, brainstem tumors or as an epileptic phenomenon. We report a case of oculopalatofacial myoclonus secondary to brainstem stroke with independent lingual myoclonus. A 52 year old man suffered brainstem infarction, with a one and a half syndrome, left sided lower motor nerve facial palsy, quadriplegia, and sensory loss in the right hemibody and left face. Rhythmic ocular bobbing with synchronous palatal and facial contractions were noted, as well as independent tongue myoclonus. Polymography of multiple cranial and limb muscles revealed synchronous, rhythmic myoclonic bursts at a frequency of 1.5-2 Hz in the orbicularis oculi, mentalis, palatal and sternocleidomastoid muscles. However, the lingual myoclonic bursts occurred asynchronously, at the same frequency but with variable latency. The neurophysiological evaluation demonstrates a second generator causing rhythmic tongue movements, completely independent and asynchronous from the classic generator of oculofaciopalatal myoclonus, a novel description in our patient. Study supported by: N/A Blood flow is controlled by local mechanisms including mechanotransduction. Vascular endothelial cells (VEC) are exposed to a ubiquitous yet unexamined flow-induced electrical force, the electrostatic vascular streaming potential (EVSP). Previously membrane potential and nitric oxide production in cultured VEC were shown to respond to isolated EVSP-modeled electric fields. We test the hypothesis that the EVSP and mechanical shearing forces are separable and act in homeostatic opposition. Using a laminar flow chamber, VECs were exposed to shearing forces including the EVSP. With flow (shear and EVSP), the membrane potential hyperpolarized within 100 seconds and then depolarized back to baseline. With the EVSP neutralized, flow induced a persistent hyperpolarization (8 mV) without subsequent depolarization. Isolated electrical field exposure induced depolarization (2 mV). Application of channel blocking agents showed the EVSP effect attributable to a flow-sensitive chloride channel. The production of NO was proportional to flow but with the EVSP neutralized the NO signal was potentiated. We conclude that mechanotransduction and EVSP show biologically independent effects and that the EVSP has a homeostatic role in vascular biology. Its derangement may contribute to cerebrovascular disease. Study supported by: NIH S110. Does the NMDA Receptor Biomarker Predict Impaired Cerebral Vascular Function in Diabetes? Kerstin Bettermann, Julia E. Slocomb, Mary E.J. Lott and Svetlana Dambinova; Hershey, PA and Atlanta, GA S112. Evaluation of Gender Disparities in Hemicraniectomy Utilization in the United States Mahmoud Rayes, Seemant Chaturvedi and Pratik Bhattacharya; Detroit, MI Background: Diabetes is a risk factor for stroke, chronic ischemic white mater disease and vascular dementia causing endothelial dysfunction and structural vascular damage. It is Randomized trials suggest a robust survival benefit from hemicraniectomy in malignant infarctions 60 years. We 34 ID: guganp I Black Lining: [ON] I Time: 09:24 I Path: N:/3b2/ANA#/Vol00000/120255/APPFile/JW-ANA#120255 J_ID: ZAY Customer A_ID: BKLT2012_Abstracts Cadmus Art: ANA12 Date: 18-September-12 have previously shown a gender disparity favoring men in the nationwide utilization of this procedure. In the present study we analyzed data from ischemic stroke discharges in the Nationwide Inpatient Sample (NIS) years 2007-2009, to explain these differences. 328937 ischemic stroke discharges were included; of which 384 (0.12%) received hemicraniectomies. Males (0.15%) were more likely to receive the procedure than females(0.09%, p<0.0001). Females were significantly older (p<0.0001); received tPA less often (p<0.0001); less likely to be in the highest income quartile (p<0.0001); more likely to have Medicare (p<0.0001) and less likely to have Medicaid (p<0.0001) or private insurance (p<0.0001)-even in the 60 years group; less likely to be treated at urban teaching centers (p<0.0001) and less likely to be transferred (p<0.0001). Upon adjustment of the gender-hemicraniectomy association by age, income quartile, primary insurance type, and urban location/teaching status of the hospital; the gender disparity was no longer significant. Many reasons for this gender disparity are physician and system-centered. Addressing these factors can extend the benefit of this potentially lifesaving procedure to more women with stroke. Study supported by: none Stage: Page: 35 Methods: Eighty-eight patients (57 men and 31 women; mean age 72611 years) diagnosed with an acute ischemic stroke within 24 hours of admission to the stroke unit were evaluated for stroke severity using the Scandinavian Stroke Scale and Glasgow Coma Scale, and for serum concentrations of free tri-iodothyronine (T3), free thyroxin, thyroid stimulating hormone and C-reactive protein (CRP). At discharge, cognitive outcome was evaluated using the Mini Mental State Examination (MMSE). Results: In univariate regression analyses higher free T3 concentrations (b Вј .332, p Вј .006) and lower CRP concentrations (b Вј -.348, p Вј .005) were associated with better cognitive outcomes (higher MMSE score) at discharge. In multivariate analyses higher free T3 concentrations was associated with better cognitive outcome (b Вј .252, p Вј .011) after adjustment for age, gender, stroke severity on admission and CRP condentrations. Conclusions: In acute ischemic stroke patients higher free T3 concentration on admission is independently associated with better cognitive outcome at discharge. Study supported by: Funding internal. S115. Angioplasty and Stenting of Patients with Carotid Artery or Vertebral Artery Stenosis: Experience from Lithuania Adomas Bunevicius, Donatas Cerniauskas, Rytis S. Kaupas and Edvardas Vaicekavicius; Kaunas, Lithuania and Chapel Hill, NC S113. Functional Weakness in tPA Candidates: Challenges and NIHSS-Minus Ilya Bragin, Mirret M. El-Hagrassy and Adham Kamel; Syracuse, NY Objective: To evaluate initial and long term outcomes of angioplasty with stenting for stenosis of carotid and vertebral arteries. Methods: From 2003 until 2006 a total of 45 consecutive patients (n Вј 39 men; mean age 6268 years) underwent angioplasty and stenting for documented stenosis of carotid or vertebral arteries. Long term outcomes were evaluated in 26 patients 2.461.1 years after the procedure. Results: There were no complications during the procedure. During in-patient period 3 (7%) patients developed ischemic complications: 1 ipsilateral stroke, 1 contralateral stroke and 1 transient ischemic attack. At discharge, clinical status was considered as improved in 33 (73%) patients, as not changed in 10 (22%) patients and as worsened in 2 (4%) patients. During follow-up period 4 (18%) patients died due to suicide (n Вј 2), stroke (n Вј 1) and lung embolism (n Вј 1). Eighteen (69%) patients were compliant with prophylactic treatment regimen. At follow-up clinical status improved in 18 (82%) patients and did not-change in 4 (18%) patients. Conclusions: Angioplasty and stenting of vertebral and carotid arteries due to stenosis are safe and effective treatment modality, however, suicide rate was high in our cohort of patients. Study supported by: No external funding Introduction: Thrombolytic associated symptomatic intracranial hemorrhage rates range 2.1% вЂ“ 9.4%. Thrombolytic administration is based on the NIHSS. No formal NIHSS component accounts for functional symptomatology or malingering. Cases: A 56 year old male presented with pleuritic chest pain and hemiparesis. He claimed to be a factor V Leiden вЂ�вЂ�heterozygoteвЂ™вЂ™ smoker arriving from a cross-country flight. He knew the exact time of onset. NIHSS was 10. He received tPA, but was subsequently found to be a fraud. Workup was negative. A 54 year old female schizophrenic with vascular risk factors presented with acute unresponsiveness, collapse and possible left sided weakness. NIHSS was 16. She received tPA; workup was negative. Discussion: Stroke mimics are frequently encountered. In one study, rt-PA was administered to 193 cases, 30 of which proved to be mimics. HooverвЂ™s sign in the legs and arms for functional weakness has been tested in small studies, and can be quickly performed. We propose that positive results cancel NIHSS Motor Leg/Arm scores (NIHSS-Minus), reducing the overall score. This could reduce inappropriate tPA administration. Conclusions: The NIHSS can be refined to address nonorganic weakness and better direct management. Study supported by: N/A S116. Risk Factors for Stroke in South Asians across Two Continents Zhongbo Chen, Muhammad S. Khan, Sunaina Yadav, Ankita Maheshwari, Tharushi Fernando, Ranil de Silva, Ranjani Gamage, Kameshwar Prasad and Pankaj Sharma; London, United Kingdom; New Delhi, India; Nugegoda, Sri Lanka and Colombo, Sri Lanka S114. Cognitive Outcomes of Acute Ischemic Stroke Patients: Association with Concentrations of Thyroid Axis Hormones and C-Reactive Protein Adomas Bunevicius, Henrikas Kazlauskas, Nijole Raskauskiene, Rima Radziuviene, Audra Anskoliene, Vinsas Janusonis and Robertas Bunevicius; Palanga, Lithuania; Klaipeda, Lithuania and Chapel Hill, NC Background: Stroke in South Asians remains poorly characterised. We assessed stroke risk factors in South Asians in the Indian subcontinent (SA) and British Asians (BA), with comparison to Europeans. Methods: This hospital-based case-control study used neuroimaging-confirmed stroke. Subjects were recruited from India, Sri Lanka and the UK. Objective: To evaluate in acute ischemic stroke patients the association of concentrations of thyroid axis hormones and CRP on admission with cognitive outcome at discharge. 35 ID: guganp I Black Lining: [ON] I Time: 09:24 I Path: N:/3b2/ANA#/Vol00000/120255/APPFile/JW-ANA#120255 J_ID: ZAY Customer A_ID: BKLT2012_Abstracts Cadmus Art: ANA12 Date: 18-September-12 Outcomes: 1030 SA stroke cases and 546 controls, 654 Europeans, and 200 BAs were recruited. SAs had strokes at a younger mean age (52.4 years) than BAs (61.6years) (p<0.001) and earlier than Europeans (68.5years) (p<0.001). SAs had a higher proportion of haemorrhagic stroke compared to Europeans (p Вј 0.001). In SAs, adjusted Odds Ratios (OR) and Population Attributable Risk (PAR) for established risk factors in cases compared to controls were: hypertension (OR 10.7, 95%CI 7.7вЂ“14.8, PAR 51.8%); diabetes (OR 3.5, 2.3вЂ“5.2; PAR 13.5%); hypercholesterolaemia (OR 14.4, 8.3вЂ“25.0, PAR 28.0%); atrial fibrillation (OR 8.0, 3.3вЂ“21.1); and migraine with aura (OR 4.8, 2.8вЂ“8.2). SAs had a higher proportion of left ventricular hypertrophy on echocardiography compared to Europeans (p<0.001). BAs had higher mean fasting glucose6SEM (7.5mmol/l 60.3) compared to Europeans (6.560.2): p Вј 0.007; and SAs (6.660.1): p Вј 0.018. Conclusions: Three modifiable risk factors, hypertension, diabetes and hypercholesterolaemia, account for $90% of stroke in South Asians. Study supported by: Department of Health; The Henry Smith Charity; British Council (UKIERI) Stage: Page: 36 Methods: QOL was assessed annually in SPS3 using the Stroke Specific QOL scale (range 1-5). We fit linear mixed models to assess the trend in QOL over time, assuming linearity of time, and adjusted for demographic, medical, and cognitive factors and functional status. Results: Among 2870 participants (mean follow-up 3.5 years), mean age was 63.4 years (SD 10.7); 63% were male; 10% had prior stroke. Factors associated with decline in QOL over time included age (-0.0003 per year, p<0.0001), any college education (-0.0013 per year, p Вј 0.01), prior stroke (-0.004 per year, p < 0.0001), and Barthel score (-0.0002 per year, p < 0.0001). In age-stratified models, prior stroke had a significant effect on change in QOL among the three older quartiles. Conclusion: In this well-defined cohort of lacunar stroke patients, age, education, prior stroke, and functional status predicted changes in QOL over time. Prior subcortical stroke may worsen decline in QOL, especially among the elderly, perhaps due to loss of functional reserve, subclinical progressive vascular disease, or reversible cerebral dysfunction. Study supported by: SPS3 is an investigator initiated study funded by a cooperative agreement from the National Institute of Neurological Disorders and Stroke of United States (Grant #2 U01 NS38529-04A1). The clopidogrel and matching placebo have been donated by Sanofi-Aventis and Bristol-Myers Squibb. Neither company has any involvement with the design, execution, or analysis of the trial. S117. Withdrawn. S118. A Fulminant Case of Atypical Posterior Reversible Encephalopathy Syndrome Associated with Status Epilepticus Bhavpreet Dham, Usman Moghal, Yadira Velazquez, Tapan Kavi, Luis Zayas and Akbar Umer; Camden, NJ S120. Primary/Familial CAA and Maeda-Type Cerebral Small-Vessel Disease: Clinicopathological Diferential Diagnosis and Role of Amyloid Deposition Diseases A.N. Viswanathan, S.M. Greenberg and Sabino Guillermo Echebarria; Boston, MA and Las Arenas, Bizkaia, Spain Introduction: Posterior Reversible Encephalopathy Syndrome (PRES) is a clinico-radiological diagnosis associated with headaches, seizures, visual complaints and radiological findings of vasogenic edema predominantly in the white matter of parieto-occipital lobes. Treatment of underlying etiologies often leads to spontaneous resolution of symptoms and imaging findings. Case: A 72-year old man with hypertension presented with a 2-week history of generalized malaise, headaches, vomiting and intermittent blurry vision. Systolic blood pressure was over 200 but the remainder of the physical examination was normal. Initial head CT was also unremarkable. Hospital course was complicated by a progressive decline in mental status. Brain MRI 3-days after a normal head CT showed development of extensive regions of vasogenic edema in the parieto-occipital lobes, basal ganglia and cerebellum with associated acute infarctions and extensive multifocal hemorrhages. Hospital course was further complicated by prolonged status epilepticus, requiring pharmacologic coma. Comfort care measures were instituted per familyвЂ™s request and the patient passed away soon thereafter. Summary: Although generally reversible, PRES can rarely have devastating clinical outcome with development of extensive cerebral hemorrhages and infarctions with associated status epilepticus, as described in this case. Study supported by: N/A Introduction: Recent series have enhanced the imnportance and frequency of the association CAA/primary cerebral vasculitis, defined as Ab -related arteritis (ABRA) with descriptives extensive to cerebral amyloid angiopathy related inflammation (CAAi). Leukoencephalopathies defined in these series may be compared with small vessel meningocortical CAAs. Methods: Comparatives in microscopic and ultrastructural neuropathological markers and diagnostic features in: -Diffuse type of CAA with leukoencephalopathy (primary cerebrovascular amyloidosis, familial CAA with nonneuritic amyloid). -Non CADASIL forms of cerebral small-vessel disease. Results: Fibronectin and carvertin deposits (TGF-b products) in tunica intima/media of autosomal recessive small-vessel disease would be a descriptive hallmark, in which extracellular matrix protein expression would be decissive (COL4A1 vascular diseases); comparable, also to demyelinating forms of subcortical amyloid with leukoencephalopathy. Conclusions: Descriptional sampling showing leukoencephalopathy commonalities between diffuse hemorrhagic CAA and Binswanger subcortical encephalopathy, may be connected with definitions derived from WM description in diffuse forms of CAA and Maeda-type small vessel disease of the brain with demyelination predominance. Study supported by: ------------ S119. Quality of Life after Lacunar Stroke: The Secondary Prevention of Small Subcortical Strokes (SPS3) Mandip S. Dhamoon, Leslie A. McClure, Carole L. White, Oscar Benavente and Mitchell S.V. Elkind; New York, NY; Birmingham, AL; San Antonio, TX and Vancouver, BC, Canada S121. TIA with New Ischemic Lesion: Clinical Features and Stroke Risk for Patients with Different TIA Subtypes Olena Y. Fartushna; Kiev, Ukraine Background: We sought to determine predictors of longterm decline in quality of life (QOL) after lacunar stroke. Transient symptoms do not exclude the possibility of associated acute ischemic lesion (AIL) on neuroimaging. 36 ID: guganp I Black Lining: [ON] I Time: 09:24 I Path: N:/3b2/ANA#/Vol00000/120255/APPFile/JW-ANA#120255 J_ID: ZAY Customer A_ID: BKLT2012_Abstracts Cadmus Art: ANA12 Date: 18-September-12 Aim is to study the causes and character of AIL and stroke risk in TIA patients with AIL and without it according to the TIA subtypes (as to TOAST criteria). Methods: DW-MRI has been performed within the first 24 h for 178 patients with acute TIA, which were divided into 2 groups according to the MRI results: 1-TIA with AIL on DWI (n Вј 66(37.0%)) and 2-without it (n Вј 112(63.0%)). Results: Stroke developed in 27(40.9%) patients after TIA with AIL and in 18(16.1%) cases - without it (OR(95% CI) Вј 19,6(19.09-20.1),p<0.001). TIA patients with AIL had a significantly greater volume (p<0.05) and duration (p< 0.001) of neurological deficit compared with persons with TIA without AIL. The diameter of AIL ranged from 1.5 to 26mm (13.461.2mm) and as well as localization it was significantly different of TIA subtypes (p<0.001). Most often AIL were determined for cardioembolic (39.4%) TIA. Conclusions: The duration and volume of the neurological deficit as the risks of stroke were much higher in patients with TIA with AIL than without it and differ depending on TIA subtypes. Study supported by: Bogomolets National Medical University Stage: Page: 37 We present a 41-year-old lady who underwent caesarean section following the development of pre-eclampsia 30 weeks into her pregnancy. 2 days after delivery she developed sudden onset total visual loss followed by weakness of her left leg. MRI brain revealed areas of hyperintensity with restricted diffusion in both parieto-occipital cortices consistent with acute infarction. Imaging of intracranial vessels with MRA and CTA demonstrated marked diffuse vasoconstriction involving both the anterior and posterior circulation. Vasculitic screen was negative. The patientвЂ™s vision started to return within 24 hours and her symptoms almost completely resolved over the following days. A repeat MRI 4 weeks after the event showed evolution of the hyperintense signal in both parieto-occipital cortices with scarring and volume loss, consistent with recent infarction. MRA revealed complete resolution of the vasoconstriction. This case illustrates the spectrum of reversible cerebral vasoconstriction syndromes and highlights the importance of (repeated) cerebral vascular imaging in the diagnosis of women presenting with neurological symptoms in association with (pre)-eclampsia or shortly after delivery. Study supported by: none S124. Endothelial Engulfment of Emboli вЂ�вЂ�AngiophagyвЂ™вЂ™ Is a Fundamental Mechanism of Microvascular Recanalization Jaime Grutzendler; New Haven, CT S122. Risk Factors for Intracranial Haemorrhage in Acute Ischaemic Stroke Patients Treated with rtPA William N. Whiteley, Karsten Bruins-Slot, Peter M. Fernandes, Peter A.G. Sandercock and Joanna Wardlaw; Edinburgh, United Kingdom and Oslo, Norway We have found a mechanism of recanalization in the cerebral microcirculation independent of the fibrinolytic system. This involves endothelial engulfment of emboli followed by their transendothelial translocation into the perivascular space. Here we compare the efficacy of this mechanism of microvascular clearance with that of the fibrinolytic system and determine if it is unique to the brain or if it occurs in other microvascular beds. Mice expressing GFP in endothelial cells were embolized with fibrin microclots and studied with high-resolution confocal, two-photon, and transmission electron microscopy. In the first 6-hours, endogenous fibrinolysis and hemodynamic forces cleared a significant portion of emboli but clearance dropped dramatically 6-hours post-occlusion. Tissue plasminogen activator had a modest additional effect that was limited to the first 6-hours postembolization. Emboli that failed to be washed-out underwent transendothelial translocation 2-7 days postocclusion. This occurred in the brain as well as the microvasculature of the heart, retina and skeletal muscle. Thus endothelial engulfment of emboli,вЂ™вЂ™angiophagyвЂ™вЂ™, is a robust mechanism of microvascular clearance likely to be important at maintaining vessel patency throughout life and could have important implications in the pathogenesis of a variety of embolic disorders. Study supported by: NIH/NIA Intravenous thrombolysis with recombinant tissue plasminogen activator is an effective treatment for acute ischaemic stroke, but is associated with an increased risk of fatal or disabling intracranial haemorrhage (ICH). We sought to identify the risk factors for ICH with a comprehensive systematic review of the published literature. We searched for relevant studies of stroke patients treated with rtPA that reported an association between a variable measured before rtPA infusion and subsequent, significant ICH. We calculated associations between baseline variables and ICH. We identified 55 studies that measured 43 baseline variables in 65,264 stroke patients. Post-rtPA ICH was associated with higher age (odds ratio [OR] 1.03 per year; 95%CI:1.01-1,04), higher stroke severity (OR 1.08 per NIHSS point; 95%CI:1.06-1.11), and higher glucose (OR 1.10 per mmol/L, 95%CI :1.05-1.14). There was approximately a doubling of the odds of ICH with the presence of atrial fibrillation, congestive heart failure, renal impairment, prior antiplatelet agents, leukoariaosis and a visible acute ischaemic lesion on pre-treatment brain imaging. Individual baseline variables are modestly associated with post-rtPA ICH. Prediction of post-rtPA ICH is therefore likely to be difficult if based on individual clinical or imaging factors alone. Study supported by: MRC Clinician Scientist Fellowship G0902303 to Dr. Will Whiteley S125. Chronic Inflammatory Diseases and Stroke: Evidence for Heterogeneous Mechanisms Jose Gutierrez and Mitchell S.V. Elkind; New York, NY Background: Increased inflammatory markers predict cardiovascular events. The relationship between chronic inflammatory diseases, inflammatory markers and stroke has been less well characterized. Methods: Using data from the 2005-2010 NHANES (n Вј 2210), we calculated odds ratios and 95% confidence intervals (OR, 95% CI) for the association of inflammatory diseases with stroke before and after adjusting for demographics, risk factors and inflammatory markers. S123. Reversible Cerebral Vasoconstriction in Pre-Eclampsia Pablo Garcia-Reitboeck, Phil Rich and Ali Al-Memar; London, United Kingdom Postpartum angiopathy forms part of the spectrum of reversible cerebral vasoconstriction syndromes, and typically presents with severe headaches, neurological deficits secondary to stroke or seizures. 37 ID: guganp I Black Lining: [ON] I Time: 09:24 I Path: N:/3b2/ANA#/Vol00000/120255/APPFile/JW-ANA#120255 J_ID: ZAY Customer A_ID: BKLT2012_Abstracts Cadmus Art: ANA12 Date: 18-September-12 Results: Stroke was associated with arthritis (OR 4.83, 3.82-6.09). Asthma was only associated with stroke in participants ! 55 years (2.25, 1.71-3.32), while hepatitis B and hepatitis C were associated with stroke in those < 55 years (OR 7.22, 2.76-18.87; and OR 9.57, 2.77-33.04, respectively). Adjusting for demographics and cardiovascular risks attenuated the association of stroke with asthma (OR 1.88, 0.93-3.81) and arthritis (OR 1.81, 0.90-3.65) and further controlling for inflammation did not modify the odds. The association of stroke with hepatitis B (OR 19.40, 4.82-77.90) and hepatitis C (OR 9.61, 2.58-35.78) persisted after adjusting for all potential confounders. Conclusions: The associations of asthma and arthritis with stroke prevalence may be confounded by cardiovascular risk factors, while viral hepatitis may be associated with stroke through other direct mechanisms. Study supported by: No support or finantial disclosure received for this workl Stage: Page: 38 using a grading scale based on visualization of the vessel wall, lumen, and plaque components. Results: The final imaging protocol was selected from the sequences that provided the best image quality without unacceptable scan duration. The final sequences include 3D acquisition of T1 weighted images (pre- and post-contrast), T2 weighted images, and FLAIR sequences. Summary: HRMRI can be used to identify IPH, fibrous cap, and lipid rich core in ICAS. Further studies are planned using this protocol to determine inter-rater reliability and the prognostic value of these plaque features in ICAS. Study supported by: NIH/NINDS 1K23NS069668 S128. Outcomes of Perfusion Based Endovascular Therapy in Witnessed Onset and Unwitnessed Onset of Stroke Deependra Khanal, Pratik Bhattacharya and Seemant Chaturvedi; Detroit, MI S126. Dabigatran Etexilate: Management in Acute Ischemic Stroke Parisa P. Javedani, B. Zane Horowitz, Wayne M. Clark and Helmi L. Lutsep; Portland, OR Around 25% of strokes occur during sleep, excluding them from intravenous tPA. While perfusion imaging has helped identify patients with salvageable tissue for endovascular therapy in patients with unwitnessed onset, it is unclear how the outcomes compare with those with known time of stroke onset. Patients admitted to a large volume stroke center from January 2009-December 2011 were reviewed. Patients who had a CT perfusion demonstrating penumbra and treatment by endovascular methods were selected. Outcomes were compared between those with witnessed and unwitnessed stroke onset. 39 patients (median age 62, males 51%, median NIHSS 13) were reviewed. At discharge, 46% showed NIHSS improvement by! 4 (witnessed onset: 13/28-46%, unwitnessed onset: 5/11-45%; p Вј 0.95). Six of seven deaths in the study, and two cases of symptomatic intracerebral hemorrhages were in the witnessed onset group. Similar rates of patients in both groups were discharged home or to rehabilitation centers (p Вј 0.30). Endovascular intervention can achieve comparable outcomes in patients with witnessed and unwitnessed stroke onset by using perfusion imaging. Contemporary therapies in acute stroke may see a paradigm shift from time-based treatments to tissue physiology based options. Study supported by: None. Background: The use of long-term oral anticoagulation is indicated for prevention of cardiac thromboembolism in patients with non-valvular atrial fibrillation. With the emergence of dabigatran, physicians must become familiar with the management of such patients. Case Report: A 54-year-old man on with dabigatran presented 69 minutes after an ischemic stroke. A National Institutes of Health Stroke Scale (NIHSS) was 9. Recombinant tissue plasminogen activator (rtPA) administration was not recommended secondary to dabigatran therapy. Angiography demonstrated occlusion of the left middle cerebral artery (L MCA), and suction thrombectomy achieved flow through the inferior division of the L MCA. CT showed possible intracranial hemorrhage (ICH), and dabigatran reversal was attempted with prothrombin complex concentrate (PCC) and recombinant factor VIIa (rFVIIa). He was discharged to rehabilitation with an NIHSS score of 8. Conclusion: The thrombin time, Hemoclot thrombin inhibitor assay, and ecarin clotting time are sensitive assays, but PTT is insensitive. Although PCC and rFVIIa can reverse the anticoagulant effect, a true antidote is not available. Conservative recommendations suggest waiting 48 hours since the last dabigatran dose before administering rtPA. Study supported by: Unfunded S127. High Resolution Magnetic Resonance Imaging (HRMRI) in Intracranial Atherosclerosis Tanya N. Turan, Truman R. Brown, Zoran Rumboldt and Robert J. Adams; Charleston, SC S129. A Retrospective Study of Complications and Discharge Dispositions after Treatment for Acute Ischemic Stroke Based on the Nationwide Inpatient Sample from 2006-2009 Tobias B. Kulik, Kate C. Young, Ann M. Leonhardt, Babak S. Jahromi and Curtis G. Benesch; Rochester, NY Introduction: HRMRI can identify prognostically important plaque features (intraplaque hemorrhage (IPH), fibrous cap, and lipid core) in extracranial carotid disease, but plaque features in intracranial atherosclerosis (ICAS), a more common cause of stroke worldwide, have not been systematically examined. This study aimed to refine a HRMRI protocol that will consistently visualize the arterial lumen, vessel wall, and atherosclerotic plaque components in patients with ICAS. Methods: 36 patients with 50-99% ICAS underwent a brain MRI using a 3Tesla Siemens scanner with a 32 channel head coil. Stepwise adjustments to the imaging protocol were made to refine the image quality. Images were assessed We sought to establish national estimates for the frequency of complications, the need for additional procedures, and discharge disposition for patients with acute ischemic stroke treated with either intravenous tPa (IVtPa), intra-arterial therapy (IAT) or without interventional treatment. In addition, we analyzed the discharge disposition by region (Northeast, Midwest, South, West) and teaching hospital status. Discharge records from the Nationwide Inpatient sample between the years of 2006-2009 were obtained and admissions for acute ischemic stroke identified utilizing the ICD-9 discharge diagnosis code. Data were analyzed with Microsoft Excel and SPSS. 38 ID: guganp I Black Lining: [ON] I Time: 09:24 I Path: N:/3b2/ANA#/Vol00000/120255/APPFile/JW-ANA#120255 J_ID: ZAY Customer A_ID: BKLT2012_Abstracts Cadmus Art: ANA12 Date: 18-September-12 In patients who had undergone IAT the rate of ICH and the need for a craniotomy, mechanical ventilation and tracheostomy placement, were significantly higher compared to patients treated with IVtPa (p 0.05). However, the rates of PEG tube placement, aspiration pneumonia and DVT did not differ significantly between both treatment groups. The rate of routine discharges after IVtpA were significantly higher compared to IAT, while the rates of discharge to short-term care, SNF rehab and hospice were comparable. The rate of fatal demise was significantly higher with IAT. Study supported by: N/A Stage: Page: 39 Parental hypertension was associated with SVD events (OR Вј 1.8, 95%CI 1.2-2.7) and with higher DBP: mean DBP Вј 82.1/7.6 vs.80.8/7.7, p Вј 0.04; most recent DBP Вј 80.7/10.4 vs. 77.8/10.6, p<0.0001. Conclusion: Increased DBP but not SBP is associated with lacunar events and with parental history of hypertension. DBP might play a particular role in the heritability of SVD. Study supported by: CSC S132. Is the Susceptibility to Carotid Atherosclerosis Reduced in Small Vessel Disease? Evidence from a Population-Based Study Linxin Li, Ziyah Mehta, Ursula Schulz and Peter M. Rothwell; Oxford, United Kingdom S130. No Significant Association of Aspirin Use with Cerebral Microbleeds in the Asymptomatic Elderly Chi Kyung Kim, Hyuk Tae Kwon, Jong-Ho Park and Hyung-Min Kwon; Seoul, Korea and Koyang, Korea Background: The distribution of atherosclerosis between intracranial vessels and carotid bifurcation differs between ethnic groups. Such difference in site-specific susceptibility may also exist within ethnic groups. We hypothesised that patients with small vessel ischaemic events may be less susceptible to atherosclerosis at the carotid bifurcation. Methods: In a population-based study of Caucasian stroke/TIA patients, we compared the frequency of atherosclerotic risk factors and the site-specific prevalence of atherosclerosis related disease (coronary disease; PVD; carotid stenosis) in patients with lacunar (LACI) versus non-LACI events. Results: Of 1659 stroke/TIA patients, the prevalence of coronary disease (19.7% vs.19.3%) and PVD (6.7% vs.7.1%) was similar in both groups. However, despite similar age and sex-adjusted prevalences of hypertension (OR Вј 1.1, 95%CI 0.8-1.5), diabetes (1.2, 0.8-1.8), hyperlipidemia (0.9, 0.7-1.2), and smoking (1.3, 1.0-1.8), patients with LACI events had lower prevalence of !70% carotid stenosis (5.1% vs.9.5%, p Вј 0.03). Conclusion: Within a Caucasian population, patients with lacunar events have a similar risk factor profile to those with non-lacunar events and a similar frequency of PVD and coronary disease, but less severe carotid stenosis, possibly due to reduced susceptibility to atherosclerosis at the carotid bifurcation. Study supported by: CSC Background and purpose: Cerebral microbleeds (CMBs) may predict future risk for intracerebral hemorrhage (ICH). We sought to investigate whether aspirin use is associated with CMBs in subjects without previous history of stroke. Methods: Asymptomatic elderly subjects (n Вј 1,452) were included. The subjects were categorized into two groups depending on CMB location: strictly lobar and deep or infratentorial microbleeds. Information about aspirin use was obtained using a structured questionnaire. Results: A total of 138 subjects (9.5%) were found to have CMBs. In the group of aspirin use, 43 subjects (11.2%) had CMBs. Compared with the non-use group, the risk for CMBs did not increase in the group of aspirin use (OR, 1.10; 95% CI, 0.73-1.66) and the risk for strictly lobar microbleeds and deep or infratentorial microbleeds also did not increase. For the group of aspirin use above 5 years, the proportion of CMBs did not increase compared with the group of short-term use and non-use group. Conclusions: The prevalence of CMBs did not increase in the group of aspirin use, and the presence of CMBs was not associated with the duration of aspirin use in asymptomatic elderly subjects. Study supported by: This work was supported by a grant from the Boramae Medical Center (03-2011-9). The funding organization had no role in the design, conduct, or analysis conducted during this study or in the preparation of this report. S133. The Secondary Degeneration in Red Nuclei Following Striatum Infarction Revealed by Diffusion Tensor Imaging Zijun Wang, Chao Qin, Zhijian Liang, Xuean Mo, Daobin Cheng, Yajuan Chen, Wei Ye and Yi Dai; Nanning, Guangxi, China S131. A Population-Based Study of Pre-Morbid Blood Pressure in Patients with Small Vessel TIA and Stroke Linxin Li, Nicola L.M. Paul, Linda Bull, Ziyah Mehta and Peter M. Rothwell; Oxford, United Kingdom Background: There is some evidence that hypertension is a particularly important risk factor for small vessel (SVD) stroke. However, the relative importance of systolic (SBP) versus diastolic (DBP) blood pressure is uncertain. We studied pre-morbid DBP and SBP in patients with SVD events versus other subtypes and in relation to parental family history of hypertension. Methods: In a population-based study with stroke/TIA, we studied all pre-morbid BP measurements over the 10 years preceding the event. Aetiological subtype was categorised using the TOAST classification. Results: In 1659 patients with over 20,000 pre-morbid BP measurements, mean (SD) pre-morbid SBP (mmHg) was similar in patients with SVD versus others (145.7/14.7 vs.145.2/15.8), but DBP was higher in those with SVD: mean DBP Вј 83.0/7.1 vs. 80.6/7.6, most recent DBP Вј 80.7/9.6 vs. 77.7/10.9, both p<0.0001. Results were similar in the subset of 1238 patients with family history data. Objects: To investigate the secondary degeneration in red nuclei after striatum infarction with diffusion tensor imaging (DTI) and its significance. Methods: Thirty two patients with striatum infarction underwent a DTI scan and a clinical evaluation with modified Rankin Scale (mRS) and Barthol Index, and the five patients with symptoms like Parkinson disease underwent an additional evaluation with the third subscale of unified ParkinsonвЂ™s disease rating scale (UPDRS III) in the twelve weeks from symptom onset. Thirty two healthy volunteers underwent a DTI scan as controlled. Results: Compared with the control group, the MD of ipsilateral side red nuclei in patients increased 27.72 percent (P<0.01), and the FA value of ipsilateral side red nuclei decreased 31.36 percent (P<0.01). Compared with the other patients, the MD of ipsilateral side red nuclei in the five patients with some symptoms like Parkinson disease 39 ID: guganp I Black Lining: [ON] I Time: 09:25 I Path: N:/3b2/ANA#/Vol00000/120255/APPFile/JW-ANA#120255 J_ID: ZAY Customer A_ID: BKLT2012_Abstracts Cadmus Art: ANA12 Date: 18-September-12 Stage: Page: 40 trol). Exclusions: TIA without infarct (n Вј 9), cerebral venous thrombosis (n Вј 1), dissection (n Вј 7), laboratory evidence of liver disease/disseminated intravascular coagulation (n Вј 4), or inherited/acquired factor deficiency (n Вј 17). Mean factor activities of cases and controls were compared using StudentвЂ™s t-test. Results: We enrolled 105 cases (47% female, mean age 67) and 99 controls (57% female, mean age 57). Mean activities: Factor IX cases 137% (SD 26.1), controls 137% (SD 28.9), p NS; Factor XI cases 113% (SD 24.2), controls 111% (SD 24.2), p NS. Results were unchanged after excluding control patients with history of stroke/TIA. Conclusions: Our study did not demonstrate higher mean factor IX or XI activities in subjects with ischemic stroke as compared to those with stroke mimics. Study supported by: no sponsor increased 5.87 percent(P <0.05). Moreover, he MD of ipsilateral side red nuclei in the five patients correlated with their UPDRS III positively(P<0.05). Conclusions: The secondary degeneration in red nuclei may be partly responsible for the symptoms like Parkinson disease in striatum infarction patients. Study supported by: national natural science foundation of china S134. Early Plasma Biomarkers of Ischemic Penumbra in Acute Stroke Svetlana Lorenzano, Natalia S. Rost, Hens B. Brouwers, Alfredo J. Caceres, Matthew S. Siket, Octavio M. Pontes Neto, Hua Li, Rebecca E. Green, Tijy Thankachan, Allison J. Dipietro, Brenda J. Thornell, Ona Wu, Ken Arai, Sophia Hartdegen, Angel T. Som, Loc-Duyen D. Pham, Peter J. Kelly, Gordon J. Harris, Eng H. Lo, Steven K. Feske and Karen L. Furie; Boston, MA and Dublin, Ireland S136. Partial to Complete Recanalization in Middle Cerebral Artery Occlusion Following Intra-Arterial tPA and Transcranial Doppler Monitoring Amer M. Malik, Krislynn Barnhart and Yince Loh; Seattle, WA Introduction: Advanced neuroimaging techniques may provide fundamental data with regard to brain tissue viability in acute ischemic stroke (AIS). We sought to assess whether plasma biomarkers of oxidative stress predict diffusion-perfusion mismatch in AIS patients. Methods: We measured plasma levels of high sensitivityCRP (hs-CRP), matrix metalloproteinase (MMP)-2 and MMP-9, F2-isoprostane(F2isoP), 8-hydroxydeoxyguanosine (8OHdG), and the Oxygen Radical Absorbance Capacity Assay (ORAC) in consecutive AIS patients presenting within 9 hours from symptom onset. Diffusion-(DWI) and perfusion-weighted(PWI) MRI sequences were analyzed using semi-automated volumetric method. Mismatch was defined as baseline mean transit time (MTT) volume on PWI minus DWI volume. A percent mismatch cut-off of 20% was considered clinically significant. Results: Mismatch was present in 154/228 (67.5%) patients (69.4614.4 years; 41.2% women). Compared to those without MRI evidence of mismatch, patients with mismatch were more likely to have higher ORAC-PCA (p Вј 0.03)and F2isoP (p Вј 0.07). After adjustment for confounders, multivariate logistic regression demonstrated that plasma F2isoP (OR1.74, 95%CI 1.06-2.9; p Вј 0.04) and ORAC-PCA (OR3.66, 95%CI 1.27-11.012; p Вј 0.02) were independent predictors of PWI-DWI mismatch. Conclusions: Elevated hyperacute plasma levels of F2isoP and ORAC-PCA are associated with radiographic evidence of mismatch in AIS subjects. If validated, these findings may provide further understanding of the role of oxidative stress in cerebral tissue fate during acute ischemia. Study supported by: SPOTRIAS - Specialized Program of Translational Research in Acute Stroke, NIH/NINDS Grant P50-NS051343 Background: As new primary and adjunct applications are pursued for sonothrombolysis, it is becoming increasingly accepted as a therapeutic strategy because it achieves the desired dual outcomes of increasing the rate of arterial recanalization while keeping hemorrhagic complications at a minimum. Methods: We report a case utilizing the minimally invasive combination of sonothrombolysis sequentially after intra-arterial tPA without direct clot manipulation in order to facilitate recanalization. Results: Following 5 mg of IA tPA without direct manipulation of clot, a remaining subocclusive MCA thrombus was treated with targeted TCD to facilitate complete recanalization. Conclusions: This case demonstrates the utility of TCD to monitor initial findings and subsequent recanalization. When necessary, direct insonation with TCD to achieve full recanalization immediately following IA tPA delivery without requiring direct manipulation of a thrombus may offer an alternative, safer approach to treating patients with intracranial occlusions. Additionally, this case suggests that there may be a basis for taking a subset of acute ischemic stroke patients to the angiography suite despite a low NIHSS score, or when outside the window of systemic thrombolysis. Study supported by: Amer M. Malik reports no disclosures. Krislynn Barnhart reports no disclosures. Yince Loh reports no disclosures. S137. Clinical and Radiologic Significance of Dilated Perivascular Spaces in Patients with Cognitive Impairment Sergi Martinez-Ramirez, Amy Halpin, Megan Quimby, Andrew P. Dumas, Mahmut Edip Gurol, Eithan Auriel, Steven M. Greenberg and Anand Viswanathan; Boston, MA S135. Elevated Factor IX and XI Activities May Not Be a Risk Factor for Ischemic Stroke Jennifer J. Majersik, George M. Rodgers, Kevin D. Call, Jana J. Wold, Ronda A. Crist, Anna M. Sherr, Elaine J. Skalabrin and Kristi J. Smock; Salt Lake City, UT; Provo, UT and Springfield, OR Objectives: To investigate the role of dilated perivascular spaces(DPVS), along with other markers of small-vessel disease, in patients with cognitive impairment. Methods: Review of prospective data from patients admitted to our memory clinic having high-resolution neuroimaging (structural 3T MRI) and a neuropsychological assessment performed within 2 years of scan. DPVS were rated in basal ganglia (BG-DPVS) and white matter (WMDPVS) on T1 sequences, using an established 4-point semiquantitative score. Additionally, microbleeds, white matter Background: Elevated factor IX and XI activities contribute to venous thromboembolism risk. Restrospective data suggests elevations may be associated with arterial thrombosis. Methods: We conducted a prospsective case-control study of Factor IX and XI activities to determine if they are elevated in patients with ischemic stroke. Subjects were eligible if they presented to the ED with suspected acute stroke. Stroke neurologists adjudicated ischemic stroke (case) vs. stroke mimic (con- 40 ID: guganp I Black Lining: [ON] I Time: 09:25 I Path: N:/3b2/ANA#/Vol00000/120255/APPFile/JW-ANA#120255 J_ID: ZAY Customer A_ID: BKLT2012_Abstracts Cadmus Art: ANA12 Date: 18-September-12 hyperintensities (WMH), lacunar infarcts and brain parenchymal fraction were quantified. DPVS degree was classified as high(score >2) or low (score 2). We compared characteristics between DPVS subgroups. Results: Ninety-three patients were included (mean age 72.7 6 9.99 years, 57% female). Fifty-five (59.1%) patients had CDR Вј 0.5 and 38 (40.9%) had CDR ! 1. High BGDPVS degree was associated with increasing age (80.462.9 vs 71.7 6 1 years, p Вј 0.005), hypertension (90.91% vs 45.12%, p Вј 0.007), higher WMH volumes (36.1065.77 vs 15.2662.11 ml,p Вј 0.001) and higher global CDR scores(p Вј 0.03). No significant associations were found for high WM-DPVS degree. In multivariate analysis, age and hypertension were independent predictors of high BG-DPVS degree. Interpretation: In individuals with cognitive impairment, BG-DPVS are associated with vascular risk factors. WMDPVS may arise from distinct mechanisms, requiring further investigation. Study supported by: NIA grant 5P50AG005134-28 Stage: Page: 41 patients who were on heparin in the presence of intraluminal thrombi. Prior studies imply recanalization can be achieved with heparin;however heparin should only prevent thrombus propagation theoretically. Methods: We compared patients with complete/partial recanalization or improved flow versus those that did not on CTA and angiograms;with both groups on a standard heparin infusion protocol. Recanalization was noted in 30patients and failure to recanalize in 12patients. Demographics, average PTT during heparin infusion, time between CTAs, time from stroke onset to receiving heparin, and vessel occluded were compared between groups. Results: Using t-test, the average PTT between the recanalization group(60.43833) and non-recanalization(67.91833) was not significantly different (p>0.05). The average time between CTAs was not either(78.03 vs.70.33hrs). Durational stratification did not yield significance using the Fischer exact test(p>0.05). Discussion: Other studies, clinical implications, and future directions are discussed. Conclusion: This is the first study to compare patient characteristics associated with recanalization of intraluminal thrombi in acute stroke patients who received heparin infusion. Recanalization of intraluminal thrombi were not associated with average PTT or duration on heparin. Study supported by: The authors have no disclosures relating to the abstract. S138. Protective Association between ACE Inhibitors and Lobar Intracerebral Hemorrhage Sharyl R. Martini, Matthew L. Flaherty, William M. Brown, Charles J. Moomaw, Mary E. Comeau, Mary Haverbusch, Dawn O. Kleindorfer, Brett M. Kissela, Joseph P. Broderick, Carl D. Langefeld and Daniel Woo; Cincinnati, OH and Winston-Salem, NC Background: Treating hypertension reduces the risk of spontaneous intracerebral hemorrhage (ICH). The PROGRESS study found fewer lobar ICHs in subjects randomized to ACE inhibitor (ACEI) Гѕdiuretic versus placebo, but few outcome events were ICHs. Methods: This prospective case-control study identified primary ICHs by hot-pursuit at Cincinnati area hospitals. Controls were matched to each case by age, race, and gender. Each consenting subject underwent structured interview, including self-reported medications and hypertension status. Hemorrhage location was classified as lobar or non-lobar. A multiple logistic regression model was computed to test for association between ACEI use and lobar/non-lobar location; covariates were hypertension, warfarin use, first-degree relative with ICH, education level, prior ischemic stroke, and Apolipoprotein E genotype. Results: 597 of 2,850 ICH cases consented and were matched to controls (n Вј 1548). In logistic regression, treatment with ACEI was negatively associated with lobar ICH in hypertensive subjects (P Вј 0.001; OR Вј 0.39, 95% CI Вј 0.21вЂ“0.76), compared with non-hypertensive subjects. This association was not significant for subjects on other antihypertensive class regimens (P Вј 0.141; OR Вј 0.69; 95% CI Вј 0.42вЂ“1.15). Conclusion: Treated hypertension is associated with reduced risk for lobar ICH, and this protective association may be greatest with ACEI. Study supported by: NIH Salaries for several authors are/ have been paid from the NIH grant supporting this study, or from the stroke T32 training grant at University of Cincinnati. Other co-authors are contracted researchers paid from the NIH grant supporting the study. S140. Cerebral Vasospasm and Anterior Circulation Stroke Secondary to an Exacerbation of Hereditary Corproporphyria вЂ“ First Reported Case Stephen Mullin, Andrew Platts and Kashmir Randhawa; London, United Kingdom Neurological sequalae are a well documented complication of acute porphyria. Vasospam has been described in exacerbations of acute intermittent porphyria (AIP), but has not been previously been reported in an acute attack in hereditary coproporphyria (HCP). We describe the first reported case of porphyric crisis (triggered by rifampicin) leading to vasospasm and stroke in a previously undiagnosed case of HCP. Study supported by: no support to declare S141. Physiologic Device-Based Diagnosis of Stroke in Acute Vertigo: Proof-of-Concept Ali S. Saber Tehrani, Georgios Mantokoudis, John H. Pula, Cindy Guede, Kevin A. Kerber, Richard Rothman, Daniel F. Hanley, David S. Zee, Jorge C. Kattah and David E. Newman-Toker; Baltimore, MD; Peoria, IL and Ann Arbor, MI Objective: Experts distinguish central from peripheral causes of acute vestibular syndrome (AVS) using oculomotor findings (вЂ�вЂ�HINTSвЂ™вЂ™вЂ“Head Impulse test, Nystagmus, Test of Skew). We sought to generalize this approach by using a quantitative, portable video-oculography device to diagnose posterior circulation stroke. Methods: Prospective observational study at two academic medical centers (08/2011-03/2012). Convenience sample of adult emergency department (ED) patients with AVS defined as >24hrs of acute dizziness/vertigo, nausea/ vomiting, head motion intolerance, gait unsteadiness, and nystagmus. We measured tolerability, usability, and diagnostic oculomotor findings according to a standard protocol (вЂ�вЂ�HINTSвЂ™вЂ™). Funding limitations precluded uniform gold standard neuroimaging (MRI DWI >48hrs after onset) in all patients, but was available clinically in most. S139. Heparin May Not Improve Recanalization of Intraluminal Thrombi in Acute Stroke Patients Haris Kamal, Ping Li, Mohammed Shafie, Max Mokin and Bijal K. Mehta; Buffalo, NY and Torrance, CA Background: Intravenous heparin is usually contraindicated in acute stroke patients. We present a study of acute stroke 41 ID: guganp I Black Lining: [ON] I Time: 09:25 I Path: N:/3b2/ANA#/Vol00000/120255/APPFile/JW-ANA#120255 J_ID: ZAY Customer A_ID: BKLT2012_Abstracts Cadmus Art: ANA12 Date: 18-September-12 Stage: Page: 42 tein(LDL)] measured at the Offspring 4th examination to 10year risk of incident ischemic stroke and MI. During a mean follow-up of 9 years, 296 participants experienced incident ischemic stroke. In multivariateadjusted analyses HDL 40 was associated with increased risk of ischemic stroke (HR [95%CI]:1.58[1.23-2.0], p<0.001). We did not observe any association with TC,TG or LDL and incident ischemic stroke. In MI-free sample (N Вј 5795, 389 events), we observed strong associations between TC, HDL, TG and LDL and MI risk. Conclusion: In our stroke-free sample, we observed that low HDL, but no other lipid biomarkers were associated with risk of incident ischemic stroke. We also observed the usual associations between lipid biomarkers and risk of MI. Study supported by: This work was supported by National Institutes of Health/National Heart, Lung, and Blood Institute Contract and the National Institute of Neurological Disorders and Stroke R01 NS17950. Results: 88 screened; 14 eligible; 13 AVS patients enrolled (mean age 61 years, 46% female). All patients completed testing; none vomited. Mean patient-reported comfort was 8.9/10. Mean research assistant-reported usability was 8.4/10. In the 11 patients with definitive neuroimaging, accuracy of stroke (n Вј 6) versus peripheral vestibular (n Вј 5) diagnosis by video-oculography-based вЂ�вЂ�HINTSвЂ™вЂ™ exam was 100%. Conclusion: It is feasible to perform the HINTS battery in the ED using a video-oculography device. Preliminary results show promising diagnostic accuracy, and further study is warranted. Study supported by: No funding supported this project. The video oculography goggles were provided free of charge by GN Otometrics, Sydney, Australia. S142. Ischemic Burden in Relation to Apolipoprotein B/AI Ratio in Intracranial Atherosclerotic Stenosis Jong-Ho Park; Goyang, Republic of Korea and Seoul, Republic of Korea S144. Transient Aura Attacks in Cerebral Amyloid Angiopathy Respond to Migraine Prophylactics Patrick Pullicino, Ross W. Paterson and Ken Uchino; Canterbury, Kent, United Kingdom and Cleveland, OH Background: Preexisiting brain infarct (PBI), usually silent is frequently seen on MR imaging in stroke patients. High levels of apolipoprotein B (apoB)/apoAI ratio are a risk predictor of ischemic stroke and associated with intracranial atherosclerotic stenosis (ICAS). Little is known about association of apoB/apoAI ratio with PBI in stroke patients with ICAS. Methods: A total of 522 statin/fibrate naД±ВЁve patients with acute ischemic stroke were categorized into ICAS (n Вј 254), extracranial (ECAS, n Вј 51), and no cerebral atherosclerotic stenosis (NCAS, n Вј 217). The apoB/apoAI ratio and demographics were compared between those with and without PBI. PBIs were divided into deep subcortical (dsPBI) and hemispheric (h-PBI) by location. Results: Patients with PBI showed a higher apoB/apoAI ratio than those without (0.8160.28 versus 0.7260.23, P<0.001). Patients with higher quartiles of the apoB/apoAI ratio had a higher number of ds-PBI (P Вј 0.025) in the ICAS group. With multivariable analyses, the highest apoB/ apoAI ratio quartile was associated with ds-PBI (OR Вј 2.48; 95% CI, 1.33вЂ“4.62) and advanced (!3) ds-PBIs (2.68, 1.27вЂ“5.63) in the ICAS group. ApoB/apoAI ratio conferred no increased risk for h-PBI. Interpretation: A higher apoB/apoAI ratio might constitute deep subcortical ischemic burden in Asian patients with ICAS. Study supported by: This study was supported by a clinical research grant from Kwandong University Myongji Hospital. We report three patients with cerebral amyloid angiopathy (CAA) with recurrent stereotyped migraine aura-like episodes with response to migraine prophylactics. Three women (74, 71, 81yrs) had MRI typical of CAA. None had prior history of migraine. Patient 1 had left sided numbness migrating from the face to leg over minutes seven times a day over three years. They resolved on topirimate 50mg bd. Patient 2 had bilateral visual bright lights and pinwheels lasting half an hour five times a day over three months resolving with verapamil 120mg bd. Patient 3 had ten episodes of arm numbness, weakness and mumbling speech lasting five minutes. The duration of attacks and response to migraine prophylactics supports a вЂ�вЂ�spreading depressionвЂ™вЂ™ pathogenesis. The clinical distinction of these attacks from TIAs is important as antiplatelet agents could increase the risk of hemorrhage. Gradient echo MRI should be performed in all elderly patients with recurrent migraine like auras. Topiramate or verapamil should be tried as treatment. Study supported by: none S145. Superposition of Stents in the Management of Intracranial Aneurysms in Arterial Bifurcations Ricardo A. Rangel-Guerra and Alberto Garcia-de la Fuente; Monterrey, NL, Mexico and Monterrrey, NL, Mexico Introduction: The management of aneurisms in the intracranial artery bifurcation with wide neck, was conservative in nature and with surgical complicated techniques. Objective: Experience with 8 cases of this type of lesions. Material and Methods: Year 2010-2011, we collected 8 cases with intracranial aneurysms both incidental and symptomatic. Age of the patients ranged from 35-74. 7 women and 1 man. In all patients STENTS ENTRPRICE were used, placing the first STENT in the most angulated artey, leaving the micro catheter within the aneurysm for positioning the coils inside the aneurysm for its final occlusion. All patients received platelad antiaggregation with 600 mg of clopidogrel, 100 mg of aspirin and they were heparinized. Results: From the 8 patients, one did not received the coils. In all cases there was proof of complete occlusion of the aneurysm. In 4 patients digital Pan angiography was performed 6 months later, and it was confirmed that was no S143. Lipid Measurements and Risk of Ischemic Vascular Events: Framingham Study Aleksandra Pikula, Alexa S. Beiser, Jayandra J. Himali, Margaret Kelly-Hayes, Carlos S. Kase, Sudha Seshadri and Philip A. Wolf; Boston, MA and Framingham, MA Background: Lipid biomarkers are used to assess the risk of ischemic heart disease, but their value in stroke risk assessment remains controversial. We explored the relationship between plasma lipid measurements and incident ischemic vascular events in our middle-aged community cohort. Methods/Results: In 6187 stroke-free Framingham participants (64610yrs,56%F), we related plasma lipid levels [total cholesterol (TC) and high density lipoprotein (HDL)], measured at the Original cohort 15th and 20th examination, and [TC, HDL, triglycerides (TG) and low-density lipopro- 42 ID: guganp I Black Lining: [ON] I Time: 09:25 I Path: N:/3b2/ANA#/Vol00000/120255/APPFile/JW-ANA#120255 J_ID: ZAY Customer A_ID: BKLT2012_Abstracts Cadmus Art: ANA12 Date: 18-September-12 recanalization or growing of the aneurysm or intra Stent stenosis. Conclusion: The use of DUAL вЂ�вЂ�YвЂ™вЂ™ STENTS is useul for the management of aneurysms when located in arterial bifurcations, avoiding the recanalization of the aneurysms. Study supported by: I Stage: Page: 43 can precede the onset of hematologic abnormalities in TTP. TTP should be part of the differential diagnosis of cryptogenic stroke despite absence of hematologic abnormalities. Study supported by: UTSW Medical Center S148. Genetic Variants Associated with Severity of Leukoaraiosis Predict Ischemic Stroke Risk Natalia S. Rost, William J. Devan, Jing Wang, Guido Falcone, Poneh Adib-Samii, Matthew Traylor, Alesandro Biffi, Kaitlin M. Fitzpatrick, Valerie Valant, Alexa Beiser, Steven Bevan, Bradford B. Worrall, Christopher Levi, Cathie Sudlow, Peter Rothwell, Giorgio Boncoraglio, Martin Dichgans, James Meschia, Philip A. Wolf, Hugh Markus, Karen L. Furie, Qiong Yang, Sudha Seshadri and Jonathan Rosand; Boston; London, United Kingdom; Charlottsville; Newcastle, Australia; Edinburgh, United Kingdom; Oxford, United Kingdom; Milan, Italy; Munich, Germany and Jacksonville S146. A Recombinant Human Neuron-Binding IgM Protects the Brain Against Experimental Stroke by Improving Motor Function, Reducing Infarct Volume and Preserving Tissue Integrity Bharath Wootla, Aleksandar Denic, Makoto Eriguchi, Istvan Pirko and Moses Rodriguez; Rochester, MN Cerebral ischemia induces an inflammatory pervasive environment that results in neuronal damage. We demonstrated that the recombinant form of a natural human IgM antibody, rHIgM12, binds to neurons in vitro and promotes neurite outgrowth. Here we show that administration of rHIgM12 protects mice from ischemia-induced damage and improves neurologic deficits in the photo-thrombotic model of experimental ischemic stroke. Animals administered with a single low dose of 200 lg rHIgM12 30 minutes after stroke induction demonstrated improved locomotor function beginning 3 days after treatment, persisting until experiment termination at 30 days. Conversely, the saline control group deteriorated in function below the baseline and did not recover (p<0.05). The functional improvement mirrored a reduction of infarct volume and a concomitant increase of the magnetization transfer ratio (rHIgM12 [46.060.9] vs saline [41.9Гѕ08], P Вј 0.01) in the ischemic region (control region [59.960.9]), which suggests preservation or partial normalization of tissue integrity. This is the first demonstration that a fully recombinant natural human monoclonal IgM antibody directed against neurons is efficacious in improving behavioral and MRI outcomes in animals after experimental cerebral ischemia. Study supported by: This work was supported by grants from Minnesota Partnership for Biotechnology and Medical Genomics. Background: MRI-detectable white matter hyperintensity (WMH), or leukoaraiosis is a common and heritable stroke risk factor. We hypothesized that the common genetic variants which contribute to WMH severity also affect individual ischemic stroke (IS) risk. Methods: We identified single nucleotide polymorphisms (SNPs) associated with WMH volume in a genome-wide data meta-analysis of 2,504 IS cases enrolled through the International Stroke Genetic and Wellcome Trust Case Control Consortia. A genetic risk score (GRS) derived as a sum of the risk alleles across 961 loci of interest associated with WMH at p-value<10e-4 and applied to 4,176 healthy Framingham Heart Study participants, of whom 168 developed IS. Results: Entered as an independent variable into the multivariable Cox proportional hazards model with incident IS as outcome, the GRS was associated with incident IS risk (OR Вј 1.16, p Вј 0.03), corresponding to 16% risk increase per each GRS unit. Conclusions: The GRS comprised of SNPs related to WMH burden in a large, genome-wide IS study is associated with incident IS risk among healthy adults. Shared genetic variation may contribute to severity of leukoaraiosis and individual stroke risk. Study supported by: The American Heart Association Bugher Foundation; the Massachusetts General Hospital Deane Institute for Integrative Research in Atrial Fibrillation and Stroke; the National Institutes of Health: NINDS K23NS064052, R01NS059727, P50NS051343, R01 NS42733; NHLBI N01-HC-25195, and N02-HL-6-4278, and NIH AG033193, HL093029 and NS17950; the Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine and Boston Medical Center; the Australian Stroke Genetics Consortium; and the Wellcome Trust (085475/B/08/Z, 085475/Z/08/Z, WT084724MA). S147. Acute Ischemic Stroke Caused by Thrombotic Thrombocytopenic Purpura without Significant Hematologic Abnormalities Julio C. Rojas, Fazeel Siddiqui, Bardia Nourbakhsh, Chirantan Banerjee and Craig Powell; Dallas, TX Background: Thrombotic thrombocytopenic purpura (TTP) is a hematologic condition that can present with transient ischemic attack (TIA) or stroke. Neurological manifestations of TTP are typically associated with profound thrombocytopenia, and the diagnosis is rarely suspected in the setting of normal or near-normal platelet counts. Case summary: We present the case of a 29 year-old Hispanic woman who presented with an acute right middle cerebral artery (MCA) territory stroke and mild thrombocytopenia. Her vascular imaging, transesophageal echocardiogram, hypercoagulable and autoimmunity markers, were unremarkable. Her stroke was considered cryptogenic in the setting of oral contraceptive use. She presented two months later with a left MCA territory TIA and profound thrombocytopenia. She had evidence of microangiopathic hemolytic anemia and the diagnosis of TTP was confirmed by severe ADAMTS13 deficiency and increased ADAMTS13 inhibitory antibodies. She was treated with plasmapheresis and steroids, with rapid improvement of thrombocytopenia and anemia and no further neurovascular events. Conclusion: This case highlights the major therapeutic implications of recognizing that neurological manifestations S149. Body Mass Index and Mortality in Acute Ischemic Stroke Lesli E. Skolarus, Brisa N. Sanchez, Deborah A. Levine, Kevin A. Kerber, Lewis B. Morgenstern, Melinda A. Smith and Lynda D. Lisabeth; Ann Arbor Background and Purpose: Guidelines for patients with acute ischemic stroke (AIS) recommend a goal BMI of 18.5 to 24.9 kg/m2 and are largely extrapolated from primary cardiovascular disease prevention studies. We examined the relationship between BMI and all-cause mortality in AIS patients. 43 ID: guganp I Black Lining: [ON] I Time: 09:25 I Path: N:/3b2/ANA#/Vol00000/120255/APPFile/JW-ANA#120255 J_ID: ZAY Customer A_ID: BKLT2012_Abstracts Cadmus Art: ANA12 Date: 18-September-12 Methods: AIS patients (n Вј 1,791) were identified from the population-based Brain Attack Surveillance in Corpus Christi (BASIC) study from June 1, 2005 to December 31, 2010. Median follow-up was 660 days (range 0-2038 days). All AIS patients had in-hospital self-reported BMI recorded. The association between BMI and mortality was estimated using Cox regression models. Results: Median BMI was 27.1 kg/m2. After adjusting for demographics, stroke severity, stroke and mortality risk factors, the relationship between BMI and mortality was U-shaped. As BMI increased from 17 to 30 kg/m2, mortality decreased. As BMI increased above 31 kg/m2 mortality increased becoming significantly harmful when BMI reached 38 kg/m2. Conclusion: BMI has a heterogeneous effect on mortality in AIS patients with a protective effect for mild obesity and a detrimental effect for severe obesity. More research is needed on individual and incremental benefits and harms of weight management post-stroke. Study supported by: NIH/NINDS R01NS038916 Dr. Skolarus was supported by an American Academy of Neurology Foundation Clinical Research Training Fellowship and is supported by NIH grant K23NS073685. Stage: Page: 44 Methods: The mononuclear cells (MNCs) were extracted from carotid endarterectomy (CEA) samples by enzymatic digestion and magnetic cell sorting. Gene expression of proinflammatory/pro-thrombotic (P38, ERK-1, JNKb1, EGR1, PAI-1, TLR-2 TLR-4, MMP-9, TNF-a, MCP-1, TF, mTOR) and anti-inflammatory (PPAR-c and TGF-b) mediators were compared with the Ficoll-derived peripheral MNCs. Results: The expression levels of both pro-inflammatory/ pro-thrombotic and ant-inflammatory mdiators were higher in the the CEA MNCs as compared to the peripheral MNCs. An inverse relationship was observed between the expression levels of inflammatory mediators in the CEA MNCs and the peripheral MNCs of CDPS. The p38 and PPAR-c expression levels were lower in the CEA MNCs of symptomatic as compared to asymptomatic patients. TLR-2, TLR-4 and PPAR-c expression levels were higher in the peripheral MNCs of diabetic patients as compared to non diabetic patients. Higher expression levels of MMP-9 and PPAR-c, and lower expression levels of MCP-1 in CDPs as compared to HCs were observed. Conclusion: Pro-inflammatory and anti-inflammatory mediators are upregulated in the immune cells of the plaque. Study supported by: Jug for the Jake S150. Comparative Gene Expression Profiling of Simvastatin Single and Vytorin Combination Therapy in Hypercholesterolemic Subjects Zohara Sternberg, Trevor Chichelli, David Hojnacki, Alison Drake and Frederick Munschauer; Buffalo S152. A Comparative Study of Immune Cells, and Their Activation State, in the Carotid Plaque and in the Peripheral Circulation Zohara Sternberg, Kristen Glotti, Joseph Tario, Richard Curl, Sonya Noor, Paul Wallace, Frederick Munschauer and Paresh Dandona; Buffalo, NY Objectives: To test the hypothesis that treatment with Ezetimibe/Simvastatin (Vytorin), a combination of lipid-lowering agent which inhibits both intestinal cholesterol absorption and cholesterol synthesis, leads to broader changes in immunomodulatory genes, independent from their lipid lowering effects, when compared to Simvastatin monotherapy. Methods: IlluminaвЂ™s GenomeStudio gene expression module was used to compare both the global and the immunomodulatory gene profiles of Vytorin and Simvastatin in 20 hypercholesterolemic subjects in a randomized crossover design. Results: We observed alterations in gene expression postVytorin and post-Simvastatin therapy. However, broader changes in both global gene expression and immunomodulatory gene expression were observed by Vytorin combination therapy compared to Simvastatin monotherapy. In addition, the characteristics of the immunomodulatory genes altered by Vytorin were different from those altered by Simvastatin: Vytorin mostly altered the expression levels of genes related to inflammation/oxidative stress and cellular adhesion/migration/coagulation, while Simvastatin mostly altered the expression levels of genes related to cellular apoptosis/cell proliferation. Furthermore, Vytorin combination therapy reduced various components of lipid profiles more effectively than Simvastatin monotherapy. Conclusion: The nature of the pleiotropic effects may play a role in VytorinвЂ™s and SimvastatinвЂ™s clinical efficacy. Study supported by: Merck Objective: This study aimed to characterize, quantify and compare mononuclear cellsвЂ™(MNCs) subpopulations between carotid endarterectomy (CEA) samples and those cells in the peripheral circulation. Methods: MNCs were extracted from 16 CEA samples by enzymatic digestion. Peripheral MNCs of the carotid patients (CPs) and 12 age- and gender-matched healthy controls (HCs) were separated by Ficoll. Resting (R) and activated (A) MNCs were compared between carotid CEA and peripheral circulation. Results: The percentage of R-MNCs was lower, and that of A-MNCs was higher in the CEA samples as compared to the peripheral circulation. The percentage of the peripheral A-T cells and A-B cells were higher in CPs as compared to HCs, Symptomatic patients showed a trend toward a higher percentage of peripheral A-MNCs, and a lower percentage of the CEA A-MNCs as compared to asymptomatic patients. Patients stratification based on the use of anti-diabetic medications showed a trend toward a higher percentage of A-MNCs in both the peripheral circulation and in the CEA samples of those patients on anti-diabetic drugs. Conclusion: The immune inflammatory status is upregulated in the environment of the carotid plaque. Study supported by: Jug for the Jake S153. Dissection in the VeteransвЂ™ Administration (DIVA): Re-Examining Spinal Manipulation and Cervical Artery Dissection David E. Thaler, Xuemei Cai, Ali Razmara, Karen Switkowski, Sergey D. Goryachev, Leonard DвЂ™Avolio, Pari J. Fariborz and Edward Feldmann; Boston, MA S151. Immune Inflammatory Cross-Talk between Carotid Plaque and Peripheral Circulation Zohara Sternberg, Husam Ghanim, Elad Levy, Adnan Siddiqui and Paresh Dandona; Buffalo, NY Objectives: To characterize, quantify and compare the contribution of immune cells to the inflammatory status in the carotid plaque and in the peripheral circulation. Background: Cervical artery dissection (CAD) has been associated with spinal manipulative therapy (SMT) in case 44 ID: guganp I Black Lining: [ON] I Time: 09:25 I Path: N:/3b2/ANA#/Vol00000/120255/APPFile/JW-ANA#120255 J_ID: ZAY Customer A_ID: BKLT2012_Abstracts Cadmus Art: ANA12 Date: 18-September-12 series and case-control studies. Cassidy et al also associated case status with primary care physicians (PCP) visits, so questioning the causal effect attributed to SMT. We hypothesized that CassidyвЂ™s case definition included subjects with strokes unrelated to dissection which would confound their conclusion. Methods: We searched the national VA electronic medical record (EMR) for ICD9 codes that defined cases for Cassidy (433.0x, 433.2x). EMR text from these records was searched for the word вЂ�вЂ�dissection.вЂ™вЂ™ Records were manually reviewed by vascular neurologists to diagnose atraumatic CAD. Results: The EMR contained 11,372 unique subjects with the specified ICD9 codes. Of those, вЂ�вЂ�dissectionвЂ™вЂ™ was found in EMR text documents in 19%. Manual review of 50 randomly selected records found 2 (4%) atraumatic dissections and 1 (2%) involving the vertebral artery. Conclusions: Our data suggest that ICD-9 codes have low specificity for dissection and misclassify cases. Assuming that misclassification does not differ by exposure to SMT, Cassidy likely underestimated the association of SMT and dissection. Uncontrolled confounding likely explains the relationship between cases and PCPs. Study supported by: CTSI Pilot Grant Stage: Page: 45 posterolateral thalamic nucleus (VPL). Lesioned mice develop robust and long-lasting mechanical allodynia and cold hypersensitivity in the contralateral hind paw. We tested two prevailing hypothesis concerning CPSP pathogenesis, namely (1) that disinhibition of the medial pain system after VPL lesion contributes to CPSP and (2) that the thalamic lesion itself induces lateral thalamic hyperexcitability. Our results show that inhibiting the medial pain system by blocking TRPV1 positive nerve endings peripherally or ablation of a major afferent projection (spinal cord lamina I) did not reduce pain behavior in the CPSP model. In contrast, microinjecting lidocaine into VPL of CPSP mice to reduce hyperexcitability completely reversed tactile and cold hypersensitivity. In conclusion, we have generated the first mouse model of CPSP and provided evidence that CPSP results from increased lateral thalamic excitability rather than a disinhibited medial pain system. In addition to providing pathophysiologic insights, this model might prove useful for testing new therapies. Study supported by: Post-doc fellowship of the Medical Faculty of the University of Heidelberg S156. The Third International Stroke Trial (IST-3) of Intravenous rt-PA: Effect of Age and Time among 3035 Patients Randomised Graham Venables, Richard Lindley, Peter Sandercock, Joanna Wardlow and Geoff Cohen; Sheffield, United Kingdom; Sydney, Australia and Edinburgh, United Kingdom S154. Lobar Microbleeds without Intracerebral Hemorrhage: A Clinical, Genetic and Neuroimaging Analysis Ellis S. van Etten, Eitan Auriel, Alison M. Ayers, Anastasia Vashkevich, Kristin M. Schwab, Jonathan Rosand, Anand Viswanathan, Steven M. Greenberg and M. Edip Gurol; Boston, MA Background and aims: IST-3 seeks to improve the external validity and precision of the estimates of the overall treatment effects (efficacy and safety) of rtPA in acute ischaemic stroke, and to determine whether a wider range of patients might benefit. Methods: International, multi-centre, prospective, randomized, open, blinded endpoint (PROBE) trial of intravenous rtPA 0.9 mg/kg in acute ischaemic stroke. Patients had to be assessed and able to start treatment within 6 hours of developing symptoms, and brain imaging must have excluded intracranial haemorrhage and stroke mimics; detailed protocol at www.ist3.com. Results: We will report effects of time to randomisation and age on response to treatment among the 3035 patients recruited. Conclusion: The data from the trial will provide new evidence on the effect of age and time on the benefit from intravenous rtPA in a wider range of patients, especially among patients over 80 years, a group which has largely been excluded from previous randomised acute stroke thrombolysis trials. Study supported by: Australian Heart Foundation, Australian NHMRC, Dalhousie University Internal Medicine Research Fund. Norwegian Research Council. Government of Poland. AFA Insurances, the Swedish Heart Lung Fund, Karolinska Institutet, Stockholm County Council, ALF-project grants. Swiss National Science Foundation, Swiss Heart Foundation. Medical Research Council UK, The Health Foundation, The Stroke Association, DeSACC, The University of Edinburgh. Drug and placebo for the 300 patients in the double-blind component of the start-up phase were supplied by Boehringer-Ingelheim UK. Background/Objective: The classical presentation of cerebral amyloid angiopathy (CAA) is lobar intracerebral hemorrhage (ICH), but lobar microbleeds (MB) are frequently detected on MRI in the absence of ICH. We compared the risk factors, genetic and radiologic features of these patients to CAA patients with lobar ICH. Methods: Data on vascular risk factors and apolipoprotein E (APOE) genotype were compared between 511 CAA patients presenting with ICH and 79 without ICH. Microbleed counts and Pittsburgh Compound B (PiB) retention on PET were also compared. Results: Patients presenting without ICH were younger (70610 vs 7469.9,p Вј 0.002), more likely to have ApoE4 allele (54% vs 37%,p Вј 0.009) and hypercholesterolemia (47% vs 32%,p Вј 0.011) after adjustment for other risk factors and statin use. Patients without ICH had more lobar MBs(p<0.001). Global and regional values of amyloid deposition on PiB-PET were similar between the groups, including high occipital/frontal ratios characteristic of CAA pathology. Conclusion: Patients who present with lobar MBs on MRI without ICH have a clinical, genetic, and neuroimaging profile suggestive of severe CAA pathology. These data raise the possibility that particular clinical or genetic factors may influence whether advanced CAA proceeds to trigger lobar ICH. Study supported by: S155. A New Mouse Model for Central Post-Stroke Pain Simon Gritsch, Rohini Kuner and Daniel Vardeh; Heidelberg, Germany and Boston S157. Should We Thrombolyse the Oldest Old? Julio R. Vieira, Shankar Awasthi and Barbara Koppel; New York, NY Approximately 8% of stroke victims suffer from chronic post stroke pain (CPSP), but the underlying pathophysiology and anatomical substrate remain poorly understood. We generated a mouse model of CPSP, produced by either a hemorrhagic or excitotoxic lesion of the ventral Objective: Determine if patients age >80 or with recent Coumadin use can safely receive thrombolysis. 45 ID: guganp I Black Lining: [ON] I Time: 09:25 I Path: N:/3b2/ANA#/Vol00000/120255/APPFile/JW-ANA#120255 J_ID: ZAY Customer A_ID: BKLT2012_Abstracts Cadmus Art: ANA12 Date: 18-September-12 Background: Although age >80 is a relative tPA exclusion, this includes many stroke patients. We sought predictors of poor outcome in this group. Design/Methods: Analysis of all stroke codes, 20072011, for outcome in elderly and those recently using coumadin. Results: A 90 year-old woman on Coumadin (INR Вј 1.1) for atrial fibrillation presenting with aphasia and hemiparesis suffered terminal multifocal hemorrhages three hours after thrombolysis. During this period, tPA was given to five patients with history of Coumadin use and INR<1.6, with one other death due to GI bleeding. Hemorrhagic transformation occurred in a 63 year-old man. A 94 year-old woman did not improve with tPA. Overall, 19% of 214 stroke-codes were for patients >80 years. Conclusions: Clinicians will increasingly have to decide on tPA use in the elderly. Without recent Coumadin use, (mortality rate 40%), its use appears safe. Coumadin, advanced age, and possible amyloid angiopathy contributed to ICH in our patient. In our center, tPA is now avoided in anyone who has used Coumadin in the previous week, or dementia, but clinical judgement is needed in the oldest old. Study supported by: No financial support Stage: Page: 46 abnormal findings such as cerebral venous sinus thrombosis(CVST). She had high fever, tachycardia, bloody stool and diarrhea. Blood examination showed anemia and elevated erythrocyte sedimentation rate(ESR), suggesting her UC was uncontrolled. We started intravenous(iv) glycerol, antibiotics and mesalazine for UC. Neurological deficit improved quickly but on the fifth day of hospitalization, brain CT showed another intracerebral hemorrhage at the right occipital lobe, and the initial edema increased. We considered her condition as brain hemorrhage caused by cerebral vasculitis due to UC and added iv steroids followed by oral prednisolone. After steroid therapy, edema on brain MRI improved in a short time and the patient discharged with no sequela. UC is a rare cause of stroke. Although most of them are CVST, there are few reports of cerebral vasculitis with brain hemorrhage. Study supported by: none S160. Genetic Variants on 9p21.3 Are Associated with Brain Arteriovenous Malformations with Associated Flow-Related Arterial Aneurysms Helen Kim, Nasrine Bendjilali, Jeffrey Nelson, Shantel M. Weinsheimer, Mark Segal, Charles E. McCulloch, Ludmila Pawlikowska and William L. Young; San Francisco, CA Background: The 9p21.3 locus is associated with risk of coronary artery disease and intracranial and abdominal aortic aneurysms (rs10757278). We investigated whether previously reported 9p21.3 SNPs are associated with risk of brain arteriovenous malformations (BAVM), which often have accompanying flow-related arterial aneurysms. Methods: Genotypes for 6 SNPs, including rs10757278, were imputed using 1000 Genomes Phase 1 CEU data (R2>0.9). We tested for association using logistic regression of imputed dosages adjusting for age, sex and top 3 components of ancestry in: (a) 338 BAVM cases vs. 504 controls, (b) 75 BAVMГѕ(with) aneurysm cases vs. 504 controls, and (c) 150 BAVM-(without) aneurysm cases vs. 504 controls. Results: rs10757278-G was marginally associated with BAVM (OR Вј 1.23, 95% CI Вј 0.99-1.53, P Вј 0.064). Compared to controls, the association was stronger in BAVMГѕaneurysm (OR Вј 1.50, 95% CI Вј 1.03-1.89, P Вј 0.035) than in BAVM-aneurysm cases (OR Вј 1.03, 95% CI Вј 0.77-1.33, P Вј 0.832). Similar effects were observed for other SNPs in linkage disequilibrium (r2>0.8) with rs10757278. Conclusion: Common 9p21.3 variants showed similar effect sizes as previously reported for aneurysmal disease. The SNP association with BAVM appears to be explained by known association with aneurysms, suggesting that BAVM associated aneurysms share similar vascular pathology mechanisms. Study supported by: K23 NS058357 (HK), R01 NS034949 (WLY), and P01 NS044155 (WLY) S158. Early Arrival to Stroke Centers Should Be Most Emphasized in Public Education Concerning Strokes Kuniyasu Wada, Tadashi Terasaki, Yasuhiro Ogata and Yukio Ando; Kumamoto, Japan Objective: To clarify effective methods for public stroke education, we investigated the chronological change of stroke awareness after the approval (2005) of the intravenous alteplase treatment in Japan. Methods: Every December from 2006 to 2009 a questionnaire was conducted for subjects subscribed to the complete health screening checkup program of our hospital. Results: The questionnaire response rate was 77.1% (7,814/10,130 subjects). While the respondents who knew the name or method of alteplase treatment had increased between first and second year (30.5% vs. 38.6%; p<0.0001), no change was seen between second, third or fourth years (38.6% vs. 39.6% vs. 38.0%). During the survey period, public knowledge of stroke risk factors and symptoms remained unchanged. However, there was a continuous increase in the number of respondents from first to forth year, who would decide on consultation вЂ�вЂ�immediatelyвЂ™вЂ™ or вЂ�вЂ�several minutes -1 hourвЂ™вЂ™ after the onset of symptoms (33% vs. 40%; p<0.0001). Conclusion: Since knowledge of the necessity of haste is easier to improve and maintain than that of stroke risk factors, symptoms or specific treatment, early arrival to stroke centers should be most emphasized in public education. Study supported by: N/A S161. Impact of Acute Ischemic Stroke Treatment in Patients over Age 80: The SPOTRIAS Consortium Experience Joshua Z. Willey, Santiago Ortega-Gutierrez, Nils Petersen, Pooja Khatri, Andria L. Ford, Natalia S. Rost, Latisha K. Ali, Nichole R. Gonzales, Jose G. Merino, Brett C. Meyer and Randolph S. Marshall; New York, NY; Cincinnati, OH; St. Louis, MO; Boston, MA; Los Angeles, CA; Houston, TX; Bethesda, MD and San Diego, CA S159. Recurrent Brain Hemorrhage Caused by Cerebral Vasculitis Due to Ulcerative Colitis: A Case Report and Review Heisuke Mizukami, Toshiyuki Yanagisawa, Hisanao Akiyama, Yuta Hagiwara, Takahiro Shimizu, Makoto Shiraishi and Yasuhiro Hasegawa; Kawasaki, Kanagawa, Japan 53 year-old right-handed female, with a 23-year history of ulcerative colitis(UC), presented with sudden onset of disorientation and sensory aphasia. Brain CT showed intracerebral hemorrhage at the left temporal lobe and low density area surrounding the hemorrhage which was considered as edema. Angiography and CT Angiography showed no Background: Few acute stroke studies have included patients !80 years. We outline in-hospital outcomes in (1) patients !80 years versus <80, and (2) those !80 receiving 46 ID: guganp I Black Lining: [ON] I Time: 09:25 I Path: N:/3b2/ANA#/Vol00000/120255/APPFile/JW-ANA#120255 J_ID: ZAY Customer A_ID: BKLT2012_Abstracts Cadmus Art: ANA12 Date: 18-September-12 intra-arterial therapy (IAT) compared to those treated with intravenous recombinant tissue plasminogen activator (IVrtPA). Methods: SPOTRIAS (Specialized Program of Translational Research in Acute Stroke) centers prospectively collected data on all patients treated with IVrtPA or IAT from 1/1/2005 to 12/31/2010. IAT was categorized as bridging therapy (BT: IAT after IVrtPA), and endovascular therapy alone (ETA). In-hospital mortality was compared in (1) patients age !80 versus <80, and (2) IAT/BT/ETA versus IVrtPA only among those age !80 using multivariable logistic regression. Results: 3378 were treated with IVrtPA, 808 with IAT (383 with ETA and 425 with BT). Patients !80 (n Вј 1182) had a higher risk of in-hospital mortality compared to younger counterparts. Among those age !80, IAT (OR 0.95, 95%CI 0.60-1.49), BT (OR 0.82, 95%CI 0.47-1.45), and ETA (OR 1.15, 95%CI 0.64-2.08) versus IVrtPA were not associated with increased in-hospital mortality. Conclusions: IAT does not appear to increase the risk of in-hospital mortality among those over age 80 compared to intravenous thrombolysis alone Study supported by: SPOTRIAS is funded by the National Institutes of Neurological Diseases and Stroke (NINDS P50 NS049060). JZW was funded by NINDS 1K23 NS 073104-01A1 and the NIH Loan Repayment Program (AG 31009). Stage: Page: 47 Conclusion: The NGT method succeeded in streamlining the process of identifying competencies, learner levels, and prerequisites used to develop competency-based curricula for training clinicians in appropriate use of neuromodulation device therapies. Study supported by: Medtronic, Inc Some authors are employees or consultants for Medtronic S202. Improved Timeliness of Neurology Consults in the Emergency Department Marius Birlea*, Charles Braun, Drew Kern, William Jones, Steven P. Ringel and Kenneth L. Tyler; Aurora, CO Efficient neurological consultation in the Emergency Department (ED) is desirable because of a high volume of ED patients, ED congestion and delays in care. Neurology residents at the University of Colorado, who are responsible for both ED consults and inpatients, documented 136 randomly selected consults they performed in the ED over 4 months. A structured questionnaire was used to analyze components of the consult response process for 60 consults evaluated during an initial 2 months phase, and then following an intervention, response times for 76 consults during the subsequent 2 months were evaluated. The intervention was to вЂ�вЂ�prioritizeвЂ™вЂ™ consults in the ED over other inpatient activities: time limits were set for the Neurology residents to start examination (вЂ�вЂ�time to startвЂ™вЂ™) and complete the consult (вЂ�вЂ�time to peakвЂ™вЂ™). Consequently, the median вЂ�вЂ�time to startвЂ™вЂ™ and вЂ�вЂ�time to peakвЂ™вЂ™ were reduced by 21 minutes and 30 minutes respectively. Also, the median length of stay in ED for all patients receiving Neurology consults decreased by 37 minutes, and by 83 minutes for those directly discharged from the ED. There were no adverse outcomes in inpatient care or education using this new strategy. Study supported by: N/A. None Education S201. Competency-Based Curricula in Neuromodulation Device Therapies Bruce Bellande, Zev Winicur, John Huffman, Maged Hamza, David Caraway, Michael Saulino, Michael Turner, David Charles, Bruno Gallo, Kevin Benson, Steven Siegel, Mary Elizabeth Nelson, Susan Bennett, Susan Heath, Gail McGlothlen, Myra Joseph-Gonzales, Glenn Sulley, Cynthia Reese, Suzanne Dawidowicz, Kathleen Cox, Jamie Boche, Andrea Larson and Peter Scott; Carmel, IN; Silver Spring, MD; Richmond, VA; Huntington, WV; Philadelphia, PA; Indianapolis, IN; Nashville, TN; Miami, FL; Sioux Falls, SD; Woodbury, MN; Milwaukee, WI; Buffalo, NY; San Francisco, CA; Napa, CA; San Antonio, TX; Oklahoma City, OK and Minneapolis, MN S203. What? No Ascending Paralysis? Joseph Khalil and Frank Hrisomalos; Indianapolis, IN Guillain-Barre syndrome should be categorized as a group of syndromes with several distinct subtypes. The common presentation of ascending paralysis is not essential for diagnosis. A 53 yo Male presented with a constellation of neurologic symptoms following a giardial diarrhea treated with flagyl. Recent history included extensive camping in Colorado and Kentucky, spring water ingestion, and multiple mosquito bites. Notable findings included generalized weakness, hyporeflexia, severe lower back pain, bilateral posterior leg and hand pains and paresthesias, perioral numbness, and dysautonomia including constipation, urinary retention, hot/cold reversal, and hypertension. Differential diagnosis was wide given this unique history and nonspecific pattern of findings. Among the many conditions considered were an acute neurological process, acute infectious process, flagyl toxicity, vitamin deficiency, and rare toxic exposure. CSF, EMG, MRI strongly revealed classic findings for GBS. Viral serologies and serum assays were negative. We concluded that the patient displayed an atypical presentation of GBS. Notably, his autonomic instability and extremity pains/paresthesias, classify his disease as a mixture of pure sensory and dysautonomic subtypes. Symptoms improved with 5 days of IVIG. Our patients atypical presentation provides insight into the heterogeneity of this disease and resulting diagnostic challenges that may arise. Study supported by: self Introduction: Education in neuromodulation devices has generally lacked a systematic curriculum, using instead a loosely related series of didactic and hands-on activities heavily dependent on individual faculty input. To improve neuromodulation device education, systematic development of competency-based curricula in four therapeutic areas was proposed, and a short-term, modified Nominal Group Technique (NGT) was tested to more efficiently validate and stratify competencies identified by educational planners from existing course content in deep brain stimulation for ParkinsonвЂ™s disease, tremor, and dystonia; sacral nerve stimulation for bladder and bowel control; neurostimulation for pain control; and intrathecal drug delivery for pain and spasticity. Methods: In three NGT rounds, therapy-specific physician and midlevel provider panels reviewed the identified competencies to validate relevance; assess learner level; and specify sequencing. Results: In 10 weeks, panelists validated 109 neurostimulation competencies for physicians/fellows and 44 for midlevels; 108/93 in sacral nerve stimulation; 121/98 in deep brain stimulation; 234/277 for intrathecal baclofen for spasticity; and 117/97 for intrathecal drug delivery for pain. 47 ID: guganp I Black Lining: [ON] I Time: 09:25 I Path: N:/3b2/ANA#/Vol00000/120255/APPFile/JW-ANA#120255 J_ID: ZAY Customer A_ID: BKLT2012_Abstracts Cadmus Art: ANA12 Date: 18-September-12 Stage: Page: 48 S204. A Survey To Identify Neurology Education in Africa Heather Koons and Gretchen Birbeck; Nashville, TN and East Lansing, MI S207. The Neurology Boot Camp: Tackling the вЂ�вЂ�July PhenomenonвЂ™вЂ™ Wazim Mohamed, Maysa M. Basha and Benjamin E. Atkinson; Detroit, MI Objective: We sought to develop an overview of neurology educational opportunities in Africa. Methods: The survey was constructed for general physicians or non-physician healthcare workers involved in neurologic care. Email addresses were identified through the World Federation of Neurology. The survey was distributed electronically but recipients were offered the option of feedback by post, fax, or return call. For non-responding countries, inactive email addresses, or where no respondent was identified, we conducted a Pub Med and Google Scholar search with criteria using country names. Results: 26 respondents from 15 countries provided information for 28% of African countries. Respondents were neurologists (34.6%) and non-neurologist physicians (65.4%). All reported that non-physician healthcare workers provide neurologic care in their country. There were no neurologists or neurosurgeons practicing within country for 20 and 12% respectively. Where specialist care was available, 33% were trained in country, 29% partly in other countries, and 38% entirely in other countries. Neuro-educational opportunities identified included pharmaceitical seminars and local medical society meetings. Conclusions: This 2011 survey yielded response rates and data similar to the WHO Neurology Atlas (20052006), suggesting little has changed in terms of neurologic resources in Africa of the past 5 years. Study supported by: No one. Introduction: The вЂ�вЂ�July PhenomenonвЂ™вЂ™ is the propensity of newly appointed residents to make medical errors. Our residency program requires the incoming residents to manage neurological emergencies they face in the intense care unit. We hypothesize that a вЂ�вЂ�boot campвЂ™вЂ™ would help the residents make this transition. Methods: A 4 day camp was held in July for incoming residents. The camp dealt with neurological emergencies including training in acute stroke management. Residents took a pre-test, post-test and an 8 month post-test. Residents were also asked to complete an anonymous survey. Results: The median pre-test,post-test and 8 month post-test scores were 98(35-149),158(150-166) and 142(124-164) respectively. There were significant differences between the pre-test and post-test(p < 0.001); the pretest and 8 month post-test(p < 0.001); the post-test and 8 month post-test (p Вј 0.006). 82% of residents agreed that the camp helped them prepare for emergency situations. Discussion: Admissions at the beginning of July are associated with increased number of preventable errors. Training in competency based education can prepare residents for these challenges. A neurosurgical bootcamp conducted in 2010 concluded that it provides a model for enhanced learning and safety. The median score after our camp increased significantly and helped the residents deal with emergent neurological situations as reflected by 82% in the survey. Study supported by: None S205. Withdrawn S206. Neurological Diagnoses among the Uninsured Farrah J. Mateen; Baltimore, MD S208. Who Needs Us Most? вЂ“ Seeking out Those Needing Rapid Neurological Assessment Catriona L. Gribbin, Edward J. Newman, Paul Gallagher and John Paul Leach; Glasgow, United Kingdom Background: An estimated 48.2 million people, or 18% of the U.S. population, <65 years old, lack health insurance. Methods: A search was performed of all billing records at the Johns Hopkins Medical Institutions in Maryland including 2 large urban referral hospitals and 3 outpatient centers (July 2000-Feb 2012) for all inpatient and outpatient international classification of disease-9 diagnoses made within the Department of Neurology for Medicaid, pending Medicaid, charity care, and non-voluntary self-pay visits. Comparison was made to all visits insured by Blue Cross/Blue Shield CareFirst. Results: There were 913 separate diagnoses for 43,268 visits among the uninsured including self-pay (54%), Medicaid (39%), pending Medicaid (7%), and Charity Care (<1%). The leading diagnoses were other convulsions(8%), transient alteration of awareness(6%), cerebrovascular disease(4%), scoliosis and kyphoscoliosis unspecified(3%), intractable partial epilepsy(3%), cerebral artery occlusion with cerebral infarction(3%), and unspecified neuropathy(3%). There were 40,644 diagnoses among those covered by CareFirst with the most frequent being unspecified neuropathy(6%), intractable partial epilepsy(6%), transient alteration of awareness(5%), multiple sclerosis(4%), and dizziness(3%). Conclusions: The uninsured and insured have similar common chronic neurological diagnoses but the uninsured bear a heavier burden of acute, life-threatening neurological diagnoses upon presentation compared to an insured group. Study supported by: Dr. Mateen is supported by the American Academy of Neurology Practice Research Fellowship Grant. Introduction: Up to 30% of neurology out-patient referrals result from functional symptoms, many of which are purely sensory. We need to provide faster access to those most in need of our expertise. Methods: General referrals to a neurology service were vetted by a single neurologist (JPL) over a 3-month period (June- August 2011). Communications reporting isolated sensory symptoms were recorded. Histories suggesting peripheral neuropathy or mononeuropathy were excluded. We recorded additional history, examination findings, results of investigations and final diagnosis. Results: 69 patients (68% female, median 43 years) were included. Eleven (15.9%) patients failed to attend. The final diagnosis was as follows: medically unexplained symptoms (MUS) (56.9%); degenerative spinal disease (12.1%); mononeuropathy (12.1%); migraine with aura (6.9%); and multiple sclerosis (5.2%). In 5.2%, the diagnosis remained elusive. The strongest predictors of organic disease were abnormal clinical examination, odds ratio 5.1 (95% CI 1.7 вЂ“ 16.0), and additional history of non-sensory symptoms, odds ratio 2.5 (0.8-7.5). Conclusion: The most common underlying diagnosis was functional disorders. The proportion of functional disorders was higher than in previous studies, but only 13.0% had significant neurological conditions unheralded by the referral letter. Study supported by: No funding required for study 48 ID: guganp I Black Lining: [ON] I Time: 09:25 I Path: N:/3b2/ANA#/Vol00000/120255/APPFile/JW-ANA#120255 J_ID: ZAY Customer A_ID: BKLT2012_Abstracts Cadmus Art: ANA12 Date: 18-September-12 S209. ChurgвЂ“Strauss Syndrome in a Patient Previously Diagnosed with Multiple Sclerosis: A Case Report Pamela Sarkar, Richard T. Ibitoye and Douglas A. Promnitz; London, United Kingdom; Preston, United Kingdom and Ipswich, United Kingdom Stage: Page: 49 S302. Emerging Therapeutic Targets in Merlin-Deficient Tumors Clemens O. Hanemann, Sylwia Ammoun and Lu Zhou; Plymouth, United Kingdom Deficiency of the tumor suppressor protein merlin leads to the development of benign tumors of the nervous system such as schwannomas, ependymomas and meningiomas. These tumors can occur spontaneously or as part of a tumor predisposition syndrome called neurofibromatosis type 2 (NF2), which involves multiple tumors. Schwannomas are the hallmark tumors of NF2 and are the most frequent and well-characterized of the merlin-deficient tumors. Surgery or radiotherapy are used to treat single tumors and can leave the patient with substantial morbidity. Limitations of other treatment options for merlin-deficient tumors, such as the lack of effectiveness of chemotherapy, have led to an urgent requirement for new pharmaceutical therapies. Merlin-deficient tumors are genetically well-defined, which allows rational testing of new molecular therapies that have been developed and successfully used to treat various cancers in the past few years. We will prsent data on receptor tyrosine kinasesвЂ”the ErbB family, platelet-derived growth factor receptor b, insulin-like growth factor 1 receptor, and vascular endothelial growth factor receptors вЂ”focusing on their role in schwannoma pathobiology and the therapeutic potential of targeting these receptors and their downstream signaling pathways. Initial results of early clinical trial results will also be presented. Study supported by: none Objective: We present how a systemic vasculitis such as ChurgвЂ“Strauss Syndrome (CSS) can clinically be missed, by discussing a case with Multiple Sclerosis (MS), the diagnosis of which we questioned. Case Report: We discuss a case of a woman in her 70s, admitted with cough and breathlessness. MS was diagnosed in her 50s with a 5-year history of right leg weakness. Positive findings included oligoclonal immunoglobulin G bands in CSF unmatched with serum, and bilateral delay on visual evoked responses. Myelography was normal. In her 60s, asthma was diagnosed, with symptoms refractory to corticosteroids, and features suggestive of rhinosinusitis. Transient eosinophilia was noted. During this admission, she developed left-sided weakness. Eosinophils were increased and p-ANCA was positive. MRI head showed multiple areas of increased signal intensity on the diffusion weighted, T2 and fluid-attenuated inversion recovery sequences, consistent with vasculitis. NCS confirmed extensive axonopathy, again consistent with vasculitis. CSS was thus identified as the unifying diagnosis for the chronic and acute illness. Conclusions: CSS is often diagnosed late due to insidious onset, vague symptoms, and masking of disease by steroid treatment. Neurological sequelae of CSS may be misdiagnosed as MS. Study supported by: No conflict of interests S303. Ataxia, Ophthalmoplegia and Areflexia: What Would You Think? Nazia Karsan, Phillip Fletcher, Istvan Bodi and Bridget K. Macdonald; London, United Kingdom A fit and well 44 year old man presented with a short history of fever, abdominal pain, headache and vomiting. The case posed diagnostic difficulty as in quick succession he developed multiple problems including an antibody-negative Miller Fisher Syndrome (MFS). A post-mortem showed carcinomatous meningitis secondary to signet cell adenocarcinoma. We present this case of carcinomatous meningitis presenting as MFS, alongside a literature review of previously reported cases. There are four further cases described in the literature with evidence of tumour invasion within the central nervous system shown either on cerebrospinal fluid examination or histology. There are a further five cases described in which an association between cancer and a Miller Fisher phenotype has been shown. Some of these have identified anti-ganglioside antibodies in the serum and one case also showed antibodies deposited within the primary tumour itself. We hypothesise whether there could be a paraneoplastic form to MFS. It would be informative when further cases present in this way to histologically examine for malignant CNS invasion, and the presence of anti-ganglioside antibodies in both the malignant primary and in areas of nervous system thought to be affected in MFS. Study supported by: No financial support required Neuro-oncology S301. Cerebrospinal Fluid and MRI Analysis in Leptomeningeal Carcinomatosis Ameya Save, Nicholas Blondin and Joachim Baehring; New Haven, CT Given the importance of prompt diagnosis of neoplastic meningitis (NM), measurement of the sensitivity of diagnostic methods (CSF cytopathology (CYT), MRI) and evaluation of the impact of diagnostic delay on patient survival is critical. We performed a retrospective analysis of patients with NM referred to a single investigator between 2002 and 2010. We calculated the sensitivity of CYT and MRI. Diagnostic delay was calculated as the time from symptom onset to objective diagnosis of NM. 83 patients were identified (primary CNS tumors 24, Non-Hodgkin lymphoma (NHL) 19, breast cancer 15). The overall sensitivity of CYT and MRI for all tumors was 0.49 and 0.79, respectively. Sensitivity was 0.22 (CSF)/0.91 (MRI) in patients with primary CNS tumors, 0.29/0.50 in NHL, and 0.60/0.77 in breast cancer. Patients with melanoma had the largest mean diagnostic delay (56 days) followed by those with primary lung cancer (39 days). This study represents one of the largest series of patients with NM evaluated at a single institution. In our experience, MRI provides a higher sensitivity than CYT analysis, however, the sensitivity of both diagnostic methods depends largely on the type of primary cancer. Study supported by: not applicable S304. Use of Rituximab in a Case of Paraneoplastic Sensorimotor Neuropathy with Positive ANNA-1 Antibodies Inhyup Kim, Shyla Kodi and Etta Eskridge; Valhalla, NY A 62 year old Caucasian woman smoker, presented with gait dysfunction, lower extremity numbness and pain. Both sensory and motor deficits lead to a diagnosis of 49 ID: guganp I Black Lining: [ON] I Time: 09:25 I Path: N:/3b2/ANA#/Vol00000/120255/APPFile/JW-ANA#120255 J_ID: ZAY Customer A_ID: BKLT2012_Abstracts Cadmus Art: ANA12 Date: 18-September-12 inflammatory demyelinating sensorimotor polyneuropathy. She was treated with IVIG with marked improvement and discharged home. One week later, she was readmitted with seizures and found to have a frontal lobe lesion which upon biopsy showed perivascular cuffing and gliosis. Subsequently she developed respiratory failure and worsening motor strength, leading to a diagnosis of paraneoplastic syndrome with elevated anti-Hu autoantibodies. She again received IVIG, plasmapheresis and oral prednisone with some improvement in upper extremity strength but remained ventilator dependent. A course of rituximab was initiated, after which a lung biopsy finally revealed Small Cell Lung Carcinoma (SCLC) after seven bronchoscopies. She elected to undergo chemotherapy but remains ventilator dependent with no use of her upper extremities. Our case shows that multiple immunomodulator treatments may have limited effect in paraneoplastic sensorimotor neuropathy but the role of rituximab remains unclear and may have the effect of unmasking the underlying neoplasm. The Hu antibody titer increased following rituximab treatment and remains elevated. Study supported by: none Stage: Page: 50 MRI of the brain demonstrated multiple cystic and nodular enhancing intraparenchymal lesions, some containing blood products. Biopsy of a right frontal lesion confirmed metastatic prostate adenocarcinoma. No meningeal, calvarial, or spinal metastases were detected. Intraparenchymal brain metastasis from prostate cancer is rare, and multiple infratentorial and supratentorial metastases are exceedingly uncommon. In the largest case series to date, of 16,280 patients with prostate carcinoma, 103 (0.63%) had parenchymal metastases. In most cases, metastases were singular and supratentorial. Only three of the 103 (3%; 0.0189% overall) patients had both infratentorial and supratentorial metastases. In general, the distribution of metastases in the central nervous system is thought to depend on hemodynamics (the mechanical hypothesis) as well as genetic changes in some cancer cells that allow them to find the biochemical environment of the brain a favorable place in which to grow (the seed and soil hypothesis). Study supported by: N/A S307. Evaluating Corneal Innervation as a Surrogate for Skin-Biopsy Diagnosis of Small-Fiber Polyneuropathy Giulio Ferrari, Nambi Nallassamy, Heather Downs, Reza Dana and Anne Louise Oaklander; Boston, MA S305. Use of Body-CT and PET-CT in the Investigation of Paraneoplastic Neurological Syndromes: Retrospective Audit of Practice in a UK Neuro-Science Unit Deacon Z.J. Lee, Ammar Kheder, Mhairi Forbes, Ian Craven and Marios Hadjivassiliou; Sheffield, South Yorkshire, United Kingdom Peripheral neuropathy (PN) can cause disabling widespread pain, sensory loss, weakness, and dysautonomia. Cancer chemotherapy drugs are common causes, and onset of PN sometimes forces withdrawal or retrenchment of effective chemotherapy treatments, hence careful monitoring for PN is essential. Electrodiagnostic study effectively detects and quantifies PN affecting myelinated fibers but is insensitive to the small-fiber PN that causes neuropathic pain, often the most disabling symptom. Objective testing for small-fiber PN currently involves quantitating epidermal innervation in distalleg skin biopsies, however chemotherapy magnifies the small risk of infection. In vivo corneal confocal microscopy now enables noninvasive imaging of sensory nerve endings, so its diagnostic utility for PN is worth investigating. We compared small-fiber innervation of plantar-hindpaw skin and cornea in mice intoxicated by a common chemotherapy neurotoxin. Paclitaxel (0, 5, 10, or 20mg/kg) was administered to C57/ Bl6 mice; at sacrifice, biopsies of cornea and hindpaw skin were immunolabeled against beta-3 tubulin and PGP9.5 respectively to quantitate innervation. Both tissues demonstrated dose-dependent axonal losses that correlated moderately (r Вј 0.66). Corneal-innervation measurements might thus provide non-invasive surrogate markers for monitoring painful small-fiber PN in chemotherapy patients. Study supported by: Supported in part by a grant from the Public Health Service (K24NS059892) and the Bietti Eye Foundation. Background: Positron emission tomography (PET) has emerged as a more sensitive tool for diagnosis of paraneoplastic neurological syndromes (PNS) compared to conventional imaging modalities such as body-CT. Aims: To analyse use of whole-body CT and PET-CT in the investigation of PNS. Methods: Retrospective review of 42 patients with suspected PNS referred for imaging between April 2007-March 2008 was conducted, followed by recommendations that PET-CT is considered in cases where body-CT is negative. We re-audited 45 patients referred between July 2008-June 2009 and identified each patientвЂ™s final diagnosis along with any additional investigations undertaken. Results: In the first cycle, 42 patients underwent wholebody CT for investigation of PNS. 4 scans were positive for malignancy; 38 were negative, of which only one was followed up with PET-CT. In the second cycle, whole-body CT was performed in 45 patients, 11 of which proceeded to PET-CT. 4/45 patients had a final diagnosis of PNS, of which only 3 had undergone PET-CT. Conclusion: Early PET scanning in clinically suspected PNS may prevent expensive and often unnecessary investigations. Trust guidelines now advise use of PET-CT rather than conventional body-CT in clinically suspected PNS. Study supported by: None S308. Neurophysiologic Tests Do Not Correlate Well with Pain Measures and Quality of Life in Taxane Neuropathy Harry Openshaw, Karen Knight, Wei Ye, Gloria Juarez, Paul Frankel and George Somlo; Duarte, CA S306. Widespread Intracerebral Metastases from Prostate Adenocarcinoma Devin D. Mackay, Eli L. Diamond and Joshua P. Klein; Boston, MA and New York, NY To determine if neurophysiologic measures correlate with pain and quality of life (QOL) in taxane neuropathy, 70 women with stage II/III breast cancer on docetaxel 75mg/ m2 or nab-paclitaxel 100mg/m2 protocols were assessed prospectively by neurophysiologic tests, neuropathy composite score, Neuropathic Pain Symptom Inventory (NPSI), and QOL questionnaires. At completion of chemotherapy, 8 of 11 QOL measures had a worsening mean score (p<0.05) as A 62 year-old man with prostate cancer and only pulmonary metastases presented with a partial seizure involving forced leftward head deviation and tonic limb posturing. He complained of diplopia without other symptoms. Physical examination revealed mild bilateral papilledema, limited ocular abduction bilaterally, left-sided ataxia, and bilateral extensor plantar responses. 50 ID: guganp I Black Lining: [ON] I Time: 09:25 I Path: N:/3b2/ANA#/Vol00000/120255/APPFile/JW-ANA#120255 J_ID: ZAY Customer A_ID: BKLT2012_Abstracts Cadmus Art: ANA12 Date: 18-September-12 did all neurophysiologic measurements. The change was greater for sensory than motor conductions and greater for vibration than cold detection. At 12 months after chemotherapy, all neurophysiologic measures except cold detection and 5 of 11 QOL measures were still significantly worse than baseline; only QOL emotional well-being was significantly improved (P<0.001). At completion of chemotherapy, there were correlations between NPSI and 8 QOL measures (r from -0.26 to 0.63, p<0.05). Neither NPSI nor QOL correlated strongly with neurophysiologic measures. In conclusion, there is correlation between QOL and NPSI, but neurophysiologic measures do not correlate well with each other or with NPSI or QOL. It is important to include pain and QOL measures in investigative studies of neuroprotective agents. Study supported by: NCI Grant CA 33572, NIH M01RR00043, and American Bioscience/Celgene Stage: Page: 51 factors are peripheral neuropathies/radiculopathies or central causes with antagonistic rather than co-contraction. Exact etiology remains unclear. Polysomnographic (PSG)/polymyographic (PMG) findings in PPLMTS have not been studied. Seven PPMTS patients (five women, two men; two with painful symptoms and four without; two had ParkinsonвЂ™s disease) underwent overnight PSG with specialized foot montage (extra muscle channels involving bilateral abductor digiti minimi, flexor hallucis brevis and extensor digitorum brevis). In five patients, toe movements were bilateral and frequent in wakefulness, stage N1 and sleep-wake transitions, rarely persisting into REM sleep in three of these patients and very frequent in REM sleep in another. They were associated with cortical arousals in both REM and NREM sleep in one patient. Movements were a combination of synchronous and asynchronous, myoclonic (>200 msecs) and dystonic (<200 msecs) bursts; in two patients bursts were purely dystonic. In two patients, one with ParkinsonвЂ™s disease, movements disappeared in sleep. PPLMTS is clinically and neurophysiologically heterogeneous. The mixture of myoclonic, dystonic, synchronous and asynchronous patterns suggests a complex pathophysiology determined by both peripheral afferent/efferent and supraspinal efferent control. Study supported by: n/a S309. Leveraging Expression of the GABA-A Receptor, alpha 5 in Medulloblastoma as a Novel Therapeutic Target Soma Sengupta, Shyamal D. Weeraratne, Hongyu Sun, Bela Kosaras, Jillian Phallen, Natalia Teider, Sundari Rallapalli, Mirna Lechpammer, Dimitrios Mathios, Vlad Amani, Jessica Pierre-Francois, Tenley Archer, James Cook, Frances Jensen, Michael Lim, Scott Pomeroy and Yoon-Jae Cho; Boston; Baltimore; Milwaukee and Stanford S402. Complex Sleep Behavior with Multiple Etiologies: A Diagnostic Challenge Rony Dekermenjian, Nancy Gadallah, Sushanth Bhat, Sumaiya Salim, Luidmila Lysenko, Disha Patel and Sudhansu Chokroverty; Edison, NJ Neural tumors display molecular markers suggestive of their developmental lineage, including the expression of neurotransmitter receptors. Although neurotransmitter receptors have been well-characterized in normal neurophysiological, developmental and pharmacological settings, their importance in the maintenance and progression of brain tumors, and importantly, the effect of their targeting in brain cancers remains obscure. We previously demonstrated high levels of GABRA5 expression in a particularly aggressive molecular subtype of medulloblastoma, and we hypothesized that modulation of its activity would alter medulloblastoma cell survival. We treated GABRA5 expressing medulloblastoma cells with a series of GABA-A receptor agonists and antagonists and then assayed for proliferation, cell cycle distribution, apoptosis, and changes in electrophysiological properties, in vitro and in/ex vivo. While GABA-A receptor antagonists, had limited effects on cell survival, QHii066, a highly specific A5/GABA-A receptor agonist, significantly decreased medulloblastoma cell survival through the induction of apoptosis. Furthermore, QHii066 markedly sensitized GABRA5 positive medulloblastoma cells to radiation and chemotherapy, in vitro and in vivo. Thus, these results provide a novel strategy for the treatment and management of a highly lethal subtype of medulloblastoma. Study supported by: My salary is supported by an NIH research grant (R25NS070682). Otherwise, I have no other conflicts of interest. We report a case of complex sleep behavior with multiple etiologies in a patient with medical comorbidities. A 49 year-old diabetic woman, noncompliant with continous positive airway pressure (CPAP) use for obstructive sleep apnea, had an episode of sleep violence. Dreaming of trying to escape from a barrel as the world was ending, she got out of bed confused with her eyes open, damaged property, threw stones at neighborвЂ™sвЂ™ windows, and awoke without recollection of the event. During polysomnography (PSG), she displayed complex movements at apnea termination (limb/trunk abduction-adduction, flexion-extension and ballistic posturing, fiddling with wires and clothing, tapping her abdomen, scratching limbs). On her second PSG study, CPAP eliminated these movements, but she later became confused, pulled off her CPAP mask, had dystonic-ballistic movements, and became diaphoretic and tachycardic. EEG showed theta-delta slowing. She was severely hypoglycemic, responding to intravenous dextrose, with no recall of these events. She later admitted to frequent nocturnal hypoglycemia, caused by taking higher doses of insulin in the evenings when she forgot afternoon doses. Complex sleep behavior has multiple etiologies, causing acute and urgent events during PSG studies that necessitate immediate interventions. Study supported by: N/A Sleep Disorders and Circadian Rhythm S403. Sleep and Circadian Rhythm Disruption in Incident ParkinsonвЂ™s Disease вЂ“ A Multimodal Analysis David P. Breen, Romina Vuono, Kate Fisher, Shani Nawarahtna, John M. Shneerson, Akhilesh B. Reddy and Roger A. Barker; Cambridge, United Kingdom S401. Polysomnographic and Polymyographic Characteristics of Painful/Painless Limbs Moving Toes Syndrome (PPLMTS) Syndrome Rony Dekermenjian, Nancy Gadallah, Sushanth Bhat, Phillip Hanna, Fouzia Siddiqui and Sudhansu Chokroverty; Edison and Harrisonburg, VA Sleep disturbances are present from the earliest stages of Parkinsons disease (PD), often getting worse as the condition progresses, but their neural basis is poorly understood. We PPLMTS consists of continuous/semicontinuous involuntary foot muscle movement, with or without pain. Predisposing 51 ID: guganp I Black Lining: [ON] I Time: 09:25 I Path: N:/3b2/ANA#/Vol00000/120255/APPFile/JW-ANA#120255 J_ID: ZAY Customer A_ID: BKLT2012_Abstracts Cadmus Art: ANA12 Date: 18-September-12 probed the nature and extent of these sleep disturbances in an incident PD cohort. We studied 30 early PD patients and 15 matched elderly controls. Alongside clinical assessments, participants underwent actigraphy assessment, polysomnography and 24-hour circadian rhythm analysis (melatonin, cortisol and peripheral clock gene expression). PD patients had significantly higher Parkinsons Disease Sleep Scale (PDSS) score compared to controls. Five PD patients had Rapid Eye Movement (REM) sleep behaviour disorder but no group differences were seen in periodic limb movements, Apnoea-Hypopnoea Index or Desaturation Index. PD patients had reduced sleep efficiency and increased nocturnal awakenings. They also spent significantly less time in slow wave and REM sleep. There was a significant correlation between sleep efficiency and several measures of cognitive performance. We will present the extent to which these sleep disturbances are driven by circadian pathology. As well as detecting specific sleep diagnoses, we have found reduced sleep efficiency and altered sleep architecture in early PD patients compared to matched controls. Study supported by: ParkinsonвЂ™s UK/Big Lottery Fund; Cure PD Trust; NIHR Biomedical Award to AddenbrookeвЂ™s Hospital/University of Cambridge; and Raymond and Beverly Sackler Studentship Stage: Page: 52 S405. A Longitudinal Study of 322 Individuals with Narcolepsy Maurice M. Ohayon; Palo Alto, CA Objectives: Many progresses have been done in understanding the genetic basis of Narcolepsy. However, little is known about the evolution of narcoleptic individuals in terms of mortality and comorbidity. Methods: A total of 322 narcoleptic individuals interviewed at first time between 2005 and 2007 were contacted again between October 2011 and January 2012. The success rate in contacting the initial sample was 95.65%. As with the initial interview, during the followup, the interview covered sleep, mental and organic diseases. Initial and follow-up interviews were performed using the Sleep-EVAL system. Results: Of the 308 narcoleptic individuals located, 4 refused to participate, 1 was unavailable for other reasons, 5 were too ill and 7 were deceased. At follow-up, subjects were aged between 21 and 84 years. The most frequently reported new disease was hypertension (3.1%) followed by diabetes (2.6%) and cancer (2.2%). Overall death rate was comparable between narcoleptic sample and the U.S. general population for the same time period. However, suicide rate was seven times higher in the narcoleptic sample (RR:7.35 [1.84-29.41]). Conclusion: Narcolepsy is accompanied by various medical conditions but also mental disorders, which place narcoleptic individuals at greater risk for suicide. Study supported by: NIH (R01NS044199) and unrestricted educational grant from Jazz Pharmaceuticals S404. The Tuberous Sclerosis Complex-Mammlian Target of Rapamycin (mTOR) Pathway Regulates Mammalian Circadian Rhythms Jonathan Lipton, Elizabeth Yuan, Ashwin Nathan, Jarrett Leech, Juliette Han, Fred Davis and Sahin Mustafa; Boston, MA S406. Medical Conditions and Psychiatric Disorders Associated with Narcolepsy Maurice M. Ohayon; Palo Alto, CA Disruption of sleep and circadian rhythms is common in patients with Tuberous Sclerosis Complex (TSC). TSC manifests with epilepsy, intellectual disability, tumor formation, and sleep disruption. The Tsc1/Tsc2 gene products collaborate to suppress the activity of the mammalian target of rapamycin (mTOR), a major integration point for anabolic signaling and protein synthesis initiation. We have studied the circadian timekeeping system in mouse models of TSC to target mechanisms of circadian dysfunction and identify molecular relationships between the clock and anabolic signaling. Mice deficient in Tsc1 or Tsc2 gene function вЂ“ in which mTOR activity is constitutively increased вЂ“ demonstrate aberrant circadian physiology, behavior, and gene expression. Similarly, genetic or pharmacologic modification of mTOR signaling results in altered circadian timing in peripheral cells. We have identified a specific biochemical mechanism by which mTOR signaling modulates the function of the core clock protein BMAL1, contributing to its subcellular localization and degradation. Our results provide a mechanistic link between the TSC/mTOR signaling pathway and the circadian clock and add to our understanding of how anabolic information is directly relayed to circadian oscillators in health and disease. Study supported by: American Academy of Neurology Clinical Research Training Program, Tuberous Sclerosis Alliance Post-doctoral grant, the William Randolph Hearst Foundation of Harvard Medical School, and an American Sleep Medicine Foundation Physician Scientist Training Award, and the NIH/NICHD (K08HD071026-01) (J.L);. NIH R01 NS058956, Tuberous Sclerosis Alliance, Autism Speaks, John Merck Fund, Nancy Lurie Marks Family Foundation, and the ChildrenвЂ™s Hospital Boston Translational Research Program (M.S.). Objectives: Individuals affected by Narcolepsy represent a vulnerable segment of the population. We have, however, only a partial understanding of this vulnerability. This study aims to examine psychiatric disorders and medical conditions associated with Narcolepsy. Methods: A total of 320 narcoleptic individuals were interviewed sleeping habits; health; medication consumption, medical conditions (ICD-10), sleep disorders (ICSD) and mental disorders (DSM-IV-TR) using the SleepEVAL. system A general population comparison group (N Вј 1,464), matched for age, sex and BMI and interviewed with the same instrument, was used to estimate odds ratios. Results: Five diseases were more frequently observed among narcoleptic individuals: Hypercholesterolaemia (OR: 1.51); Diseases of the digestive system (OR: 3.27); Heart diseases (OR: 2.07); Upper respiratory tract diseases (OR: 2.52) and Hypertension (OR: 1.32). Most frequent psychiatric disorders among the narcolepsy group were Major Depressive Disorder (OR: 2.67) and Social Anxiety Disorder (OR: 2.43) both affecting nearly 20% of narcoleptic individuals. However, most mood and anxiety disorders were more prevalent among narcoleptic group. Alcohol Abuse/Dependence was comparable between groups. Conclusions: Narcolepsy is associated with a high comorbidity of both medical conditions and psychiatric disorders that need to be addressed when developing a treatment plan. Study supported by: NIH (R01NS044199) and unrestricted educational grant from Jazz Pharmaceuticals 52 ID: guganp I Black Lining: [ON] I Time: 09:25 I Path: N:/3b2/ANA#/Vol00000/120255/APPFile/JW-ANA#120255 J_ID: ZAY Customer A_ID: BKLT2012_Abstracts Cadmus Art: ANA12 Date: 18-September-12 S407. Bmal1 Provides a Molecular Link between Circadian Clock Function, Brain Metabolism, and Neurodegeneration Erik S. Musiek, Miranda M. Lim, Adam Q. Bauer, Guangrui Yang, Jee Hoon Roh, Benoit I. Giasson, David M. Holtzman and Garret A. FitzGerald; St. Louis, MO; Philadelphia, PA and Gainesville, FL Stage: Page: 53 topia, 1/24 focal cortical dysplasia, 1/24 optic chiasma hypoplasia, 2/24 brainstem hypoplasia, 4/24 microcephaly, 2/ 24 hemimegalencephaly. 10/50 (20%) had PMG as part of a syndrome. One karyotype showed a reciprocal translocation 46,XY t(8;22)(p23.1;p11.2). Of 27 CGH microarray results, 23 (85%) were normal. The detected CGH anomalies included a 22q11del, a 1p36del, a 2p21del of unknown significance, and a 2p13.3-p16.3duplication. We fine mapped a subgroup of bilateral perisylvian polymicrogyria (BPP) patients to 2p16.1-p16.3. Conclusions: Our data support previous suggestions of PMG loci on chromosomes 22q11 and 1p36, and narrow a locus for BPP to 2p13.1-p16.3. These data can help to identify the causative genes located in these regions. Study supported by: N/A Circadian clock proteins regulate many aspects of cellular function, and circadian oscillation declines with aging and in neurodegenerative diseases. Deletion of the master clock gene Bmal1 in mice causes loss of circadian rhythms, systemic oxidative injury, peripheral metabolic dysfunction, and accelerated aging. We hypothesized that the circadian clock might regulate bioenergetics and redox homeostasis in the brain, and examined the impact of Bmal1 deletion on brain pathology. Deletion of Bmal1 in mice caused severe age-dependent astrogliosis and microglial activation in cerebral cortex and hippocampus, and was accompanied by neuronal lipid peroxidation and impaired expression of the redox defense protein mitochondrial aldehyde dehydrogenase (ALDH2). Bmal1 deletion triggered ATP depletion and activation of the metabolic sensor AMPK, consistent with cerebral metabolic stress, and optical imaging of resting state functional connectivity demonstrated neural network dysfunction. Similar neuropathology and biochemical changes were observed in mice with brain-specific Bmal1 deletion (Nestin-Cre::Bmal1flox), which have intact sleep/wake cycles, suggesting that neuropathology was not due to sleep deprivation or peripheral circadian dysregulation. Our findings implicate Bmal1 as a novel regulator of cerebral bioenergetics and oxidative stress, and suggest that circadian dysfunction may promote neurodegeneration. Study supported by: NIH grants K08NS079405 (ESM), HL097800 (GAF), P01NS074969 (DMH), P30NS057105 (DMH), an Ellison Medical Foundation Senior Scholar Award (DMH), and the Cure AlzheimerвЂ™s Fund (DMH). Dr. FitzGerald is the McNeill Professor of Translational Medicine and Therapeutics. S502. The Phenotypic Spectrum of Subcortical Band Heterotopia in Patients Negative for DCX/LIS1 Gene Mutations Eva Andermann, Dina Amrom, FrancВёois Dubeau, Maria D. DвЂ™Agostino, William B. Dobyns and Frederick Andermann; Montreal, QC, Canada and Seattle, WA Objective: To delineate the phenotypic spectrum and elucidate the genetic cause(s) of subcortical band heterotopia (SBH) in patients negative for DCX and LIS1 gene mutations. Method: Chart review, karyotype and/or array CGH in patients with SBH negative for both DCX and LIS1 mutations. Results: Fifteen sporadic patients presenting with various degrees of epilepsy, with or without associated cognitive delay, had SBH for which no DCX or LIS1 mutation was found. They were evaluated with a karyotype and DCX and/or LIS1 mutation analysis, depending on the pattern of distribution of their SBH. A few patients had both sequencing and deletion/duplication analysis of one or both genes. In one woman, the karyotype showed a de novo paracentric inversion of the q13->q22.3 region of one chromosome 9. CGH microarray (with 135,000 oligonucleotides) did not reveal any deletion/duplication. Higher resolution CGH microarray is ongoing in order to detect a possible microdeletion/duplication. Conclusion: Genetic evaluation of SBH deserves DCX and/or LIS1 sequencing and deletion/duplication analysis, but this does not always reveal the genetic cause of this brain malformation, especially in sporadic cases. Karyotype and/or CGH array analysis is indicated in these unsolved cases. Study supported by: N/A Neurogenetics S501. Nonsyndromic and Syndromic Polymicrogyria: Illustration of Clinical, Radiological and Genetic Heterogeneity in a Cohort of 50 Patients Dina R. Amrom, Jacques Michaud, Grant Mitchell, Emmanuelle Lemyre, Annapurna Poduri, Jennifer Partlow, Vijay Ganesh, Bernard Dan, Giorgi Kuchukhidze, Ingrid Unterberger, Eugen Trinka, Nicolas Deconinck, Catherine Christophe, BenoД±Л†t Pichon, FrancВёois Dubeau, Donatella Tampieri, Jean-Claude DeВґcarie, William B. Dobyns, Frederick Andermann, Christopher A. Walsh and Eva Andermann; Montreal, QC, Canada; Boston, MA; Brussels, Belgium; Innsbruck, Austria; Salzburg, Austria; Seattle, WA and Montreal, QC S503. Subarachnoid Hemorrhage and Acute Hydrocephalus in a Patient with Familial Transthyretin Type Amyloidosis Matthew B. Bevers, Nivedita U. Jerath and Patricia L. Musolino; Boston, MA We present the case of a 47 year old Nepalese woman with a history of developmental delay who presented with headache and vomiting, found to have hydrocephalus, subarachnoid hemorrhage and mineralization within the Sylvian fissure. Neither CT nor conventional angiogram demonstrated evidence of aneurysm or vascular malformation. CSF was notable for elevated RBCs and xanthochromia, but no inflammatory pleocytosis. MRI showed diffuse leptomeningeal enhancement as well as mineralization of the meninges in the Sylvian fissure. Such findings have been reported in transthyretin type meningocerebrovascular amyloidosis, a Objective: To llustrate the heterogeneity of nonsyndromic and syndromic polymicrogyria (PMG). Methods: Patients with any type of PMG, excluding schizencephaly and confirmed congenital CMV/toxoplasmosis. This includes review of medical records; karyotype and/or CGH and/or genomic SNP microarray; and specific gene analysis when indicated. Results: We studied 46 sporadic patients and two families with two siblings each. Their PMG pattern was variable. 24/50 (48%) had associated brain malformation(s), including 2/24 corpus callosum dysgenesis, 5/24 nodular hetero- 53 ID: guganp I Black Lining: [ON] I Time: 09:25 I Path: N:/3b2/ANA#/Vol00000/120255/APPFile/JW-ANA#120255 J_ID: ZAY Customer A_ID: BKLT2012_Abstracts Cadmus Art: ANA12 Date: 18-September-12 rare genetic condition that causes amyloid deposition in leptomeninges and subarachnoid vessels that can be a cause of subarachnoid hemorrhage. The patient had a duodenal biopsy, which confirmed the presence of amyloid deposition in vessel walls. Genetic testing showed an A to G substitution at position 113 of exon 2 of the TTR gene. This finding has previously been reported in individuals with leptomeningeal amyloidosis. Therapy is supportive, and genetic counseling is being offered to the patientвЂ™s children. Mutations in the transthyretin gene represent a rare cause of regional amyloid deposition and subarachnoid hemorrhage. Study supported by: Residency Program Stage: Page: 54 subjects. In our eGWAS, we tested the PSP risk loci for association with expression levels of transcripts within 6100kb. Using semi-quantitative neuropathology scores on 458 autopsied PSP subjects and latent modeling, we obtained quantitative neuropathology endophenotypes to test for associations. Brain expression levels of SLCO1A2, MAPT and MOBP were associated with PSP risk variants. MAPT and MOBP loci showed biologically consistent associations with neuropathology endophenotypes. We conclude that regulatory variants may explain part of the PSP genetic risk. Some of these regulatory variants may influence neuropathology, which has implications for search of functional variants at these loci. Study supported by: R01 AG032990, P50 AG016574, KL2 RR024151, CurePSP S504. Exome Sequencing Identifies Two Separate Mutations in a Novel Gene as Cause of Autosomal Dominant Cervical Dystonia in Two Families Gavin Charlesworth, Jose M. Bras, Rita Guerreiro, Una M. Sheerin, Kailash Bhatia and Nicholas W. Wood; London, United Kingdom S507. Hexanucleotide Repeat Expansion in c9orf72 Is Associated with Increased Risk of Bulbar Amyotrophic Lateral Sclerosis (ALS) Paloma Gonzalez-Perez, Peter Sapp, Zack C. Kennedy, Diane McKenna-Yasek, Ru-Ju Chian, Andrew Fox and Robert H. Brown; Worcester, MA Cervical dystonia is the most common focal dystonia. We identified a moderately-sized kindred from the UK with autosomal dominant inheritance of cervical dystonia and jerky dystonic tremor of the upper limbs, with negative mutational screening for the known dystonia genes (THAP1 & TOR1A). We performed whole-exome sequencing on two individuals from this kindred, combined with linkage analysis, in order to identify novel candidate causal variants. Subsequent screening of one of these variants by Sanger sequencing of the exon in which it was located in a further 250 cases of cervical dystonia revealed a second, novel, missense mutation 4 amino acids downstream, predicted to be pathogenic and affecting a highly conserved base, which segregated with disease in a second, separate autosomal dominant family. The gene in which the two mutations were found is an ion channel thought to modulate neuronal excitability that is highly expressed in the striatum and is thus biologically plausible as a cause of dystonia. Sequencing of the remaining exons of this large gene to look for further mutations will soon be completed. Study supported by: MRC/Wellcome Trust Research Grant An expansion of a hexanucleotide repeat in c9orf72 (c9orfГѕ ) has been recently identified as the genetic cause of 9p-linked ALS associated with frontotemporal lobar dementia (Dejesus-Hernandez et al, Renton et al 2011). Objectives: Determine the frequency of c9orfГѕ in a large set of ALS patients and controls; and investigate the impact of c9orfГѕ on phenotype in sporadic and familial ALS. Methods: A short-tandem-repeat assay was performed on 224 FALS, 900 SALS and 900 controls DNA samples. Repeat-PCR was carried out on samples with potential c9orf72 expansions using an ABI3730 DNA Analyser. Southern blots determined the sizes of the hexanucleotide expansions. Results: Expansions were identified in approximately 25% of FALS, 5% of SALS and 0.6% of control cases. Our data document a significant association between the presence of the hexanucleotide expansions and bulbar onset ALS but not age of onset or duration of disease. Conclusions: c9orfГѕ frequency in our ALS DNA set is comparable to that previously reported. C9orfГѕ significantly predisposes to bulbar onset. Studies are in progress to define the minimum expansion size threshold for ALS susceptibility. Study supported by: This study was supported by the National Institute for Neurological Disease and Stroke (5R01-NS050557-05), the Angel Fund, the ALS Association, P2ALS, Pierre L. de Bourgknecht ALS Research Foundation and the ALS Therapy Alliance. S505. Withdrawn. S506. Progressive Supranuclear Palsy Genetic Risk Variants Associate with Brain Gene Expression and Neuropathology Endophenotypes Nilufer Ertekin-Taner, Mariet Allen, Melissa Murray, Julia Crook, Daniel Serie, Fanggeng Zou, High Seng Chai, Curtis Younkin, Shane Pankratz, Minerva Carrasquillo, Christopher Rowley, Asha Nair, Sumit Middha, Sooraj Maharjan, Thuy Nguyen, Li Ma, Kimberly Malphrus, Ryan Palusak, Sarah Lincoln, Gina Bisceglio, Constantin Georgescu, Naomi Kouri, Christopher Kolbert, Jin Jen, Gerard Schellenberg, Ronald Petersen, Neill Graff-Radford, Steven Younkin and Dennis Dickson; Jacksonville; Rochester and Philadelphia S508. Infrequent NaV1.7 Mutation in Insensitivity to Pain, Erythromelalgia and Small Fiber Neuropathy Christopher J. Klein, Dean H. Kilfoyle, Yanhong Wu, Paola Sandroni, Phillip A. Low, Mark D. Davis and Peter J. Dyck; Rochester, MN and Epsom, Aucklund, New Zealand Seven genetic risk loci for progressive supranuclear palsy (PSP) were identified in a genome-wide association study (GWAS). We postulate that some of these loci influence PSP by modifying brain gene expression, given the importance of regulatory variants in human traits. We tested the association of the PSP GWAS variants with brain gene expression and neuropathology endophenotypes. We completed an expression GWAS (eGWAS) of brain transcript levels measured in $800 samples from the cerebellum and temporal cortex of autopsied subjects with AlzheimerвЂ™s disease (AD) and other neuropathologies including $100 PSP Mutations in Nav1.7 (SCN9A) cause congenital insensitivity to pain (CIP), erythromelalgia and small fiber sensory neuropathy. SCN9A was sequenced in 19 patients, 6 Вј CIP, 9 Вј erythromelalgia, 4 Вј small fiber neuropathy. In one erythromelalgia patient, a novel Q10K mutation was identified. In one CIP patient, a novel (IVS8-2), de novo splicing mutation was identified, this mutation compounded with nonsense mutation (R523>X) and reduced SCN9A expression to 5% compared to unaffected family members. In another CIP patient, we identified P610T previously 54 ID: guganp I Black Lining: [ON] I Time: 09:25 I Path: N:/3b2/ANA#/Vol00000/120255/APPFile/JW-ANA#120255 J_ID: ZAY Customer A_ID: BKLT2012_Abstracts Cadmus Art: ANA12 Date: 18-September-12 considered causal for erythromelalgia, P610T has 2% MAF in 1000-Genome and is unlikely causal. A splicing junction deletion mutation (IVS24-7) previously linked to CIP was found in all indexed patients (het-del in 3 CIP, homdel in 3 CIP and 13 erythomelalgia), suggesting this deletion has limited effect in pain related phenotypes. Also, a variant (rs6746030) previously linked to the increased pain perception was found among three CIP indexed patients. Our results support genetic heterogeneity for CIP, erythomelalgia, small fiber neuropathy by rare occurrence of SCN9A mutations. The extent polymorphisms in our cohort emphasizes other factors likley contribute to pain related disorders, and some variants considered causal in previous studies need further investigation. Study supported by: Mayo Foundation Clinical Research Grant, National Institutes of Health (NIH) Grant (K08 NS065007-01A1)(NS36797). Stage: Page: 55 Results: Truncating mutation in two familial cases and a novel point mutation in one sporadic case were identified. Conclusion: PRRT2 gene mutations are also confirmed in Japanese PKC cases including sporadic case. Study supported by: None S511. C9ORF72 Hexanucleotide Repeat Expansion Analysis in Multiple System Atrophy and Progressive Supranuclear Palsy Karen E. Morrison, Rachel V. Denyer, Gilbert Bensimon, Albert Ludolph, Yves Agid, P. Nigel Leigh, Ammar Al-Chalabi and on Behalf of NNIPPS Consortium; Birmingham, United Kingdom; Paris, France; Ulm, Germany; Falmer, Brighton, United Kingdom and London, United Kingdom Expanded C9ORF72 hexanucleotide repeats have recently been described in conjunction with both amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (Renton, Neuron, 2011). C9ORF72 expansions are associated with distinct neuropathological findings (Snowden, Brain, 2012) and, in those with ALS, more frequent cognitive and behavioural disturbance (Byrne, Lancet Neurology, 2012). Only one previous study examined whether C9ORF72 expansion plays a role in other neurodegenerative disorders, demonstrating presence of the expansion in <1% of patients with AlzheimerвЂ™s disease (Majounie, NEJM, 2012). Using a repeat primed PCR assay and DNA extracted from peripheral blood lymphocytes we screened 136 UK patients enrolled in the NNIPPS trial (Bensimon, Brain, 2009) with either multisystem atrophy (MSA) or progressive supranuclear palsy (PSP) for C9ORF72 expansions. The expansion (>23 repeats) was identified in one 75 year-old male patient with MSA. Further clinical details regarding this patient will be presented. There was no evidence of C9ORF72 expansion in any of the PSP patients. These results suggest that C9ORF72 expansion may rarely be associated with other neurodegenerative disorders. Further investigation into the effects of C9ORF72 expansions may offer broader insights into the pathophysiology of neurodegenerative disorders. Study supported by: Research supported by grant from University Hospital Birmingham Charities and Midlands Neuroscience Teaching and Research Fund. S509. Improvement of Learning and Memory in Ts65Dn Mouse Model of Down Syndrome (DS) by GABAB Receptor Antagonists: DS-Specific and Non-Specific Mechanisms Francisco Madamba, Yasaman Pirahanchi, Brett Rasmussen and Alexander Kleschevnikov; La Jolla, CA Down syndrome is characterized by deficient learning and memory. Ts65Dn mice, a genetic DS model, exhibit reduced synaptic plasticity and deficient learning. It was shown that efficiency of the GABAergic neurotransmission is increased in the dentate gyrus (DG) of Ts65Dn mice, and that GABAB antagonists can improve learning. Interestingly, the improvement was observed only in Ts65Dn, but not in WT controls, suggesting that some mechanisms are DS - specific. To examine potential mechanisms, we measured hippocampal levels of BDNF after injections of the GABAB antagonist CGP55845. The BDNF levels were increased equally in Ts65Dn and WT mice (p Вј 0.55). In hippocampal slices, CGP52432 increased paired-pulse inhibition of the population spikes suggesting an increase of feedback inhibition. Again, the effects were equal in Ts65Dn and WT (p Вј 0.6). Finally, application of CGP55845 significantly increased NMDA receptor-mediated EPSPs. This change was greater in Ts65Dn mice (p < 0.03). Consequently, long-term potentiation (LTP) was restored in Ts65Dn to the WT level. Thus, GABAB antagonists improve memory in Ts65Dn mice by a number of DS-specific and non-specific mechanisms. Study supported by: The Larry L. Hillblom Foundation; The Down Syndrome Research and Treatment Foundation S512. No Association of CETP Genotypes with Evolution of Dementia Due to AlzheimerвЂ™s Disease Fabricio F. Oliveira, Paulo H. Bertolucci, Marilia A. Smith and Elizabeth S. Chen; SaЛњo Paulo, SP, Brazil Objective: To investigate whether CETP polymorphisms I422V and TaqIB are associated with cognitive change in patients with dementia due to AlzheimerвЂ™s disease (AD). Methods: Participants with late-onset AD were screened with MMSE and/or severe MMSE and followed for one year. Diagnosis of AD was in accordance with NIA-AA criteria, and hypercholesterolemia was treated according to National Cholesterol Education Program guidelines. GenoR Real-Time PCR typing was undertaken with TaqManV technology. FisherвЂ™s exact test was employed, p<0.05. Results: All 119 patients (67.2% female, mean age of AD onset 72.2366.42 years-old, mean education 4.4663.82 years) were treated with a cholinesterase inhibitor and/or Memantine, and 66 (55.5%) were also using statins with or without Ezetimibe. For I422V (rs5882), minor allele frequency (V422) was 0.34, and 50 patients (42%) were heterozygous. For TaqIB (rs708272), minor allele frequency (A) was 0.36, and 57 patients (48%) were heterozygous. Age of AD onset was not susceptible to V422 (p Вј 0.11) or TaqIB S510. PRRT2 Mutations in Japanese PKC Cases Mitsuya Morita and Imaharu Nakano; Shimotsuke, Tochigi, Japan Introduction: Paroxysmal kinesigenic choreoathetosis (PKC) is characterized by brief attacks of involuntary movement triggered by sudden onset of movement. PKC is commonly inherited as an autosomal dominant trait, and PRRT2 gene was recently identified as the causative gene. Objectives: To search for mutations in PRRT2 gene in Japanese cases with PKC. Patients and Method: Two cases with a family history of PKC and two sporadic cases were studied. All cases developed symptoms during childhood. Blood samples were collected after obtaining informed consent, and genomic DNA was extracted using standard procedure. Three exons of the PRRT2 gene were amplified by PCR, and sequencing was then carried out using ABI 310 automated sequencer. 55 ID: guganp I Black Lining: [ON] I Time: 09:25 I Path: N:/3b2/ANA#/Vol00000/120255/APPFile/JW-ANA#120255 J_ID: ZAY Customer A_ID: BKLT2012_Abstracts Cadmus Art: ANA12 Date: 18-September-12 (p Вј 0.93) genotypes. Evolution of AD was not affected by these genotypes or by use of statins or Ezetimibe. Conclusion: No association was found between common CETP polymorphisms and age of onset or evolution of AD on this sample. Study supported by: CAPES - CoordenacВёaЛњo de AperfeicВёoamento de Pessoal de NД±Вґvel Superior & FAPESP - The State of SaЛњo Paulo Research Foundation Stage: Page: 56 dation and accumulation of autophagosomes despite mTOR activation. Similar defects were also observed in vivo in a neuronal Tsc1 mouse model and in TSC cortical tuber specimens. These findings reveal that compared to non-neuronal cells, loss of TSC1/2 in neurons results in unexpected autophagy deficits that may contribute to altered neuronal homeostasis in TSC. Study supported by: Intellectual and Developmental Disabilities Research Center (P30HD18655), R01 NS058956 (to MS) and P01 NS024279 (to DJK), the Tuberous Sclerosis Alliance (to ADN), Nancy Lurie Marks Family Foundation and ChildrenвЂ™s Hospital Boston Translational Research Program (to MS) S513. GLRB Is the 3rd Major Gene-of-Effect in Hyperekplexia Charlotte Hunt, Anna Derrick, Thomas Cushion, Sian Wood, Cheney Drew, Owain W. Howells, Rhys H. Thomas, Seo Kyung Chung and Mark I. Rees; Swansea, Wales, United Kingdom and Wales, United Kingdom S515. Homozygous Nonsense Mutations of C12orf65 in Patients with Spastic Paraplegia, Optic Atrophy and Neuropathy Haruo Shimazaki; Shimotsuke, Tochigi, Japan Purpose: Glycinergic neurotransmission is a major inhibitory influence in the central nervous system (CNS) and defects are associated with paroxysmal neuromotor disorder, hyperekplexia or startle disease. The alpha1 subunit of the glycine receptor (GlyR) gene (GLRA1) and its cognate postsynaptic transporter (SLC6A5) are well-established genes in hyperekplexia, nevertheless, 60% of hyperekplexia cases remain gene-negative. The beta subunit of the glycine receptor (GLRB), the partner subunit to GLRA1, was selected for further mutation analysis. Method: 92 gene-negative hyperekplexia patients were selected for variation screening of the GLRB using multiplex PCR and direct Sanger sequencing approach. Mutation constructs were prepared for functional characterisation and Molecular modelling predicts protein-damaging outcomes. Results: This study identified 9 novel GLRB mutations within 8 independent hyperekplexia index-cases accounting for approximately 9% of the gene-negative cohort. This included 5 recessive, 2 dominant and 1 compound heterozygote inheritance scenarios. The biological consequence of the nonsense and indel mutations was unambiguous and the 2 missense mutations were further investigated for electrophysiological analysis. Conclusion: This study describes the largest genetic screening of GLRB in hyperekplexia and represents a 3rd major gene for hyperekplexia. It further implicates the glycinergic proteome as the basis for further analysis. Study supported by: Medical Research Council - UK Objective: To identify the causative gene responsive to autosomal recessive spastic paraplegia (AR-HSP) with optic atrophy and neuropathy. Methods: This study included two patients in a consanguineous family. Two patients underwent neurological examination and DNA analysis, one underwent skin biopsy. We performed genomewide linkage analysis with SNP array, copy-number variation analysis and whole-exome sequencing. Results: We identified a homozygous nonsense mutation (c.394C>T, p.R132X) in Chromosome 12 open reading flame 65 (C12orf65) gene in two patients. C12orf65 gene mutation was not found in 74 Japanese AR-HSP patients without known HSP gene substitutions. Interpretation: The novel nonsense mutation in C12orf65 could be causative for AR-HSP with optic atrophy and neuropathy, resulting in a premature stop codon. Truncated C12orf65 protein would lead to the mitochondrial protein synthesis defect and respiratory complex enzyme activity reduction. Mitochondrial translation dysfunction could be one of the pathogenic mechanisms for the AR-HSP. Study supported by: This work was supported by a grant from the Research Committee for Ataxic Diseases (Y.T. and H.S.) of the Ministry of Health, Labor and Welfare, Japan. This work was also supported by Grants-in-Aid from the Research Committee of CNS Degenerative Diseases (I.N. and Y.T.), and the Ministry of Health, Labor and Welfare of Japan, and supported by a Grant-in-Aid for Scientific Research (C) (23591253 to H.S.) from The Ministry of Education, Culture, Sports, Science and Technology in Japan. This work was supported by a grant from the Research Committee for Ataxic Diseases (Y.T. and H.S.) of the Ministry of Health, Labor and Welfare, Japan. This work was also supported by Grants-in-Aid from the Research Committee of CNS Degenerative Diseases (I.N. and Y.T.), and the Ministry of Health, Labor and Welfare of Japan, and supported by a Grant-in-Aid for Scientific Research (C) (23591253 to H.S.) from The Ministry of Education, Culture, Sports, Science and Technology in Japan S514. Neuronal Loss of Tuberous Sclerosis Complex Activity Results in Increased Autophagosome Accumulation Despite mTOR Activation Alessia Di Nardo, Mary H. Wertz, Jarrett Leech, Emily Greene-Colozzi, June Goto, Dennis Wall, David J. Kwiatkowski and Mustafa Sahin; Boston, MA Tuberous Sclerosis Complex (TSC) is a genetic disorder characterized by the development of benign tumors in various organs. The most severe manifestations include epilepsy, intellectual disability, and autism. A major cellular function of the TSC1/2 complex is to inhibit the mammalian target of rapamycin (mTOR), a master regulator of protein synthesis and cell growth. Previous studies performed in nonneuronal cells have reported that mTOR inhibits autophagy, which is a lysosomal degradation process for the removal of long-lived proteins and damaged organelles in double membrane organelles called autophagosomes. Therefore, nonneuronal Tsc-deficient cells have reduced autophagosome number. Here, we investigated autophagy in Tsc-deficient neurons. We found that, loss of TSC1/2 in neurons results in increased autophagosome formation via the activation of mTOR-independent autophagy initiating signals. As a result, Tsc-deficient neurons have reduced autophagic degra- S516. Hyperekplexia Phenotypes Associated with GLRB Mutations Rhys H. Thomas*, Cheney J. Drew, Owain W. Howell, Thomas Cushion, Sian E. Wood, Jonathan G. Mullins, SeoKyung Chung and Mark I. Rees; Swansea, United Kingdom Introduction: Classical hyperekplexia is a rare glycnergic synaptopathy; 40% have mutations in the a1 subunit of the 56 ID: guganp I Black Lining: [ON] I Time: 09:25 I Path: N:/3b2/ANA#/Vol00000/120255/APPFile/JW-ANA#120255 J_ID: ZAY Customer A_ID: BKLT2012_Abstracts Cadmus Art: ANA12 Date: 18-September-12 glycine receptor (GLRA1) or the presynaptic glycine transporter 2 (SLC6A5). The glycine receptor is a pentameric ligand-gated Cl- channel with 2a1:3b stoichiometry. We present the largest cohort with variants in the beta subunit of the glycine receptor (GLRB). Methods: Over 200 families with suspected hyperekplexia have been evaluated on a research basis. Twelve probands were identified as having variants in GLRB not seen in population studies and deemed likely to be pathogenic following functional modelling analyses. Clinical questionnaires were scrutinised to identify patient characteristics. Results: All twelve cases had autosomal recessive inheritance and were unrelated; four were from India and one from Japan (where GLRA1 variants are less frequently reported). All had symptoms from birth and startle was ubiquitous. The presentation includes a neurodevelopmental spectrum with delayed milestones at one end and severe intellectual disability at the other. Conclusion: The more severe phenotype associated with GLRB mutations is similar to that seen with SLC6A5 and distinct from that associated with GLRA1. Therefore early identification of the GLRB genotype may enable targeted genetic counselling and therapeutic studies. Study supported by: There are no conflicts of interest Stage: Page: 57 the potassium channel KCNC3. SCA13 is interesting in that three distinctive allelic forms are known. The first two described were p.Arg420His and p.Phe448Leu. The phenotypes, though overlapping, are distinct in that p.Arg420His results in a slowly progressive pure cerebellar adult onset ataxia. In contrast, p.Phe448Leu appears developmental, presenting with delayed motor milestones. This phenotypic bifurcation appears attributable to the biophysical effect of each mutation on the channel. We provide a detailed phenotypic description of a novel allelic form of SCA13 caused by a p.Arg423His mutation. Though reported in screening ataxia DNA repositories, we describe a de novo case presenting at 16 months, and a three-generation family with multiple affecteds. This mutation is unique in its biophysical properties and phenotypic manifestation. Heralding features include infantile onset with delayed gross/fine motor milestones, seizures, mental retardation, gait/appendicular ataxia, dysarthria, nystagmus and hypereflexia. MRI confirms cerebellar atrophy as early as nineteen months of age without progression. Longitudinal follow-up suggests moderate lifetime improvement in motor and cognitive function. Study supported by: none S519. A Meta-Analysis of Genome Wide Association Studies To Identify Loci Associated with Brain Atrophy in Multiple Sclerosis Zongqi Xia*, Nikolaos Patsopoulos, Charles Guttmann, PierreAntoine Gourraud, Sergio Baranzini, Jorge Oksenberg, Jeroen Geurts, Bernard Uitdehaag, Raija Lindberg, Yvonne Naegelin, Stephen Hauser, Ludwig Kappos, Chris Polman, Howard Weiner and Philip De Jager; Boston, MA; Cambridge, MA; San Francisco, CA; Amsterdam, Netherlands and Basel, Switzerland S517. Increased Cancer Incidence in LRRK2-G2019S Mutation Carriers BjГёrg Johanne WarГё, Krisztina K. Johansen and Jan Olav Aasly; Trondheim, Norway LRRK2 mutations are the most common genetic cause of late-onset PD. The pathophysiological mechanism is unclear, but evidence indicates gain-of-function with increased LRRK2 kinase activity. Several kinase inhibitors are FDA-approved as cancer treatments. Kinase inhibitors may prove valuable in modulating PD. Epidemiological studies show that PD patients have reduced risk for most cancers but increased for some. Few studies have examined cancer risk in LRRK2-G2019S mutation carriers. Our aim was to study this risk. Manifesting and non-manifesting carriers of the Trondheim LRRK2 PD cohort and their healthy first-degree relatives were interviewed for cancer history. Medical records of the individuals confirming cancer were reviewed. Cancer type was labelled as non-skin cancer or melanoma. Smoking history was obtained. 142 individuals participated in the study, 71 carriers, 58 non-carriers. 13 were of unknown LRRK2-status. 9/71 mutation carriers had cancer (8 non-skin, 1 melanoma). 6/ 13 of unknown LRRK2-status had non-skin cancer. The significantly lowest age-adjusted cancer rate was observed in the first-degree relatives without the LRRK2 mutation. LRRK2 mutation carriers seem to have increased cancer risk compared to their healthy first-degree relatives. This might be associated with the presumed gain-of-function and increased LRRK2 kinase activity. More studies are needed. Study supported by: Liaison Committee between the Central Norway Regional Health Authority (RHA) and the Norwegian University of Science and Technology (NTNU). Multiple Sclerosis (MS) causes progressive neurodegeneration. Genetic variants associated with MS susceptibility are poorly correlated with brain atrophy. We performed a meta-analysis of genome-wide association studies to discover variants influencing brain volume estimated from cross-sectional magnetic resonance imaging data. The discovery analysis comprises three strata from GeneMSA that includes subjects from Amsterdam (n Вј 218), Basel (n Вј 260) and UCSF (n Вј 510). Subjects from the Partners MS center in Boston were used for replication (n Вј 690). We additionally performed a joint meta-analysis using a sample size weighted z-score method. 7.4 million SNPs were imputed with the 1000Genomes reference. A linear regression model was applied with gender, symptom duration, and principal components as covariates. While several intriguing candidates emerged, no variant achieved genome wide significance (P<10-8) in the discovery or joint analyses, suggesting that the genetic architecture of brain volume in MS resembles that of most other complex human traits where common genetic variants have modest effects Pathway analyses using the top candidate SNPs are ongoing, as are efforts to enlarge the meta-analysis using existing collections of MS subjects with volumetric data. Study supported by: National Multiple Sclerosis Society S520. Engineering Mouse Chromosomes To Facilitate Genetic Analysis of Down Syndrome Xiaoling Jiang, Chunhong Liu, Li Zhang, Pavel V. Belinchenko, Alexander M. Kleschevnikov, Annie Pao, William C. Mobley and Y. Eugene Yu; Buffalo, NY and La Jolla, CA S518. Detailed Phenotype of a Novel Allelic Form of Spinocerebellar Ataxia Type 13 Michael F. Waters, Kristina Santiago, Alexis K. Harmeling and Richard P. Morse; Gainesville, FL and Lebanon, NH Trisomy of human chromosome 21 (Hsa21) is the most frequent live-born human aneuploidy and causes a constellation of the abnormalities classified as Down syndrome (DS), which include developmental cognitive disabilities and The dominant cerebellar ataxias are a heterogeneous group of neurological diseases anchored by the phenotypic feature of motor incoordination. SCA13 is caused by mutations in 57 ID: guganp I Black Lining: [ON] I Time: 09:25 I Path: N:/3b2/ANA#/Vol00000/120255/APPFile/JW-ANA#120255 J_ID: ZAY Customer A_ID: BKLT2012_Abstracts Cadmus Art: ANA12 Date: 18-September-12 Stage: Page: 58 including Creutzfeldt-Jakob disease (CJD). Spiroplasma spp. have been cultured from brains affected with TSE. Experimental spiroplasmosis in rodents and ruminants is characterized by neurological deterioration and spongiform encephalopathy. Here the ability of spiroplasma to bind to stainless steel was tested as possible route of iatrogenic transmission of CJD. Experimental transmission of TSE occurs via stainless steel wires exposed to TSE-infected mouse brains when implanted into normal mouse brains. When stainless steel wires were incubated with S. mirum cultures biofilms were detected on the metal surfaces using scanning electron and confocal laser microscopy. Wires with spiroplasma biofilm dried for three weeks, then explanted onto SP-4 agar plates grew out spiroplasma colonies after 14 days incubation at 30 C. Spiroplasma grew from wires exposed to 5% glutaraldehyde for 5 minutes. Spiroplasma had a propensity to survive other agents used to clean surgical instruments. Recognition of involvement of spiroplasma in transmission of TSEs may lead to new strategies in detection, treatment and prevention of TSEs, and development of new methods for cleansing surgical instruments. Study supported by: This research was supported in part by NSF#0731908 and USDA-NRT Grant LAB03922, gifts from families affected with CJD, and the Joseph P. Sardo family for TSE research. Alzheimer-type neurodegeneration. The mouse is a premier model organism for DS because the regions on Hsa21 are syntenically conserved with three regions in the mouse genome, which are located on mouse chromosome 10 (Mmu10), Mmu16 and Mmu17. Recently, we have developed a mouse model trisomic for all three Hsa21 orthologous regions in mice. To further genetic analysis of DS, we are in the process of generating smaller chromosomal duplications and deletions in the Hsa21 orthologous regions in mice using recombinase-mediated long-range chromosome engineering. The phenotypic analysis of these new mouse mutants may result in the establishment of minimal critical genomic regions and eventually new dosage-sensitive genes associated with the cognitively relevant phenotypes. The success of our effort should enhance the understanding of the mechanisms underlying the disease phenotypes and may lead to novel strategies for developing effective therapeutic interventions. Study supported by: NIH, ChildrenвЂ™s Guild Foundation S521. Body-Wide Correction of Myotonic Dystrophy Type 1 (DM1) in Transgenic Mice by RNase H-Active Antisense Oligonucleotides (ASOs) Thurman M. Wheeler, Andrew J. Leger, Sanjay K. Pandey, A. Robert MacLeod, Masayuki Nakamori, Seng H. Cheng, Bruce M. Wentworth and C. Frank Bennett; Rochester, NY; Framingham, MA and Carlsbad, CA S602. Upstate Eastern Equine Encephalitis: A Case Report Mirret M. El-Hagrassy and Yaman Eksioglu; Syracuse, NY Objective: To determine whether systemic delivery of RNase H-active ASOs can reduce or eliminate RNA toxicity in a transgenic mouse model of DM1. Background: DM1 is caused by expression of an expanded CUG repeat (CUGexp) in the 30 UTR of the DMPK transcript. Human skeletal actin-long repeat (HSALR) transgenic mice express CUGexp RNA in the 30 UTR of an hACTA1 transgene. Antisense knockdown of pathogenic RNA would be expected to mitigate clinical features of DM1. Design/methods: ASOs were administered by subcutaneous injection. Treatment assignments were randomized and analysis was blinded. In vivo efficacy was determined by, 1) transgene mRNA knockdown (qRT-PCR), 2) alternative splicing (RT-PCR), 3) myotonia, 4) global gene expression (microarray), and 5) histologic myopathy. Results: Two ASOs reduced transgene levels by up to 80%, eliminated myotonia, and corrected RNA mis-splicing in all muscles examined. More than 85% of changes in gene expression were normalized or improved. Knockdown of RNA toxicity for 1 year rescued myopathy. Conclusions/relevance: ASOs that act through the RNase H pathway may be viable therapeutic agents for DM1. Study supported by: NIH (K08NS064293, U01NS072323) Authors SK Pandey, AR MacLeod, and CF Bennett are employees of Isis Pharmaceuticals, which develops antisense drugs. Authors AJ Leger, SH Cheng, and BM Wentworth are employees of Genzyme Corporation, which develops biological therapeutics. Case: A 4-year-old girl had multiple seizures over several days with left gaze deviation, unresponsiveness and fever. She was taken to PICU as seizures and mental status worsened. EEG suggested encephalopathy, probable left hemispheric pathology. LP suggested viral infection. CT and MRI suggested meningoencephalitis. Therapeutic hypothermia was recommended for high fever. Viral panels confirmed Eastern Equine Encephalitis (EEE) 3 days later. She deteriorated despite receiving phenytoin, acyclovir and antibiotics. Repeat CT showed bilateral ischemia and left temporal uncal herniation. A ventricular drain improved ICP, but she did not survive. Discussion: EEE is a rare neuroinvasive arbovirus borne disease with 50% US case-fatality in 2010. Culiseta melanura mosquito transmits to birds; bridge mosquito vectors transmit to humans (dead end hosts). MRI differentiates from HSV. Nucleic acid amplification assays, reverse transcriptase-PCR and real time RT-PCR are more sensitive and specific than EEEV antibodies. Treatment is empiric and symptomatic. Mouse studies suggest hematogenous CNS viral invasion and early amplification in metaphyseal osteoblasts; peripherally inoculated mature animals resist encephalitis. Conclusion: EEE is a rare fatal arboviral disease. Hypothermia may reduce metabolic demands and ischemia. Public health measures are crucial; future vaccines and antiviral agents may be developed. Study supported by: N/A Neuroinfectious Disease S603. HIV-1 Exposure Affects Neural Progenitor Cell Renewal and Accelerates Astrocyte Differentiation in Human Brain Slices Ricardo Martinez, Rebeca Geffin and Micheline McCarthy; Miami, FL S601. Spiroplasma Biofilm on Stainless Steel Is a Model for Iatrogenic Transmission of CJD Via Surgical Instruments Frank O. Bastian, Xiaochu Wu and Philip H. Elzer; Baton Rouge, LA To study how HIV-1 affects neurogenesis, our вЂ�вЂ�two-cultureвЂ™вЂ™ assay system exposes human fetal brain slices to H9 T-cells that chronically produce HIV-1 IIIB (H9/IIIB). Brainstem Spiroplasma are linked by ultrastructural and molecular studies to transmissible spongiform encephalopathies (TSE), 58 ID: guganp I Black Lining: [ON] I Time: 09:25 I Path: N:/3b2/ANA#/Vol00000/120255/APPFile/JW-ANA#120255 J_ID: ZAY Customer A_ID: BKLT2012_Abstracts Cadmus Art: ANA12 Date: 18-September-12 slices exposed to neural progenitor culture medium only for 21 days showed midline and para-midline nestin extensively co-localized with glial fibrillary acidic acid protein (GFAP). This suggested renewal of neural progenitor cells. Brainstem slices exposed to uninfected H9 cells or H9/IIIB cells showed more dense GFAP, which did not co-localize with nestin. This suggested preferential differentiation into astrocytes. When analyzed for mRNA expression patterns, brainstem slices exposed to H9/IIIB for 7 days expressed 2-3 fold higher levels of mRNA for neuronal structural proteins, as compared to slices cultured in medium alone or slices exposed to uninfected H9 cells. GFAP mRNA level was approximately ten-fold higher in H9/IIIB-exposed slices compared to H9-exposed slices. Thus GFAP mRNA expression at day 7 predicted increased GFAP antigen at day 21. mRNA for transcripts associated with progenitor cell renewal (Hes1, Hes5, nestin) were 2-5 fold lower in H9and H9/IIIB-exposed slices. These data suggest that HIV-1 exposure impairs neuroepithelial progenitor maintenance and accelerates astrocyte differentiation. Study supported by: Department of Veterans Affairs Stage: Page: 59 northeast. In addition, cases of recurrent coccidioidal meningitis are not well-described in the literature. A 53-year-old female with history of hepatitis C, hepatocellular carcinoma, and coccidioidal meningitis in 2009 presented with gait instability and confusion. After a normal CT head and CSF (including negative coccioidal antibody) 4 months prior to presentation, she had been taken off fluconazole, on which she had been placed for chronic suppressive therapy after her episode of coccidioidal meningitis. With her current presentation, she was found to have hydrocephalus, bilateral cerebral edema, and extensive meningeal enhancement along with CSF findings of 273 leukocytes per microliter, high protein, and low glucose. Coccioidal antibody was eventually found to be positive, and she has thus far responded to fluconazole. Our patient demonstrates a severe case of relapsing coccidioidal meningitis complicated by hydrocephalus that to date has responded to fluconazole. Study supported by: Not applicable. S606. A Mouse Model of Arachnoid Granulation Obstruction by Cryptococcus Jeffrey A. Rumbaugh, Angela Pool, Lindsey Gainey and Yu Hui Wu; Atlanta, GA S604. Anti-Ganglioside Antibodies Positive Influenza Encephalopathy Hitoshi Mori and Katuro Shindo; Kurashiki, Okayama, Japan Raised intracranial pressure causes much morbidity and mortality from HIV-associated cryptococcal meningitis, but mechanisms leading to increased pressure are not well studied. Blockage of CSF reabsorption at arachnoid villi by organisms and shed polysaccharide is widely hypothesized. However, high organism load is necessary but not sufficient, suggesting other factors must play a role. We have developed a murine model of cryptococcal infection. We have used a wildtype, normocapsular strain of C. neoformans, called H99, and a hypervirulent, hypercapsular strain which is isogenic to H99, called PKR1. We are comparing differences in the ability of these strains to infiltrate the CNS and obstruct arachnoid villi, using quantitative immunohistochemical techniques. We are also examining in vivo capsule thickness and its relation to CSF blockage over time. If these strains obstruct arachnoid granulations similarly, then other factors must account for their difference in virulence. With this model, we have easy availability of genetic and immunologic reagents, and we have chosen intravenous inoculation because it most closely mimics physiological hematogenously disseminated disease. This mouse model will be a powerful tool, allowing us to dissect complex fungalhost relationships involved in neuropathogenesis of Cryptococcus in the brain. Study supported by: Emory Center for AIDS Research Background: There is no report about relationship between anti-ganglioside antibodies and influenza encephalopathy. Some authors say that anti-ganglioside antibodies were not detected in human subjects infected with 2009 pandemic influenza A(H1N1) virus. The mechanism of influenza encephalopathy is incompletely known, we think neuron specific antibodies will exist in some type of influenza encephalopathy. Method: 5 influenza encephalopathy patients were admitted to our hospital from April 2009 to February 2012. We examined their anti-ganglioside antibodies in serum on admission. Results: Anti-ganglioside antibodies were detected in two of them. A 78-year-old woman with loss of consciousness and low grade fever was diagnosed as influenza encephalopathy by influenza A (H3N2) virus.GM3, GD3, GQ1b antibodies were detected in her serum. She was successfully treated by methylprednisolone pulse therapy and peramivir. A 31-year-old man with delirium and fever was diagnosed as influenza encephalopathy by 2009 pandemic influenza A (H1N1) virus.GD1a, GT1b antibodies were detected in his serum. He recovered by the combination therapy including methylprednisolone pulse, plasma exchange, intravenous immunoglobulin, oseltamivir. Conclusion: This is the first report about influenza encephalopathy with positive anti-ganglioside antibodies. This finding accounts for the usefulness of methylpredonisolone pulse, plasma exchange, intravenous immunoglobulin in influenza encephalopathy. Study supported by: Kurashiki Central Hospital IвЂ™m employed by Kurashiki Central Hospital S607. Pathways to Neurodegeneration: The Effects of HIV & Aging on Resting State fcMRI Jewell B. Thomas, Matthew R. Brier, Florin F. Vaida, Abraham Z. Snyder and Beau M. Ances; St. Louis, MO and San Diego, CA Background: HIVГѕ patients are living longer due to highly active antiretroviral therapy (HAART). However, many HIVГѕ individuals still have cognitive impairment. Older HIVГѕ patients may be at increased risk for developing neurodegenerative disorders. Methods: This study used resting state functional MRI (rs-fMRI) to investigate the neurobiology of five functionally-defined brain networks in 52 HIVГѕ (44% on HAART) and 52 HIV- controls. Composite scores were computed for five networks: default-mode (DMN), control (CON), salience (SAL), dorsal attention (DAN) and sensorimotor S605. A Severe Case of Recurrent Coccidioidal Meningitis Complicated by Hydrocephalus Sarah Nelson and Michal Vytopil; Burlington, MA Coccidioidal meningitis is an unusual manifestation of the fungal infection coccidioidomycosis and is also the most fatal. Recommendations are that patients remain on lifelong therapy following treatment of their meningitis because relapses can occur. Coccidioides fungi are endemic to the southwestern United States and thus not often seen in the 59 ID: guganp I Black Lining: [ON] I Time: 09:25 I Path: N:/3b2/ANA#/Vol00000/120255/APPFile/JW-ANA#120255 J_ID: ZAY Customer A_ID: BKLT2012_Abstracts Cadmus Art: ANA12 Date: 18-September-12 (SMN). Independent changes in rs-fMRI due to HIV and aging were assessed by ANCOVA. Results: Reduced rs-fMRI correlations were seen within DMN (p Вј .003), CON (p Вј .006), and SAL (p Вј .03) while DAN and SMN were spared. Neither markers of HIV (HIV viral load or CD4Гѕ cell count) nor degree of HIV-associated cognitive impairment correlated with rs-fMRI measures. Aging led to decreased correlations within the DMN (p Вј .03) and SAL (p Вј .006) for both HIVГѕ and HIV- subjects. No interaction was seen between HIV and aging. Conclusions: These results suggest that HIV and aging cause similar decreases in rs-fMRI. Further longitudinal studies of older HIVГѕ patients are needed. Study supported by: This work was supported by the National Institutes of Health (NIMH K23MH081786, NINR R01NR012907, NINR R01NR012657) (BMA) and (P30 NS048056) (AZS) as well as Dana Foundation (DF10052) (BMA) Mr. Brier, Mr. Thomas, Dr. Snyder, and Dr. Raichle report no disclosures. Dr. Ances is on a scientific advisory board for Lily Pharmaceuticals. Stage: Page: 60 Concordance between clinical history and VER was 66%. Nerves with a clinical history of ON were more likely to have the radiological finding of fluid around the nerve (p Вј 0.017). Within patients with prior unilateral clinical ON, there was an association with reduced minimum cross sectional area (p Вј 0.03) with a trend towards association with total optic nerve volume (p Вј 0.06) in the affected eye. At the group level however, neither of these atrophy measures were statistically associated with prior clinical ON or positive VER, with significant inter-subject variability. This pilot study demonstrated that some radiological features on 3T MRI may be helpful in the assessment of the optic nerve and workup of possible demyelination, and further study is warranted. Study supported by: St. JamesвЂ™ Hospital S703. The Lone Abducting Eye and Laterality of Motor Control: Congresswoman GiffordsвЂ™ вЂ�вЂ�Wrong-Way EyesвЂ™вЂ™ Denotes Crossed Right Hemisphere Syndrome in a Right Hander Iraj Derakhshan; Veckeley, WV and Cleveland, OH S608. Clearance of Low Copy JC Virus from CSF of MS Patients on Natalizumab Gloria von Geldern, Caroline Ryschkewitsch, Peter Jensen, Avindra Nath and Eugene O. Major; Bethesda, MD Backgrounds and Methods: It is commonly believed that supratentorial lesions affecting the right (minor) hemisphere is associated with conjugate eye deviation toward that hemisphere (i.e. вЂ�вЂ�the eyes have itвЂ™вЂ™). Data indicate that this kind of eye deviation is often associated with left hemi-sensory neglect in right handed people. The вЂ�вЂ�eye-signвЂ™вЂ™ is ascribed to the unopposed action of the left (major) hemisphere in pulling both eyes to the right, with the left eye joked by the right via the medial longitudinal bundle. Often associated with left hemiplegia, these cases are not aphasic as the left hemisphere remains intact. The вЂ�вЂ�wrong wayвЂ™вЂ™ eye deviation is often ascribed to hemorrhage in contralateral thalamus, without further explanation as to its mechanism. The CongresswomanвЂ™s photos in the initial stage of her traumatic illness demonstrate that her left eye was deviated to the extreme left (i.e. towards the damaged hemisphere) as her right eye stopped at the middle. Conclusion: Congresswoman GiffordsвЂ™ is similar to those of right handers with lesions affecting their left (but minor) hemispheres; able to communicate fully nervertheless. Study supported by: entire private Background: Reactivation of JC virus (JCV) causes progressive multifocal leukoencephalopathy (PML), a devastating demyelinating brain disease. Diagnosis can be challenging and the significance of low copy numbers of JCV DNA in cerebrospinal fluid (CSF) needs further investigation. Methods: CSF of multiple sclerosis (MS) patients on natalizumab was analyzed by quantitative polymerase chain reaction (PCR). Forty four patients with <100 copies/mL were identified. Clinical and magnetic resonance imaging (MRI) findings were reviewed. Results: 21/44 had repeat CSF analysis after discontinuation of natalizumab. 8/21 had high copies, 6/21 continued to have low copies, and 7/21 had undetectable JCV on repeat. 5/44 patients (all <50 copies/mL) had atypical clinical or MRI findings. 3/5 atypical patients had subsequent CSF analysis, all had undetactable JCV. Discussion: Only a third of PML patients with low copy numbers cleared the virus and this included patients with atypical clinical or MRI findings. Another third have persistent low virus in CSF and a third have high copy numbers. While detection of JCV DNA in CSF by itself is not sufficient for diagnosis, attention should be paid even to low copy numbers. Study supported by: None S704. MOG Antibody Positive Optic Neuritis in Adults Jithin S. George, Joanna Kitley, Mark Woodhall, John Elston, Maria I. Leite, Angela Vincent and Jacqueline Palace; Oxford, Oxfordshire, United Kingdom Objectives: To characterise the clinical features of optic neuritis (ON) in four adults seropositive for myelin oligodendrocyte glycoprotein (MOG) antibodies. Methods: MOG antibody was tested using cell based assay. Optical coherence tomography, visual evoked responses and visual function assessments were performed in all patients. Results Conclusions: MOG antibody positive optic neuritis can be unilateral or bilateral and synchronous with longitudinally extensive myelitis. Neuromyelitis optica may be diagnosed in such cases, however, unlike the aquaporin-4 antibody mediated spectrum of CNS demyelination, MOG antibody positive cases appear to have better visual function outcomes. Study supported by: JG has received support for scientific meetings from Biogen Idec. JK has received support for scientific meetings from Biogen Idec and is supported by the NHS National Specialised Commissioning Group for Neuromyelitis Optica. MIL is supported by the NHS National Neuro-ophthalmology S701. Withdrawn. S702. 3-Tesla MRI of the Optic Nerve: A Pilot Study David Bradley, Iqbal Mudassir, Gerard OвЂ™Connor, Lisa Costelloe, Derbhail OвЂ™Driscoll, Andrew Fagan, Jim Meaney and Janice Redmond; Dublin, Ireland Optic neuritis (ON) is common in MS. Diagnosis is based on clinical evaluation and visual evoked responses (VERs). Standard MR imaging of the optic nerve is uninformative due to regional structural characteristics. This pilot aimed to examine the ability of 3-tesla (3T) MRI to image the optic nerve. 9 patients (3 female, mean age 43.3yrs) underwent MR scans at 3T and had VERs recorded, providing data on 18 optic nerves. 5 had prior clinical ON (2 bilateral). 60 ID: guganp I Black Lining: [ON] I Time: 09:25 I Path: N:/3b2/ANA#/Vol00000/120255/APPFile/JW-ANA#120255 J_ID: ZAY Customer A_ID: BKLT2012_Abstracts Cadmus Art: ANA12 Date: 18-September-12 Specialised Commissioning Group for Neuromyelitis Optica and AV and MIL are involved in AQP4 and MOG antibody testing, supported by the NHS National Specialised Commissioning Group for Neuromyelitis Optica and by the NIHR Oxford Biomedical Research Centre. JE has nothing to disclose. JP has received unrestricted grants and support for scientific meetings and scientific advisory honorariums from Merck Serono, TEVA, Biogen, Bayer Schering and Novartis, has held MS society grants and is a clinical lead for the UK Department of Health Risk Sharing Scheme. Stage: Page: 61 constriction OD, and visual acuity 20/100 and paracentral scotomas OS were present at the first and second attack, respectively. MRI revealed widespread enhancement and thickening in the meninges and ONS, and T2-hyperintense SON lesion in the right/left episodic side, respectively. Proteinuria and multiple pulmonary CT nodules suggested the systemic WG. Steroid therapy attenuated visual disturbance and orbital lesions. Conclusion: The clinicoradiological courses of our patients indicated the common mechanism of inflammatory hypertrophy between pachymeningitis and HPN in WG patients. Study supported by: None. S705. Longitudinally Extensive Optic Neuritis in Pediatric Patients Jennifer Graves, Verena Kraus, Bruno Soares, Jonathan Strober and Emmanuelle Waubant; San Francisco and Munich, Germany S707. Is This the Tolosa-Hunt Syndrome? Ulya S. Malik and Odai Jumma; Birmingham, United Kingdom Objective: Optic neuritis (ON) as a first demyelinating event is common. While extensiveness of spinal cord lesions predict diagnoses such as neuromyelitis optica, the importance of lesion extent in ON is unknown. We address whether lesion length of a first ON predicts a non-MS diagnosis. Methods: This is a retrospective study of pediatric patients who presented with a first ON event seen at the pediatric MS clinic at UCSF since inception in 2006. Those with brain or orbit MRI scans within 3 months of symptom onset were included. Lesion length, determined by T2 hyperintensity or contrast enhancement, was graded by a blinded neuro-radiologist as absent, focal or longitudinally extensive (at least two segments of the optic nerve). Results: 26 Patients were identified who met criteria and had interpretable MRI imaging of the optic nerves. Of these 9 (35%) had longitudinally extensive (LE) ON. Almost half of MS cases had LEON. Extensive lesions were not associated with non-MS vs. MS diagnosis (RR 0.94, 95% CI: 0.21 to 4.2). Younger patients tended to be more likely to have LEON (p Вј 0.21). Conclusions: LEON is common and not necessarily associated with a non-MS diagnosis in pediatric patients. Study supported by: Dr. Graves is supported by a Sylvia Lawry Fellowship from the National Multiple Sclerosis Society. Further grants from NMSS and the Nancy Davis Foundation supported this work. Introduction: Pathology underlying painful ophthalmoplegia is localised to the cavernous sinus/superior orbital fissure with causes being traumatic, neoplastic, aneurysmal or inflammatory. Of the latter, a small category develop symptoms secondary to a non-specific mass in the cavernous sinus and respond to corticosteroid therapy. The disorder is termed Tolosa-Hunt syndrome. Case presentation: We present a 27 year old female with 3 weeks history of severe right periorbital pain, progressive ipsilateral ptosis and numbness affected the first and second divisions of the trigeminal nerve. A 6mm mass was located in the right cavernous sinus on MRI exerting mass effect on the right internal carotid artery. Diagnosis was complicated by the patientвЂ™s depression, manifesting as mixed neurological symptoms including hemiparesis and dysarthria. Symptoms persisted until high dose corticosteroid therapy caused complete resolution within 24 hours. Although cessation of headache was expected, resolution of hemiparesis and dysarthria following corticosteroids remains unexplained. Conclusion: Although essentially a diagnosis of exclusion, the rare Tolosa-Hunt syndrome is an important differential in patients with painful ophthalmoplegia. While some variation in symptoms among patients is expected, a dramatic improvement with corticosteroid therapy is almost pathognomonic of the condition. Study supported by: N/A S706. Hypertrophic Perioptic Neuritis (HPN) in Wegener Granulomatosis (WG) Ken Ikeda, Takanori Takazawa, Tetsuro Nagaoka, Takehisa Hirayama, Osamu Kano, Kiyokazu Kawabe and Yasuo Iwasaki; Tokyo, Japan S708. Ethambutol Induced Optic Chiasmopathy Subin Mathew, Raghavendra Seetharam, Ravindra Kamble and Rajani Battu; Bangalore, Karnataka, India Introduction: Ethambutol (EMB) induced chiasmopathy is rarely reported. Results: A 59 year gentleman during evaluation of headache and giddiness was detected to have pituitary mass lesion (hyperplastic on retrospect) without any effect on the optic chiasm. His visual fields were normal. He underwent transnasal endoscopic excision of pituitary lesion. Histopathology showed granulomatous inflammation. Sarcoid workup was negative. Antitubercular treatment (ATT)was empirically started. He received EMB, isoniazid, rifampicin, and pyrazinamide for 9 months. 7 months into therapy he noticed progressive worsening of vision bilaterally. He continued on ATT for 9 months. His visual acuity by then was CF at 1 m along with impaired bilateral color vision. Visual fields revealed centrocecal scotoma. MRI brain showed empty sella alone. ATT was immediately stopped with a presumptive diagnosis of EMB induced optic neuropathy, a course of prednisone was administered. Despite EMB Background: To elucidate a novel pathogenesis of WGassociated HPN. Methods: We highlighted clinicoradiological hallmarks of two patients with hypertrophic pachymeningitis and HPN due to WG. Results: Patient 1: a 71-year-old man developed bilateral blurred vision. Visual acuity and field were no light perception and diffuse constriction OD, and 6/12 and nasal constriction OS. MRI disclosed widespread enhancement and thickening in the mineninges and optic nerve sheets (ONS). T2-hyperintensity lesions existed along the superficial optic nerve (SON). Seropositive proteinase-3-antineutrophil cytoplasmic antibody and multiple pulmonary CT nodules supported the limited WG. Steroid and cyclophosthamide treatment improved visual dysfunction and orbital lesions. Patient 2: a 74-year-old man developed blurred vision alternatively for one year. No light perception and diffuse 61 ID: guganp I Black Lining: [ON] I Time: 09:25 I Path: N:/3b2/ANA#/Vol00000/120255/APPFile/JW-ANA#120255 J_ID: ZAY Customer A_ID: BKLT2012_Abstracts Cadmus Art: ANA12 Date: 18-September-12 withdrawal visual fields showed progressive worsening of bitemporal field defects. Conclusion: The presence of bitemporal field defects particularly in the setting of pituitary surgery as in this patient, can lead to potential consideration of compressive optic chiasmopathy that was negated by repeated MRI studies. EMB toxicity can worsen despite withdrawal and needs prompt early recognition of this complication. Study supported by: All the authors have read and agreed with the content and its educational motives and have allowed me to submit the abstract in the conference. I am currently doing my externship/observership as Resident Doctor in the department of Neuroscience, Vikram hospital Bangalore. I have done the study myself with the assistance on my senior faculty members. Stage: Page: 62 Conclusion: This patient had sequential ON due to syphilis. Classic dermatologic findings led to a prompt diagnosis. With its increasing incidence and reputation for being вЂ�вЂ�the great imitator,вЂ™вЂ™ syphilis should be considered in all patients with ON. When treated appropriately, syphilitic ON has a good prognosis. Study supported by: N/A S711. Correlation of the Retinal Ganglion Cell Complex and Contrast Sensitivity in Parkinson Disease Eric M. Shrier, Christopher R. Adam, Yin Ding, Sophya Glazman and Ivan Bodis-Wollner; Brooklyn, NY Purpose: To evaluate functional visual and morphological correlation of foveal impairment in PD. Methods: 32 eyes of 16 PD and 34 eyes of 17 matched controls. Monocular and binocular contrast sensitivity (CS) was quantified by Pelli-Robson chart. Retinal thickness was measured using RTVue RT100 EMM5 scans. Thickness measurements of the retinal ganglion cell complex (GCC) at 0.25 mm intervals at sequential radial distances from the foveola in all quadrants were obtained. Raw data files were imported and analyzed in MATLAB. Results: Multivariate analysis demonstrated pairwise correlation between monocular CS and age, binocular CS and, age and IRL thickness at 1.00 mm inferiorly and 1.00 mm nasally. Age was controlled for in all statistical comparisons. Mean monocular CS differed between healthy controls and PD. Bivariate analysis of monocular CS by thickness revealed a significant difference in the inner retina in a specific perifoveolar annular zone. Conclusions: Thinning of the GCC in the foveal pit correlates with CS loss in PD. To our knowledge this is the first time correlation of foveal morphology and visual impairment is shown in PD. Study supported by: Michael J Fox Foundation, award# 53947 S709. Optic Disc Edema Does Not Always Correlate with Retinal Nerve Fiber Layer (RNFL) Thickening Mark J. Morrow; Torrance, CA Background: The peripapillary retinal nerve fiber layer (RNFL) is typically thickened in conditions that cause visible optic disc edema (ODE), including idiopathic intracranial hypertension (IIH). I sought to determine whether this is always true. Methods: I quantified optic nerve head (ONH) volume and compared it with RNFL thickness in patients with ODE. Spectral-domain optical coherence tomography (OCT) assessed the RNFL with a standard 3.45mm circle scan and the ONH with parallel vertical scans. I defined cylinders of 2mm and 3mm diameter centered on the ONH and established the volumes of tissue contained therein, inside the level of BruchвЂ™s membrane. Results: Using normal subject-derived cutoffs, I identified 70 eyes with enlarged ONHs in 44 subjects. Of these 70 eyes, 28 (16 patients) demonstrated normal or reduced mean RNFL thickness, only 7 of which showed increased thickness in any quadrant. Diagnoses in these eyes included IIH, hydrocephalus and drusen. Conclusions: Mismatches between optic disc volume and RNFL thickness may be explained by limited intraocular extent of axoplasmic engorgement, by mixed populations of dead and swollen axons, or by intrusions of non-neural material in the ONH with drusen. Study supported by: Not applicable. S712. Late Diffusion Changes in Optic Radiations Predicted by Early Optic Nerve Structure after Optic Neuritis, Suggesting Trans-Synaptic Effects Olivia Goodkin, Olga Ciccarelli, Daniel Altmann, Camilla Fini, Alessia Mirigliani, Thomas M. Jenkins, Alan J. Thompson and Ahmed T. Toosy; London, United Kingdom Introduction: We wished to address whether trans-synaptic changes occur in the optic radiations (ORs) after optic neuritis (ON), by answering: 1) Do longitudinal structural changes in the ORs occur after ON; 2) Do earlier optic nerve changes predict later OR changes, suggesting a transsynaptic lag effect. Methods: Twenty-eight acute ON patients and 8 healthy controls were recruited. Assessments were at baseline, 3, 6 and 12 months. DTI tractography of the ORs was performed as well as optic nerve MRI. Results: Lower optic nerve areas in patients at 3 months were associated with lower fractional anisotropy (FA) (p Вј 0.028) and higher radial diffusivity (RD) (p Вј 0.038) of the ORs at 12 months. These associations survived after adjusting for OR lesion load. ON patients also showed reductions in OR FA (p Вј 0.014) and increases in OR RD (p Вј 0.003) over the year. Controls were stable. Conclusions: Following ON, affected optic nerve area at 3 months predicts OR structure at 12 months, suggesting trans-synaptic effects. The reduction in FA of the ORs can be explained by an increase in RD presumably reflecting ongoing axonal loss and/or demyelination. S710. Syphilitic Optic Neuritis: Possibly Forgotten but Not Gone Robert K. Shin, Marc A. Malouf, Shalom E. Kelman, Larysa D. Kwintkiewicz and Stephen G. Reich; Baltimore, MD Objective: To report a case of acute syphilitic optic neuritis (ON), an historically important and common cause of ON rarely encountered today. Background: The incidence of syphilis is rising in the US. Syphilis frequently involves the eye or central nervous system, though ON is rare. Case Report: A 46 yo man with hypertension and diabetes awoke with blurred vision OS. Multiple ophthalmologic evaluations were inconclusive. One week later, he developed blurred vision OD and was referred to the ED for possible retinal ischemia. Visual acuity was 20/400 OD and CF OS. He had a left afferent pupillary defect and mild left optic disc pallor. An erythematous, scaly rash was present on the face, palms and soles suggestive of syphilis. Serum RPR was reactive (1:4) with positive FTA. CSF showed 48 WBCs and protein 600 mg/dl. He was treated with intravenous penicillin with improvement in vision. 62 ID: guganp I Black Lining: [ON] I Time: 09:25 I Path: N:/3b2/ANA#/Vol00000/120255/APPFile/JW-ANA#120255 J_ID: ZAY Customer A_ID: BKLT2012_Abstracts Cadmus Art: ANA12 Date: 18-September-12 Study supported by: MS Society. Higher Education Funding Council of England. Stage: Page: 63 S802. Cognitive Assessment in Rett Syndrome: A Pilot Study of Eyetracking Aleksandra Djukic, Maria Valicenti-McDermott, Kathleen Mavrommatis and Cristina Martins; Bronx, NY S713. Cerebellar Esotropia Misdiagnosed as VI Nerve Paresis: A Case Series Sui H. Wong, Leena Patel and Gordon T. Plant; London, United Kingdom and London, United Kingdom Cognitive testing in Rett Syndrome(RTT) have been difficult because most patients are nonverbal,with limited hand use. Eye tracking may be invaluable in neuropsychological assessment in RTT. Objectives: to determine the accuracy of eye gaze for pointing, to identify clinical characteristics predictive of eye pointing accuracy; to examine visual preferences in RTT. Methods: 50 consecutive patients with RTT at Rett Center July-October/2010 were tested using eye-tracker(Tobii technology). To test eye pointing accuracy 25 stimuli were displayed, results were associated with clinical characteristics. To test visual preferences 5 stimuli were displayed(cartoons/ shapes/faces). Number/duration of looks for targets were determined. Statistics: Chi-square/analysis of variance. Results: Mean age1067y., 86% had classical RTT, 80% good eye contact, 26% no hand use; 35 (70%) demonstrated eye pointing accuracy. Girls with eye pointing accuracy were more alert (68%vs.44% p Вј 0.02), had better eye contact (91vs.50%p Вј 0.002), poorer hand use (hand use: 3% vs. 44% p<0.001) and worse language (verbal: 6% vs. 31% p Вј 0.02). They displayed preferences, looking longer (2.862вЂ™вЂ™vs.0.961вЂ™вЂ™p Вј 0.024) to cartoons than shapes. With faces, they focused on eyes(1.76 1вЂ™вЂ™ (eyes)vs.161вЂ™вЂ™ (nose)vs.0.860.4вЂ™вЂ™ (mouth) p Вј 0.04). Conclusions: 70% of patients exhibited accurate eye gazepointing. Girls who were more alert, with good eye contact, poorer hand use and worse language skills were more likely to complete testing. Eye tracking represents a feasible method to assess cognition in RTT. Study supported by: This study was funded in part by the International Rett Syndrome Foundation Background: Cerebellar dysfunction causing horizontal diplopia is under-recognised. We report a case series of patients presenting with horizontal diplopia, misdiagnosed as VI nerve paresis or with no clear cause identified. Methods: Prospective observational case series Results: Seven patients (3 male) with cerebellar degeneration were referred for assessment of binocular horizontal diplopia. One patient had SCA3 cerebellar degeneration, two (father and daughter) had familial cerebellar ataxia, and four were idiopathic. The age of presentation of was 31-76 years (mean 56, median 63). 6/7 had bilateral mild lateral recti under-action at presentation. All had mild and slowly progressive cerebellar ataxia. All had comitant esotropia to distance vision worse than for near, which was also slowly progressive. Conclusion: We present a series of 7 patients with esotropia secondary to cerebellar dysfunction, causing horizontal diplopia to distance vision. The relative preservation of near fusion suggests that this is due to a divergence paresis, rather than a supranuclear deficit. The comitant esotropia is unlikely to be due to bilateral VI nerve paresis in these patients. Study supported by: None S714. Withdrawn. Pediatric Neurology S801. Elevated Immune Response to Gliadin in Autism: Association with Gastrointestinal Symptoms but Not Celiac Disease Nga M. Lau, Peter H. Green, Donald D. Kasarda, Luan To, Abhishek Chandra, Barry E. Kosofsky, Joseph J. Higgins, Anjali M. Rajadhyaksha and Armin Alaedini; New York, NY and Albany, CA S803. Asymptomatic Abnormalities in the White Matter of Patients with CMT-X Amy R. Viehoever, Linda Schimmoeller, Tammie Benzinger, Soe Mar and Amy Viehoever; St. Louis, MO Background: X-linked Charcot-Marie-Tooth (CMT-X) is an X-linked dominant hereditary peripheral neuropathy, Transient and recurrent central nervous system involvement with white matter changes on magnetic resonance imaging (MRI) has been reported in this condition, but usually in the context of abnormal neurologic symptoms. We initiated a study of CNS involvement in a large family with CMT-X to understand the relationship between genotype and phenotype of CNS white matter involvement. Methods: We performed the standard of care clinical MRI, directional diffusivity DTI sequences, and detailed neurological evaluation of 9 family members with CMT-X; All participants had peripheral neuropathy and genetic confirmation of CMT-X. Only one subject had symptoms of CNS disease. Results: White matter signal changes were found in all cases of varying degrees of severity affecting the corpus callosum and periventricular areas with a posterior predominance similar to previous reported cases. In one case, there were profound multifocal white matter abnormalities. Conclusions: There can be changes in the white matter of patients with CMT-X in absence of symptoms of CNS disease. Further analysis of the changes in the directional diffusivities could potentially differentiate between the axonal and myelin pathology. Study supported by: None Previous studies examining the link between autism and gluten sensitivity have been inconclusive due to methodological shortcomings. The aim of this study was to measure markers of gluten sensitivity and celiac disease in children with autism, diagnosed according to DSM-IV criteria. IgG and IgA antibodies to gliadin, deamidated gliadin, and transglutaminase-2 were measured in serum from 37 children with autism, 28 unaffected siblings, and 76 agematched healthy controls. Children with autism had significantly higher levels of IgG antibody to gliadin compared with unrelated healthy controls (p<0.01). In addition, there was a significant association between elevated anti-gliadin antibody and gastrointestinal symptoms in autistic children (p<0.01). There was no difference in levels of celiac-specific markers (antibodies to deamidated gliadin and transglutaminase-2) between affected patients and controls. The data demonstrate an association between autism and elevated immune response to gliadin, which correlates with increased gastrointestinal symptoms. However, the majority of patients with autism and elevated anti-gliadin antibody do not have celiac disease. Further research is needed to better understand the antigenic specificity and pathogenic relevance of the immune response to gliadin in autism. Study supported by: Department of Defense 63 ID: guganp I Black Lining: [ON] I Time: 09:25 I Path: N:/3b2/ANA#/Vol00000/120255/APPFile/JW-ANA#120255 J_ID: ZAY Customer A_ID: BKLT2012_Abstracts Cadmus Art: ANA12 Date: 18-September-12 S804. Visual Function and Optical Coherence Tomography in Pediatric Demyelinating Diseases Amy T. Waldman, Girish Hiremath, Robert A. Avery, Amy Conger, Michael Loguidice, Lauren S. Talman, Kristin M. Galetta, Michael J. Shumski, James Wilson, EвЂ™tona Ford, Benjamin M. Greenberg, Jonas Ellenberg, Elliot M. Frohman, Laura J. Balcer and Peter A. Calabresi; Philadelphia, PA; Baltimore, MD and Dallas, TX Stage: Page: 64 that targeting EGFR after injury is clinically feasible for treatment of white matter injury in premature children. Study supported by: K08NS073793 (JS); P01NS062686 (VG); Childhood Brain Tumor Foundation (JS) S806. Drosophila Peroxisomal Biogenesis Defects Produce Shortened Lifespan and Excess Cystene-String Protein at the Synapse Michael F. Wangler, Lucy Liu, Nikolaos Giagtzoglou, Vafa Bayat, Joseph Faust, James McNew and Hugo J. Bellen; Houston, TX Objective: To examine visual function scores and retinal nerve fiber layer (RNFL) thickness in children with demyelinating diseases and disease-free controls. Methods: Children (5 to <18 years) with demyelinating diseases and controls were enrolled across 3 academic centers. Visual function was assessed using high-contrast (ETDRS) charts and low-contrast Sloan letter charts (LCSLC, 2.5% and 1.25% contrast). Optical coherence tomography (OCT) was performed using Stratus OCT-3. Linear regression was used to compare visual tests and RNFL thickness between patients and controls. Results: 56 subjects were enrolled and compared to 47 controls. Only LCSLC (1.25% contrast) differed between the groups for both monocular and binocular data (p<0.001 and 0.012, respectively). Binocular summation resulted in a 10-letter improvement in the binocular score compared to the better eye score for patients and controls (p Вј 0.4979). RNFL thickness for all disease eyes (110 lm) was decreased compared to control eyes (100 lm, p Вј 0.001); however, RNFL thickness was preserved among non-optic neuritis (ON) eyes of children with multiple sclerosis (MS) (109 lm, p Вј 0.554). Conclusions: LCSLC captured subtle vision changes in children. In contrast to adult data, RNFL thickness was preserved in non-ON eyes of children with MS. Study supported by: National Multiple Sclerosis Society and American Academy of Neurology Foundation (now the American Brain Foundation) Peroxisomal biogenesis is encoded by a group of evolutionarily conserved genes called the pex genes. Peroxisomal defects produce neurologic problems in patients with Peroxisomal Biogenesis Disorders (PBD). To further understand the role of peroxisomes within the nervous system, we have turned to Drosophila melanogaster. We have generated and characterized loss-of-function alleles of pex16, and of pex2. As predicted, peroxisomes are grossly abnormal in these mutants. Interestingly, these mutants are viable, and they display a crumpled wing phenotype, locomotor defects and dramatically shortened lifespan. Furthermore, a detailed biochemical analysis reveals a unique lipid metabolism defect. To better understand the role of peroxisomes in synaptic biology we performed a detailed characterization of the Neuromuscular junction (NMJ) for pex2. While vesicle release is normal in these mutants, FM1-43 dye loading during stimuation is increased. Additionally, cysteine-string protein (CSP), a synaptic vesicle protein is dramatically increased in the synaptic boutons. CSP overexpression has been reported to result in phenotypes similar to what we have observed in the pex mutants which suggests the novel hypothesis that CSP underlies nervous system dysfunction in peroxisomal biogenesis defects. Study supported by: K08 NS076547-01 Rehabilitation and Regeneration S805. Epidermal Growth Factor Treatment Rescues Neonatal White Matter Injury Joseph Scafidi, Maria Roncal, Tamas L. Horvath, Robert J. McCarter and Vittorio Gallo; Washington, DC and New Haven, CT S901. Time Limited Functional Properties of Transplanted Neural Stem Cells Nina Fainstein, Ofira Einstein, Mikhal Cohen and Tamir Ben-Hur; Jerusalem, Israel Neural stem cells (NSC) possess powerful immunomodulatory and neurotrophic properties. NSCs effectively attenuate neuroinflammation, protect the brain from immune-mediated injury and facilitate its self repair capacity. However, the therapeutic value of NSC therapy in chronic diseases is critically dependent on their long term functions. We therefore examined whether transplanted NSCs maintain their immunomodulatory and trophic properties over time. Transplanted NSCs could not support their own long term survival, becoming highly dependent on environmental cues. Damaging versus induction of a local neurogenic environment significantly compromised or improved graft survival, respectively. In accordance, long term cultured NSC spheres exhibited dramatic decline in proliferative activity, increased apoptosis and reduced neurotrophic factor secretion. Then, in two experimental paradigms, intracerebroventricular transplanted syngeneic NSCs attenuated an early relapse of experimental autoimmune encephalomyelitis, but failed to inhibit delayed relapses, albeit good survival of transplant. Moreover, following allogeneic transplantation, NSC grafts failed to inhibit the allogeneic immune reaction and were rejected from the host brain. In correlation, long A significant public health concern is the growing numbers of very preterm infants with neonatal brain injury. Diffuse white matter injury (DWMI) is a common finding in these children and correlates with their sustained neurodevelopmental impairments. There are no clinically relevant targeted therapies available that improve function. As shown recently, failure in oligodendrocyte progenitor cell maturation contributes to DWMI. It has been demonstrated that epidermal growth factor receptor (EGFR) plays an important role in oligodendrogenesis. Here, we examine whether enhanced EGFR signaling stimulates the endogenous response of EGFR-expressing progenitor cells during a critical period after injury, and promotes cellular, ultrastructural and behavioral recovery. Using a model of premature brain injury, we demonstrate that overexpression of EGFR in oligodendrocyte-lineage cells or the administration of intranasal EGF immediately after injury decreases oligodendroglia death, promotes oligodendrogenesis and accelerates maturation. Furthermore, these interventions diminish ultrastructural abnormalities and alleviate behavioral deficits on white matter-specific paradigms. We also demonstrate that EGFR signaling is crucial with loss of function experiments in vivo. Our multidisciplinary study provides direct evidence 64 ID: guganp I Black Lining: [ON] I Time: 09:25 I Path: N:/3b2/ANA#/Vol00000/120255/APPFile/JW-ANA#120255 J_ID: ZAY Customer A_ID: BKLT2012_Abstracts Cadmus Art: ANA12 Date: 18-September-12 term cultured NSCs lost their capacity to inhibit immune cell proliferation in vitro. In conclusion, long-term functional changes in transplanted NSCs lead to loss of their therapeutic immunomodulatory and neurotrophic properties. Study supported by: The Taubman Foundation Stage: Page: 65 Study supported by: the National Research Foundation (NRF-2010-0020408; NRF-2010-0024334; SC-4160), and the Chyung Ki Lee Research Fund S904. OnabotulinumtoxinA Plus Rehabilitation Improves Functional Outcome in Post-Stroke Upper Limb Spasticity: A Single-Blind, Randomized Trial Deidre J. Devier, JoAnn Harnar, Leandro M. Lopez, Allison Brashear and Glenn D. Graham; New Orleans, LA; Albuquerque, NM; Albuqueruque, NM; Winston Salem, NC and Washington, DC S902. Recovery of Motor Function after Complete Unilateral Injury of the Corticospinal Tract Using Electrical Stimulation of Motor Cortex on the Uninjured Hemisphere in Rats Jason B. Carmel, Hiroki Kimura, Gabriel Felder, Ashley Khalili, Melissa Lopresti, Chelsea Jin and John H. Martin; White Plains, NY and New York, NY Background and Purpose: This multi-center, prospective randomized, single-blind, clinical trial explored the potential benefit of adding weekly occupational therapy to a background of onabotulinumtoxinA (BoNT-A) treatments for upper limb spasticity, using the upper limb Fugl-Meyer to assess short-term improvement in patient functional outcome. Methods: Thirty-one patients with post-stroke upper limb spasticity aged 36вЂ“75 were enrolled and treated with BoNT-A. They were randomly assigned to either BoNTAГѕRehab or BoNT-A no rehab. They were injected up to 2 times and followed for 24 weeks. Results: Both groups showed significant improvement in Fugl-Meyer scores. There was also a significant Fugl-Meyer by Group interaction with the BoNT-AГѕRehab group showing significantly more functional improvement. This improvement was driven primarily by change in the upper extremity movement and pain subscales. Two self-report measures, Disability Assessment Scale and Patient Disability Scale, also showed improvement across study visits, but did not differ between the two treatment groups. Conclusions: Rehabilitation therapy following injection of onabotulinumtoxinA for post-stroke upper limb spasticity results in improved functional recovery. This effect was measured over approximately seven months and may continue beyond that time period. Study supported by: This project was supported by an unrestricted research grant from Allergan Inc. to the Biomedical Research Institute of New Mexico (BRINM). Dr. Graham is a consultant for D-Pharm, Ltd. and is a member of the Global Stroke Community Advisory Panel, which indirectly receives support from Allergan. Dr. Brashear performs research and consults with Ipsen, Allergan and Merz and her conflict of interest is managed by Wake Forest School of Medicine. We hypothesized that in mature animals with complete unilateral lesion of the corticospinal tract (CST), electrical stimulation of motor cortex (M1) on the uninjured side would promote recovery of skilled motor function after chronic injury. We cut one pyramid and tested motor skill weekly to show a stable forelimb deficit. We then implanted electrodes over forelimb area of M1 on the intact side. 8 weeks after CST injury, we used the epidural electrodes to deliver stimulation 6 hours a day for10 days. At 4 weeks after stimulation, treated rats performed the motor task significantly better that rats with CST injury alone and similar to uninjured rats. To determine whether the ipsilateral (stimulated) M1 was responsible for mediating this motor recovery, we performed pharmacological inactivation of M1. In rats with stimulation, inactivation of stimulated M1 caused a worsening in the initially impaired forepaw to an error rate similar to that before stimulation. Thus, in rats with chronic and complete unilateral CST injury we restored motor control from M1 on the intact side using electrical stimulation. Study supported by: N/A S903. Synergic Effects of Enriched Environment and Mesenchymal Stem Cells in Hypoxic-Ischemic Brain Injury through FGF-2 Dependent Mechanism Jung Hwa Seo, Ji Hea Yu, Yang Hyun Cho and Sung-Rae Cho; Seoul, Republic of Korea We investigated environmental enrichment (EE) after transplantation of mesenchymal stem cells (MSCs) could synergistically enhance functional recovery in an animal model of hypoxic-ischemic brain injury. Brain damage was induced in CD-1 (ICR) mice (P7). At 6 weeks of age, the mice were randomly treated with MSCs (1x105 cells) or PBS into the striatum, assigned to 5 groups: MSC-EE (n Вј 18), MSCcontrol (n Вј 19), PBS-EE (n Вј 12), PBS-control (n Вј 17), untreated control (n Вј 23). As a result, MSC-EE synergistically improved rotarod latency by 8 weeks after treatment (p<0.05). Cylinder, ladder walking, and grip strength tests also showed enhanced motor functions in MSC-EE mice. They also showed a significant increase of Tuj-1Гѕ neurons of grafted cells prelabeled with BrdU and endogenous striatal neurogenesis (p<0.05). In addition, MSCs and/or EE exhibited an increment of CD31Гѕ vessel density and GFAPГѕ astroglial activation over controls (p<0.05). Furthermore, FGF-2 were significantly overexpressed in MSCEE when evaluated using multiplex ELISA system (Quantibody array) (p<0.05). In conclusion, EE after transplantation of MSCs elicited synergistically beneficial effects for neurorestoration by promoting endogenous repair process of neurogenesis coupled with angiogenesis and astroglial activation through FGF-2 dependent mechanism. S905. Peripheral and Cutaneous Nerve Fiber Regeneration in the Distal Foot of Macaques after Spinal Nerve Ligation (SNL) Gigi J. Ebenezer, Jasenka Borzan, Matthias Ringkamp, Lun Chen, Justin C. McArthur, Peter Hauer, James N. Campbell, Richard A. Meyer, John W. Griffin and Michael Polydefkis; Baltimore We examined morphological and quantitative changes of nerve fibers and Schwann cells in the distal nerve and foot epidermis of Macaque monkeys after SNL to investigate the mechanisms of neuropathic pain. Methods: Four months following lesion, peripheral nerves and skin roll encompassing L5/6 dermatomes were examined and quantified using electron microscopic and immunohistochemical techniques. Results: Though injured nerves showed significant loss of nerves with marked Wallerian degeneration, the size of remaining unmyelinated axons and Remark Schwann cells was preserved with evidence of disregulated axonal 65 ID: guganp I Black Lining: [ON] I Time: 09:25 I Path: N:/3b2/ANA#/Vol00000/120255/APPFile/JW-ANA#120255 J_ID: ZAY Customer A_ID: BKLT2012_Abstracts Cadmus Art: ANA12 Date: 18-September-12 regeneration. There was robust reinnervation of L5/6 dermatome with PGP9.5 Гѕve and CGRP Гѕve dermal nerve fibers with proliferation of Schwann cells. The epidermal nerve fiber reinnervation was patchy with increased intraepidermal terminal branching on the plantar side. Conclusion: SNL resulted in pronounced Wallerian axonal degeneration in peripheral nerves with evidence of irregular axonal regrowth, while there was robust re-innervation of the skin at the distal foot. The remodeling and collateral sprouting of uninjured nerve fibers, upregulation of Schwann cells and release of neuropeptides by regenerating CGRP fibers at the plantar skin provide a pathological correlate to neuropathic pain. Study supported by: Blaustein Pain Research fund Stage: Page: 66 Measurements included: fatigue (Modified Fatigue Impact Scale); balance (computerized posturography). Results: The experimental group improved in fatigue (p < 0.001), improving greater than the exercise control group (p Вј 0.024) and the control group (p Вј 0.005), and in balance (p < 0.001), improving greater than the exercise control group (p Вј 0.001) and control group (p Вј 0.003). Conclusion: A 6-week vestibular rehabilitation program demonstrated both statistically significant and clinically-relevant changes in fatigue and balance in persons with MS. Study supported by: This study was partially supported by the National Multiple Sclerosis Society, Pilot Project no. PP1501. This study was published in August of 2011 in the Physical Therapy Journal. Permission to reprint/reproduce for the purpose of abstract submissions and publications, and conference presentations has been requested and granted. See mandated requirement for the full citation of this duplicated material below: вЂ�вЂ�Reprinted from Hebert JR, Corboy JR, Manago MM, Schenkman M. Effects of Vestibular Rehabilitation on Multiple Sclerosis-Related Fatigue and Upright Postural Control: A Randomized Controlled Trial. Physical therapy. 2011;91(8):1166-1182, with permission of the American Physical Therapy Association. This material is copyrighted, and any further reproduction or distribution requires written permission from APTA.вЂ™вЂ™ S906. Vestibular Rehabilitation and Multiple Sclerosis: Do Patients with Infratentorial Lesions Benefit More? Jeffrey R. Hebert; Aurora, CO Background: Multiple sclerosis (MS) frequently affects infratentorial structures including the brainstem and cerebellum, resulting in impaired balance often leading to advanced disability. Evidence is evolving that indicates interventions targeting brain lesion involvement may prove more effective. Yet to be determined is whether vestibular rehabilitation, balance and eye movement training, is most effective for those with brainstem and/or cerebellar involvement. Methods: Single-group analysis from a 3-group (N Вј 38 persons with MS), 14-wk randomized controlled trial, where the experimental group underwent vestibular rehabilitation. Experimental group-only (N Вј 12) analysis of changes in balance (posturography) was performed based on brainstem and/or cerebellar lesion involvement: participants with (n Вј 8) and without (n Вј 4). Results: Balance improved significantly for participants with brainstem and/or cerebellar involvement (21.6, p Вј 0.002) and insignificantly for those without (10.3, p Вј 0.134), with a large between-group standard effect size (d Вј 0.99; p Вј 0.155). Conclusion: A 6-wk vestibular rehabilitation program demonstrated statistically significant and clinically relevant improvements in balance for persons with MS who have brainstem and/or cerebellar involvement. The small sample size is a limitation; however, the results warrant larger investigations. Study supported by: This study was partially supported by the National Multiple Sclerosis Society, Pilot Project no. PP1501. S908. RTMS in Treatment of Poststroke Aphasia Wolf-Dieter Heiss, Alexander Hartmann, Josef Kessler, Nora Weiduschat, Ilona Rubi-Fessen, Carole Anglade and Alexander Thiel; Cologne, Germany and Montreal, Canada Non-invasive repetitive transcranial magnetic stimulation (rTMS) might improve the effect of speech therapy in poststroke aphasia. A randomized, controlled and blinded study examined the effect of 1Hz rTMS over the non-dominant BrocaвЂ™s homologue. Results of 21 subjects with poststroke aphasia in the subacute stage are reported. According to group allocation patients received, additionally to conventional speech and language therapy, 10 sessions of rTMS either over the inferior frontal gyrus of the non-dominant-hemisphere (intervention group) or over the vertex (control group). The primary outcome measure is the change in the global score of the Aachen Aphasia Test (AAT) battery, secondary outcome variables are AAT subtests and the extent of interhemispheric activation shift as measured with language activation PET. There was a significant difference in pre- and post treatment global AAT scores between TMS-treated and shamtreated groups with significantly higher mean scores in the treatment group (TMS-group: 22.8 Гѕ/- 12.36, Sham-group 9.4 Гѕ/- 12.79, p Вј 0.032). A repeated measures analysis of variance demonstrated a highly significant treatment effect across all subtests (P Вј 0.002). PET revealed a shift of activated language-related cortex towards the left hemisphere in the intervention group. Repetitive TMS might be an effective complementary therapy for poststroke aphasia. Study supported by: Marga and Walter Boll Foundation S907. Effects of Vestibular Rehabilitation on Multiple Sclerosis-Related Fatigue and Upright Postural Control: A Randomized Controlled Trial Jeffrey R. Hebert, John R. Corboy, Mark M. Manago and Margaret Schenkman; Aurora, CO Background: Fatigue and impaired upright postural control (balance) are the two most common findings in persons with multiple sclerosis (MS), with treatment approaches varying greatly in effectiveness. The objective of the study was to investigate the benefits of implementing a vestibular rehabilitation program for the purpose of improving fatigue and balance in persons with MS. Methods: The study was a 14-week, single-blinded, stratified blocked, randomized controlled trial. 38 persons with MS were randomized to: experimental group, exercise control group or wait-listed control group. The experimental group underwent vestibular rehabilitation and the exercise control group underwent bicycle endurance and stretching exercises. S909. Regulatory Experience with Orphan Disorders of the Nervous System Orest Hurko, Andra E. Miller, Ruth Wolff and James G. Kenimer; Alexandria, VA Concerns that pharmaceutical companies are dissuaded from pursuit of therapeutics for neurological disorders with 66 ID: guganp I Black Lining: [ON] I Time: 09:25 I Path: N:/3b2/ANA#/Vol00000/120255/APPFile/JW-ANA#120255 J_ID: ZAY Customer A_ID: BKLT2012_Abstracts Cadmus Art: ANA12 Date: 18-September-12 limited commercial opportunities prompt interest in the role of alternate sponsors and FDAвЂ™s Orphan Product program. We reviewed the performance of both from the inception of the program in 1983. As of March 14, 2012, there were 610 FDA designations of Orphan Status for proposed treatments of disorders affecting the nervous system. In descending order, designations in this category were awarded to small to medium cap firms (413), large firms (147), unaffiliated individuals (24), academic institutions (16), disease-related charities (7) and government agencies (3). Neurologic orphans sponsored by large companies achieved an overall approval of 29.3% vs. 8.72% for those by small-cap biotechs. The approval advantage of large companies and governmental agencies over smaller sponsors spanned therapeutic classes: proteins, 40.0% vs. 5.88%; small molecules, 26.7% vs. 11.3%. This disparity accords with our observations of difficulties experienced by emerging sponsors in demonstrating consistent manufacture and safety, as well corroboration of findings published by Heemstra: failures from вЂ�вЂ�clinical trial design, the level of experience of the sponsor and the level of interaction with the FDA.вЂ™вЂ™ Study supported by: Biologics Consulting Group, Inc. All four authors are full-time employees and part owners of Biologics Consulting Group, Inc. Stage: Page: 67 We developed Shefstim, a 64 channels stimulator which automatically determines the best site of stimulation. Twenty one participants were recruited. They performed two walks of 10 m for each of the following conditions: own setup (PS), clinician setup (CS), automated setup (AS) and no stimulation (NS). PS and CS used a conventional stimulator. In AS stimulation used Shefstim. Outcome measures were walking speed andfoot angle at initial contact. Compared to NS, mean walking speeds improved significantly with all three FES setups. Speed for both AS (0.65 m/s) and CS (0.68 m/s) were comparable. Speed with PS (0.72 m/s)was significantly better than with AS and CS. Frontal plane foot orientation at heel-strike was more neutral for AS than others. Dorsiflexion angles for AS were larger than NS, not different to PS and less than CS. This study has demonstrated that Shefstim produces results comparable to clinician setup. The technique seems sufficiently reliable to warrant further studies. Study supported by: This work was generously funded by the Sheffield Hospitals Charitable Trust. The Trust had no involvement in any aspects of the work or publication. S912. Deconditioning in Patients with Orthostatic Intolerance Ajay K. Parsaik, Thomas G. Allison, Wolfgang Singer, David M. Sletten, Michael J. Joyner, Eduardo E. Benarroch, Phillip A. Low and Paola Sandroni; Rochester, MN S910. Examining Driving Ability in Multiple Sclerosis Maria Schultheis, Chelsea Morse, Josh McKeever, Lisa Zhao and Thomas Leist; Philadelphia, PA Objective: To examine the relationship between driving ability, cognition, and physical impairment in drivers with Multiple Sclerosis (MS). Methods: Participants include persons with clinically defined MS (n Вј 14). Driving performance was defined using a virtual reality driving simulator (VRDS). Specifically, speed and lane deviation during basic (highway) and complex (following a vehicle, dual task) driving were examined. All participants were administered the Multiple Sclerosis Functional Composite (MSFC), visual measures and neuropsychological measures relevant to driving ability. Results: Individuals with MS and cognitive impairment demonstrated greater lane deviation during a truck following task (t Вј -2.37, p Вј .04) and while simultaneously performing an attention demanding behavioral task (t Вј -2.65, p Вј .02). Correlational analysis revealed that the MSFC (R2 Вј -.73, p Вј .04) and contrast sensitivity (R2 Вј -.71, p Вј .048) were significantly related to VRDS performance. Conclusions: The presence of cognitive impairment in individuals with MS may contribute to greater difficulties in lane management during complex but not basic driving. Additionally, MS severity and contrast sensitivity may contribute to driving performance. Together, these preliminary findings indicate that impairment across various domains (cognitive, visual, severity) may contribute to changes in driving ability. Study supported by: National Multiple Sclerosis Society Background: Recent evidence suggests a central role of deconditioning in orthostatic intolerance. Frequency and degree of deconditioning and its relationship with autonomic parameters in these patients have not been studied. Methods: We retrospectively studied orthostatic intolerance patients seen at Mayo Clinic between January 2006 and June 2011, who underwent autonomic and exercise testing. Results: 184 [84 Postural Orthostatic Tachycardia Syndrome (POTS), 100 without orthostatic tachycardia (OI)] fulfilled inclusion criteria. 89 % were females; mean age 27.5 years and symptoms duration 4 years. 93 % patients had deconditioning (predicted VO2 max % <85%) during exercise. Deconditioning was unrelated to age, gender, and duration of illness and prevalence was similar between POTS (95%) and OI (91%). Predicted VO2 max % had a weak correlation with a few autonomic and laboratory parameters, but adequate predictors of deconditioning could not be identified. Conclusion: Deconditioning is present in almost all patients with orthostatic intolerance and may play a central role in pathophysiology. This finding provides a strong rationale for retraining in the treatment of orthostatic intolerance. None of the autonomic indices are reliable predictors of deconditioning. Study supported by: This work was supported in part by National Institutes of Health (NS 32352 Autonomic Disorders Program Project; NS 44233 Pathogenesis and Diagnosis of Multiple System Atrophy, U54 NS065736 Autonomic Rare Disease Clinical Consortium), Mayo CTSA (UL1 RR24150), and Mayo Funds. S911. Shefstim: Automated Setup of Functional Electrical Stimulation for Drop Foot Using a 64 Channel Prototype Stimulator and Electrode Array Ben W. Heller, Alison J. Clarke, Timothy R. Good, Jamie Healey, Krishnan P.S. Nair, Emma J. Pratt, Mark L. Reeves, Jill M. van der Meulen and Anthony T. Barker; Sheffield, South Yorkshire, United Kingdom S913. Orthostatic Intolerance with or without Postural Orthostatic Tachycardia Ajay K. Parsaik, Thomas G. Allison, Wolfgang Singer, David M. Sletten, Michael J. Joyner, Eduardo E. Benarroch, Phillip A. Low and Paola Sandroni; Rochester, MN Background: We recently reported that deconditioning is universal in patients with Postural Tachycardia Syndrome (POTS) and orthostatic intolerance without orthostatic tachycardia (OI-NP). In this study we compared clinical and Functional electrical stimulation can correct foot drop following upper motor neuron disorders. Some patients have difficulty identifying sites to place stimulating electrodes. 67 ID: guganp I Black Lining: [ON] I Time: 09:25 I Path: N:/3b2/ANA#/Vol00000/120255/APPFile/JW-ANA#120255 J_ID: ZAY Customer A_ID: BKLT2012_Abstracts Cadmus Art: ANA12 Date: 18-September-12 autonomic characteristics between: POTS vs OI-NP, Deconditioned vs non-deconditioned. Methods: We retrospectively studied all patients referred for orthostatic intolerance at Mayo Clinic between January 2006June 2011, who underwent autonomic and exercise testing. Results: 84 POTS and 100 OI-NP fulfilled inclusion criteria, 89% were females, mean age 25 and 32 years respectively. Clinical presentation, presence and degree of deconditioning, and autonomic parameters were similar between the 2 groups, Responses to different medications for OI were poor in both groups. Severely deconditioned patients were clinically similar to non-deconditioned, except in the following: TST% anhydrosis 1.5% vs 0.5% (clinically insignificant), 24 hour urine volume (ml) 1555 vs 2417, peak heart rate change during exercise (beats/min) 78 vs 103, peak respiratory rate 33/min vs 37/min, tidal volume (ml) 1656 vs 2054, breathing reserve (ml) 61 vs 48, respectively. Conclusion: POTS and OI-NP are similar entities. Clinically, deconditioned patients are similar to non-deconditioned but have lower 24 hour urine volume, peak heart rate and respiratory parameters. Study supported by: This work was supported in part by National Institutes of Health (NS 32352 Autonomic Disorders Program Project; NS 44233 Pathogenesis and Diagnosis of Multiple System Atrophy, U54 NS065736 Autonomic Rare Disease Clinical Consortium), Mayo CTSA (UL1 RR24150), and Mayo Funds. Stage: Page: 68 function. Similar advances are commencing in spinal-cord imaging, despite challenges related to the small cross-sectional size of the spinal cord and physiological-related motions. Emerging techniques including ultra-high-field MRI, custom coil design, and multi-parametric MRI promise more sensitive and quantitative assessment of spinal-cord pathology. We report preliminary evidence of new radiologic capabilities for evaluating myelopathy. One case involved a young woman left with motor and sensory hemideficits after inadvertent intramedullary injection into her cervical spinal cord. Combining high-resolution structural imaging, diffusion tensor imaging and magnetization transfer using 3T MRI allowed us to detect and serially characterize Wallerian degeneration of one ascending dorsal column that was unseen on her clinical MRIs. Another patient had persistent limb clumsiness, pain, and itch after hemorrhage of a spinal-cord cavernoma. Ultra-high field 7 Tesla MRI and custom-made coils enabled very-high spatial resolution (370 micron). This permitted exquisite localization of specific symptoms to sub-parts of spinal-cord structures, including associating neuropathic itch to specific dorsal-horn laminae. Greater understanding of spinal-cord function and lesions appears likely to follow. Study supported by: Public Health Service [NIHK24NS59892], National Center for Research Resources [P41-RR14075] National MS Society [FG 1892A1/1] S1002. Neuregulin-1 Effects on Endothelial and BloodBrain Barrier Permeability after Experimental Injury Josephine Lok, Song Zhao, Wendy Leung, Ji Hae Seo, Deepti Navaratna, Xiaoying Wang and Lo Eng; Boston, MA and Jilin, China S914. Efficacy of Vitamin E Supplementation in Cisplatin-Induced Neuropathy: A Meta-Analysis of Randomized Controlled Trials Rechilda Rhea P. Reyes, Rechilda Rhea Reyes, Rechilda Rhea Reyes, Rechilda Rhea Reyes and Rechilda Rhea Reyes; Davao City, Davao, Philippines Blood-brain-barrier disruption contributes to brain edema, inflammation, and neuronal cell death after brain injury. Thus, BBB integrity is an important potential therapeutic target in the treatment of traumatic brain injury. The effects of neuregulin-1 (NRG1) on endothelial permeability and BBB permeability are reported here. Incubation of brain microvascular endothelial cells with IL-1b increased endothelial permeability, while NRG1 co-incubation ameliorated this pathological increase. Similarly, incubation with TNFa decreased the expression of ZO-1 and VE-cadherin. The decrease was less extensive with NRG1 co-incubation. For in-vivo studies, C57Bl mice were subjected to controlled cortical impact (CCI) under anesthesia and BBB permeability was assessed by measuring Evans blue dye extravasation. NRG1-treated mice exhibited a 35% decrease in BBB permeability compared to vehicle-treated mice. Hemoglobin ELISA performed at the same time point showed a trend towards lower levels of hemoglobin extravasation in the NRG1 group, but the results did not reach statistical significance. MMP-9 activity was not different between groups at 2h. These data suggest that NRG1 decreases the permeability of endothelial cells exposed to inflammatory cytokines and reduces BBB permeability following experimental brain trauma. Study supported by: NINDS The clinical use of platinum-based antineoplastic agents is limited by severe peripheral neurotoxicity reported in up to 90% of patients receiving a cumulative dose higher than 300 mg/m2. Recent studies support that cisplatin-induced neuropathy is related to degeneration of large dorsal root ganglion cell bodies with loss of large myelinated fibers. Evidence suggests that side effects induced by cisplatin treatment are, at least in part, the result of the formation of free radicals. In animals, supplementation with antioxidants protects against renal toxicity and ototoxicity induced by cisplatin; moreover, human studies indicate that cisplatin treatment induces a decrease in plasma antioxidant levels due to oxidative stress. It has been noticed that clinical and neuropathologic features observed in cisplatin-induced neuropathy are similar to those observed in vitamin E deficiency neuropathy. The objective of this paper is to evaluate the efficacy of Vitamin E as prophylaxis against cisplatin-induced peripheral neuropathy. Based on this meta-analysis, vitamin E supplementation is effective in the prevention of cisplatin-induced neurotoxicity. It can also be concluded that Vitamin E may also be effective in the prevention of other polyneuropathy caused by other diseases. Study supported by: none Trauma/Injury S1003. Widely Used Clinical Predictors Do Not Account for Outcome Variability in Mild Traumatic Brain Injury Paolo Moretti, Stephen McCauley, Elisabeth Wilde and Harvey Levin; Houston S1001. Preliminary Clinical Utility of Advanced SpinalCord MRI Julien Cohen-Adad, Wei Zhao, Lawrence L. Wald, Bradley Buchbinder and Anne Louise Oaklander; Charlestown, MA and Boston, MA We hypothesized that methods used in the acute evaluation of mild traumatic brain injury (mTBI) do not allow prospective identification of individuals at risk of unfavorable outcome. We analyzed data from a prospective study of Advances in brain imaging have revolutionized neurological diagnosis and knowledge of normal and pathological brain 68 ID: guganp I Black Lining: [ON] I Time: 09:25 I Path: N:/3b2/ANA#/Vol00000/120255/APPFile/JW-ANA#120255 J_ID: ZAY Customer A_ID: BKLT2012_Abstracts Cadmus Art: ANA12 Date: 18-September-12 consecutive patients with mTBI. All subjects had negative acute CT findings and no sources of secondary gain at follow-up. Based on Glasgow Outcome Scale-Extended results at 3 months post-injury, we compared two groups: Upper Good Recovery (n Вј 116; 57.1% of total) and Lower Moderate Disability (n Вј 21; 10.3% of total). The groups did not differ on gender, injury severity/mechanism, Glasgow Coma Scale score, alcohol/toxicology results, or history of drug/alcohol use. The groups differed on age, education, and history of psychiatric difficulties (all p<.05). Regression analysis indicated that although each factor made a significant contribution, the model only accounted for 29% percent of the variance (adjusted r-square Вј .29). This demonstrates that some of the most widely used predictors of outcome following mTBI account for only a small fraction of the outcome variance. Further studies are needed to dissect the factors associated with outcome variability and to develop more effective prognostic tools in mTBI. Study supported by: CDC Grant R49/CCR612707 Stage: Page: 69 neurological deficit (ND) or PTSD correlated with episodes of mTBI with LOC, not with episodes of altered consciousness. 2) Before any interventions, cognitive impairment and headache frequency correlated with PTSD severity. 3) During treatment of PTSD, cognitive performance correlated with headache frequency and intensity, PTSD severity and IS. Headache frequency correlated with ND severity, IS and PTSD severity. Pain correlated with PTSD severity and IS. Thus cognitive impairment and headache severity were most consistently correlated with PTSD and IS. We felt that NDs were markers of brain injury. For mTBI, the important role that brain injury plays is to potentiate the genesis of PTSD as suggested by the correlation between the prevalence of PTSD and the number of episodes of mTBI with LOC. Study supported by: Rehabilitation Research and Development Service of the Office of Research and Development, Department of Veterans Affairs, United States S1006. Delayed Imaging Findings in Delayed Posthypoxic Leukoencephalopathy Kevin A. Shapiro, Mai Anh Huynh, Riley M. BoveВґ, Stephanie L. Cincotta and Jeffrey M. Ellenbogen; Boston, MA S1004. Systematic Review and Meta-Analysis of Glasgow Coma Scale and Simplified Motor Scale in Predicting Traumatic Brain Injury Outcomes Balwinder Singh, M. Hassan Murad, Larry J. Prokop, Patricia J. Erwin, Zhen Wang, Shannon K. Mommer, Sonia S. Mascarenhas and Ajay K. Parsaik; Rochester, MN and London, United Kingdom Delayed posthypoxic leukoencephalopathy (DPHL) is a rare sequela of prolonged cerebral hypoxia, characterized by parkinsonism or akinetic mutism beginning 2-40 days after the anoxic insult. Brain MRI typically demonstrates diffuse white matter hyperintensity on T2- and diffusion-weighted sequences, reflecting acute demyelination. However, the temporal evolution of imaging findings with respect to the appearance of clinical symptoms is poorly defined. We describe the case of a 47-year-old woman who presented with rigidity and cognitive decline one month after cardiopulmonary arrest. She recovered from the arrest within 10 days, and returned home with only mild memory difficulties. Approximately 10 days later, she developed worsening short-term memory deficits, emotional lability, and shuffling gait, which progressed to diffuse rigidity, hyperreflexia, and akinetic mutism. Brain MRI on day 22 showed patchy T2 hyperintensities in biparietal white matter, without diffusion changes. Repeat MRI on day 34 showed diffuse white matter hyperintensity on T2weighted images with corresponding diffusion restriction. To our knowledge, this is the first reported case in which serial MRI examinations have shown that neuropsychiatric symptoms may precede the development of characteristic imaging findings, suggesting that white matter injury may be advanced before it becomes radiographically obvious. Study supported by: The authors are employed by Massachusetts General Hospital. There are no other relevant disclosures. Objective: To compare the Simplified Motor Scale (SMS) and Glasgow Comma Scale (GCS) in predicting traumatic brain injury (TBI) outcomes. Data Sources and study selection: A search of Ovid EMBASE, Ovid Medline, Ovid PsycInfo, evidence-based medicine Reviews, Scopus and related conference proceedings was performed through February 28, 2012 for studies comparing SMS and GCS in predicting TBI outcomes [emergency tracheal intubation (ETI), clinically significant brain injuries (CSBI), neurosurgical intervention (NSI) and mortality]. Data Synthesis: Five retrospective studies including 102132 TBI subjects (63.4% males), with 14670 (14.4%) ETI, 16201 (15.9%) CSBI, 4730(4.6%) NSI and 6725 (6.6%) mortality, were eligible. Pooled AUC of the GCS vs SMS was as follows: CSBI 0.79 vs 0.75 (p Вј 0.16), NSI 0.83 vs 0.81(p Вј 0.34), ETI 0.85 vs 0.82 (p Вј 0.31) and mortality 0.90 vs 0.87 (p Вј 0.01), respectively. Large heterogeneity between the studies was observed in all analysis (I2 > 50%) Conclusion: Even though CSBI, NSI and ETI after TBI can be predicted by SMS with accuracy similar to total GCS, but mortality is better predicted by GCS. Due to heterogeneity and limited number of studies, further prospective studies are required. Study supported by: None S1007. When Mild Traumatic Brain Injury IsnвЂ™t so Mild Latha G. Stead, Aakash N. Bodhit, Keith R. Peters, Lawrence Lottenberg and Bayard D. Miller, Sr; Gainesville, FL S1005. Headaches and Cognitive Performance after Combat Mild Traumatic Brain Injury (mTBI) Correlate with Episodes of Loss of Consciousness (LOC), Post-Traumatic Stress Disorder (PTSD) and Impaired Sleep (IS) Ronald G. Riechers, Robert L. Ruff, Xiao-Feng Wang, Suzanne S. Ruff and Traci Piero; Cleveland, OH Objective: The present study characterizes patients with mild traumatic brain injury (TBI) findings on neuroimaging. Methods: We conducted an observational cohort study of consecutive adults presenting to the Emergency Department with TBI and Glasgow Coma Score 15 upon arrival. Results: The cohort (n Вј 409) was 60% male, median age 38 yrs (IQR 24-59). Racial composition was 76% white, 18% black, 4% Hispanic and 2% other. The CT was abnormal in 25% (103),; 81% with bleed; 36% with fracture; 25% having both. The mechanism of MVC vs. fall was significantly associated with bleed (p Вј .0075). This held true even after adjusting for age, sex, and associated symptoms of injury We correlated headaches and cognitive performance with episodes of mTBI, PTSD and IS in 126 Middle East combat veterans. Study group obtained from 2091 veterans sequentially screened for episodes of mTBI with loss of consciousness (LOC). Final steps were neurological and psychological examinations. Important observations were: 1) Prevalence of 69 ID: guganp I Black Lining: [ON] I Time: 09:25 I Path: N:/3b2/ANA#/Vol00000/120255/APPFile/JW-ANA#120255 J_ID: ZAY Customer A_ID: BKLT2012_Abstracts Cadmus Art: ANA12 Date: 18-September-12 (p Вј .0245, R2 Вј 13.7%). Regression modeling showed older age and vomiting demonstrating a statistical trend t(p Вј 0.0666). For bleeds, vomiting demonstrated a strong association, p Вј 0.0076, R2 Вј 23.6%. Conclusions: This study underscores: 1) the importance of neuroimaging in all patients with TBI, including those with a GCS 15. Fully 8% of our cohort was not imaged. Extrapolating, these would represent 4.8% bleeds, and 2.9% fractures. 2) The limitations of GCS in classifying TBI, as patients with even the mildest of mild TBI have a high frequency of gross CT abnormalities. Study supported by: n/a Stage: Page: 70 risk. Resting state functional connectivity (rs-fc) may be an early biomarker. We studied if a FH of AD disrupts rs-fc in cognitively normal individuals. Methods: rs-fc was obtained in participants with at least one biological parent with AD (FHГѕ) (n Вј 196) and those without parents having AD (n Вј 152) (FH-). Results: To obtain optimal seed regions, rs-fc was compared between 8 AD participants and 8 cognitively normal individuals. Significant decreases in rs-fc were observed between the posterior cingulate cortex (PCC) and retrosplenial cortex, left and right hippocampi, left and right lateral parietal lobules, and anterior cingulate. These regions were subsequently used to assess rs-fc differences between FHГѕ and FH- cognitively normal individuals. While rs-fc was decreased between each seed, only rs-fc between bilateral hippocampi and the PCC were significantly decreased for FHГѕ compared to FH- subjects after controlling for age, sex, apolipoprotein E genotype. Conclusion: FHГѕ of AD decreases rs-fc between the hippocampi and PCC. These changes may be an early biomarker of AD, but larger longitudinal studies are required. Study supported by: NIH (NINR and NIMH) Dr. Ances is on the advisory board for Lily and Medscape. 2012 Annual Meeting Monday, October 8, 2012 Poster Session Abstracts Posters will be displayed in Gloucester, located on the 3rd floor in the Back Bay Hall of the Marriott Copley Place from 11:30 am вЂ“ 6:30 pm, with authors present from 5:30 pm вЂ“ 6:30 pm. NOTE: An asterisk designates a resident/fellow travel award winner. M1103. Interactive Visual Analysis of Diffusion-Tensor MRI Data Using the Expectation Maximization Algorithm Jian Chen, Andrew Maxwell, Haipeng Cai and Alexander P. Auchus; Hattiesburg and Jackson Dementia and Aging M1101. Epigenetics of Induced Neuronal Cells to Model Neurologic Diseases Andy J. Liu, Bradley T. Hyman, Asa Abeliovich, Benjamin S. Bleier and Mark W. Albers; Boston, MA; North Chicago, IL and New York, NY Background: Three-dimensional visualization of dense streamtube from DT-MRI tractography often produces visual clutter and poor legibility. This limits the ability to reveal valuable clinical information effectively and efficiently to the end-user. Methods: We designed an analysis toolkit which makes use of tube clustering to facilitate visual data mining from human brain DT-MRI images. An expectation maximization (EM) algorithm provides the clustering information to represent the likelihood of a line belonging to an anatomical fiber bundle. We tested the algorithm with several artificial line sets. Results: We found that the EM algorithms could provide a principal way to cluster lines with different lengths and orientations. The algorithm is also computationally efficient. We are currently comparing usage of the algorithm on normal and pathological cases for automatic detection of neuropathology. Initial applications include AlzheimerвЂ™s disease and related neurodegenerative disorders. Conclusion: Our work contributes to the design of an automatic toolkit for facilitating clinical diagnosis of brain disorders. Study supported by: National Science Foundation Grant recipient Direct conversion of human fibroblasts into induced neuronal cells (HiNs) have generated cell-based models for genetic and sporadic neurologic disease. One concern of this approach is epigenetic memory, i.e. do HiNs retain genomic features of fibroblasts that may confound mechanistic investigations, therapeutic screens, and ultimately, cell replacement therapies. To address this concern, we have developed a technique beginning with neural progenitor cells derived from nasal biopsies to induce HiNs with cortical properties. The Ascl1 gene вЂ” essential for conversion вЂ” is expressed in immature olfactory neuronal precursors. Introduction of Brn2 and Zic1, two transcription factors that enhance conversion, result in HiNs exclusively derived from neuronal precursor cells. Simultaneous induction of HiNs from fibroblasts of the same patient will provide the reference cells for epigenetic analysis. Ongoing functional characterization to validate that the HiNs fulfill criteria for neurons will be followed with an epigenetic analysis using next generation sequencing and DNA methylation mapping. These results will illuminate the differences in gene expression patterns and epigenetic changes underlying conversion from these two donor cell types. This methodology has potential for broad applicability to derive neuronal subtypes relevant to many neurologic diseases. Study supported by: NIH M1104. The Hypothalamus in AlzheimerвЂ™s Disease: A Golgi and Electron Microscope Study Stavros J. Baloyannis, Ioannis Mavroudis and Ioannis S. Baloyannis; Thessaloniki, Greece M1102. Family History of Alzheimer Disease Disrupts Functional Connectivity between the Hippocampus and Posterior Cingulate Cortex Liang Wang, Abraham Z. Snyder, Matthew Brier, Jewell Thomas and Beau M. Ances; Saint Louis, MO AlzheimerвЂ™s disease is a neurodegenerative disorder, characterized by progressive decline of mental faculties, affective and behavioural changes, loss of motor skills, eventual autonomic dysfunction and disruption of circadian rhythms. We describe the morphological findings of the hypothalamus in twelve early cases of AlzheimerвЂ™s disease, focusing our study on the suprachiasmatic, the supraoptic and the Objective: Cognitively normal individuals with family history (FH) of Alzheimer disease (AD) are at increased AD 70 ID: guganp I Black Lining: [ON] I Time: 09:25 I Path: N:/3b2/ANA#/Vol00000/120255/APPFile/JW-ANA#120255 J_ID: ZAY Customer A_ID: BKLT2012_Abstracts Cadmus Art: ANA12 Date: 18-September-12 paraventricular nuclei. Samples, excised immediately after death,were processed for electron microscopy and silver impregnation techniques. The hypothalamic nuclei demonstrated a substantial loss of neurons, particularly prominent in the suprachiasmatic nucleus, abbreviation of dendritic arborisation and spinal pathology. Supraroptic and paraventricular nuclei demonstrated a substantial number of dystrophic neurites,and synaptic pathology. Deposits of Ab peptide and neurofibrillary degeneration were not found. Proliferation of astocytes was minimal. Electron microscopy revealed mitochondrial alteration in the soma and the dendritic branches in a substantial number of neurons. The morphological alterations of the hypothalamic nuclei in Alzheimers disease may be related with the gradual disruption of the circadian rhythms, concerning sleep and appetite as well as with the instability of the autonomic regulation of the blood pressure and cardiac rhythm. Study supported by: No disclosure Stage: Page: 71 signaling proteins, and a decrease in surface binding of BDNF. Using array tomography, we analyzed sub-cellular locus of these abnormalities and found a specific increase in pTrkB colocalization with the signaling-endosome related proteins Rab5, pERK, and pAKT in synapses in Ts65Dn. Automated classification of synapse subtypes revealed increase in the number of GABAergic and a decrease glutamatergic and cholinergic synapses. Proteomic analysis at the single synapse level of resolution demonstrated that increased TrkB signaling is specific to both pre- and postsynaptic sites at GABAergic synapses. These findings demonstrate that TrkB mediated signaling is abnormal in the cortex of DS model mice, a phenomenon which may contribute to the pathogenesis underlying cognitive deficits in DS and AD. Study supported by: Grant and a postdoctoral fellowship from the Larry L. Hillblom Foundation (to RLN), The Down Syndrome Research and Treatment Foundation, The Thrasher Foundation and NIH grants NS066072, NS055371 M1105. Mixed-Risk Vascular Cognitive Impairment: Hypertension Plus Hypoperfusion Decrease Cognition and Gait and Increase Fiber Tract Pathology and Inflammation Frank C. Barone, Jin Zhou, Jie Li, Alison E. Baird, Adamski G. Mateusz, Diana L. Dow-Edwards, Peter J. Bergold, Samah G. Abdel Baki, Howard Crystal and Daniel M. Rosenbaum; Brooklyn, NY M1107. Degeneration of Brainstem Respiratory Nuclei in Dementia with Lewy Bodies Michael F. Presti, Ann M. Schmeichel, Phillip A. Low, Joseph E. Parisi and Eduardo E. Benarroch; Rochester, MN Respiratory dysfunction is characteristic of multiple system atrophy (MSA) and may reflect degeneration of brainstem respiratory nuclei, including the pre-BoВЁtzinger complex (pBC), nucleus raphe pallidus (RPa) and nucleus raphe obscurus (ROb). However, impaired ventilatory responses to hypercapnia have also been reported in dementia with Lewy bodies (DLB), suggesting that these nuclei may also be affected in DLB. We applied stereological methods to analyze sections immunostained for the neurokinin-1 receptor and tryptophan hydroxylase in neuropathologically confirmed cases of DLB, MSA, and controls. There was reduction of neuronal density in all three nuclei in DLB, as well as in MSA. The magnitude of neuronal depletion in ROb was similar in DLB and MSA (49% vs. 56% respectively compared to controls, p<0.05), but neuronal loss in the pBC and RPa was less severe in DLB than in MSA (pBC 40% in DLB, p <0.05 and 68% in MSA, p<0.0001, compared to controls; RPa 46% in DLB, p<0.05 and 73% in MSA, p<0.0001, compared to controls). Thus, medullary respiratory nuclei are affected in DLB but less severely than in MSA. This may help explain differences in the respiratory manifestations of these two disorders. Study supported by: N/A Hypertension and carotid injury on cognition were assessed in patients and applied to create a rat translational VCI model. Common carotid artery stenosis- (reduced forebrain perfusion) or sham-surgery were performed in hypertensive rats (SHR). Gait and cognitive (active; AA and passive; PA avoidance) behaviors were measured. Corpus collosum (CC) myelin (Luxol Fast Blue) and astro- (GFAP) and micro(Iba1) gliosis and circulating CD34Гѕ progenitor cells were measured. In patients, carotid lesions (p < 0.01) and hypertension (p< 0.05) predicted cognitive impairment. In SHR, stenosis decreased forebrain perfusion and impaired AA and gait (p<0.01). PA was not affected. CC myelin was reduced (48%; p<0.01) with increased astro- (69%; p<0.05) and micro- (140%; p<0.01) gliosis. Circulating CD34Гѕ progenitor cells were significantly increased (p< 0.02). Here cerebrovascular risk factors are important components necessary to model VCI. Forebrain hypoperfusion in hypertensive rat results in cognitive and gait deficits, like VCI, and are associated with CC injury and inflammation-gliosis. Increased progenitor cells suggest restorative therapy potential in VCI. This mixed-risk VCI model provides a tool to probe VCI white matter injury, mechanisms and interventions. Study supported by: SUNY Downstate Medical Center M1108. Pathological Accumulation of a-Synuclein and Ab in Dementia Associated with Parkinson Disease Meghan C. Campbell, Paul T. Kotzbauer, Nigel J. Cairns, Allison W. Willis, Brad A. Racette, Samer D. Tabbal and Joel S. Perlmutter; St. Louis, MO M1106. Excessive Trk-B Signaling in GABAeric Synapses Revealed by Array Tomography in the Ts65Dn Mouse Model of Down Syndrome Rachel L. Nosheny, Pavel V. Belichenko, Brad Busse, Kristina D. Micheva, Stephen J. Smith and William C. Mobley; La Jolla, CA and Stanford, CA Prior studies have identified cortical synucleinopathy (Lewy bodies/neurites) and changes thought to be consistent with Alzheimer disease (AD) as the two major causes of dementia in Parkinson disease (PD). To determine relative contributions of individual molecular pathologies to dementia in PD, we analyzed thirty-two autopsy cases with neuropathological confirmation of PD and a history of dementia. Three pathologic subgroups were identified: (1) predominant synucleinopathy (38%), (2) predominant synucleinopathy with b-amyloidosis but minimal or no cortical tau (59%), and (3) synucleinopathy and b-amyloidosis with at least moderate tauopathy (3%). Pathologic subgroups were similar in clinical and demographic characteristics. However, Down syndrome (DS) is characterized by learning, memory, language, and motor deficits throughout the lifespan, development of neuropathological and clinical manifestations of AlzheimerвЂ™s disease (AD) late in life, and progressive cognitive decline. Ts65Dn mice, which are trisomic for 140 genes orthologous to those on human chromosome 21, model DS. Here we show that in Ts65Dn mice have increased levels and activation of TrkB and associated downstream 71 ID: guganp I Black Lining: [ON] I Time: 09:25 I Path: N:/3b2/ANA#/Vol00000/120255/APPFile/JW-ANA#120255 J_ID: ZAY Customer A_ID: BKLT2012_Abstracts Cadmus Art: ANA12 Date: 18-September-12 participants with synucleinopathy plus b-amyloidosis had significantly shorter survival rates (PD onset until death and dementia onset until death) than participants with synucleinopathy only. We conclude that dementia in PD has two major pathologic subgroups: synucleinopathy and synucleinopathy with b-amyloidosis. Furthermore, accumulation of Ab is associated with lower survival rates in PD patients with dementia. Additional studies are needed to determine the relationship between a-synuclein and Ab accumulation, and the role of Ab in the development and progression of dementia in PD. Study supported by: National Institute on Aging of the National Institutes of Health (P50 AG05681 and P01 AG03991), and the Friedman Award to NJC; NINDS grant NS075321, NS41509, NS058714, NS48924; NIH NCRR UL1RR024992; the American Parkinson Disease Association (APDA) Advanced Research Center for Parkinson Disease at Washington University in St. Louis; the Greater St. Louis Chapter of the APDA; the Barnes Jewish Hospital Foundation (Elliot Stein Family Fund and Parkinson Disease Research Fund). Stage: Page: 72 M1110. Apples Far from the Tree: Clinical and Electrophysiologic Variability in a Family with c9FTD/ALS Elizabeth A. Coon, Jasper R. Daube, Mariely DeJesusHernandez, Anahita Adeli, Rodolfo Savica, David S. Knopman, Josephs E. Parisi, Rosa Rademakers and Bradley F. Boeve; Rochester, MN and Jacksonville, FL Objective: To describe the clinical and electrophysiologic motor neuron disease features of frontotemporal dementia (FTD) and/or amyotrophic lateral sclerosis (ALS) in a kindred with the chromosome 9 open reading frame 72 gene (C9ORF72) expanded repeat. Background: A hexanucleotide repeat expansion in C9ORF72 is a major cause of familial FTD and/or ALS (c9FTD/ALS). Initial studies describe variability in the presentation of ALS while little is known of the electrophysiologic findings. Methods: Clinical and electrophysiologic data was analyzed in a c9FTD/ALS kindred of Scandinavian ancestry. Results: Of 6 affected family members, 3 had only ALS, 3 had FTD and 1 had FTD and ALS. Each ALS patient presented differently; 1 had only bulbar symptoms, 1 had bulbar and limb involvement, 1 had limb findings, and 1 had primarily upper motor neuron disease. All ALS patients eventually had bulbar involvement and died from respiratory causes an average of 3.75 years from onset. Electrophysiologic studies demonstrated progressive lower motor neuron dysfunction except in the patient with upper motor neuron features. Interpretation: The ALS presentation within families harboring the C9ORF72 expansion may vary considerably and electrophysiologic findings reflect this heterogeneity. Study supported by: Grants AG016574, AG006786, ALS Association, and Robert H. and Clarice Smith and Abigail Van Buren Alzheimers Disease Research Program of the Mayo Foundation. M1109. Impaired Default Network Functional Connectivity in Autosomal Dominant AlzheimerвЂ™s Disease: Findings from the DIAN Study Jasmeer P. Chhatwal*, Aaron P. Schultz, Keith A. Johnson, Tammie L.S. Benzinger, Clifford R. Jack, Stephen Salloway, John M. Ringman, Robert A. Koeppe, David L. Marcus, Paul M. Thompson, Andrew J. Saykin, Sonia C. Correia, Peter R. Schofield, Christopher C. Rowe, Nick C. Fox, Adam M. Brickman, Richard Mayeux, Miroslava Rimajova, Chester A. Mathis, Eric M. McDade, William E. Klunk, Michael W. Weiner, Randall J. Bateman, Alison M. Goate, Chengjie Xiong, Virginia Buckles, Krista L. Moulder, John C. Morris and Reisa A. Sperling; Boston, MA; St. Louis, MO; Rochester, MN; Providence, RI; Los Angeles, CA; Ann Arbor, MI; New York, NY; Indianapolis, IN; Coimbra, Portugal; Randwick, Australia; Melbourne, Australia; London, United Kingdom; Perth, Australia; Pittsburgh, PA and San Francisco, CA M1111. Withdrawn. M1112. Neural Correlates of Face-Name Encoding Using Simultaneous Eye-Tracking and ERP Ali Ezzati, Meghan B. Mitchel, Steven D. Shirk, Donald G. Mclaren, Brandon A. Ally and Alireza Atri; Boston, MA; Bedford, MA and Nashville, TN Design: Decreased functional connectivity of the default mode network (DMN) has been observed in sporadic, lateonset AlzheimerвЂ™s disease (AD), but remains largely unstudied in familial AD. We examine DMN dysfunction using functional connectivity MRI (fcMRI) in 83 carriers of dominantly-inherited AD mutations (PS-1, PS-2, and APP) and 37 asymptomatic non-carriers from the same families. Results: Using independent component analysis, we observed significantly decreased DMN fcMRI in mutation carriers, with progressive decreases seen with increasing clinical impairment, and with the strongest effect seen in the Precuneus/Posterior Cingulate (PPC; p<0.001). Post-hoc comparison of asymptomatic mutation carriers to non-carriers demonstrated significantly decreased fc-MRI in the PPC, lateral parietal, and medial prefrontal cortices. Mutation carriers showed a negative correlation between DMN connectivity and increasing proximity to their familial age of symptom onset (R Вј -.42; p<0.001). Conclusions: Impaired connectivity among multiple nodes of the DMN was observed with advancing clinical decline in familial AD, similar to reports in sporadic AD. Additionally, early decreases in DMN fcMRI were observed in asymptomatic mutation carriers compared to non-carriers, suggesting decreasing DMN fc-MRI may be useful as a biomarker across a wide spectrum of the disease. Study supported by: NIA U19 AG032438 (DIAN; JCM as PI) We combined neuropsychological assessments, and simultaneous quantitative eye-tracking (ET) and event-related brain potentials ERP during encoding of novel and repeated facename pairs (FN-pairs) in 16 young healthy adults (18-39y) to delineate essential spatiotemporal processes underlying normal memory function and as a necessary first step toward development of a potential complementary noninvasive biomarker (for trait/state/rate/treatment-effect) of cognitive aging and dementia. At study 40 FN-pairs, 20 4x-repeated (4R) and 20 shown once (1R), were presented. At test, new/old judgment and high/low confidence ratings were assessed for 80 FN-pairs (40 old, 40 new [novel Вј N]). Response accuracy increased with number of presentations (4R>1R, p<0.001). Classic ERP old/new effects were seen: 1R>N hits were more positive bifrontally between 300-500ms, reflecting enhanced familiarity; 4R>N hits were more positive at superior parietal electrodes between 500-800ms, reflecting enhanced recollection; and 4R>1R hits showed positive parietal 500-800ms effects, reflecting enhanced recollection for material studied numerous times. Longer mean fixations and larger pupil sizes were observed with higher number of stimuli presentations. 72 ID: guganp I Black Lining: [ON] I Time: 09:25 I Path: N:/3b2/ANA#/Vol00000/120255/APPFile/JW-ANA#120255 J_ID: ZAY Customer A_ID: BKLT2012_Abstracts Cadmus Art: ANA12 Date: 18-September-12 These results support combining neuropsychological/clinical assessments with simultaneous ET-ERP during paired-associate encoding to probe essential brain networks that sustain cognitive processes important in health, aging and dementia. Study supported by: K23 AG027171-05 (Atri) and GRECC Stage: Page: 73 hypothesized and empirical models of pre-diagnostic declines in AD. Study supported by: Eli Lilly and Company M1115. Hippocampal Volumes Predict Response to Acetylcholinesterase Inhibitors in Patients with Dementia with Lewy Bodies Jonathan Graff-Radford*, Bradley F. Boeve, Otto Pedraza, Tanis J. Ferman, Scott Przybelsk, Timothy Lesnick, Matthew Senjem, Glenn E. Smith, David S. Knopman, Clifford R. Jack, Jr, Ronald C. Petersen and Kejal Kantarci; Rochester and Jacksonville M1113. Efficacy of a Brain/Cognitive Training Therapeutic Program for Diagnosed Dementia Barbara C. Fisher and Danielle M. Garges; Shelby Township, MI Background: Patients with dementia with Lewy bodies (DLB) may respond more favorably to acetylcholinesterase inhibitors (AChI) than patients with AlzheimerвЂ™s disease (AD). Hippocampal volumes in pathologically-confirmed DLB with low likelihood AD are preserved. Few studies have investigated imaging predictors of treatment response in DLB. Objective: To determine whether hippocampal volumes predict response to AChI in DLB patients. Methods: We performed a retrospective analysis on consecutive treatment-naive DLB patients (n Вј 54) from the Mayo Clinic ADRC who subsequently received AChI and underwent MRI with hippocampal volumetry. Assessments with the Mattis Dementia Rating Scale (DRS) were performed at baseline and follow-up. Patients were divided into three groups (reliable improvement, stability, reliable decline) using DRS reliable change indices determined previously. Associations between hippocampal volumes and treatment response were tested with ANCOVA adjusting for age, gender, DRS baseline and interval. Results: Using a conservative psychometric method of assessing treatment response, there were 12 patients with reliable decline, 29 stable patients and 13 with reliable improvement. The improvers had larger hippocampi than those that declined (p Вј 0.02) and the stable group (p Вј 0.04). Conclusion: DLB patients with preserved hippocampal volumes are more likely to improve on AChEI. Study supported by: This work was supported by the National Institutes of Health: P50-AG16574/P1 and R01AG040042 to K.K., P50-AG16574/P1 VJL, R01AG11378 to CRJ, R01-AG015866 to TJF., P50-AG16574 to RCP.; Mangurian Foundation and the Robert H. and Clarice Smith and Abigail Van Buren Alzheimer s Disease Research Program. Introduction: Examine the efficacy of an individually designed therapeutic program for the remediation of memory deficits resulting from dementia, diagnosis determined through treating neurologist/cardiologist and neuropsychological testing. Evaluation completed prior to and following therapeutic intervention in a clinic population. Method: Adults referred for assessment of memory difficulties (age 64 to 80 years, n Вј 10). The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) was utilized to measure memory functioning pre and post treatment. On average a total of 2 to 4 months elapsed between pre and post testing. Results: Immediate memory, visuospatial/visuoconstructive, language, attention, delayed memory, total dementia score improved following treatment when mean differences were assessed. Between 7.87 and 12 point differences were found for immediate memory, language, delayed memory and total dementia score. Paired samples t-tests revealed significant differences between pre and post treatment scores for overall memory (p < 0.052). Conclusions: Findings indicate that all areas assessed evidenced improvement following as short a duration of time as 2 months of treatment. The individualized therapeutic program appears to be effective in augmenting overall functioning in diagnosed dementia population. Study supported by: nothing to disclose M1114. Cognitive, Functional, and Neuropsychiatric Trajectories before and after an AlzheimerвЂ™s Disease Diagnosis Joseph E. Gaugler, David L. Roth, Robert Kane, Martha Hovater, Joseph Johnston and Khaled Sarsour; Minneapolis, MN; Baltimore and Indianapolis M1116. Sustained Cognitive Improvement with Extended-Release Memantine (28 mg, Once Daily) in Moderate to Severe AlzheimerвЂ™s Disease Michael Tocco, Suzanne Hendrix, Michael L. Miller, Vojislav Pejovic and Stephen M. Graham; Jersey City, NJ; Salt Lake City, UT and Chicago, IL The purpose of this study was to examine trajectories of stability or decline in individualsвЂ™ cognitive function, functional dependence, and neuropsychiatric dimensions in the years prior to and following an AlzheimerвЂ™s disease (AD) diagnosis. 15,443 visits from the National AlzheimerвЂ™s Coordinating Center-Uniform Data Set (N Вј 3,812 individuals) were utilized that included individuals who did (n Вј 444) or did not (n Вј 3,368) receive an AD diagnosis. Multi-level linear change models were used to estimate longitudinal trajectories of change before and after AD diagnosis. When compared to individuals who did not receive an AD diagnosis, persons with AD experienced significant declines across a range of clinical dimensions that serve as markers for AD progression, including cognitive decline (e.g., MMSE: B Вј -.17 and Logical Memory test B Вј .18 (p < .001)) and functional status (e.g., FAQ: B Вј .22; (p < .001). One exception was neuropsychiatric disturbances, where no significant difference was found prior to AD diagnosis when compared to usual controls in the same time period. The results of this trajectory analysis lend additional support to In this post hoc analysis, sustained cognitive improvement was assessed in a 24-week, randomized, placebo-controlled trial of once-daily, extended-release (ER) memantine (28 mg) in ChEI-treated patients with moderate to severe AD. Five positive SIB response levels to double-blind treatment were selected (improvements of !0, !5, !10, !15, and !20 points), corresponding to 0-2 standard deviations (SDs) of the observed baseline-to-endpoint score change. Numbers of patients in each group who attained such responses at weeks 4, 8, 12, or 18 and maintained them through week 24 were compared using FisherвЂ™s exact test. Significantly more memantine ER-treated than placebo-treated patients maintained week 8 SIB responses of !5 points (26.1% vs 17.0%; P Вј 0.014) and !10 points (14.6% vs 7.6%; P Вј 0.012) through 73 ID: guganp I Black Lining: [ON] I Time: 09:25 I Path: N:/3b2/ANA#/Vol00000/120255/APPFile/JW-ANA#120255 J_ID: ZAY Customer A_ID: BKLT2012_Abstracts Cadmus Art: ANA12 Date: 18-September-12 week 24. Similar results were observed for sustained responses attained at week 12 (!5 points: 28.5% vs 19.9%, P Вј 0.025; !10 points: 16.3% vs 8.2%, P Вј 0.005; !15 points: 9.5% vs 4.1%, P Вј 0.015) and week 18 (!10 points: 18.8% vs 10.0%, P Вј 0.004; !15 points: 10.9% vs 4.5%, P Вј 0.006). In conclusion, memantine ER was associated with cognitive improvement attained after 8-18 weeks and sustained through week 24. Study supported by: Forest Laboratories, Inc. Drs. Stephen Graham and Michael Tocco are employed by Forest Research Institute. Drs. Michael L. Miller and Vojislav Pejović are employed by Prescott Medical Communications Group, an independent contractor to several pharmaceutical companies, including Forest Laboratories, Inc. Dr. Suzanne Hendrix is employed by Pentara Corporation, an independent contractor to several pharmaceutical companies, including Forest Laboratories, Inc. Stage: Page: 74 FTLD caused by GRN mutations. However, the relationship between PGRN-deficiency, TDP-43 mislocalization, and neuronal death remains unclear. Though brains from PGRNdeficient mice display some pathologic features of FTLD, they do not exhibit a robust neurodegenerative phenotype or TDP-43 redistribution. Because the retina is easily accessible for clinical imaging of the CNS and since retinal degeneration has been identified in other neurodegenerative disorders, we sought to determine if retinal abnormalities occur in FTLD. We report that retinal imaging of living FTLD patients via optical coherence tomography reveals significant retinal nerve fiber layer (RNFL) thinning compared to agematched controls. Substantial death of of retinal ganglion cells (RGCs), microgliosis, and lipofuscinosis also occur in Grn KO mouse retinas. Notably, we observe key pathologic features of TDP-43 mislocalization in Grn KO RGCs, including intranuclear inclusions, nuclear clearing, and cytoplasmic redistribution of TDP-43, all of which precede significant RGC death. This newly described and clinically-relevant FTLD phenotype in humans and mice may prove useful in exploring the intricate relationship between PGRN deficiency, TDP-43 mislocalization, and neurodegeneration. Study supported by: UCSF Research Allocation Program Chartrand Foundation The Bluefield Project to Cure Frontotemporal Dementia M1117. Response across Multiple Outcome Measures in Patients with Moderate to Severe AlzheimerвЂ™s Disease Taking Extended-Release Memantine (28 mg, Once Daily) Stephen M. Graham, Suzanne Hendrix, Michael L. Miller, Vojislav Pejovic and Michael Tocco; Jersey City, NJ; Salt Lake City, UT and Chicago, IL This post hoc analysis explored the effects of extended-release (ER) memantine on combinations of outcome measures from a 24-week, randomized, placebo-controlled trial of memantine ER (28 mg, once daily) in ChEI-treated patients with moderate to severe AD. Outcomes included the SIB, ADCS-ADL19, NPI, and CIBIC-Plus. For each measure, two response levels were defined: improvement/stabilization (вЂ�вЂ�no declineвЂ™вЂ™) and clinically notable response (baseline-to-endpoint improvement of !3 points for the SIB, ADCS-ADL19, and NPI; endpoint score 3 for the CIBIC-Plus). Treatment groups were compared (WaldвЂ™s test) by calculating the proportions of patients who achieved a response on various combinations of efficacy measures. For both response levels and all outcome combinations, proportions of responders in the memantine ER group (n Вј 266-269) exceeded those in the placebo group (n Вј 271-272). For clinically notable responses, memantine ER was significantly superior to placebo for the 2-measure combination of ADCS-ADL19/NPI (21.3% vs 15.8%; P Вј 0.042, NNT Вј 18) and the 3-measure combinations of ADCS-ADL19/NPI/SIB (15.4% vs 9.6%; P Вј 0.027, NNT Вј 17) and ADCS-ADL19/SIB/CIBIC-Plus (12.4% vs 7.4%; P Вј 0.030, NNT Вј 20). In conclusion, this analysis suggests that memantine ER may provide simultaneous benefits on multiple clinical domains. Study supported by: Forest Laboratories, Inc. Drs. Stephen Graham and Michael Tocco are employed by Forest Research Institute. Drs. Michael L. Miller and Vojislav Pejović are employed by Prescott Medical Communications Group, an independent contractor to several pharmaceutical companies, including Forest Laboratories, Inc. Dr. Suzanne Hendrix is employed by Pentara Corporation, an independent contractor to several pharmaceutical companies, including Forest Laboratories, Inc. M1119. Cerebral Amyloid Angiopathy Independently Contributes to Ischemic White Matter Disease: A PET/ MRI Correlative Study Edip M. Gurol, Christopher Gidicsin, Andrew Dumas, Trey Hedden, Alison Ayres, Alex Becker, Anastasia Vashkevich, Sergi R. Martinez, Eitan Auriel, Kristen Schwab, Anand Viswanathan, Jonathan Rosand, Keith A. Johnson and Steven M. Greenberg; Boston, MA Objective: We hypothesized that vascular amyloid contributes to chronic brain ischemia, therefore amyloid burden measured by Pittsburgh Compound B retention on PET (PiB-PET) would correlate with the extent of white matter disease (WMD) in patients with Cerebral Amyloid Angiopathy (CAA) but not in healthy elderly (HE) or AlzheimerвЂ™s Disease (AD). Methods: Thirty-five non-demented CAA patients, 50 HE subjects and 20 AD patients had brain MRI and PiBPET analyzed. Multivariate linear regression was used to assess the association between PiB retention and WMD volume while controlling for age, gender and vascular risk factors within each group. Results: CAA patients were younger than HE and AD (67610 vs 7367 and 7569, p<0.01) but CAA cases had higher amounts of WMD (medians:19ml vs 3.2ml and 6.5ml respectively, p<0.05 for both comparisons). Global PiB retention and WMD showed a strong correlation (rho Вј 0.52, p<0.001) in the CAA cohort but not in HE or AD. These associations did not substantially change in the multivariate model. Conclusions: Our findings support the view that vascular amyloid burden directly contributes to chronic cerebral ischemia in the CAA population and highlights the possible utility of amyloid imaging as a marker of CAA severity. Study supported by: Supported by NIH (T32NS048005, 5R01NS070834-01/02, R01AG026484). M1118. Retinal Degeneration in FTLD Patients and PGRN-Deficient Mice Preceded by TDP-43 Mislocalization Michael E. Ward*, Alice Taubes, Bruce L. Miller, Jeffrey M. Gelfand, Li Gan and Ari J. Green; San Francisco, CA M1120. Gephyrin Plaques Identified in Frontal Cortex of AlzheimerвЂ™s Disease Brains Chadwick M. Hales, Howard Rees, James J. Lah, Allan I. Levey and Thomas Wingo; Atlanta, GA Neurodegeneration and cytoplasmic mislocalization of TDP43 are pathologic hallmarks of sporadic FTLD-U and familial A hallmark of many neurodegenerative disorders is the abnormal accumulation of protein evident at 74 ID: guganp I Black Lining: [ON] I Time: 09:25 I Path: N:/3b2/ANA#/Vol00000/120255/APPFile/JW-ANA#120255 J_ID: ZAY Customer A_ID: BKLT2012_Abstracts Cadmus Art: ANA12 Date: 18-September-12 neuropathologic examination. In addition to well known findings of neurofibrillary tangles and b-amyloid plaques in AlzheimerвЂ™s disease (AD), here we show that abnormal accumulations of gephyrin immunoreactivity are highly correlated with the neuropathologic diagnosis of AD (odds ratio of 72.7; p Вј 6.844x10-6, n Вј 17 AD and n Вј 14 controls). Gephyrin is an inhibitory receptor anchoring protein also important for molybdenum cofactor biosynthesis and synaptic protein translation. Furthermore, the gephyrin accumulations are specific for AD and not observed in ParkinsonвЂ™s disease (n Вј 5), corticobasal degeneration (n Вј 3), frontotemporal lobar degeneration (n Вј 5) and progressive supranuclear palsy (n Вј 3). Gephyrin accumulations overlap with b-amyloid plaques but do not completely co-localize. Neurofibrillary tangles occasionally contain gephyrin immunoreactivity. The normal gephyrin staining of neuronal processes is significantly reduced in AD cases as compared to controls. Biochemical studies suggest alterations in the gephyrin isoform expression profile. Given the involvement of gephyrin in synaptic organization and that synaptic dysfunction is an early event in AD, these findings suggest a possible role for gephyrin in AD pathogenesis. Study supported by: American Academy of Neurology Foundation Clinical Research Training Fellowship no conflict of interest Stage: Page: 75 HD060406, JB is supported by a grant of the Deutsche Forschungsgemeinschaft DFG (AOBJ586910) and JBT is supported by a grant of the Alfonso MartД±Вґn Escudero Foundation. David J Irwin reports no disclosures. Corey T McMillan reports no disclosures. Johannes Brettschneider reports no disclosures. David J Libon reports no disclosures. Ashley Boller reports no disclosures. John Powers reports no disclosures. Keerthi Chandrasekaran reports no disclosures. Elizabeth McCarty Wood reports no disclosures. Jon B. Toledo reports no disclosures. Leslie Shaw reports no disclosures. Katya Rascovsky reports no disclosures. John Woo reports no disclosures. Dr. David Wolk has received research support from NIH (R01 AG037376, R01 MH086492, K23 AG028018, P30 AG010124), GE Healthcare, and Pfizer, Inc. He has served as a consultant for GE Healthcare and Leclair Ryan. He received speaking honoraria from the American Academy of Neurology. Steven E. Arnold reports board membership for Cowan Group, Eli Lilly and BMS; Consulting services for Philadelphia district attorneyвЂ™s office and Bonner Kiernan Trebach & Cociata LLP; Grants from American College of Radiology Imaging Network, Pfizer, AlzheimerвЂ™s Disease Neuroimaging Initiative, Johnson & Johnson, National Institute of Drug Abuse, Neuronetrix, National Institute of Mental Health, Eli Lilly; Payments for lectures at Harvard University, Rush University Medical Center, Trinitas Regional Medical Center, and University of Puerto Rico. Vivianna Van Deerlin reports no disclosures. Leo F. McCluskey reports no disclosures. Lauren Elman reports no disclosures. Virginia M.-Y. Lee reports singleconsulting services to Pfizer, J&J, MetLife, and BMS; Royalty payments through Penn licenses; Research support from AstraZeneca and BMS. John Q. Trojanowski reports singleconsulting services to Pfizer, J&J, MetLife, and BMS; Royalty payments through Penn licenses; Research support from AstraZeneca and BMS. Murray Grossman reports no disclosures. M1121. Clinical, Imaging and Pathologic Features of C9ORF72 Hexanucleotide Expansion in ALS and FTLD David J. Irwin, Corey T. McMillan, Johannes Brettschneider, David J. Libon, Ashley Boller, John Powers, Keerthi Chandrasekaran, Elisabeth McCarty Wood, Jon B. Toledo, Leslie Shaw, Katya Rascovsky, John H. Woo, David A. Wolk, Steven E. Arnold, Vivianna Van Deerlin, Leo F. McCluskey, Lauren Elman, Virginia M.Y. Lee, John Q. Trojanowski and Murray Grossman; Philadelphia, PA We hypothesized that C9ORF72 expansion-positive (C9P) cases will have unique clinical characteristics compared with expansion-negative (C9N) TDP-43 proteinopathies. Available clinical data including neuropsychological testing, MRI voxel-based morphometry (VBM) and neuropathological assessment were obtained in a cohort of 54 C9P cases (ALS Вј 29,FTLD Вј 17, ALS-FTD Вј 8) and compared to 78 C9N cases with presumed TDP-43 neuropathology (ALS n Вј 37,FTLD n Вј 30,ALS-FTLD n Вј 11). C9P cases overall had an earlier age of onset (p Вј 0.040), and death (p Вј 0.007) than C9N. C9P FTLD showed greater cognitive decline than C9N FTLD in MMSE (12.2Гѕ4.5 vs. 2.6Гѕ1.0;p Вј 0.003) and letter fluency (4.8Гѕ0.3 vs. 0.5Гѕ0.6;p Вј 0.004) tests. VBM revealed greater atrophy in right frontal and inferior-parietal cortex for C9P relative to C9N, and a regression related verbal fluency scores to atrophy in these regions. Neuropathological analysis revealed a higher burden of frontal (p Вј 0.007) and inferior-parietal cortex (p Вј 0.034) gliosis in C9P relative to C9N, and severity also correlated with verbal fluency performance (p<0.0001). C9P cases appear to have a significantly greater rate of cognitive decline, gray matter disease, and neuropathologic burden in frontal and parietal regions. C9ORF72 genotyping may provide useful prognostic and diagnostic clinical information for ALS and FTLD patients. Study supported by: This study was supported by the NIH P30AG010124-20, P01 AG017586, R01 NS44266, R01 AG15116, P01 AG32953, P01 NS53488, R21 NS06311-01A1 and the Wyncote Foundation. DJI is supported by the NIH T32-AG000255, CTM is support by M1122. Inflammatory Cerebral Amyloid Angiopathy: An Unrecognized Cause of Reversible Dementia Nivedita Jerath, Aarti Jerath, Keri Oxley, Matt Bevers, Shelley Waite and Steve Greenberg; Boston, MA An 87 year old woman with a right cavernous sinus meningioma and atrial fibrillation on warfarin developed episodes of disorientation, falls, memory loss, and urinary and fecal incontinence. The symptoms progressed over two months to aggressiveness, an inability to follow commands, and a refusal of medications. On exam, her eyes were clenched and she repeated a Hail Mary prayer. An EEG showed no epileptiform activity. An MRI showed non contrast enhancing lesions consistent with inflammatory cerebral amyloid angiopathy: exclusive lobar-based hemorrhages, and confluent subcortical FLAIR white matter hyperintensities with no evidence of vasculitis, tumor, vascular malformation, or coagulopathy. Although neoplastic etiologies were considered, the progression was too rapid and no hemosiderin deposition was seen in the basal ganglia. An empiric course of 5 days of 1 gram of IV methylprednisolone was started for inflammatory cerebral amyloid angiopathy. The day after 75 ID: guganp I Black Lining: [ON] I Time: 09:25 I Path: N:/3b2/ANA#/Vol00000/120255/APPFile/JW-ANA#120255 J_ID: ZAY Customer A_ID: BKLT2012_Abstracts Cadmus Art: ANA12 Date: 18-September-12 Stage: Page: 76 starting steroids, she opened her eyes, and briskly followed commands. She was discharged on a tapering regimen of high dose oral prednisone as well as aspirin instead of warfarin. She is now back to baseline. Inflammatory cerebral amyloid angiopathy should be recognized as a cause of reversible dementia. Study supported by: none Conclusions: These results demonstrate, for the first time, that PFA is associated with a phenomenon of enhanced temporoparietal neurodegeneration, a finding that improves our understanding of the biological basis of AlzheimerвЂ™s disease presenting as PFA. Study supported by: NIH grants R21 AG038736; R01 AG037491 and P50 AG16574 M1123. Inclusion of Axial Rigidity May Improve Diagnostic Accuracy for Dementia with Lewy Bodies Fariha Zaheer, John T. Slevin, Erin L. Abner, Peter T. Nelson and Gregory A. Jicha; Lexington, KY M1125. Hippocampal CA1 Apical Neuropil Atrophy and Memory Performance in Alzheimer Disease Geoffrey A. Kerchner, Gayle K. Deutsch, Michael Zeineh, Robert F. Dougherty and Brian K. Rutt; Stanford, CA Objective: The diagnostic accuracy of dementia with Lewy bodies (DLB) is poor. This study examined demographic and clinical features that may improve diagnostic accuracy for the prediction of underlying Lewy body pathology (LBP). Methods: Eighty cases with pathological and/or clinical diagnoses of DLB were identified in the University of Kentucky Brain Bank (n Вј 523), including 13 cases positive for DLB clinically and pathologically, 14 cases with DLB but no LBP, and 52 cases negative for clinical DLB but positive for LBP. Demographic and clinical metrics were analyzed between groups to identify variables that might improve diagnostic accuracy in DLB. Results: Only axial (p Вј 0.017; t-test) and lower extremity rigidity (p Вј 0.034; t-test) differed between true positive and false positive cases. Interpretation: Including assessment of axial or lower limb rigidity as a component of diagnostic criteria for DLB would improve the positive predictive value from 48% currently to 82% without a significant tradeoff in negative predictive value (10.5% currently to 11%). The diagnostic criteria for DLB need to be revised to detect underlying pathology based on this and further findings from similar studies in large pathologic series. Study supported by: NIA 1 P30 AG028383 In preclinical Alzheimer disease (AD), episodic memory deficits emerge as neurofibrillary tangle pathology spreads from the entorhinal cortex to the hippocampal CA1 apical neuropil. The CA1 apical neuropil is visible in vivo using ultra-high field 7-Tesla MRI, and its thickness sensitively discriminates patients with mild AD from normal controls (Kerchner et al., 2010, Neurology 75:1381-1387). We tested whether CA1 apical neuropil thickness scales with the severity of memory deficits amongst patients with mild AD. Each subject underwent a comprehensive neuropsychological assessment that included tests of episodic memory, and a 7-Tesla MRI that yielded cross-sectional images of the hippocampus at an in-plane resolution of 0.22 mm. Delayed recall performance correlated tightly with CA1 apical neuropil thickness, especially in the left hemisphere. Slightly weaker associations were apparent for the entorhinal cortex and the CA1 cell body layer, but not the dentate gyrus or CA3 subfields. These correlations were specific to delayed episodic memory: Hippocampal microstructure correlated neither with working memory nor with psychometric tests of other cognitive domains. Thus hippocampal microstructure, visualized by 7T MRI, sensitively tracks one of the core features of AD, possibly representing a novel biomarker. Study supported by: AlzheimerвЂ™s Association Stanford Institute for Neuro-Innovation and Translational Neuroscience NIH M1124. Quantitative Neurofibrillary Tangle Density and Brain Volumetric MRI Analyses in AlzheimerвЂ™s Disease Presenting as Progressive Fluent Aphasia Keith A. Josephs, Dennis W. Dickson, Melissa E. Murray, Matthew L. Senjem, Joseph E. Parisi, Ronald C. Petersen, Clifford R. Jack and Jennifer L. Whitwell; Rochester, MN and Jacksonville, FL M1126. Dimensions of Dementia: Item Response Analysis of the AlzheimerвЂ™s Disease Assessment Scale (ADAS-Cog) Christian Yavorsky, Anzalee Khan, Mark Opler, Guillermo DiClemente and Sofija Jovic; New York, NY; Hamilton, NJ and Orangeburg, NY Background: Neurofibrillary tangles are one of the key histological lesions that define AlzheimerвЂ™s disease, and are associated with brain atrophy. Methods: We quantified regional neurofibrillary tangle density in hippocampus and three neocortical regions in 30 subjects with AlzheimerвЂ™s disease, 10 of which presented with progressive fluent aphasia (PFA) and 20 that presented as dementia of the AlzheimerвЂ™s type (DAT) with loss of episodic memory. Regional grey matter volumes of the hippocampus and the same three neocortical regions were measured on subjectвЂ™s antemortem volumetric MRIs. Results: Neurofibrillary tangle density was significantly higher in the temporoparietal cortices in PFA compared to DAT, with no differences observed in hippocampus. The ratio of temporoparietal-to-hippocampal neurofibrillary tangle density was higher in PFA than in DAT. The imaging findings mirrored the pathological findings, with smaller left temporoparietal volumes observed in PFA compared to DAT, in the absence of any differences in hippocampal volume. Objective: The aim was to investigate the dimensions of cognitive impairment, and highlight response patterns and scale properties of the ADAS-Cog to improve the measure for screening and evaluating dementia. Methods: 2618 subjects from 7 randomized, doubleblind, placebo-controlled, trials used Item Response Theory (IRT). An item analysis by mixed Rasch models explored cognitive dimensions of the ADAS-Cog, and assessed item bias. Results: Results showed that recall, recognition, expressive language/naming, and praxis/construction items demonstrated a good relationship between responses and dementia severity. Orientation was the most sensitive item to differentiate across levels of cognitive impairment. Language comprehension was problematic with regard to its ability to discriminate over the full range of dementia severity. Mixed Rasch resulted in two dimensions of cognitive function, agecorrelated (expressive language/naming, praxis/construction) 76 ID: guganp I Black Lining: [ON] I Time: 09:25 I Path: N:/3b2/ANA#/Vol00000/120255/APPFile/JW-ANA#120255 J_ID: ZAY Customer A_ID: BKLT2012_Abstracts Cadmus Art: ANA12 Date: 18-September-12 and non age-correlated (orientation, recall, language comprehension, recognition). Conclusions: Some items are better at discriminating across all severity levels of dementia than others, indicating that an abbreviated version of the ADAS-Cog may correctly discriminate dementia across various stages. Study supported by: Investigator Initiated Study: ProPhase LLC, New York, NY; CROnos CCS, Hamilton, NJ Stage: Page: 77 these five patients confirmed their increasing spontaneous speech amounts. In conclusion, rivastigumine seems to have a trend of efficiency on PPA symptoms. We need more cases as well as a placebo-controlled, double-blind randomized trial to prove the efficiency of rivastigmine on PPA. Study supported by: Nothing M1129. Rest/Activity Fragmentation and the Risk of AD in Older Adults Andrew S. Lim, Matthew Kowgier, Lei Yu, Aron S. Buchman and David A. Bennett; Toronto, ON, Canada and Chicago, IL M1127. Quantifying Differences in the Shape Complexity of the Cerebral Cortex across the Adult Lifespan Richard D. King, Sourav Kole and Nikhil Singh; Salt Lake City, UT Background: Sleep disturbance and neurodegeneration may be linked. We recently demonstrated an association between objective measures of rest/activity fragmentation and crosssectional cognitive performance in older adults. However, it is unclear whether rest and activity fragmentation predispose to subsequent cognitive impairment or vice-versa. Methods: Up to 10 days of actigraphy were obtained from 734 older individuals without dementia in the Rush Memory and Aging Project, a prospective observational cohort study. Rest and activity fragmentation were quantified using recently developed state transition metrics. Subjects underwent structured annual evaluation with a battery of 19 neuropsychological tests. Results: Over a mean follow-up of 3.3 years, 96 individuals developed AD. In Cox proportional hazards models, both rest and activity fragmentation were associated with an increased risk of AD (HR Вј 1.21 95%CI 1.03-1.44 and HR Вј 1.26 95%CI 1.10-1.44 for 1 SD increases in rest and activity fragmentation respectively). In linear mixed effect analyses, both rest and activity fragmentation were associated with faster cognitive decline (p Вј 0.037 and p Вј 0.003 for rest and activity fragmentation respectively). Interpretation: Rest and activity fragmentation are associated with a higher risk of incident AD and more rapid cognitive decline in old age. Study supported by: CIHR Bisby Fellowship AAN Foundation Clinical Research Training Fellowship NIH R01AG17917 R01AG24480 P30AG010161 Objective: To develop novel neuroimaging biomarkers of cortical shape to aid in the clinical diagnosis of age-related diseases by 1) calculating the complexity of the cerebral cortical ribbon using fractal dimension and 2) computing the degree of similarity between images by calculating the deformation energy required to morph images together. Design/Methods: Magnetic resonance images (MPRAGE) came from a database of cognitively normal adults in the Dallas Lifespan Brain study (N Вј 322; Ages Вј 2090). 3D cortical surface models were generated using FreeSurfer. Fractal dimension (FD) was computed using a custom software program, the Cortical Complexity Calculator. Large Deformation Diffeomorphic Metric Mapping (LDDMM) was used to calculate the energy required to morph images together. Atlases were created based upon age or FD. Results: There is a significant negative correlation between aging and cortical fractal dimension (r Вј -0.797, p< 0.001). Variability in cortical structure is highest in brains of higher age or lower FD. Atlases based upon FD capture more of the variance in cortical shape than atlases based upon age (R2 Вј 0.6245 and R2 Вј 0.3274 respectively). Conclusions: Cortical FD is a novel imaging biomarker that improves upon вЂ�вЂ�age-relatedвЂ™вЂ™ characterization of brain shape changes. Study supported by: This project was supported by the Center for AlzheimerвЂ™s Care, Imaging and Research (CACIR) and the National Institute of Aging (K23AG03835) M1130. Does Sporadic Atonia Occur in Alzheimer Disease? Leopold Liss; Columbus, OH Patients with Alzheimer disease do sometimes fall while standing and are considered the result of a sporadic atonic episode. Material and Methods: Patient population of over 2,000 which were followed in the Cognitive Disorders Clinic (1978-2010) and in the Columbus Alzheimer Care Center (1991- 2012). All incidences were witnessed. A few were observed by reliable family caregivers and the interrogation used questions which were suggestive of other etiologies rather than atonia. The description of the atonic event has been described as a meltdown. These falls are soft fall, without injury, with the patient frequently surprised and without any deficits. The possibility of transient ischemic attack, orthostatic hypotension, or an ictal episode were all ruled out before the fall was assigned to a sporadic atonia. The only characteristic feature which was observed in some of the falls was a rapidly disappearing muscular weakness, but there was no problem in returning to the upright position. Study supported by: Supported in part by OSU Development Fund # 30-62-46 Alzheimer Initiative Research M1128. Treatment of Primary Progressive Aphasia with Rivastigmine Hisatomo Kowa, Tsuneyoshi Seki, Mikiko Yamamoto, Fumio Kanda and Tatsushi Toda; Kobe, Japan Primary Progressive Aphasia (PPA) is one of the clinical types of frontotemporal dementia characterized by an isolated language dysfunction with asymmetric atrophy of perisylvian association cortices. There have been no established treatments for PPA. In this study, we tried rivastigumine for PPA and saw its efficiency on aphasia. One patient diagnosed with semantic dementia and five patients diagnosed with non-fluent progressive aphasia were treated with rivastigmine patch (starting from 4.5 mg/day and finally dosing up to 18 mg/day). The patients were evaluated by WAB, Boston naming test and other batteries. One patient had a skin rash as a reaction of patch and needed corticosteroid ointment therapy. The others had no side effects or no gastrointestinal symptoms. Five of the six patients exhibited some improvements of language function, especially in naming and repeating. The family members of 77 ID: guganp I Black Lining: [ON] I Time: 09:25 I Path: N:/3b2/ANA#/Vol00000/120255/APPFile/JW-ANA#120255 J_ID: ZAY Customer A_ID: BKLT2012_Abstracts Cadmus Art: ANA12 Date: 18-September-12 M1131. Diminished Thalamocortical Feedforward Inhibition in an Aging Mouse Model of Chronic Tinnitus: Implications for Deafferentation Syndromes and Aging Daniel A. Llano, Jeremy Turner and Don Caspary; Urbana, IL; Jacksonville, IL and Springfield, IL Stage: Page: 78 sophisticated biomarkers are more efficient than simple screening or neuropsychological tests focused on memory. The goal of this work was to evaluate the predictive value of the Memory Impairment Screen (MIS), a simple and brief memory test in elderly subjects with subjective memory loss. Methods: We recruited a prospective cohort of 105 patients with subjective memory loss and normal global cognitive function. They scored 0.5 in the CDR. The final point was the conversion to dementia, mainly of Alzheimer type. Results: After a mean follow-up of 3 years (range: 2-4 years) 57 patients developed AD, and 48 did not. A baseline score of 0 or 1 in the MIS test predicted conversion to AD at 42.9 % sensitivity and 98% specificity with a positive predictive value of 96%. The area under the curve was 0.76 (95% CI: 0.66-0.86). Conclusions: In the clinical setting the MIS test in patients referred by memory complaints is useful to predict the development of AD but it should be combined with a higher sensitivity test. Study supported by: NONE Mechanisms underlying the generation of spontaneous percepts (e.g. pain, tinnitus, visual hallucinations) in deafferentation syndromes are not known. Here, we use an aging mouse model of tinnitus after peripheral defferentation to explore potential thalamocortical mechanisms of these disorders. Flavoprotein autofluorescence imaging was used to examine auditory thalamocortical synaptic responses in aged animals with evidence of tinnitus. Mice were exposed to noise trauma at 2 months of age and were assessed at 26 months. Noiseexposed animals showed a marked increase in amplitude of thalamocortical activation compared to controls and they showed a diminished sensitivity to GABAergic blockade. The strength of thalamocortical activation was significantly correlated to the degree of tinnitus behavior. Finally, there was no relationship between auditory cortical activation and activation of the somatosensory cortex in the same slices, suggesting that the increases in activation were not due to a generalized hyperexcitable state in noise-exposed animals. These data suggest that peripheral deafferentation is associated with a maladaptive downregulation of cortical GABAergic synaptic transmission. Potential general implications regarding aging and deafferentation syndromes are discussed. Study supported by: NIDCD M1134. Decreased Life Expectancy When Seizures Develop in AlzheimerвЂ™s Lauren R. Moo and Steven D. Shirk; Bedford, MA and Boston, MA While those with AlzheimerвЂ™s Dementia (AD) are at increased risk for seizures, the underlying relationship between seizures and AD is not well characterized. We retrospectively examined the clinical history of Veterans who were resident on the Bedford VA Severe Dementia Care Unit (SDCU) with pathologically confirmed AD to determine the effect of seizures on mortality in AD. Preliminary analyses limited to those males with confirmed AD, no evidence of stroke, and no history of epilepsy prior to dementia onset, suggest that those with post-AD onset seizures (ADГѕS) have a significantly shorter life expectancy (p<0.01). This reduction appears to be driven by earlier age of dementia onset (p<0.01) in the ADГѕS group as the ADГѕS and AD-S groups had comparable times from SDCU admission to death (p>0.2). Thus, while the development of seizures in the setting of AD is correlated with a shorter life expectancy, it is not clear that the seizures themselves lead to a younger demise. Instead, those who develop seizures late in AD appear to be a distinct cohort within the AD population. Further investigation regarding whether those with AD who develop seizures represent a pathophysiological sub-phenotype is warranted. Study supported by: GRECC/VA employment M1132. Does Education Slow Functional Decline in AlzheimerвЂ™s Disease? Revisiting the Reserve Hypothesis Meghan B. Mitchell, Steven D. Shirk and Alireza Atri; Boston, MA and Bedford, MA Objective: To investigate the role of education, a proxy for cognitive reserve, on the long-term course of daily function in AlzheimerвЂ™s disease (AD). Method: 1026 participants with probable AD enrolled in the MADRC Patient Registry underwent serial evaluations and dementia treatment as part of routine Memory Disorders Unit clinical care. Mixed effects modeling examined effects of education on trajectory of functional decline as measured by the Weintraub activities of daily living (ADL) scale; models adjusted for baseline levels of cognitive performance and ADL function and their interactions with time. Results: Higher education was associated with slower rate of decline in individuals with mild functional impairment, but as baseline functional impairment increased, the association of education and functional decline weakened. Discussion: There remains considerable debate regarding the effect of education on rate of decline in aging an AD; some studies suggest that education is associated with concurrent level of cognitive function but does not affect rate of decline. These results support the potential protective effects of education to facilitate a вЂ�вЂ�functional reserveвЂ™вЂ™ that is above and beyond cognitive ability and may be particularly effective in earlier stages of AD. Study supported by: NIA grant AG027171 (Alireza Atri, PI) and the Department of Veterans Affairs M1135. Comparison of the Impact of AlzheimerвЂ™s Disease on Medicare and Medicaid Lisa Mucha, Amanda Forys, Huai-Che Shih, Joel Bobula, Trent McLaughlin, Kara Suter, Machaeon Bonafede and Robert Fowler; Collegeville, PA; Arlington, VA; Abbott Park, IL and Cambridge, MA Objective: The objective of the study was to characterize the economic impact of AlzheimerвЂ™s disease (AD) to Medicare and Medicaid. Methods: Studies were undertaken using claims from Medicare 5% sample, and a multistate Medicaid file 20018. AD patients age 50 or older were retrospectively identified via the first instance of ICD-9 code 331.0 using the Medicare 5% Sample and the MarketScan Medicaid MultiState Database (2001-2008). Total direct costs by type of M1133. Predictive Value of the Memory-ImpairmentScreen Test in Subjects with Subjective Memory Loss Pedro J. Modrego, JoseВґ Gazulla and Pedro J. Modrego; Zaragoza, Spain Objective: The use of biomarkers in early AlzheimerвЂ™s disease detection is growing. However it is not clear whether 78 ID: guganp I Black Lining: [ON] I Time: 09:25 I Path: N:/3b2/ANA#/Vol00000/120255/APPFile/JW-ANA#120255 J_ID: ZAY Customer A_ID: BKLT2012_Abstracts Cadmus Art: ANA12 Date: 18-September-12 service are reported for the subsequent 12 month period, adjusted to 2008 dollars. Results: The highest costs were associated with long term care by Medicaid ($26,793). For inpatient care, average cost was highest for Medicare ($15,713) relative to Medicaid ($7,605). Outpatient costs were higher for Medicare ($1,102) than Medicaid ($57). Medicare incurred more costs for outpatient services such as durable medical equipment ($1,404) and home health ($6,819). Conclusions: The economic burden of AD is substantial to both Medicare and Medicaid but differs by payer. The site of care impacted the effect on each payer differently. Medicaid costs were driven by LTC expenses while Medicare costs were driven by inpatient expenses. Study supported by: This study has been supported by Pfizer Inc., and Janssen Alzheimer Immunotherapy. Dr. Mucha and Mr. Bobula are employees of Pfizer Inc. Stage: Page: 79 reconstruct three temporal fasciculi: fornix, parahippocampal cingulum, and uncinate fasciculus. Tract microstructural measures were corrected for partial volume errors. Results: In controls, episodic memory was associated exclusively with variations in fornix microstructure. In contrast, in MCI, memory was associated with integrity of parahippocampal cingulum and uncinate fasciculus, but not the fornix. Familiarity-based memory was associated specifically with parahippocampal cingulum microstructure. Conclusions: In the healthy brain, the fornix bears most of the episodic memory load. When this system is compromised, structure of other temporal association tracts become critical to performance. This patterm may reflect functional reorganisation or a greater reliance on familiarity-based or semantic memory, which are not dependent on integrity of the hippocampus and fornix. Study supported by: Medical Research Council, UK through a Clinician Scientist Fellowship to MOS M1136. Optineurin Immunoreactivity in Neuronal and Glial Intranuclear Inclusions in Adult-Onset Neuronal Intranuclear Inclusion Disease Masataka Nakamura, Melissa E. Murray, Wen-Lang Lin, Hirofumi Kusaka and Dennis W. Dickson; Jacksonville, FL and Moriguchi, Osaka, Japan M1138. Cingulum Bundle Microstructure Predicts Cognitive Control in Ageing and Mild Cognitive Impairment Michael J. OвЂ™Sullivan, Claudia Metzler-Baddeley, Derek K. Jones, Jessica Steventon, Laura Westacott and John P. Aggleton; London, United Kingdom and Cardiff, United Kingdom Background: Recently, optineurin (OPTN) immunoreactivity has been reported in neuronal intranuclear inclusions (NII) of neuronal intranuclear inclusions disease (NIID). Other studies have shown that the RNA-binding protein, fused in sarcoma (FUS), is a component of NII in NIID. Aims: To investigate the relationship between OPTN, FUS and Ubiquitin (Ub) in intranuclear inclusions of NIID. Methods: Sections of hippocampus from 4 NIID and 4 control patients were analyzed immunohistochemically. Results: In control subjects, OPTN was located in the cytoplasm of neurons. In NIID patients, NII and glial intranuclear inclusions (GII) were immunopositive for OPTN. The intensity of OPTN immunostaining of neuronal cytoplasm was reduced compared to that of control subjects. Double immunofluorescence for OPTN, FUS and Ub revealed co-localization of these proteins within NII and GII. All of the Ub positive NII was OPTN positive. The percentage of co-localization of Ub with FUS in NII was approximately 50%. Electron microscopic examination revealed both thin and thick filaments in NII were immunolabeled by Ub and OPTN. Conclusions: These findings suggest that OPTN plays a central role in the pathogenesis of NIID and that contribution of FUS is a less consistent. Study supported by: None Background: Brain injury and fMRI studies implicate the prefrontal cortex in cognitive control. The anterior cingulate cortex is involved in control of goal-directed behaviour, through top-down control of attention and maintenance of task set. Increasingly such functions are seen as subserved by distributed networks. Their efficiency might therefore depend on the status of prefrontal connections. Methods: We employed diffusion MRI-based tractography and several executive control tasks in 20 healthy older adults and 25 individuals with amnestic MCI, matched for age, education and premorbid intelligence. Anterior, medial, posterior, and parahippocampal portions of the cingulum were reconstructed. Tract microstructural measures were corrected for partial-volume errors. Results: Correlations with cognitive control were specific to the cingulum compared with control tracts (fornix and corticospinal tract). Verbal/symbolic tasks showed strong left laterality (Category Fluency and anterior cingulum, left r Вј 0.71, p<0.001, right r Вј 0.44, p Вј 0.06). In MCI, this pattern was maintained; a more spatial task (Tower of London) also related to right anterior cingulum. Conclusions: Cognitive control in older adults is exquisitely sensitive to variations in anterior cingulum microstructure. Shifts in pattern of association in MCI illustrated how alternative networks/processes become differentially involved with onset of disease. Study supported by: Medical Research Council, UK through a Clinician Scientist Fellowship to MOS (G0701912) AlzheimerвЂ™s Research UK (MOS) CONNECT (EU) (DKJ) M1137. Redistribution of Memory Load in Temporal Association Tracts in Mild Cognitive Impairment Claudia Metzler-Baddeley, Sarah Hunt, Derek K. Jones, John P. Aggleton and Michael J. OвЂ™Sullivan; Cardiff, United Kingdom and London, United Kingdom Background: Episodic memory is supported by networks that connect medial temporal, frontal and parietal regions. We have shown that the fornix is critical in age-related memory decline. We evaluated the relationships between structure of major temporal tracts and memory in amnestic MCI, where the hippocampus-fornix system is often compromised. Methods: 25 patients with MCI and 20 controls matched for age, education, and premorbid IQ underwent MRI and detailed evaluation of memory. Tractography was used to M1139. AlzheimerвЂ™s Disease Progression Rates: New Estimates Natalia Olchanski, Pei-Jung Lin, Joshua T. Cohen and Peter J. Neumann; Boston, MA Background: Estimates of AlzheimerвЂ™s disease (AD) progression based on older data may not reflect current clinical management. This study estimated transition rates from mild cognitive impairment (MCI) to more advanced AD using recent data from a large, longitudinal database. 79 ID: guganp I Black Lining: [ON] I Time: 09:25 I Path: N:/3b2/ANA#/Vol00000/120255/APPFile/JW-ANA#120255 J_ID: ZAY Customer A_ID: BKLT2012_Abstracts Cadmus Art: ANA12 Date: 18-September-12 Methods: We analyzed data (2005-2011) from the Uniform Data Set maintained by the National AlzheimerвЂ™s Coordinating Center. Analysis included patients aged 50 and older, excluding patients with non-AD dementia at baseline (n Вј 19,845 patients, 50,413 patient-visits). Disease severity was defined by the Clinical Dementia Rating: 0.5 (MCI); 1 (mild AD); 2 (moderate AD); and 3 (severe AD). We applied survival analysis to calculate age- and sexadjusted transition probabilities. Results: The sample included 40.5% males, mean age 76.3. Annual transition probabilities from MCI to mild AD were 0.091 in males and 0.085 females age 65, 0.100 (male) and 0.094 (female) age 75, and 0.113 (male) and 0.104 (female) age 85. Transition probabilities from mild to moderate AD ranged from 0.125 to 0.148, and from moderate to severe AD, 0.065 to 0.087. Conclusion: Disease progression rates were slightly higher in males and older patients, overall lower compared with previous CERAD analysis. Study supported by: Pfizer; NACC UDS data are supported by NIA grant number U01 AG016976 Stage: Page: 80 tial therapeutic effects of b-adrenergic antagonists in AD. In two transgenic AD mouse-models, chronic oral-administration of carvedilol, a b-adrenergic antagonist FDA-approved for several cardiac indications, decreased brain monomeric/ oligomeric b-amyloid contents, attenuated cognitive deterioration and improved brain basal neuronal transmission. Additionally, it may have beneficial effects on AD vascular risk-factors by stabilizing blood pressure and improving brain perfusion since itвЂ™s approved for treatment of hypertension and congestive heart-failure and is neuroprotective in brain ischemia models. WeвЂ™re clinically exploring a targetdose of 25mg/day carvedilol to 50 AD patients in a 6month randomized, placebo-controlled, double-blind, single-site trial; change in episodic recall is the primary outcome and biomarker change and safety/tolerability are secondary measures. If we observe significant improvements in clinical outcomes, weвЂ™ll propose a definitive trial of carvedilol in AD. If we observe changes only in biomarker outcomes, this will inform further studies of similar treatment mechanisms. Carvedilol has advantages in clinical trials since it has a well-characterized, well-tolerated safety profile and is available as a generic drug. Study supported by: Supported by NIH AG037504 to Giulio Maria Pasinetti. M1140. Impact of Cerebrovascular Risk over Age of Onset of Dementia Due to AlzheimerвЂ™s Disease in a Sample of Patients with Low Schooling from Brazil Fabricio F. Oliveira, Paulo H. Bertolucci, Marilia A. Smith and Elizabeth S. Chen; SaЛњo Paulo, SP, Brazil M1142. Changes in Specific Resting State Brain Networks Correlate with Clinical Measures in PSP and CBD Timothy Rittman, Boyd Ghosh, William R. Shirer, Michael D. Greicius and James B. Rowe; Cambridge, Cambridgeshire, United Kingdom and Stanford, CA Objective: To establish the impact of cerebrovascular (CV) risk factors and schooling over age of onset of dementia due to AlzheimerвЂ™s disease (AD). Methods: Patients with late-onset AD were assessed for gender, schooling, age of dementia onset, and CV risk factors (systemic hypertension, diabetes mellitus, hypercholesterolemia, alcoholism, smoking, family history of cardiovascular diseases, obesity and midlife physical inactivity). Multiple logistic regression was employed for statistical analysis, significance at p<0.05. Results: Among all 146 included patients, 97 (66.4%) were female and 49 (33.6%) were male, 52 (35.6%) reported physical inactivity, 125 (85.6%) had systemic hypertension, 38 (26.1%) had diabetes mellitus, and 103 (70.5%) had hypercholesterolemia, all under treatment; mean waist circumference was 94.7612.1cm, mean body mass index was 25.8364.45kg/m2, mean schooling was 4.463.6 years (range 0-15), and mean estimated age of dementia onset was 72.566.3 years-old. Smoking (OR Вј 1.159;95%CI 0.967-1.389) and obesity (OR Вј 1.145;95%CI 0.995-1.317) were the strongest risk factors for AD onset before 70 years-old (p Вј 0.003). Schooling and all other CV risk factors were not statistically significant. Conclusion: Smoking and obesity seem to impact the age of AD onset in Brazil. Study supported by: CAPES - CoordenacВёaЛњo de AperfeicВёoamento de Pessoal de NД±Вґvel Superior & FAPESP - The State of SaЛњo Paulo Research Foundation Functional connectivity network measures reliably reflect disease (Zhou 2010; Greicius 2004). Corticobasal Degeneration (CBD) and Progressive Supranuclear Palsy (PSP) often exhibit tau pathology, but have distinct phenotypes. Resting fMRI (3T) scans were acquired (21 controls, 30 PSP, 19 CBD). Individual Independent Component Analysis was performed and components compared to standard network templates to: 1. derive Goodness of Fit (GOF) scores, 2. identify a best fitting component for each network template, 3. correlate GOF with clinical measures. In the basal ganglia network GOF scores were lower than controls in PSP (p Вј 0.0003) and CBD (p Вј 0.04), and in PSP correlated with disease duration (r Вј -0.37, p Вј 0.04). In the left executive control network GOF scores differed between PSP and controls (p Вј 0.03) and in PSP correlated with verbal fluency (r Вј 0.38, p Вј 0.04). In the high visual network, GOF scores differed between CBD subjects compared with controls (p Вј 0.03) and PSP subjects (p Вј 0.02). These findings support functional connectivity measures as biomarkers of disease, and a tool to understand selective vulnerability of brain networks to neurodegeneration. Study supported by: The funders for this study are: MRC Wellcome Trust Sackler Studentship M1141. Repurposing Anti-Hypertensive Drugs for AlzheimerвЂ™s Disease Giulio M. Pasinetti and Paul Rosenberg; New York, NY and Baltimore, MD M1143. Patterns of Longitudinal Brain Atrophy in the Logopenic Variant of Primary Progressive Aphasia Jonathan D. Rohrer, Francesca Caso, Colin Mahoney, Maya Henry, Howard Rosen, Martin N. Rossor, Bruce Miller, Jason D. Warren, Gerard R. Ridgway and Maria Luisa GornoTempini; London, United Kingdom and San Francisco FDA-approved AD treatments do not significantly modify disease course. In a population-based sample of incident AD, we observed that using b-adrenergic antagonists was associated with slower functional decline, implicating poten- The logopenic variant of primary progressive aphasia is associated with phonological deficits and impaired word 80 ID: guganp I Black Lining: [ON] I Time: 09:25 I Path: N:/3b2/ANA#/Vol00000/120255/APPFile/JW-ANA#120255 J_ID: ZAY Customer A_ID: BKLT2012_Abstracts Cadmus Art: ANA12 Date: 18-September-12 retrieval. Little is currently known about what happens with disease progression. In this study 21 patients with longitudinal T1 MR imaging (mean interval 1.2 years) were studied using volumetric analysis and voxel-based morphometry (VBM). Baseline imaging showed asymmetrical (left greater than right) involvement of the posterior superior temporal and inferior parietal lobes as well as posterior cingulate and medial temporal lobes. The whole brain rate of volume loss was 2.0% per year with a greater rate of left hemisphere atrophy (2.3%) than right hemisphere (1.6%). Longitudinal VBM analysis showed increasing involvement of other language areas in the left hemisphere and atrophy of areas in the right hemisphere that had been seen earlier in the disease in the left hemisphere, particularly posterior cingulate. With disease progression there was worsening of anomia, sentence repetition and sentence comprehension but also deficits in single word comprehension, single word repetition and verbal memory. The logopenic variant appears to remain an asymmetrical disease as it progresses but with increasing involvement of the mirror regions in the right hemisphere. Study supported by: This work was undertaken at UCLH/UCL who received a proportion of funding from the Department of HealthвЂ™s NIHR Biomedical Research Centres funding scheme. The Dementia Research Centre is an AlzheimerвЂ™s Research UK Co-ordinating Centre. This work was also funded by the Medical Research Council UK. Dr Warren has received research support from the Wellcome Trust (Intermediate Clinical Fellowship). Stage: Page: 81 neuronal membrane formation), is designed to support syntaptogenesis in AlzheimerвЂ™s disease (AD). The Souvenir I study demonstrated that Souvenaid improved 12-week memory performance in drug-naД±ВЁve mild AD (n Вј 225; MMSE 20-26). Two additional RCTs were completed: SConnect: 24-week study investigating cognition in 527 mild-to-moderate AD patients (MMSE14-24) using AD medication; Souvenir II: 24-week study, investigating effects on memory in drug-naД±ВЁve mild AD (n Вј 259; MMSE!20). S-Connect did not show an effect on cognition in mildto-moderate AD on AD medications. Souvenir II showed significant improvement on the primary outcome memory measure in drug-naД±ВЁve mild AD. Compliance was high (>94%) and Souvenaid was well-tolerated in both studies. The hypothesis that Souvenaid acts via improving synapse formation and function was supported by significant effects on electroencephalography measures of functional connectivity. These findings offer hope towards a management strategy directed at one of the major hallmarks of early AD. Clinical studies on the long-term effects and biomarkers are ongoing (LipiDiDiet2). 1 Souvenaid is a registered trademark and Fortasyn is a trademark of N.V. Nutricia 2 Funded by the EU FP7 project LipiDiDiet, Grant Agreement N 211696 Study supported by: Nutricia Advanced Medical Nutrition, Danone Research, Centre for Specialised Nutrition, Wageningen, The Netherlands. Salary: R.L. Wieggers and P.J.G.H. Kamphuis are employees of Nutricia Advanced Medical Nutrition, Danone Research, Centre for Specialised Nutrition, Wageningen, The Netherlands. M1144. Differential Patterns of White Matter Degeneration as a New Biomarker for Dementia Seyed Ahmad Sajjadi, Julio Acosta-Cabronero and Peter J. Nestor; Cambridge, Cambridgeshire, United Kingdom Prediction of the clinical course and underlying pathology at early stages of dementia remains an unresolved challenge. In this work we assessed the utility of diffusion tensor imaging (DTI) maps acquired at the early stages of the disease in 42 clinically diagnosed cases of typical AlzheimerвЂ™s disease (AD), semantic dementia (SD), corticobasal degeneration (CBD), and progressive supra-nuclear palsy (PSP). DTI maps were acquired in 63 non-collinear directions and each patientвЂ™s map was separately compared to 26 age-matched controls using the non-parametric method implemented in Tract Based Spatial Statistics and statistical maps were obtained for three DTI metrics (fractional anisotropy and radial and axial diffusivities). Discrete patterns of tract degeneration were readily identifiable using visual rating scales. Inferior longitudinal and uncinate fasciculi, different components of the limbic system, and thalamic and midbrain tracts were abnormal in individual cases of SD, AD, and PSP respectively. Furthermore, diffuse bilateral white matter involvement in the motor and premotor areas was the salient abnormality in CBD. Our findings imply that the topographically distinct patterns of white matter degeneration seen in individual patients can be utilised as a diagnostic biomarker in neurodegenerative syndromes. Study supported by: Donald Forrester Trust NIHR Cambridge Biomedical Research Centre M1146. Relationship between Гџ-Amyloid Retention and Ischemia in the Patients with Subcortical Vascular Cognitive Impairment Young Noh*, Sang Won Seo, Geon Ha Kim, Seun Jeon, Jong Min Lee, Seung Jun Oh, Jae Seung Kim, Yearn Seong Choe, Kyung-Han Lee, Jae-hong Lee and Duk L. Na; Seoul, Republic of Korea Objective: Previous clinical studies suggested close relationship between cerebrovascular disease and risk of AlzheimerвЂ™s disease. However, direct correlation between Гџ-amyloid retention and ischemia has not been elucidated in human. Moreover, it is possible that ApoE4 might modify this relationship because ApoE4 contribute to the clearance of amyloid. The purpose of this study was to evaluate this relationship in the patients with both vascular and Гџ-amyloid pathology. Methods: We measured brain amyloid deposition using 11C-Pittsburgh compound B (PiB) PET in 136 patients with subcortical vascular cognitive impairment (SVCI). Among them, 52 patients with positive result for cortical PiB binding were study population (mean age 77.46 5.5). We divided the patients into two groups, ApoE4 carriers and noncarriers and then performed multiple linear regression analysis separately. Results: In the patients without ApoE4 allele, significant positive correlation was shown between the volume of white matter hyperintensities (WMH) and global cortical PiB retention ratio (B Вј 25311, SE Вј 11299, p value Вј 0.034), whereas, no significant correlation was found in ApoE4 allele carriers (B Вј -14143, SE Вј 10450, p value Вј 0.193). M1145. Souvenaid Improves Memory in Mild AD вЂ“ Results from the Clinical Study Program P. Scheltens, R. Shah, D.A. Bennett, R.L. Wieggers, T. Hartmann, H. Soininen and P.J.G.H. Kamphuis; Amsterdam, Netherlands; Chicago, IL; Wageningen, Netherlands; Homburg, Germany and Kuopio, Finland R , containing the specific nutrient combination SouvenaidV FortasynTMConnect1 (including precursors and cofactors for 81 ID: guganp I Black Lining: [ON] I Time: 09:25 I Path: N:/3b2/ANA#/Vol00000/120255/APPFile/JW-ANA#120255 J_ID: ZAY Customer A_ID: BKLT2012_Abstracts Cadmus Art: ANA12 Date: 18-September-12 Interpretation: This is the first clinical study showing that cerebrovascular disease and amyloid interactively develop in PiBГѕ SVCI patients without ApoE4. Study supported by: This study was supported by a grant from the Korean Healthcare Technology R&D Project, Ministry for Health, Welfare & Family Affairs, Republic of Korea. Stage: Page: 82 norms calculator provides clinician-researchers with an additional tool for gauging normative test performance in older adults, and especially guides interpretation of individual performances that appear to fall in borderline realms including classification of subtle impairments according to the NIAAA criteria. Study supported by: VA/GRECC NIA K23AG027171 (Atri) M1147. Prefrontal Cortex: Unilateral Disruption Differentially Affects Verbal Working Memory in Young and Older Adults Jessica A. Shields, Jeffrey Mock and Anne L. Foundas; New Orleans, LA M1149. Integrating Human and Fly Genetics To Understand AlzheimerвЂ™s Disease Susceptibility Joshua M. Shulman, Selina Imboywa, Allison E. Diamond, Portia Chipendo, Philip L. De Jager and Mel B. Feany; Boston, MA Unilateral repetitive transcranial magnetic stimulation (rTMS) was used to test the hypothesis that the laterality of verbal working memory (WM) changes in healthy older adults [Hemispheric Asymmetry Reduction in Older AdultsHAROLD]. This model stipulates that, under similar taskconditions, prefrontal activity tends to be less lateralized in older than in younger adults. Right-handed adults (young, n Вј 36, 18 female, mean 29.4 years; old n Вј 34, 18 female, mean 68.4) completed verbal n-back task. rTMS was then administered (90% motor threshold, 1Hz, 900 pulses) to: left, right, or sham dorsolateral prefrontal cortex (DLPFC) followed by repeat WM testing. Following right (p Вј .001) and sham (p Вј .007) conditions the expected practice effects were found in young adults; left DLPFC rTMS (p Вј .2) did not show practice effects. Older adults showed practice effects following left (p Вј .009), right (p Вј .001), and sham (p Вј .001) stimulation. The observed differences in stimulation effects between groups support the postulate that a more bilateral representation of verbal WM may develop with healthy brain aging [i.e., HAROLD/compensation model]. It may be that older adults shift cognitive resources to use a top-down executive processing strategy with input from left and right prefrontal networks. Study supported by: n/a The critical next step following recent discoveries of AlzheimerвЂ™s disease (AD) susceptibility loci is to confirm responsible genes and define mechanisms. We have coupled human genome-wide association studies with an efficient functional screen in Drosophila. From published studies, 130 candidate AD susceptibility genes achieved suggestive associations, nominating 89 fly orthologs for study. Lines predicted to activate or disrupt function were screened for modification of retinal toxicity due to human Tau or Amyloid-Beta (AГџ). Selected genes were also evaluated for impact on age-dependent brain neurodegeneration. 12 genes demonstrated robust interactions with Tau or AГџ neurotoxicity in vivo. Disruption of the fly integrin receptor scb (orthologous to human ITGAM and ITGA9) or the integrin modulators, Fit1/2 (orthologous to the kindlin, FERMT2), enhanced Tau toxicity. We also find that gain- and loss-of-function in cindr, a regulator of actin dynamics and the ortholog of CD2AP, reciprocally suppress and enhance Tau toxicity. Our cross-species strategy highlights several additional molecular pathways, including kinases (EPHA1) the microtubule cytoskeleton (MAST4), and RNA-binding proteins (SNRPN). Based on associations with human disease and functional interactions in Drosophila, we implicate integrin-mediated adhesion and several other pathways as important in AD susceptibility. Study supported by: Grants from the NIH and the Burroughs Wellcome Fund. M1148. Normative Scores and Calculator for the NACC UDS Neuropsychological Test Battery Steven D. Shirk, Meghan B. Mitchell, Joseph J. Locascio, Sandra Weintraub and Alireza Atri; Bedford, MA; Boston, MA and Chicago, IL M1150. Genetic Susceptibility for Amyloid Pathology in AlzheimerвЂ™s Disease Joshua M. Shulman, Kewei Chen, Brendan T. Keenan, Lori B. Chibnik, Pradeep Thiyyagura, Cristin McCabe, Jason J. Corneveaux, Lei Yu, Matthew J. Huentelman, Denis A. Evans, Julie A. Schneider, Eric M. Reiman, Philip L. De Jager and David A. Bennett; Boston, MA; Phoenix, AZ and Chicago, IL The revised AA-NIA criteria for the AlzheimerвЂ™s disease clinical spectrum necessitates tools that provide clinicians/ researchers additional information to aid detection and tracking of subtle cognitive impairment and decline. Comparing results of neuropsychological testing using different demographic adjustments, particularly age and pre-morbid functional ability/attainment, may increase AD-specturm classification accuracy. Recently, using published regression coefficients and RMSEs (Weintraub et al., 2009), we developed an estimated normative z-score calculator for the National AlzheimerвЂ™s Coordinating Center Uniform Data Set neuropsychological test battery that adjusts for sex, education, age, and their combination (Shirk et al., 2011). This simple method provides researchers an accessible tool to create norms for their own unique data sets. This study provides an updated calculator based on raw test data from an updated NACC-UDS sample of clinically cognitively normal participants (N Вј 6836). Using conventional methods of calculating regression-based scores, we provide updated norms, and provide validation of our earlier calculator. This Amyloid pathology is among the earliest brain changes of AlzheimerвЂ™s disease (AD); however, the discovery of susceptibility genes for AD has largely focused on the end-stage of clinically-diagnosed dementia.We evaluated recently reported AD susceptibility loci for associations with amyloid neuritic plaque burden in 725 autopsy cases from prospective, community-based studies. In addition to the previously reported APOE and CR1 susceptibility loci, we find that the ABCA7 (rs3764650, p Вј 0.02) and CD2AP (rs9349407, p Вј 0.03) loci are associated with neuritic plaque burden. In order to identify novel susceptibility loci, a genome-wide association study (GWAS) was performed using the neuritic plaque trait. Among the top results, we discover a novel variant near the amyloid precursor protein gene (APP, rs2829887) that is associated with amyloid neuritic plaques (p Вј 3.3x10-6), and this finding was validated in two independent cohorts of cognitively-normal subjects with positron 82 ID: guganp I Black Lining: [ON] I Time: 09:25 I Path: N:/3b2/ANA#/Vol00000/120255/APPFile/JW-ANA#120255 J_ID: ZAY Customer A_ID: BKLT2012_Abstracts Cadmus Art: ANA12 Date: 18-September-12 emission tomography imaging of fibrillar amyloid (p<0.005). Our results enhance understanding of AD risk factors by relating validated susceptibility alleles to increased amyloid neuritic pathology and implicating common variation at the APP locus in the earliest, pre-symptomatic stages of AD, extending the established association of rare APP mutations with early-onset, familial disease. Study supported by: Grants from the National Institutes of Health and the Burroughs Wellcome Fund. Stage: Page: 83 between nutrition and AD risk. Lower plasma nutrient status in AD patients compared to controls have been observed. Supplementation with combinations of DHAГѕEPA, UMP, choline, phospholipids, vitamins B, C, E, and selenium showed increased muscarinic receptor density, enhanced receptor-mediated G-protein activation, increased synaptic proteins mRNA expression and improved learning and memory. Based on these insights the specific nutrient combination FortasynTMConnect (UMP, DHA, EPA, choline, phospholipids, folate, vitamins B6, B12, C, E, selenium) was designed to support synapse formation and function in AD patients. R , conIn two randomised controlled studies SouvenaidV taining FortasynConnect, improved memory in drug-naД±ВЁve mild AD patients. Souvenaid is a registered trademark and Fortasyn is a trademark of N.V. Nutricia. Study supported by: Nutricia Advanced Medical Nutrition, Danone Research, Centre for Specialised Nutrition The authors ar employees of and salaries are payed by Nutricia Advanced Medical Nutrition, Danone Research, Centre for Specialised Nutrition M1151. Impaired Nutritional Status in Patients with Mild AlzheimerвЂ™s Disease Compared to Healthy AgeMatched Controls J.W. Sijben, M.G.M. Olde Rikkert, P. Scheltens, A.M.J. van Hees, M. Groenendijk and P.J.G.H. Kamphuis; Wageningen, Netherlands; Nijmegen, Netherlands and Amsterdam, Netherlands Epidemiological studies suggest that low intake of n-3 fatty acids, B-vitamins, and antioxidants increase risk of AlzheimerвЂ™s disease (AD). Other studies suggest that patients with AD have lower plasma levels of these nutrients compared to age-matched controls, either due to reduced daily consumption, their increased use, different metabolism, or a combination of these factors. In this study, nutritional status in AD patients was further explored. Nutritional status was assessed in a subgroup of 84 Dutch drug-naД±ВЁve mild AD patients (MMSE!20) participating in the Souvenir II study and in 98 Dutch healthy control subjects, matched for age and gender. Between-group differences in nutritional blood parameters and anthropometrics were analysed using ANCOVA. Plasma selenium (p<0.001), vitamin D (p Вј 0.084), the proportion of DHA (p Вј 0.006) and total long-chain n-3 PUFA (p Вј 0.024) in erythrocyte membranes and Mini Nutritional Assessment screening score (p Вј 0.008) were lower in AD vs. controls. No statistically significant differences were observed for plasma fatty acids, choline and folate. The nutritional status of patients with mild AD is impaired vs. healthy controls, suggesting that these patients could benefit from nutritional support, designed to meet specific nutritional requirements in AD. Study supported by: Nutricia Advanced Medical Nutrition, Danone Research, Centre for Specialised Nutrition, Wageningen, The Netherlands Salary: J.W. Sijben, A.M.J. van Hees, M. Groenendijk and P.J.G.H. Kamphuis are employees of Nutricia Advanced Medical Nutrition, Danone Research, Centre for Specialised Nutrition, Wageningen, The Netherlands M1153. A Return to Clinical Skills in the Early Diagnosis of AlzheimerвЂ™s Disease Cassandra Szoeke, Kathryn Ellis, Ping Zhang, Christopher Rowe, Ralph Martin, Colin Masters, David Ames and AIBL Research Group; Melbourne, VIC, Australia and Melbourne, Australia Early detection of the prodromal stages of Dementia is crucial to preventing onset of disease. We have identified a sub-group within the healthy cognition (HC) category at increased risk of progression to manifest cognitive impairment (MCI) over 18 to 36 months. The cognitive scores of 704 AIBL HC subjects were modeled at baseline to see if clear classes were apparent within this group. Two groups were distinguished within the HC population for cognitive performance. The performance on a simple word list recall was able to distinguish between these two groups with high accuracy. The predictive significance of this classification at 18 and 36 month follow-up was tested. Those in the lower performing group had significant risk for converting to MCI or AD over 18months with OR of 7.5 (CI 2.6-27.3). Being in the lower performing group at 18 months was higher risk for conversion at 3years with OR 10.2 (CI 3.438.1). All analyses were adjusted for age, education, sex and APOE4. A simple word recall test was able to identify those with healthy cognition who have 10 times higher risk of progression to MCI within 18-36 months. Study supported by: The AIBL Research Group M1152. Supporting Synapse Formation and Function in AlzheimerвЂ™s Disease: Mechanism of Action of the Specific Nutrient Combination FortasynTM Connect John W. Sijben, Patrick J. Kamphuis, Martijn C. de Wilde, Robert J. Hageman, Laus M. Broersen and Martine Groenendijk; Wageningen, Netherlands and Utrecht, Netherlands M1154. Gait and Balance Dysfunction in Dementia Yutaka Tanaka, Masao Miyazaki and Lisa T. Connor; IkomaGun, Nara, Japan; Ise, Mie, Japan and St. Louis, MO Objective: This study was designed to evaluate cerebral mechanisms underlying gait and balance disturbances in demented subjects. Subjects and Methods: 124 consecutive right вЂ“handed subjects with both gait disturbance and cognitive impairment, and 32 age- and education-matched healthy subjects were studied. Detailed cognitive exams were administered to all Ss. EEG recordings for 22 of the demented Ss were made with special attention to primary motor areas, supplementary motor areas, and premotor areas during motor execution and motor imagery tasks (foot extension and flexion) for 10 seconds each. AlzheimerвЂ™s disease (AD) is a progressive neurodegenerative disease, leading to gradual decline in cognitive and behavioral function.It is recognized that synaptic loss is the strongest structural correlate with memory impairment. Synapses and neurites consist of neuronal membranes largely composed of phosphatides. Phosphatide synthesis depends on the presence of the dietary precursors DHA, UMP and choline. Co-factors in the synthesis pathway of neuronal membranes are B-vitamins, phospholipids and antioxidants. Several studies have demonstrated a significant link 83 ID: guganp I Black Lining: [ON] I Time: 09:25 I Path: N:/3b2/ANA#/Vol00000/120255/APPFile/JW-ANA#120255 J_ID: ZAY Customer A_ID: BKLT2012_Abstracts Cadmus Art: ANA12 Date: 18-September-12 Results: No alpha or beta band blocking was detected in seven or more recordings in 17 of the 22 demented subjects. Significant вЂ�вЂ�no-blockingвЂ™вЂ™ was found in the right supplementary motor area and premotor area during motor execution and motor imagery in the dementia group. No relationship was found between dementia severity and EEG results. Conclusion: In a group of demented persons with clinically relevant disturbances of gait and balance, EEG abnormalities during tasks of motor execution and motor imagery were seen in the premotor and supplementary motor areas, especially in the right hemisphere. Study supported by: none Stage: Page: 84 patients receiving memantine ER performed significantly better than those receiving placebo on the SIB subscales of Reading/Writing (OC: P Вј 0.002; LOCF: P<0.001; MMRM: P<0.001) and Comprehension/Repetition/Discourse (OC: P Вј 0.048; LOCF: P Вј 0.004; MMRM: P Вј 0.006). There was no significant difference between treatment groups on the SIB subscale of Naming (OC: P Вј 0.093; LOCF: P Вј 0.073; MMRM: P Вј 0.057) or on the Functional Communication Score (OC: P Вј 0.257; LOCF: P Вј 0.131; MMRM: P Вј 0.116). In conclusion, for patients with moderate to severe AD receiving stable ChEI treatment, the addition of memantine ER may be associated with benefits in language abilities. Study supported by: Forest Laboratories, Inc. Drs. Stephen Graham and Michael Tocco are employed by Forest Research Institute. Drs. Michael L. Miller and Vojislav Pejović are employed by Prescott Medical Communications Group, an independent contractor to several pharmaceutical companies, including Forest Laboratories, Inc. Dr. Suzanne Hendrix is employed by Pentara Corporation, an independent contractor to several pharmaceutical companies, including Forest Laboratories, Inc. M1155. Pharmacodynamic and Pharmacokinetic Properties of Novel gamma-Secretase Modulators in Multiple Animal Model Systems Brian S. Bronk, Timonthy D. McKee, Robyn M.B. Louriero, JoAnn Dumin, Vladislav Zarayskiy, Wesley F. Austin, Nathan O. Fuller, Jed L. Hubbs, Ruichao Shen, Paul Pearson, Jeffrey Ives, Jeffrey Jonker and Barbara Tate; Cambridge, MA Gamma-secretase enzyme modulation is a promising therapeutic approach for the treatment of AlzheimerвЂ™s disease. Satori has identified a novel class of small molecule gamma secretase modulators (GSMs). The pharmacokinetic/pharmacodynamic relationship of these novel compounds was investigated in multiple species. Satori compounds display low clearance and high volumes of distribution, providing an extended half-life in all species. These compounds were capable of crossing the blood-brain barrier and displayed good oral bioavailability and a delayed Tmax. The PK profile of SPI GSMs provides brain exposures over a 24 hour period sufficient to afford a statistically significant PD response. Reductions in both Ab42 and Ab38 were robust, while Ab40 was not lowered in vivo, replicating the pharmacology of these compounds in in vitro systems. This effect was shown to be dose responsive and long lasting. Based on the preclinical data, the clinical PK profile of Satori compounds is predicted to modulate the gamma-secretase enzyme complex for 24 hours with once daily dosing. These compounds are expected to lower brain Ab42 levels in patients, leading to an effective treatment of AlzheimerвЂ™s disease. Study supported by: Satori Pharmaceuticals All authors are employees or consultants to Satori Pharmaceuticals M1157. Ile143Thr Presenilin 1 Mutation in Sporadic Atypical Early-Onset AlzheimerвЂ™s Disease Maria Travasarou, Stella Marousi, Vasiliki Kyrimi and Clementine E. Karageorgiou; Athens, Greece Introduction: Early-onset AlzheimerвЂ™s Disease (EOAD) accounts for about 5% of all AD cases, typically presents with gradual memory impairment, followed by progressive global cognitive decline, affecting subjects <65 years-old. Most commonly, EOAD concerns genetically predisposed families carrying mutations in the Amyloid-Precursor-Protein, Presenilin (PSEN) 1 and PSEN2 genes. Methods: We present a case of sporadic EOAD with an atypical clinical presentation, positive for the ile143thr PSEN1 mutation. Results: A 34 year-old previously healthy male with no family history of dementia, presented with a 12-month history of apathy, withdrawal, concentration disturbance, and confabulation for which he had been treated with antidepressants and antipsychotics. Ten months later, memory and visuospatial impairment appeared. Neurological examination revealed only generalized myoclonic jerks. Neuropsycological assessment showed significant deficits in memory, visuospatial ability, and executive functions. Extensive laboratory and neuroimaging investigations were normal. CSF levels of ptau and Ab42-amyloid indicated a neurodegenerative condition, later confirmed by identification of the ile143thr PSEN1 mutation. Conclusion: This atypical case of EOAD underlines the importance of genetic testing even in patients with sporadic, non-familial EOAD, and suggests that the disease may initially present with refractory neuropsychiatric symptoms and non-amnestic cognitive decline. Study supported by: The study has not received any financial or other support M1156. Effects of Extended-Release Memantine (28 mg, Once Daily) on Language and Communication Abilities in Patients with Moderate to Severe AlzheimerвЂ™s Disease Michael Tocco, Suzanne Hendrix, Michael L. Miller, Vojislav Pejovic and Stephen M. Graham; Jersey City, NJ; Salt Lake City, UT and Chicago, IL In this post hoc analysis, language and communication abilities were assessed in a 24-week, randomized, placebo-controlled trial of once-daily, extended-release (ER) memantine (28 mg) in ChEI-treated patients with moderate to severe AD. Language items from the SIB were grouped into subscales of Naming, Reading/Writing, and Comprehension/ Repetition/Discourse, and a Functional Communication score was constructed using communication-related items from 2 scales administered to caregivers: the 19-item ADCS-ADL19 and the Caregiver-Perceived Burden Questionnaire. For each post hoc measure, the change from baseline at week 24 was compared between groups. At week 24, M1158. Brain Imaging and Cognitive Predictors of Incident Stroke, Dementia and AlzheimerвЂ™s Disease (AD) Galit Weinstein, Alexa Beiser, Charles DeCarli, Rhoda Au, Philip A. Wolf and Sudha Seshadri; Boston, MA and Sacramento, CA Objectives: To test the hypothesis that specific patterns of brain Magnetic Resonance Imaging (MRI) and cognitive 84 ID: guganp I Black Lining: [ON] I Time: 09:25 I Path: N:/3b2/ANA#/Vol00000/120255/APPFile/JW-ANA#120255 J_ID: ZAY Customer A_ID: BKLT2012_Abstracts Cadmus Art: ANA12 Date: 18-September-12 Stage: Page: 85 The LipiDiDiet study2 is a 24-month, randomized, controlled, double-blind parallel-group study designed to investigate the effects of Souvenaid in 300 prodromal AD patients (Dubois 2007). Primary outcome is cognitive functioning (modified version of the Neuropsychological Test Battery). Secondary outcomes include progression to AD, cognitive performance (MMSE, ADAS-cog), functional abilities (ADCS-ADL), depression (MADRS), MRI atrophy rate, dementia biomarkers, safety, tolerance and nutritional parameters. The LipiDiDiet study started in 2009. Enrolment for the study is expected to be completed in 2012 and the first results of the intervention are expected to be available in 2014. Baseline data from the total group of prodromal AD patients will be presented. 1 Souvenaid is a registered trademark of N.V. Nutricia. Fortasyn is a trademark of N.V. Nutricia.2Funded by the EU FP7 project LipiDiDiet, Grant Agreement N 211696. Study supported by: - EU FP7 project LipiDiDiet, Grant Agreement N 211696. - Nutricia Advanced Medical Nutrition, Danone Research, Centre for Specialised Nutrition, Wageningen, The Netherlands. Salary: presenting author is an employee of Nutricia Advanced Medical Nutrition, Danone Research, Centre for Specialised Nutrition, Wageningen, The Netherlands measures predict incident strokes, and that these patterns differ from those associated with AD or dementia. Methods: A total of 3,135 Framingham participants (1,679 Offspring, 1,456 Original cohort) underwent cognitive testing (mean ages 65.767.0 and 67.567.3 years, respectively). About 87% of the Offspring and 15% survivors from the Original cohort (mean age 84.863.3 years) also underwent MRI. Cox models were used to estimate the associations of cognitive and brain MRI measures with 10year risk of incident stroke, dementia and AD. Results: During follow-up, Offspring participants sustained 55 strokes and Original cohort participants with cognitive and MRI data sustained 95 and 29 strokes, respectively. Offspring with impairment in tests of executive function had a higher risk of future stroke (HR Вј 2.27;95%CI:1.06-4.85), dementia and AD. A low total brain volume (TBV) and high WMHV predicted stroke in the Offspring (HR Вј 1.97;95%CI:1.03-3.77 and HR Вј 2.74;95%CI:1.51-5.00,respectively) and TBV also predicted dementia in both cohorts. Conclusions: There is a specific pattern of cognitive and brain structure measures observed in middle-aged persons that can predict stroke risk. Study supported by: National Institute of Neurological Disorders and Stroke (NS17950), the National Heart, Lung and Blood Association (HL93029, U01HL 096917) and the National Institute of Aging (AG08122, AG16495, AG033193, AG031287, P30AG013846). M1161. Pellagra: The Forgotten American Neurological Epidemic Adrian C. Williams; Birmingham, United Kingdom M1159. Beyond the Myths: Forgetting the Fictions of AlzheimerвЂ™s and Facing the Facts Peter J. Whitehouse; Cleveland, OH Pellagra caused, as documented in the epidemic of the southern states of the USA a century ago, all forms of dementia and many neuropsychiatric diseases. Earlier epidemics in Europe described Parkinsons, Multiple sclerosis and Motor neurone disease mimics. A festinant gait and fasciculation of the tongue was first described in pellagrins. Curable neurological syndromes should never be forgotten for reasons that include lessons about their mechanism and that we should ensure that less obvious cases have been eliminated. For instance mitochondrial/NADH aberrations permeate most current diseases: and the neurology of HIV bears an uncanny resemblance to pellagrins - who were also prone to many chronic infections such as TB. There is curent interest in nicotinamide metabolism and the evolution and ageing of all species both as being integral to energy paths and NAD-consumer hubs that control many aspects of behaviour of individuals and cell fates. Degeneration like cancerous change and chronic infections changes these dynamics and may be homeostatic responses to local energy/NAD circumstances. вЂ�вЂ�Too much of a good thingвЂ™вЂ™ by way of nicotinamide dosage is a possibilty in more affluent economies and might cause a mirror image of pellagra with an equally broad phenotype. Study supported by: No financial support Starting with the historical origins of dementia, this presentation will progressively expose the fundamental myths about Alzheimers that have led to failed pharmacological misadventures, the proliferation of limited brain fitness products, and the spread of damaging imagery, metaphors, and meanings about brain aging. It will then present new ideas and stories вЂ” grounded in lived experiences вЂ” for how we can act now to truly protect our brains and the brains of other vulnerable members of society, and how we might design local communities capable of supporting the brain health and quality of life of persons of all ages. An intergenerational health and wellness health practice based in a school will be used to illustrate what a Healthy Brains and Healthy Communities public health effort can achieve at the local level. Nutrition, exercise, cognitive activity, and social engagement are seen as key factors to maintain and enhance cognitive function and quality of life. Study supported by: None M1160. Baseline Characteristics of Subjects with Prodromal AlzheimerвЂ™s Disease: The LipiDiDiet Study Y. Freund-Levi, P.J. Visser, M. Kivipelto, R.L. Wieggers, T. Hartmann and H. Soininen; Huddinge, Sweden; Maastricht, Netherlands; Amsterdam, Netherlands; Stockholm, Sweden; Wageningen, Netherlands; Homburg, Germany and Kuopio, Finland M1162. Induction of Autophagy Protects Against TDP43-Mediated Neurodegeneration Sami Barmada, Aaron Daub, Michael Ando, Andrea Serio, Andrey Tsvetkov, Arpana Arjun, Siddharthan Chandran and Steve Finkbeiner; San Francisco, CA and Edinburgh, United Kingdom R , containing the specific nutrient combination SouvenaidV FortasynTM Connect1, is designed to support synapse formation and function in patients with AlzheimerвЂ™s Disease (AD). Two earlier randomised controlled clinical trials have shown that Souvenaid improves memory performance in drug-naД±ВЁve mild AD patients (Scheltens 2010; Scheltens 2011), indicating that Souvenaid may have a promising effect in the early phases of AD. TDP43, a nuclear DNA- and RNA-binding protein, plays a prominent role in the pathogenesis of both amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). We demonstrated previously that expression of wild-type and mutant TDP43 in primary rodent cortical neurons 85 ID: guganp I Black Lining: [ON] I Time: 09:25 I Path: N:/3b2/ANA#/Vol00000/120255/APPFile/JW-ANA#120255 J_ID: ZAY Customer A_ID: BKLT2012_Abstracts Cadmus Art: ANA12 Date: 18-September-12 recapitulates key features of ALS and FTD, including nuclear mislocalization, cytoplasmic aggregation, and mutant-specific neuronal loss. Two important predictors of cell death in this model were TDP43 levels and cytoplasmic mislocalization. Because stimulation of autophagy could potentially address both factors, we investigated a family of small-molecule compounds capable of inducing autophagy for their ability to prevent TDP43-mediated neurodegeneration. Using a novel method of measuring protein turnover in living cells, we first confirmed that the compounds enhance autophagy in neurons. We then demonstrated that the compounds lower TDP43 half-life, prevent cytoplasmic mislocalization, and decrease overall levels of TDP43. Not only did the compounds prevent TDP43-mediated cell death in primary neurons, but they were also beneficial in human stem cell-derived neurons carrying TDP43 mutations. Our data strongly suggest that induction of autophagy through the use of small molecules may be a promising and effective therapy for many patients suffering from ALS and FTD. Study supported by: NIH/NINDS (5-K08-NS072233-02) Stage: Page: 86 QD) may provide TPM exposure equivalent to immediaterelease topiramate dosed every 12 hr (TPM-IR Q12hr), but with a lower Cmax, higher Cmin, and reduced fluctuation index (FI). In this Phase 1, 2-way crossover, steady-state study, healthy subjects were up-titrated to 200mg of study drug (USL255 QD or TPM-IR Q12hr) and maintained at 200mg for 14 days. Subjects were immediately crossed over to the alternate formulation and maintained for another 14 days, followed by down-titration off study drug. Pharmacokinetic parameters for both formulations were assessed at steady state, and immediately following formulation switch. At steady state, both formulations provided equivalent TPM exposure. As compared with TPM-IR Q12hr, USL255 QD displayed a significantly lower Cmax (P<.001), higher Cmin (P<.001), longer Tmax, and approximately 26% lower FI. Additionally, no significant differences were observed in trough concentrations during formulation switch. As predicted by modeling, these results confirm that USL255 QD provides an improved PK profile at steady state. Further, it may be possible to switch patients from TPM-IR Q12hr to USL255 QD while maintaining steadystate trough plasma concentrations. Study supported by: Upsher-Smith Laboratories, Inc. All authors are employees of Upsher-Smith Laboratories, Inc. Epilepsy M1201. Extended-Release Topiramate Exhibits Linear and Dose-Proportional Pharmacokinetics Tricia L. Braun, Lawrence J. Lambrecht, Wesley M. Todd, Mark B. Halvorsen and T.L. Braun; Maple Grove, MN M1203. Magnetic Resonance Volumetry Reveals Focal Brain Atrophy in Transient Epileptic Amnesia Christopher R. Butler, Willemijn van Erp, Amit Bhaduri, Alexander Hammers, Rolf Heckemann and Adam Z. Zeman; Oxford, United Kingdom; Nijmegen, Netherlands; London, United Kingdom; Lyon, France and Exeter, United Kingdom Once-daily administration of USL255, an extended-release topiramate (TPM) formulation, provides TPM exposure equivalent to immediate-release TPM (TMP-IR) dosed twice daily, but demonstrates an improved PK profile (eg, lower Cmax, higher Cmin, decreased fluctuation index [FI]). This randomized, 5-way crossover, single-dose study in healthy subjects evaluated tolerability and the pharmacokinetics of five USL255 doses (25, 50, 100, 200, 400mg). Maximum plasma concentration (Cmax) and area under the plasma concentration-time curve (AUC) were determined for each dose and assessed for dose proportionality and linearity. Tolerability was assessed by monitoring treatmentemergent adverse events (TEAE). Total TPM exposure (AUC) was linear and dose proportional from 25mg вЂ“ 400mg. Maximum TPM concentration (Cmax) neared dose-proportionality for the 100mg вЂ“ 400mg doses. Subsequent analyses of dose-normalized TPM Cmax values, comparing 400mg to 200mg, and 200mg to 100mg, demonstrated that Cmax changed proportionally with dose. All doses of USL255 were generally well tolerated. USL255 exhibited a linear and dose-proportional TPM exposure profile from 25mg вЂ“ 400mg, and maximum plasma concentration appeared dose proportional over higher doses. Together these data suggest that USL255, a once-daily alternative to TPM-IR, provides flexible dosing options and dose adjustments should result in predictable TPM plasma concentrations. Study supported by: Upsher-Smith Laboratories, Inc All authors are employees of Upsher-Smith Laboratories, Inc. Introduction: Transient epileptic amnesia (TEA) is a syndrome of epilepsy in which the principal manifestation of seizures is recurrent episodes of isolated memory loss. Many patients with TEA also demonstrate unusual forms of persistent memory impairment including accelerated long-term forgetting (ALF) and autobiographical amnesia. Methods: 40 patients with TEA and 20 healthy controls underwent neuropsychological testing and brain MRI. Two volumetric methods were used: i) manual segmentation of the medial temporal lobe and ii) automated, multi-atlasbased segmentation of the whole brain. Results: ALF and autobiographical amnesia were detected in the patient group. Both volumetric methods confirmed the presence of subtle, bilateral hippocampal atrophy in the patient group. Additional volume loss was revealed in perirhinal and orbitofrontal cortices. The volumes of these regions correlated with performance on standard memory tests. No structural correlates were found for ALF or remote autobiographical amnesia. Conclusions: The results are consistent with the hypothesis that TEA is a focal medial temporal lobe epilepsy syndrome, but reveal additional pathology in connected brain regions. The interictal memory deficits of TEA remain unexplained by structural pathology and may reflect physiological disruption of memory networks by subclinical epileptiform activity. Study supported by: National Institute for Health Research M1202. Pharmacokinetics of Extended- and Immediate-Release Topiramate at Steady State and after Formulation Switch Tricia L. Braun, Lawrence J. Lambrecht, Wesley M. Todd and Mark B. Halvorsen; Maple Grove, MN M1204. SOS for Seizures in SESA Mirret M. El-Hagrassy and Robert Beach; Syracuse, NY A 49 year old male alcoholic had body stiffening, fall and head trauma after 2 daysвЂ™ drinking. Neurology exam, MRI, urine toxicology and serum alcohol were unremarkable. He Modeled steady-state PK data suggests a once-daily, extended-release topiramate (TPM) formulation (USL255 86 ID: guganp I Black Lining: [ON] I Time: 09:25 I Path: N:/3b2/ANA#/Vol00000/120255/APPFile/JW-ANA#120255 J_ID: ZAY Customer A_ID: BKLT2012_Abstracts Cadmus Art: ANA12 Date: 18-September-12 developed variable episodes of blank staring, facial twitching, head and gaze to the right, with aphasia, paraphasias and bizarre behavior. Initial EEG showed slowing, but follow-up showed left frontal non-convulsive status epilepticus. Subsequent EEGs showed PLEDs during treatment with lorazepam, levetiracetam, and lacosamide; then gradual improvement. He returned almost to his clinical baseline. Discussion: Subacute encephalopathy with seizures in chronic alcoholism (SESA) is rare, distinct from alcohol withdrawal. It is characterized by transient neurological deficits, seizures, EEG abnormalities such as focal slowing, spikes, PLEDs. Seizures were originally described as motor, but complex partial status epilepticus (CPSE) has been recently reported. Pathophysiology is unclear; a vascular cause was proposed. One case reported MRI with left frontal, insular cortical hyperintensity, and SPECT showing left frontal/temporal hyperperfusion with crossed cerebellar hyperperfusion. Another reported reversible MRI findings. Conclusions: Confused alcoholics may be thought to be delirious, but SESA with CPSE should be considered and treated if identified. Study supported by: N/A Stage: Page: 87 decreases synaptic glutamate concentration. It is unknown whether leucine has anticonvulsant mechanisms similar to treatments that affect metabolism, including the ketogenic diet or rapamycin. We investigated the effects of leucine using acute seizure tests in normal mice. Methods: Male NIH Swiss mice aged 3 weeks received leucine in drinking water (1.5% w/v) for 12 days (controls received water without leucine). Seizures were induced using 6 Hz, pentylenetretrazol, and kainate tests. Blood ketones were measured prior to seizure testing. Results: Leucine-treated mice were protected against 6 Hz-induced seizures (P Вј 0.02). In the pentylenetetrazol test, mice treated with leucine had a prolonged latency to first tail twitch (P Вј 0.04) but did not differ in other parameters. In contrast, leucine had no effect on kainateinduced seizures. Leucine had no effect on blood ketone levels. Interpretation: Leucine has an acute seizure test profile similar to the ketogenic diet. Anticonvulsant effects could not be attributed to differences in blood ketone levels. Study supported by: NINDS/NIH Johns Hopkins University School of Medicine Clinician Scientist Award Salary M1205. Reduced GABAA Receptor Endocytosis in a Mouse Model of Absence Epilepsy Chengwen Zhou, Li Ding and Martin J. Gallagher; Nashville, TN M1207. Withdrawn. M1208. Antiphospholipid Syndrome Presenting as Epilepsia Partialis Continua Fenella F. Johnstone and Odai Jumma; Birmingham, United Kingdom Recently, we reported that heterozygous deletion (Heta1KO) of the GABAA receptor (GABAAR) a1 subunit, a protein associated with human generalized epilepsy, causes electrographic and behavioral absence seizures in mice. We showed that Heta1KO increases a3 subunit expression and shifts intracellular a1 subunit-containing receptors to the cell surface, effects which alter inhibitory postsynaptic currents (IPSCs). Here, we determined whether these changes in GABAAR trafficking resulted from GABAAR recruitment from the endoplasmic reticulum (ER) or from reduced endocytosis. We measured the fraction of ER-resident a1 subunits in wild type (wt) and Heta1KO cortices using an endoglycosidase-H sensitivity assay. Surprisingly, in contrast to recombinant GABAAR expression systems, neither wt nor Heta1KO cortices possessed any ER-resident a1 subunit. Therefore, Heta1KO does not recruit ER receptors. Next, we determined the effects of Heta1KO on endocytosis. The endocytosis inhibitor, dynasore, increased mIPSC amplitudes in wt neurons by 28%, but had no effect on Heta1KO neurons, results consistent with Heta1KO reducing GABAAR endocytosis. Although reducing baseline GABAAR endocytosis partially compensates for Heta1KO, it also removes a major mechanism by which neurons dynamically increase synaptic inhibition. This latter effect may contribute to the development of paroxysmal hyperexcitability and seizures. Study supported by: National Institute of Neurological Disorders and Stroke Case presentation: A 64-year-old woman, with a past medical history of hypertension and cerebrovascular disease, presented with twitching attacks involving her face and left arm. Each attack lasted 3-5 minutes with ten each hour. On close examination, these were clearly focal motor seizures presenting as epilepsia partialis continua. Further examination revealed residual left sided weakness and normal cranial and systemic examinations. Her blood tests showed a persistently raised anticardiolipin antibody. Her CT head showed an old right parietal lobe infarct with MRI revealing re-infarction. Her electroencephalogram (EEG) revealed focal motor seizures. Further history confirmed previous miscarriage and deep vein thrombosis (DVT). She has subsequently started antiepileptic treatment and clopidogrel added to her aspirin therapy with remarkable improvement of her seizure control. She was eventually diagnosed with antiphospholipid syndrome (APS) based on the clinical manifestations of recurrent stroke, epilepsy, DVT, miscarriage and the presence of persistently positive anticardiolipin antibody. Conclusion: Although there are published cases describing APS presenting as status epilepticus, there are no documented case reports of APS presenting as epilepsia partialis continua. This case highlights the importance of recognising the neurological sequelae of APS and demonstrates a new presentation of APS. Study supported by: Nil M1206. Leucine Has Anticonvulsant Effects in Acute Seizure Tests Adam L. Hartman, Polan Santos and J. Marie Hardwick; Baltimore, MD M1209. Race and Sex Differences in Characteristics of Temporal Lobe Epilepsy Robert Knowlton, Suzanne Miller, Maria Pisu, Lawrence Ver Hoef, Kristen Riley and Nita Limdi; Houston, TX and Birmingham, AL Objective: Leucine is a ketogenic amino acid that protects against picrotoxin- and pentylenetetrazol-induced seizures, but not hexafluorodiethyl ether seizures, in rats. Similar to rapamycin (which suppresses seizures), leucine depletion suppresses mTOR activity in cell culture. Leucine also Objective: To determine differences in characteristics of temporal lobe epilepsy (TLE) with respect to race and sex 87 ID: guganp I Black Lining: [ON] I Time: 09:25 I Path: N:/3b2/ANA#/Vol00000/120255/APPFile/JW-ANA#120255 J_ID: ZAY Customer A_ID: BKLT2012_Abstracts Cadmus Art: ANA12 Date: 18-September-12 in a large population of patients from Alabama and surrounding states. Methods: The UAB seizure monitoring unit database was queried for discharge diagnoses between 2000 and 2010. A prior study of the entire population (n Вј 4188) revealed a significantly greater proportion of blacks compared to whites (especially females) diagnosed with TLE, while rates of other epilepsy types and psychogenic seizure diagnoses were not significantly different between groups. Differences were analyzed between the four race-sex groups for the cardinal features of TLE--age of onset, duration, and whether an epileptogenic lesion was identified on MRI. Results: Black females versus the other groups had significantly greater mean age of onset (31.0 vs 22.8 yrs, P<0.0001), shorter epilepsy duration (10.8 vs 18.8 yrs, P<0.0001), and greater proportion with negative MRI (58.4 vs 38.7%, a Вј 0.002). Interpretation: As part of a greater rate specific for TLE, African American women develop more adult onset, idiopathic TLE than whites or black males. Race and sex differences, amongst other genetic factors, may be critical to explaining the enigma of late onset idiopathic localizationrelated epilepsy. Study supported by: The UAB Epilepsy Center Stage: Page: 88 Yang, J Zhu and A Laurenza are salaried employees of Eisai Inc. M1211. Optogenetic Treatment Approaches for Focal Neocortical Epilepsy Laura Mantoan, Rob Wykes, Stephanie Schorge, Matthew C. Walker and Dimitri M. Kullmann; London, United Kingdom A new generation of optical probes, the light-sensitive ionchannels, channel rhodopsin-2 and halorhodopsin, allow modulation of electrical signals with high temporal resolution. These characteristics make optical inhibition a potentially advantageous new anti-epileptic treatment strategy that relies on optical activation of neurons to interrupt seizures. This approach is especially promising in focal epilepsy, which is often drug-resistant and characterized by a defined ictogenic zone. We show that optical stimulation of halorhodopsin in excitatory neurons successfully reduced high frequency epileptic activity in the tetanus toxin (TeNT) rat model of focal epilepsy in animals co-injected with TeNT and lentivirus carrying halorhodopsin. Control animals injected with halorhodopsin virus alone or TeNT/GFP virus showed no significant changes in EEG upon laser illumination. Halorhodopsin was reliably expressed and can be stimulated in vivo in rat motor cortex, without clinical signs of dysfunction in the live animal, nor histological features of cytotoxicity. Our results indicate that optical inhibition of epileptic discharges represents an exciting new strategy to be pursued in models of epilepsy: optogenetic techniques will not only help to dissect the neural networks underlying epileptic circuits but may one day translate into a radically new treatment alternative for human disease. Study supported by: PhD studentship from the Brain Research Trust and the Guarantors of Brain M1210. A Higher Hurdle? Baseline Frequency and Severity of Seizures in Trials of Perampanel, a New AED, Compared with Previously Approved AEDs Gregory L. Krauss, Frank Kerling, Vicente Villanueva, David Squillacote, Haichen Yang, Jin Zhu and Antonio Laurenza; Baltimore, MD; Ulm, Germany; Valencia, Spain and Woodcliff Lake, NJ Background: Successive studies of new adjunctive AEDs recruit many patients resistant to current therapies. We describe baseline seizure frequency and severity in registration trials for the new AED perampanel, compared with five approved newer-generation AEDs and three older AEDs. Methods: We evaluated baseline seizures and AED use in registration trials for perampanel, levetiracetam, zonisamide, lacosamide, eslicarbazepine, and retigabine. We also evaluated these parameters for lamotrigine, valproate, and carbamazepine - these will be included in the full presentation. Results: Median number of seizures/28 days at baseline was generally higher for perampanel (9.3-14.3) versus other AEDs: levetiracetam (6.7-10.5); lacosamide (5.5-15.0); eslicarbazepine (6.7-9.0); retigabine (7.9-12.1) (zonisamide data not available). More patients had a history of secondary generalized seizures in perampanel studies (67.9-71.9%) versus levetiracetam (26.0-27.0%); zonisamide (21.0-24.0%); lacosamide (43.8-78.8%); eslicarbazepine (28.2-47.1%); retigabine (23.2-33.7%). A high proportion of patients required three concomitant AEDs at baseline in perampanel trials (28.9-38.6%) compared with most AEDs: levetiracetam 5.0-5.1%; zonisamide 21.7-28.8%; lacosamide 0.0-36.9%; eslicarbazepine 0.09.9%; retigabine 0.0-33.8%. Conclusions: Patients entering perampanel registration trials generally experienced more frequent and severe seizures at baseline compared with other AED trials. Study supported by: Eisai Inc. G Krauss is an investigator and consultant for Eisai Inc. F Kerling has no disclosures to report. V Villanueva has participated in advisory boards and pharmaceutical industry sponsored symposia for Eisai Inc. D Squillacote, H M1212. Effect of Ocimum basilicum Extract Against Pentylenetetrazole-Induced Seizure in Mice Mehrdad Modaresi and Arezoo Pouriyanzadeh; Isfahan, Islamic Republic of Iran Epilepsy always noticed as a most important nerves disease. In traditional medicine, Ocimum basilicum used to treatment seizure and effects of anticonvulsant of this drug is reported. To access this anti-seizures drug with low imposition we survey effect of anticonvulsant drug of extract of Ocimum basilicum in seizure induced with pentylenetetrazole. Hydro-alcohol extract of Ocimum basilicum with physiologic serum and various dozes (50-100вЂ“250вЂ“300вЂ“350 mg/ kg) of extract inject to mices via interperitoneal 65 minutes before injection of pentylenetetrazole. And survey factors onset time of showing seizure effects, number of showing seizure effects The percentage of dead. We select the slot time (15-30-50-60-65-80-120 minutes) To survey the relevant slot time between relevant injection doze and pentylenetetrazole. Results of using various dozes (50- 100вЂ“250вЂ“ 300вЂ“350 mg/kg) shows that onset time of showing seizure effects, number of showing seizure effects and The percentage of dead at 250 mg/kg doze, 65 minutes before injection of pentylenetetrazole dependently (P < 0.05) sequencely increased, decreased and decreased. The results can be obtained at a dose of hydroalcoholic mg/kg250 effective as medication in preventing seizures in animal models introduced. Study supported by: Department of Physiology, Khorasgan Branch, Islamic Azad University, Isfahan, IRAN 88 ID: guganp I Black Lining: [ON] I Time: 09:25 I Path: N:/3b2/ANA#/Vol00000/120255/APPFile/JW-ANA#120255 J_ID: ZAY Customer A_ID: BKLT2012_Abstracts Cadmus Art: ANA12 Date: 18-September-12 M1213. MRI Volumetry of the Temporal Lobe in Sudan; Comparative Study between Epileptics and Matching Control Mohamed A. Nurein, Mohamedsalah M. Magzoub, Tahir O. Ali, Abdullah M. Jabir and Abdulrahman M. Fadlalmola; Umdurman, Khartoum, Sudan and Khartoum, Sudan Stage: Page: 89 M1215. Synaptic Reporter Labeling of Adult-Born Hippocampal Neurons in Experimental Epilepsy Alison L. Althaus, Helen Zhang, Hisashi Umemori and Jack M. Parent; Ann Arbor, MI Altered hippocampal neurogenesis may play a role in mesial temporal lobe epilepsy (mTLE) pathogenesis. Dentate granule cells (DGCs) generated after epileptogenic insults in rodents are especially vulnerable to abnormal plasticity, including ectopic migration, axonal sprouting, and persistent basal dendrites. These features promote potentially epileptogenic recurrent excitation. To investigate aberrant axonal plasticity in birthdated DGCs, we generated retrovirus (RV) carrying a synaptophysin-yellow fluorescent protein (YFP) fusion construct that labels presynaptic terminals. RV only integrates into dividing cells, enabling axon terminal labeling of age-defined DGC cohorts based on timing of dentate gyrus RV injections. We modeled mTLE in male Sprague Dawley rats using pilocarpine-induced status epilepticus (SE) at P56. RV was injected at P7 (labeling cells mature at onset of SE) or P60 (labeling cells born after SE). Animals survived 10 weeks after SE and hippocampi were immunostained for YFP and bassoon (pre-synaptic marker). Confocal analysis revealed changes in CA3 mossy fiber bouton size and structure, and increased hilar bouton density in post-SE generated DGC axons vs. controls. These findings indicate abnormal axonal development of DGCs generated after an epileptogenic insult. Ongoing work aims to determine whether these changes are proepileptogenic. Study supported by: NIH NS058585 Introduction: Hippocampal MRI volumetric changes in temporal lobe epilepsy are documented. Controversy is displayed in other regions. This study provided preliminary database in Sudan. Methodology: This cross sectional analytic study, in National Ribat University hospital. Epileptics compared to healthy matching group. 3D structural MRI for temporal lobe, superior temporal gyrus, entorhinal cortex and hippocampus in 1.5 Siemens scanner. Volume computed in 3D slicer 2.6. Each region is compared across genders and between hemispheres. Results: 69 control (34 males and 35 female) and 63 patients (32 males and 31 females). Controls displayed larger volumes in males than in females in all ROIs, left lateralization of temporal lobe, superior temporal gyrus and hippocampal right lateralization in males. No lateralization in entorhinal cortex. Epileptics displayed loss of lateralization in temporal lobe of males and left lateralization in superior temporal gyrus of females. Bilateral volume reduction in the hippocampus of both genders, and in males entorhinal cortices. Conclusions: Morbid anatomy in temporal lobe epilepsy differs between genders. Temporal lobe volumetry is altered in temporal lobe epilepsy. Study supported by: minstry of higher education sudan M1214. Epileptic Aphasia as an Initial Manifestation of Lyme Meningoencephalitis Dipakkumar P. Pandya, Anery Patel, Jennie Luna, Megan McGarry and Sourav Sen; Paterson, NJ M1216. Dravet Syndrome Patient-Derived Cells and Mouse Model Suggest SUDEP Mechanisms David Auerbach, Huilin Shi, Yu Liu, Julie M. Jones, Miriam H. Meisler, Lori L. Isom and Jack M. Parent; Ann Arbor, MI Ictal aphasia is a very rare manifestation of status epilepticus in adults. It is well known as an acquired aphasia with epileptic encephalopathy in children. The sustained reversible aphasia may be ictal and it is extremely rare. We report a case of epileptic aphasia as an initial manifestation of lyme meningo encephalitis. Based on our literature search this is first case report. 48-year-old woman came to emergency room because of global aphasia. She had spontaneous repetitions of words without sense. Her initial chemistry, blood counts, toxicology, and MRI brain were within normal limit. Her EEG monitoring showed left hemisphere periodic lateralizing electrographic discharges. She was started on antiepileptic medications with significant improvement. Her CSF serology was consistent with Lyme meningoencephalitis. She had near complete resolution of symptoms and EEG changes after intravenous ceftriaxone treatment. After 4 weeks of intravenous ceftriaxone in conjunction with antiepileptic medications, she had complete recovery that was correlated with neuropsychological evaluations. Lyme disease is a tick borne illness caused by Borrelia Burgdorferri. Our patient has complete recovery from symptoms. Any adult patient with aphasia should have comprehensive evaluations including electroencephalogram and CSF evaluations when imaging studies are normal. Study supported by: None Dravet Syndrome (DS) is a catastrophic childhood epilepsy largely caused by dominant mutations in the SCN1A gene encoding the NaV1.1 sodium channel. Sudden unexplained death in epilepsy (SUDEP) is a major concern in DS. Because NaV1.1 is also expressed in heart, we hypothesize that altered Na currents in DS cardiac myocytes (CMs) lead to arrhythmias and SUDEP. To test this, we generated induced pluripotent stem cells (iPSCs) and CMs from DS subjects and controls. We examined CM markers, beating rate and sodium currents in iPSCderived CMs. We also examined sodium currents in CMs from DS knock-in mice that express a human SCN1A mutation causing seizures and premature death. CM differentiation of DS and control iPSCs led to beating cells that expressed CM markers a-actinin and cardiac troponin-T. Preliminary results indicate higher beating rate and sodium current density in DS CMs vs. controls. Similarly, ventricular CMs from P17-19 DS mice show increased sodium current density vs. wild-type. Characteristics of the current suggests that it results from enhanced NaV1.5 (SCN5A gene) current that overcompensates for 50% NaV1.1 loss. These findings suggest a potential cardiac arrhythmogenic SUDEP mechanism in murine and human DS. Study supported by: Citizens United for Research in Epilepsy, University of Michigan Center for Organogenesis, NIH P20NS076916 89 ID: guganp I Black Lining: [ON] I Time: 09:25 I Path: N:/3b2/ANA#/Vol00000/120255/APPFile/JW-ANA#120255 J_ID: ZAY Customer A_ID: BKLT2012_Abstracts Cadmus Art: ANA12 Date: 18-September-12 M1217. Hypothermia Attenuates Glial Injury and Prevents EEG Progression during Status Epilepticus Sandipan Pati, J.X. Yin, Y. Gan, J. Georges, F.D. Shi, M. Maalouf and D.M. Treiman; Phoenix, AZ Stage: Page: 90 M1219. Mutations in the Novel Protein PRRT2 Cause Infantile Convulsions with Paroxysmal Kinesigenic Dyskinesia Hsien-Yang Lee, Yong Huang, Nadine Bruneau, Patrice Roll, Elisha D.O. Roberson, Mark Hermann, Emily Quinn, James Maas, Robert Edwards, Tetsuo Ashizawa, Betul Baykan, Kailash Bhatia, Susan Bressman, Michiko K. Bruno, Ewout R. Brunt, Roberto Caraballo, Bernard Echenne, Natalio Fejerman, Steve Fruct, Christina A. Gurnett, Edouard Hirsch, Henry Houlden, Joseph Jankovic, Wei-Ling Lee, David R. Lynch, Shehla Mohammed, Ulrich MuВЁller, Mark P. Nespeca, David Renner, Jacques Rochette, Gabrielle Rudolf, Shinji Saiki, Bing-Wen Soong, Kathryn J. Swoboda, Sam Tucker, Nicholas Wood, Michael Hanna, Anne M. Bowcock, Pierre Szepetowski, Ying-Hui Fu and Louis J. Ptacek; San Francisco, CA; Marseille, France; Saint Louis, MO; Gainesville, FL; Istanbul, Turkey; London, United Kingdom; New York, NY; Honolulu, HI; Groningen, Netherlands; Buenos Aires, Argentina; Montpellier, France; Strasbourg, France; Houston, TX; Novena, Singapore; Philadelphia, PA; Giessen, Germany; San Diego, CA; Salt Lake City, UT; Amiens, France; Ishikawa, Japan and Taipei, Taiwan The aim of this study is to assess the neuroprotective effects of hypothermia therapy in a validated rodent model of limbic SE. Adult male Sprague-Dawley rats (n Вј 38) were induced SE for 4.5 hours using lithium-pilocarpine and monitored by continuous EEG. Half of the rats were subjected to hypothermia (rectal temperature 31-33C) beginning at the time of SE induction. The outcome was assessed at 24 hours. 13 out of 16 rats treated with hypothermia during SE survived in comparison to 5 out of 16 in the non treatment SE arm (p < 0.05; odds ratio of surviving 9.53 (p <0.05). Quantitative analysis of neuronal damage (by H & E; cresyl violet) revealed less neuronal damage in CA1,CA 3 following SE treated with hypothermia (p <0.05). This neuroprotective effect by hypothermia was confirmed by western blotting and by immunofluorescent imaging using markers: NeuN, activated caspase-3 and IbA1 (for microglial), oxidized protein and IL-1B (p<0.05). Hypothermia prevented EEG progression of SE from Treiman Stage 3 to Stage 5. Hypothermia attenuates neuro-glial injury and progression of EEG during prolonged status epilepticus. Study supported by: None Paroxysmal kinesigenic dyskinesia with infantile convulsions (PKD/IC) is an infantile convulsion/episodic movement disorder with autosomal-dominant inheritance and high penetrance, but the causative genetic mutation is unknown. We have now identified four truncating mutations involving the gene PRRT2 in the vast majority (24/25) of well-characterized families with PKD/IC. PRRT2 truncating mutations were also detected in 28 of 78 additional families. PRRT2 encodes a proline-rich transmembrane protein of unknown function that has been reported to interact with the t-SNARE, SNAP25. PRRT2 localizes to axons but not to dendritic processes in primary neuronal culture, and mutants associated with PKD/IC lead to dramatically reduced PRRT2 levels, leading ultimately to neuronal hyperexcitability that manifests in vivo as PKD/IC. Study supported by: HHMI, DMRF M1218. Weight Change Associated with Anti-Epileptic Drugs W.O. Pickrell, A.S. Lacey, R.H. Thomas, M.I. Rees and P.E.M. Smith; Swansea, United Kingdom and Cardiff, United Kingdom Introduction: Prediction and quantification of potential side effects from anti-epileptic drugs (AEDs) are important to both patients and clinicians. Weight change is an important side effect and is known to occur with several AEDs. However, population and objective data are lacking. Aim: To determine weight change after starting AEDs. Method: We analysed retrospectively anonymised electronic primary care records of approximately 1.3 million adult patients in Wales. 19 622 (1.5%) patients had a diagnosis of epilepsy and of these, 1499 (7.6%) had their body weight measured within 12 months before starting and between 3 and 12 months after starting one of five AEDs. Results: The mean difference between body weight, after and before starting each AED (together with 95% confidence intervals and p-values for no difference) were:- topiramate -2.1kg (-3.6,-0.6) p Вј 0.008; carbamazepine 0.5kg (-0.2,1.2) p Вј 0.13; lamotrigine -0.02kg (-0.5,0.5) p Вј 0.94; levetiracetam 1.2kg (0.6,1.7) p<0.005 and sodium valproate 1.1kg (0.3,1.9) p Вј 0.007. Conclusions: Lamotrigine and carbamazepine were not associated with significant weight change, topiramate was associated with significant weight loss and levetiracetam and sodium valproate were associated with significant weight gain. The study does not account for other factors, such as polytherapy or genetic backgrounds, which may influence weight change. Study supported by: National Institute for Social Care and Health Research The author receives an unrestricted clinical fellow training grant from UCB Pharma M1220. Appropriate Drug Treatment for Status Epilepticus Does Not Influence Its Prognosis Andrea O. Rossetti, Vicent Alvarez, Jean-Marie Januel and Bernard Burnand; Lausanne, Switzerland Objective: Status epilepticus (SE) prognosis, is mostly related to non-modifiable factors (especially age, etiology), but the specific role of treatment appropriateness (TA) has not been investigated. Methods: In a prospective cohort with incident SE (excluding postanoxic), TA was defined, after recent European recommendations, in terms of drug dosage (630% deviation) and sequence. Outcome at hospital discharge was categorized into mortality, new handicap, or return to baseline. Results: Among 225 adults, treatment was inappropriate in 37%. In univariate analyses, age, etiology, SE severity and comorbidity, but not TA, were significantly related to outcome. Etiology (95% CI 4.3-82.8) and SE severity (95% CI 1.2вЂ“2.4) were independent predictors of mortality, and of lack of return to baseline conditions (etiology: 95% CI 3.9вЂ“14.0; SE severity: 95% CI 1.4вЂ“2.2). Moreover, TA did not improve outcome prediction in the corresponding ROC curves. Conclusions: This large analysis suggests that TA plays a negligible prognostic role in SE, probably reflecting the outstanding importance of the biological background. Awaiting treatment trials in SE, it appears questionable to apply 90 ID: guganp I Black Lining: [ON] I Time: 09:25 I Path: N:/3b2/ANA#/Vol00000/120255/APPFile/JW-ANA#120255 J_ID: ZAY Customer A_ID: BKLT2012_Abstracts Cadmus Art: ANA12 Date: 18-September-12 further resources in refining treatment protocols involving existing compounds; rather, new therapeutic approaches should be identified and tested. Study supported by: None Stage: Page: 91 ECT treatment and urgent evaluation and treatment is warranted as it can increase morbidity and mortality. Study supported by: None M1223. The Role of RhoA, Filamin and Formin in Cortical Development Gewei Lian, Markus Dettenhofer, Russell Ferland and Volney Sheen; Boston, MA and Albany, NY M1221. Planes Trains and Automobiles: Neurologic Disorders and the Workforce. A Systematic Review Eva Pilcher, Maria Baldwin and Michael J. Schneck; Maywood, IL and Pittsburgh, PA Periventricular heterotopia (PH) is a malformation of cortical development characterized by nodules of neurons along the lateral ventricles of the brain and microcephaly. Human mutations in the actin-binding protein filamin A (FLNA) cause PH. Although FLNA interacts with a variety of transmembrane receptors (including integrins) and transmits extracellular signals to cytoskeleton, the mechanism by which FLNA gives rise to PH is unclear. Here, we report that FLNA specifically interacts and binds to RhoA. RhoAdependent activation of integrin receptors is dependent on FLNA in neural progenitor cells and regulates progenitor proliferation. Moreover, endogenous levels of activated RhoA are diminished in the null FlnA mouse. We also find that both activated RhoA and FLNA bind to formin 2 (FMN2), a protein involved in actin polymerization. Activated RhoA competes with the binding of FMN2 C-terminus to the FMN2 N-terminus thereby activating FMN2 dependent actin nucleation. RhoA activation leads to internalization of both FlnA, FMN2, and integrin to the Golgi through a cholera toxin/ caveolin mediated mechanism. Overall, actin dependent mechanisms through RhoA, FLNA and FMN2 regulate integrin activation and internalization at the cell surfuce and thereby determine brain size. Study supported by: NYSTEM, State of New York NIH Objective: To investigate how neurological disorders impact upon employment in regulated occupations related to public safety and welfare. Methods: A systematic search was conducted of MEDLINE databases from 1995 to May 2011 using terms for employment, occupation or occupation injury and a broad range of neurological diseases and impairments with particular emphasis on epilepsy, sleep disorders, cerebrovascular disorders, headache, and dementia or other neurodegenerative disorders. Results: We found 36 relevant papers for a literature review. We reviewed work limiatiosn relevant to firefighters, police officers, military personnel, commercial drivers, airplane pilots, train conductors, ship operators, and health care providers. We found that the regulations applying to different occupations are variable and inconsistent both within occupations as related to different disorders (ie stroke versus epilepsy versus sleep disorders) and between occupations (ie firefighters versus police) including highly variable requirements for length of disease-free interval. Conclusion: Uniform guidelines should be established for the determination of work-place restrictions on workers with neurological disorders employed in occupations that affect public safety or public welfare as current regulations are not evidence-based or supported logically by clinical data. Study supported by: no support M1224. Seizure Etiology & Outcome in HIVГѕ Zambian Adults Omar K. Siddiqi, Melissa Elafros, Izukanji Sikazwe, Chris Bositis, Michael J. Potchen, Igor J. Koralnik, William Theodore and Gretchen L. Birbeck; Boston, MA; Lusaka, Zambia; East Lansing, MI; Baltimore, MD; Lawrence, MA and Bethesda, MD M1222. Electroconvulsive Therapy Induced Absence Status Epilepticus Umang Shah, Evren Burakgazi and Usman Mogul; Camden, NJ Objective: Recognize finding of absence status epilepticus (SE) after electroconvulsive therapy (ECT). Background: ECT uses an electric current to produce a seizure as a treatment for refractory depression. Most therapeutic ECT seizures last from 15 to 70 seconds. Prolonged seizures or SE can be seen as rare complication after ECT treatment. Design/Method: Case of absence SE after ECT treatment. Result/Case: Forty-four year old female with history of major depression is brought to the hospital for change in mental status. She has undergone fourteen ECT treatments and last was week before her presentation. Her initial electroencephalogram (EEG) was markedly abnormal with frequent generalized ten to thirty seconds of high-voltage rhythmic two to three Hz spike and wave discharges during which she was having staring spell with lapses of memory. She was treated with valproic acid and zonegran with good response. Discussion: Absence seizures are non-convulsive seizures. Increased oscillation between thalamus and cortex is considered as underlying cause in addition to decreased cortical inhibition on thalamic oscillations. Seizure and SE should be considered in patients with change in mental status after Background: Epilepsy risk factors in people with HIV/ AIDS in sub-Saharan Africa with new onset seizures are unknown. Objective: To characterize seizure etiology and recurrence risk in HIVГѕ Zambian adults. Methods: We enrolled HIVГѕ adults presenting with new onset seizure who recovered to a Karnofsky of >50. CD4, Na, glucose, malaria RDT, RPR, and extensive CSF analyses were performed. Patients were followed for recurrent seizures. Results: Of 89 HIVГѕ adults with seizure, 21(24%) met inclusion criteria. Karnofsky < 50 was the commonest reason for exclusion. Patient characteristics were mean age 35.4 years, 11 males (52.4%), mean CD4 167cells/ll, with 7(33.3%) on ARVs. Ten (47.6%) had some focal aspects to their seizures and/or examination. Two patients with serum RPRГѕ had CSF VDRL-. CSF PCR revealed 5/21(23.8%) EBV DNA and 1/21(4.8%) each for MTB and JCV DNA. One sample was both EBV and TBГѕ and one sample was both EBV and serum RPRГѕ. India ink identified one cryptococcal infection. Within 2 months, 4(19.0%) patients suffered recurrent seizures and another 4(19.0%) died. 91 ID: guganp I Black Lining: [ON] I Time: 09:25 I Path: N:/3b2/ANA#/Vol00000/120255/APPFile/JW-ANA#120255 J_ID: ZAY Customer A_ID: BKLT2012_Abstracts Cadmus Art: ANA12 Date: 18-September-12 Conclusions: Seizures in HIVГѕ adults in Zambia are associated with significant morbidity and mortality. An infectious etiology can often be identified. Study supported by: NIH grant R21NS073509 American Academy of Neurology Clinical Research Training Fellowship Stage: Page: 92 M1227. Intravenous Sodium Valproate for Status Epilepticus Yuan Wu, Xiaofei Liu, ZiBin Chen, MeiGang Ma and Li Su; Nanning, Guangxi, China To determine whether intravenous sodium valproate was more effective or safer than other drugs in patients with status epilepticus, we performed a meta-analysis. A literature search was performed using Medline, Embase, and the Cochrane Central Register of Controlled Trials CENTRAL. From 544 articles screened. Main outcomes were SE controlled, risk of seizure continuation. The metaanalysis was performed with the Random-effect model. The quality of the included studies was evaluated by Grade software. There was no statistically significance in SE controlled between Intravenous sodium valproate and Phenytoin. Compared with diazepam, sodium valproate had a statistically significant lower risk of time interval for control of RSE after giving drugs, however, there was no statistically significant difference in SE controlled within30 minutes between the two groups. There was no statistically significant difference in cessation from status between Intravenous sodium valproate and Levetiracetam. Intravenous sodium valprate was as effective as intravenous phenytoin for SE controlled and risk of seizure continuation. Study supported by: the First Affiliated Hospital, Guangxi Medical University M1225. Ketamine in the Treatment of Refractory Status Epilepticus Andrea S. Synowiec, Deepinder S. Singh, Vamsi Yenugadhati, James P. Valeriano, Carol J. Schramke and Kelly M. Kevin; Pittsburgh, PA and Philadelphia, PA Refractory status epilepticus (RSE) is a neurological emergency with high morbidity and mortality. Limited data exist regarding ketamine use in this population. We describe our experience with ketamine in RSE between 2003 and 2011. Eleven adults who had previously failed standard treatment protocols were treated with ketamine via continuous intravenous infusion. Data were collected on age, gender, history of epilepsy, etiology of RSE, daily total dosing of ketamine, co-therapeutic agents, treatment response, and disposition. RSE was successfully terminated in all 11 patients. Co-infused continuous anesthetic agents were able to be discontinued in 8/11 (73%) of patients within 72 hours. Ketamine was the last AED used prior to resolution of RSE in 7/11 (64%) cases. Administration of ketamine was uniformly associated with decreased pharmacological vasopressor support, and during ketamine infusion, pressors were discontinued in 6/7 (85%) patients who required them previously. Favorable outcome as defined by discharge to home or inpatient rehabilitation facility was attained in 5/11 (45%) patients. No acute adverse effects were noted. These findings suggest that ketamine may be a useful adjunctive agent in the treatment of RSE, especially in patients whose treatment options for RSE are limited by hypotension. Study supported by: None M1228. Protective Effect of Alpha -Asarone in SombatiвЂ™s Cell-Based Model of Epilepsy Yuan Wu, Xiao-Fei Liu, Yue-Juan Wu, Jie Su and Mei-Gang Ma; Nanning, Guangxi, China To explore the effect of alpha-asarone on neuronal apoptosis with mitochondrial damage, and changes in neuron cellular ultrastructure in SombatiвЂ™s cell-based model of epilepsy. Dissociated hippocampal neurons from rats were cultured in vitro to induce SombatiвЂ™s cell-based model. The apoptotic ratio of neurons was measured after treatment with alphaasarone. JC-1 staining was used to detect apoptosis with mitochondrial damage, and neuronal ultrastructure was observed by transmission electron microscopy. Compared with the model group, the apoptosis of groups treated with alpha-asarone that had sustained mitochondrial damage was significantly reduced. JC-1 staining revealed bright green and red fluorescence of the normal group but faint red and bright green fluorescence in the model group. With alpha-asarone treatment, the red fluorescence was restored, and both the number and area of red fluorescent faculae increased. Electron microscopy revealed nuclear distortion, chromatin condensation and margination, and mitochondrial swelling in neurons of the model group, and the mitochondria of 120 lg/ml alpha-asarone group were slightly swollen. Neuronal apoptosis was observed in SombatiвЂ™s cellbased model, and treatment with a-asarone was able to alleviate this effect. Alpha-asarone reduced mitochondrial damage and decreased the apoptosis of neurons in this model. Study supported by: This study was supported by grants from the National Natural Science Foundation of China(No.30960111), the Natural Science Foundation of Guangxi Province of China(No.2010GXNSFA013168), and the Major Program of Health Commission of Guangxi Province, China(No.200916). M1226. Self Reported Anger and Depression in Patients on Levetiracetam in Mono and Polytherapy Udo C. Wieshmann and Gus Baker; Liverpool, United Kingdom Objective:To ascertain the frequency of self-reported anger and depression in Levetiracetam (LEV). Methods: We included 158 patients with epilepsy (PWE) on LEV in monotherapy or as part of polytherapy and 260 patients on Anti Epileptic Drugs (AED) other than LEV and 41 control subjects. All PWE and controls completed the Liverpool Adverse Event Profile (LAEP). Results: Forty nine percent of PWE on LEV and 39% on AED other than LEV reported anger as sometimes or always being a problem (p(chi square) Вј 0.042). Forty eight percent of PWE on LEV and 45% on AED other than LEV reported depression as sometimes or always being a problem (p(chi square) Вј 0.584). Only 7% of control subjects reported anger as sometimes being a problem. No control reported depression. Conclusion: Anger and depression were more frequently reported as a problem by PWE than by control subjects. Our unblinded observational study of self reported symptoms suggested anger being more often a problem in patients taking LEV than in PWE taking other AED. PWE should be cautioned about the potential side effects of AED. Study supported by: Epilepsy Action 92 ID: guganp I Black Lining: [ON] I Time: 09:25 I Path: N:/3b2/ANA#/Vol00000/120255/APPFile/JW-ANA#120255 J_ID: ZAY Customer A_ID: BKLT2012_Abstracts Cadmus Art: ANA12 Date: 18-September-12 M1229. The Syndrome of Transient Epileptic Amnesia (TEA) Adam Zeman and Christopher R. Butler; Exeter, Devon, United Kingdom and Oxford, Oxfordshire, United Kingdom Stage: Page: 93 add valuable perspective on identification of eloquent cortex by classical fMRI paradigms. A Study supported by: merican Epilepsy Society (Milken Family Early Career Award); Center for Clinical and Translational Sciences, University of Texas Health Science Center, Houston, TX TEA is a recently described - but controversial and underdiagnosed - syndrome of temporal lobe epilepsy, mainly affecting people over fifty, characterised by episodes of anterograde and/or retrograde memory impairment (Butler, Annals of Neurology, 2007; Zeman, Current Opinion in Neurology, 2010). These episodes often occur on waking and usually last about thirty minutes. Other less prominent manifestations of epilepsy, particularly olfactory hallucinations, occur in 2/3 of cases. Attacks generally cease on anticonvulsant treatment. To date, none of the proposed etiologies (cerebrovascular, immune-mediated, neurodegenerative) accounts for the majority of cases. In addition to the amnestic seizures, persistent, interictal, treatment-resistant, memory problems often develop, in particular accelerated longterm forgetting of recently-formed memories, and impairment of remote autobiographical memory. While these deficits are invisible to standard neuropsychological tests, we have quantified them using tailor-made instruments (Milton, Brain, 2010; Muhlert, Neuropsychologia, 2010). Similar deficits have recently been described in other forms of temporal lobe epilepsy. These forms of memory loss are of clinical relevance to epileptologists and cognitive neurologists, and of theoretical interest to memory science. We will describe the UK-wide TIME project (The Impairment of Memory in Epilepsy, http://sites.pcmd.ac.uk/time/ index.php) which is investigating these disorders. Study supported by: Academy of Medical Sciences Epilepsy Research UK ESRC Great Western Research Initiative Health Foundation Microsoft Research Mrs Dale Medical Neurology Research Fund Patrick Berthoud Charitable Trust Wellcome Trust M1231. Attenuated and Augmented Emotional Face Processing Networks in Temporal Lobe Epilepsy Brett W. Fling, Jeff Riley and Jack J. Lin; Irvine, CA Rationale: Emotional processing deficits are common in temporal lobe epilepsy (TLE) but the functional underpinnings remain unclear. We hypothesize that functional MRI signals in emotional face processing regions will be altered, according to the side of seizure onset in TLE. Methods: Functional MRI data were obtained using a dynamic fear-face paradigm in 24 TLE patients (Left Вј 15; TLE Вј 9) and 19 age/gender matched healthy controls (HC). Face-responsive regions (fusiform, FFA; occipital face area, OFA; superior temporal sulcus, STS; temporal pole, TP) were identified in each individual using the peak voxel of the activation clusters. Analyses were performed according to the side of seizure onset (ipsilateral vs. contralateral). Results: TLE patients demonstrated significantly decreased activation in the ipsilateral OFA (P < 0.02), and a trend toward decreased activation in the ipsilateral STS (P Вј 0.06) compared to HC. Conversely, TLE subjects activated the contralateral TP significantly more than HC (P < 0.02). Conclusions: Emotional face processing regions were attenuated, ipsilateral and augmented, contralateral to the side of seizure onset, implying both local network disturbances and compensatory mechanisms in distant regions. Study supported by: NINDS K23 NS060993 M1232. Microelectrodes Produce Unreliable EEG Recordings William Stacey, Spencer Kellis, Christopher Butson, Paras Patil, Trevor Assaf, Temenuzhka Mihaylova and Simon Glynn; Ann Arbor, MI; Pasadena, CA and Milwaukee, WI M1230. Oxygen-Enhanced MRI: A New Imaging Tool for Localization of Focal Epilepsy and Eloquent Cortex Giridhar P. Kalamangalam, Timothy M. Ellmore, Nelson T. Nelson and Narayana A. Ponnada; Houston, TX Recent work has shown the utility of recording intracranial EEG (iEEG) with greater spatial resolution. We recently measured the impedances of several commercial microelectrodes and demonstrated that they will distort EEG signals if connected to commonly-used EEG amplifiers. In this study we demonstrate the clinical implications of this effect. Human iEEG data were digitally filtered to simulate the signal recorded by 2 macro- and 8 microelectrodes connected to a standard EEG amplifier. The filtered EEG data were read by three trained epileptologists, and high frequency oscillations (HFOs) detected with a well-known algorithm. Several electrodes underwent scanning electron microscopy (SEM). Macroelectrode recordings were unaltered, but microelectrodes attenuated low frequencies, which disturbed clinical interpretations of slowing, spikes, seizures, and HFOs. SEM demonstrated marked variability in exposed electrode surface area, as well as frequent sharp edges that could damage tissue. In addition, during experimental recordings the microelectrodes produced much greater noise, which led to large baseline fluctuations and false HFOs. While the attenuation can be mitigated by using high impedance amplifiers, the increased noise cannot. Great care must be taken when analyzing iEEG from microelectrodes. Study supported by: NIH K08NS069783 The paramagnetic nature of deoxyhemoglobin compared to oxyhemoglobin generates the differential MRI signal that forms the basis of classical BOLD fMRI. Artificially increasing arterial oxygen content (e.g. inhalation of 100% O2) directly boosts BOLD signal, and potentially provides metabolic contrast for diagnosing dysfunctional cortex. The latter hypothesis was confirmed in eight right-handed adult normal volunteers and ten right-handed patients with temporal lobe epilepsy who underwent echo-planar MR imaging under phasic hyperoxia. Hyperoxia-associated BOLD deflections from the temporal lobe revealed a significant group difference between normals and epilepsy patients, with seven patients exhibiting large deviations from normalcy that diagnosed and lateralized their disease. Two such patients were nonlesional on conventional high-field structural MRI. In a separate set of experiments, eight normal subjects were scanned while performing a finger-tapping motor task under hyperoxia and normal conditions. Increased task-related activation was seen in six subjects over the motor areas during hyperoxia compared to normoxia. Oxygen-enhanced MRI appears to be a novel and potentially valuable imaging tool in the diagnosis and localization of focal epilepsy, and may 93 ID: guganp I Black Lining: [ON] I Time: 09:25 I Path: N:/3b2/ANA#/Vol00000/120255/APPFile/JW-ANA#120255 J_ID: ZAY Customer A_ID: BKLT2012_Abstracts Cadmus Art: ANA12 Date: 18-September-12 Stage: Page: 94 M1303. Rapid High Volume CSF Loss вЂ“ A New Cause of Coma Minjee Kim, Rose Du and Sherry H.-Y. Chou; Boston, MA Neurology Critical Care M1301. Fatal Hyperammonemic Brain Injury from Valproic Acid Exposure Danny Bega, Henrikas Vaitkevicius, Torrey Boland, Rebecca Folkerth, Michael Murray, Katia Meirelles and Sherry Chou; Boston, MA Background: CSF loss can occur with dural tear. We report a case of coma secondary to rapid high volume CSF loss following craniotomy. Case: A 74 year-old man had sudden >200cc of serosanguinous fluid output from subgaleal drain after uncomplicated aneurysm clipping, likely from CSF leak. CT scan showed bilateral thalami and basal ganglia hypodensity, subarachnoid and intraventricular hemorrhage, and cerebral edema. He developed obtundation, a generalized seizure and PEA arrest despite drain removal. He was successfully resuscitated. His ICP was <5 mmH2O. 2 month later, patient is able to follow simple commands and ambulated with assistance. Discussion: We add to a literature linking rapid high volume CSF loss to coma with bilateral thalamic infarction. Unlike prior reports where the dural tear is below the foramen magnum, our case demonstrates that supratentorial dural tear may produce the same clinical features. One characteristic feature is the low ICP despite CT findings of cerebral edema. We postulate that the basal ganglia and thalami may be particularly prone to infarction because sudden large change in CSF pressure may tether and compress small penetrating arteries that supply these structures. Study supported by: No disclosures Background: Hyperammonemia is known to cause neuronal injury, and can result from valproic acid (VPA) exposure. Prompt reduction of elevated ammonia levels may prevent permanent neurological injury. We report a case of fatal hyperammonemic brain injury in a woman exposed to valproic acid. Case: A 38 year-old woman with schizoaffective disorder and recent increase in VPA dosage presented with somnolence and confusion and rapidly progressed to obtundation. Brain MRI showed diffuse bilateral restricted diffusion in nearly the entire cerebral cortex. She had normal liver function tests but serum ammonia level was severely elevated at 288 umol/L. Genetic testing showed no mutation in urea cycle enzymes. Despite successful elimination of ammonia with CVVH she developed fatal cerebral edema. Conclusion: Cerebral edema secondary to hyperammonemia is potentially reversible if recognized early. Ammonia excretion can be facilitated by initiation of CVVH and administration of scavenging agents (sodium phenylacetate and sodium benzoate). Severe hyperammonemia can result from valproic acid exposure even in the absence of hepatotoxicity or inborn errors of metabolism. It is important to check serum ammonia in any patient with encephalopathy who has had recent VPA exposure. Study supported by: No conflicts of interest or disclosures to make. M1304. Serum Sodium Values and Their Association with Adverse Outcomes in Moderate-Severe Traumatic Brain Injury (TBI) Lucia Rivera-Lara, Raphael Carandang, Wiley Hall, Cynthia Ouillette, Frederick A. Anderson, Robert J. Goldberg and Susanne Muehlschlegel; Worcester, MA M1302. A Population-Based Study of Aetiology and Outcome in Acute Neuromuscular Respiratory Failure Aisling S. Carr, Anne I. Hoeritzaur, Rachel Kee, Michael Kinney, Aoibhean Hutchinson and Gavin V. McDonnell; Belfast, Northern Ireland, United Kingdom Hypernatremia in neurocritically ill patients has been associated with worse neurological outcomes. There may, however, be a treatment effect from osmotherapy combating herniation and hyponatremia, which in turn may exacerbate brain edema, resulting in iatrogenic sodium repletion. In moderate-severe TBI, serum sodium (sNa) disturbances are common, but their impact on patient outcomes is unknown. In a prospective cohort study of 144 consecutive moderate-severe TBI patients admitted to a Level I trauma center over the period 11/2009вЂ“11/ 2011, we examined the association of mean, nadir, and peak sNa and hospital discharge neurological outcome (Glasgow Outcome Scale [GOS]). The mean age of this cohort was 51 years, 70% were men, and the median GCS and injury severity scores were 5 and 32, respectively. Using ordinal regression analysis, controlling for admission variables, length of ICU stay, severity of injury, presence of brain edema on head CT, administered hypertonic saline and mannitol, higher mean (p<0.001), higher peak (p Вј 0.01), and higher nadir (p<0.001) sNa values were significantly associated with worse outcome. Our findings suggest that higher sNa values are associated with worse neurological outcome, independent of treatment effect by osmotherapy. Study supported by: Muehlschlegel: American Heart Association AHA 09SDG2030022 Worcester Research Foundation Faculty Scholar Award, University of Masschusetts Medical School Goldberg: NIH/NHLBI 5 R01HL077248-05, 5 R01HL070283-07, 2R01HL035434-26, 5 R37 HL6987409 Background: Acute neuromuscular respiratory failure (NMRF) is a life-threatening feature of various neurological conditions. Population-based data on the frequency, outcome and aetiological spectrum is lacking. Methods: Regional ICU databases were searched for patients admitted with acute NMRF from 1/1/2000-31/12/ 2010. Demographics, diagnosis, length of stay, follow up and outcome (mRS) were recorded. A comparison dataset of all non-NMRF Neurology patients admitted to ICU was obtained. Results: 55 acute NMRF patients were identified; age: 17-88 (median: 63 years), M:F ratio 1:1.5. IR: 2.8 (0.8, 4.8) cases per million person-years; MR: 0.3 (0, 2.2) deaths per million person-years. Final diagnosis was inflammatory neuropathy (36 cases), myasthenia gravis (10), rhabdomyolysis (1) and motor neuron disease (5). 3 cases were undiagnosed. Follow up ranged from 0-7 years (median: 500.5 days); long term mRS: 1 (range 0-6). NMRF patients were older (p<0.0001), had longer ICU stay (p:0.02) but significantly better outcome (p<0.0001) than 93 non-NMRF neurology patients requiring ICU admission whose RR of long term dependence: 2.0 (1.5, 2.7) and RR death in hospital: 1.1 (1.0, 1.3) was higher. Conclusion: This work provides the first populationbased data on acute NMRF and highlights the potential for favourable outcomes. Study supported by: Nothing to declare 94 ID: guganp I Black Lining: [ON] I Time: 09:25 I Path: N:/3b2/ANA#/Vol00000/120255/APPFile/JW-ANA#120255 J_ID: ZAY Customer A_ID: BKLT2012_Abstracts Cadmus Art: ANA12 Date: 18-September-12 M1305. Impact of Medical and Neurological ICU Complications on Moderate-Severe Traumatic Brain Injury (TBI) Susanne Muehlschlegel, Raphael Carandang, Wiley Hall, Fred A. Anderson and Robert J. Goldberg; Worcester, MA Stage: Page: 95 American Heart Association AHA 09SDG2030022 Worcester Research Foundation Faculty Scholar Award, University of Masschusetts Medical School Goldberg: NIH/NHLBI 5 R01HL077248-05, 5 R01HL070283-07, 2R01HL035434-26, 5 R37 HL6987409 Certain admission characteristics are known predictors of adverse outcomes in patients with moderate-severe TBI, but explain only 1/3 of outcome variability. Intensive care unit (ICU) complications occur frequently in this population, but their impact on patient outcomes remains poorly defined. In a prospective cohort study of 170 consecutive moderate-severe TBI patients admitted to a Level I trauma center over the period 11/2009вЂ“2/2012, we examined the association of ICU complications and 3-month outcome (Glasgow Outcome Scale [GOS]). The mean age was 51 years, 72% were men, and the median GCS and injury severity scores were 4 and 29, respectively. Using multiple logistic regression analysis, hypotension requiring vasopressors (HRV) was the strongest predictor of poor outcome (GOS 1-3 [OR 2.8; 95% CI 1-7.5]) among medical complications. After combining medical with neurological ICU complications, brain herniation (OR 5.8; 95% CI 1.1-30.2) and intracranial rebleeding (OR 2.9; 95% CI 1-8.4) were the strongest predictors of poor outcome, while HRV approached significance (OR 2.4; 95% CI 0.9-6.4). We identified important potentially modifiable predictors of adverse outcomes after moderate-severe TBI. Confirmation of our findings in a larger cohort is warranted. Study supported by: Muehlschlegel: American Heart Association AHA 09SDG2030022 Worcester Research Foundation Faculty Scholar Award, University of Masschusetts Medical School Goldberg: NIH/NHLBI 5 R01HL077248-05, 5 R01HL070283-07, 2R01HL035434-26, 5 R37 HL6987409 Neuromuscular Disease M1401. Novel Choline Kinase Beta Gene Mutation Associated with Exercise Induced Myalgia and Mitochondrial Changes Hena Ahmad, Aleksander Radunovic, Angharad Davis, Sylvia Marino, Heinz Jungbluth, Chieko Aoyama, Steve Abbs and David Moore; London, United Kingdom and Tochigi, Japan Introduction: Choline kinase is a vital part of the phosphatidylcholine (PC) pathway. Impaired phosphatidylcholine homeostasis is caused by homozygous and compound heterozygous mutations in genes encoding CHKb which cause congenital muscular dystrophy and mitochondrial structural abnormalities. We present a case with a novel mutation in CHKb gene supporting this link. Case description: A 16-year old Caucasian male, with mild ichthyosis presented with a seven year history of exercise induced myalgia. Examination was normal. CK varied between 202-2070. Muscle biopsy showed prominent subsarcolemmal mitochondrial staining with mildly increased lipid content. Electron microscopy confirmed peripheral abundant, large mitochondria. Genetic testing revealed a deletion of the steroid sulphatase gene and a novel apparent homozygous c.-74_-55del20 variant detected in 50 untranslated region of CHKb gene showing conservation and likely functionally significant. Phosphorus quantification after thin layer chromatography showed reduced Phosphatidylcholine/ Phosphoethanolamine ratio: 50.6/28.8. Discussion: This is the first case demonstrating this novel mutation in CHKB with functionally decreased PC content, increased CK, mitochondrial changes and exercise induced myalgia. Recognition of this association is important in selecting appropriate tests to reach a diagnosis. References: Mitsuhashi S American Journal of Human Genetics 2011 Study supported by: N/A M1306. Incidence Rates of ICU Complications in Moderate-Severe Traumatic Brain Injury (TBI) Susanne Muehlschlegel, Raphael Carandang, Cynthia Ouillette, Wiley Hall and Robert J. Goldberg; Worcester, MA Retrospective studies suggest that non-neurologic organ failure may contribute to 2/3 of all deaths after TBI, but the actual incidence rates of specific intensive care unit (ICU) complications in moderate-severe TBI are not known. In a prospective cohort study of consecutive TBI patients from a single Level I trauma center over the period 11/2009 вЂ“ 2/ 2012, we identified the ten most common medical complications after ICU admission according to strict pre-specified criteria in 170 moderate-severe TBI patients. The mean age of the study sample was 51 years, 72% were men, and the median GCS and injury severity scores were 4 and 29, respectively. Incidence rates of the ten most common medical complications in the ICU were: hyperglycemia (75%), fever (62%), systemic inflammatory response syndrome (38%), cardiac complications (36%), hypotension requiring vasopressors (35%), pneumonia (any type [34%]); sepsis (33%), anemia requiring transfusion (31%), other pulmonary complications (ARDS, pulmonary edema [26%]), and hyponatremia (sodium 134mEq/L; [23%]). Medical complications in moderate-severe TBI are very common, and their association with important patient outcomes should be further investigated. Specific medical complications may pose attractive modifiable treatment targets to improve the outcome of TBI patients. Study supported by: Muehlschlegel: M1402. Might Sodium Phenylbutyrate (PBA) Be a Drug for Sporadic Inclusion-Body Myositis (s-IBM)? Anna Nogalska, Carla DвЂ™Agostino, W. King Engel and Valerie Askanas; Los Angeles, CA s-IBM is a common aging-associated degenerative muscle disease causing severe disability, and it has no enduring treatment. Characteristic are vacuolated muscle fibers having accumulations of multi-protein aggregates containing amyloid-b42 (Ab42) and its cytotoxic oligomers. Demonstrated defective protein-degradation through impaired proteasomal and lysosomal pathways contributes importantly to the muscle-fiber degeneration. PBA, an FDA-approved orally-active chemical chaperone, allegedly mimics the function of intracellular molecular chaperones in preventing protein aggregation and oligomerization. Our experimental IBM model, based on exposing cultured human muscle fibers to chloroquine, an inhibitor of lysosomal activity, expresses abnormalities similar to those of s-IBM muscle viz.: a) prominent vacuolization; b) increased Ab42 and its oligomers; c) decreased activity of the two 95 ID: guganp I Black Lining: [ON] I Time: 09:25 I Path: N:/3b2/ANA#/Vol00000/120255/APPFile/JW-ANA#120255 J_ID: ZAY Customer A_ID: BKLT2012_Abstracts Cadmus Art: ANA12 Date: 18-September-12 major lysosomal proteases, cathepsin D and B; d) increased autophagosomal marker LC3-II; and e) increased NBR1, a marker of impaired autophagy. Treatment of this model with PBA: a) virtually eliminated vacuolization; b) increased activities of both cathepsin D (1.5-fold, p<0.01) and B (2.3-fold, p<0.001); c) decreased LC3-II (90%, p<0.001); d) decreased NBR1 (45%, p<0.05); e) substantially decreased Ab42 (45%, p<0.05), and Ab oligomerization. Those data provide a rationale for considering therapeutic trials of s-IBM patients with PBA. Study supported by: MDA and the Helen Lewis Research Fund. Stage: Page: 96 Results: Of the fourteen current ALS genetic syndromes, nine are consistent with classical adult-onset ALS. A further two syndromes currently not classified as genetic ALS could be included in a new system. Conclusion: The current classification system is derived from genetic studies which are driven by historically available genetic techniques rather than the clinical syndromes seen in ALS clinics. A rational redesign would benefit clinicians, patients and researchers. Study supported by: European CommunityвЂ™s Health Seventh Framework Programme 259867; Motor Neurone Disease Association; the NIHR Specialist Biomedical Research Centre for Mental Health at the South London and Maudsley NHS Foundation Trust (SLaM) and the Institute of Psychiatry, KingвЂ™s College London. AAC is a consultant for two pharmaceutical companies. M1403. Chaperone-Mediated Autophagy (CMA) in Sporadic Inclusion-Body Myositis (s-IBM) Muscle Fibers Mafalda Cacciottolo, Anna Nogalska, Carla DвЂ™Agostino, W. King Engel and Valerie Askanas; Los Angeles, CA M1405. Putative Mechanisms Involved in Primary Hyperoxaluria Type 1 Polyneuropathy Sarah E. Berini, JaNean K. Engelstad, Jennifer A. Tracy, Dawn S. Milliner, P. James B. Dyck and Peter J. Dyck; Rochester, MN Muscle fibers of s-IBM, a common muscle disease associated with aging, have ubiquitinated aggregates containing multiple proteins, including amyloid-b, phosphorylated tau and a-synuclein (a-syn). As we previously demonstrated in sIBM, these protein accumulations were associated with impairment of both the proteasomal and lysosomal degradation. CMA is a form of lysosomal degradation involving the lysosome receptor Lamp2a, which selectively targets proteins containing the KFERQ motif, such as a-syn. Proteins to be degraded are first recognized by Hsc70, which subsequently binds to Lamp2a and facilitates protein transfer to the lysosome. CMA has not been previously studied in either normal or disease human muscle. Compared to age-matched controls (n Вј 8), in s-IBM (n Вј 9) muscle fibers Lamp2a and Hsc70 were: a) by immunoblots, increased (6-fold p<0.005,and 2-fold p<0.05, respectively); b) by immunocytochemistry, accumulated in the form of aggregates which co-localized with a-syn; and c) by immunoprecipitation physically associated with each other and with a-syn. Lamp2a and Hsc70 mRNAs were increased 4-fold p<0.005 and 1.9-fold p<0.05, respectively). This first demonstration that CMA components are upregulated in s-IBM further illustrates a perturbation of the complicated cascade of protein degradation in this complex disease. Study supported by: Partially by MDA and the USC NMC Research Fund. MC is Ruth Ziegler Research Fellow. Two cases of primary hyperoxaluria type 1 were investigated for the underlying cause of their length-dependent sensorimotor polyneuropathy affecting both upper and lower limbs. The electrophysiologic features suggested prominent axonal degeneration and segmental demyelination. Diameter histograms of biopsied sural nerves showed moderate loss of fibers with a shift of the large diameter peak to smaller sizes. The index of dispersion showed slight variability in the density of fibers. Minimal inflammation was noted. Under polarizing light, bright cuboidal, hexagonal and starburst inclusions typical of calcium oxalate monohydrate crystals were seen. These inclusions were found in teased fiber preparations, paraffin and epoxy sections. Electron microscopy along the length of teased fibers is being performed to determine their ultrastructural location. The following mechanisms of fiber degeneration are being considered: The neuropathy is attributable to 1- direct toxic effects of calcium oxalate on nerve, 2- crystalline deposition in nerve and microvessels, 3- uremia. In conclusion, the crystals of primary hyperoxaluria type 1 polyneuropathy are distinctive and diagnostic. Their role in polyneuropathy remains unsettled; they might simply represent cellular sequestration of toxic material. The disease provides a biologic model for the study of peripheral neuropathy. Study supported by: No funding source M1404. Is the Familial Amyotrophic Lateral Sclerosis (ALS) Classification Fit for Purpose? Rubika Balendra and Ammar Al-Chalabi; London, United Kingdom Aim: To review the familial ALS genetic classification. M1406. Cachexia in Two Adults with Single Mitochondrial DNA Deletions Is Due to Dysphagia Sergiu C. Blumen, Ron Dabby, Yaron River, Esther LeshinskySilver and Itzhak Braverman; Hadera, Israel and Holon, Israel Background: The past twenty years have seen great advances in identifying familial ALS genes. A numbered classification system exists incorporating fourteen genes, but does not accurately reflect the ALS clinical syndrome as there are several anomalies. For example, genes for very slowly progressive motor syndromes, for juvenile onset, or for pure upper motor neuron syndromes are over-represented. On the other hand, genes known to be responsible for a significant proportion of ALS are listed as ALS-FTD (Frontotemporal Dementia) genes. We therefore propose an overhaul of the existing ALS genetic classification system. Methods: Clinical syndromes of genetic ALS were compared with criteria for classical adult-onset ALS. Genes known to cause ALS as a phenotype were reviewed for classification as ALS genes. Cachexia in mitochondrial diseases may be due to dysphagia, recurrent vomiting, intestinal pseudo-obstruction or combinations of the above. To elucidate its main cause, we followed, from the ages of 42 and 22, two sporadic cases of progressive external ophthalmoplegia (PEO) with life threatening weight loss. The symptoms started in the early teens and progressed insidiously together with dysphagia, dysphonia and proximal weakness. Electrophysiological studies confirmed severe myopathy and excluded polyneuropathy. Normal cognition, brain MRI, CSF, cardiologic evaluation and retinal appearence contributed to excluding the Kearns Sayre syndrome. Normal thymidine phosphorylase activity 96 ID: guganp I Black Lining: [ON] I Time: 09:25 I Path: N:/3b2/ANA#/Vol00000/120255/APPFile/JW-ANA#120255 J_ID: ZAY Customer A_ID: BKLT2012_Abstracts Cadmus Art: ANA12 Date: 18-September-12 excluded MNGIE syndrome. Muscle biopsies showed myopathy with many ragged red, COX negative and SDH positive fibers. Southern blot analysis of the mtDNA revealed single deletions of 3.5Kb and 7Kb respectively. Fiberoptic endoscopic evaluation of swallowing showed severe salivary pooling with aspirations and decreased pharyngeal food propulsion. With gastric feeding patientsвЂ™ weights increased from 24 to 42 kg. and from 31 to 39 kg in six months. Conclusions: 1. These patients had PEO due to sporadic, single, large, mitochondrial DNA deletions. 2. Dysphagia was the main cause of extreme cachexia and gastric feeding was life saving. Study supported by: nobody Stage: Page: 97 Methods: Labial articulation rates (words/minute/breath) were compared with swallowing rates (mL/minute/swallow/ breath). Results: Labial [pre-46.1648.8/post-60.2653.1:paired-ttest-p Вј 0.0003] articulation rates [normal-198.3655.2 words/min/breath] increased significantly. Swallowing rates [pre-97.66100.3/post-104.7690.9; paired-t-test-p Вј 0.02] increased significantly[normal-220646 mL/minute/swallow/ breath]. Rate improvements did not correlate with changes in ALSFRS-R, vtial capacity or other clinimetrics. Conclusion: Bulbar speech-articulation/swallowing rates improved over 2-9 months in ALS/PBA patients having abnormal speech-articulation rates [3-132 words/minute/ breath]. Treatment effect size for bulbar speech-articulation/ swallowing rates will permit sample-size determination to employ these outcomes for future controlled clinical trials of Nuedexta on bulbar function in ALS patients. Improved speech/swallowing seen in ALS/PBA patients on Nuedexta requires evaluation in bulbar ALS patients without PBA. Further studies are needed to assess the clinical importance and significance of these observations. Study supported by: Carolinas ALS Research Fund and Pinstripes Foundation of Carolinas Healthcare Foundation and Muscular Dystrophy Association - ALS Division Richard A Smith MD receives royalty payments from Avanir Pharmaceuticals and is a recipient of an ALS Association grant to study the effect of Nuedexta on bulbar function in ALS. Benjamin Rix Brooks MD was principal investigator and Elena Bravver MD was investigator on clinical trials leading to registration of dextromethorphan/quinidine for treatment of PBA. Other authors have no financial relationship with Avanir Pharmaceuticals. M1407. Slowly Progressing Familial ALS with Bulbar Onset Due to a Novel VCP Mutation Sergiu C. Blumen, Paloma Gonzales-Perez, Vivian E. Drory, Ron Dabby, Diane McKenna-Yasek and Robert H. Brown, Jr; Hadera, Israel; Worcester; Tel Aviv, Israel and Holon, Israel Mutations in the valosin containing protein (VCP) gene produce familial ALS as well as autosomal dominant inclusion body myopathy, frontotemporal dementia and Paget disease (IBMFPD). We studied a large Arab Israeli family in which patients from three generations fulfilled the El Escorial clinical and electrophysiological criteria for definite (N Вј 4) and probable (N Вј 3) ALS. All patients recalled nasal speech many years before formal diagnosis (at 30 to 48 years). At presentation most had hyperlordosis, rigid spine, proximal weakness with weddling gait and peculiar cervical and upper thoracic paraspinal muscle atrophy. EMG showed both neuropathic and myopathic features and CPK was moderatly elevated. Insidiously, weakness with upper and lower motor neuron features affected distal limbs too, and the definite patients became pseudobulbar. One patient died after 6 years and two required assisted ventilation at 9 years from presentation. By whole exome sequencing and VCP screening, a novel, R191G, mutation, co-segregating with the disease was identified. While myopathy belongs to the spectrum of IBMFPD, other features in this family are unusual; identification of new R191G carriers may indicate whether this phenotype is the rule or the exception for this genotype. Study supported by: friends M1409. Assessment of Clinical Disease Trajectory [CDT] in Amyotrophic Lateral Sclerosis [ALS] Patients by вЂ�вЂ�ALS DashboardвЂ™вЂ™ Containing Cognitive- Behavior (Depression-Pseudobulbar Affect (PBA)-BulbarRespiratory-Arm-Leg Domains вЂ“ Longitudinal Validation over Time and by El Escorial/Awaji Shima Criteria [EEC/ASC] Clinically-Definite [EECD/ASCD] Classification at Diagnosis Benjamin Rix Brooks, Mohammed S. Sanjak, Elena K. Bravver, William L. Bockenek, Urvi G. Desai, Scott S. Lindblom, Thomas J. Paccio, Nicole M. Williams, Mindy S. Nichols, Amber L. Ward, K. Amy Wright, Velma L. Langford, Michael P. Fischer, Kristy L. Walgren, Louise H. Frumkin, Priscilla C. Russo, Anne S. Blythe, Nicole P. Smith, Jessica N. Scrmina, Scott E. Holsten and Heather L. Oplinger; Charlotte, NC M1408. Bulbar Speech-Articulation/Swallowing Rate Changes Measured in Amyotrophic Lateral Sclerosis (ALS) Patients Treated with Dextromethorphan/ Quinidine(Nuedexta) for Pseudobulbar Affect (PBA) вЂ“ Determination of Treatment Effect Size for Future Clinical Trials Benjamin Rix Brooks, Elena Bravver, Urvi G. Desai, K. Amy Wright, Velma L. Langford, Nicole M. Williams, Mohammed S. Sanjak and Richard A. Smith; Charlotte, NC and La Jolla, CA Background: CDT is currently evaluated per-patient by ALSFRS-R without attention to cognitive and behavioral (depression/pseudobulbar-affect-PBA) domains which are not included in current staging algorithms. Objective: Assess CDT with вЂ�вЂ�ALS DashboardвЂ™вЂ™ cross-sectionally and longitudinally. Setting: Multidisciplinary ALS Clinic. Methods: ALS patients(199/263), categorized as EECD(90) or ASCD(109) were staged longitudinally according by ALS Dashboard criteria. Results: At diagnostic visit in EECD/ASCD ALS !stage3 cognitive [8.9%/13.8%] and respiratory dysfunction [7.8%/4.6%] was similar, but !stage-3 PBA [11.1%/2.8%; p Вј 0.04], depression [25.6%/10.0%; p Вј 0.007], bulbardysfunction [45.6%/13.8%; p Вј 0.0001], arm-dysfunction [35.6%/8.3%;p Вј 0.0001], leg-dysfunction [55.6%/33.9%; p Вј 0.004] were significantly increased in EECD-ALS. ALS Background: Dextromethorphan is a sigma-1 receptor-agonist and NMDA receptor-antagonist in the CNS. Sigma-1 receptors are highest in cranial motor nerve nuclei followed by subcortical and cortical neurons. 57 ALS/PBA patients treated with Nuedexta showed PBA improvement. One patient, who had to interrupt treatment reported decreased swallowing which improved on resumption of Nuedexta. Objective: Measure treatment effect size of quantitative bulbar outcome measurements from pre-Nuedexta to 2-9 months post-Nuedexta in 18 ALS/PBA patients. 97 ID: guganp I Black Lining: [ON] I Time: 09:25 I Path: N:/3b2/ANA#/Vol00000/120255/APPFile/JW-ANA#120255 J_ID: ZAY Customer A_ID: BKLT2012_Abstracts Cadmus Art: ANA12 Date: 18-September-12 Dashboard identifies earlier development of Affect-BulbarArm-Leg, but not Cognitive-Respiratory !stage-3 disease in EECD- than ASCD-ALS patients with subsequent faster progression in EECD-ALS patients. Riluzole was associated with lower proportion of developing cognitive !stage-3 disease. Conclusion: ALS Dashboard is a new tool for analyzing disease severity within a single patient and across different patients. ALS severity in some, but not all domains, segregates differently with a higher proportion of !stage-3 legarm-bulbar disease in EECD than ASCD ALS. ALS Dashboard provides description of ALS changes and CDT associated with specific FVC % predicted cutoffs. Study supported by: Carolinas ALS Research Fund and Pinstripes Foundation of Carolinas Healthcare Foundation and Muscular Dystrophy Association - ALS Division Stage: Page: 98 neurology providers and the drivers of these costs are unknown. Design/Methods: The 1996-2007 Health and Retirement Study (HRS) - Medicare Claims linked database was used to identify individuals with an incident diagnosis of neuropathy using ICD-9 codes. We examined test utilization by provider type and expenditures performed 6 months before and after the incident neuropathy diagnosis. Results: Neuropathy patients with a neurology provider are more likely to receive electrodiagnostic testing and/or a MRIs of the neuroaxis compared to those with other provider types (p<0.001). These tests were also more likely completed after seeing a neurologist (p<0.001). Significant expenditures are related to electrodiagnostic testing ($475 per patient receiving test) and MRIs of the neuroaxis ($370 per patient receiving test). Conclusions: Neuropathy patients with a neurology provider are more likely to have electrodiagnostic tests and MRIs, most of which are ordered after a visit with a neurologist. Future studies are needed to define the role of these tests, and whether they are cost-effective for the evaluation of neuropathy. Study supported by: The first author is supported by an ADA Junior Faculty award M1410. Peripheral Nerve Function Following Treatment with Tanezumab Mark T. Brown, William J. Litchy, David N. Herrmann, Mark Goldstein, Aimee M. Burr, Michael D. Smith, Christine R. West, Kenneth M. Verburg and Peter J. Dyck; Groton, CT; Rochester, MN; Rochester, NY and Atlantis, FL The novel analgesic mechanism of action of tanezumab, an NGF inhibitor, and reported cutaneous sensory symptoms raised safety concerns regarding nerve function. This randomized, double-blind, placebo-controlled study of 219 neurologically normal patients with knee or hip osteoarthritis investigated whether tanezumab (3 administrations of 5 or 10 mg IVq8w for 24 weeks) caused clinically significant changes from baseline (cfBL) relative to placebo in a composite measure of nerve function (R5NCГѕHRdb) or in intraepidermal nerve fiber density (IENFD). The R5NCГѕHRdb score included nerve conduction (NC) tests of peroneal, tibial and sural nerves; and heart rate deep breathing (HRdb). Skin biopsy assessed IENFD. Measurements were taken at baseline and Week 24 or Early Termination. Least squares mean (standard error) cfBL in R5NCГѕHRdb scores at Week 24 were -0.11 (0.29) for placebo, and 0.17 (0.30) and -0.06 (0.30) for tanezumab 5 and 10 mg, respectively. R5NCГѕHRdb and IENFD cfBL were not significantly different for either tanezumab-versusplacebo comparison. The magnitude of cfBL in R5NCГѕHRdb and IENF density was small, unrelated to dose, and treatment differences versus placebo were not statistically significant. Evidence linking tanezumab to detrimental (neurotoxic) effects on the peripheral or autonomic nervous system was not found. Study supported by: Pfizer, Inc. Mark T Brown, Michael D Smith, Christine R West and Kenneth M Verburg are employees of Pfizer and hold stock & options in Pfizer. Aimee Burr is a paid contractor to Pfizer and holds stocks in Pfizer. David N Herrmann provided professional consulting to Inflexion Point LLC within the past year. Peter J Dyck is an Assoc. ed. of Diabetes. William Litchy and Mark Goldstein have no conflicts to disclose. M1412. Clinical, Neurophysiological and Histological Differentiators of Congenital Myasthenic Syndromes from the General Neuromuscular Disease Cohort Aisling S. Carr, Estelle Healy, Brian Herron, Stephen Haffey, Kiang Pang, Jacqueline Palace, David Beeson and John McConville; Belfast, Northern Ireland, United Kingdom and Oxford, United Kingdom Background: Syndrome-specific case series provide best current information on CMS but do not describe diagnosis and identification from within the general neuromuscular population. Methods: A population-based study of CMS in Northern Ireland (population 1.7 million) between 1/1/2000-31/12/2010. Results: IR:0.6 (0.2, 1.0) cases per million personyears;PR: 9.5 (5.1, 13.9) cases per million; MR:0.1 (0.01, 0.71) deaths per million person-years. 17 definite and 2 possible cases were identified, M:F ratio 2.2: 1, onset: 0-63 years. Dok-7 mutations were most common (7/19), followed by slow channel (5), AChR deficiency (2), fast channel (2) and COLQ (2) mutations. Phenotype was variable: myasthenialike (3); PEO-like (2); limb-girdle syndrome (4); congenital myopathy-like (6); distal upper limb syndrome (4). Lid twitch in ptosis, micro-saccades in ophthalmoplegia and Dok-7 waddling gait were useful clinical signs. RNS and SFEMG abnormalities were seen in 6/10 and 6/6 tested. Muscle histology showed type II fibre predominance in 8/9 cases. Prevalent patients responded to treatment. Conclusion: Here we provide estimates for frequency of CMS in the NI population and highlight useful clinical and paraclinical clues in the identification of this treatable group of conditions. Study supported by: Neuromuscular research fellow Ulster Hospital Dundonal (AS Carr): August 2007-July 2008 Neuromuscular research fellow Royal Victoria Hospital Belfast (AS Carr): August 2008-Jul 2009 M1411. Evaluation of Neuropathy: Tests and Expenditures by Provider Type Brian C. Callaghan, Ann Rodgers, Kevin Kerber, Ken Langa and Eva L. Feldman; Ann Arbor, MI M1413. High Fat Diet Induces Impaired Glucose Tolerance and Painful Peripheral Neuropathy Hsinlin T. Cheng, Jacqueline R. Dauch, John M. Hayes, Sangsu Oh and Eva L. Feldman; Ann Arbor, MI Background: Test utilization and expenditures are significantly higher around the time of diagnosis in those with neuropathy compared with matched controls. The effect of Impaired glucose tolerance (IGT) is a common condition that causes idiopathic neuropathy and pain. Current 98 ID: guganp I Black Lining: [ON] I Time: 09:25 I Path: N:/3b2/ANA#/Vol00000/120255/APPFile/JW-ANA#120255 J_ID: ZAY Customer A_ID: BKLT2012_Abstracts Cadmus Art: ANA12 Date: 18-September-12 understanding for IGT-induced neuropathic pain is very limited. In order to study IGT-induced neuropathy, we treated male C57BL/6 mice with high fat (HF, 45% fat calorie) and control chow (CC, 13% fat calorie) starting at 5 wk of age. IGT was determined by a 2 hour-glucose tolerance test. Mechanical and thermal thresholds, as well as nerve conduction velocities, were measured periodically. By 36 wk of age, HF mice developed obesity, hyperlipidemia and hyperinsulinemia. However, the fasting glucose and glycosylated hemoglobin levels remained within control ranges. We detected IGT in HF mice starting at 11 wk of age. In parallel, mechanical allodynia and thermal hyperalgesia were detected at 12 wk in HF mice. Impaired sciatic motor and sural sensory nerve conduction velocities along with significantly higher levels of oxidative stress in peripheral nerves were detected in HF mice at 36 wk, indicating the presence of peripheral neuropathy. Our findings suggested that HF mice could serve as an animal model for studying painful neuropathy from IGT. Study supported by: NIH Stage: Page: 99 a number of ALS patient derived cell lines, including fibroblasts, induced-pluripotent stem cells (iPS cells), and iPSdifferentiated astrocytes and neurons. We have identified unique expression and splicing patterns in cells derived from patients carrying the C9orf72 repeat expansion. We have further validated these data by comparing autopsy tissue and CSF from multiple human ALS patients carrying the C9orf72 expansion and control patients. Therapeutic strategies using antisense oligonucleoties (ASO) and RNA knockdown (siRNA) are under development for other neuromuscular disorders caused by repeat expansions (e.g., DM1/2, FXTAS). Using these techniques, we were able to knockdown C9orf72 expression in the patient-derived C9orf72 cells without obvious cytotoxicity. Furthermore, transcriptome profiling yielded a number of candidate biomarkers, whose aberrant expression in the mutant C9orf72 cells can be rescued with ASO/siRNA treatment. Study supported by: National Institute of Neurological Disorders and Stroke (NINDS), The Robert Packard Center for ALS Research at Johns Hopkins, P2ALS, Johns Hopkins University M1414. Iatrogenic Mitochondrial Disease Emerging Years after Stopping Anti-HIV Treatment: The Tip of the Iceberg in 2012? Brendan Payne, David A. Price, David Samuels, Ian Wilson, Kris Gardner, Michael Trenell, Mauro Santibanez-Koref and Patrick F. Chinnery**; Newcastle upon Tyne, United Kingdom and Nashville M1416. Withdrawn. M1417. Often-Treatable вЂ�вЂ�Multi-MicrocrampsвЂ™вЂ™ (MMCs) Are Common and Frequently Overlooked Manifestations of Peripheral Neuropathy W. King Engel; Los Angeles, CA We still see untreated patients with aching, painful muscles, 6 visible writhing of small bundles of muscle fibers. They are often called вЂ�вЂ�fibromyalgiaвЂ™вЂ™, etymologically and pathogenically wrong, sometimes вЂ�вЂ�neuromyotoniaвЂ™вЂ™, confused mechanistically with myogenic myotonias; or вЂ�вЂ�restless legsвЂ™вЂ™, a non-mechanistic complaint. MMCs are neurogenic, seemingly generated by frequent spontaneous discharges from any part of numerous lower motor neurons (LMNs). Muscle-biopsy reveals small angular fibers and type-grouping, proving neuropathic pathogenesis. Hypothetically, activation limited to only a few of a motor-unitвЂ™s total fibers is due to: a) the actual discharges arising in only a few distal twigs of the LMNs, and/or b) pathologic relative-inactivability of other distal twigs. The latter can produce EMG-detected fractionated motor-units manifested as BSAPs (Brief Small Abundant Potentials), often deemed a вЂ�вЂ�myopathic patternвЂ™вЂ™, incorrectly in this case. Increased daytime activity can increase MMCs that evening and next day Stretching MMC-muscles gives temporary relief. MMCs can occur in: a setting of minimal genetic Гѕ/- acquired neuropathy, often with a sensory component; 6 CSF protein increase - e.g. diabetoid-2 dysimmune neuropathy treatable with IVIG. Most gratifying symptomatic treatment is prn clonazepam, e.g. 0.5-1 mg hs 6 0.5mg 1-2x in daytime. Study supported by: Neuromuscular Center Research Fund There is emerging evidence that patients with treated HIV infection develop unexplained neuromuscular and neurodegenerative disease, but the reasons for this are not known. Here we show that HIV patients treated with nucleotide reverse transcriptase inhibitors (NRTIs) develop an acquired defect of mitochondrial function in mid-life, detectable ten years after stopping these drugs. Up to 9.8% of skeletal muscle fibers had a cytochrome c oxidase defect caused by high levels of mitochondrial DNA (mtDNA) mutations resembling those found in healthy ageing and neurodegenerative diseases, but at a much earlier age. Ultra-deep nextgeneration sequencing indicated that the increase in somatic mutations was not due to increased mutagenesis. In vitro experiments treating mtDNA deletion cell lines with NRTIs showed that the drugs lead to the preferential amplification of pre-existing mtDNA mutations through clonal expansion, accelerated by the mtDNA depletion during NRTI therapy. This leads to reduced basal ATP levels in vivo shown by 31P-magnetic resonance spectroscopy. These observations support the role of somatic mtDNA mutations in the aging and neurodegeneration, and raise the specter of progressive iatrogenic mitochondrial neurological disease emerging over the next decade. Study supported by: The Wellcome Trust. The Medical Research Council, UK. M1418. Q-Fever IgM-Positivity in 3/5 sALS Patients: Any Pathogenic Significance Regarding the XYZ Hypothesis? W. King Engel; Los Angeles, CA M1415. Development of C9orf72 ALS Biomarkers and Therapeutics Christopher J. Donnelly, Lyle W. Ostrow, Ying Li, Svetlana Vidensky, Pingwu Zhang, Alan E. Renton, Rita G. Sattler, Bryan J. Traynor and Jeffery D. Rothstein; Baltimore, MD and Bethesda, MD Coxiella burnetii infection causes Q-Fever. Neurologic complications are uncommon, e.g. headache, meningoencephalitis during acute infection. We report 3/5 afebrile sALS men, ages 41,43,54, showing IgM-Phase-II 6 IgM-Phase-I QFever antibodies (IgM antibodies generally indicate current/ recent infection). One was positive 4 times. None had live ungulate exposure. Two treated for 2 & 6 months with doxycycline 100 mg bid Гѕ rifampin 300 mg/d failed to A hexanucleotide вЂ�вЂ�GGGGCCвЂ™вЂ™ repeat expansion in the noncoding region of the C9orf72 gene has recently been identified in greater than 30% of familial and 4-10% of sporadic ALS cases. Interestingly, the function of the C9orf72 protein is unknown. In order to begin investigating the pathogenicity of this repeat expansion, we have generated and profiled 99 ID: guganp I Black Lining: [ON] I Time: 09:25 I Path: N:/3b2/ANA#/Vol00000/120255/APPFile/JW-ANA#120255 J_ID: ZAY Customer A_ID: BKLT2012_Abstracts Cadmus Art: ANA12 Date: 18-September-12 improve. Controls: 2/64 afebrile CIDP patients were IgMpos, 41 other neuromuscular patients were IgM-neg -- 17/ 103 of those patients were Q-fever IgGpos-IgMneg, that being of uncertain significance. Our previously-reported XYZ Hypothesis of ALS pathogenesis is: 1- remote Cells-X (? in gut, liver, elsewhere) are infected with a virus, bacterium, etc); 2- Cells-X either a) fail (due to induced autoimmunity or another mechanism) to produce their circulating Beneficial Factor-Yb for Cells-Z (Motor-Neurons, MNs), or b) fail to prevent a selectively Toxic Factor-Yt from circulating; 3Yb or Yt causes, directly or indirectly, a gradually non-recoverable failure of Cells-Z (MNs). Identifying Cells-X and modulating Factor-Y might allow rejuvination of non-functioning but still-alive MNs, and some clinical improvement. A possible role of Q-fever in sALS merits exploration. Study supported by: Neuromuscular Center Research Fund Stage: Page: 100 mitochondrial and nuclear DNA damage; 2) Mitochondrial and nuclear DNA damages are significantly higher in DM1 skeletal muscles; 3) Mutant CUG-RNA stimulates phosphorylation of Ataxia Telangiectasia-Mutated (ATM) kinase, AMP-activated kinase (AMPK) and cAMP-regulated transcriptional co-activator TORC2; 4) Phosphorylation of TORC2 results in its nuclear exclusion, reduced occupancy of the CREB-TORC2 in the PGC-1a promoter and suppression of PGC-1a transcription. These results suggest that aberrantly activated ATM!AMPK!TORC2 signaling plays an important role in suppressing PGC-1a expression in DM1. Study supported by: John Seally Fundation M1421. A Common Link between Three Sporadic Amyotrophic Lateral Sclerosis Cases in Annapolis, MD Nicholas C. Field, Sandra Banack, Tracie A. Caller, James Metcalf, Paul A. Cox and Elijah W. Stommel; Lebanon, NH and Jackson, WY M1419. Disruption of Intracellular Redox Homeostasis by Mutant CUG-RNA in Myotonic Dystrophy Type 1 (DM1) Xiang Fang, Rui Gao, Arpita Chatterjee, Tapas K. Hazra, Robert Glen Smith and Partha S. Sarkar; Galveston, TX The majority of amyotrophic lateral sclerosis (ALS) cases occur sporadically, and spatial clustering of ALS has been described. A number of environmental triggers have been implicated, including beta-methylamino-L-alanine (BMAA), a cyanobacteria-produced neurotoxin linked to ALS on Guam. We report a cohort of three ALS patients diagnosed within 8 years of each other, who lived for a minimum of 10 years on the same street in a suburb of Annapolis, Maryland, USA. After confirming diagnosis, a questionnaire was completed by a surviving family member of each patient, ascertaining lifelong dwelling history, exposure history and social history. One common link identified was the regular consumption of fresh Chesapeake Bay blue crabs. Cyanobacteria blooms have been present in the Chesapeake Bay for decades. Chesapeake Bay crabs from the same fish market where the three patients regularly bought their crabmeat were collected and tested for BMAA. Two out of the three crabs tested were positive for BMAA. The regular consumption of blue crab contaminated with BMAA may be a common risk factor for sporadic ALS in all three patients. Other factors may have also contributed to disease development. Study supported by: Private donation to the ALS Center at DHMC DM1 is an autosomal dominant neuromuscular disease resulting from the massive expansion of CTG repeats in the 30 untranslated region of DMPK gene. DM1 patients develop a complex array of degenerative phenotypes which greatly resemble premature aging symptoms. However, although elevated oxidative stress has been implicated in the pathogenic mechanism of several degenerative dystrophic muscle diseases, including DM1, how expanded CTG repeats stimulate oxidative stress remains unknown. In this study, we investigated the mechanism by which expanded CTG repeats interrupt the intracellular redox homeostasis in DM1 in vitro. We found that myoblasts stably expressing 500 CUG repeats showed $45% higher intracellular reactive oxygen species (ROS) levels than control myoblasts expressing 25 CUG repeats. Transient expression of CUG repeats also increased intracellular ROS levels, and these effects were partially inhibited by DPI, a NADPH oxidase inhibitor. Western blot analyses revealed that expression of NADPH oxidase subunit p67phox was markedly increased in myoblasts expressing 500 CUG repeats, while expression of NADPH oxidase subunits gp91phox, p47phox, and Rac1 remained unaltered. These results indicate that p67phox mediated ROS generation may play an important selective role in DM1 pathogenesis. Study supported by: John Sealy Fundation M1422. Infections in Myasthenia Gravis (MG) Raghav Govindarajan, Dennys Reyes, John Morren, Evelio Velis and Nestor Galvez; Weston, FL and Miami Objective: MG patients are on long-term immunosuppressants,increasing their chance to infectious complications/ MG exacerbation. Method: Data of MG patients with at least 1y follow-up was collected (2001 - 2011). Infections were divided: general infectious processes (GIP) (self reported during visits, an infection for which patients seek medical attention, or infections causing an exacerbation); opportunistic (OI) (infection attributed to immunosuppressant); catheter borne (CBI) (as an IVIG/plasmapheresis complication). Result: There were 82 patients (mean age: 53y (33-73), 57% women). URIs were the most frequently reported GIPs (37%, p< 0.05) and also the most common infection causing MG exacerbation (17%, p<0.05). Lower respiratory infections such as bronchitis/pneumonia (17%) were the next most commonly reported GIP and second most common cause of MG exacerbation(7.3%). The overall GIP incidence was 65% and that of OI was 17%,with non-healing soft tissue/visceral abscess and Candida esophagitis the most common of OI (3%). There was a significant association between OI and steroid-only Rx (SORx)(v2 Вј 5.48, p < 0.05) with M1420. Expanded CUG-RNA Suppresses PGC-1a Transcription Via Activating DNA Damage Response ATM Signaling in Myotonic Dystrophy Type 1 (DM1) Xiang Fang, Rui Gao, Arpita Chatterjee, Tapas K. Hazra, Robert Glen Smith and Partha S. Sarkar; Galveston, TX DM1 is the most common form of adult onset muscular dystrophy in humans. The mutation in DM1 is the expansion of a CTG tri-nucleotide repeat in the 30 untranslated region of DMPK gene. Massive expansion of CTG repeats results in degenerative muscle defects, mitochondrial and metabolic abnormalities in DM1. Our recent study shows that PGC-1a, a key regulator of mitochondrial respiration and cellular energy metabolism, is downregulated in DM1 skeletal muscles. In the present study, we investigated the mechanism by which expanded CTG repeats suppress PGC-1a transcription in DM1. We found that 1) Ectopic expression of expanded CUG repeats in myoblasts increase 100 ID: guganp I Black Lining: [ON] I Time: 09:25 I Path: N:/3b2/ANA#/Vol00000/120255/APPFile/JW-ANA#120255 J_ID: ZAY Customer A_ID: BKLT2012_Abstracts Cadmus Art: ANA12 Date: 18-September-12 OR:8.6 (p<0.05). 85% of these occurred within the first 5 years of SORx. No CBI was observed in our study. Conclusion: Respiratory tract infections must be sought and treated aggressively, particularly URIs, as they are the most common cause of MG exacerbation. Steroid-only patients should be monitored for signs of opportunistic infections especially in the first 5 years of Rx. Study supported by: none Stage: Page: 101 M1425. Transgenic Mouse Models of FUS/TLS-Mediated ALS Lawrence J. Hayward, Hongru Zhou, Guohong Gao and Robert H. Brown; Worcester, MA Mutations in the RNA/DNA binding protein FUS/TLS cause $5% of familial ALS and are associated with neuronal and glial cytoplasmic inclusions. Multiple functional roles of FUS have been proposed in both the nucleus and the cytoplasm. We established transgenic mice that constitutively express human wildtype or mutant FUS (H517Q, R521G, or R495X) in the brain and spinal cord. FUS mutations caused a variable extent of cytoplasmic FUS accumulation in spinal cord motor neurons and other neurons. A high burden of cytoplasmic FUS(R495X) was tolerated in neurons for >1 year without causing toxicity. Cytoplasmic FUS accumulated focally in the perikaryon in a pattern resembling Nissl bodies without the formation of well-defined inclusions. Transgenic FUS mutant mice exhibited normal nuclear TDP-43 staining. In a subset of mice, FUS mutant expression was associated with age-related motor deficits (decreased mobility, generalized tremor, or circling behaviors), but these abnormalities were not consistently observed. Ongoing experiments will assess the sensitivity of these mice to increased mutant gene dosage, decreased expression of endogenous mouse FUS, and external stresses to determine whether FUS mutants impair neuronal homeostatic mechanisms that could be relevant to ALS. Study supported by: NIH-NINDS (RC1-NS068391) ALS Therapy Alliance M1423. Anti Acetylcholine Receptor Antibodies in a Patient with LEMS and Idiopathic Thromobocytopenic Purpura Raghav Govindarajan and Virgilio Salanga; Weston, FL Background: Whether myasthenia garvis and LEMS can co-exist as two separate entities in the same patient remains controversial.Previous case reports have found a LEMS like finding on repetitive nerve stimulation (RNS) with positive AChR antibodies.We report the case of a 70-year-old with chronic idiopathic thrombocytopenic purpura (ITP) who had both anti AChR antibodies and antibodies to pre-synaptic voltage gated calcium channel (VGCCA) with LEMS like pattern on RNS. Case Report: A 70-year-old male with a history of chronic ITP for a year,presented with increasing fatigue,inability to get up from chair,instability while walking,droopy eyes and intermittent dysphagia for last 4 months.Reflexes were absent throughout which did not improve with voluntary contraction for 10 seconds.Ach modulating/blocking and VGCCA were elevated.Compound muscle action potential (CMAP) amplitude were low in all the nerves tested on conduction studies.High frequency RNS and brief exercise resulted in a 200% incremental response in the CMAPs.Periodic cancer screening(last 5 years)have remained negative. Conclusion: It remains unknown if the presence of AChR antibodies is of clinical significance or merely a nonpathogenic epiphenomenon.Is there are a common etiopathogenic antigen triggering antibodies to presynaptic VGCC and postsynaptic AChR also needs to be explored. Study supported by: none M1426. A Novel Mutation in the CACNA1S Gene in a Japanese Family with Hypokalemic Periodic Paralysis Makito Hirano, Yosuke Kokunai, Yusaku Nakamura, Kazumasa Saigoh, Susumu Kusunoki and Masanori P. Takahashi; Sakai, Osaka, Japan; Suita, Osaka, Japan and Osakasayama, Osaka, Japan Hypokalemic periodic paralysis (HypoPP) type 1 is an autosomal dominant disease caused by mutations in the calcium channel encoded by the CACNA1S gene. In HypoPP type 1, only seven mutations have been found since the discovery of the causative gene in 1994. However, the prevalence of HypoPP is not extremely low (1:100,000), suggesting that a few common mutations affect many families. Here we report a novel mutation in this gene in a Japanese family with HypoPP. This novel mutation, p.Arg900Gly, may cause a gating pore current leak, a common pathomechanism in HypoPP, since this amino acid change loses positive charge of arginine at the conserved Arg900 residue located in S4 voltage sensors. We also report a clinically important finding that one patient had a high serum potassium concentration after recovery from a recent paralysis, though most patients had low serum potassium concentrations during their acute phases. This finding complicated the correct diagnosis. Study supported by: N/A M1424. Blockade of Matrix Metalloproteinase-3 after Traumatic Nerve Injury Preserves the Motor End Plate Tom Chao, Derek Frump, Vincent J. Caiozzo, Tahseen Mozaffar and Ranjan Gupta; Orange, CA Functional recovery after repair of traumatic nerve injuries is poor due to loss of end targets following repair. It has been found that matrix metalloproteinase-3 (MMP-3) is responsible for removing agrin, an essential protein for maintaining the NMJ. This study explores whether the NMJ may be preserved after denervation if MMP-3 is inactivated. A murine model for a segmental sciatic nerve injury was created and plantaris muscles were extracted from wildtype and MMP-3 knockout mice at 1 week, 2 week, 1 month, and 2 months after injury to evaluate NMJ components. Functional evaluation of 1 month denervated muscles was performed ex vivo. In contrast to wildtype mice, MMP3 knockouts showed that AchRs remained intact up to 2 months. Agrin immunofluorescence was also observed late after denervation in the knockout but not the wildtype. MuSK remained significantly phosphorylated 1 month after denervation in knockouts. Functional assessment of muscles demonstrated that activation with acetylcholine in MMP-3 knockouts was greater than wildtypes. The data provides evidence that the motor end plate might be preserved following long-term denervation by inhibition of MMP-3. Study supported by: Jacqueline Glass foundation M1427. Pathological Involvement of ubiquilin2 in Autophagy in Sporadic Amyotrophic Lateral Sclerosis Makito Hirano, Keiji Shimada, Tatsuki Itoh, Yoshiyuki Mitsui, Kazumasa Saigoh, Hikaru Sakamoto, Shuichi Ueno, Takao Satou, Noboru Konishi, Yusaku Nakamura and Susumu Kusunoki; Sakai, Osaka, Japan; Kashihara, Nara, Japan and Osakasayama, Osaka, Japan Ubiquilin2, encoded by the UBQLN2 gene, is very recently identified as a causative protein for familial amyotrophic lateral sclerosis (ALS). Because penetrance is incomplete, mutations might be found in sporadic patients. We thus 101 ID: guganp I Black Lining: [ON] I Time: 09:25 I Path: N:/3b2/ANA#/Vol00000/120255/APPFile/JW-ANA#120255 J_ID: ZAY Customer A_ID: BKLT2012_Abstracts Cadmus Art: ANA12 Date: 18-September-12 sequenced the UBQLN2 gene in 38 Japanese patients with sporadic ALS, but found no mutations. Our pathological analyses of autopsied spinal cords from 3 Japanese patients with sporadic ALS revealed that ubiquilin2 aggregated in ubiquitin-positive inclusions. We found for the first time that this protein also colocalized with Atg5 and Atg7, proteins associated with autophagy. These results suggest that ubiquilin2 may be involved in the ubiquitin-proteasome system and autophagy even with its wild-type form. Ubiquilin2 may be a key molecule to connect two major protein quality control systems in pathomechanisms in ALS. Study supported by: N/A Stage: Page: 102 atrophy in the biceps muscle (p<0.01), suppressed loss of motor neurons (p<0.01) and inhibited astrocyte proliferation in the C5-C6 cord (p<0.01). Conclusion: The present study indicated neuroprotective effects of ZNS in wobbler mouse spinal motor neuron degeneration. This drug may have a therapeutic potential for motor neuron damage. Study supported by: None M1430. Serum Lipid, Creatinine, Urate and Ferritin Levels at the First Time Diagnosed with Amyotrophic Lateral Sclerosis (ALS) Contribute to Disease Progression Ken Ikeda, Takehisa Hirayama, Kiyokazu Kawabe, Osamu Kano and Yasuo Iwasaki; Tokyo, Japan M1428. An Unbiased Phenotypic Screen Identifies Ethoxyquin as an hsp90 Activity Modulating Neuroprotective Compound for Peripheral Neuropathies Jing Zhu, Weiran Chen and Ahmet Hoke; Baltimore, MD Background: Distinct profiles of serum lipid, urate and ferritin levels were reported in Western ALS patients. We aimed to analyze the relationship between those levels and disease progression in Japanese patients. Methods: ALS functional rating scale (ALS-FRS), forced vital capacity (FVC) and serological variables were measured in 92 consecutive patients at the first time diagnosed with ALS. Results: As compared to 92 age/sex/body mass indexmatched controls, urate and creatinine (Cr) levels were decreased, and ferritin levels were increased significantly in sera of male and female ALS patients. Serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and triglyceride levels were increased in female patients. Annual decline of ALS-FRS and FVC were correlated inversely with serum TC, LDL-C, Cr and urate levels, and linked to serum ferritin levels. Multivariate analysis showed that ALS-FRS decline ! 1/month and annual FVC decline ! 30% were associated with baseline serum TC, LDL-C, Cr, urate and ferritin levels. Conclusion: Our clinico-serological results were in the similar patterns to Western patients and highlighted a therapeutic impact on metabolism and nutrition of lipid, urate and iron in ALS patients. Study supported by: None Chemotherapy induced peripheral neuropathy (CIPN) is a significant dose-limiting complication of many chemotherapeutic drugs. Although CIPN is an ideal target for neuroprotective approaches, there are no effective therapies. We carried out a phenotypic screen looking for small molecules that prevented paclitaxel-induced axonal degeneration in a dorsal root ganglion (DRG) sensory neuronal line and identified ethoxyquin as a compound that provided >50% neuroprotection. Confirmatory studies in primary DRG-Schwann cell co-cultures validated the findings for ethoxyquin with peak efficacy in the 30-300 nM range. Novel analogues of ethoxyquin provided neuroprotection with similar dose response curves. Ethoxyquin and one of its analogues prevented distal axonal degeneration by 70% in an animal model of paclitaxel CIPN. Ethoxyquin did not have any observable toxicity and did not block paclitaxelвЂ™s ability to kill 4 different human breast cancer cell lines. Binding studies identified hsp90 as the primary target and demonstrated that ethoxyquin modulates hsp90 chaperone activity without inhibiting ATPase activity. These studies identifies a novel neuroprotective mechanism involving hsp90 that is different than typical hsp90 inhibition and shows that ethoxyquin can be developed as neuroprotective therapy for paclitaxel CIPN. Study supported by: Adelson Medical Research Foundation, Foundation for Peripheral Neuropathy, and JHU Brain Sciences Institute M1431. Protective Effect of Erythropoietin on Glutamate-Mediated and Axotomy Induced Motor Neuron Death Yasuo Iwasaki, Ken Ikeda, Kiyokazu Kawabe and Osamu Kano; Tokyo, Japan M1429. Zonisamide (ZNS) Treatment Attenuates Motor Neuron Degeneration and Astrocytosis in the Wobbler Mouse Ken Ikeda, Yasuhiro Yoshii, Takehisa Hirayama, Kiyokazu Kawabe, Osamu Kano and Yasuo Iwasaki; Tokyo, Japan Several members of hematopoietic factors are known to have neuroprotective effect against glutamate and axotomized motor neuron death. We carried out a study to determine whether eruthropoietin(EPO) rescue spial motor neuron death due to glutamate- and axotomy-induced motor neuron death. Of 10 day old rats were used for organotypic spinal cord cultures and new born rats were used for axotomy induced motor neuron death. EPO prevented spinal motor neuron death not only glutamate but axotomy induced neuronal death. In addition ChAT activity were increased in both EPO-treated group. Amyotrophic lateral sclerosis(ALS) is characterized by death of motor neurons and our results show EPO may be candidated in therapeuic strategy in ALS. Study supported by: none Background: ZNS had multifunctional effects on several kinds of neurons. Little is known about ZNS effects on motor neurons. We aimed to study whether this drug can prevent spinal motor neuron degeneration in wobbler mice. Methods: Two doses of ZNS (0.2 mg/kg, 2.0 mg/kg, i.p.) or vehicle were injected daily to affected mice from aged 3-4 weeks at disease onset for 4 or 8 weeks. Forelimb motor function of pull-strength and deformity scale, and body weight were measured weekly for 8 weeks (n Вј 10/ group). Neuropathological changes of the biceps muscle and the cervical cord were evaluated at 4 weeks post-treatment (n Вј 10/group). Results: Progression of forelimb motor dysfunction was delayed significantly from 3 weeks after ZNS (2.0 mg/kg) treatment compared to vehicle (p<0.01). Gain of body weight did not differ statistically between three groups. Higher doses of ZNS administration decreased denervation M1432. Denervation Causes Lower Expression of Insulin-Like Growth Factor (IGF) mRNA in Regenerating Skeletal Muscle Takahiro Jimi, Yoshiriro Wakayama and Hiroo Ichikawa; Yokohama, Japan To maintain functions of skeletal muscle, neural factors might be essential. Denervation results in incomplete 102 ID: guganp I Black Lining: [ON] I Time: 09:25 I Path: N:/3b2/ANA#/Vol00000/120255/APPFile/JW-ANA#120255 J_ID: ZAY Customer A_ID: BKLT2012_Abstracts Cadmus Art: ANA12 Date: 18-September-12 Stage: Page: 103 recovered in WT whereas in SOD1G127X it did not recover, consistent with partial loss of motor axons confirmed by morphological studies. After 1 day there were deviations in excitability in WT and SOD1G127X, measured by thresholdtracking, consistent with membrane hyperpolarization: increased rheobase, increase in threshold during hyperpolarizing electrotonus, reduced resting current-threshold slope and decreased subexcitability of the recovery cycle. Changes were larger in WT than in SOD1G127X. After 3 days of recovery, excitability measures returned to near-normal in WT and SOD1G127X. Our data suggest that in the SOD1G127X there is inadequate energy-dependent NaГѕ pumping, as indicated by the reduced post-stimulation hyperpolarization, which may lead to neurotoxic NaГѕ overload. Study supported by: Danish Medical Research Council Lundbeck Foundation Elsass Foundation regeneration of skeletal muscle. So we examined mRNA expression of insulin-like growth factor (IGF) in regenerating rat muscles in innervated and denervated conditions. We made rat regenerating muscles by injection of bupivacaine hydrochloride in both extensor digitorum longus (EDL) muscles. At the same time of injection, the unilateral (right) sciatic nerve was removed. At one week after surgery, both innervated and denervated EDL muscles were excised from five rats. We carried out RT-PCR of IGF-1 and IGF-2 for each sample using specific primers. Both IGF-1 and IGF-2 mRNA were down-regulated in the denervated rat skeletal muscles as compared with the innervated condition. According to these results, we speculated that denervation causes decreased expression of IGF-1 and IGF-2 mRNA in the regenerating skeletal muscle. The lower expression of IGF mRNA may be involved in the incomplete regeneration under denervated conditions. Study supported by: none M1435. More MS Patients Remain Free from Disease Activity with Teriflunomide Versus Placebo in TEMSO, a Phase III Trial Marcelo Kremenchutzky, Paul W. OвЂ™Connor, Jerry Wolinsky, Christian Confavreux, Giancarlo Comi, Ludwig Kappos, Tomas P. Olsson, Philippe Truffinet, Deborah Dukovic and Aaron Miller; London, ON, Canada; Toronto, Canada; Houston; Lyon, France; Milan, Italy; Basel, Switzerland; Stockholm, Sweden; Chilly-Mazarin, France; Bridgewater and New York M1433. Quantitative Image Analysis of Brain Abnormality in Myotonic Dystrophy Nam-Hee Kim, Dong-Eog Kim, Sang-Wuk Jeong, Ho Jin Kim and Kyung Seok Park; Goyangsi, Korea and Bundang, Korea Background: Myotonic dystrophy type 1 (DM1) is a myopathy with myotonia and other multi-system involvement caused by DMPK gene mutation with CTG repeats. Brain abnormalities have been reported with neurodegenerative pathologic finding. The purpose of this study was to characterize brain structural abnormalities by mapping of DM1related brain lesions on MRI onto brain template. Methods: Sixteen patients (17-68 years old) were included and evaluated with genetic test, neuropsychologic test, and brain MRI. Brain lesions were quantified by software package (Image_QNA) which can visualize the cumulative data of brain lesion by overlapping image data on a standard brain template. Results: Fifteen patients presented multiple high signal intensities in frontal and temporal lobe. The cumulative data revealed that periventricular and subcortical white matter were frequently involved and the most overlapping hot spot was located in subcortical white matter near anterior horn. Neuropsychologic test demonstrated that the most frequent deficit was frontal lobe dysfunction, corresponding to the brain involvement. The lesion load and the number of CTG repeat or disease duration demonstrated no correlations. Conclusions: Anterior subcortical white matter was the most frequent involved site in DM1 through quantitative imaging method, which is consistent with neuropsychological impairment. Study supported by: none Background: Teriflunomide, an oral disease-modifying therapy with a unique mechanism of action compared to existing disease modifying therapies in development for the treatment of relapsing forms of MS (RMS), reduced clinical and MRI disease activity in a large placebo-controlled Phase III trial (TEMSO: NCT00134563). Here, we report its effects on a composite endpoint of disease activity in TEMSO. Methods: 1088 RMS patients were randomized to placebo, teriflunomide 7mg or 14mg once daily for 108 weeks. Time to disease activity (either clinical relapse, 12-week sustained disability progression or new unique active lesions) was assessed by a log-rank test. Hazard ratios (teriflunomide versus placebo) were estimated using a Cox regression model. Results: Teriflunomide reduced the risk of disease activity compared with placebo (p Вј 0.0002 for 14mg, p Вј 0.0293 for 7mg). 14.3%, 18.4% and 22.9% of patients receiving placebo, teriflunomide 7mg and 14mg remained free of disease activity. Hazard ratios were 0.834 and 0.726 for 7mg and 14mg teriflunomide. Conclusions: Teriflunomide dose-dependently increased the number of patients free from disease activity compared with placebo. These findings support previously reported positive efficacy findings from the TEMSO study. Study supported by: Genzyme, a Sanofi Company Drs. Kremenchutzky, OвЂ™Connor, Wolinsky, Confavreux, Comi, Kappos, Olsson, and Miller are all investigators on this study and have received financial support for the TEMSO study. Mr. Truffinet and Ms. Dukovic have received personal compensation as employees of Genzyme, a Sanofi Company. M1434. Prolonged High Frequency Electrical Nerve Stimulation Precipitates Motor Axon Degeneration in Presymptomatic SOD1G127X Mutant Mice Susana Alvarez, Alexandru Calin, Stefan Marklund, Karin Graffmo, Mihai Moldovan and Christian Krarup; Copenhagen, Denmark; Bucharest, Rwanda and UmeaЛљ, Sweden Strenuous activity may precipitate axonal degeneration in ALS. We performed prolonged high frequency electrical nerve stimulation of the right tibial nerve of the SOD1G127X mouse model at 200 Hz for 3 hours. After 1 hour there was a drop in CMAPs recorded from plantar muscles and CNAPs from the exposed sciatic nerve in SOD1G127X and WT as compared to the un-stimulated side. Within 3 days, the drop M1436. Anxiety in Benign Fasciculation Syndrome Alexandra LaMela, Stephanie Scala, Ioannis Karakis, James A. Russell and Doreen T. Ho; Biddeford, ME and Burlington, MA Objective: To study anxiety in patients with benign fasciculation syndrome (BFS). 103 ID: guganp I Black Lining: [ON] I Time: 09:25 I Path: N:/3b2/ANA#/Vol00000/120255/APPFile/JW-ANA#120255 J_ID: ZAY Customer A_ID: BKLT2012_Abstracts Cadmus Art: ANA12 Date: 18-September-12 Background: Despite the favorable prognosis of BFS, patients frequently become distressed. Awareness of fasciculation significance may increase anxiety and the motivation to seek care. However, psychological correlates of BFS have not been systematically studied. We postulate that awareness of fasciculation significance produces anxiety, thus perpetuating symptoms. Design/Methods: We enrolled nine patients. Patients were diagnosed by a neuromuscular physician. Anxiety was measured using the Zung Anxiety Scale (SAS) at diagnosis, and months one, three, and six, with plans to continue for two years. Results: There were seven men and two women with a mean age of 46.7 66.4 years. Four patients were in a medical field. All patients fell within the normal range (20-44) on the SAS with a mean score of 32.4 64.72. In eight patients, fasciculations persisted at six months. Conclusions/Relevance: Our tentative conclusions are descriptive due to small sample size. During a six month follow-up period, mean SAS scores were lower than published normative data. We plan to enroll further patients and add controls, but our findings suggest that anxiety may not be higher than normal in this population, despite the persistence of fasciculations. Study supported by: None. Stage: Page: 104 Methods: The authors conducted a retrospective review of medical records of psoriasis patients seen at the Mayo Clinic from January 1, 1996 to May 31, 2011. Patients who had pathologically-confirmed myopathy or inflammation in muscle were included. Results: Thirteen patients with pathologically-confirmed myopathies (4 inclusion body myositis, 3 polymyositis, 3 necrotizing myopathy, 2 dermatomyositis and 1 sporadic late-onset nemaline myopathy) and 2 patients with focal inflammation in muscle were recruited. The median age-atonset of myopathy was 57 years. Psoriasis preceded the onset of weakness in two-thirds of patients (median 14.7 years). Psoriatic arthritis and other autoimmune disorders were seen in 50% and 60% of patients, respectively. Onefourth of the patients received anti-TNF-a therapy before the onset of myopathy. Conclusions: While rare, inflammatory myopathies were the most common type of psoriatic myopathy. Most patients who developed myopathies had not been exposed to antiTNF-a therapy. Psoriatic arthritis and concomitant autoimmune disorders may be associated with increased risk of developing myopathy. Study supported by: None M1439. Dynactin Mutations in HMN7B Disrupt Initiation of Retrograde Transport at NMJ Terminal Boutons Thomas E. Lloyd, James Machamer, Sarah H. Collins, Yunpeng Yang and Alex L. Kolodkin; Baltimore, MD M1437. Myositis with Autoantibodies to c/d Sarcoglycan: A New Disease Russell Lane, Chiara Marini-Bettolo, Peter Charles and Federico Roncaroli; London, United Kingdom p150Glued is the major subunit of dynactin, a complex that functions with dynein in retrograde axonal transport. The CAP-Gly microtubule-binding domain of Glued is mutated in Hereditary Motor Neuropathy type VIIB (HMN7B) and Perry Syndrome; however, the function of this domain in neurons is unknown. We generated a Drosophila model of HMN7B that replicates key features of the disease including aggregate formation, distal-predominant NMJ phenotypes, and adult-onset locomotor dysfunction. Interestingly, axonal transport occurs normally in Glued flies, but rather we find a specific disruption of retrograde vesicle trafficking at terminal boutons (TBs), the distal-most ends of synapses. Loss of Glued function causes both the dynein retrograde motor and the kinesin anterograde motor to accumulate on endosomes at TBs, and live imaging data demonstrate that p150Glued is required for initiating dynein-mediated retrograde transport at TBs. Interestingly, distinct CAP-Gly mutations that cause Perry Syndrome, characterized by neurodegeneration of dopaminergic neurons, do not cause mislocalization of dynein. Together, these data suggest that the distal axonopathy that occurs early in motor neuron degenerative disease begins with an inability to initiate retrograde transport at synaptic termini. Study supported by: NIH/NINDS Robert Packard Center for ALS Research We report two cases of inflammatory myopathy with autoantibodies to c/d sarcoglycan. The presenting features were generally typical of polymyositis but from the outset, the pattern of muscle involvement in the upper limbs was reminiscent of IBM but the quadriceps remained clinically unaffected throughout. Muscle biopsies showed IBM-like features but the inflammation included a significant component of CD4 helper cells and plasma cells, and there was prominent deposition of C5b-9 on muscle cell membranes. None of the recognised myositis specific autoantibodies were detected in patientsвЂ™ sera using line-immunoblot and western blotting techniques against HeLa cell extracts but a previously unidentified band of 35kB was identified. Subsequent immunoblotting studies using patientsвЂ™ sera against normal human sarcolemma and recombinant sarcoglycans showed that this antibody was reactive with c/d sarcoglycan. Both patients responded to steroids and also showed objective temporary improvement in strength following plasma exchange. This is the first inflammatory myopathy in which pathogenic antibodies to a muscle-specific surface membrane antigen have been identified. The existence of this new disease also supports the concept that myositis is a clinical and pathological continuum, in which different entities are determined by their immunopathic characteristics. Study supported by: The Myositis Support Group and the Jani Foundation M1440. Phenotypic Diversity of Mutations in the Ryanodine Receptor (RYR1): A Series of Six Cases Charles Marshall, Hena Ahmad, Nicholas Parkin, Stephen Abbs, Silvia Marino, Sujit Vaidya, Heinz Jungbluth and Aleksandar Radunovic; London, United Kingdom M1438. Psoriatic Myopathies: The Mayo Clinic Experience Teerin Liewluck and Jennifer A. Tracy; Rochester, MN The ryanodine receptor 1 (RyR1) is a calcium channel responsible for excitation-contraction coupling in striated muscle. Mutations in the RYR1 gene that encodes this channel have long been known to cause malignant hyperthermia, but the broad spectrum of muscle disease phenotypes is expanding. Introduction: Psoriasis is a T-cell mediated skin disorder with uncommon associated extracutaneous autoimmunity except for seronegative arthritis and inflammatory bowel diseases. Rare patients with psoriatic myopathies with or without exposure to TNF-a antagonists were reported. 104 ID: guganp I Black Lining: [ON] I Time: 09:25 I Path: N:/3b2/ANA#/Vol00000/120255/APPFile/JW-ANA#120255 J_ID: ZAY Customer A_ID: BKLT2012_Abstracts Cadmus Art: ANA12 Date: 18-September-12 Here, we present a series of six cases with muscle MRI and muscle biopsy findings, as well as genetic analysis. The phenotypes include: axial myopathy; exercise-induced rhabdomyolysis; proximal myopathy; proximal myopathy with ptosis and ophthalmoplegia; myalgia; and mixed proximal and distal myopathy. All six cases carry one of four heterozygous mutations affecting highly conserved amino acids within the RYR1 gene. Study supported by: None Stage: Page: 105 ing; enhanced carer wellbeing; improved breathing; and increased speech clarity. Discussion: A range of obstacles need to be overcome by patients initiating NIV, however those achieving regular use perceive a range of gains to their quality of life. Key recommendations are: the need for early accessible in-person advice; pre-empting potential issues and solutions with users; early and regular discussion of the potential benefits of NIV. Study supported by: National Institute for Health Research, Research for Patient Benefit Programme. M1441. Advanced Neuroimaging Study of Molecularly Defined Hereditary Spastic Paraplegias (HSPs) Andrea Martinuzzi, Domenico Montanaro, Nicola Martino, Hana Hlavata, Giuseppe Rossi, Gabriella Paparella, Francesca Peruch, Maria G. Rossetto, Alessandra T. Baratto and Maria T. Bassi; Conegliano and Bosisio Parini, Italy; Pisa-Massa, Italy and Conegliano, Italy M1443. Steroid Responsive Anti-GAD Antibody Positive Spino-Cerebellar Ataxia Shri K. Mishra, Yama Akbari and Parampreet Singh; Los Angeles, CA; Baltimore, MD and Sylmar, CA We describe a case of Anti-GAD antibody positive Spinocerebellar ataxia (SCA), responsive to high dose corticosteroids. Anti-GAD antibody targets Glutamic-Acid-Decarboxylase enzyme, which transforms glutamate to GABA. It is highly specific for autoimmune disorders such as diabetes, rheumatoid arthritis, and вЂ�вЂ�stiff-man syndromeвЂ™вЂ™. Recently, Anti-GAD has been associated with SCA, presumably an autoimmune disease; the exact pathogenesis of this disorder is unknown. We report a 44 year-old female with an 11 yrs history of chronic-progressive ataxia. There is consanguinity in her parents, with however, no additional relevant family history. On exam she demonstrated truncal and appendicular ataxia, ocular dysmetria, pyramidal and dorsal column signs. Electrodiagnostics exhibited a sensory-predominant polyneuropathy, and MRI showed cerebellar atrophy. Her serology, CSF analysis, and an exhaustive paraneoplastic and ataxia testing including common SCAвЂ™s were all normal. Remarkably, an elevated anti-GAD titer of 2.3 (N<0.5) was observed. A course of high-dose prednisone(60mg/day) improved her symptoms. However, low-dose prednisone (20mg/day), and four-cycles of IVIG were not beneficial. The clinical gains were transient; however, her overall disease course has not worsened. Anti-GAD positive SCA is an extremely rare presentation. Furthermore, patientвЂ™s responsiveness to high-dose steroids supports a possible autoimmune hypothesis for the syndrome. Details will be presented. Study supported by: None Background: HSPs are clinically defined molecularly heterogeneous conditions for which a definite neuroimaging (MRI) pattern discriminating HSPs patients from controls is not described. Objective: To explore in a large and composite cohort of HSP patients the presence of objective markers for cortical or white matter involvement by non conventional MRI techniques. Methods: 18 HSP patients (10 SPG4, 4 PG3a, 2 SPG5, 1 SPG10, 1 SPG31) and 22 age matched controls were studied using a 1.5T device. All but the two SPG5 patients showed a normal conventional MRI. Rolandic regions were bilaterally sampled with single voxel H-MRS technique. Diffusion Fractional Anisotropy (FA) and average apparent Diffusion Coefficient (avADC) were sampled with ROIs along the cortico-spinal tract. Results: FA and avADC were significantly different in patients compared to controls. No specific pattern could be identified for H-MRS. There was a trend for correlation between DTI values and clinical data. Conclusion: In spite of normal conventional imaging and the small number of patients DTI can detect objective quantitative changes in the cortico-spinal tract of HSP patients. Larger series and longitudinal studies will now be needed to explore MRI/genetic correlations and indicators of progression. Study supported by: Italian Ministry of Health M1444. Confocal Microscopy Analysis of Altered TDP-43 Expression in Peripheral Blood Lymphocytes from ALS Patients Jean-Luc C. Mougeot, Sriparna Ghosh, Anne C. Lutin, Andrea E. Price, Richelle A. Hemendinger, Edward J. Armstrong and Benjamin R. Brooks; Charlotte, NC M1442. The Use of Non-Invasive Ventilation for Patients with Motor Neurone Disease: Patient and Carer Perceptions of Obstacles and Outcomes Susan K. Baxter, Wendy O. Baird, Sue Thompson, Stephen Bianchi, Stephen Walters, Sam H. Ahmedzai, Alison Proctor, Pamela J. Shaw and Christopher J. McDermott; Sheffield, United Kingdom Objective: Advances in amyotrophic lateral sclerosis (ALS) gene expression studies in whole blood, peripheral blood mononuclear cells (PBMCs) and peripheral blood lymphocytes (PBLs) have been made. Our objective was to investigate changes in non-nuclear and nuclear expression of TAR DNA-binding Protein 43 (TDP-43) in PBLs from ALS patients compared to healthy controls (HCs). Methods: PBMCs were collected from ALS patients and HCs at an academic medical center-based ALS clinic. AntiTDP-43 antibody was used for immunocytochemistry. A Zeiss LSM 710 confocal microscope was used to determine TDP-43 non-nuclear and nuclear staining in PBLs. Results: Non-nuclear expression of TDP-43 is increased in PBLs from ALS patients (n Вј 13) compared to HCs (n Вј 17). Changes in TDP-43 non-nuclear expression in PBLs Objectives: The purpose of this study was to examine the perceptions and experiences of patients with Motor Neurone Disease and their carers following the recommendation to use non-invasive ventilation (NIV). It aimed to describe factors impacting on acceptance and patient perceptions regarding any benefits gained. Methods: The work used a qualitative design, interviewing patients and carers within one month of NIV being initiated. Results: The study identified themes relating to: first impressions of the technology; issues of sleep disturbance; adverse sensations of pressure and pulsing; dry mouth; design of the mask; and fitting the mask. Patients/carers perceived benefits related to: increased energy; improved sleep- 105 ID: guganp I Black Lining: [ON] I Time: 09:25 I Path: N:/3b2/ANA#/Vol00000/120255/APPFile/JW-ANA#120255 J_ID: ZAY Customer A_ID: BKLT2012_Abstracts Cadmus Art: ANA12 Date: 18-September-12 from ALS patients did not correlate with riluzole (Rilutek) treatment, disease duration or the ALS functional rating scale-revised (ALSFRS-R). Conclusions: Confocal microscopy is a useful tool to assess TDP-43 expression in PBLs from ALS patients as a potential biomarker for diagnosis, rate of progression and response to therapy. Investigation of ALS-specific mechanisms involved and the generation of longitudinal data are necessary to establish correlations with clinical variables. Study supported by: Carolinas ALS Research Fund and the Pinstripes Fund of the Carolinas Healthcare Foundation at Carolinas Medical Center Stage: Page: 106 ness, and trabecular microarchitecture did not significantly differ between subjects and controls. Men with biopsy-proven SFPN thus have apparently healthy skeletal parameters proximally and distally. This small study cannot exclude modest influences but substantial or consistent skeletal effects of adult-acquired SFPN appear unlikely. Study supported by: Funded in part by the Public Health Service NIH-K24NS59892. M1447. Mononeuropathy of the Lateral Cutaneous Nerve of the Calf (LCNC) in Patients Previously Labeled with вЂ�вЂ�Complex Regional Pain Syndrome-IвЂ™вЂ™ Anne Louise Oaklander and JoseВґ Ochoa; Boston, MA and Portland, OR M1445. Myasthenia Gravis Associated with GravesвЂ™ Disease Hiroyuki Murai, Natsumi Yamashita and Jun-ichi Kira; Iizuka, Fukuoka, Japan; Matsuyama, Ehime, Japan and Fukuoka, Japan вЂ�вЂ�CRPSвЂ™вЂ™ is a descriptive label for patients reporting persistent pain plus sensory, motor and microvascular symptoms after limb trauma. Some have objectively identified nerve pathology (вЂ�вЂ�CRPS-IIвЂ™вЂ™; formerly causalgia), but most do not (вЂ�вЂ�CRPS-IвЂ™вЂ™; formerly reflex sympathetic dystrophy), and their symptoms remain unexplained. Here we report an unrecognized cause of symptoms among вЂ�вЂ�CRPS IвЂ™вЂ™-labeled patients; mononeuropathy of the LCNC branch of the common peroneal. Five women presented with post-traumatic вЂ�вЂ�CRPS-IвЂ™вЂ™ centered lateral and distal to one knee; all had remote knee surgery. Mean onset was at age 27; interval to diagnosis averaged 6 years. All had LCNC-territory hypoesthesia, allodynia, and microvascular abnormalities. 2/2 routine electrodiagnostic studies were normal. When detectable, LCNC responses were absent unilaterally (1/1). Skin biopsy revealed profound LCNC-territory denervation in 1/1 patients studied and restudy documented cutaneous reinnervation after the вЂ�вЂ�CRPS-IвЂ™вЂ™ resolved. These findings demonstrate that rigorous neurological and neurophysiological evaluation can detect undiagnosed mononeuropathies among patients descriptively classified as вЂ�вЂ�CRPS-I.вЂ™вЂ™ LCNC mononeuropathy should be considered among patients with posterolateral-calf-predominant вЂ�вЂ�CRPSвЂ™вЂ™ because identification and localization of nerve injuries enables evidence-based and disease-modifying treatments, plus facilitating insurance and disability assessments. Study supported by: Funded in part by the Public Health Service NIH-K24NS59892 The aim of the present study was to clarify the characteristics of myasthenia gravis (MG) associated with GravesвЂ™ disease. We used the data of the nationwide epidemiological survey 2006. We studied onset-age, sex, coexistence of thymoma, MG classification, anti-AChR antibodies, history of crisis and outcome of Graves-associated MG (Group G) and compared these results with the results from patients who did not have GravesвЂ™ disease (Group N). Among 3,141 MG patients, 165 (5.3%) had GravesвЂ™ disease. Average onset ages were 34.3 years in Group G and 42.8 years in Group N. When compared with Group N, Group G showed higher percentage of early-onset, and lower percentage of elderlyonset cases. Group G showed the characteristics of female predominancy, a lower percentage of thymoma-coexistence, and a higher percentage of ocular type. Anti-AChR antibody positivity was lower in Group G (63.3% vs 74.5%). Frequency of crisis was lower in Group G (7.3% vs 13.6%). The rate of good outcome (CSR, PR or MM in MGFA postintervention status) was higher in Group G (63.9% vs 57.1%). Graves-associated MG seems to affect relatively young females, with a low rate of thymoma, and a reduced likelihood of falling into crisis. Study supported by: N/A M1446. Effects of Small-Fiber Polyneuropathy (SFPN) on Bone Mineral Density and Skeletal Microarchitecture Benjamin Z. Leder, Ruchit Khumbani, Erica Siwila-Sackman, Heather Downs and Anne Louise Oaklander; Boston, MA M1448. The Incidence and Prevalence of CIDP in Iceland Brynhildur Hafsteinsdottir, Elias Olafsson and Sigurjon Stefansson; Reykjavik, Iceland There is increasing recognition of neural influences on bone development and health. Bone innervation is largely by sensory and autonomic small-fibers. Although the effects of SFPN on skeletal health have not been systematically studied, skeletal malformation, dysmetabolism, and resorption are well described in genetic (e.g., HSAN, neurofibromatosis-I), infectious (e.g., leprosy) and traumatic (e.g., complex regional pain syndrome) small-fiber-predominant sensory neuropathies. We performed high-resolution quantitative computed tomography of distal tibia, dual energy x-ray absorptiometry (DXA) of the hip and spine, and measured bone-related serum markers in 12 men with SFPN (age 3060y) and 12 healthy, age-matched male controls. Exclusions comprised diabetes, calcium regulatory disorders, hypogonadism, recent fracture, and bone-active medications. SFPN was quantified using standard PGP9.5-immunolabeled distal-leg skin biopsies. Comparisons between patients and agematched controls were performed by paired t-test. Despite skin-biopsy confirmation of profound SFPN in subjects; tibial, hip, and spine bone mineral density, cortical-bone thick- Objective: We determined the incidence and prevalence of chronic inflammatory demyelinating polyneuropathy (CIDP) in Iceland, over a 20 year period (1991-2011). Methods: We did a retrospective population-based study. Cases were identified from records of the only neurology department, neurophysiology laboratories and all practicing neurologists in Iceland. All cases fulfilled the EFNS/PNS diagnostic criteria for CIDP (Hughes RAC et al., J Peripher Nerv Syst 2005). Patients were excluded if they had diabetes mellitus, paraproteinemia, malignancy or history suggestive of Charcot-Marie-Tooth disease. Results: We identified 20 individuals, who met the criteria. The prevalence (31 Dec. 2011) was 4.69/100,000 and the average annual incidence 0.32/100,000. Average age at diagnosis was 57 years and M:F ratio 4:1. The course was chronic progressive (30%), remitting-relapsing (25%) and monophasic (45%). The symptoms were symmetrical proximal and distal weakness with sensory impairment in all extremities (55%), predominantly distal weakness (30%), predominantly sensory 106 ID: guganp I Black Lining: [ON] I Time: 09:25 I Path: N:/3b2/ANA#/Vol00000/120255/APPFile/JW-ANA#120255 J_ID: ZAY Customer A_ID: BKLT2012_Abstracts Cadmus Art: ANA12 Date: 18-September-12 Stage: Page: 107 symptoms (10%) and one had pure motor affection. Immunomodulating treatment was given to 85%. Conclusion: Very few studies are available on the frequency of CIDP. We report the incidence and prevalence of CIDP, in a well defined population, over a 20 year period. Study supported by: This study had no financial support M1451. Sub-Regional Dual-Energy X-Ray Absorptiometry (DEXA) Analysis: A Potential Endpoint Measure for Therapeutic Trials in Myotonic Dystrophy Type 1 (DM1) Araya Puwanant, Noya Rackovsky, Jeffrey M. Statland, Katy J. Eichinger, Richard T. Moxley, III and Charles A. Thornton; Rochester, NY M1449. Abundant FUS-Immunoreactive Pathology in the Skin in Sporadic Amyotrophic Lateral Sclerosis Seiitsu Ono, Takahiko Yamano, Hirotsugu Mikami, Takeshi Watanabe, Tomomi Tsukie, Hiroyuki Fukazawa, Kazuhiro Higashida, Yoshihiko Oketa, Hiroaki Ishikawa, Kanako Yasui, Makoto Nomura and Megumi Suzuki; Ichihara, Chiba, Japan Objective: To determine whether sub-regional DEXA analysis of lower leg lean tissue mass (LTM) correlates with quantitative strength (QMT) of ankle dorsiflexion and six-minute walk distance in DM1. Background: Distal weakness is common in DM1, but correlation of lower leg LTM with six-minute walk distance has not yet been evaluated. Methods: We performed segmental DEXA analysis of LTM in both legs dividing each leg into thigh, lower leg, and foot segments in 48 DM1 patients. LTM was correlated with right and left foot dorsiflexor QMT and with a 6-minute walk test. Results: LTM of lower leg segments significantly correlated with the 6-minute walk test (right, r Вј 0.57; left, r Вј 0.57) and with QMT of ankle dorsiflexion (right, r Вј 0.53; left, r Вј 0.56). The LTM of lower leg segments provided the strongest correlation with dorsiflexor QMT and 6-minute walk distance compared to segments of thigh and foot or whole leg. Conclusion: Sub-regional DEXA analysis is a simple, cost-effective, and time-efficient method that may be used as an appropriate endpoint for studies of disease progression and therapeutic efficacy in DM1. Study supported by: NINDS U54NS48843 Background: Recently, mutations in a gene coding the fused in sarcoma (FUS) have been identified in familial amyotrophic lateral sclerosis (ALS). Also, FUS has been found in neuronal cytoplasmic inclusions in sporadic ALS, suggesting that FUS has an important role in the neurodegeneration occurring in ALS, However, there has been no study of FUS in ALS skin. Methods: We have performed a quantitative immunoreactive study of FUS in biopsied skins from 22 patients with sporadic ALS and from 22 controls. Results: The proportion of FUS-immunoreactive (ir) cells in the epidermis in ALS patients was significantly higher (p<0.001) than in controls. There was a significant positive relationship (r Вј 0.78, p<0.001) between the proportion and duration of illness in ALS patients. The optical density of FUS-ir cells in the epidermis in ALS patients is markedly stronger (p<0.001) than in controls. There was a significant positive relation (r Вј 0.49, p<0.05) between the immunoreactivity and duration of illness in ALS patients. Conclusions: These data suggest that changes of FUS in ALS skin are related to the disease process and that metabolic alterations of FUS may take place in the skin of patients with ALS. Study supported by: No. M1452. A Recombinant Human Neuron-Binding IgM Promotes Survival and Protects Spinal Cord Anterior Horn Cells in a Transgenic Murine Model of Amyotrophic Lateral Sclerosis Aleksandar Denic, Laurie Zoecklein, Bharath Wootla, Arthur E. Warrington and Moses Rodriguez; Rochester, MN M1450. Brown Sequard Syndrome as an Initial Manifestation of Idiopathic Spinal Cord Herniation Dipakkumar P. Pandya, Anery Patel, Jennie Luna, Megan McGarry, Sourav Sen and Gaetan Moise; Paterson, NJ We demonstrated that a recombinant human antibody, rHIgM12, binds to neurons in vitro, promotes axonal outgrowth, and improves spontaneous activity function in a virus-induced murine model of demyelinating disease. Based on laboratory evidence of the neuroprotective properties of this antibody, we studied rHIgM12 on survival and spinal cord pathology in animals with the SOD mutation (FVB-Tg(SOD1*G86R)M1Jwg/J). Mice were randomized for treatment by one investigator and were observed for neurological deficits by another blinded investigator to determine when the mice became moribund. Compared to both saline- and control IgM-treated mice, rHIgM12-treated mice showed an increased survival of approximately 21 days, which, by Kaplan-Meier curves was statistically significant (p<0.0001 and p Вј 0.003 respectively). Moribund mice were sacrificed and spinal cords collected for histological analysis. We demonstrated that the number of preserved anterior horn cells was significantly increased in rHIgM12-treated mice as compared to saline- and control IgM-treated mice (p<0.001 and p Вј 0.02 respectively). To our knowledge, this is the first demonstration that a fully recombinant neuron-binding human monoclonal antibody increases the survival of animals with an ALS phenotype. Study supported by: This work was supported by grants from the Mayo Clinic Center for Translational Science Activities (CTSA) Idiopathic spinal cord herniation is an extremely rare entity characterized by progressive spastic paraparesis. It occurs in middle-aged woman. It is manifested with dural defect sleeve through which spinal cord prolapsed. The most common manifestation is Brown Sequard syndrome. We present a unique case of progressive myelopathy in a middle age woman with idiopathic spinal cord herniation. Forty seven year old woman with bilateral progressive paraparesis of last 6-8 months. Current symptoms were associated with severe posterior abdominal pain involving both sides with extreme heaviness of both lower legs. She had diminished pain, temperature over right side and decrease touch and deep pressure sensations over left side. MRI thoracic spine showed spinal cord herniation at T4-T5 thoracic spine with severe narrowing of the spinal cord at anterior level. She underwent successful thoracic laminectomy and spinal cord duraplasty. Her postoperative course was uneventful and she is improving. Idiopathic spinal cord herniation is a rare medical condition. It should be considered in differential diagnosis in middle age woman with predominantly brown sequard syndrome, which is usually resultant from tethering of the spinal cord at the side of the herniation. Study supported by: None 107 ID: guganp I Black Lining: [ON] I Time: 09:25 I Path: N:/3b2/ANA#/Vol00000/120255/APPFile/JW-ANA#120255 J_ID: ZAY Customer A_ID: BKLT2012_Abstracts Cadmus Art: ANA12 Date: 18-September-12 M1453. A Clinical Study of the Distal Hereditary Motor Neuropathies Alexander M. Rossor, Henry Houlden and Mary M. Reilly; London, United Kingdom Stage: Page: 108 M1456. SMN Controlled MiR-183 Regulates Neuronal Morphology Via mTOR and Akt1 Min J. Kye, Mary H. Wertz, Bikem Akten, Pierre Neveu, Kenneth S. Kosik and Mustafa Sahin**; Boston, MA; Santa Barbara, CA and Heidelberg, Germany The distal hereditary motor neuropathies (dHMN) are a genetically heterogeneous group of diseases characterised by distal lower motor neuron weakness. To date, mutations in eleven genes have been identified that account for 20% of cases. We describe the genotypic and phenotypic spectrum of a cohort of patients with dHMN attending the hereditary neuropathy clinic at the National Hospital for Neurology and Neurosurgery. Sanger sequencing of the known dHMN genes, was performed to determine the genetic frequency and phenotypic spectrum of these mutations. Each patient with an identified pathogenic mutation underwent a clinical examination and in selected cases a MRI of the leg musculature. No pathogenic mutations were identified in ATP7A or HSJ1. Of 61 patients with dHMN, 5 patients had a mutation in HSPB1, 1 in HSPB8, 1 in GARS, 2 in BSCL2 and 5 in TRPV4. In patients with mutations in HSPB1, ankle plantar flexion weakness was greater than or equal to ankle dorsiflexion weakness providing a useful diagnostic clue to direct genetic testing. Muscle MRI in these patients confirmed the selective and early involvement of the gastrocnemius and soleus muscles. Study supported by: This study was supported by the Medical Research Council (MRC), the Muscular Dystrophy Campaign and the National Institutes of Neurological Diseases and Stroke and office of Rare Diseases (U54NS065712). Reduced levels of SMN protein result in deficits in various aspects of neuronal development, such as axonal growth, leading to the devastating pediatric motor neuron disease, spinal muscular atrophy (SMA). However, the molecular mechanisms by which SMN regulates neuronal development are not well understood. Here we report that reduction in SMN protein alters miRNA expression and distribution in neurons. In particular, the levels of miR-183 are increased in neurites of SMN deficient neurons. While reducing SMN protein lowers the expression of genes in the mTOR pathway, leading to arrest of neurites outgrowth, inhibition of miR-183 expression rescues phenotype of SMN knockdown neurons by upregulating mTOR activity. This effect appears to be due to translational regulation of mTOR, Akt1 and Rictor by direct miR-183 binding to their 3вЂ™UTRs. Moreover, elevated level of miR-183 can block Akt1 and mTOR translation in growing axons. Taken together, these observations suggest that microRNAs can regulate local translation of specific genes directly and control protein synthesis broadly by modulating the activity of mTORC1 and mTORC2 and highlight a new molecular mechanisms contributing to SMA pathology. Study supported by: Slaney Family Fund, Whitehall Foundation, ChildrenвЂ™s Hospital Boston Translational Research Program, the ChildrenвЂ™s Hospital Boston Intellectual and Developmental Disabilities Research Center (P30 HD18655), Harvard NeuroDiscovery Center and the Hearst Foundation M1454. Withdrawn. M1455. Electrical Impedance Alterations in Muscle Induced by Hindlimb Unloading Jia Li, Andrew Spieker, Glenn D. Rosen and Seward B. Rutkove; Boston, MA M1457. Clinical, Molecular and Muscle Histopathological Features in Myotonic Dystrophy Type 1 (DM1) Associated with Variant CCG Expansions Marcella Masciullo, Massimo Santoro, Giulia Conte, Roberta Pietrobono, Anna Modoni, Maria Laura E. Bianchi, Valentina Rizzo, Maria Grazia Pomponi, Enzo Ricci, Giovanni Neri and Gabriella Silvestri; Rome, Italy Objective: Improved approaches for quantifying muscle disuse are needed. Here we evaluate the potential role of electrical impedance myography (EIM) to serve in this role. Methods: 62 male Wistar rats underwent hind limb suspension for two weeks; this was followed by 2 weeks of recovery with full-weight bearing. EIM was performed on the gastrocnemius-soleus complex weekly using surface electrodes. Ten rats were euthanized weekly and their gastrocnemius muscles extracted and muscle fiber size measured using stereological probes. Results: Hindlimb unloading caused significant alterations in tissue impedance with mean EIM phase decreasing 16.0%, from 16.3 6 0.29 to 13.7 6 0.55 degrees (mean 6 SEM, p < 0.001) over the two-week period; the changes only partially reversed after 2 weeks of recovery, reaching a final value of 14.0 6 0.58 degrees. A moderate correlation was present between muscle fiber size and the impedance values when including the baseline and two-week suspension data (r Вј 0.48, df Вј 20, P < .05). Conclusions: These data suggest that EIM is capable of measuring the effects of disuse. EIM may be useful for measuring muscle loss due to illness, prolonged bed rest, microgravity, or age-related sarcopenia. Study supported by: National Institutes of Health Dr. Rutkove holds equity interest and receives consulting fees from Convergence Medical Devices, Inc, a company whose main focus is the development of devices for the measurement of muscle impedance. We assessed clinical, molecular and histopathological features in five unrelated Italian DM1 patients carrying вЂ�вЂ�variantвЂ™вЂ™ expansions containing CCG interruptions within the CTG array at the 30 -end of DMPK, detected by bidirectional TP-PCR and sequencing. In three patients, manifesting a typical SteinertвЂ™s disease, routine long-range PCR testing was negative; two other cases were identified among 100 DM1 patients re-evaluated to estimate the prevalence of variant expansions. The overall prevalence of variant expansions was 4.8%. Excluding the lack of a significant cognitive involvement, variant DM1 patients showed no other atypical clinical features vs SteinertвЂ™s patients. Variant expansions included either short as well as large expanded alleles, and the repeat size was similar both in muscle and leukocytes. Also in such cases, muscle RNA-FISH, immunofluorescence for MBNL1 and RT-PCR analysis documented the presence of ribonuclear inclusions co-localizing with MBNL1 and an aberrant splicing pattern known to be involved in DM1 pathogenesis. Our data suggest that CCG interruptions at the DM1 locus would modulate the phenotype mostly influencing the replication dynamics of expanded DNA repeats, rather than 108 ID: guganp I Black Lining: [ON] I Time: 09:25 I Path: N:/3b2/ANA#/Vol00000/120255/APPFile/JW-ANA#120255 J_ID: ZAY Customer A_ID: BKLT2012_Abstracts Cadmus Art: ANA12 Date: 18-September-12 affecting the RNAs higher structure and/or their interaction with MBNL1. Study supported by: Partially funded by grants from the Italian Ministry for the Scientific Research Stage: Page: 109 M1460. In Sensory Neuropathy Contact Heat Evoked Potential Stimulation (CHEPS) Small Fiber Conduction Velocity (CV) Is Faster in Peripheral Than in Central Spinothalamic Pathways Benn E. Smith, Mark A. Ross, Brent P. Goodman, E.P. Bosch and Lyell K. Jones, Jr; Scottsdale, AZ and Rochester, MN M1458. Metabolic Syndrome Reduces Cutaneous Nerve Regenerative Capacity J. Robinson Singleton, Robin Marcus, Collin J. Arsenault, Michael Porzio, Justin E. Jackson and A. Gordon Smith; Salt Lake City, UT Introduction: Nerve conduction studies (NCS) predominantly assess large diameter myelinated fibers. CHEPS provides an objective measure of A delta fiber pathway CV. Methods: To assess small (A delta) fiber CV in the periphery vs. in the CNS twenty-one patients with sensory neuropathy were recruited with IRB approval. Evaluations included CHEPS of limb and spine (L1 and C7) sites. CV values were calculated between skin stimulation sites and scalp. Results: CV values from distal limb sites showed means of 3.6 m/s (foot) and 2.3 m/s (hand) while spine CV values had mean values of 1.4 m/s (L1) and 0.7 m/s (C7). These values are similar to those found in controls. Conclusions: 1) Small (A delta) fiber CV values are higher from distal limb than from corresponding spinal sites, and 2) with the vast majority of the pathway between spine and cerebral cortex being central and the peripheral extent of this pathway being longer in peripheral than central segments when stimulating distal limb sites, it may be hypothesized that peripheral small (A delta) fiber CV is greater than central small (A delta) fiber CV. Study supported by: Mayo Foundation Capsaicin application for 48 hours induces cutaneous fibers to die back into the dermal skin layer. Re-growth over 90 days can be monitored by serial 3mm punch skin biopsies to determine intraepidermal nerve fiber density (IENFD). We used capsaicin axotomy to compare regeneration rate for subjects without neuropathy symptoms, ages 30-65, in three categories: normal controls (N Вј 7), metabolic syndrome with prediabetes (MSP) (25), or diabetes (29). Capsaicin axotomy was repeated during the final half of six months of intensive diet counseling and weekly observed exercise. Baseline thigh IENFD (but not other baseline neuropathy measures), and 30 day regeneration rate were significantly reduced in MSP subjects (0.088 Гѕ/- 0.047 fibers/mm/day) and diabetes (0.092Гѕ/- 0.067) compared to controls (0.137, p<0.05 for both comparisons). BMI and fasting glucose correlated with baseline 90 day reinnervation rate (p<0.05 for each). Following 3 and 6 months of dietary counseling and exercise, change in BMI significantly correlated with change in 30 day and 90 day regeneration ratio (Pearson correlate -0.719 (p Вј 0.003) and -0.485 (p Вј 0.04) respectively, as did change in triglycerides. MSP is associated with reduced IENFD and cutaneous regeneration capacity, while improved obesity and hypertriglyceridemia predict increased regeneration capacity. Study supported by: American Diabetes Association M1461. Bortezomib Alters Microtubule Localization and Mitochondrial Dynamics in Rat Dorsal Root Ganglion Neurons Nathan P. Staff, Jewel L. Podratz, Lukas Grassner, Miranda Lange, Justin Paz, Andrew M. Knight, Charles L. Loprinzi, Eugenia Trushina and Anthony J. Windebank; Rochester, MN Bortezomib is part of a newer class of chemotherapeutic agents whose mechanism of action is inhibition of the proteasome-ubiquitination system. Primarily used in multiple myeloma, bortezomib causes a sensory-predominant axonal peripheral neuropathy in approximately 30% of patients. There are no established useful preventative agents for bortezomibinduced peripheral neuropathy (BIPN), and the molecular mechanisms of BIPN are unknown. We have developed an in vitro model of BIPN using rat dorsal root ganglia neuronal cultures. At clinicallyвЂ“relevant dosages, bortezomib produces a sensory axonopathy as evidenced by whole explant outgrowth and cell survival assays. This sensory axonopathy is associated with alterations in tubulin dynamics and results in accumulation of somatic tubulin without changes in microtubule ultrastructure or total tubulin levels. Similar findings are observed with lactacystin, an unrelated proteasome-inhibitor, which argues for a class effect of proteasome inhibition on dorsal root ganglion neurons. Finally, there is a change in mitochondrial motility and morphology induced by bortezomib in a time-dependent fashion. This robust model will be used in future mechanistic studies of BIPN and its prevention. Study supported by: This work was supported by NIHNS40471 (AJW) and NIH-CA124477 (CLL). M1459. Confocal Microscopy Is a Reliable Measure of Corneal Innervation A. Gordon Smith, Gene Kim, Michael Porzio, Blaine Allen, Kathleen Digre, Mark Mifflin and Rob Singleton; Salt Lake City, UT There is an urgent need for surrogate small fiber measures. Corneal confocal microscopy (CCM) directly visualizes axons in BowmanвЂ™s layer. This study aimed to develop a standard CCM imaging method. 11 Normal subjects underwent CCM (Heidelberg HRTIII). ! 5 nerve fiber layer images were collected in 5 locations (central, inferior/ superior nasal/ temporal) on the left. A blinded observer measured nerve fiber length (NFL) and tortuosity coefficient (TC) at each site (CCMetrics) and averaged the results. CCM was repeated 1 week later. 2 technicians analyzed images. Mean NFL was 2001Гѕ/-398 uM and TC 29Гѕ/-4.5. The intraobserver relative intertrial variability (RIV) was 6.8Гѕ/-4.0% for NFL (ICC 0.89, p<.0001) and 17 Гѕ/-15% for TC (ICC 0.612, p<0.003). Interobserver RIV was 4.6Гѕ/-2.8% for NFL (ICC 0.98, p<0.001) and 14Гѕ/-8% for TC (ICC 0.94, p<0.003). ANOVA revealed no differences between location. Gender, age, height and weight had no effect. CCM was well tolerated. Average visit time was 15 minutes (5 minutes of image acquisition). CCM is well tolerated and NFL measurement is highly reproducible. Study supported by: ADA08-CR52, ADA 7-11AEC23, NIH R01 DK064814, University of Utah VP for Research M1462. Facioscapulohumeral Dystrophy (FSHD): D4Z4 Fragment Size in Patients with CoatвЂ™s Syndrome Jeffrey M. Statland and Rabi Tawil; Rochester, NY Background: Symptomatic exudative retinal vascular disease (CoatвЂ™s syndrome) is a rare but treatable complication of FSHD. Although a correlation between severe clinical phenotype and large D4Z4 deletions has been reported, the relationship of deletion size to CoatвЂ™s syndrome is unknown. 109 ID: guganp I Black Lining: [ON] I Time: 09:25 I Path: N:/3b2/ANA#/Vol00000/120255/APPFile/JW-ANA#120255 J_ID: ZAY Customer A_ID: BKLT2012_Abstracts Cadmus Art: ANA12 Date: 18-September-12 Methods: We searched a national FSHD registry, reviewed the literature, and sent surveys to 12 FSHD referral centers in the United States and overseas to identify genetically confirmed FSHD patients with a diagnosis of CoatвЂ™s syndrome. Results: Out of 343 genetically confirmed patients in an FSHD registry (21 with D4Z4 fragments 15 kb) no subjects reported CoatвЂ™s syndrome. We identified 8 genetically confirmed subjects with CoatвЂ™s syndrome: 6 from our survey and 2 from the literature. The age of onset of CoatвЂ™s syndrome ranged from 1st year of life to 53 years old. The median D4Z4 fragment size was 12.5 kb (range 10-13 kb). 1 patient was mosaic (55% 11 kb, and 45% 78 kb). Conclusions: CoatвЂ™s syndrome is a very rare extramuscular complication of FSHD associated with large D4Z4 deletions. Closer surveillance for retinal complications is warranted in FSHD patients with D4Z4 fragments 15kb. Study supported by: none Stage: Page: 110 Results: Forty infants were enrolled at 8 sites in North America and Europe over an 18 month period; 2 subjects immediately withdrew, leaving 38 subjects. Average age was 5.5 months; 11/38 had a feeding tube and 23/38 had respiratory insufficiency at baseline. 261 adverse events occurred, including 83 SAEs, and13/38 subjects (34.2%) died; death/ ventilator dependence more than 16 hrs/day occurred in 37%. Over the first six months, motor function (TIMPSI scores) declined by -4.75, mean ulnar CMAP amplitude/ area declined by more than 50%, and caregiver questionnaire scores increased by 11 points, indicating worsening of overall status. Conclusions: We demonstrate feasibility for successful enrollment of SMA type I infants in multicenter clinical trials. The exploratory endpoints used here demonstrate promise for future trials, indicating measurable disease progression over a six-month period. Presymptomatic diagnosis or a mechanism for early enrollment of infants in trials immediately following initial diagnosis would maximize benefit and minimize adverse outcomes in this fragile population. Study supported by: Families of Spinal Muscular Atrophy M1463. SMN May Have Multiple Functions Necessitating Widespread Restoration for Maximal Therapeutic Benefit in SMA Tara L. Martinez, Lingling Kong, James P. Van Meerbeke, Rebecca Gibbs, Crystal Davis, Heather L. Plaster, Chien Ping Ko, James R. Rusche, Cathleen M. Lutz, Mark M. Rich and Charlotte J. Sumner; Baltimore, MD; Dayton, OH; Bar Harbor, ME; Waltham, MA and San Diego, CA M1465. Fetal Stem Cells in DuchenneвЂ™s Muscular Dystrophy (DMD) Nataliia S. Sych, Mariya O. Klunnyk, Olena V. Ivankova and Iryna G. Matiyaschuk; Kiev, Ukraine Though modern methods can prolong life expectancy of DMD patients, but fetal stem cell therapy (FSCT) can be more promising. Goal of research was to study FSC efficacy in integrated treatment of DMD. Study included 27 male DMD patients aging 4-27. Diagnosis was confirmed clinically and on the basis of test results (high CPK and LDH), EMG, genetic testing, muscle biopsy. Functional capacity of patients was assessed on Total Functional Grade (TFG) scale, quality of life вЂ“ on SF-36. Patients were examined before stem cell therapy treatment and 6 months after it. All patients underwent transplantation of hematopoietic and non-hematopoietic mesenchymal and ectodermal FSC harvested from germ layers of internal organs of 4-8 weeks old fetuses. FSCT resulted in improvements on TFG вЂ“ from 8,5760,66 before the treatment to 7,7560,54 after the treatment, p<0,05. 0,5-point improvement was reported in 85,19% cases, 1-point вЂ“ in 11,11%, and 1,5-point in 3,7%. FSCT also resulted in physical and psychoemotional improvement, higher self-esteem and spiritual realization. FSCT improved functional capacity and life quality of DMD patients, which proves that this method is very promising and should be researched and advanced. Study supported by: Our own company, not by any sponsors SMA is caused by inadequate expression of the ubiquitous survival motor neuron (SMN) protein. In SMA mice, disruptions of peripheral and central synaptic function precede synaptic retraction and motor neuron loss. This period of impaired synaptic connectivity may define a temporal window of disease reversibility. To characterize the cellular determinants of this synaptic vulnerability, we generated conditional SMA mice in which SMN expression was increased specifically in motor neurons or muscle. We show that synaptic function and maintenance is solely dependent on SMN expression in motor neurons, but SMN plays an independent role in myofiber growth. Thus, SMN has distinct functions in different tissues and widespread restoration of SMN may be necessary for maximal therapeutic benefit. The novel SMA drug RG3039 is in phase I clinical trials and shows excellent biodistribution in multiple tissues. SMA mice treated with RG3039 show increased survival and improved synaptic integrity. Conditional SMA mice with partial restoration of SMN selectively in motor neurons show enhanced responsiveness to RG3039 suggesting that RG3039 may work synergistically with therapies that would increase SMN specifically in the CNS including gene therapy and antisense oligonucleotides. Study supported by: HHMI, NINDS, Repligen M1464. A Multicenter Phase II Open-Label Trial of Valproic Acid and L-Carnitine in Infants with SMA Type I Kathryn J. Swoboda, Kristin Krosschell, Thomas Crawford, Charles Scott, John Kissel, Mary K. Schroth, Gyula Acsadi, Priya Kishnani, Jurgen-Christoph von Kleist-Retzow, Guy DвЂ™Anjou, Edward C. Smith, Bakri Elsheik, Louise R. Simard, Thomas W. Prior and Sandra P. Reyna; Salt Lake City, UT; Chicago, IL; Baltimore, MD; Fort Washington, PN; Columbus, OH; Madison, WI; Detroit, MI; Durham, NC; Cologne, Germany; Montreal, QC, Canada and Winnepeg, MB, Canada M1466. The Survival Motor Neuron (SMN) Gene as a Therapeutic Target in Amyotrophic Lateral Sclerosis Kevin Talbot, Neza Alfazema, Kay E. Davies and Bradley J. Turner; Oxford, United Kingdom and Melbourne, Australia Reduced levels of the SMN protein are the cause of spinal muscular atrophy. Genetic studies have implicated SMN as a risk factor for the development of amyotrophic lateral sclerosis (ALS). Crossing the SOD1 G93A mouse model of familial ALS with a mouse expressing 50% of normal SMN levels results in an accelerated ALS phenotype. Here we test the hypothesis that increased levels of SMN can ameliorate the ALS phenotype by crossing SOD1G93A strain with Objectives: To perform an open label multicenter study of valproic acid (VPA) and L-carnitine in SMA type I infants to explore feasibility and potential efficacy endpoints. 110 ID: guganp I Black Lining: [ON] I Time: 09:25 I Path: N:/3b2/ANA#/Vol00000/120255/APPFile/JW-ANA#120255 J_ID: ZAY Customer A_ID: BKLT2012_Abstracts Cadmus Art: ANA12 Date: 18-September-12 mice (PrP-SMN) overexpressing SMN in neurons. Weight, survival, locomotor activity and motor neuron number were compared with control SOD1G93A littermates. Two-fold SMN upregulation significantly delayed weight loss, delayed disease onset and preserved spinal motor neurons in SOD1G93A PrP-SMN animals. There was no effect on overall lifespan, which is most likely to be due to the depletion of SMN at the end stage of disease by misfolded SOD1 protein. These results suggest that SMN upregulation protects against early stages of disease and neurodegeneration in this model of ALS and supports the use of drugs and biological agents which increase SMN levels in clinical trials in ALS. Study supported by: Motor Neurone Disease Association, National Health and Medical Research Council, Australia Stage: Page: 111 Typically this has used independent component analysis. However, alternative complex network or system measures, including machine-learning classification, have the potential to capture more subtle patterns of activity. They have been applied to other conditions indicating that diseased brains exhibit profound deviances from healthy patterns of synchronicity. We have applied multiple kernel optimization techniques to patterns of complexity derived from R-fMRI scans obtained from a large group of clinically well characterized ALS patients seen as part of the Oxford Study for Biomarkers in Motor Neuron Disease (BioMOx). Preliminary results demonstrate separation of patients from age-matched healthy volunteers, with significant potential for clinical translation of this novel biomarker approach in ALS. Study supported by: Medical Research Council & Motor Neurone Disease Association Lady Edith Wolfson Fellowship M1467. Quantitative Analysis of FLAIR Images in ALS Has Diagnostic Potential Jez Fabes, Lucy Matthews, Nicola Fillipini, Kevin Talbot, Mark Jenkinson and Martin R. Turner; Oxford, United Kingdom M1469. Congenital Amyelinating Neuropathy: A Genetically Heterogeneous Syndrome Jean-Michel Vallat, Pierre-Marie Gonnaud, Philippe Latour, Federico Garcia Bragado and Benoit Funalot; Limoges, France; Pierre Benite, France; Lyon, France and Pamplona, Spain Therapeutic development in amyotrophic lateral sclerosis (ALS) would benefit from diagnostic biomarkers to permit earlier administration of candidate drugs, as well as those that capture phenotype heterogeneity. A biomarker derived from routine investigations, such as standard clinical MRI sequences, would have obvious appeal. T2-weighted MRI corticospinal tract (CST) hyperintensity is frequently observed in ALS, but regarded as insufficiently sensitive when reported visually. Quantitative objective MRI analysis was performed on T2-weighted fluid-attenuated inversion recovery (FLAIR) images acquired at 3 Tesla from 49 patients (33 вЂ�вЂ�classicalвЂ™вЂ™ ALS, 10 вЂ�вЂ�flail-armвЂ™вЂ™ ALS, 6 primary lateral sclerosis (PLS)) and compared with 21 age-matched healthy controls. FLAIR intensity was significantly greater in the CST (p Вј 0.001) and corpus callosum (p Вј 0.003) of MND patients. Of the phenotype subgroups, the highest intensity was found in PLS and the lowest in flail-arm patients. Classification of MND patients into the appropriate phenotype improved from 52% accuracy with clinical measures alone, to 82% with the addition of FLAIR intensities. In a longitudinal analysis, the increase in FLAIR intensity was correlated with the rate of clinical progression. Quantitative measurement of regional FLAIR intensity might provide additional diagnostic value in the clinical setting. Study supported by: Medical Research Council and Motor Neurone Disease Association Lady Edith Wolfson Fellowship We report on 2 cases of congenital amyelinating neuropathy (CAN) for which the causal genetic abnormalities have been identified. In one case, the disease was caused by a homozygous 10.7 kilobase-long deletion encompassing a myelin-specific enhancer of EGR2. This patient had a very severe neuropathy and died at 7.5 months of age. Autopsy showed pathological abnormalities recapitulating the peripheral nervous system phenotype of homozygous Egr2-null mice. No EGR2 immunoreactivity was observed in Schwann cell nuclei. The other case was due to the combination of a 17p11.2 deletion inherited from the father and a PMP22 point mutation inherited from the mother. The patient had a much less severe clinical phenotype but showed a complete absence of peripheral myelin on sural nerve biopsy. Our findings confirm that CAN can be caused by various genetic abnormalities. The frequency of this disease is underestimated and should be systematically discussed when a вЂ�вЂ�floppy infantвЂ™вЂ™ is examined. The complete absence of myelin sheath can only be demonstrated by an ultrastructural study of nerve biopsy. Study supported by: No one M1470. Cerebral Metabolic Features of Clinically Heterogenous A3243G Mitochondrial DNA Mutation Carriers: Prognostic Implications Nora Weiduschat, Petra Kaufmann, Xiangling Mao, Kristin Engelstad, Vanessa Battista, Mary Sano, Michio Hirano, Salvatore DiMauro, Darryl C. DeVivo and Dikoma C. Shungu; New York, NY M1468. Complexity-Based Classification of Resting-State fMRI in Amyotrophic Lateral Sclerosis Tomer Fekete, L. R. Mujica-Parodi and Martin R. Turner; Stony Brook, NY and Oxford, United Kingdom Anticipating the long-term outcome in asymptomatic mitochondrial mutation carriers is challenging and appropriate biomarkers predicting prognosis do not exist. In the present study we investigated 135 clinically heterogeneous carriers of the A3243G mutation and 30 healthy controls (HC). Mutation carriers included 45 fully symptomatic MELAS patients; 11 asymptomatic individuals who would develop the MELAS syndrome during the natural history study (converters); and 79 individuals who would remain asymptomatic (non-converters). Brain proton magnetic resonance spectroscopic imaging (1H MRSI) revealed lactate elevations and reduced N- Amyotrophic lateral sclerosis (ALS) is a neurodegenerative process involving extra-motor as well as motor cortical regions. A robust non-invasively acquired cerebral вЂ�вЂ�signatureвЂ™вЂ™ reflecting disease activity in ALS, ideally also sensitive to phenotype, would be extremely valuable diagnostically and in the development of therapeutics. Capturing the in vivo neurodegenerative process as a whole is challenging. Resting-state functional MRI (RfMRI) uniquely allows the assessment of patterns of neuronal synchronicity (in space and time). Changes in R-fMRI functional connectivity have been demonstrated in ALS. 111 ID: guganp I Black Lining: [ON] I Time: 09:25 I Path: N:/3b2/ANA#/Vol00000/120255/APPFile/JW-ANA#120255 J_ID: ZAY Customer A_ID: BKLT2012_Abstracts Cadmus Art: ANA12 Date: 18-September-12 acetylaspartate (NAA) levels in fully symptomatic MELAS patients compared to HC, as described previously. Surprisingly, converters not only had significantly higher lactate values, but also higher NAA, choline and creatine values than HC and non-converters, presumably reflecting compensatory changes preceding cerebral energy failure. Furthermore, in carriers significant linear correlations were found between brain NAA and lactate levels, clinical indices and peripheral mutation levels. Cerebral metabolite values as determined by 1H MRS might help to identify individual mutation carriers at increased risk for developing MELAS. Continued longitudinal studies will be necessary to further clarify the prognostic value of 1H MRS for individuals harboring the A3243G mutation. Study supported by: NICHD grant P01-HD32062; CTSA 1-UL1-RR024156; an Irving Scholar Award; the Marriott Mitochondrial Disorder Clinical Research Fund; and the Colleen Giblin Foundation Stage: Page: 112 VAPB) were PCR-amplified from these pools and deeply sequenced. The SPLINTER algorithm performed read alignments and variant calling. C9ORF72 expansions were assayed by repeat-primed PCR. Results: 39% of familial and 6% of sporadic patients had C9ORF72 expansions. Ten published mutations were found in 13 individuals. 14 novel and potentially pathogenic variants were identified in 8 genes. 25 rare variants (MAF 0.5%) and many common polymorphisms were also present. Conclusion: Pooled-sample sequencing allowed the simultaneous screening of 17 ALS genes in a cohort of familial and sporadic ALS cases. In addition to rapidly and efficiently finding novel mutations for further characterization, we identified a cohort of patients without mutations for future gene discovery efforts. Study supported by: NINDS K08 M1473. Optimizing the Total Neuropathy Score for HIV-Associated Distal Symmetric Polyneuropathy Jessica Robinson-Papp, Sandeep Sharma, David M. Simpson and Susan Morgello; New York, NY M1471. The Role for Macrophages in Nerve Repair in an Animal Model of Autoimmune Neuropathy Gang Zhang, Nataliia Bogdanova, Lixia Gao and Kazim A. Sheikh; Houston, TX Objective: The Total Neuropathy Score (TNS) has been validated in diabetic and chemotherapy-induced neuropathy. A modified TNS is used in HIV-associated distal symmetric polyneuropathy (HIV-DSP), but has not been validated. We sought to determine if this modification is valid and optimal for assessing HIV-DSP. Methods: Seventy-one HIV-infected individuals underwent neurologic examination, symptom assessment, nerve conductions, quantitative sensory testing (QST), and autonomic testing (heart rate response to deep breathing (HRDB) and quantitative sudomotor axon reflex testing (QSART)). Modifications of the TNS were assessed for internal consistency reliability (ICR), and validity as determined by correlation with the TNS and agreement with clinical diagnosis. Results: The modified TNS had acceptable ICR (CronbachвЂ™s a Вј .7), was highly correlated with the TNS (r Вј .94; p<.001), and showed excellent agreement with clinical diagnosis (CohenвЂ™s j Вј .77). However diagnostic accuracy was improved by elimination of QST (j Вј .83), and improved further by the addition of autonomic measures (symptoms, QSART, and HRDB; j Вј .88). INTERPRETATION. HIV-DSP is best diagnosed using a modified TNS that includes measures of autonomic function and eliminates QST. However if autonomic tests are unavailable, an abbreviated TNS is still reliable and valid. Study supported by: K23NS066789 Autoantibodies against specific gangliosides contribute to the development of certain forms of Guillain BarreВґ syndrome (GBS), and are associated with slow and poor recovery in some GBS patients. Our previous work indicates that human and mouse-derived anti-ganglioside antibodies (Abs) inhibit nerve repair/axon regeneration both in-vivo and in-vitro by engaging nerve cell membrane gangliosides. Now we have determined that this Ab-mediated inhibition is dependent on expression of activating Fc gamma receptors. Macrophages play a vital role in cleaning myelin debris during Wallerian degeneration. Successful recruitment of hematogenous macrophages after nerve injuries has been suggested to help the process of nerve repair in peripheral nervous system (PNS). In the present study, we sought to evaluate the contribution of macrophages in the anti-gangliosides Abs mediated-inhibition of axonal regeneration after PNS injury in osteopetrotic mice with macrophage deficiency (op/op mice). Our results show that, after treatment with anti-gangliosides Abs, op/ op mice have significantly more regenerated myelinated nerve fibers compared to wild type animals, implicating that the antibody mediated-inhibition is dependent on the presence of macrophages. Our studies provide an example of context-dependent negative influence of macrophages in nerve repair. Study supported by: Acknowledgements: These studies were supported by GBS/CIDP Foundation and NIH/ NINDS (NS42888 and NS54962). M1474. Motor Neuron Disease-Associated Mutations in p150/Glued Disrupt the Initiation of Retrograde Axonal Transport at Synaptic Termini Thomas E. Lloyd, James Machamer, Sarah Collins and Alex L. Kolodkin; Baltimore, MD M1472. Comprehensive Genetic Screening of a Large ALS Cohort Using Pooled-Sample Sequencing Matthew B. Harms, Janet Cady, Peggy Allred, Taha Bali, Ryan T. Libby, Alan Pestronk, John Ravits and Robert H. Baloh; Saint Louis, MO; La Jolla, CA and Los Angeles, CA Increasing evidence suggests that defects in axonal transport may be a primary cause of neurodegenerative diseases. p150/Glued is the major subunit of dynactin, a complex that functions with dynein in minus-end-directed microtubule transport. Different mutations within the p150 CAPGly microtubule-binding domain cause distinct autosomal dominant neurodegenerative syndromes, termed Hereditary Motor Neuropathy 7B (HMN7B) and Perry Syndrome. HMN7B-associated mutations introduced into Drosophila Glued using homologous recombination generate a partial loss-of-function allele (Gl[G38S]) with impaired Objective: Genetically characterize a cohort of ALS patients using pooled-sample sequencing to circumvent costly, timeconsuming, and sample-depleting traditional sequencing. Methods: DNA from 41 familial probands and 373 sporadic ALS patients was pooled in groups of 25-50 individuals. Coding exons of 17 genes (ANG, C9ORF72, DAO, DCTN1, EWSR1, FIG4, FUS, OPTN, SETX, SIGMAR1, SOD1, SQSTM1, TAF15, TARDBP, UBQLN2, VCP, 112 ID: guganp I Black Lining: [ON] I Time: 09:25 I Path: N:/3b2/ANA#/Vol00000/120255/APPFile/JW-ANA#120255 J_ID: ZAY Customer A_ID: BKLT2012_Abstracts Cadmus Art: ANA12 Date: 18-September-12 neurotransmitter release at the neuromuscular junction (NMJ) and adult-onset locomotor dysfunction. Interestingly, Gl[G38S] animals accumulate endosomes within swollen terminal boutons of the NMJ due to a neuron autonomous loss of Glued function. Live imaging analysis of vesicle transport along axons and at the NMJ suggests that this phenotype is not due to a generalized defect in axonal transport, but rather a specific defect of dynactin in coordinating initiation of retrograde transport at microtubule plus ends of the distal-most NMJ boutons, called terminal boutons. Together, these data suggest that the presynaptic retractions that occur early in motor neuron degenerative diseases begin with an inability to initiate retrograde axonal transport at terminal boutons. Study supported by: NINDS K08 award; Robert Packard Center for ALS Research Stage: Page: 113 T1502. Antipsychotic Drug Effects at Nicotinic AChRs Studied in a Novel Model System Tai-Xiang Xu, Limin Hao, Bruce M. Cohen and Edgar A. Buttner; Belmont, MA We have shown that pharmacogenomic experiments in C. elegans identify novel and mechanistically important pathways modulated by antipsychotic drugs (APDs). Recently, we conducted the first genetic screen for APD targets in an animal, a genome-wide RNA interference (RNAi) screen for Suppressors of Clozapine-induced Larval Arrest (scla genes). The screen covered $17,000 C. elegans genes and led to the identification of $40 suppressors. We have characterized the suppressor acr-7, which encodes a homolog of the human a-like nicotinic acetylcholine receptors (nAchRs). Our preliminary results indicate that acr-7 is strongly expressed in the pharynx and that clozapine activates ACR-7, leading to a depolarizing neuromuscular blockade of pharyngeal muscle and subsequent larval arrest. Importantly, the observation that APDs activate a-like nAchRs is novel and might be relevant to clinical drug effects. Since human orthologs of acr7 may mediate the therapeutic and/or toxic effects of APDs in clinical use, we are using physiological studies in heterologous systems to identify mammalian orthologs of acr-7. These orthologs may pose inviting drug targets for the development of compounds that replicate clozapineвЂ™s therapeutic effects but that do not share its side effects. Study supported by: Shervert Frazier Research Institute 2012 Annual Meeting Tuesday, October 9, 2012 Poster Session Abstracts Posters will be displayed in Gloucester, located on the 3rd floor in the Back Bay Hall of the Marriott Copley Place from 11:30 am вЂ“ 7:00 pm, with authors present from 5:30 pm вЂ“ 7:00 pm. NOTE: An asterisk designates a resident/fellow travel award winner. T1503. From Molecule to Mechanism: How Listening to Synapses Reveals Novel Insights to OCD Pathogenesis Nicole Calakos, Yehong Wan, Meng Chen, Kristen Ade, William Wetsel and Guoping Feng; Durham, NC and Boston, MA Behavioral Neurology T1501. Metabolic Abnormalities in the Caudate in Patients with Mitochondrial Disorders Measured Using Proton Magnetic Resonance Spectroscopy Rebecca Anglin, Patricia Rosebush, Michael Noseworthy, Mark Tarnopolsky and Michael Mazurek; Hamilton, Canada Compulsive behaviors are disruptive, maladaptive behavioral responses that occur in diverse conditions and across our life span; arising in conditions such as Obsessive Compulsive Disorder (OCD), TouretteвЂ™s Syndrome, autism, drug addiction, medication side effects and neurodegenerative diseases. Knowledge of the molecular pathways, cellular mechanisms, and circuits that drive compulsive motor behaviors can greatly accelerate development of effective treatments and is at present greatly lacking. Using a mouse model that lacks a postsynaptic scaffold protein and exhibits intransigent grooming, anxiety-like behaviors and therapeutic response to fluoxetine (Welch et al., 2007), we have found a role for excessive metabotropic glutamate receptor (mGluR) signaling at cortico-striatal synapses in driving OCD-like behavior. Defects in synaptic function and plasticity first implicated an overactive mGluR signaling pathway and can be used to predict circuit function and behavioral states. These results implicate a new class of receptors in compulsive behavioral disorders and elucidate synaptic and circuitlevel mechanisms. Study supported by: NINDS, Klingenstein Foundation, Tourette Syndrome Association, Duke Institute for Brain Sciences Mitochondrial disorders are clinical syndromes associated with mutations in the mitochondrial or nuclear genome that result in impaired oxidative phosphorylation and deficient energy production. To date there has not been a systematic investigation of brain metabolites in patients with mitochondrial disorders compared to matched healthy controls. This study used single voxel proton magnetic resonance spectroscopy (PRESS, TE Вј 35 ms, TR Вј 2000 ms, 256 acquisitions) to measure N-acetyl-aspartate (NAA), creatine (Cr), glycerophosphocholine (GPC), GPCГѕphosphocholine (PCh), myoinositol (mI), and glutamine Гѕ glutamate (Glx) in the caudate, anterior cingulate and hippocampus in 15 patients with mitochondrial disorders and 15 age and sex-matched healthy controls. Patients with mitochondrial disorders had significantly reduced NAA (p Вј 0.023) in the caudate compared to controls. Cr, GPCГѕPCh and Glx were also reduced in the caudate in patients compared to controls. These results support previous assertions that NAA is a useful marker of mitochondrial dysfunction and that the striatum is highly susceptible to mitochondrial oxidative phosphorylation defects. Given the caudates role in cognitive and executive functions, our findings also suggest that metabolic abnormalities in the caudate may contribute to neuropsychiatric symptoms in these patients. Study supported by: Physicians Services Incorporated (Grant R06-24) T1504. Brainstem Lesions and Central Auditory Processing Gastone G. Celesia; Chicago, IL Auditory processing can be disrupted by brainstem lesions. Lesions below or within the cochlear nuclei result in ipsilateral auditory processing abnormalities detected in routine testing, disorders rostral to the cochlear nuclei may result in bilateral abnormalities or may be silent. 113 ID: guganp I Black Lining: [ON] I Time: 09:25 I Path: N:/3b2/ANA#/Vol00000/120255/APPFile/JW-ANA#120255 J_ID: ZAY Customer A_ID: BKLT2012_Abstracts Cadmus Art: ANA12 Date: 18-September-12 Lesions in the superior olivary complex and trapezoid body show a mixture of ipsilateral, contralateral and bilateral abnormalities, whereas lesions of the lateral lemniscus, inferior colliculus and medial geniculate body do not affect peripheral auditory processing and result in predominantly subtle contralateral abnormalities that may be missed by routine auditory testing. In these cases psychophysical methods developed for the evaluation of central auditory function should be employed (dichotic listening, inter-aural time perception, sound localization, etc.).The extensive connections of the auditory brainstem nuclei not only are responsible for binaural interaction but also assure redundancy in the system. This redundancy may explain why small brain stem lesions are sometimes clinically silent. Any disorder of the brainstem (neoplasms, vascular disorders, infections, trauma, demyelinating disorders, neurodegenerative diseases, malformations, etc.) that involves the auditory pathways and/or centers may produce hearing abnormalities. Study supported by: none no conflicts of interest Stage: Page: 114 such as when administered as intermittent theta-burst stimulation (iTBS) to the vermis in schizophrenia (Demirtas-Tatlidede,2010). Although classically mainly associated with movement control, the functional role of cerebellum has recently been also linked to emotion and cognitive regulation (Schmahmann,2010). It is suggested that cerebellum may exert this regulatory control via cerebello-cortical loops and its connectivity to areas associated with higher order cognitive processing including the prefrontal cortex (PFC). However, human cerebellum-PFC connectivity and the neurophysiological effects of cerebellar stimulation remain relatively unexplored. TMS combined with EEG permits measuring PFC and motor cortex dynamics in healthy and diseased (Farzan,2010). Here, we employ TMS-EEG to probe cortical processes in the PFC and motor cortex before and after active and sham vermis and lateral cerebellar iTBS. Results to date suggest that active cerebellar iTBS modulates PFC cortical dynamics compared to sham, a mechanism which may explain the therapeutic efficacy of cerebellar stimulation. The results and methods presented here may ultimately help identify patients who would benefit from cerebellar stimulation therapy. Study supported by: Supported in part by the Sydney R. Baer Jr, MINDlink, and Birmingham Foundations. FF received postdoctoral fellowship scholarship from Canadian Institute of Health Research (CIHR). This work was conducted with support from Harvard Catalyst | The Harvard Clinical and Translational Science Center (National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health Award #UL1RR 025758 and financial contributions from Harvard University and its affiliated academic health care centers). The content is solely the responsibility of the authors and does not necessarily represent the official views of Harvard Catalyst, Harvard University and its affiliated academic health care centers, or the National Institutes of Health. FF, MAH, APC and JDM have no conflicts of interests. APL serves on the scientific advisory boards for Nexstim, Neuronix, Starlab Neuroscience, Allied Mind, Neosync, and Novavision, and holds intellectual property on the real-time integration of transcranial magnetic stimulation (TMS) with electroencephalography (EEG) and magnetic resonance imaging (MRI). T1505. Frequency of Elevated ASO Titer in Children and Adolescents at Onset or Exacerbation of Tic, OCD or Aggression and Symptomatic Effect of Antibiotic Treatment Brittany M. DiVito, Karen D. Ellis and Drake D. Duane; Scottsdale, AZ and Tempe, AZ Background: Whether streptococcal infection with immune response causes or exacerbates tic, obsessive-compulsiveness (OCD), or aggressive (Agg) in pediatric patients is debated (Swedo, 1998; Singer, 2005). This study examines the frequency with which in referred behavioral pediatric patients, with a history of the above symptoms at onset or increment within six months or less, an elevated anti-streptolysin O (ASO) titer was obtained and, if antibiotics (ab) treatment, no adjustment in concomitant Rx, the course of presenting symptom(s). Method: Retrospective chart analysis of pediatric behavioral patients in whom ASO titers were drawn, the frequency of elevated titers, the course of presenting symptom(s) if ab therapy was employed. Results: N-45(34M), mean age 13Гѕ/-4.5 years; Dx Tourette-10; OCD-24; AD(H)D-11 Elevated ASO titer 16(36%)(13M); 10 ab Rx(2-all 3 sx, 3-with 2 sx) Symptom Improved/Total Tic 7(86%) OCD 5/7(7%) Agg3/3(100%) No ab Rx: unchanged-3, unknown-3 Conclusions: ASO titers are not infrequently elevated in behavioral pediatric patients (one-third). Ab Rx may be associated with acute Sx reducton, whether tic, OCD or Agg; the mechanism remains obscure. Study supported by: N/A T1507. Changes in Cortical Functional Connectivity Introduced with Intermittent Theta Burst TMS to the Cerebellum Assessed with fMRI Mark A. Halko, Faranak Farzan, Andrea Pousada-Casal, Jeremy Schmahmann and Alvaro Pascual-Leone; Boston, MA Increasing evidence points to the cerebellum as a universal modulator of cortical activity, via connections with motor and non-motor cortical areas which are organized topographically throughout the cerebellum (Schmahmann 1991). Understanding how the cerebellum modulates nonmotor cortical networks is central to understanding the cerebellar role in cognition and neuropsychiatric disorders. Resting state functional connectivity (rs-fcMRI) has recently emerged as a tool to investigate network function and dysfunction, allowing for study of complex network functions in humans. Transcranial magnetic stimulation (TMS) combined with rs-fcMRI can be used to characterize dynamics in large-scale brain networks (Eldaief 2011). Here we apply this technique to evaluate the role of cerebellar modulation on cortical network function. Healthy subjects received intermittent theta-burst (iTBS) TMS to T1506. Modulation and Assessment of the CerebelloCortical Connectivity through Transcranial Magnetic Stimulation (TMS) Combined with Electroencephalography (EEG) Faranak Farzan, Mark A. Halko, Andrea Pousada-Casal, Jeremy D. Schmahmann and Alvaro Pascual-Leone; Boston, MA Clinical studies have demonstrated the efficacy of cerebellar TMS in ameliorating emotional and cognitive impairments, 114 ID: guganp I Black Lining: [ON] I Time: 09:25 I Path: N:/3b2/ANA#/Vol00000/120255/APPFile/JW-ANA#120255 J_ID: ZAY Customer A_ID: BKLT2012_Abstracts Cadmus Art: ANA12 Date: 18-September-12 vermal or lateral cerebellar targets. Network activity was assessed before and after stimulation using rs-fcMRI. Preliminary data suggests vermal stimulation differentially modulates functional connectivity from the medial frontal cortex, when compared to lateral or sham stimulation. These results suggest modulation of cerebellar function with iTBS TMS may have utility to assess and characterize network-level abnormalities. Study supported by: Supported in part by the Sydney R. Baer Jr, MINDlink, and Birmingham Foundations. FF is supported by Canadian Institutes of Health Research. This work was conducted with support from Harvard Catalyst | The Harvard Clinical and Translational Science Center (National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health Award #UL1RR 025758 and financial contributions from Harvard University and its affiliated academic health care centers) MAH, FF, APC and JDM have no conflicts of interest. APL serves on the scientific advisory boards for Nexstim, Neuronix, Starlab Neuroscience, Allied Mind, Neosync, and Novavision, and holds intellectual property on the real-time integration of transcranial magnetic stimulation (TMS) with electroencephalography (EEG) and magnetic resonance imaging (MRI). Stage: Page: 115 T1509. Effects of the Dopamine Agonist Rotigotine on Hemispatial Neglect Following Stroke Nikos Gorgoraptis, Yee-Haur Mah, Bjoern Machner, Victoria Singh-Curry, Paresh Malhotra, Maria Hadji-Michael, David Cohen, Robert Simister, Ajoy Nair, Elena Kulinskaya, Nick Ward, Richard Greenwood and Masud Husain; London, United Kingdom; LuВЁbeck, Germany and Norwich, United Kingdom Hemispatial neglect following right-hemisphere stroke is a common and disabling disorder for which there is currently no established treatment. Dopamine agonists have been shown to play a role in selective attention and working memory, two core cognitive components of the syndrome. Here, we investigated the effects of the dopamine agonist rotigotine using a double-blind, randomised placebo-controlled ABA design. Each patient was assessed for 20 testing sessions, in three phases: pre-treatment, on transdermal rotigotine for 7-11 days, and post-treatment, with the exact duration of each phase randomised within limits. 16 right-hemisphere patients completed the trial. Performance on the Mesulam shape cancellation task improved significantly while on rotigotine, with the number of targets found on the left increasing 12.8% (P Вј 0.012) on treatment and spatial bias reducing by 8.1% (P Вј 0.016). This improvement in visual search was associated with an enhancement in selective attention but not in working memory or sustained attention measures. Overall, rotigotine was not associated with any significant improvement in motor performance. This proof-of-concept study suggests a beneficial role of dopaminergic modulation on visual search and selective attention in patients with hemispatial neglect following stroke. Study supported by: Medical Research Council (Experimental Medicine grant) and Wellcome Trust Senior Fellowship T1508. PRISM Registry: A Novel Tool To Determine the Prevalence of Pseudobulbar Affect Daniel Kantor, Jonathan Fellus and Randall E. Kaye; Ponte Vedra Beach, FL; Secaucus, NJ and Aliso Viejo, CA Background: Pseudobulbar affect (PBA) is characterized by uncontrollable, inappropriate laughing and/or crying outbursts in patients with neurologic insult. While US prevalence is estimated at 1.5вЂ“2 million, clinicians seldom ask proactively about symptoms. The PBA registry (PRISM) was initiated to evaluate PBA prevalence prospectively. Objective: Identify barriers to registry participation and implement strategies to facilitate enrollment. Methods: Sites enroll via a centralized Web portal and register with a central Institutional Review Board (IRB). Patient screening begins following IRB approval. In all, 500 sites will enroll 10,000 patients at PBA risk in AlzheimerвЂ™s disease, ALS, MS, ParkinsonвЂ™s disease, stroke, or brain injury. Patients complete the Center for Neurologic StudyвЂ“ Lability Scale (CNS-LS) and a QoL measure. Demographic/ disease characteristics are also collected. Results: Initial site-recruitment uncovered obstacles including community-physician unfamiliarity with GoodClinical-Practice processes, need for local IRB use at some sites, and lack of startup-cost recognition. Counterstrategies increased patient-enrollment rate $fivefold, to $500/ month. Currently, 2,244 patients have enrolled, with PBA prevalence 43.3% (by CNS-LS score !13). Conclusions: PRISM is a novel tool to estimate PBA epidemiology across settings. Successful registries require community-physician training/support, plus flexibility to accommodate local IRBs. Study supported by: Avanir Pharmaceuticals, Inc. Dr. Kantor received personal compensation for serving as a speaker and consultant for Avanir Pharmaceuticals, Inc. Dr. Fellus has served on speakers bureau and has been paid honoraria and consultancy fees by Avanir Pharmaceuticals, Inc. Dr. Kaye is an employee of Avanir Pharmaceuticals, Inc. and received stock options as a term of employment. T1510. Sudden Visual Spatial Memory Loss as Presenting Manifestation of CJD Nivedita Jerath, Aarti Jerath, Shelley Waite, Deborah Forst, Shivraj Sohur and Jeremy Schmahmann; Boston, MA A 62 year old previously healthy man awoke from propofol anesthesia for a colonoscopy with visual spatial memory impairment. He was disoriented in the hospital room, and whereas he drove himself to the procedure, he was unable to drive home. T1, T2 and DWI-MRI were unremarkable, but there was subtle FLAIR hyperintensity in right posterior and medial parietal cortices. Over the ensuing month, symptoms progressed to right-left confusion, and trouble finding rooms in his house, although he still paid bills and sent emails. Examination findings were restricted to difficulty producing the floor plan of his house, and suboptimal visual encoding and visual memory. Worsening spatial disorientation and forgetfulness prompted a PET scan showing right parietal and occipital hypometabolism, EEG with runs of frontal sharp waves and triphasic morphology, and LP subsequently positive for 14-3-3 protein. DWI-MRI 2 months into the course showed restricted diffusion in right frontal, parietal, and occipital lobes consistent with CJD. Symptoms progressed to short-term memory loss, increasing confusion, and myoclonus, and he succumbed 3 months after onset. Sudden onset of spatial predominant features with initially normal DWI-MRI are distinctive and unusual manifestations of CJD. Study supported by: Supported in part by the MINDlink and Birmingham Foundations 115 ID: guganp I Black Lining: [ON] I Time: 09:25 I Path: N:/3b2/ANA#/Vol00000/120255/APPFile/JW-ANA#120255 J_ID: ZAY Customer A_ID: BKLT2012_Abstracts Cadmus Art: ANA12 Date: 18-September-12 T1511. Inflammation and Cognitive Decline in Normal Elderly Joel H. Kramer, Brianne Bettcher, Ralph Green and Josh Miller; San Francisco, CA and Davis, CA Stage: Page: 116 ing disability. The transition into adulthood is a critical phase in the management of these patients, which is further complicated by the evolution of the psychiatric symptoms. Objective: To describe the evolution of the psychiatric co-morbidity in a cohort of patients with neurologic disabling perinatal conditions during the transition phase. Materials and methods: 200 subjects with perinatal neurologic conditions were retrospectively traced and analysed for their psychiatric co-morbidity and therapeutic needs. The same group was re-analysed after transition into adulthood. Results: Psychiatric co-morbidity is seen in 26% of patients under age 18, with behavioural disturbances in intellectual disability (5.5%) followed by obsessive compulsive disorder and personality disorders (both around 4%) being the most prevalent diagnosis. 12% of these patients, once transitioned into adulthood, required psychiatric care, with a shift towards the diagnosis of psychosis in most, and need for psychopharmacological treatment in 86%. New psychiatric co-morbidity emerged in 4%. Conclusion: The transition phase for children with neurological disabling condition is a critical point of change including psychiatric co-morbidity requiring appropriate management. Study supported by: Institutional Funds Inflammation represents a normal response to injury. Sustained neuroinflammation, however, can affect cognition and brain structure. The goal of this study was to determine if plasma levels of C-reactive protein (CRP), a marker of chronic inflammation, was associated with longitudinal change in executive functioning in normal elderly. We studied 44 normals whose informants corroborated intact daily functioning and on whom we obtained CRP levels at baseline. The sample include 23 subjects with no detectible CRP (mean age Вј 70), and 21 subjects with detectible CRP (mean age Вј 72; CRP Вј 0.35 mg/dL). Executive functioning was measured using the NINDS EXAMINER battery at baseline and 20 months later. The primary dependent measure was the EXAMINER executive score. Data were analyzed using general linear model controlling for age and education. The primary analysis, the group by time interaction, was significant (p<.05). Follow-up analyses indicated that the two groups performed similarly at baseline. At follow-up, the executive score in the undetectable CRP group was stable, whereas the score in the detectible CRP group dropped by almost one standard deviation. Mechanisms underlying this association between inflammation and rate of cognitive decline are unclear, but potentially include white and grey matter vulnerability. Study supported by: NIH T1514. fMRI Study of Yogic Meditation Shri K. Mishra, Manbir Singh and Parampreet Singh; Los Angeles, CA and Sylmar, CA We present the results of a pilot fMRI study involving 4 subjects to observe and understand the selective activations of certain brain areas during Meditation. The neural substrates of Yogic meditation are not well understood. Meditation is theorized to be a conscious mental process that induces a set of integrated physiological changes within the cortex, hypothalamus and other parts of the brain termed as the вЂ�вЂ�relaxation response.вЂ™вЂ™ Trained (Patanjali Yoga) practitioners were studied. A 3-part 1-min block design alternating between a relaxation(control), and meditation(test) with an imaginary visual fixation and an auditory stimulation, was used to acquire 10 contiguous 8mm thick axial sections in a 1.5T GE MRI. The data was analyzed using standard SPM software. Images showed strongly activated right prefrontal regions during the visual and auditory meditation phases compared to no activations during the relaxation state. A comparison between the visual and auditory fixations revealed shifts within the prefrontal and temporal regions. Activations in occipital and temporal regions were also observed. Specific cortical activations could be modulating the known neurophysiological and biological effects of meditation. Another larger study utilizing DTI-fMRI to further comprehend these effects is currently underway. Details will be presented. Study supported by: None T1512. Acute Impairments of Empathy Richard Leigh and Argye E. Hillis; Baltimore, MD Hypothesis: Impaired perception of another personвЂ™s pain, positive or negative emotions may differentially depend on cingulate and insula, as indicated by fMRI studies of empathy in healthy participants. Methods: We identified areas of acute ischemia associated with errors in identifying discomfort, positive, or negative emotions from hearing stories and watching videos in 30 patients with acute right hemisphere ischemic stroke symptoms. Ten were excluded for errors on facts about the stories/ videos. We identified DWI abnormality in 12 regions in frontal, temporal, parietal cortex, cingulate, insula, and thalamus. We identified associations between ischemia in each region and impairment empathy tests with FisherвЂ™s Exact. Results: Ischemia in the right cingulate (p Вј 0.004) and premotor cortex (p Вј 0.02) was associated with errors in perception of negative emotions. Volume of infarct (ADC <600) was not significantly different for patients with and without errors on empathy tasks (mean Вј 19.7 vs 1.9 cc; t Вј -1.1; p Вј .28). Patients with insular ischemia made empathy errors, but most were excluded for factual errors and had large lesions due to MCA occlusion. Conclusion: Ischemia in right cingulate or premotor cortex or can cause impaired perception of anotherвЂ™s negative emotions acutely; more power is needed to confirm the role of the insula. Study supported by: NINDS R01 NS047691 T1515. Withdrawn. T1513. Evolution of Psychiatric Co-Morbidity in the Transition Phase in a Cohort of Patients with Neurological Perinatal Disability Sara Piccoli, Gianni De Polo and Andrea Martinuzzi; Conegliano, Italy T1516. A Randomised Controlled Trial of Cognitive Behaviour Intervention for Impulse Control Behaviours Affecting ParkinsonвЂ™s Disease Patients and Their Caregivers David Okai, Sally Askey-Jones, Michael Samuel, Sean S. OвЂ™Sullivan, Ray Chaudhuri, Anne Martin, Joel Mack, Richard G. Brown and Anthony David; London, United Kingdom; Ashford, United Kingdom and Portland, OR Background: Psychiatric and behavioural disturbances frequently accompany perinatal neurologic conditions worsen- Background: Impulse control behaviours (ICBs) are a complication of treatment for ParkinsonвЂ™s disease (PD). They 116 ID: guganp I Black Lining: [ON] I Time: 09:25 I Path: N:/3b2/ANA#/Vol00000/120255/APPFile/JW-ANA#120255 J_ID: ZAY Customer A_ID: BKLT2012_Abstracts Cadmus Art: ANA12 Date: 18-September-12 comprise failure to resist an impulse harmful to self /others and include compulsive gambling, shopping, eating and sex. There is currently no treatment. Methods: A randomised-controlled trial of a cognitivebehavioural therapy (CBT) for PD patients with clinically significant ICBs. Aims were to improve symptom severity, in the patients and carer burden and distress. The intervention comprised 12 sessions of CBT, compared with waiting list control. Findings: 27 patients were randomised to the intervention and 17 to the waiting list. There was significant improvement in symptom severity in the CBT intervention group vs. controls (v2 (1, N Вј 40) Вј 16.46, p < 0.001). Anxiety and depression also improved as secondary outcomes. No significant changes in carer burden and distress were shown, but general psychiatric morbidity improved significantly in the carer group. Interpretation: This CBT intervention is the first to show efficacy in ICBs related to PD.ICBs in those on the waiting list show no tendency to remit. The study demonstrates the potential benefit of a psychosocial treatment approach for ICBs. Study supported by: The project was funded by ParkinsonвЂ™s UK with additional support from NIHR Biomedical Research Centre for Mental Health at the South London and Maudsley NHS Foundation Trust (SLaM) and Institute of Psychiatry, KingвЂ™s College London. Stage: Page: 117 Felicia Bergstrom, Rachael Mann, Caroline Schaefer, and Rebecca Baik are employees of Covance Market Access Services Inc., who were paid consultants to Pfizer in the development of this study. Dr. Srivinas Nalamachu is a paid investigator for this study. T1518. Characteristics of Subjects with Painful Diabetic Neuropathy (PDN) in the US: BEAT Neuropathic Pain Observational Study Felicia Bergstrom, Rachael Mann, Alesia Sadosky, Bruce Parsons, Caroline Schaefer, Rebecca Baik, Gergana Zlateva, Brett Stacey, Srivinas Nalamachu, Edward Nieshoff and Michael Tuchman; Gaithersburg, MD; San Diego, CA; New York, NY; Portland, OR; Leawood, KS; Detroit, MI and Palm Beach Gardens, FL Objective: Characterize pain, sleep, function and healthcare utilization in US subjects with PDN. Methods: This was observational, cross-sectional study of 112 PDN subjects recruited during routine visits from general practitioner and specialist sites. Subjects completed a one-time questionnaire; investigators completed a case report form based on 6-month retrospective chart review to capture utilization. Subject-reported pain and function were assessed using the Brief Pain Inventory-Short Form, and sleep using the MOS Sleep Scale. Results: SubjectsвЂ™ mean age: 61 years; 53% were female. Most common conditions included sleep disturbance/insomnia (44%), depressive symptoms (41%), and anxiety (36%). Mean pain severity score was 5.2 (0-10 scale), and 29% reported severe pain. Mean MOS Sleep Disturbance score: 51.1, MOS Sleep Problems Index: 48.5 (0-100 scale). Mean pain interference with function was 5.0 (0-10 scale). 86% of subjects were prescribed medications; top 3 classes prescribed: anticonvulsants (54%), opioids (31%), and NSAIDs: (19%). Subjects averaged 2.8 physician visits over 6 months. Conclusions: PDN subjects exhibited high pain levels which were associated with poor sleep and function. Medication and healthcare resource utilization in PDN were prevalent. Study supported by: Pfizer Inc. Alesia Sadosky, Bruce Parsons, and Gergana Zlateva are employees of Pfizer Inc. Felicia Bergstrom, Rachael Mann, Caroline Schaefer, and Rebecca Baik are employees of Covance Market Access Services Inc., who were paid consultants to Pfizer in the development of this study. Dr. Srivinas Nalamachu is a paid investigator for this study. T1517. Characteristics of Subjects with Chronic Low Back Pain-Related Neuropathic Pain (CLBP-NeP) in the US: BEAT Neuropathic Pain Observational Study Alesia Sadosky, Caroline Schaefer, Bruce Parsons, Rebecca Baik, Rachael Mann, Felicia Bergstrom, Gergana Zlateva, Brett Stacey, Srivinas Nalamachu, Michael Tuchman and Edward Nieshoff; New York, NY; Gaithersburg, MD; San Diego, CA; Portland, OR; Leawood, KS; Palm Beach Gardens, FL and Detroit, MI Objective: To characterize health-related quality of life (HRQoL), pain, function, and impact on productivity in subjects with CLBP-NeP. Methods: The BEAT Neuropathic Pain study is a crosssectional observational study of 106 subjects diagnosed with CLBP-NeP recruited during routine physician office visits with primary care or specialty physicians. Subjects completed a questionnaire and physicians completed a case report form based on 6-month retrospective chart review. Subject-reported pain and function were assessed using the Brief Pain Inventory-Short Form, HRQoL using the EQ5D, and productivity using the Work Productivity and Activity Impairment scale. Results: SubjectsвЂ™ mean age was 54 years, 58% were female, 24% were employed. 88% had comorbid conditions (sleep disturbance/insomnia: 59%, depressive symptoms: 52%, headache/migraine: 46%). Mean pain severity score was 6.0; mean pain interference with function was 6.6 (010 scale), with most affected domains being; normal work, sleep, enjoyment of life. 41% reported severe pain. Mean EQ-5D utility was 0.50 (-0.1 to 1.0 scale). Lost productivity was exhibited as 51% overall work and 64% activity impairment. Conclusions: CLBP-NeP subjects exhibit high pain levels, poor HRQoL, and diminished function and productivity. Study supported by: Pfizer Inc. Alesia Sadosky, Bruce Parsons, and Gergana Zlateva are employees of Pfizer Inc. T1519. Increased Phosphorylation of the MAPK/ERK Pathway Is Associated with Social Impairment in BTBR Mice Alireza Faridar, Dorothy M. Jones-Davis, Mu Yang, Adam M. Katz, Michael D. Weber, Eric Rider, Saunak Sen, Jacqueline Crawley and Elliott H. Sherr; San Francisco, CA and Bethesda, MD Increased activation of the MAPK/ERK signaling pathway has been found in the brains of BTBR TГѕtf/J mice, a strain exhibiting behaviors with face validity to autism. In this study we evaluated whether dysregulation of the pathway directly correlates with autism-relevant traits in the strain. Levels of phospho-ERK were significantly increased in the frontal cortex of BTBR vs. C57BL/6J mice; although no significant difference in total ERK protein expression was 117 ID: guganp I Black Lining: [ON] I Time: 09:25 I Path: N:/3b2/ANA#/Vol00000/120255/APPFile/JW-ANA#120255 J_ID: ZAY Customer A_ID: BKLT2012_Abstracts Cadmus Art: ANA12 Date: 18-September-12 observed. Next, we intercrossed BTBR and C57BL/6J mice and assessed social behaviors in 400 F2 offspring. The expression levels and state of phosphorylation of ERK and related signaling kinases were evaluated in the prefrontal cortex of F2 mice that lie on the two extremes of the social behavior spectrum. We observed a significant correlation between juvenile social behavior and phospho-MEK/ERK (p Вј 0.008, p Вј 0.03, respectively); although, we did not find any significant association between this behavior and total protein levels of MEK/ERK. Our findings demonstrate that autism-relevant behaviors may correlate with activity of the ERK signaling pathway, and suggest that this pathway may provide novel diagnostic markers and therapeutic targets for autism. Study supported by: Pfizer Stage: Page: 118 ever there was a non-significant trend for patients with family history to have longer remissions. Family history does not seem to predict electroconvulsive therapy efficacy. A larger sample size is needed to explore trends fully, which may prove that the time to relapse is significantly affected, possibly because patients with family history have a more вЂ�вЂ�biologicalвЂ™вЂ™ type of depression. Study supported by: Cardiff University School of Medicine T1522. Syphilitic Polyradiculoneuropathy in an Immunocompetent Patient Safaa Zahlane, Nissrine Louhab and Najib Kissani; Marrakesh, Morocco Introduction: The neurosyphilis is still prevalent. Its most common clinical presentation includes tabes dorsalis and general paresis. In contrast, polyradiculoneuritis has rarely been reported during syphilis. Case report: 45 years old man without medical past history, reffered to neurology out patient for acute leg weakness and heaviness. Clinical examination revealed bilateral leg weakness. Deep tendon reflexes were absent. Cutaneous hypoesthesia was on the legs. There were no pyramidal signs, no cranial nerves abnormalities and no incontinence. Electroneuromyograms showed sensorimotor demyelination and axonal loss evoking polyradiculoneuretis. Lumbar punctures showed an albumino-cytological dissociation. VDRL and TPHA were positive in both serum (VDRL: 1/16, TPHA :1/1280) and CSF (VDRL: 1/6, TPHA1/640). A serodiagnostic tests (HIV, Borrelia, hepatitis C and B) were negative.The patient received 30 million units of intravenous penicillin G daily for 10 days, four times with delay of 3 months, Muscular leg weakness disappeared and his clinical condition improved. Conclusion: Syphilitic polyradiculoneuropathy has rarely been reported. Infection due to T. pallidum is a curable cause of polyradiculoneuritis which may occur in HIV-negative patients; appropriate tests in both serum and CSF should be performed in patients with polyradiculoneuritis. Study supported by: Department of neurology and laboratory of neuroscience T1520. Stepwise Onset of Memory Impairment, Encephalopathy and Hearing Loss Presenting as Susac Syndrome Alvin Shrestha, Tatiana Mihalova, Daniel Burns and Mark Willmot; Birmingham, United Kingdom A 40 year old lady was seen in the neurology clinic with migraines on a background of mild memory impairment and behavioural changes. An initial MRI brain was normal. Four months later, she was admitted with acute confusion, fever and drowsiness, requiring ventilation on ITU. She was treated empirically with Aciclovir and Cefotaxime. Lumbar puncture was acellular, with a protein of 0.71g/L. An MRI brain revealed several subcortical white matter lesions. EEG showed non-specific encephalopathy. Vasculitis screen was negative. She improved clinically but repeated MRI scans over the next 2 months showed new white matter lesions, including pericallosal lesions. She developed gradual sensorineural hearing loss, requiring a hearing aid. She was diagnosed with Susac syndrome, although an ophthalmology review failed to demonstrate retinal artery occlusions. MRI brain 8 months following her encephalopathy showed a reduction in white matter lesions, but did demonstrate classic punched-out pericallosal lesions. Late attempts with steroids treatment led to a minimal improvement of memory, headache and behavioural problems. Susac syndrome should be considered when pericallosal lesions are seen with an atypical history, including new onset of progressive hearing loss. Study supported by: Conflict of interest: Nil Headache and Pain/Neuro-otology T1521. The Effect of a Family History of Major Depression on the Outcome of Electroconvulsive Therapy Ceri A. Smith; Cardiff, Wales, United Kingdom T1601. Lidocaine Desensitizes TRPA1 Receptors in Human Sural Nerves Anupam Bhattacharjee, Lionel Ginsberg, Richard Orrell, Saqiba Jadoon and Reginald Docherty; London, United Kingdom Electroconvulsive therapy is an effective treatment for major depression, however few predictors of response have been established. The study aims to examine whether a family history of unipolar or bipolar depression is a predictor of response, remission and relapse rates after electroconvulsive therapy in patients with unipolar or bipolar depression. Data on 121 patients treated at Whitchurch hospital, Cardiff was analysed. It was established whether patients had a family history of unipolar or bipolar depression. Patients were then administered electroconvulsive therapy and outcome measures were compared using independent ttests, regression analysis and Kaplan-Meier survival curves. A high proportion of patients had family history, and these patients had a significantly earlier age of onset of depression. Family history does not predict outcomes, how- TRPA1 and TRPV1 are ion channels of the TRP family that are expressed in a subset of sensory neurones in human sensory nerves. They are molecular sensors of environmental stimuli. In primary sensory neurons their activity is thought to mediate sensory symptoms of peripheral neuropathy such as pain and paraesthesia. We conducted in vitro recordings from human sural and rat saphenous nerves to study the effects of capsaicin and mustard oil which are selective activators of TRPV1 and TRPA1 respectively. Both human and rat nerves were depolarized by capsaicin. However, we failed to demonstrate any depolarizing response to mustard oil in any human sural nerves tested whereas all rat nerves showed robust depolarizing responses. When rat nerves were pretreated with 30mM lidocaine to mimic the exposure of human sural nerve biopsies to the local anaesthetic during surgery, effects on action potential conduction reversed 118 ID: guganp I Black Lining: [ON] I Time: 09:25 I Path: N:/3b2/ANA#/Vol00000/120255/APPFile/JW-ANA#120255 J_ID: ZAY Customer A_ID: BKLT2012_Abstracts Cadmus Art: ANA12 Date: 18-September-12 completely but there was a selective abolishment of the response to mustard oil but not of that to capsaicin. This study demonstrates that local anaesthetics selectively desensitize TRPA1 ion channels and indicates that they may have additional mechanisms for treating neuropathic pain that endure beyond simple sodium channel blockade. Study supported by: none Stage: Page: 119 CM(9.1365.81lV) was insignificantly higher compared to EM(7.9363.14lV) and MOH(7.8664.29lV). In controls, significant habituation of N19 amplitude in block 2(7.2562.80lV) and block 3(7.0162.96lV) compared to block 1(7.9162.91lV) was observed. In migraine patients, there was no habituation in block 2(8.2564.02lV) compared to block 1(8.1764.15lV). Reduction of N19 amplitudes in block 2(P<0.001) and block 3(P<0.001) compared to block 1(P<0.001) were also significantly higher in controls compared to migraine patients. The lack of habituation significantly correlated with allodynia(P Вј 0.03). Conclusion: Lack of habituation of SEP may be a biological marker of migraine. Study supported by: Nil T1602. Analysis of the Development of Allodynia: Correlation between Migraine Duration and Severity Biao Lu, Xiaodong Li, Songyang Zhao, Emilee Connors and Shashidhar Kori; Mountain View, CA Background: Allodynia is the perception of pain from nonnociceptive stimuli. Common during migraine, allodynia is a manifestation of central sensitization. Mediating factors for allodynia are not well understood but may include severity and duration of migraine. We evaluated allodynia and migraine severity and duration to identify mechanisms of migraine-induced central sensitization. Methods: In this retrospective analysis, 794 patients from the double-blind period of a phase 3, placebo-controlled, randomized trial of an investigational acute treatment for R ) recorded pain levels in migraine (MAP0004/LEVADEXV an electronic diary and provided allodynia status via standard questionnaire. FisherвЂ™s exact test and chi-square test were used to correlate percentage of patients with allodynia with migraine severity and duration. Results: At baseline, 53% of patients experienced allodynia. Migraine duration did not influence development of allodynia (chi-square P Вј 0.2182), regardless of pain severity (moderate baseline pain, chi-square P Вј 0.1807; severe baseline pain, chi-square P Вј 0.5830). Significantly more patients reporting severe pain had allodynia (58.4%) compared with patients reporting moderate pain (48.2%; FisherвЂ™s exact P Вј 0.0053). Conclusions: Development of allodynia was associated with severity but not duration of migraine, suggesting that severity is a significant predictor of central sensitization. Study supported by: MAP Pharmaceuticals, Inc. Biao Lu is a full-time employee of MAP Pharmaceuticals Xiaodong Li was a consultant to MAP Pharmaceuticals from 2010 - 2011. From 2011 - present he is a full-time employee and stockholder of MAP Pharmaceuticals. Emilee Connors is a full-time employee and stockholder of MAP Pharmaceuticals. Shashidhar Kori is a full-time employee, stockholder and has equity interests of MAP Pharmaceuticals. T1604. Dextromethorphan Plus Quinidine for Headache Prophylaxis: The First Case Report Daniel Kantor; Ponte Vedra, FL Objective: To report the use of fixed combination dextrometherophan/quinidine (DM/Q) in chronic daily headache (CDH) prophylaxis. R is a non-competitive N-MethylBackground: NuedextaV D-aspartic acid (NMDA) receptor antagonist and sigma-1 agonist combination of DM/Q 20/10mg approved for pseudoublbar affect. DM/Q is being studied in diabetic and multiple sclerosis pain. Other NMDA receptor antagonists are sometimes used for headaches. Methods: Case report. Results: A 54-year-old woman with a >20 year history of refractory CDH (intensity 2вЂ“7/10) is started on DM/Q due its role in down-regulating glutamate. Within the first month of treatment, her headache intensity dropped to 1/ 10 (infrequently 2/10) and headache frequency dropped from daily to several times a week. Her infrequent migraines became even less frequent and severe. Excedrin use dropped from four times a day to twice in the first month and she discontinued percocet. This dramatic result has been sustained for over a year. Conclusions: Mechanistically, DM/Q may be expected to be helpful in the treatment of headache/pain. Although it is possible that our patient demonstrated a placebo response, the failure of multiple other medications suggests that this may represent a true therapeutic response. Further research is warranted. Study supported by: N/A T1603. Is Lack of Habituation of Somatosensory Evoked Potential (SEP) a Biological Marker of Migraine? Jayantee Kalita, Sanjeev K. Bhoi and Usha K. Misra; Lucknow, UP, India T1605. Sustained Pain Relief with Dihydroergotamine in Migraine Is Potentially Due to Persistent Binding to 5HT1B/5-HT1D Receptors Shashidhar Kori, Jian Zhang, Donald Kellerman, Thomas Armer and Peter J. Goadsby; Mountain View, CA and San Francisco, CA Aims: To evaluate the sensitization and habituation of median SEP (MSEP) in migraine patients and correlate with allodynia. Methods: 74 migraine patients, aged 16-65 years and 63 females were included. Their demographic and clinical characteristics were noted. The patients were categorized into episodic migraine (EM), chronic migraine (CM) and medication overuse headache (MOH). MNSEP was recorded in 3 consecutive blocks of 100 epochs each and the N19 amplitudes of each block were measured. MSEP was also done in 28 matched controls. Results: The baseline N19 amplitude did not differ between migraine patients (8.1764.15lV) and controls(7.9162.91lV,P Вј 0.73). The N19 amplitude in Background: Dihydroergotamine (DHE) produces up to 48 hoursвЂ™ migraine pain relief despite a 10-13 hour serum half-life. This sustained action was attributed to 80 -OHDHE metabolite half-life, but this is not supported in recent studies. We investigated sustained pain relief by DHE and sumatriptan by comparing duration of binding to serotonin receptors 5-HT1B/5-HT1D. Methods: We determined the 50% inhibitory concentration (IC50) of test compound (50lL; 0.01-10,000 nM) by incubating with 25lL [3H]5-HT (0.6nM [5-HT1B], 0.5nM [5-HT1D]) and 25lL of membrane extracts (recombinant CHO-K1-5-HT1B [7lg], CHO-K1-5-HT1D [10lg] membrane/well) for 60 minutes. The mixture was filtered, washed, and mixed and incubated with MicroScintTM-20 119 ID: guganp I Black Lining: [ON] I Time: 09:25 I Path: N:/3b2/ANA#/Vol00000/120255/APPFile/JW-ANA#120255 J_ID: ZAY Customer A_ID: BKLT2012_Abstracts Cadmus Art: ANA12 Date: 18-September-12 (50lL). Ionizing radiation was measured with TopCountTM scintillation counter (1 min/well). Test compound dissociation constant (koff ) was measured at 20 timepoints (0-120 min [5-HT1B], 0-150 min [5-HT1D]) at three concentrations (0.3, 1.0, 3.0 x IC50), and dissociation half-life was calculated. DHE and sumatriptan were tested with human 5-HT1B/5-HT1D receptors. Results: Dissociation half-life of DHE vs. sumatriptan: 5HT1B: 1.38 vs. 0.17 h; 5-HT1D: 1.28 vs. 0.09 h. Conclusions: DHE binds 5-HT1B/5-HT1D receptors 814 times longer than sumatriptan, potentially explaining DHEвЂ™s sustained pain relief in migraine. Study supported by: MAP Pharmaceuticals, Inc. Shashidhar Kori is a full-time employee, stockholder and has equity interests of MAP Pharmaceuticals. Jian Zhang is a full-time employee, stockholder and has equity interests of MAP Pharmaceuticals. Donald Kellerman is a full-time employee, stockholder and has equity interests of MAP Pharmaceuticals. Thomas Armer is a full-time employee of MAP Pharmaceuticals. Peter J Goadsby has had research support or consulted, or both for MAP, as well as GSK, Amgen, Allergan, MSD, eNeura, Neuraxon, Autonomic Technologies, Colucid, EliLilly, Metronic, Linde, BristolMyersSquibb, Boston Scientific, and Pfizer. Stage: Page: 120 parison meta-analysis (MTC) allows for comparative effectiveness when direct evidence is unavailable. Using an MTC, we aimed to determine the relative efficacy of triptans for abortive treatment of migraine. Methods: We included all randomized clinical trials (RCTs) evaluating triptans versus placebo or another triptan with outcomes of headache-free and headache relief at 2 and 24 hours post-migraine treatment. We used Bayesian random-effects MTC adjusting for dosage using metaregression. Results are reported as odds ratios (OR) with 95% Credible Intervals. Results: We included 97 RCTs. For the outcome of headache free and headache relief at 2-hour, there were no significant differences between triptans. At 24 hours, elitriptan had the highest probability of treatment success for headache-free (77%) and headache-relief (95%). For headache-relief, elitriptan was significantly more effective than other triptans: sumatriptan (OR 1.69, 1.21-2.40), almotriptan (OR 2.31, 1.12-4.72), naratriptan (OR 2.05, 1.074.16), zolmatriptan (OR 1.09-2.44), and rizatriptan (OR 1.81, 1.08-3.06). Conclusion: Triptans appear to offer differing treatment effects. Eliptriptan offered the largest treatment effects at 24 hours. Study supported by: Pfizer Ltd T1608. Repetitive Transcranial Magnetic Stimulation (rTMS) Results in Elevation of b Endorphin Level and Relief of Migraine Headache Usha K. Misra, Jayantee Kalita, Gyanesh M. Tripathi and Sanjeev K. Bhoi; Lucknow, UP, India T1606. Valsalva Test Responses in Cough Headache Patients Russell J.M. Lane and Paul T.G. Davies; London, United Kingdom and Oxford, United Kingdom Cough headache is defined as вЂ�вЂ�headache of sudden onset lasting from one second to 30 minutes, brought on by coughing, straining and/or Valsalva manoeuvreвЂ™вЂ™ [1]. The implication is that cough headache results from transient increase in intracranial pressure. 13 consecutive cough headache patients with normal neurological examinations were asked to exhale into a sphygmomanometer tube to 60 mm Hg for 10 seconds and to report the resulting symptoms. A вЂ�вЂ�positiveвЂ™вЂ™ test was recorded if the test reproduced the headache exactly. 8 had positive tests. All had intracranial pathology in the posterior fossa on MRI (вЂ�вЂ�secondaryвЂ™вЂ™ cough headache: 7 Chiari 1 malformations and one asymptomatic posterior fossa meningioma). Four patients had negative Valsalva tests, and one experienced minimal headache, not characteristic of the spontaneous symptom. These 5 patients had normal MRI scans (вЂ�вЂ�primaryвЂ™вЂ™ cough headache). Secondary cough headache was relieved following surgical treatment in all cases. We conclude that while secondary cough headache is provoked by Valsalva manoeuvre and presumably results from transient increase in intracranial pressure, the mechanism of primary cough headache must be different. This should be recognised in the forthcoming International Headache Classification definition. 1. IHC2 2nd Edition. Cephalalgia 2003;24, Supplement 1:63. Study supported by: Not supported Aim: To evaluate b endorphin (BE) level in migraine patients before and after rTMS to explain the mechanism of pain relief. Methods: 25 migraine patients, aged 20-65years having >4 attacks/mo were included. Their demographic and clinical details were recorded. Plasma BE level was estimated before and after rTMS in patients and 25 matched controls using ELISA. rTMS was applied in left hand motor area and 600 pulses in 412.4 seconds at 70% of motor threshold were delivered in 3 sessions on alternate days. The headache outcome parameters were assessed before rTMS and weekly for 4 weeks. The project was approved by Ethics Committee and patients consented. Results: Baseline plasma BE levels was lower in migraine(4.3562.29ng/ml) compared to controls(6.6862.93ng/ ml,P Вј 0.005). BE levels were lower in chronic migraine (3.7462.20ng/ml) compared to episodic migraine(5.6562.02ng/ml,P Вј 0.04). Following rTMS migraine frequency, duration, severity, functional disability, and analgesic use significantly reduced on seventh day compared to baseline. Following rTMS BE levels significantly increased(6.5863.33ng/ml) compared to baseline(4.3562.29ng/ ml P Вј 0.001) and the change in BE correlated with clinical improvement. Conclusion: Pain relief in migraine following rTMS may be due to increase in BE level. Study supported by: None T1607. Comparative Efficacy of Triptans for the Abortive Treatment of Migraine: A Multiple Treatment Comparison Meta-Analysis (MTC) Edward J. Mills, Kristian Thorlund, Ping Wu and Anjan Chatterjee; Ottawa, ON, Canada; Hamilton, ON, Canada and New York, NY T1609. Alice in Wonderland Syndrome: Epilepsy, Migraine or Both? W.O. Pickrell, R.H. Thomas, J.A. Johnston, C.P. White and M.I. Rees; Swansea, United Kingdom and Cardiff, United Kingdom Background: Little is known about the comparative efficacy of triptans for migraine treatment. Multiple treatment com- We present a family where 10 members of the pedigree suffer distinct, stereotyped episodes of hyper and 120 ID: guganp I Black Lining: [ON] I Time: 09:25 I Path: N:/3b2/ANA#/Vol00000/120255/APPFile/JW-ANA#120255 J_ID: ZAY Customer A_ID: BKLT2012_Abstracts Cadmus Art: ANA12 Date: 18-September-12 hyposchematia, metamorphopsia including teleopsia and pelopsia and altered time awareness consistent with the Alice in Wonderland Syndrome (AIWS). Amongst the 10 affected family members, 4 also have epilepsy, 1 also has migraine and 3 people only have AIWS. Since the first published description of AIWS in 1955, there have been several reports describing associations with migraine, epilepsy, viral Illnesses and also drugs. The fact that AIWS can occur with or without migraine or typical epileptic seizures raises the question as to its exact nature вЂ“ is it a form of migraine, epilepsy, both (migralepsy) or neither? There is phenotypic overlap between migraine, epilepsy and AIWS. Mutations in genes encoding ion channels have been associated with both migraine and epilepsy. The abnormally high incidence of AIWS, migraine and epilepsy in this family means there is a underlying genetic cause which we are currently investigating. A biological model for the pathogenesis of AIWS could help further our understanding of both migraine and epilepsy - the two most common paroxysmal brain disorders. Study supported by: National Institue for Social Care and Health Research; Welsh Government Stage: Page: 121 ing neurons (nociceptors) derived from patient fibroblasts. Marius Wernig showed that it is possible to convert fibroblasts into generic neurons using just three transcription factors. We hypothesized that by expressing additional transcription factors known to be important in nociceptor development, we could directly reprogram patient fibroblasts into functional nociceptors. We have created mice that express a fluorescent reporter specifically in nociceptors by using a nociceptor-specific NaV1.8 Cre driver. Starting with mouse embryonic fibroblasts from the NaV1.8::reporter mice, we transduce the fibroblasts with combinations of transcription factors and demonstrate that we can obtain activation of the nociceptor-specific reporter. We use wholecell patch clamp to confirm that the neurons are physiologically functional. We are currently performing additional characterization using immunohistochemistry, expression profiling, calcium imaging, and patch clamp. Study supported by: GlaxoSmithKline T1612. The Prevalance of Anxiety and Depression in Migraine Patients Hakan Balibey, Halit Yasar, Nalan Bayar and Hakan Tekeli; Ankara, Turkey and Istanbul, Turkey Introduction: Migraine is one of the most common primary headaches which worldwide affects more than 10% of people. Anxiety disorder and depression often accompany this disease and increase the number and severity of migraine attacks. The purpose of this study is to determine the prevalence of anxiety and depression disorders in patients with migraine. Methods: Two groups are formed with migraine patients and healthy volunteers. So far 51 patients are included to migraine group by the neurologist according to ICHD, 2nd edition. There are 60 subjects in the healthy control group. After being examined by the psychiatrist both of the groups meet the psychologist and have the Beck Depression Inventory (BDI) and Beck Anxiety Inventory (BAI). Results: Until now, in the migraine group BAI is high with 15 patients (29%) and BDI is high with 19 patients (37%) whereas in the control group BAI is high with 6 subjects (10%) and BDI is high with 10 subjects (16%). Both tests have significantly higher scores than the control group (p < 0.001). Discussion: The prevalence of anxiety and depression in patients with migraine is higher than the normal population. Study supported by: -None -There is no conflict of interest T1610. Analysis of EEG and MRI for Localization of Structures Affected in Temporal Lobe Epilepsy Ildefonso RodrД±Вґguez-Leyva, Ana A. RenterД±Вґa Palomo, Luis Concha-Loyola and Adriana MartД±Вґnez-Mayorga; San Luis Potosi, Mexico Objective: To determinate the relationship between both hippocampal atrophy and severity of epilepsy in patients with temporal lobe epilepsy (TLE). Methods: Volumetric MRI of the hippocampus was performed in 50 consecutive patients (25 men; mean age 40) with TLE. TLE diagnosis, lateralization and severity (mild, moderate, severe) of the seizure were based on a comprehensive evaluation including neurologic examination and EEG in all patients. Patient with evidence of a lesion were not included in the study. We compare the relation between the volumetric measurements from both hippocampal using the C (development at Mayo Clinic) and Software Analyze 10.0V the relation with the severity of the epilepsy based in the EEG. Results: We found a statistically significant difference (p < 0.001) in volume, according to the affected side based in the EEG; and a correlation between the severity of epilepsy and hippocampal atrophy. Conclusion: Our results confirm that volume loss to the hippocampus in patients with TLE correlate with the severity of the epilepsy based in the EEG. The detection of these differences may help to make early surgery for refractory temporal lobe epilepsy. Study supported by: COPOCYT T1613. Endogenous l-Opioid System as a Research and Therapeutic Target in Migraine Alexandre F. DaSilva, Thiago D. Nascimento, Tiffany Love, Marcos F. DosSantos, Ilkka K. Martikainen, Misty DeBoer, Chelsea M. Cummiford, Felipe Fregni, Yolanda R. Smith, Eric Maslowski and Jon-Kar Zubieta; Ann Arbor, MI and Boston, MA T1611. Direct Conversion of Fibroblasts into Functional Nociceptors Brian J. Wainger, Amy J. Wang, Lee Barrett, Justin Ichida, Qiufu Ma, Lee L. Rubin, Kevin Eggan and Clifford J. Woolf; Boston, MA and Cambridge, MA We investigated how the endogenous opioid system is affected in migraine, and how it can be safely modulated for research and therapeutic purposes. First, we examined changes in the l-opioid system during spontaneous migraine attacks using positron emission tomography (PET) with [11C] carfentanil, which measures l-opioid receptor (lOR) availability [Non-Displaceable Binding Potential (BPND)]. We noticed substantial reductions in lORBPND (increase in l-opioid release) during the headache phase in multiple pain-modulatory regions, including PAG. Second, Multiple difficulties confound the study of pain in humans. Pain is subjective and discordance often exists between the severity of pain and the severity of pathology. Animal models and heterologous expression studies also have marked limitations, and a large number of drugs have appeared promising in animal models but then failed in clinical trials. We planned to generate and phenotype primary pain-sens- 121 ID: guganp I Black Lining: [ON] I Time: 09:25 I Path: N:/3b2/ANA#/Vol00000/120255/APPFile/JW-ANA#120255 J_ID: ZAY Customer A_ID: BKLT2012_Abstracts Cadmus Art: ANA12 Date: 18-September-12 we investigated the analgesic effect of ten active/sham sessions of motor cortex (M1) modulation in chronic migraine patients using transcranial direct current stimulation (tDCS). There was a significant decrease in pain intensity of migraine episodes in the follow-up period in the active group. In addition, using a high-resolution computational model, we found that M1-tDCS generated significant electric fields in the pain-matrix. Third, M1-tDCS was performed during the PET session, without posing risks to the patient. We noticed that there is an immediate reduction in lORBPND in the pain-matrix. The studies above represent a change of paradigm, as we directly investigate and modulate our own endogenous opioid mechanism by applying novel neuroimaging and neuromodulatory tools. Study supported by: No conflict of interest. The study was supported by non-profitable organizations: NIHNINDS:K23 NS062946, DANA FoundationвЂ™s Brain and Immuno-imaging award, Migraine Research Foundation Award Stage: Page: 122 This dysfunction might result from underlying synucleinopathy, tauopathy, amyloidopathy, or a combination of each. To explore this hypothesis, we assessed amyloid pathology using neuroimaging and molecular cerebrospinal fluid (CSF) analysis in these patients. Methods: In a cross-sectional design, subjects underwent Dementia Rating Scale (DRS-2) assessment, lumbar puncture, and quantitative amyloid imaging using AV-45, an 18F-based PET ligand. Results: 40 subjects, 32 men and 8 women, were recruited. Average age was 70.3567 years and disease duration was 9.9765.6 years. Mean total DRS-2 score was lower in PDD (106.3618, p<0.005) and DLB (119.3610) as compared with PD (133.1616). Higher cortical amyloid burden correlated with lower total DRS-2 score (R Вј -0.39, p<0.05), lower attention subscore (R Вј -0.57, p<0.005), and CSF amyloid-b (R Вј 0.41). Memory subscore and CSF tau did not significantly correlate with cortical amyloid burden. Conclusions: PD and DLB patients may have underlying amyloid pathology that differs from patterns seen in other dementias. Longitudinal examination of these parameters may elucidate amyloid profiles that identify PD patients at risk of dementia. Study supported by: This study was supported by a Morris K. Udall ParkinsonвЂ™s Disease Research Center of Excellence grant from NINDS (NS-053488) and by Avid Radiopharmaceuticals. Dr. Akhtar and Ms. Brennan report no financial disclosures. Dr. Weintraub participated on scientific advisory boards or received honoraria for speaking from Teva Pharmaceuticals, Eli Lilly and Company, Lundbeck Inc., Biogen, Pfizer, and Avanir Pharmaceuticals. Dr. Weintraub received a portion of licensing fees from use of the QUIP instrument, which is copyrighted to the University of Pennsylvania. Dr. Weintraub received research support for an investigator-initiated study from Novartis. Dr. Siderowf has been supported by SAP4100027296, a health research grant awarded by the Department of Health of the Commonwealth of Pennsylvania from the Tobacco Master Settlement Agreement under Act 2001-77. Dr. Siderowf has received consulting fees or speaking honoraria from Teva Neuroscience, Supernus Pharmaceuticals, Schering-Plough, and Merck Serono. Movement Disorder T1701. PARK2 Mutant hiPSC-Derived Neural Progenitors Exhibit Altered Sensitivity and Mitochondrial Dysfunction to Neurotoxic Metal Exposure Asad A. Aboud, Andrew M. Tidball, Kevin K. Kumar, M. Diana Neely, Michael Litt, Peter Hedera, Charles C. Hong, Kevin C. Ess and Aaron B. Bowman; Nashville, TN Through toxicological studies in human induced pluripotent stem cells (hiPSCs), we sought to investigate potential disease-toxicant interactions in familial PD. We generated hiPSCs from an individual with large exonal deletions in the familial PD associated gene, PARK2. We then differentiated these cells into early CNS neural progenitors which were exposed to a number of heavy metals, and the PARK2 mutant hiPSC-derived neural progenitors were selectively vulnerable to copper and cadmium-induced cell death. This phenotype could not be replicated using fibroblasts used to generate the stem cells. The PARK2 mutant neural progenitors also demonstrated increased reactive oxygen species production, mitochondrial fragmentation and depolarization under copper exposure. We conclude that loss of functional PARK2 gene product, Parkin, leads to selective susceptibility to copper-induced mitochondrial dysfunction. Parkin plays a key role in recycling damaged mitochondria; therefore, our data recapitulates previous findings. We also demonstrate the utility of hiPSCs to study the patient-specific toxicological differences in a particular cell type of interest. Furthermore, this study opens the door to developing highthroughput screening for specific gene interactions with a wide array of environmental agents. Study supported by: Grants descriptions: NIH R01 ES016931; NIH P30 ES000267; NIH/NIGMS P01 GM0895354 - RR166-737/4787736 subcontract; Peterson Foundation for ParkinsonвЂ™s; Doris Duke Research Foundation T1703. Reversal of Levodopa-Induced Dyskinesia Mathew Alias and Mohamed Hassan; Farmington, CT Objective: To evaluate treatment regimens that can reverse levodopa-induced dyskinesias (LID). Background: Levodopa treatment for ParkinsonвЂ™s Disease (PD) eventually leads to dyskinesia. вЂ�вЂ�PrimingвЂ™вЂ™ is caused by the pulsatile stimulation of striatal dopamine receptors and the supra-physiologic concentrations of synaptic dopamine resulting from levodopa therapy. Reversal of the neurochemical imbalance associated with LID can be achieved by the gradual reduction of levodopa along with the addition of longer-acting medications. Design/Methods: At the University of Connecticut Movement Disorders Clinic, a total of 2134 new PD patients were seen from January 1, 2001 to December 31, 2011. Of these, six representative patients are illustrated with symptoms of LID up to 10 years. Results: All six cases showed complete reversal of dyskinesias, as the short acting levodopa/carbidopa tapering and with the concomitant increase of longer acting dopamine agonists and/or MAO -B inhibitors. Motor symptoms were T1702. Amyloid Profiles of Subjects with Lewy Body Disease Rizwan S. Akhtar, Laura Brennan, Daniel Weintraub and Andrew D. Siderowf; Philadelphia, PA Objective: Cognitive dysfunction is a frequent non-motor symptom of ParkinsonвЂ™s disease (PD), ParkinsonвЂ™s disease dementia (PDD), and dementia with Lewy bodies (DLB). 122 ID: guganp I Black Lining: [ON] I Time: 09:25 I Path: N:/3b2/ANA#/Vol00000/120255/APPFile/JW-ANA#120255 J_ID: ZAY Customer A_ID: BKLT2012_Abstracts Cadmus Art: ANA12 Date: 18-September-12 improved and the time for reversal of LID was related to the dyskinesia duration. Conclusions: LID can be reversed/reduced by tapering levodopa in a very gradual manner. These findings may help LID patients who do not qualify for DBS and prompt laboratory scientists to study animal models in further elucidating the pathophysiology of the basal ganglia. Study supported by: Dr. Hassan has received speaker honoraria from Teva Pharmaceutical Industries Ltd. and GlaxoSmithKline. Stage: Page: 123 T1706. Low Frequency DBS in PD Patients with Gait and Speech Problems Diana Apetauerova, Janet W. Zani and Stephanie A. Scala; Burlington, MA Objective: To analyze the effect of bilateral low frequency stimulation (60Hz) in patients with ParkinsonвЂ™s disease. Methods: 10 PD patients post DBS STN surgery with gait freezing and falls were studied on low frequency stimulation for 1 month with 2 week follow up visits consisting of UPDRS, gait and speech assessment. Results: Three patients completed study tolerating low frequency stimulation throughout study duration; 7 prematurely withdrew due to intolerance of tremor recurrence, bradykinesia and/or rigidity. Speech improved in 3 patients. Gait improved transiently, eventually worsening due to severe immobility. 3 patients tried combination stimulation with less affected body side on low frequency and more affected side to high and remained on this setting at study completion with gait, balance and speech improvement. Bradykinesia and rigidity did not worsen significantly on low stimulation side; mild dyskinesia occurred on low frequency side only. Conclusions: Bilateral low frequency stimulation didnвЂ™t show to be beneficial in our study. Speech was the only symptom which improved. A combination of high and low frequency stimulation might be a reasonable option for PD patients with gait and speech problems. This study remains ongoing. Study supported by: Robert E. Wise Foundation Grant T1704. L-Dopa Induced Dystonia, Dyskinesia in Juvenile ParkinsonвЂ™s Disease Sarah M. Misbah El-Saadig; Khartoum, Sudan Quest Deep Brain stimulation This is a follow up study to one of the biggest families of AREOP (Autosomal Recessive Early onset ParkinsonвЂ™s) disease in North Africa and the Middle-East apart from Algeria which has the biggest. This Sudanese family has been diagnosed with Juvenile ParkinsonвЂ™s disease in 2005. 8 family members have been affected amongst 2-3 generations. Those alive, have been affected by the disease and side effects of the medication. They canвЂ™t even withstand the smallest dose of L-Dopa and sinemet. They become very dystonic and dyskinetic, which was very evident in the video tape of this family. I think this family might benefit from a surgical procedure including DBS with a rechargeable memory which can improve morbidity, mortality, and improve their life style. Other types of genetically related Dystonias did benefit from this procedure. Thus DBS availability as a way of treatment is very essential. This family and its new genetic disorder has been published in Neurology archives 2006. Study supported by: No sponsor T1707. Chronic Parkinsonism Associated with Liver Cirrhosis Diana Apetauerova, Peter G. Hildenbrand, Janet W. Zani and Stephanie A. Scala; Burlington, MA T1705. Amelioration of Somatic and Autonomic Neuropathy in Patients with Idiopathic ParkinsonвЂ™s Disease Following Cobalamin Therapy Sabrina Apel and Cory Toth; Calgary, AB, Canada Objective: To study parkinsonism prevalence in patients with liver cirrhosis and establish correlations between cirrhosis severity, parkinsonism, neuroradiological and biological findings. Methods: A prospective study of patients with cirrhosis undergoing transplantation at Lahey Clinic. Each patient underwent Unified ParkinsonвЂ™s Disease Rating Scale (UPDRS) testing, standard liver pre-transplant evaluation and repeat testing post-transplant at 6 weeks, 3 and 12 months. Patients with parkinsonism also underwent brain MRI. Correlation was measured among MELD, motor and total UPDRS, copper, ammonia, manganese, iron levels and signal MRI changes. Results: 62 of 120 patients exhibited parkinsonism. Of these, we found no correlation between MELD severity and motor UPDRS (p Вј 0.71) nor among laboratory levels. All parkinsonian patients had abnormal signal in the basal ganglia. Thirteen patients with parkinsonism underwent liver transplant. Improvement was found in gait (p Вј 0.001), bradykinesia (p Вј .02), motor UPDRS (p Вј 0.02) and total UPDRS (p Вј 0.03) 3 months post transplantation. Additional results will be provided at time of abstract presentation. Conclusions: Our study demonstrates high incidence of parkinsonism in patients with cirrhosis. No correlations were found between cirrhosis severity, manganese levels and parkinsonism severity. Improvement was found in UPDRS, gait and bradykinesia post transplant. Our study remains ongoing. Study supported by: Robert E. Wise Foundation Grant Idiopathic ParkinsonвЂ™s Disease (IPD) patients have greater prevalence of peripheral neuropathy (PN) than matched controls. We examined intervention with long-term monthly intramuscular cobalmin (Cbl) to prevent progression of PN. We prospectively followed 58 IPD patients with pre-identified PN for clinical, electrophysiological, autonomic and laboratory measures of PN and IPD over 4 years. All patients were prescribed open-label Cbl. Complete compliance with Cbl occurred in 32/58 of IPD patients; the remaining 26/58 received <50% of designated Cbl. Non-paired ANOVA testing was performed to compare compliant/non-compliant groups. Our primary outcome measure was change in Utah Early Neuropathy Scale (UENS) score, with cumulative levodopa dosing, IPD severity, electrophysiology, R-R interval testing, and fasting methylmalonic acid (MMA) levels as secondary measures. Compliant patients had a smaller changes in UENS, sural sensory amplitude and distal latencies, R-R interval testing (for resting and deep breathing, but not Valsalva), and downregulation in serum MMA, with no differences in IPD scores or levodopa intake. Although limited as an open-label study, regular use of Cbl may prevent progression of PN in IPD patients using levodopa. We advocate for randomized controlled trials to further assess. Study supported by: Alberta Heritage Foundation for Medical Research 123 ID: guganp I Black Lining: [ON] I Time: 09:25 I Path: N:/3b2/ANA#/Vol00000/120255/APPFile/JW-ANA#120255 J_ID: ZAY Customer A_ID: BKLT2012_Abstracts Cadmus Art: ANA12 Date: 18-September-12 T1708. A Genetic Study of Wilson Disease in the UK Oliver Bandmann, Alison Coffey, Magnus Rattray and Ann Dalton; Sheffield, United Kingdom and Cambridge, United Kingdom Stage: Page: 124 Twelve PD patients (7M/5F; 6168) and 7 healthy controls (4M/3F; 6069) underwent resting-state fcMRI scanning. Striatal functional connectivity was calculated for 6 striatal seeds using voxel-wise cross correlation analyses. Significant differences in connectivity were found between: dorsal putamen and pallidum, inferior parietal lobe (IPL), amygdala, and cerebellum (Cbl); dorsal caudate and amygdala; and ventral caudate and precentral gyrus, supplementary motor area (SMA), middle cingulum (MCC), and superior medial frontal cortex (MeFC). L-dopa tended to normalize connectivity throughout the striatum. Dorsal putamen connectivity to IPL and Cbl correlated with H&Y stage (r Вј -0.71, r Вј 0.59); dorsal and ventral putamen to Cbl with MDS-UPDRS motor score (r Вј 0.63, r Вј -0.58); dorsal caudate to amygdala with Neuropsychiatric Inventory score (NPI; r Вј 0.64); and ventral caudate to SMA and MeFC with MDS-UPDRS motor score (r Вј 0.64, r Вј 0.58), to MeFC with Beck Depression Inventory (r Вј -0.59), and to MeFC and MCC with NPI (r Вј -0.74, r Вј -0.79). These findings suggest altered functional connectivity within dorsal and ventral striatal networks may underlie some of the motor and non-motor symptoms seen in PD. Study supported by: University of Colorado Department of Neurology Objective: To evaluate the prevalence and spectrum of ATP7B mutations in clinically diagnosed Wilson Disease (WD) and determine the genetic prevalence of WD in the UK. Methods: ATP7B sequence analysis was undertaken in 181 WD index cases. The entire ATP7B coding region was sequenced in 1000 controls. Results: The overall mutation detection frequency in WD patients was 98%. We report the first cases of WD due to segmental uniparental isodisomy, three patients with three ATP7B mutations and three families with WD in two consecutive generations. The SNP frequency in the 1000 controls is 0.047 or 0.029 if only those SNPs were included which had previously been reported in WD patients (WDSNP). This frequency of heterozygote mutation carriers is considerably higher than the previously reported occurrence of 1:90 or 0.011 (p < 10-14 if all SNPs included, p Вј 1.31x10-5 for WD-SNPs only). Conclusion: Our study provides strong evidence for monogenic inheritance of WD. The marked discrepancy between the genetic prevalence and the number of clinically diagnosed cases of WD may be due to both reduced penetrance of ATP7B mutations and failure to diagnose patients with this eminently treatable disorder. Study supported by: N/A T1711. Short Hairpin RNA Targeting Endogenous aSynuclein Prevents Degeneration of Dopaminergic Neurons in the Rat Rotenone Model of ParkinsonвЂ™s Disease Jason R. Cannon, Qing Bai, Maxx Horowitz, Victor Tapias, J. Timothy Greenamyre and Edward A. Burton; Pittsburgh, PA and West Lafayette, IN T1709. Metronidazole-Induced Reversible Ataxia and Numbness Chirantan Banerjee, Fazeel Siddiqui and Jessica Lee; Dallas, TX Background: Metronidazole induced neurotoxicity is rare but severe. Ataxia, encephalopathy, seizures, visual dysfunction and peripheral neuropathy have been reported. Cerebellar dysfunction is almost always associated with MRI abnormalities. Case Summary: We present a 65y/o male with diabetes mellitus, rheumatoid arthritis, systemic lupus erythematosus, coronary artery disease, and hyperlipidemia who presented with 2-3 days of gradual-onset dysarthria, ataxia, and worsening of baseline hand/feet numbness. He was on oral metronidazole 500 mg PO TID for 8 weeks prior to presentation for recurrent clostridium difficile colitis. Exam revealed scanning speech, gait and symmetric appendicular ataxia, and decreased sensation to pinprick and vibration in hands/toes. MRI brain revealed bilateral symmetric cerebellar dentate flair hyperintensities without enhancement. CSF was unremarkable. His renal and hepatic functions were normal. Symptoms improved after metronidazole was discontinued. Patient was changed to oral vancomycin for continued clostridium difficile treatment. Conclusion: Clinicians should suspect cerebellar toxicity in patients with subacute ataxia/dysarthria and history of prolonged metronidazole therapy, even at normal doses with normal renal and liver function. MRI must be obtained for diagnosis. Prognosis is favorable once metronidazole is discontinued, although peripheral nerve deficits sometimes persist. Study supported by: Case report. No funding source. Convergent evidence implicates both a-synuclein and mitochondrial dysfunction in the pathogenesis of sporadic ParkinsonвЂ™s disease (PD). Rats exposed chronically to rotenone, a pesticide linked epidemiologically to PD, show systemic mitochondrial defects but develop specific PDlike neuropathology, including degeneration of substantia nigra dopaminergic neurons and a-synuclein accumulation and aggregation. We specifically inhibited expression of endogenous a-synuclein unilaterally in the adult rat substantia nigra by viral delivery of a short haipin RNA (shRNA) targeting the SNCA transcript. Compared with contralateral dopamine neurons expressing normal levels of endogenous a-synuclein, substantia nigra dopamine neurons lacking a-synuclein were robustly protected against chronic rotenone. Consequently, unlike wild-type animals, vector-transduced rats did not develop severe Parkinsonism. These data show that a-synuclein is a critical factor in the specific vulnerability of dopaminergic neurons to systemic mitochondrial dysfunction, supporting a model in which genetic modulation of a-synuclein expression can determine whether environmental exposures trigger PD pathogenesis. Since loss of a-synuclein did not cause detectable toxicity in the nigrostriatal system, shRNA targeting the SNCA transcript should be further evaluated as a neuroprotective therapy in PD patients. Study supported by: VA Merit Review Award: 1I01BX000548 VA Pittsburgh GRECC Pilot Grant ParkinsonвЂ™s Chapter of Greater Pittsburgh Pilot Grant NIEHS: 1K99ES019879, 4R00ES019879 T1710. Striatal Functional Connectivity during Rest in ParkinsonвЂ™s Disease Brian D. Berman, Erika Shelton, Mark Hallett and Tor Wager; Denver, CO; Bethesda, MD and Boulder, CO Functional connectivity MRI (fcMRI) may be able to give insight into basal ganglia circuit disturbances in PD and how these disturbances relate to specific symptoms. 124 ID: guganp I Black Lining: [ON] I Time: 09:25 I Path: N:/3b2/ANA#/Vol00000/120255/APPFile/JW-ANA#120255 J_ID: ZAY Customer A_ID: BKLT2012_Abstracts Cadmus Art: ANA12 Date: 18-September-12 T1712. Effect of Deep Brain Stimulation on Autonomic Function in Early ParkinsonвЂ™s Disease Anna L. Molinari, Fenna T. Phibbs, Lily Wang, Yanna Song, Amanda Currie, Maxim Turchan, Danielle S. Cherdak and David Charles; Nashville, TN Stage: Page: 125 trols. MT-based cargo transport kinetics into CSF were different in neurons and astrocytes. This method appears to identify biomarkers in PD subjects that may reflect abnormalities in axonal transport. Discovery of such biomarkers holds promise to improve diagnosis and to perhaps to monitor disease activity. We also expect that such biomarkers will speed drug discovery since they can be measured in animal models of disease. Study supported by: Michael J Fox Foundation and KineMed, Inc Background: We conducted a pilot trial assessing the safety and tolerability of deep brain stimulation (DBS) in early ParkinsonвЂ™s disease (PD) (NCT00282152). The FDA required additional autonomic safety monitoring as a condition of the Investigational Device Exemption (G050016). Methods: 30 early PD patients were equally randomized to optimal drug therapy (ODT) or ODT plus DBS. Assessments were conducted during week-long medication (and DBS, if present) washouts at baseline and biannually for two years and included daily seated and standing blood pressure (BP) and heart rate. Results: Changes in systolic BP (SBP) due to orthostatic stress ON and OFF medicine (and DBS, if present) were not significantly different between groups after two years. The mean rate of deterioration in SBP OFF medicine from baseline to two years was 5.30 mmHg in the ODT group and 4.67 mmHg in the DBS group (p Вј 0.75). Conclusions: This pilot study suggests that DBS in early PD is not associated with worsening autonomic function (AF) when compared to ODT. A future multicenter trial should utilize interval medication washouts to clarify the deterioration of AF and the effect of DBS on AF in early PD. Study supported by: The clinical trial from which this study is presented is supported by Vanderbilt CTSA grant 1 UL 1 RR024975 from the National Center for Research Resources, National Institutes of Health, by a research grant from Medtronic, Inc., and by gifts from private donors. Vanderbilt University has received grants in excess of $10,000 from Allergan, Ipsen, Medtronic, Merz, and Teva for research or educational programs led by Dr. Charles. Dr. Charles has received income for education or consulting services from Medtronic, Allergan, Ipsen, Teva, and Merz. Dr. Phibbs has served as a consultant for Boston Scientific and Medtronic. She has also received payment for educational presentations for Teva. T1714. Predictors of Cognitive Performance Following Bilateral Subthalamic Nucleus Deep Brain Stimulation Lidia Yaguez, Angela Costello, John Moriarty, Natasha Hulse, Richard Selway, Chris Clough, Michael Samuel and Keyoumars Ashkan; London, United Kingdom and Kent, United Kingdom The beneficial effects of deep brain stimulation of the subthalamic nucleus for the treatment of motor symptoms in advanced ParkinsonвЂ™s disease are well established. Its effect on cognitive functions is still controversial. Attempts to determine which pre-operative cognitive measures may help to predict post-operative cognitive change warrant further attention. 30 non-demented PD patients underwent detailed neuropsychological assessment pre and post STN-DBS surgery. The individual significance of deficits, as well as the group statistical differences pre and post surgery were analysed. Stepwise regression analysis was used to identify best cognitive predictors of post-operative changes. Post surgery, immediate story recall showed a significant decline in its group mean; with a large size effect. The best predictors for this change were pre-surgical list learning and Full IQ. These results suggest that non-demented patients with even mild impairments in general intellectual functions and list learning memory functions may be at greatest risk of decline in other aspects of verbal memory after STN-DBS. These should be taken into account when selecting and consenting patients for surgery. The results also demonstrate for most PD patients there was no significant decline in cognitive functions following STN-DBS. Study supported by: No funding obtained T1713. Identification of Axonal Transport Biomarkers in ParkinsonвЂ™s Disease Christine W. Chadwick, Michael J. Aminoff, Po- Yin A. Wong, Kristofor H. Husted, Shanshan Liu, Victoria M. Liu, Lori A. Kohlstaedt, Johan Protasio, Timothy Riff, Drina Boban, Maudi Killian, Lorrie Epling, Elisabeth Sinclair, Julia Peterson, Richard Price, Marc K. Hellerstein and Patrizia Farnara; San Francisco; Emeryville, CA and Berkeley T1715. What Patient Factors Associate with Inaccuracies in Reporting of Parkinsonian Signs? Nabila Dahodwala, Andrew Siderowf and Jason Karlawish; Philadelphia Identifying early parkinsonism utilizes patient self-reports, but patient self-reports are often inaccurate. Little is known about why patients are inaccurate. Older adults (mean age 68) seen at primary care clinics completed a self-report questionnaire for parkinsonian signs. Parkinsonian signs were defined as at least two of four cardinal signs (bradykinesia, rigidity, tremor, gait dysfunction) identified by examination. Logistic regression determined whether demographics, mood, cognition, and aging expectations associated with false positive or false negative cases on the self-report questionnaire. Results: 18.5% (N Вј 128) of 692 participants had parkinsonian signs on exam. A cut-point of 2 on the self-report questionnaire maximized sensitivity (63.6%) with a moderate specificity (53%) for parkinsonian signs: 43 cases categorized as false negatives and 275 cases were false positives. Older age was associated with a false negative result (p<0.001). Lower aging expectations and higher depression Sensitive biomarkers for neurodegenerative diseases would facilitate early diagnosis and therapeutic advances. Defects in microtubule-based neuronal transport may be a common pathway for neurodegeneration. Microtubule transport (MT) can be studied using 2H2O pulse labeling in animals and humans since certain newly synthesized 2H-labeled proteins are transported by this system and can be measured in cerebrospinal fluid (CSF). Twelve patients with ParkinsonвЂ™s disease (PD) and 6 controls underwent pulse administration of 2H2O (for 7 consecutive days) and then had CSF collected 1-43 days later for gas chromatographic/mass spectrometric analysis. We found striking neuronal transport deficits of 2H-labeled chromogranin-B, non-amyloidogenic secreted N-terminalfragment of amyloid-precursor-protein (sAPPa), and a-synuclein but not neuregulin-1 in PD patients compared to con- 125 ID: guganp I Black Lining: [ON] I Time: 09:25 I Path: N:/3b2/ANA#/Vol00000/120255/APPFile/JW-ANA#120255 J_ID: ZAY Customer A_ID: BKLT2012_Abstracts Cadmus Art: ANA12 Date: 18-September-12 scale scores were associated with a false positive result (p Вј 0.007 and p Вј 0.001, respectively). Conclusion: Inaccuracies in self-reported symptoms are related to older age, lower aging expectations and depression in this sample. Recognition and adjustment for these factors may improve screening for parkinsonian signs. Study supported by: NIA Stage: Page: 126 Study supported by: NIH/NINDS: K23 NS073626 NIH/NINDS: R01 NS040596 T1718. Clinical Assessment of the Effect of Tetrabenazine on Motor Function in Moderate Huntington Disease Robert Fekete, Anthony Davidson and Joseph Jankovic; Valhalla, NY and Houston, TX T1716. Previously Unspecified SETX Mutation Producing AOA2 in Two Siblings Neil Datta and Anna Hohler; Boston, MA Objective: We designed a study to test motor performance using validated scales of hand function and gait on and off tetrabenazine in patients with Huntington disease (HD). Background: Tetrabenazine is a monoamine depleter with well documented effect against chorea associated with HD. There is paucity of data about how reduction in chorea relates to better performance in activities of daily living. Methods: The following instruments were used to assess cognitive, behavioral, and motor function in 10 patients with documented HD: The Montreal Cognitive Assessment, Beck Depression Inventory II, Dynamic Gait Index, Jebsen Hand Test, Timed 25 foot walk, Berg Balance Test, QuickDASH, and the Unified Huntington Disease Rating Scale (UHDRS). Results: Subjects performed significantly better while on tetrabenazine as measured by the Berg Balance Test, Dynamic Gait Index, UHDRS Total Motor and Maximum Chorea scores, and the Stroop Color-Word tests. Conclusions: Tetrabenazine treatment is associated with improvement not only in chorea but also in measures of motor performance. Study supported by: Lundbeck, Inc. Dr. Fekete has served as a consultant for Lunbeck, Inc. The study documents a unique case wherein a previously unidentified SETX mutation combined with a previously recognized recessive SETX mutation produces AOA2. Myriad mutations in the SETX gene (encoding senataxin) have been associated with the recessive disorder ataxia with oculomotor apraxia type 2 (AOA2). AOA2 is characterized by symptoms such as cerebellar atrophy, ataxia, and oculomotor apraxia. We document a novel SETX mutation combination causing AOA2 in a sibling pair. A detailed family history, neurological exam, and genetic analysis were conducted for both patients. AOA2 symptoms presented $17 y.o., with no previous indications. Symptoms included hypophonia, trace dysarthria, extraocular muscle dysfunction, etc. Family history includes neurological difficulties in paternal relatives at advanced ages. AOA2 diagnosis was confirmed by MRI, AFP elevation, and genetic testing. The older brother began physical therapy and 1200 mg CoQ10 anti-oxidant countering the mutated sentaxin. This treatment improved strength and other symptoms. The younger sisterвЂ™s early diagnosis may allow better control. This study describes a previously unknown SETX gene mutation combined with an established SETX mutation (that itself may cause milder and late-onset symptoms) that results in the onset of full AOA2 disease at normal onset. Study supported by: None. T1719. Identification of Individualized Cortical Targets for Focal Brain Stimulation Based on Intrinsic Functional Connectivity Michael D. Fox, Randy L. Buckner and Alvaro Pascual-Leone; Boston, MA T1717. Directional EEG Connectivity Method Demonstrates Complex, Reciprocal Information Flows during Praxis Performance Joshua B. Ewen, Balaji M. Lakshmanan, Stewart H. Mostofsky, Nathan E. Crone and Anna Korzeniewska; Baltimore, MD It is becoming increasingly clear that focal brain stimulation techniques such as transcranial magnetic stimulation (TMS) and deep brain stimulation (DBS) propagate beyond the site of stimulation to impact a distributed network of connected brain regions. Recently we have suggested that targets for focal brain stimulation should be selected at least partially based on their connectivity to other regions. Specifically, we have shown that intrinsic functional connectivity with the subgenual cingulate is correlated with average clinical efficacy of different TMS targets in the dorsal lateral prefrontal cortex used for depression. In this article we translate these findings into a method for individualized connectivity-based targeting of focal brain stimulation based on resting state functional connectivity MRI. We show that individuals posses large differences in their ideal stimulation site and that these differences are reproducible across repeated sessions. Application to Depression and ParkinsonвЂ™s disease are discussed. Study supported by: We thank the Brain Genomics Superstruct Project for contributing data. MDF was supported by NIH Grant R25NS065743. APL serves on the scientific advisory boards for Nexstim, Neuronix, Starlab Neuroscience, Allied Mind, Neosync, and Novavision, and is listed as inventor in issued patents and patent applications on the real-time integration of transcranial magnetic stimulation (TMS) with electroencephalography (EEG) and magnetic resonance imaging (MRI). Work on this study was Praxis function is known from lesion studies to depend on left parietal and premotor regions. While the typical physiological model suggests that praxis вЂ�вЂ�commandsвЂ™вЂ™ are sent from the left parietal region to left premotor regions and then to primary motor cortex, EEG studies of go/no-go praxis tasks suggest more complex interactions between bilateral anterior and posterior brain regions. Using a high density EEG array, we recorded data from a praxis task and analyzed them with Event Related Causality (ERC; Granger-Causality-based method which estimates dynamical changes in brain activity flow). Because the ERC method has been not previously been applied to scalp EEG, we investigated optimal analysis parameters. Data from the mental rehearsal portion of the task demonstrated activity flows between left and right posterior regions and flows from both posterior regions toward left frontal regions. Data from the initiation of the pantomime portion demonstrated reciprocal flows, suggesting feedback from left anterior regions to bilateral posterior regions. These results demonstrated the utility of ERC in analyzing scalp EEG recordings and suggest generally that systems-level neural complex motor circuits function with reciprocal information flows. 126 ID: guganp I Black Lining: [ON] I Time: 09:25 I Path: N:/3b2/ANA#/Vol00000/120255/APPFile/JW-ANA#120255 J_ID: ZAY Customer A_ID: BKLT2012_Abstracts Cadmus Art: ANA12 Date: 18-September-12 also supported by grants from the National Institutes of Health and National Center for Research Resources: Harvard Clinical and Translational Science Center (UL1 RR025758) and the Howard Hughes Medical Institute. Stage: Page: 127 T1722. Progressive Ataxia and Palatal Tremor Syndrome (PAPTS): Clinical and Radiological Findings Pablo Garcia-Reitboeck, Marie-Helene Marion and Salah Omer; London, United Kingdom PAPTS is a rare syndrome of largely unknown aetiology, although genetic forms have been described. We present clinical and radiological findings and videos of three male patients with PAPTS. Age at presentation ranged from 6269. All patients had cerebellar ataxia and palatal tremor. Onset in patient 1 was with blurring of vision and difficulty with balance, while in patient 2 palatal tremor preceded development of balance problems, blurring of vision, speech and swallowing difficulties. Patient 2 had suffered a REM sleep behavioural disorder for 4 years prior to the onset of palatal tremor. Patient 3 presented with progressive unsteadiness and sensorineural hearing loss. Only one patient experienced the characteristic ear clicks associated with palatal tremor. None had a relevant family history. MRI brain demonstrated the presence of hypertrophic olivary degeneration in all patients. Video-oculography of patient 2 showed torsional right eye oscillation, synchronous with pupillary oscillations. Testing for mutations in the GFAP gene (Alexander disease) was negative in patient 2 and pending in patient 3. No mutations were detected in POLG1 gene in patients 2 and 3. Our 3 cases demonstrate the clinical heterogeneity of this syndrome. Study supported by: none T1720. Does Iron Play Different Roles in Various Neurodegenerations? Andrzej Friedman and Jolanta Galazka-Friedman; Warsaw, Poland Background: Iron may play deleterious role in neurodegeneration by triggering oxidative stress via Fenton reaction. Iron was studied in ParkinsonвЂ™s disease (PD) with controversial results. In other neurodegenerations, e.g. Alzheimer disease (AD) and progressive nuclear palsy (PSP) it still needs evaluation. Aim: to assess the concentrations of total and labile iron, and ferritin in PD, AD and PSP. Material and Methods: samples of substantia nigra (SN), globus pallidus (GP) and hippocampal cortex (Hip) from PD, PSP and AD brains were assessed with ELISA, MoВЁssbauer spectroscopy, and atomic absorption. Results: No increase in the concentration of iron in PD vs. control was detected, however there was an increase of labile iron, which constitutes only 2% of total iron in SN. A significant decrease of the concentration of L chains in PD compared to control was found. In AD an increase in the concentration of ferritin was noticed, without a significant increase in iron concentration. In PSP an increase of total iron was observed. Conclusion: Our findings suggest that the mechanisms leading to nervous cells death in these three diseases may be different, although all may be related to iron mediated oxidative stress. Study supported by: No financial support T1723. Progressive Bilateral Parkinsonism Secondary to a Unilateral Midbrain Lesion Maiya R. Geddes, A. Jon Stoessl, Alain Dagher, Jean-Paul Soucy and Anne-Louise Lafontaine; Montreal, QC, Canada and Vancouver, BC, Canada Background: Idiopathic ParkinsonвЂ™s disease (IPD) is characterized by gradual loss of nigrostriatal dopaminergic neurons. Transient toxic or infectious exposure can produce a progressive syndrome resembling IPD. Evidence from animal studies extends this finding: Unilateral nigral damage affects contralateral dopamine turnover. Methods: An individual presenting with left-sided parkinsonism and resting tremor secondary to a right midbrain aneurysm was assessed for ten years. We measured presynaptic nigrostriatal integrity with [11C]-dihydrotetrabenazine, [11C]-d-threo-methylphenidate, and 6-[18F]-fluoro-L-dopa and postsynaptic dopamine function with [11C]-raclopride positron emission tomography (PET). Findings: After seven years, bradykinesia and rigidity emerged ipsilateral to the lesion. Despite progression of parkinsonism, clinical signs and structural imaging of the aneurysm remained unchanged. The patient never experienced anosmia or a sleep disorder, making coincidental IPD unlikely. Striatal PET imaging showed bilateral, asymmetric reduced presynaptic and increased postsynaptic radiotracer uptake: A rostral-caudal gradient was observed with relative preservation of the caudate and preferential involvement of the posterior putamen, a pattern typical of IPD. Interpretation: This case provides evidence of a static unilateral midbrain lesion producing progressive, bilateral dopaminergic dysfunction. This result shows that discrete nigrostriatal damage can lead to progressive pathology and unilateral interruption of dopaminergic pathways influences contralateral dopamine function. Study supported by: M.R.G. is supported by a Richard and Edith Strauss Fellowship. A.J.S. is supported by the Canadian Institutes for Health Research, The Michael Smith Foundation for Health Research, the Pacific T1721. Asymmetric Upper Motor Neuron Disease (MillsвЂ™ Syndrome) Presenting as Corticobasal Syndrome Shinsuke Fujioka, Masataka Nakamura, Melissa E. Murray, Zbigniew K. Wszolek and Dennis W. Dickson; Jacksonville, FL Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease involving both upper and lower motor neurons bilaterally. A rare hemiplegic form of ALS with asymmetric upper motor neuron degeneration has been reported under the rubric of MillsвЂ™ syndrome. We present clinical findings and neuropathology of five patients with MillsвЂ™ syndrome. The cases were referred to the CurePSP brain bank with final clinical diagnoses of corticobasal degeneration (CBD). Review of available medical records revealed a mean age of symptomatic onset of 59 years. All patients had asymmetric clinical features, with asymmetric increased muscle tone, lack of lower motor neuron signs and no evidence of lower motor neuron disease on those patients who had electrophysiological tests. They all had rigidity and bradykinesia. Pathologically, both upper and lower motor neurons were involved; however, neuronal loss, gliosis, and cytoplasmic TDP-43 inclusions were much more severe in the motor cortex than in the brainstem motor neurons or the anterior horns of the cervical spinal cord. The histopathological features of CBD were absent with tau immunohistochemistry. The results suggest that asymmetrical upper motor neuron predominant presentations of ALS can clinically masquerade as corticobasal syndrome. Study supported by: Nothing to disclose 127 ID: guganp I Black Lining: [ON] I Time: 09:25 I Path: N:/3b2/ANA#/Vol00000/120255/APPFile/JW-ANA#120255 J_ID: ZAY Customer A_ID: BKLT2012_Abstracts Cadmus Art: ANA12 Date: 18-September-12 Stage: Page: 128 Alzheimer Research Foundation, and the Canada Research Chairs program. A.D. is supported by Fonds de Recherche en SanteВґ du QueВґbec, Canadian Institutes of Health Research T1726. GABA Receptor Changes and Functional Connectivity Abnormalities in Focal Hand Dystonia Cecile Gallea, Priyantha Herath, Valerie Voon, Alicja Lerner and Mark Hallett; Bethesda, MD T1724. Rapid Onset Dystonia-Parkinsonism Associated with the I758S ATP1A3 Mutation: A Neuropathologic Study of Three Affected Siblings Bernardino Ghetti, Matthew C. Hagen, Joseph Maldjian, Christopher T. Whitlow, Laurie J. Ozelius, Kathleen J. Sweadner and Allison Brashear; Indianapolis, IN; Cincinnati, OH; Winston-Salem, NC; New York, NY and Boston, MA Focal hand dystonia is characterized by excessive muscle co-contraction producing abnormal movements. It is associated with impaired inhibitory mechanisms, but the pathophysiology of the lack of inhibition and its consequence on sensorimotor network functioning is not clearly understood. We hypothesized that inhibitory impairment originates in reduced efficacy of GABA-ergic interneurons of the primary motor cortex and the putamen. Density of GABA-A receptors using [11C] Flumazenil was measured with positron emission tomography. Eighteen patients with right focal hand dystonia and 18 age and gender matched healthy volunteers participated. Fourteen of the patients performed right hand motor tasks during functional MRI acquisition to measure functional connectivity in the sensorimotor network. Compared to controls, patients had decreased GABA-A receptor density in primary sensorimotor cortex and in the putamen contralateral to the symptomatic hand, as well as in the sensorimotor cerebellum ipsilateral to the symptomatic hand. Abnormal GABA-A receptor density in the left hand knob of the motor area and in the right cerebellum correlated with functional connectivity in the striato-cortical and the cerebello-cortical loops, respectively. We conclude that the changes in GABA binding affect sensorimotor network activity indicating functional relevance in dystonia. Study supported by: NINDS Intramural Program. Rapid-Onset Dystonia-Parkinsonism (RDP) is associated with mutations in the ATP1A3 gene. Clinical features include dysarthria, dysphagia, limb dystonia, bradykinesia and postural instability. The symptomatology remains stable for decades. This report is a neuropathologic analysis of three siblings carrying the I758S ATP1A3 mutation. Immunohistochemical studies included using antibodies against GFAP, calbindin, synaptophysin, and neuron-specific enolase. Neuronal rarefaction and a moderate astrocytosis in the globus pallidus, subthalamic nucleus, red nucleus, and inferior olivary nucleus were seen. In the cerebellar cortex, torpedoes of Purkinje cell axons and a moderate rarefaction of granule cells were noted, while in the dentate nucleus (DN) there was a significant neuronal rarefaction. Synaptophysin immunohistochemistry showed synaptic losses in areas of the DN where neuronal rarefaction was evident. We postulate that in RDP associated with I758S ATP1A3 mutation there is a damage of the connectivity of the globus pallidus, subthalamic nucleus and red nucleus. In addition, the cerebellum shows a significant abnormality in the density of neurons of the DN and related presynaptic terminals. It is hypothesized that the dentatorubral-pallidal, olivocerebellar and dentato-olivary pathways are affected. Study supported by: R01 NS058949, P30 AG010133 T1727. What Issues Face ParkinsonвЂ™s Patients at Ten Years and beyond? Anhar Hassan, Samuel Wu, Peter Schmidt, Irene A. Malaty, Yun Feng Dai, Janis Miyasaki and Michael S. Okun; Gainesville, FL; Miami, FL and Toronto, Canada T1725. Alcoholic Cerebellar Degeneration: Not All Due to Alcohol Marios Hadjivassiliou, Stuart Currie, David Sanders and Nigel Hoggard; Sheffield, United Kingdom Background: ParkinsonвЂ™s disease (PD) leads to cumulative disease burden. Clinical status and health-related quality of life (HRQoL) at the 10-year milestone are not welldocumented. Methods: Cross-sectional study of PD patients ! 10-year disease duration (PD-10) (n Вј 1835) enrolled in the multicenter National Parkinson Foundation Quality Improvement Initiative (NPF-QII). Results: PD-10 patients (62.2% male), mean age 67.8 years (69.5), mean age of PD onset 52.7 years (610.6), and median disease duration 14 years (range 11-18). Many had minimal disability, (HY 1-2, 44.0%), or postural instability (HY 3, 40.3%). Most (88.2%) stood unaided but 54.8% reported falls. Almost all lived at home (93.1%) with a caregiver (83.8%). Patients had 1.9 (61.4) of surveyed co-morbidities, with arthritis (48.9%) and cardiac (31.7%) most common. Majority (86.7%) took !2 medications: levodopa (95.7%), dopamine-agonists (45.6%) or antidepressants (37.3%). 22.4% had deep-brain-stimulation. Mean HRQoL and caregiver-burden was impaired in all domains. Conclusions: PD-10 patients attending NPF-centers mostly remain mobile and living at home (93%), compared to previous studies, which may reflect better care or other biases. Falls, caregiver-burden, and impaired HRQoL are common. Policies to improve in-home patient/caregiver support are crucial to maintain patients at home. Study supported by: No disclosures Amongst 885 patients with progressive cerebellar ataxia attending a specialist ataxia clinic at the Royal Hallamshire Hospital, Sheffield, UK, there were 100 patients whose ataxia was thought to be secondary to chronic excessive alcohol intake. These patients had hematological markers of alcohol excess (raised MCV, gamma GT). All patients had MR imaging, were screened for other causes of ataxia and had their HLA typed. Sixty one percent had the DQ2 HLA type compared to 30% in healthy local blood donors. HLA DQ2 is associated with autoimmune diseases such as celiac disease, hypothyroidism etc. Forty four percent of patients had positive antigliadin antibodies (IgG and/or IgA) compared to 12% in the healthy local population and 10% in patients with genetically confirmed ataxias. None had celiac disease on duodenal biopsy. Voxel-based morphometric analysis of brain MR showed a different pattern of cerebellar involvement in those patients with alcoholic ataxia with and without positive serology for gluten sensitivity to what is seen in gluten ataxia. Alcohol excess may cause cerebellar degeneration in genetically susceptible individuals and may induce sensitization to gluten. Study supported by: no financial support receieved 128 ID: guganp I Black Lining: [ON] I Time: 09:25 I Path: N:/3b2/ANA#/Vol00000/120255/APPFile/JW-ANA#120255 J_ID: ZAY Customer A_ID: BKLT2012_Abstracts Cadmus Art: ANA12 Date: 18-September-12 T1728. Dysphagia i Spinocerebellar Ataxia Type 3 and Type 6 Chiharu Isono, Makito Hirano, Hikaru Sakamoto, Shuichi Ueno, Susumu Kusunoki and Yusaku Nakamura; Sakai, Osaka, Japan and Osakasayama, Osaka, Japan Stage: Page: 129 ticularly in motor compensation and development of levodopa-induced-dyskinesia (LID). The red nucleus (RN) mediates cerebellar involvement in motor control, and iron changes in the RN may reflect cerebellum-related compensation and/or mark the intrinsic capacity of PD subjects to develop LID. This is the first study focused on the RN to test this hypothesis. Multi-echoes T2*-weighted MRI images were acquired from 38 PD subjects [12 with (PD/DYSГѕ) and 26 without (PD/DYS-) history of dyskinesia] and 23 Controls. Iron content was estimated from transverse relaxation rates (R2*) of RNs and SNs. We found that PD subjects overall displayed higher R2* values in both the SN (p Вј 0.002) and RN (p Вј 0.019). RN R2* values were significantly higher in PD/DYSГѕ (p Вј 0.002), but not PD/DYS(p Вј 0.180) when compared to Controls. RN R2* values also were significantly greater in PD/DYSГѕ than PD/DYS(p Вј 0.011). The association of higher RN iron content with PD-related dyskinesia is consistent with the hypothesis that increased iron content reflects greater cerebellar compensatory capacity and thus increased likelihood of LID development. Study supported by: National Institutes of Health (NS060722 and ES019672 to XH), the Penn State Clinical & Translational Science Institute, Pennsylvania State University CTSA (UL-1RR033184), and the Pennsylvania Department of Health Tobacco Settlement Funds (C06 RR016499) Spinocerebellar ataxia type 3 (SCA3) and type 6 (SCA6) are the most common forms of autosomal dominant ataxia. Dysphagia in these diseases is important clinically, since dysphagia-related aspiration commonly causes fatal pneumonia. In this study we evaluated dysphagia in 7 patients with SCA3 and 13 patients with SCA6 by videofluoroscopic examination of swallowing (VF). The evaluation was based on the scale established by Japanese Society of Dysphagia Rehabilitation, which can evaluate oral and pharyngeal phases separately, and on dysphagia outcome severity score (DOSS), a scale used world-widely. The result showed that mild dysphagia was detected in SCA6 and severe one in SCA3 on the Japanese scale. By contrast, DOSS revealed the abnormality in SCA3 but not in SCA6. The extent of swallowing abnormalities in SCA3 or SCA6 did not parallel that of physical disability or durations of diseases, suggesting that patients with well-preserved physical functions or in even early stages of the diseases had risks of aspiration. In conclusion, SCA6 had mild but significant involvement of swallowing as compared to SCA3. The evaluation of swallowing ability by VF is essential to prevent potential aspiration in both diseases. Study supported by: N/A T1731. Side of ParkinsonвЂ™s Disease Onset Predicts Gray Matter Loss and Cognitive Impairments Suman Sen, Paul J. Eslinger, Daymond Wagner, Michele L. Shaffer, Mechelle M. Lewis, Guangwei Du and Xuemei Huang; Hershey, PA T1729. Multiple System Atrophy with Inappropriate Secretion of Antidiuretic Hormone Makoto Samukawa, Makito Hirano, Hikaru Sakamoto, Mari Kitada, Susumu Kusunoki and Yusaku Nakamura; OsakaSayama, Osaka, Japan and Sakai, Osaka, Japan Although ParkinsonвЂ™s disease (PD) frequently presents with asymmetric onset, cortical and subcortical gray matter (GM) changes associated with onset-side have not been investigated. Moreover, while the causes of motor symptoms have been established, the relationships between onset-side, neurocognitive dysfunctions, and its neural underpinnings have not been clearly characterized. To address these issues, we obtained brain magnetic resonance imaging and neuropsychological testing data from 23 left-onset and 23 right-onset PD, and 23 healthy controls. Subjects were all right-handed, matched in age, gender, and disease severity. Voxel-based morphometry measured cortical and subcortical GM differences between the groups, while neuropsychological tests assessed right and left hemisphere dysfunction. Neuropsychological data were also examined for correlation to GM changes in PD. Results indicated that PD subjects sustained lateralized GM loss depending on the onset-side, with leftonset PD showing more extensive cortical and subcortical GM loss in the right hemisphere that correlated with decrements in select executive function, visuospatial learning and memory, and procedural learning tasks. Findings support an anatomical basis for early cognitive change in PD and underscore the importance of classifying PD based on onset-side for future research and clinical practice. Study supported by: National Institute of Health Multiple system atrophy (MSA) is a slowly progressive neurodegenerative disease, characterized by cerebellar, pyramidal, extrapyramidal, and autonomic disturbances. MSA also affects the hypothalamus and tracts from the medulla to the hypothalamus. Hypothalamic cells synthesize antidiuretic hormone (ADH), which increases water reuptake in the kidney. Hypothalamic disturbances can lead to the syndrome of inappropriate antidiuretic hormone secretion (SIADH) and resultant hyponatremia. So far six patients with MSA and SIADH have been reported. We here report a patient who had MSA with extreme hyponatremia (99 mEq/l) and the highest reported ADH concentration (25.5 pg/ml). This patient recovered from coma, but became ventilator dependent. We also measured ADH in 14 severely disabled patients with MSA without symptomatic SIADH, and found significantly higher ADH levels than disease controls with similar disabilities. Taken together, these findings suggest that patients with MSA have a risk of hyponatremia or SIADH. Clinicians and caregivers should thus be aware that patients with MSA carry a risk of SIADH and should carefully regulate salt and water intake to avoid further disability and potentially fatal outcomes. Study supported by: N/A T1732. Patient Expectations and Outcome after DBS Nasrin Esnaashari, Jospehine Hwu, Jennifer S. Hui and Daniel Togasaki; Los Angeles, CA T1730. Higher Iron in the Red Nucleus Marks ParkinsonвЂ™s Dyskinesia Mechelle M. Lewis, Guangwei Du, Michal Kidachi, Nisargkumar Patel, Michele L. Shaffer, Richard B. Mailman and Xuemei Huang; Hershey, PA Background: Many publications have examined the outcome of deep brain simulation (DBS) for ParkinsonвЂ™s disease, but none have assessed patient satisfaction and fulfillment of patientsвЂ™ expectations. This study determined patientsвЂ™ expectations preoperatively, evaluated their Although dopamine cell loss and increased iron in the substantia nigra (SN) are well known in ParkinsonвЂ™s disease (PD), cerebellar involvement is increasingly recognized, par- 129 ID: guganp I Black Lining: [ON] I Time: 09:25 I Path: N:/3b2/ANA#/Vol00000/120255/APPFile/JW-ANA#120255 J_ID: ZAY Customer A_ID: BKLT2012_Abstracts Cadmus Art: ANA12 Date: 18-September-12 Stage: Page: 130 (DTBZ) and [11C] 2beta-carbomethoxy-3beta-4-fluorophenyltropane (CFT) with in vitro measures of nigral cell counts and striatal dopamine in monkeys after intracarotid MPTP (0-0.31 mg/kg) injection. Striatal BPND for each radiotracer linearly correlated with stereologic nigral cell counts only for nigral loss < 50% (r2! 0.91, p<0.001). In contrast, striatal BPND correlated with striatal dopamine over the full range of dopamine depletion (r2! 0.94, p<0.001). Interestingly, BPND for each radiotracer correlated with the others (r2 Вј 0.98, p<0.001). Striatal uptake of each tracer did not consistently reflect nigral neurons. This may explain discordant results between neuroimaging and clinical endpoints in PD trials. Furthermore, strong correlations among BPND values do not support differential regulation of decarboxylase activity, vesicular monoamine transporter type 2, and dopamine transporter. Study supported by: NIH (NS050425, NS058714, NS41509, and NS075321); Michael J Fox Foundation; Murphy Fund; American Parkinson Disease Association (APDA) Center for Advanced PD Research at Washington University; Greater St. Louis Chapter of the APDA; McDonnell Center for Higher Brain Function; Hartke Fund; Barnes-Jewish Hospital Foundation (Elliot Stein Family Fund for PD Research & the Jack Buck Research Fund). fulfillment postoperatively (6 months) and correlated this with their self-rated motor improvement and with clinical evaluations. Methods: Patients undergoing surgery completed a questionnaire recording three goals for DBS. At 6, 12, 18, and 24 months after surgery patients completed follow-up surveys. Clinicians assessed each patient before and at 6, 12, 18, and 24 months after DBS placement using the Clinical Global Impression-Improvement (CGI-I) scale. Results: Six patients have 6-month data. Their individual expectations were largely met, with 16 of 18 goals improving. All patients reported improvement in their neurologic symptoms, but the extent of improvement did not correlate with CGI-I scores. Self-rated improvement in neurologic symptoms correlated much better, however, with how well preoperative expectations were fulfilled. Conclusions: PatientsвЂ™ self-rated improvement in neurologic status after DBS for ParkinsonвЂ™s disease did not correlate with physician-rated improvement (CGI-I), but showed stronger correlation with the degree of fulfillment of their initial expectations. Study supported by: N/A T1733. Lewy Body Negative Idiopathic Parkinsonism Fariha Zaheer, John T. Slevin, Erin L. Abner, Peter T. Nelson and Gregory A. Jicha; Lexington, KY T1735. Randomized, Double-Blind, Double-Dummy Study of Levodopa-Carbidopa Intestinal Gel in Patients with Advanced ParkinsonвЂ™s Disease: Functional and Quality-of-Life Outcomes K. Kieburtz, A. Antonini, C.W. Olanow, H.H. Fernandez, A.J. Espay, D.G. Standaert, S. Hass, K. L. Widnell, W.Z. Robieson, Y. Pritchett, K. Chatamra and J. Benesh; Rochester, NY; Padua, Italy; New York, NY; Cleveland, OH; Cincinnati, OH; Birmingham, AL and Abbott Park, IL Objective: Pathologic Lewy body (LB) inclusions in the substantia nigra (SN) are considered the classic anatomic substrate for idiopathic Parkinsonism (iPD). The present study was designed to investigate the pathologic substrate in LB negative iPD. Methods: Thirty-eight cases with a clinical diagnosis of iPD proximal to death were identified in the University of Kentucky brain bank (n Вј 523), with Lewy body pathology (LBPГѕ, n Вј 19) and without Lewy body pathology (LBP-, n Вј 19). Cases were analyzed for differences in semiquantitative pathological variables including LB, cerebrovascular disease, cerebral amyloid angiopathy, and quantitative differences in neuronal density and pigmentary incontinence. Results: Half cases with clinically diagnosed iPD/DLB did not have evidence for LBPГѕ. There were no differences between LBP-and LBPГѕ cases across demographic variables (age, gender, education). Vascular pathology did not differ between groups. Further analysis of SN neuronal loss using stereologic quantitative techniques failed to reveal differences between LBPГѕ and LBP- cases (p Вј 0.39; t-test). Interpretation: Pathologically-unexplained, clinicallydiagnosed Parkinsonism is prevalent in this communitybased sample. While idiopathic substantia nigral neuronal loss may explain Parkinsonian symptoms in this group, the etiologic cause and pathological substrate for such clinical and pathological features in LBP-, iPD remains unknown and warrants further investigation. Study supported by: NIA 1 P30 AG028383 Fluctuating blood levels of levodopa are associated with motor complications in ParkinsonвЂ™s disease (PD). Levodopacarbidopa intestinal gel (LCIG) provides continuous levodopa infusion via intrajejunal percutaneous gastrostomy tube. A double-blind, double-dummy trial compared the efficacy, safety, and tolerability of LCIG to that of optimized oral levodopa-carbidopa immediate-release (IR) therapy in patients with advanced PD and motor fluctuations. Levodopa-responsive patients received LCIG infusionГѕplacebo capsules or encapsulated levodopa-carbidopa IR tabletsГѕplacebo gel infusion for 12 weeks. Outcome measures included: 39-item PD Questionnaire (PDQ-39), Clinical Global ImpressionвЂ“ Improvement (CGI-I) score, and Unified PD Rating Scale (UPDRS) Part II (Activities of Daily Living) score in the вЂ�вЂ�OnвЂ™вЂ™ state. 71 patients were randomized (n Вј 37 LCIG; n Вј 34 IR) and 66 (95% LCIG; 91% IR) completed the trial. LCIG (n Вј 36) significantly improved PDQ-39 summary index (difference in LS Mean change Вј -7.0, P Вј 0.015), CGI-I (difference in LS Mean Вј -0.7, P Вј 0.026), and UPDRS Part II (difference in LS Mean change Вј -3.0, P Вј 0.009) compared with IR (n Вј 33). These results demonstrate superior improvements by LCIG compared with optimized oral levodopa-carbidopa therapy in functional and quality-of-life outcomes in patients with advanced PD. Study supported by: Abbott Katherine Widnell, Weining Robieson, Yili Pritchett, Steve Hass, Krai Chatamra, and Janet Benesh are employees of Abbott. Karl Kieburtz, C Warren Olanow, and Angelo Antonini have received compensation from Abbott for serving as consultants and participating in scientific advisory boards. Alberto J Espay and David G Standaert were study investigators and have received compensation from Abbott for serving T1734. Comparison of In Vivo PET with In Vitro Measures of Pre-Synaptic Nigrostriatal Neurons Morvarid Karimi, LinLin Tian, Christopher A. Brown, Hubert P. Flores, Susan K. Loftin, Tom O. Videen, Steve M. Moerlein and Joel S. Permutter; St. Louis, MO Discrepancies between neuroimaging and clinical endpoints in Parkinson disease (PD) studies raise questions about relationships between neuroimaging and in vitro measures of nigrostriatal neurons. We compared striatal binding potential (BPND) of 3 PET tracers 6-[18F]fluorodopa (FD), [11C] dihydrotetrabenazine 130 ID: guganp I Black Lining: [ON] I Time: 09:25 I Path: N:/3b2/ANA#/Vol00000/120255/APPFile/JW-ANA#120255 J_ID: ZAY Customer A_ID: BKLT2012_Abstracts Cadmus Art: ANA12 Date: 18-September-12 as consultants, lecturers, and/or participating in scientific advisory boards. Hubert H Fernandez was a study investigator and has served as a consultant for Abbott through a contract between Abbott and Cleveland Clinic Foundation; he has not received any personal compensation from Abbott. Stage: Page: 131 T1738. An Unexpected Cause of Altered Mental State in a Presumed Healthy Caucasian Male Tobias B. Kulik and Irene H. Richard; Rochester, NY A 55 year-old right handed Caucasian man, former college graduate, with an unremarkable past medical history presented to the Emergency Department of a local hospital after a witnessed episode of loss of consciousness in a local grocery store. Assessment of his mental state demonstrated psycho-motor slowing, difficulty with abstract reasoning, dyscalculia and concrete thinking. His neurological examination was notable for language dysfluency, mild hypomimia, diffuse choreo-athetosis and bilateral paratonia. However, there were no abnormalities on sensory, cerebellar, reflex or gait testing. His EEG did not exhibit signs of epileptiform activity and his cardiovascular work-up, including tilt table testing, was unremarkable. A non-contrasted head CT showed extensive bilateral, symmetric calcifications of the cerebellum, the white matter tracts within the cerebral cortices and basal ganglia. After disorders of calcium homeostasis, autoimmune disease and toxin exposure had been ruled out, a diagnosis of bilateral strio-pallidodentate calcinosis (BSPDC) was made. BSPDC in the primary form is a rare disease with only 99 cases described worldwide. New insights into the genetic basis and underlying pathophysiology, typical radiographic findings and differentiating characteristics, and a diagnostic algorithm that we developed will be presented. Study supported by: N/A T1736. Videotape Assessments of Psychogenic Movement Disorders Subjects Following Immediate Versus Delayed Treatment with Short Term Psychodynamic Psychotherapy: Randomized Parallel Trial Katie Kompoliti, Vanessa K. Hinson, Burgess Wilson and Glen T. Stebbins; Chicago, IL and Charleston, SC Objective: Videotape assessments in psychogenic movement disorder patients (PMDs) following psychodynamic psychotherapy and continuing neurological observation using a clinimetrically tested videotape-based PMD scale (Hinson 2005). Background: We conducted a 6 month parallel design trial with PMD patients assigned to three months of either active psychotherapy or neurological observation in randomized order. Movements, depression and anxiety improved in both arms. In this report we compare the PMD rating scale from entry to end of the study. Design: A blinded investigator assessed videotapes using the PMD scale. Data were analyzed using KolmogorovSmirnov Z test for pre-post treatment video ratings. Results: Fourteen women and one man, age 42.36 11, disease duration 63.26 73 months, were randomized to immediate (7) or delayed (8) treatment. There were no significant differences between the treatment groups for either visit 1 vs. visit 2 or visit 2 vs. visit 3 (minimum p Вј 0.28). Conclusion: In this group of PMD patients, movements, depression and anxiety improved, but there was no change in videotape assessments. Scale limitations in assessing longitudinal changes in paroxysmal PMDs may account for these results. Study supported by: Departmental funds T1739. Withdrawn. T1740. An Unsupported Exploratory Clinical Trial on Tremor Gian L. Lenzi, Laura Troilo and Francesca Puledda; Rome, Italy Background: Tremor affects 10% of the general population. The new Rome Tremor Scale (RTS), was tested against a scale reference, the CTRS, and utilized in an exploratory clinical trial. Materials and Methods: 40 outpatients with tremor completed both CTRS (92 items; 30-90 minutes) and RTS (six items, 3 minutes). 32 patients - 13 with Parkinson Disease (PD), 19 with Essential Tremor (ET) - were enrolled in an open-label unsupported clinical trial with rotigotine, a dopamine-agonist drug. Results: Correlation coefficient between CTRS and RTS shows r Вј 0.943 (full population), r Вј 0,971 in PD, and r Вј 0,907 in ET. During treatment, the patients showed a significant reduction of tremor both after six months (T1; RTS mean score: 0,9660,11; p< 0,0001), and after 12 months (T2; RTS 1,05Гѕ0,18; p< 0,0001) in respect to T0 (RTS: 2,09360,1). The significative reduction was also present in the two subgroups, PD and ET, or dividing all population according to age (younger and older) or into SPECT-CIT positive or negative. Conclusions: Rotigotine shows a long-lasting effect on tremor, both in PD or ET, regardless of age and/or basal ganglia dopaminergic status. Study supported by: Unsupported research T1737. Binding of the Alpha-Synuclein Radioligand SIL-23 Reflects the Level of Aggregated Alpha-Synuclein in ParkinsonвЂ™s Disease Brain tissue Paul T. Kotzbauer, Devika Bagchi, Maria Udan, Lihai Yu, Robert H. Mach and Zhude Tu; St. Louis, MO Accumulation of misfolded, fbrillar alpha-synuclein (alphasyn) in Lewy bodies and Lewy neurites is the pathological hallmark of ParkinsonвЂ™s Disease (PD). Radiolabeled ligands with high affinity for alpha-syn fibrils could be utilized as imaging tracers for PD. We identified a group of phenothiazine derivatives that bind alpha-syn fibrils and synthesized the 125I-labeled phenothiazine analogue Synuclein Imaging Ligand 23 (SIL-23) to further characterize its affinity for the pathological form of alpha-syn. Radioligand binding studies demonstrated that SIL-23 has moderately high binding affinity (Kd 140 nM) for fibrils prepared from recombinant alpha-syn, and that a similar binding site is also present in the insoluble fraction from PD postmortem brain tissue. The density of SIL-23 binding sites in PD brain tissue correlates with insoluble alpha-syn levels. These results define a radioligand binding site on alpha-syn fibrils that is specifically present in PD brain tissue and that can be feasibly targeted to quantify pathological alpha-syn accumulation in vivo. Further optimization of the binding affinity and selectivity of SIL-23 analogues could yield a radiotracer for pathological alpha-syn accumulation in PD. Study supported by: Washington University Institute of Clinical and Translational Sciences Michael J Fox Foundation T1741. 4-aminopyridine for Gait Dysfunction in ParkinsonвЂ™s Disease Corneliu C. Luca and Carlos Singer; Miami, FL Objective: To determine the effect of administration of 4aminopyridine (4-AP) in ParkinsonвЂ™s disease patients with gait impairment. 131 ID: guganp I Black Lining: [ON] I Time: 09:25 I Path: N:/3b2/ANA#/Vol00000/120255/APPFile/JW-ANA#120255 J_ID: ZAY Customer A_ID: BKLT2012_Abstracts Cadmus Art: ANA12 Date: 18-September-12 Background: ParkinsonвЂ™s disease (PD) related gait dysfunction is the result of multiple neurotransmitter deficits including dopaminergic, noradrenergic and cholinergic. 4AP, a drug used for gait dysfunction in multiple sclerosis, increases neurotransmitter release at multiple levels involved in gait control and therefore may have beneficial effects in PD. Methods: We are currently conducting a single center, randomized, crossover, placebo controlled trial to evaluate the safety and efficacy of 4-AP in ParkinsonвЂ™s disease. 20 patients with PD stage1-3 and gait dysfunction will receive 10 mg po BID of 4-AP or placebo for four weeks, followed by 2 weeks washout and then 4 weeks of crossover treatment. The primary outcome measure is the change in gait velocity and stride length measured by video 3D gait analysis system. Secondary outcomes will be changes in Timed up and Go Test, Timed 25 Foot Walk Test, Freezing of Gait Questionnaire, and UPDRS motor score. Safety and efficacy of medication will be monitored during the trial. Conclusions: AMPYRA is a medication that may have beneficial effect in PD related gait disorders. Study supported by: American Academy of Neurology Clinical Research Training Fellowship and National Parkinson Foundation (66745H) Stage: Page: 132 cits metabolically effect via diet restriction that reduced weight. GTE is known to control weight, improve deficits and exerting anxiolytic effects. We testified GTE that may control HAL elicited NAS and EPS. HAL was administered (1mg/kg) with water/GTE (1gm/ liter) drink. Behavioral and neurochemical analysis performed following six weeks of treatments. HAL decreases fluid, food intakes and growth rate were greater in GTE drinking animals where GTE shown to induce anxiogenic behavior and precipitated motor deficits. HAL induced locomotor activity was suppressed, innate aversive and fear like exploratory behaviors were greater in GTE than water drinking animals. HAL induced serotonergic metabolism was increased in the caudate and nucleus accumbens and decreased serotonin in rest of the brain in GTE drinking animals. HAL induced decreased dopamine turnover ratios were increased in the nucleus accumbens of GTE than water drinking animals. We provided first time the potential mechanisms involved in anorexiogenic effects of GTE and HAL induced NAS, EPS. Study supported by: The University of Karachi Student institution relationship. Researcher institution relationship as a research officer T1744. Innovative Web-Based Matching Service, Fox Trial Finder, as a Mechanism To Improve Clinical Trial Recruitment Claire C. Meunier, Sohini Chowdhury, Todd Sherer and Deborah W. Brooks; New York, NY T1742. Risk Factors for Cardiac Arrhythmia and Syncope through QTc Prolongation in ParkinsonвЂ™s Disease Naveed Malek, Katherine A. Grosset, David Stewart, Graeme J. Macphee and Donald G. Grosset; Glasgow, United Kingdom Two obstacles prevent timely recruitment into clinical research: 1) patient access to information about trials and 2) coordinator connections to networks of motivated volunteers. A 2003 NIH survey found 85% of trials finish late due to low patient accrual. A 2005 Harris Survey found 9% of ParkinsonвЂ™s patients participated in a trial. Fox Trial Finder (FTF) leverages improvements in Web technology to address this need by matching volunteers with recruiting clinical trials. PD-specific match algorithm identifies trials based on data provided by PD users, including current and past medication use, location, etc. A PD patient or healthy individual creates a profile to match to a relevant subset of all recruiting trials. Matching users are identified as potentially qualified candidates for coordinators assigned to trials. FTF enables trial volunteers and coordinators to connect through a secure messaging interface. User contact information is only revealed once a user authorizes release of this information. Over 3,000 volunteers are registered and 185 trials posted in US, UK, Canada, and Australia. FTF is helping speed trial recruitment by bridging the gap between motivated volunteers and promising clinical trials. Study supported by: The Michael J. Fox Foundation for ParkinsonвЂ™s Research Drugs that may prolong the cardiac QT interval, causing arrhythmia, syncope, or rarely sudden death, relevant in managing ParkinsonвЂ™s disease (PD) patients have been highlighted recently. We reviewed comorbidities and medications in a crosssection of PD patients, considering risk factors for prolonged QT described by the UK Medicines Regulatory Agency (eg. age over 60, concomitant use of more than one QT-prolonging drug, etc). In 360 PD patients, median age 66.5 years (interquartile range 58.5-74.8), 86 (23.9%) were taking two or more drugs with potential to prolong QT, including antidepressants in 20.0%, domperidone in 14.2%, bronchodilators in 8.9%, bladder medications in 4.2%, antibiotics in 3.1%, and antipsychotics in 2.5%. Prevalence of cofactors increasing risk was: age over 60 years 71.7%; diuretic use 22.2%; cardiac disease 19.2%; domperidone daily dose >30mg 17.6%. There was a history of arrhythmia in 9.7% and syncope in 5.8%. There was no evidence of increased prescription of domperidone in patients taking dopamine agonists (18/136, 13.2%) versus other antiparkinson therapy (37/ 224, 16.5%), p Вј 0.452 Fisher exact test. Exploration of therapy alternatives for PD patientsвЂ™ complex needs, to reduce risks from QT prolongation, is warranted. Study supported by: Self supported. T1745. LIVECHART: A System for Recording, Evaluating and Monitoring Botulinum Toxin Treatments for Any Condition Austen P. Moore; Liverpool, Merseyside, United Kingdom T1743. Effects of Green Tea Extract (GTE) on Haloperidol (HAL) Induced Neuroleptic Anxiety Syndrome (NAS) in Rat Model of Extrapyramidal Syndrome (EPS) Tafheem Malik and Darakhshan J. Haleem; Karachi, Sind, Pakistan Botulinum toxin (Bt) users require systems for recording the treatments given and their effects. In many settings around the world documentation is inadequate and clinically suboptimal. The LIVECHART (LIVErpool botulinum toxin CHART) is a fast, concise, simple, cheap system that can be used anywhere and does not require electronic recording. It systematically records the exact treatment given and patientreported effects of treatment, including adverse effects and HAL elicits NAS along EPS. HAL induces c-Fos expression distributed anxiety-related neural scheme, selected neuronal population of nucleus accumbens. HAL elicited mood defi- 132 ID: guganp I Black Lining: [ON] I Time: 09:25 I Path: N:/3b2/ANA#/Vol00000/120255/APPFile/JW-ANA#120255 J_ID: ZAY Customer A_ID: BKLT2012_Abstracts Cadmus Art: ANA12 Date: 18-September-12 therapeutic response expressed in a weekly visual analogue score (VAS) and Likert scales. Advantages include 1) enhances understanding and involvement by patients, and can be completed with or by carers if needed, 2) flexible goal setting, individualised monitoring and effects scoring for any condition, 3) minimises injection errors through pattern recognition, 4) facilitates decisions about the next treatment cycle and overall management strategy, 5) outcome measures accepted by many payment bureaux, 6) speeds up clinics, 7) outcomes can be used in controlled n-of-1 and other crossover trials, 8) provides clear information to other health professionals. Disadvantages include 1) occasional patients unable to use LIVECHART, 2) inter-patient VAS comparisons are inappropriate, 3) harder to interpret if completed by different carer each time. Study supported by: Ipsen UK I have received travel grants, research funding, honoraria for speaking and consultancy fees from Ipsen UK, Allergan, Merz and Eisai who all market botulinum toxins for clinical use. Stage: Page: 133 differences between ParkinsonвЂ™s Disease (PD) and control patients. Post-mortem brain samples from PD and controls cases (substantia nigra, putamen, globus pallidus -internal and external parts-), and blood samples from recently diagnosed and non-treated PD and controls cases were analyzed. Gene and protein expression studies of the CB2r were carried out by real time-PCR and western blot, respectively. Gene expression analyses showed that CB2r is significantly reduced in putamen (-40%) and globus pallidus internal (47%) and external (-31%) parts, but dramatically increased in the substantia nigra (388%). Protein expression analyses showed no differences in the Putamen but a significant diminishment of CB2r protein (-73 %) in the substantia nigra of PD patients. On the other hand, in lymphocytes from non-treated PD patients, CB2r gene expression is significantly down-regulated (-30%). The results obtained in this study revealed CB2r gene and protein expression differences between PD and controls patients, suggesting that CB2r could have an important role in the neurodegenerative process of PD. Study supported by: This work was supported by вЂ�вЂ�DISTEC professorship for the study of ParkinsonвЂ™s DiseaseвЂ™вЂ™ to Jorge Manzanares. Francisco Navarrete is a predoctoral fellow supported by MICINN (Spanish Science and Innovation Ministry). We thank вЂ�вЂ�FundacioВґn CIEN brain bankвЂ™вЂ™ (Madrid, Spain) and вЂ�вЂ�London Neurodegenerative Diseases brain bankвЂ™вЂ™ (London, UK) for post-mortem brain tissue supply. T1746. C9ORF72 Hexanucleotide Repeat Expansion Analysis in Patients with ParkinsonвЂ™s Disease Joanne D. Stockton, Catriona Moorby, Rachel V. Denyer, Caroline Rick, Keith Wheatley, Carl E. Clarke and Karen E. Morrison; Birmingham, United Kingdom Recent research demonstrates that expanded C9ORF72 hexanucleotide repeats occur frequently in both amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) (Renton, Neuron 2011; DeJesus-Hernandez, Neuron 2011), accounting for around 8% of sporadic ALS and 50% of familial ALS. 35% of those with C9ORF72 expansion-associated ALS-FTD or FTD have Parkinsonism on clinical examination, mostly of the akinetic-rigid type, and this appears to be an early clinical feature (Boeve, Brain 2012). No published studies to date have examined whether C9ORF72 expansion is present in ParkinsonвЂ™s disease. We have tested over 200 patients diagnosed with ParkinsonвЂ™s disease (PD) from the UK PDGEN cohort (http:// www.pdgen.bham.ac.uk/) for C9ORF72 repeat expansions, using a repeat primed PCR method and DNA extracted from peripheral blood lymphocytes. Results from 232 patients reveal no C9ORF72 hexanucleotide expansions (!24 repeats) in any individual with PD. We will undertake further analysis examining the relationship between repeat length in those patients with 23 repeats or fewer and phenotypic characteristics, such as the presence of dementia. Our data demonstrate that C9ORF72 hexanucleotide expansion is not associated with idiopathic ParkinsonвЂ™s disease. The relationship between repeat length and specific phenotypic features remains to be explored. Study supported by: University Hospital Birmingham Charities and Midlands Neuroscience Teaching and Research Fund. T1748. Randomized, Double-Blind, Double-Dummy Study of Levodopa-Carbidopa Intestinal Gel in Patients with Advanced ParkinsonвЂ™s Disease: Efficacy and Safety C.W. Olanow, A. Antonini, K. Kieburtz, H.H. Fernandez, A.J. Espay, D.G. Standaert, A. Vanagunas, K. L. Widnell, S. Freeman, W.Z. Robieson, Y. Pritchett, K. Chatamra, J. Benesh and R.A. Lenz; New York, NY; Padua, Italy; Rochester, NY; Cleveland, OH; Cincinnati, OH; Birmingham, AL; Chicago, IL and Abbott Park, IL Fluctuating blood levels of levodopa may contribute to motor complications in ParkinsonвЂ™s disease (PD). Levodopacarbidopa intestinal gel (LCIG) infusion provides more continuous delivery of levodopa than oral levodopa. A doubleblind, double-dummy trial compared the efficacy, safety, and tolerability of LCIG to oral levodopa-carbidopa immediate-release (IR) therapy in patients with advanced PD and motor fluctuations. Levodopa-responsive patients received LCIG infusionГѕplacebo capsules or encapsulated levodopacarbidopa IR tabletsГѕplacebo gel infusion for 12 weeks. The primary endpoint was change from baseline to Week 12 in вЂ�вЂ�Off вЂ™вЂ™ time normalized to 16 waking hours. вЂ�вЂ�OnвЂ™вЂ™ time without troublesome dyskinesia (TD) was a key secondary outcome. 71 patients were randomized (n Вј 37 LCIG; n Вј 34 IR), and 66 (93%) completed the trial. LCIG produced superior improvements in вЂ�вЂ�Off вЂ™вЂ™ time (LS mean difference Вј -1.91 hr; P Вј 0.0015) and вЂ�вЂ�OnвЂ™вЂ™ time without TD (LS mean difference Вј 1.86 hr, P Вј 0.0059) compared with IR. Change in вЂ�вЂ�OnвЂ™вЂ™ time with TD was not significant. Adverse events occurred in 35 (95%) and 34 (100%) patients receiving LCIG and IR, respectively; complication of device insertion (51%), abdominal pain (42%), procedural pain (32%) and nausea (25%) were most common. Study supported by: Abbott Katherine Widnell, Weining Robieson, Yili Pritchett, Krai Chatamra, Janet Benesh, and Robert Lenz are employees of Abbott. Stefanie Freeman was an employee of Abbott when T1747. Cannabinoid CB2 Receptor Gene and Protein Expression Differences in ParkinsonвЂ™s Disease PostMortem Brain Samples and Lymphocytes from Recently Diagnosed and Non-Treated Patients Francisco Navarrete, MarД±Вґa Salud GarcД±Вґa-GutieВґrrez, JoseВґ Antonio Molina, Carlos Leiva and Jorge Manzanares; San Juan de Alicante, Spain; Madrid, Spain and Alicante, Spain The aim of this study was to analyze central (brain) and peripheral (lymphocytes) CB2r gene and protein expression 133 ID: guganp I Black Lining: [ON] I Time: 09:25 I Path: N:/3b2/ANA#/Vol00000/120255/APPFile/JW-ANA#120255 J_ID: ZAY Customer A_ID: BKLT2012_Abstracts Cadmus Art: ANA12 Date: 18-September-12 the studies were conducted. C Warren Olanow, Angelo Antonini, and Karl Kieburtz have received compensation from Abbott for serving as consultants and participating in scientific advisory boards. Alberto J Espay, David G Standaert, and Arvydas Vanagunas were study investigators and have received compensation from Abbott for serving as consultants, lecturers, and/or participating in scientific advisory boards. Hubert H Fernandez was a study investigator and has served as a consultant for Abbott through a contract between Abbott and Cleveland Clinic Foundation; he has not received any personal compensation from Abbott. Stage: Page: 134 a botulinum toxin. The mean baseline JRS total score was 5.0. The CGI-Severity at baseline was 32.8% normal-tomild, 35.5% moderate, 22.4% marked and 9.3% severe. The SF-12v2 mean scores were 49.1-Mental and 43.1-Physical. At the onset of symptoms, 105 subjects were employed. Of those employed, 33 felt that their symptoms affected their productivity (estimated productivity was 82.8% (100% Вј normal and 0% Вј no productivity). A total of 17 subjects received or were seeking employee disability benefits related to symptoms. Conclusions/Relevance: A significant proportion of blepharospasm patients find that their disorder has negative consequences on their QoL and employment status. Study supported by: Merz Pharmaceuticals, LLC LeDoux, Jankovic, Fernandez: Consulting/Clinical Research fees Sethi, Verma, Pappert: Salary (employees of Merz) T1749. A Prospective, Observational Trial Evaluating Xeomin (incobotulinumtoxinA) for Cervical Dystonia (CD) or Blepharospasm in the United States вЂ“ Preliminary Baseline Results on the Health Impact of CD on Patients Using the Cervical Dystonia Impact Profile (CDIP) Joseph Jankovic, Madhavi Thomas, Alberto Vasquez, Kapil D. Sethi, Amit Verma, Eric J. Pappert and Hubert H. Fernandez; Houston, TX; St. Petersburg, FL; Greensboro, NC and Cleveland, OH T1751. A Prospective, Observational Trial Evaluating Xeomin [IncobotulinumtoxinA] for Cervical Dystonia (CD) or Blepharospasm in the United States вЂ“ Preliminary Baseline Results for Patients with CD Daniel D. Truong, Fabio O. Danisi, Kapil D. Sethi, Amit Verma, Eric J. Pappert and Hubert H. Fernandez; Fountain Valley, CA; Kingston, NY; Greensboro, NC and Cleveland, OH Background: XCiDaBLE is an ongoing observational study to evaluate patient-reported outcomes following incobotulinumtoxinA treatment. Methods: Subjects are followed for 2 treatment cycles. Subject-reported scales include the CDIP. There are 58 items in the CDIP grouped into 8 subscales. Each subscale score was transformed to have a common range of 0 (no impact) to 100 (most impact). Results: As of September 1, 2011, 130 CD patients were enrolled and CDIP data were available for 115 subjects (mean age 57.7 years, 84.4% female, 93.0% Caucasian). 82.6% were previously treated with a botulinum toxin. At baseline, the CDIP subscales scores: Head and Neck Symptoms: 60.5; Pain and Discomfort: 58.7; Upper Limb Activities: 41.0; Walking: 35.7; Sleep: 40.4; Annoyance: 44.3; Mood (7 items): 35.8; Psychosocial Functioning: 40.6. Total CDIP score at baseline was 43.1. Conclusions: CD has a clinically meaningful adverse impact on QoL. The total CDIP and its various subscales and domains is a useful tool to measure the health impact of CD. Study supported by: Merz Pharmaceuticals, LLC Jankovic, Thomas, Vasquez, Fernandez: Consulting/Clinical Research Fees Sethi, Verma, Pappert: Salary (employees of Merz) Background: XCiDaBLE is an ongoing open-label, prospective, observational study intended to evaluate patient-reported outcomes following incobotulinumtoxinA treatment. Methods: Subjects are followed for 2 treatments. Investigators rate the Clinical Global Impression (CGI)-Severity at baseline. Subjects rate the Cervical Dystonia Impact Profile (CDIP) [CD], Subject Global Impression-Severity and Improvement, SF-12v2, an employment questionnaire, and work history. Results: As of September 1, 2011, 130 CD subjects were enrolled (80.8% female; mean age 57.6 years; 92.3% Caucasian). 83.1% were previously treated with a botulinum toxin. CGI-Severity at baseline was: 20.2% normal-to-mild, 48.1% moderate, 20.9% marked, 9.3% severe and 1.6% extreme. The CDIP score at baseline is 43.1. The SF-12v2 mean scores for CD were 44.0-Mental QoL and 38.1-Physical QoL. At the onset of symptoms, 92 CD subjects were employed. Of the subjects employed, 31 felt that their symptoms affected productivity. 25 subjects received or were seeking employee disability benefits related to symptoms. Conclusions: CD can have a significant adverse impact on QoL and employment status. Study supported by: Merz Pharmaceuticals, LLC Truong, Danisi, Fernandez: Consulting/Clinical Research fees Verma, Pappert, Sethi: Salary (employees of Merz) T1750. A Prospective, Observational Trial Evaluating Xeomin [IncobotulinumtoxinA] for Cervical Dystonia or Blepharospasm in the US вЂ“ Preliminary Baseline Results for Patients with Blepharospasm Mark S. LeDoux, Joseph Jankovic, Kapil D. Sethi, Amit Verma, Eric J. Pappert and Hubert H. Fernandez; Memphis, TN; Houston, TX; Greensboro, NC and Cleveland, OH T1752. Rapid Generation of iPSCs from Lymphoblastoid Cell Lines Using an Episomal Plasmid Containing Multi-Reprogramming Factors in a Single Cassette Sharan Paul, Warunee Dansithong, Karla Figueroa and Stefan M. Pulst; Salt Lake City, UT Background: XCiDaBLE is an ongoing observational study intended to evaluate patient- reported outcomes following incobotulinumtoxinA treatment. Design/Methods: Subjects are followed for 2 treatment cycles. Investigators rate the Clinical Global Impression (CGI)-Severity at baseline. Subjects completed the Jankovic Rating Scale (JRS), an employment questionnaire, work history and the SF-12v2 at baseline. Results: As of September 1, 2011, 184 blepharospasm subjects were enrolled (mean age 64.9 years, 72.3% female, 91.8% Caucasian). 97.8% had been previously treated with Reprogramming of skin fibroblasts is increasingly used for modeling of human neurological diseases. In contrast to skin fibroblasts, blood lymphocytes and especially lymphoblastoid (LB) cells are difficult to reprogram and induced pluripotent stem cell (iPSC) colonies are usually formed after weeks and with very low efficiency. We have developed a novel technique that requires four days to generate iPSCs 134 ID: guganp I Black Lining: [ON] I Time: 09:25 I Path: N:/3b2/ANA#/Vol00000/120255/APPFile/JW-ANA#120255 J_ID: ZAY Customer A_ID: BKLT2012_Abstracts Cadmus Art: ANA12 Date: 18-September-12 from patient lymphoblasts (EBV-B) using an episomal plasmid containing multi-reprogramming factors (RFs) (cMYC, KLF4, SOX2, and OCT3/4) in a single cassette. The four RFs are expressed under individual control of a modified CMV promoter. Plasmids are introduced into LB cells by electroporation and plated on Geltrax coated plates. Within 1 day, cells tend to attach and start to form colonies. At day 3, lymphoblasts-derived iPSCs showed ES cell morphology and expressed pluripotent cell-specific genes. Furthermore, the iPSCs could be differentiated into cells of the germ layers in vitro. The ability to reprogram banked patient EBV-transformed cell lines efficiently will offer an unprecedented opportunity to rapidly generate genetic disease models and also provide a translational platform for therapeutic drug development. Study supported by: Grants RO1NS33123 and RC4NS073009 from the National Institutes of Neurological Disorders and Stroke to SMP. Stage: Page: 135 lated by writing a letter other than that which appeared on a screen, but not by simple letter copying [2]. The rTMS of the inferior frontal cortex, but not of the dorsolateral prefrontal cortex, increased the dual-task processing speed [3]. In a three-stimulus paradigm, the distractor stimulus evoked an early potential (latency 200 ms) not known from scalp recordings [4]. Conclusion: The modulation of cognitive functions is selective. The STN might modulate non-motor activities via contextual modulation of certain cortical areas. Our findings support the hypothesis of a cortico-STN bypass of the Basal Ganglia-Thalamocortical circuitry when processing cognitive functions. There is a spatial overlap of sites regulating various functions in the STN, motor as well non-motor. That might explain that a beneficial effect of STN DBS may be accompanied by cognitive impairment. 1. 2. 3. 4. T1753. Is Psychiatric Disease a Core Phenotype of Myoclonus Dystonia Syndrome Caused by SGCE Mutations? Kathryn J. Peall, Manju A. Kurian, Mark Wardle, Martin Smith, Hardev Pall, Jean-Pierre Lin, Tammy Hedderly, Alan Whone, Cathy White, Andrew Lux, Adrian J. Waite, Michael Samuel, Timothy Lynch, Patrick F. Chinnery, George Kirov, Mary King, Derek J. Blake, Huw R. Morris, Daniel J. Smith and Michael J. Owen; Cardiff, United Kingdom; London, United Kingdom; Birmingham, United Kingdom; Bristol, United Kingdom; Swansea, United Kingdom; Dublin, Ireland and Newcastle, United Kingdom BalaВґzЛ‡ M. Mov Disord 2008 Rektor I. Parkinsonism Relat Disord 2009 BalaВґz M. Exp Brain Res 2010 BockovaВґ M. J Neural Transm 2011 Study supported by: CEITEC T1755. The AddenbrookeвЂ™s Cognitive Examination in Parkinsonian Disorders at Baseline and 18 Months Timothy Rittman, Boyd C.P. Ghosh, Jonathan R. Evans, Peter McColgan, David P. Breen, Roger A. Barker and James B. Rowe; Cambridge, Cambridgeshire, United Kingdom Differentiating ParkinsonвЂ™s disease (PD) from atypical parkinsonian syndromes is challenging. We assessed whether the Revised AddenbrookeвЂ™s Cognitive Examination (ACE-R) could separate parkinsonian disorders and track disease progression. We administered ACE-R at baseline and 18 months in 21 PD, 30 Progressive Supranuclear Palsy (PSP) 21 Corticobasal Degeneration (CBD) subjects. In distinguishing PD from PSP, the verbal fluency subscore was sensitive (0.9) and specific (0.87), with ACE-R being sensitive (0.9) but not specific (0.46). Significant group level differences were found between PD and PSP for ACE-R and all subscores except language and memory; and between CBD and PD for ACE-R, MMSE, attention/concentration, visuospatial and fluency subscores. Significant decline between visits was seen in CBD subjects for ACE-R (p Вј 0.003), visuospatial subscore (p Вј 0.00001) and MMSE (p Вј 0.02), and more weakly in PSP subjects for ACE-R (p Вј 0.04) and visuospatial subscore (p Вј 0.02). This data suggest that the ACE-R score and verbal fluency are effective methods in differentiating PD from PSP, and a useful measure of disease progression in CBD. Study supported by: This work has been funded by: MRC Wellcome Trust Sackler studentship Background: Myoclonus Dystonia Syndrome (MDS) is a childhood onset, alcohol responsive movement disorder caused by mutations in the SGCE gene in a proportion of cases. Single family and case series have suggested co-morbid psychiatric disease but have not compared cases to a control group. Aims: To establish a cohort of MDS patients with SGCE mutations and a control group of alcohol-responsive tremor patients, and to systematically assess for psychiatric symptoms using standardised questionnaires. Methods: We collected 27 patients with SGCE mutations and 45 tremor control cases. The MINI International Neuropsychiatric Interview, PHQ-9, MADRS, YBOCS and AUDIT were used to assess psychiatric disease according to DSM-IV criteria. Results: There was a higher rate of psychiatric disease in MDS patients compared to controls (p<0.05), specifically social phobia (p<0.05) and Obsessive-Compulsive disease (OCD) (p<0.001). Excess alcohol use was higher amongst the MDS group once cases <18yrs were excluded. Conclusions: Overall psychiatric disease is elevated amongst the MDS cohort compared to a control group with a chronic, socially stigmatizing disorder. OCD appears to be the greatest contributor to this effect and may reflect a pleiotropic function for the SGCE gene. Study supported by: The IPSEN fund T1754. Role of the Subthalamic Nucleus in Modulating Cognitive Functions. A Viewpoint Based on Recordings from DBS Electrodes Ivan Rektor, Marek BalaВґz, Martina BockovaВґ and Irena Rektorova; Brno, Czech Republic T1756. Alpha-Synuclein Expression in the Epidermis and Epithelial Tissue in Parkinsonism Ildefonso Rodriguez-Leyva, Ana Laura Calderon-GarciduenЛњas, Ana Arely Renteria-Palomo, Rodrigo Valdez-Rodriguez, Julio Sepulveda and Juan Pablo Castanedo-Cazares; San Luis PotosД±Вґ, Mexico; Jalapa, VER, Mexico and Monterrey, NL, Mexico The STN is implicated in tasks with increased cognitive loads. A dual task, but not a simple oddball task, evoked local field P3-like potentials [1]. Oscillations were modu- The alpha-synuclein has an unknown function is a useful marker for Parkinsons disease. Although the presence of alpha-synuclein has been reported in the nerve endings of 135 ID: guganp I Black Lining: [ON] I Time: 09:25 I Path: N:/3b2/ANA#/Vol00000/120255/APPFile/JW-ANA#120255 J_ID: ZAY Customer A_ID: BKLT2012_Abstracts Cadmus Art: ANA12 Date: 18-September-12 Parkinson patients skin, recent studies have suggested that sebaceous glands might express some of its base peptides too. We are trying to prove that it might be possible to find it in other skin structures as well. A skin biopsy was taken from 21 patients with ParkinsonвЂ™s disease (PD), 9 patients with a clinical diagnosis of atypical parkinsonism (AP) and 10 control subjects (CS). A total of 80 biopsies were examined using immunohistochemestry, confocal and electronic microscopy with a polyclonal antibody for alpha-synuclein. We observed an important expression of alpha-synuclein in patients with PD, compared to patients with AP, whereas it was not found in the control group. The biggest expression was found in the pilosebaceous units followed by the spinous cell layer (SCL) and the eccrine glands (EG). The expression of alpha-synuclein was strongly positive in PD, moderate in AP and absent in the CS. This findings ask for further confirmations because they open a window in the study of neurodegenerative diseases. Study supported by: COPOCYT Stage: Page: 136 Background: PTD patients often report delay in receiving correct diagnoses. Subjects: 623 PTD patients newly diagnosed in 20032007 in Kaiser Permanente Northern California (KPNC), 6230 matched controls. Design/Methods: Case-control comparison of diagnoses made prior to PTD in electronic medical record; interview a subset to determine consequences of mistaken diagnosis; odds ratios adjusted for age, gender, and duration of membership. Results: Diagnoses made prior to the correct PTD diagnosis included acute stress (PTD 23%, controls 15%, OR 1.7, 95% CI 1.39, 2.08, p<0.0001), anxiety (PTD 31%, controls 19%, OR 1.95, 95% CI: 1.62, 2.34, p <0.0001), musculoskeletal strain (cervical dystonia 62%, controls 47%, OR 1.83, 95% CI 1.32,2.53, p<0.001), cervical disc disease (cervical dystonia 45%, controls 18%, OR 3.96, 95% CI 2.89, 5.42, p<0.0001), laryngitis (spasmodic dysphonia 4%, controls 0.2%, OR 18.2, 95% CI 4.26, 77.86, p < 0.0001). Median time from symptom onset to correct diagnosis was 2 years. 64% reported adverse effects of delayed diagnosis. Conclusion: Correct diagnosis of PTD is commonly delayed, with associated harmful effects. Education to minimize delayed diagnosis is needed. Study supported by: AHRQ RO1 HS018413; NIH 1RO1 NS046340; Dystonia Medical Research Foundation; James & Sharron Clark T1757. Paradigm for Neuroprotection in Presymptomatic HuntingtonвЂ™s Disease H. Diana Rosas, Gheorghe Doros, Sona Gevorkian, David H. Salat, Martin Reuter, Bruce Fischl, Keith Malarick, Wayne R. Matson, Clemens R. Scherzer, Robert J. Ferrante and Steven M. Hersch; Charlestown, MA; Boston, MA; Bedford, MA; Cambridge, MA and Pittsburgh, PA T1760. Analysis of Wave III of Brain Stem Auditory Evoked Potential during Microvascular Decompression of Cranial Nerve VII for Hemifacial Spasm Balaji Krishnaiah, Parthasarathy D. Thirumala, Miguel Habeych, Donald Crammond and Jeffrey Balzer; Pittsburgh, PA HuntingtonвЂ™s disease (HD) commences more than 20 years before clinical symptoms. A major therapeutic goal is to delay or prevent onset in those who are not yet symptomatic. We report the first therapeutic trial in presymptomatic individuals at risk for HD. We utilized high dose creatine monohydrate, a leading candidate disease modifying therapy for HD and a novel recruitment strategy that included premanifest individuals known to have the HD mutation as well as 50% at risk individuals who did not wish to know their genetic status. Subjects that did not have the HD mutation provided a control group for biological measures while removing the risk of coerced genetic testing. The trial consisted of a double-blind, placebo-controlled phase lasting 6 months and an unblinded open label phase in which all subjects were followed for an additional year. Clinical, neuroimaging, and blood markers of HD were assessed longitudinally. We show that it is feasible to conduct therapeutic trials in individuals at-risk for HD, that clinical and biological markers can measure progression in these subjects, and that high dose creatine, slowed brain atrophy, beneficially impacted additional markers, and may be disease modifying in premanifest HD. Study supported by: NINDS PO1NS058793, NS042861, NCCAM AT000613 Introduction: Intraoperative monitoring (IOM) of Brainstem Auditory evoked potential (BAEP) during microvascular decompression (MVD) prevents hearing loss (HLS) in patients with hemifacial spasm. Previous studies have shown changes in wave III (wIII) is an early sign of auditory nerve injury. Objective: To evaluate changes in amplitude and latency of wIII (AwIII, LwIII) of BAEP during MVD and its association with postoperative HLS. HLSwas classified by AAOHNS criteria, based on changes in pure tone audiometry and speechdiscrimination score. Methods: Pre and post operative audiograms and BAEPs in patients who underwent IOMduring MVD were analyzed. The results classified into patients who did and did not have HLS asgroup I and II respectively. Results: The AwIII was significantly decreased in the group with HLS (p< 0.015). The LwIII was not found to be significantly different group I and II. Regression analysis did not find any changes in the amplitude of wIII to increase the odds of HLS. Conclusion: Changes in wIII did not increase the odds of HLS in patients who underwent BAEPs during MVD. This information might be valuable to evaluate the value of wIII as alarm criteria during MVD to prevent HLS. Study supported by: None T1758. Withdrawn. T1759. Diagnostic Error in Primary Torsion Dystonia Caroline M. Tanner, Stephen K. Van Den Eeden, Samuel Goldman, Raymond Y. Lo, Connie Marras, Kathleen B. Albers, Amethyst D. Leimpeter, Robin Fross, Kathleen Comyns, Zhuqin Gu, Robin Smit, Annelie de Kleijn, Laurie Ozelius, Susan Bressman, Rachel Saunders-Pullman, Cynthia Comella, Lorene M. Nelson and Jeffrey Klingman; Sunnyvale, CA; Oakland, CA; Taiwan, Taiwan; Toronto, ON, Canada; BeiJing, China; Nijmegen, Netherlands; New York City, NY; Chicago, IL and Palo Alto, CA T1761. Establishing Baseline Values for Brainstem Auditory Evoked Potentials (BAEP) during Microvascular-Decompression for Hemifacial Spasm Santhosh Kumar Mohanraj, Parthasarathy D. Thirumala, Miguel Habeych, Donald Crammond and Jeffrey Balzer; Pittsburgh, PA Introduction: Changes in brainstem auditory evoked potential (BAEP) waveforms are used to alert the surgeon during Objective: To identify delay in the diagnosis of primary torsion dystonia (PTD). 136 ID: guganp I Black Lining: [ON] I Time: 09:25 I Path: N:/3b2/ANA#/Vol00000/120255/APPFile/JW-ANA#120255 J_ID: ZAY Customer A_ID: BKLT2012_Abstracts Cadmus Art: ANA12 Date: 18-September-12 Stage: Page: 137 recognition items. Data from 96 control (mean age Вј 59; mean education Вј 14.7) and 78 HD (mean age Вј 53; mean education Вј 14.4) participants were analyzed using Maximum Likelihood models. Significant differences in recall between control and HD participants existed in freerecall and multiple-choice-recognition (v2 Вј 105.562, v2 Вј 20.325, respectively, ps < .0001). Odds-ratios showed that controls performed better in free-recall, cued-recall, and multiple-choice-recognition conditions (OR Вј 3.374; OR Вј 1.067; OR Вј 2.158, respectively), but that HD nearly matched control participants in cued-recall. These results suggest that the MoCA is able to measure memory subtype differences. Furthermore, they provide insight into the progression of memory deterioration in HD, supporting research that suggests retrieval is initially most impaired, but that for those whose deficits are advanced, encoding difficulties also occur. Study supported by: This research was supported by the UCSD HuntingtonвЂ™s Disease Society of America Center of Excellence and UCSD Shiley-Marcos AlzheimerвЂ™s Disease Research Center NIH P50 AG 005131 microvascular-decompression (MVD) for Hemifacial spasm about impending hearing-loss. These changes are compared to the baseline values of BAEP set at the beginning of the procedure. Objective: Evaluate the appropriate time to set baseline values for BAEPs during MVD for hemifacial spasm and its implications on the alarm criteria. Methods: We retrospectively identified 63 patients who had intraoperative monitoring with BAEP during MVD and compared the latency(Lw-V) and amplitude(Aw-V) of wave-V at baseline (before beginning of the procedure) and at dura-opening (before major manipulation) to the changes in Lw-V and Aw-V of BAEPs when the surgeon was alerted. Results: Higher percentages of alerts were communicated to the surgeon when baseline values were set before the beginning of the procedure when compared to baseline values set before major manipulation. Conclusions: Baseline values should be set before major manipulation rather than the beginning of the case. This information will be valuable in reducing false alarms and unnecessary anxiety during surgery. Study supported by: None T1764. Inhibitory Neurons In the Ventral Medial Medulla Modulate Gait and Tone Veronique G. VanderHorst, Brian Ellison and Clifford B. Saper; Boston, MA T1762. Proteomic Analysis of Serum Microvesicles in ParkinsonвЂ™s Disease Paul R. Tomlinson, Samuel Evetts, Michele Hu, Chris Gradner, Benedikt Kessler, Kevin Talbot and George K. Tofaris; Oxford, United Kingdom Gait abnormalities are an important source of disability, but brainstem circuitries mediating gait remain unknown. We developed methods for genetic manipulation of inhibitory or excitatory neurons in specific brainstem sites, and for evaluating their role in gait. In this study, we characterize connections and functions of inhibitory neurons in the ventral medial medulla (VMM), an important relay between fore- and midbrain motor regions and the spinal cord. Pathways from inhibitory VMM neurons that express the vesicular GABA transporter (vgat) were studied by injecting a conditional, cre-dependent viral vector into the VMM of vgat-cre mice. The function of these neurons was studied using conditional, vgat-floxed knockout mice in which motor performance was assessed using video gait analysis, kinematics, complex motor tasks, and EMG. The results show that inhibitory VMM neurons project to spinal motoneurons, with a preference for selected pools. Deletion of vgat from the VMM results in a decrease in stance duration and stride length, accompanied by postural changes, but does not affect complex motor tasks. Increased EMG activity is present during rest, gait, and REM sleep, suggesting an important role of this system in the control of tone. Study supported by: Thomas Hartman Foundation Judy Goldberg Foundation Although the clinical diagnosis of ParkinsonвЂ™s disease (PD) can be made with accuracy, by the time patients present to the clinic the majority of dopaminergic neurons have degenerated. Biomarkers are needed to identify at risk patients before clinically significant neuronal death has occurred and monitor the disease progression. Membrane vesicles termed exosomes, are 40-100nm particles that are secreted by most cell types under normal and pathological conditions. We hypothesized that serum microvesicles include brain-derived membrane particles and as such may constitute a useful biomarker of degenerating neurons. Sera were collected from participants recruited into the Oxford PD longitudinal study for biomarker discovery. Our study groups consist of age-matched control subjects and carefully characterized patients within three years of the clinical diagnosis of PD. All recruited subjects were screened for glucocerebrocidase (GBA) and Leucine-Rich Repeat Kinase 2 (LRRK2) mutations. To isolate microvesicles, we developed a protocol based on serial centrifugations and confirmed the purity of our preparations using gel electrophoresis, electron microscopy and nanoparticle tracking analysis. We used label-free quantitative nanoflow liquid chromatography mass spectrometry, MSE to compare microvesicle-associated protein changes between healthy control subjects and patients with sporadic and genetic forms of PD. Study supported by: ParkinsonвЂ™s UK T1765. Genetic Association Studies (Single Nucleotide Polymorphisms) in South Indian ParkinsonвЂ™s Disease Patients and Controls Padmaja M. Vishwanathan, Devaprasad Markandeyan, Meenakshi Jayaraman, Srikumari C.R. Srisailapathy, Bhanu K. Murthy, Srinivasan A. Venkatesan and Ramesh Arabandi; Chennai, Tamilnadu, India and Chennai, Tamil Nadu, India T1763. Examining Memory Subtypes in HuntingtonвЂ™s Disease Using the Montreal Cognitive Assessment Charles P. Van Liew, Shea Gluhm, Daniel Brown, Jody L. Goldstein and Jody Corey-Bloom; San Diego, CA Objective: To determine the association status of Single nucleotide polymorphisms (SNPs) of genes, CYP1A1, CYP 2D6*4, CYP2D6*3, DRD2, NAT2, PARK2, NR4A2 and SNCA in South Indian ParkinsonвЂ™s disease (PD) patients and controls. Methodology: The study consisted of 140 affected patients (26 familial and 114 sporadics) recruited from Brief assessments of memory subtypes (e.g., retrieval, recognition) for HuntingtonвЂ™s disease (HD) are lacking. We sought to determine whether the Montreal Cognitive Assessment (MoCA) could be used to examine memory subtypes in HD. The MoCA has an optional component that assesses short-term, verbal memory using free-recall, cued-recall, and 137 ID: guganp I Black Lining: [ON] I Time: 09:25 I Path: N:/3b2/ANA#/Vol00000/120255/APPFile/JW-ANA#120255 J_ID: ZAY Customer A_ID: BKLT2012_Abstracts Cadmus Art: ANA12 Date: 18-September-12 Movement Disorder Clinic, Madras Medical College, Chennai. Age and ethnically matched 201 unaffected subjects were also recruited. SNPs were analyzed by PCR вЂ“RFLP method. The gene frequencies were calculated by gene counting method. Multiple logistic regression analysis and odds ratio was calculated. Results and Conclusion: 1) Analysis of DRD2, CYP2D6, CYP2D6*3 and NAT2 SNPs showed no significant association with PD in our population. Stage: Page: 138 positive, with titres up to 1:5120. Undiluted CSFs were positive in 14/15. The IgG1 antibodies bound to anterior horn cell neurons, and increased internalisation of HEK cell GlyRs. Some patients had a monophasic disease, but many slowly progressed or relapsed. Excessive startle, painful spasms (often touch-sensitive), stiffness, and rigidity were found in 90%. Brainstem disturbance leading to oculomotor abnormalities, dysphagia, dysarthria or trismus were also common (60%). Autonomic or cognitive involvement, seizures or sleep disturbance were less frequent (up to 30%). MRI and CSF findings were often uninformative but two had thymomas and one had a lymphoma. All patients received symptomatic treatments and most improved substantially with steroids and plasma exchange or IvIg, but relapses have occurred, and delayed diagnosis may have been responsible for three deaths. The clinical spectrum of this immunotherapy-responsive condition is wide and not all the patients can be defined as PERM. Study supported by: The Oxford NIHR Biomedical Research Centre; the NIHR National Commissioning Service for Neuromyelitis Optica; Euroimmun AG We receive small grants from Euroimmun AG, and PW and MW are supported by the NIHR National Commisioning Service. 2) CYP1A1 - T6235C locus was a significant predisposing factor in late onset sporadic PD patients and it was not significant predisposing factor for familial and early onset (age 45) cases. 3) SNCA C-116C!G locus predisposes to the early onset sporadic PD, while NR4A2 G12803T predisposes to sporadic PD. 4) PARK2 : While the SNP G601A had no significant association with PD, the intronic polymorphism T25C (IVS2) was significantly associated to PD (40%) compared to the control group (11%). Study supported by: 1 UGC-SAP-PROGRAMME OF GENETICS DEPARTMENT 2.UICIC (UNIVERSITY INDUSTRYCOMMUNITY INTERACTION CENTRE)PROGRAMME FROM UNIVERSITY OF MADRAS T1768. Short Latency Cortical Activation during Clinically Effective Ventral Intermediate Nucleus Deep Brain Stimulation for Essential Tremor Harrison C. Walker, He Huang, Christopher L. Gonzalez, James E. Bryant, Jeffrey Killen, Robert C. Knowlton, Erwin B. Montgomery, Gary C. Cutter, Abidin Yildirim, Barton L. Guthrie and Ray L. Watts; Birmingham, AL T1766. REM Sleep without Atonia and Freezing of Gait in ParkinsonвЂ™s Disease Aleksandar Videnovic, Clare C. Marlin, Joni Planetta, Laila Alibiglou, David E. Villancourt and Colum D. MacKinnon; Chicago, IL and Gainesville, FL Background: Idiopathic RBD (iRBD) frequently precedes motor features of PD, including freezing of gait (FOG). Despite the common neuroanatomical networks involved in the pathophysiology of iRBD and FOG in PD, associations between iRBD and FOG remain poorly understood. Methods: Twenty age- and sex-matched participants (iRBD n Вј 5, PD without FOG n Вј 5, PD with FOG n Вј 5, controls n Вј 5) underwent polysomnography. The amount of excessive phasic and tonic muscle activity during REM sleep was quantified using the method by Cygan and colleagues (Cygan, J Clin Sleep Med, 2010). Freezing of gait was assessed by the FOG Questionnaire. Results: There was a significant group effect for tonic (p Вј .001) and phasic (p Вј .008) muscle activity during REM sleep. Tonic and phasic muscle activity was significantly increased relative to control subjects in both the iRBD and PD with FOG groups. There were no significant differences in REM-related muscle activity between the iRBD and PD with FOG groups. A trend toward statistical significance was observed for increased tonic EMG activity in PD with FOG versus PD without FOG (p Вј .072). Conclusions: PD with co-existent FOG may be associated with increased tonic muscle activation during REM sleep. Study supported by: Michael J Fox Foundation for Parkinson Reserach Deep brain stimulation (DBS) relieves symptoms of neuropsychiatric diseases when medical treatments fail, yet its therapeutic mechanism is unknown. We hypothesized that ventral intermediate nucleus (VIM) DBS for essential tremor activates cortex at short latencies and that this potential is related to suppression of tremor. Electroencephalography measured cortical activity in 5 subjects (7 brain hemispheres) across a range of DBS settings. Reversal of the anode and cathode contacts minimized stimulus artifact, allowing visualization of brain activity. Regression quantified the relationship between the event related potentials (ERPs) and tremor. DBS generated a polyphasic ERP in ipsilateral sensorimotor cortex with peaks at latencies beginning less than one millisecond after the stimulus (mean latencies 0.960.2, 5.660.7, and 13.961.4 milliseconds, denoted R1, R2, and R3, respectively). R1 amplitude and frequency were both closely associated with tremor suppression (p<0.0001, respectively). We demonstrate short latency cortical activation by symptomatically effective VIM DBS, which suggests that DBS may improve essential tremor by synchronizing the precise timing of discharges in nearby axons to the stimulation frequency or one of its subharmonics. Study supported by: United States National Institutes of Health / National Institutes of Neurological Disorders and Stroke (K23 NS067053-01) T1767. Clinical and Immunological Features with Glycine Receptor Antibodies Angela Vincent, M. Isabel Leite, Alexander Carvajal, Patrick Waters and Mark Woodhall; Oxford, United Kingdom T1769. Can Proton and Phosphorus MR Spectroscopy Be Used for Early Diagnosis in ParkinsonвЂ™s Disease? Nora Weiduschat, M. Flint Beal, Xiangling Mao, Melissa J. Nirenberg, Dikoma C. Shungu and Claire Henchcliffe; New York, NY Progressive encephalomyelitis with rigidity and myoclonus (PERM) has been described with GlyR antibodies. We studied patients referred for testing whose IgG antibodies bound to GlyR alpha1 expressed in human embryonic kidney (HEK) cells. 42 sera (60% males; 2-77y, median 51y) were Background: If mitochondrial dysfunction is an early event contributing to Parkinson disease (PD) development, then non-invasive quantitation of energy metabolism indices 138 ID: guganp I Black Lining: [ON] I Time: 09:25 I Path: N:/3b2/ANA#/Vol00000/120255/APPFile/JW-ANA#120255 J_ID: ZAY Customer A_ID: BKLT2012_Abstracts Cadmus Art: ANA12 Date: 18-September-12 would be a useful tool for early diagnosis and treatment monitoring. The present study aimed at assessing indices of brain energy metabolism at rest in subjects with early ParkinsonвЂ™s disease (PD) using proton and phosphorus magnetic resonance spectroscopy. Methods: During this cross-sectional study including 20 subjects with early PD (Hoehn and Yahr stage 1-2) and 15 age-matched healthy volunteers (HV), ventricular lactate, and regional levels of N-acetylaspartate, phosphocreatine, free phosphate and ATP were determined. Results: Metabolite levels were not significantly different between PD and HV nor between unmedicated PD subjects and those receiving levodopa. In the PD group, there were no significant correlations between MRS markers and age, disease duration, or UPDRS motor scores. Conclusion: In early PD and under resting conditions, proton and phosphorus MRS do not appear to reliably detect metabolic abnormalities. MRS under dynamic conditions might uncover latent energy deficits in early PD, which needs to be investigated in future studies. Study supported by: Dana Foundation Stage: Page: 139 Methods: Sixteen PPAOS subjects were age and gendermatched to 16 PSP subjects and 20 controls. All subjects were prospectively recruited, underwent detailed neurological and speech evaluations, and 3T head MRI including diffusion tensor imaging. Atrophy and white matter tract degeneration were assessed. Results: The PSP subjects had typical occulomotor/gait impairments but not speech apraxia. Both syndromes showed grey matter loss in supplementary motor area, white matter loss in posterior frontal lobes and degeneration of corpus callosum. In PPAOS, lateral grey matter loss was focal involving superior premotor cortex, while volume loss extended into the prefrontal cortex in PSP. Caudate nucleus volume loss and superior cerebellar peduncle degeneration was observed in PSP. Interestingly, midbrain area was decreased in both syndromes compared to controls, although this was greater in PSP. Conclusions: Although neuroanatomical differences were identified between these distinctive clinical syndromes, there was overlap, such as midbrain atrophy, suggesting that these two syndromes may have common pathogenetic underpinnings. Study supported by: NIH grant R01-DC010367 and the Dana Foundation T1770. Structural Abnormalities in the Brain Associated with Rapid Onset Dystonia-Parkinsonism: A Preliminary Investigation Christopher T. Whitlow, Allison Brashear, Bernardino Ghetti, Matthew C. Hagen, Kathleen J. Sweadner and Joseph A. Maldjian; Winston-Salem, NC; Indianapolis, IN; Cincinnati, OH and Boston, MA T1772. Subacute Combine Degeneration of the Cord Due to Functional B12 Deficiency Subhashie Wijemanne, Sui Li and Michal Vytopil; Boston, MA Introduction: Subacute combine degeneration of the cord(SCDC) is a well known clinical entity due to Vitamin B12 deficiency. The diagnosis is made in the appropriate clinical setting with a low or low normal B12 level, confirmed by high serum Methylmalonic acid and homocystein. We present a case of functional B12 deficiency with supra normal B12 level. Case report: 64 year old male with ParkinsonвЂ™s disease presented with progressive gait disorder of several months duration. He had slow cognitive processing, loss of joint position and vibration sense in both lower and upper extremity with sensory ataxia. Results: CBC: WBC 1.41, Hg 8.5 HCT 25.1 platelet 63, MCV 104, Blood smear macrocystic anemia with hypersegmented neutrophils. Vitamin B12 levels since 2008 >1200, never on supplements. Methylmalonic acid 23.53 (0-0.4), Intrinsic factor antibody positive.MRI spine showed T2 hyperintensity in the dorsal column without any evidence of myelopathy. Conclusion: Functional B12 deficiency is a rare cause of SCDC. It can present with a supra normal B12 level. If the clinical picture is suggestive, should proceed with Methylmalonic acid and Homocystein levels even if the B12 level is supra normal. Transcobolamine II deficiency is a potential etiology. Study supported by: None Rapid-onset dystonia-parkinsonism (RDP) is a rare inherited form of dystonia characterized by bradykinesia, postural instability and dystonic movements. In this preliminary investigation, we hypothesize that RDP may affect components of the cortico-striato-pallidothalamocortical (CSPTC) and cerebello-thalamo-cortical (CbTC) pathways, thought to be involved in other movement disorders. Standard voxel based morphometry and diffusion tensor imaging MRI methods were used to obtain voxel-wise measures of gray matter (GM) volume, as well as GM and white matter (WM) fractional anisotropy (FA) from 3 patients with RDP and 18 age-matched controls. Statistical Parametric Mapping analyses demonstrated GM volume decreases in RDP patients compared to controls in the right dentate nucleus, with decreased FA in the right superior cerebellar peduncle, known to subserve the dentate nucleus and send cerebellar feedback via efferent fibers to the motor cortex. RDP patients demonstrated additional FA decreases compared to controls in corpus callosum, as well as in bilateral striatum, extra-nuclear WM tracts, dentate nuclei and middle cerebellar peduncles. These data demonstrate RDP-associated abnormalities in GM and WM, including components of the CSPTC and CbTC, suggesting a heterogeneous distributed pattern of central nervous system disease. Study supported by: R01NS058949 T1773. MRI Signal Intensity in Dystonic Muscle Kathleen V. Woschkolup, Gonzalo J. Revuelta and Kenneth Spicer; Charleston, SC T1771. MRI Comparison of Primary Progressive Apraxia of Speech and PSP Jennifer L. Whitwell, Joseph R. Duffy, Edythe A. Strand, Mary M. Machulda, Matthew L. Senjem, Jeffrey L. Gunter, Kejal Kantarci, Scott D. Eggers, Clifford R. Jack and Keith A. Josephs; Rochester, MN Background: The term Dystonia encompasses a heterogeneous group of disorders that share one common feature: sustained muscular contraction. Currently there is a great need for a tool that can objectively measure dystonia severity. Objective:This is a pilot study to establish utility of muscle-MR in the assessment of dystonia. Methods: Records of 11 CD patients, with Sternocleidomastoid (SCM) involvement were reviewed. Population age Background: Primary progressive apraxia of speech (PPAOS) and progressive supranuclear palsy (PSP) are both motor disorders with similar patterns of cortical atrophy. We compared, for the first time, neuroanatomical features between these two syndromes. 139 ID: guganp I Black Lining: [ON] I Time: 09:25 I Path: N:/3b2/ANA#/Vol00000/120255/APPFile/JW-ANA#120255 J_ID: ZAY Customer A_ID: BKLT2012_Abstracts Cadmus Art: ANA12 Date: 18-September-12 mean: 48.9; SD: 22.2; 8 Female. MRI C-spine obtained prior to treatment for Dystonia and while symptomatic,were reviewed.Excluding patients with unclear diagnosis or history. Sternocleidomastoid muscles(SCM) in each patient were viewed in axial T2 sequences. Signal intensity determined by gray scale per SCM at three different but consistent slices for each patient.Volumes adjusted for consistency.Values in both groups were compared using two-tailed paired TTest. Results: The effect size, Cohensd, corrected for a paired sample design does fall within the small effect range and should not be dismissed as insignificant. Conclusion: Our preliminary findings suggest muscleMR may be a useful tool in the study of dystonia. Further prospective studies using this technique are warranted. Study supported by: None Stage: Page: 140 mice injected with AAV-14-3-3H-GFP showed a 37% increase in dopamine neuron counts compared to MPTPtreated AAV-GFP mice (p<0.05). Conversely, we tested the effect of 14-3-3 inhibition on MPTP toxicity by injecting transgenic mice expressing the 14-3-3 peptide inhibitor difopein with saline or MPTP. Difopein mice had a 15% increase in dopamine cell loss compared to wildtype upon MPTP treatment. Our studies suggest that 14-3-3s may be a target for PD therapeutics. Study supported by: NINDS; Parkinson Association of Alabama; CCTS/COCD Translational Research Intramural Grant Program T1776. Short Latency Afferent Inhibition: A Biomarker for Mild Cognitive Impairment in ParkinsonвЂ™s Disease? Alison J. Yarnall, Lynn Rochester, Rachel David, Tien K. Khoo, Gordon W. Duncan, Brook Galna, Mark R. Baker and David J. Burn; Newcastle, United Kingdom T1774. Evaluation of Smelling Function, F-DOPA PET Study and Transcranial Sonography of Substantia Nigra in Asymptomatic Carriers of Common LRRK2 Risk Variants: A Longitudinal Case-Control Study Ruey-Meei Wu, Chin-Yi Yu, Kai-Yuan Tzen and Meng-Ling Chen; Taipei, Taiwan Background: Mild cognitive impairment in ParkinsonвЂ™s disease (PD-MCI) is common and predicts those at risk of dementia. Cholinergic dysfunction, which can be assessed using short latency afferent inhibition (SAI), may contribute to the pathophysiology of PD-MCI. Methods: 22 PD (11 cognitively normal (PD-CN); 11 PD-MCI) patients and 22 age-matched controls participated. MCI was determined as <26 on the Montreal Cognitive Assessment. SAI was measured by conditioning motor evoked potentials, elicited by transcranial magnetic stimulation (TMS) of motor cortex, with electrical stimuli delivered to the contralateral median nerve at intervals ranging from N20 (predetermined) to N20Гѕ4ms. A generalised linear model (GLM) was used to compare SAI (% difference between test and conditioned response expressed as grand mean) between-groups after controlling for age. Results: There was no significant difference between the PD-CN and controls for SAI (62.8 6 30.3% versus 55.7 6 21.7%, p Вј 0.447). The PD-MCI group showed significantly less inhibition (88.4 6 25.8%) than both PD-CN (p Вј 0.021) and controls (p Вј 0.01). These differences remained after controlling for age. Conclusions: Cholinergic dysfunction occurs early in PD-MCI. SAI may be a useful biomarker of increased risk of dementia in PD patients. Study supported by: M J Fox Foundation Objectives: the aim of this study was to determine the value of smelling test, 18F-dopa PET and sonography of substantia nigra (SN) as the tools of premotor diagnosis of ParkinsonвЂ™s disease in asymptomatic carriers of LRRK2 G2385R in a Taiwanese cohort. Methods: Fifteen asymptomatic G2385R carriers and fifteen controls were included. University of Pennsylvania Smell Identification Test, 18F-dopa PET and TCD of SN were performed on enrollment and after 2-years follow-up. Results: There were no difference of striatal uptake of 18F-dopa in PET or olfactory function between groups neither on enrollment nor after 2 yrs follow up. Logistic regression analysis revealed G2385R carrier status were significantly associated with the manifestation of hyperechogenicity of SN, while the protective haplotype N551KR1298H-K1423K was negatively associated with the echofeature. One of the G2385R carriers who had SN hyperechogenicy developed parkinsonism and decreased striatal 18F-dopa uptake was noted in the PET study. Interpretation: Our study suggested hyperechogenicity of SN might be a valuable tool for premotor diagnosis for asymptomatic carriers of LRRK2 risk variants. Study supported by: National Science council of Taiwan T1777. Normal Striatal D1 Dopamine Receptor Binding in Primary Focal Dystonias Morvarid Karimi, Joanne Markham, Hubert Flores, Stephen Moerlein, Tom Videen and Joel S. Perlmutter; St. Louis, MO T1775. Modulation of 14-3-3 Proteins in the MPTP ParkinsonвЂ™s Disease Model Huiping Ding, Sunny Slone and Talene Yacoubian; Birmingham, AL Dystonia is characterized by repetitive patterned or sustained muscle contractions causing abnormal postures. Several lines of evidence implicate abnormalities of dopaminergic pathways. We have recently demonstrated that the abnormal striatal spiperone (nonspecific D2/D3 ligand) binding in focal dystonia is not due to a D2-receptor abnormality since the highly D2-specific NMB binding was not altered. This suggests that an abnormality in D3-receptor may be associated with focal dystonia. Interestingly, accumulating evidence indicates a synergistic interaction between D1 and D3-receptors. Thus, this study will investigate the role of D1 receptors that primarily mediate the direct pathway in the basal ganglia prior to validating a D3-specific ligand for human use. We compared striatal binding potential of NNC112 ([11C](Гѕ)-8-chloro-5-(7-benzofuranyl)-7-hydroxy-3-methyl- Disruption of 14-3-3 expression and function has been implicated in ParkinsonвЂ™s disease (PD). 14-3-3s are regulators of cell survival, and we have shown that 14-3-3 overexpression protects in cellular and invertebrate PD models. Validation of 14-3-3s in mammalian models is the next step in translating these studies into potential therapy development. We tested the consequences of 14-3-3 modulation in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model. We tested the effect of 14-3-3H overexpression using an adeno-associated virus (AAV). Mice were stereotactically injected with AAV-green fluorescent protein (GFP) or AAV14-3-3H-GFP into the substantia nigra, and four weeks later were treated with saline or 30 mg/kg MPTP intraperitoneally for five days. 21 days later, brains were collected for dopamine neuronal counts by stereology. MPTP-treated 140 ID: guganp I Black Lining: [ON] I Time: 09:25 I Path: N:/3b2/ANA#/Vol00000/120255/APPFile/JW-ANA#120255 J_ID: ZAY Customer A_ID: BKLT2012_Abstracts Cadmus Art: ANA12 Date: 18-September-12 Stage: Page: 141 2,3,4,5-tetrahydro-1H-3-benzazepine, a D1-radioligand) in primary cranial, cervical or arm dystonia to age, gender and smoking status matched healthy controls. Data from 7 healthy and 7 dystonic subjects (age: 58.4Гѕ/- 10) did not reveal any significant difference in striatal BPND between the two groups. This study had 86% power to detect 16% difference between two groups (CI: 0.08-0.44). We aim to enroll 20 subjects in each group as originally planned to improve the statistical power. Study supported by: 1K23NS069746-01A1 compared to controls within pilomotor nerves at all sites (0.7660.19 vs. 0.2660.13, P<0.001) and within sudomotor nerves at all sites (0.2060.11 vs. 0.0260.01, P<0.005). Discussion: Patients with PD have a distal sensory and autonomic neuropathy and elevated levels of a-synuclein in both sympathetic adrenergic pilomotor and sympathetic cholinergic sudomotor fibers. These findings suggest the asynuclein ratio may be a potential biomarker in patients with PD. Study supported by: NIH NINDS K23NS050209 (CHG) and the RJG Foundation (CHG) T1778. Dopaminergic Modulation of Basal Ganglia Connectivity in ParkinsonвЂ™s Disease Kathleen L. Poston, William Shire, Richard Joseph, Vinod Menon and Michael Greicius; Stanford, CA T1780. Circadian Rhythm of Melatonin Secretion Is Altered in ParkinsonвЂ™s Disease Aleksandar Videnovic, Angelica Marconi, Charleston Noble, Katherine Reid, Teresa Kuhta, Tanya Simuni, Cindy Zadikoff and Phyllis Zee; Chicago, IL Objective: To identify changes in basal ganglia and cortical connectivity in ParkinsonвЂ™s disease (PD) ON and OFF medication using resting state fMRI. Design/Methods: We acquired resting state fMRI data on 30 participants: 15 early PD (MDS-UPDRS-III 26.9Гѕ/9.8) and 15 age-matched controls (HC). PD patients were scanned both OFF and ON medications (PD-OFF and PD-ON). We performed a region-of-interest (ROI) based functional connectivity analysis, selecting regions in the caudate (CAU), and putamen (PUT). We conducted twosample t-tests and paired-sample t-tests for each ROI to identify significant connectivity differences in PD-OFF versus controls and PD-OFF versus PD-ON, respectively. Results: For the CAU ROI, PD-OFF had decreased connectivity in the contralateral caudate compared to HC; PD-ON had increased connectivity within the contralateral caudate and ipsilateral putamen compared to PD-OFF. For the PUT ROI, PD-OFF had decreased connectivity with the bilateral motor cortex compared to HC; PD-ON had increased connectivity with the ipsilateral putamen and bilateral motor cortex compared to PD-OFF. Conclusions: PD-OFF showed reduced connectivity within regions associated with motor function with strengthened connectivity when patients were ON medication. These findings suggest cortical-subcortical connectivity could serve as objective biomarkers of PD motor function. Study supported by: K23 NS075097 (KP), R01 MH084164 (VM), R01 NS073498 (MG), Michael J. Fox Foundation for ParkinsonвЂ™s disease Research (KP) Objective: To examine circadian melatonin secretion in PD. Background: Clinical studies in PD report diurnal fluctuations of motor and non-motor symptoms, suggesting modifications of circadian system in PD. Design/Methods: Rest-activity cycles of PD participants and age/gender matched controls were assessed by actigraphy and sleep diaries over 14 days. This was followed by blood sampling at 30-minute intervals for 24 hours, under constant routine conditions. Serum melatonin levels were measured by immunoassay. The area-under-the-curve (AUC) and circadian phase were calculated. Group differences were assessed using independent group t test. Results: 20 PD participants (9M/11F), age 6568.2 years, and 12 controls (1M/11F), age 6366.3 years participated in this study. 24-hour AUC of melatonin secretion was significantly diminished in PD participants compared to controls (p Вј 0.01). Both daytime and nighttime AUC were significantly diminished in the PD group (p Вј 0.03; p Вј 0.01). Melatonin midpoint was significantly delayed in PD participants (circadian time 19.4) relative to the control group (circadian time 16.6) (p Вј 0.02). Conclusions/Relevance: Circadian melatonin secretion is reduced, and phase of the melatonin rhythm delayed in PD. These results suggest that approaches aimed to improve circadian function have potential as complementary therapies for PD. Study supported by: NIH/NINDS; American Academy of Neurology Foundation; ParkinsonвЂ™s Disease Foundation T1779. Alpha Synuclein as a Cutaneous Biomarker of Parkinson Disease Christopher H. Gibbons, Ningshan Wang and Roy Freeman; Boston, MA Autoimmune Neurology T1801. A Case of Bilateral Horizontal Gaze Ophthalmoplegia: The 1Гѕ1 Syndrome Nadeem Akhtar and Sumeet Singhal; Nottingham, United Kingdom Background: ParkinsonвЂ™s disease (PD) is a multisystem neurodegenerative disease characterized by the deposition of a-synuclein in the central, peripheral and enteric nervous system. Objective: To develop a biomarker for ParkinsonвЂ™s disease. Methods: Eighteen patients with PD and 10 matched controls underwent skin biopsies at the distal leg, distal thigh and proximal thigh. Skin biopsies were stained for PGP9.5, tyrosine hydroxylase, vasoactive intestinal peptide and a-synuclein. The density of nerve fiber subtypes within specific dermal organelles (pilomotor muscles and sweat glands) and the ratio of a-synuclein deposition within nerve fibers was calculated. Results: Patients with PD had a distal neuropathy expressed by loss of intra-epidermal, pilomotor and sudomotor fibers (P<0.05). Patients with PD had higher a-synuclein ratios We describe an unusual case of complete horizontal gaze paralysis presenting as a relapse of Multiple Sclerosis. A-young woman, a known case of relapsing and remitting MS presented with sudden onset of binocular diplopia. On examination there was a complete horizontal gaze paralysis. Vertical eye movements were normal. Oculocephalic reflex failed to improve horizontal eye movement. No nystagmus and no other sign of brainstem dysfunction were observed. Visual acuity was normal in both eyes. Brain MRI scans showed white matter T2-hypersignal abnormalities. A plaque of demyelination was noted in the posterior part of the medial pontine tegmentum. Complete bilateral horizontal gaze paralysis has been exceptionally reported. To our knowledge, only 141 ID: guganp I Black Lining: [ON] I Time: 09:25 I Path: N:/3b2/ANA#/Vol00000/120255/APPFile/JW-ANA#120255 J_ID: ZAY Customer A_ID: BKLT2012_Abstracts Cadmus Art: ANA12 Date: 18-September-12 two cases of complete horizontal bilateral ophthalmoplegia in multiple sclerosis have been reported in the literature. Study supported by: No one Stage: Page: 142 and psychiatric symptoms that often progresses to include dyskinesia, decreased level of consciousness, and autonomic instability. The condition was classically described in women with ovarian teratomas, however has more recently been recognized to have a wider range of presentations. We report the case of a 38 year old woman without past medical history who presented with auditory hallucinations, headache and what was described as a non-epileptic seizure. She was felt to have had an initial psychotic break and was referred for inpatient psychiatric admission. Brain MRI and EEG were normal, but CSF was notable for mild pleocytosis. Abdominal imaging later revealed an ovarian teratoma. After removal of the mass and treatment with steroids and IVIg, she demonstrated a complete resolution of symptoms. AntiNMDA receptor antibodies were later found in the patientвЂ™s CSF. As this case demonstrates, it is important to consider paraneoplastic encephalitis - even with normal MRI and EEG - as a cause of initial psychiatric symptoms in patient populations not typical for initial psychotic break as the condition is reversible if recognized early. Study supported by: Residency program T1802. Chronic Microglial Encephalomyelitis (CME) Allen J. Aksamit, Brian G. Weinshenker and Joseph E. Parisi; Rochester, MN Six patients presented with a unique corticosteroid responsive disabling subacute encephalomyelitis evolving to chronic cognitive and behavioral dysfunction, tremor, myoclonus, and optic nerve swelling. Five patients also had myelopathy with longitudinally extensive T2 hyper-intensity on MRI of the spinal cord. MRI head was characteristic with periventricular diffuse T2 white matter abnormalities with a prominent pattern of radially oriented, linear perivascular increased signal, that enhanced after gadolinium. All had spinal fluid pleocytosis. All had a poorly defined systemic autoimmune illnesses. Brain biopsy in each case revealed prominent perivascular microglial activation and lymphocytic cuffing without demyelination or other specific features. The initial outcome after high dose corticosteroid therapy was favorable. Chronic immunosuppressive therapy was required to prevent relapse. We propose to call this syndrome chronic microglial encephalomyelitis (CME). Whether this condition represents a single disease entity or a common syndrome of many causes is unknown. However, it can be recognized and differentiated from CNS sarcoidosis, lymphoma, vasculitis, and multiple sclerosis. It can be treated effectively, but requires long term immunomodulatory therapy to prevent relapse. Study supported by: NONE T1805. Patients Can Adequately Report Their MS Severity Online; Implications for Online Research Platforms Riley Bove, Timothy Vaughan, Brian C. Healy, Elizabeth Secor, Alexander Musallam, Bonnie Glanz, Howard Weiner, Paul Wicks, Tanuja Chitnis and Philip L. De Jager; Boston, MA and Cambridge Online research platforms such as PatientsLikeMe (PLM) offer promise for research in multiple sclerosis (MS), but their patient-reported outcomes (PROs) and patient samples require clinical validation. We sought first to compare the PRO used by PLM members to rate disease severity (MS Rating Scale, revised: MSRS-R) with clinically validated tools, and second to assess biases in the PLM MS population. We deployed the MSRS-R to 122 patients and their physicians at the Partners MS Center (PMSC) in Boston. Patient- and physician-derived MSRS-R scores revealed good agreement (weighted kappa 0.483, SpearmanвЂ™s r Вј 0.732). Patient-derived MSRS-R scores showed high correlation with physician-derived EDSS, Timed 25 Foot Walk and Ambulation Index (0.50<r<0.61, p<0.001 for each). We then compared 4,039 PMSC patients to 10,255 PLM members. PLM subjects were younger, more educated, more often female, and less often white. Disease course was more often relapsing remitting, presenting at younger age, with shorter disease duration (p<0.001 for all comparisons). These differences were small in absolute terms. Large prospective datasets collected online may accelerate research studies, particularly in tracking the relationship between clinical outcomes (relapses, progression) and fluctuations in PROs (fatigue, quality of life). Study supported by: N/A Drs Vaughan and Wicks are employees of PatientsLikeMe, Inc, and own stock options in the company. T1803. Elevated IFNa Activity in Patients with a History of Lyme Disease and Persistent Symptoms Elzbieta Jacek, Brian Fallon, Mary K. Crow and Armin Alaedini; New York, NY Some Lyme disease patients suffer from persistent symptoms of pain, fatigue, and/or cognitive deficits despite recommended courses of antibiotic treatment. The mechanisms responsible for these symptoms, collectively referred to as post-Lyme disease syndrome (PLDS), remain unclear. IFNa is a cytokine that is produced in response to inflammation by a variety of cells. Several studies have shown a correlation between increased IFNa activity and neurocognitive impairment. We carried out a longitudinal analysis of serum IFNa activity in PLDS patients prior to and following treatment with ceftriaxone b-lactam antibiotic by detection of changes in IFNa target genes, including IFIT1, IFI44, and IFIT3, using a functional cell-based assay and qRT-PCR. Sera from PLDS patients caused significantly higher induction of IFIT1 (p<0.01) and IFI44 (p<0.05) than post-Lyme healthy controls, indicating elevated IFNa activity. However, patient serum IFNa activity did not moderate in response to ceftriaxone. The results provide further evidence for the existence of an immune-mediated disease process in PLDS and suggest a possible mechanism for some of the associated neurocognitive deficits. Study supported by: National Institutes of Healthy Time for Lyme T1806. Comparison of Disease Activity in SPMS and PPMS in the Context of Multicenter Clinical Trials Diego Cadavid, Rotem Orbach and Zhenming Zhao; Cambridge, MA and Tal Hashomer, Israel T1804. Anti-NMDA Receptor Antibody Encephalitis Presenting as Acute Psychosis Matthew B. Bevers, Isabel C. Arrillaga-Romany and Bradford C. Dickerson; Boston, MA Retrospective natural history studies have shown similarities in disease progression for primary (PPMS) and secondary (SPMS) progressive multiple sclerosis, suggesting these may be phenotypic variations of the same disease. We compared Limbic encephalitis caused by antibodies to the NMDA receptor is associated with a syndrome of headache, seizure 142 ID: guganp I Black Lining: [ON] I Time: 09:25 I Path: N:/3b2/ANA#/Vol00000/120255/APPFile/JW-ANA#120255 J_ID: ZAY Customer A_ID: BKLT2012_Abstracts Cadmus Art: ANA12 Date: 18-September-12 longitudinal disease activity in SPMS and PPMS in the context of international multicenter clinical trials. We analyzed outcome measures collected over 2 years for subjects randomized to placebo in one SPMS and one PPMS clinical trial. Disease activity was analyzed across 3 categories: intermittent activity, progression, and improvement. MRI measures and quality-of-life measures were included when available. We found 17,963 disease activity measurements corresponding to 101 outcome variables from 206 SPMS subjects and 9,798 disease activity measurements from 78 outcome variables from 135 PPMS subjects. Subjects with SPMS and PPMS exhibited remarkably similar disease activity except for sensory worsening (more common in PPMS) and 9-Hole Peg worsening (more common in SPMS). Intermittent activity was the most common pattern of disease activity; clinical worsening and improvement occurred at similar frequencies in both. These analyses demonstrating similar disease activity patterns in SPMS and PPMS support the concept that these forms of MS are essentially the same. Study supported by: Biogen Idec DC and ZZ are full-time employees of Biogen Idec and own stocks/options in Biogen Idec. RO was a paid intern at Biogen Idec. Stage: Page: 143 mental factors and we wondered if this also occurs in NMO. Methods: We retrospectively analysed relapse data of 128 aquaporin-4 antibody-positive NMO/NMO spectrum disorder patients from the UK (n Вј 81) and Japan (n Вј 47). The month of onset attack and months in which all subsequent relapses occurred were recorded. Results: 475 relapses (including onset attack) occurred in 128 patients. There was no obvious seasonal variation in NMO onset attacks. However, subsequent relapses were most frequent during the summer months, with fewest relapses during the winter months. This trend was seen in both the UK and the Japanese cohorts and was also seen when only relapses occurring prior to initiation of longterm immunosuppression were analysed. Discussion: Our data suggest that NMO relapses in aquaporin-4 positive patients are most frequent in summer. This is likely to be related to environmental factors that may include temperature, sunlight exposure and seasonal prevalence of various infectious agents. Larger studies are indicated to confirm our findings. Study supported by: PC-L has no disclosures. JK has received support for scientific meetings from Biogen Idec, Teva and Novartis and is supported by the NHS National Specialised Commissioning Group for Neuromyelitis Optica. MIL is supported by the NHS National Specialised Commissioning Group for Neuromyelitis Optica and by the National Institute for Health Research Oxford Biomedical Research Centre and has received speaking honoraria from Novartis. LE and AJ are supported by the NHS National Specialised Commissioning Group for Neuromyelitis Optica. IN has received funding for travel and received speaker honoraria from Bayer Schering Pharma, and Biogen Idec; has received research funding from Mitsubishi Chemical Medience Corporation, and the Grants-in-Aid for Scientific Research from the Ministry of Education, Science and Technology of Japan. KF serves on scientific advisory boards for Bayer Schering Pharma, Biogen Idec, and Merck Serono; has received funding for travel and received speaker honoraria from Bayer Schering Pharma, Biogen Idec, Eisai Inc., Mitsubishi Tanabe Pharma Corporation, Astellas Pharma Inc., Takeda Pharmaceutical Company Limited, and Asahi Kasei Kuraray Medical Co., Ltd.; serves on the editorial board of Clinical and Experimental Neuroimmunology; receives royalties from the publication of Clinical Practice Guide of Orthopedic Surgery (Bunkodo, 2007); and has received research support from Bayer Schering Pharma, Biogen Idec Japan, Asahi Kasei Kuraray Medical Co., The Chemo-Sero-Therapeutic Research Institute, Teva Pharmaceutical K.K., Mitsubishi Tanabe Pharma Corporation, Teijin Pharma, Eisai Inc., and Kowa Pharmaceuticals America, Inc., and the Grants-in-Aid for Scientific Research from the Ministry of Education, Science and Technology of Japan. JP has received unrestricted grants and support for scientific meetings and scientific advisory honorariums from Merck Serono, TEVA, Biogen, Bayer Schering and Novartis, has held MS society grants and is a clinical lead for the UK Department of Health Risk Sharing Scheme. T1807. The MS-STAT Trial: A Phase II Trial of High Dose Simvastatin for Secondary Progressive Multiple Sclerosis (SPMS): Initial Results Jeremy S. Chataway, Ali Alsanousi, Dennis Chan, David MacManus, Kelvin Hunter, Jo Foster, Charles Bangham, David Wilkie, Jennifer Nicholas, Virginia Calder, John Greenwood, Chris Frost and Richard Nicholas; London, United Kingdom and Brighton, United Kingdom Background: No current treatments are proven to reduce the rate of progression in secondary progressive MS (SPMS). Simvastatin is an attractive potential therapy which is well tolerated, with an excellent safety profile, that has both immunomodulatory and neuroprotective effects. This investigator-led study is the first trial of a statin in SPMS. Results: 140 patients were randomised as planned and 129 were followed up to year 2 (92%). At baseline mean age was 51yrs (range 35 to 65), MS duration 21.2 (8.6), SPMS duration 7.2 (5.2), and 69% were female. At baseline the median (IQR) EDSS was 6 (5.5 to 6.5) and at 24 months 6.5 (6 to 6.5). At baseline, MSIS-29 was 68.2 (14.6) and at 24 months 72.4 (16.6). The total cohort had 474 new or enlarging T2 lesions (1.9 per patient per year), with !1 relapses experienced by 34 participants. Conclusion: This 2 year trial of a novel agent in SPMS has now completed. In addition to the results above, brain atrophy and full unblinded data will be presented. ClinicalTrials.gov, number NCT00647348 Study supported by: Multiple Sclerosis Trials Collaboration Moulton Foundation T1808. Seasonal Variation of Relapses in Neuromyelitis Optica Peter Chater-Lea, Joanna Kitley, Liene Elsone, Yoshiki Takai, Anu Jacob, Ichiro Nakashima, M. Isabel Leite, Kazuo Fujihara and Jackie Palace; Oxford, United Kingdom; Liverpool, United Kingdom and Sendai, Japan T1809. PK11195-PET Enhancement in Black Holes Correlates with Disability and Outcome in Progressive Multiple Sclerosis Paolo Giannetti, Marios Politis, Paul Su, Federico E. Turkheimer, Omar Malik, Shiva Keihaninejad, Kit Wu, Richard Reynolds, Richard Nicholas and Paola Piccini; London, United Kingdom Introduction: NMO is an autoimmune inflammatory disease of the CNS, which is often relapsing. The trigger for relapses is unknown. In MS, variations in relapse rates throughout the year are seen, suggesting a role for environ- The pathophysiological correlates and contribution to persisting disability of MS black holes (BH) are still unclear. In 143 ID: guganp I Black Lining: [ON] I Time: 09:25 I Path: N:/3b2/ANA#/Vol00000/120255/APPFile/JW-ANA#120255 J_ID: ZAY Customer A_ID: BKLT2012_Abstracts Cadmus Art: ANA12 Date: 18-September-12 order to study their in vivo pathological correlates, we used PK11195-PET to investigate changes in microglial activity. Ten relapsing and 9 progressive MS subjects had a PK11195-PET and MRI scans, alongside a clinical assessment. We studied the PK11195 binding potential, specifically bound relative to the non-displaceable radioligand in tissue (BPND), in BH. Out of a total of 1,242 BHs identified, 947 were PK11195 enhancing. The PK11195 BPND was correlated with EDSS (r Вј 0.818; p<0.01) only in the progressive group. In the relapsing patients there was an inverse correlation between PK11195 BPND and BH lesion load (r Вј -0.781; p<0.01). The progressive patientsвЂ™ total PK11195 BPND at baseline was found to be a significant outcome predictor of disability at the 2 years FU assessment (p<0.01). Our findings show that MS patients have heterogeneous patterns of microglial activity in BHs. In progressive subjects PK11195 BPND was associated with disability and outcome, whereas in relapsing patients higher PK BPND was present in subjects with a smaller BH lesion load and was not associated with disability. Study supported by: PG received an EFNS (European Federation of Neorological Societies) Scientific Fellowship in 2009 and a Research Fellowship from the Fondazione Italiana Sclerosi Multipla вЂ“ Cod. 2010/B/7. FT was funded by the PET Methodology Programme Grant from the Medical Research Council (UK). The Multiple Sclerosis Society of Great Britain and Northern Ireland (747/02 to RR, RN). Stage: Page: 144 maintenance of neurologic function. We have observed hippocampal injury that compromises cognitive function and induces seizures following acute infection of C57BL/6 mice with the TheilerвЂ™s murine encephalomyelitis virus. Injury is independent of direct neuronal infection with the virus and precedes the onset of an adaptive immune response, leading us to hypothesize that an early innate immune response causes the damage. Flow cytometric analysis of brain-infiltrating leukocytes indicated that mice experiencing hippocampal injury mount a robust inflammatory monocyte and neutrophil response in the brain within hours of infection. Immunodepletion of inflammatory monocytes but not neutrophils protected the hippocampus from injury, preserved cognitive function, and reduced seizure activity. Adoptive transfer of inflammatory monocytes into hosts with a defective innate immune response recapitulated the hippocampal injury and triggered seizures. We conclude that hippocampal injury and seizures during acute picornavirus infection of the brain are the result of bystander pathology triggered by infiltration of inflammatory monocytes. Study supported by: This work was supported by grant NS64571 from the NIH/NINDS. T1813. Faciobrachial Dystonic Seizures Are Immunotherapy-Responsive and Treatment May Prevent Amnesia Sarosh R. Irani*, Susanne A. Schneider, Rosemary Pettingill, Philippa Pettingill, Bethan Lang, Shelagh J.M. Smith, Michael R. Johnson and Angela Vincent; Oxford, United Kingdom and London, United Kingdom T1810. Withdrawn. T1811. Natal Natalizumab Daniel Lashley, Kevin Gormley and Timothy Harrower; Exeter, United Kingdom Faciobrachial dystonic seizures (FBDS) have been recently described as a prodrome to LGI1-antibody encephalitis. Here we detail serial clinical and serological outcomes in 10 prospectively identified cases. The ages at onset varied widely (28-92 years) and all had LGI1-antibodies. Videos will be used to show FBDS affected arm (100%), face (90%) and leg (40%) and occurred between 8 and 200 times per day (mean Вј 75). FBDS were the first feature in nine cases, but only five had normal cognition upon presentation to neurology. All these five cases were commenced on anti-epileptic drugs and three progressed to develop amnesia, 45, 60 and 89 days after FBDS onset. By contrast, two cases also treated with immunotherapies (at 30 and 108 days), retained normal cognition (ACE-R >93). Overall, immunotherapies were far more effective than AEDs in FBDS control (p Вј 0.0002), and in three cases FBDS ceased with corticosteroids after only 10 days. In patients with persistent LGI1-antibodies, immunotherapy cessation commonly produced FBDS recurrence. Overall, time to immunotherapy administration correlated with time to return of function (r2 Вј 0.74; p Вј 0.0013). FBDS are the first adult-onset epilepsy with a consistent immunotherapy-response and their effective treatment may prevent amnesia. Study supported by: Nil Conflict of interest: AV and the University of Oxford receive royalties and payments for antibody assays and AV is the inventor on patent application WO/2010/046716 entitled вЂ�вЂ�Neurological Autoimmune DisordersвЂ™вЂ™. The patent has been licensed to Euroimmun AG for the development of assays for Lgi1 and other VGKC-complex antibodies. SRI and BL are coapplicants on the patent. The risk of rebound severe relapse on discontinuation of natalizumab therapy in relapsing-remitting Multiple Sclerosis (RRMS) remains undetermined. Similarly, there is limited data regarding safety of natalizumab use in pregnancy. The post-natal period is independently associated with an increased risk of MS relapse. We present a case of a 32 year old woman with RRMS and a 15 month history of natalizumab treatment, stopped during pregnancy. She suffered relapses at 15 and 34 weeks antenatal, then an untypical, severe, disabling relapse at 2 weeks postnatal. Sequential MRI imaging showed evolution of a diffuse leucoencephalopathy on T2, with multiple gadolinium enhancing lesions in a pattern consistent with aggressive MS. Serological testing and cerebrospinal fluid studies were negative for JC virus and in the presence of clinical improvement, natalizumab was re-introduced. The gadolinium enhancement resolved and she made rapid clinical improvement. The combination of natalizumab withdrawal and post-natal immune reconstitution may have contributed to the severe relapse. Appropriate patients should be counselled on this risk at time of treatment initiation and on diagnosis of pregnancy. If discontinued, early reintroduction of immunosuppressive treatment should be considered immediately upon delivery. Study supported by: TH has received educational grants to attend conferences from Biogen. T1812. Brain-Infiltrating Inflammatory Monocytes Injure the Hippocampus and Induce Seizures during Acute Picornavirus Infection of the CNS Charles L. Howe; Rochester, MN Immune control of acute viral infection in the CNS requires a careful balance between efficient clearance of the virus and 144 ID: guganp I Black Lining: [ON] I Time: 09:25 I Path: N:/3b2/ANA#/Vol00000/120255/APPFile/JW-ANA#120255 J_ID: ZAY Customer A_ID: BKLT2012_Abstracts Cadmus Art: ANA12 Date: 18-September-12 T1814. Withdrawn. Stage: Page: 145 Conclusion: aMSC transplantation is a safe procedure in ALS patients, with a beneficial effect on the progression of ALS and improvement in survival. Study supported by: No support T1815. Evaluation of Blood Anti-JCVirus Antibodies of Natalizumab Treated Multiple Sclerosis Patients Themistoklis Kalamatas, Nikolaos Protopapas, Ioannis Doumos, Aimilia Lafioniati, Athina Nella, Anastasios Graigos and Klimentini Karageorgiou; Athens, Attiki, Greece T1817. Chronic Pain as a Manifestation of Potassium Channel-Complex Autoimmunity Christopher J. Klein, Vanda A. Lennon, Paula A. Aston, Andrew McKeon and Sean J. Pittock; Rochester, MN Objective: The main goal of our study is to evaluate the measurements of anti-JCV antibodies found in the blood of Natalizumab treated MS patients. Design/Methods: 263 MS patients were tested with the Stratify(TM) two step ELISA assay for serum anti-JCV antibodies. Blood samples were drawn previous to Natalizumab Infusions and were sent to Unilabs. We analysed demographics data (age, sex, years of Natalizumab treatment, history of immunosuppression treatment) and results of the anti-Jcv test. Results/Conclusion: 163 patients were female and 100 patients were male and their ages varied from 15 to 72 years (mean 45.8,SD:11.30 years). The duration of Natalizumab treatment varied from 0,5 to 7 years (mean 3,17,SD:1,08). 226 patients were never treated with immunosuppressants. 37 were treated with immunosuppressants. 152 patients were found positive for serum anti-JCV and 111 were found negative (57.7% positive, 42.3% negative). We found that with aging the prevalence of positive serum anti-JCV increases (p<0.005). No other statistical significant relations could be found. Discussion: Although no significant relations were found we suggest that testing forAnti-JCV as a basic biomarker should always be performed before initiation of treatment with Natalizumab. Study supported by: Stratify (TM) JCV test kits were provided by Genesis Pharma. Genesis Pharma also financed the courier service for the transfer of blood samples to Unilabs. Autoantibodies targeting voltage-gated potassium channel (VGKC)-complexes cause a spectrum of neuronal hyperexcitability disorders. We investigated pain as a manifestation of VGKC-complex-IgG autoimmunity. VGKC-complex-IgG was identified in 1,992 patients of 54,853 tested (4%). Of 316 evaluated neurologically at Mayo Clinic, 159 (50%) had pain, in isolation (28%) or with accompanying neurological manifestations (72%). Pain was subacute in onset, chronic in course, neuropathic, nociceptive, regional or diffuse and sometimes attributed to fibromyalgia (6%) or psychogenic cause (13%). Neuropathy impairment scores and nerve-conductions, were normal in most patients. Evidence of neuronal hyperexcitability (hyperhidrosis, quantitative heat-pain hyperalgesia or electromyographic excitability) was 25-fold more common in pain patients. Pain management required multiple medications in 70% (narcotics, 30%); 13 of 16 patients reported pain relief with immunotherapy. Pain was significantly associated with CASPR2-IgG-positivity (16% positive with pain, 7% without pain; p Вј 0.014) but not with LGI1-IgG. Less than 10% of 167 patients with neural autoantibodies other than VGKC-complex-IgG reported pain. Chronic pain is a syndromic manifestation of VGKC-complex autoimmunity. Hyperexcitability of nociceptive pathways is implicated. CASPR2-IgG significantly associates with pain, but in most patients the VGKC-complex target molecule remains to be determined. Study supported by: Mayo Foundation and a National Institutes of Health grant (NS065007, C.J.K.) and Mayo Clinic CTSA through grant number UL1 RR024150 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH). T1816. Intrathecal Autologous Mesenchymal Stem Cell Transplantation in Patients with Amyotrophic Lateral Sclerosis: A Four Year Case Control Follow-Up Study Clementine E. Karageorgiou, Ioanna Chatzi, Athanasia Alexoudi, George Gortzolidis, Elissaios Karageorgiou, Helen Papageorgiou, George A. Tagaris, Theofanis Chatzistamatiou, Aikaterini Stavropoulou-Gioka and Aikaterini StavropoulouGioka; Athens, Greece and Minneapolis T1818. Targeting Innate Receptors with MIS416 Reshaped Autoimmune T Cell Responses and Suppressed CNS Inflammation and Disease Anne C. La Flamme, Gill Webster, David OвЂ™Sullivan, Madeleine White and Sarrabeth Stone; Wellington, New Zealand and Auckland, New Zealand Objective: To study the clinical course of patients with Amyotrophic Lateral Sclerosis (ALS) four years after initiation of autologous mesenchymal stem cell (aMSC) transplantation. Patients: Thirty seven patients with definite ALS who had undergone intrathecal delivery of aMSC were compared to nine ALS patients matched for age, type, and severity of ALS. Between group comparisons of the ALSFRS progression, requirement for ventilator support and number of deaths over four years were performed using analysis of variance and survival analysis. Results: No significant side effects were noticed after the aMSC injection and the main adverse effect was low grade fever. During the four year follow-up period there were five deaths (13.5%) in the aMSC group and 8 deaths (88,8%) in the control group The decrease of the ALSFRS score was significantly less in the aMSC group than in the control group (p<0,001).Ventilatory support required two patients from aMSC group(6.06%) and seven patients from the control group(77,7%). Modification of innate immune cells has recently been recognized as a viable treatment strategy for reducing autoimmune disease pathology. MIS416 is a microparticle targeting the innate receptors, NOD2 and TLR9, and is a promising new therapeutic for progressive multiple sclerosis currently in phase 2a trial. However, the precise mechanism for disease reduction in patients is unknown. Using mouse models we investigated the pathways by which activation of TLR9 and NOD2 modify the innate immune environment and subsequent T cell-mediated autoimmune responses. We found that MIS416 had profound effects on the Th subset balance by depressing Th17 and Th2 development, sustaining Th1 responses, and augmenting splenic regulatory T cells. These effects coincided with increased levels of serum IFN-c induced by MIS416 treatment. We believe that this enhanced systemic IFN-c is key to MIS416-mediated protection as serum levels correlated strongly with disease reduction and the protective effect of MIS416 was 145 ID: guganp I Black Lining: [ON] I Time: 09:25 I Path: N:/3b2/ANA#/Vol00000/120255/APPFile/JW-ANA#120255 J_ID: ZAY Customer A_ID: BKLT2012_Abstracts Cadmus Art: ANA12 Date: 18-September-12 abrogated in IFN-c-deficient animals. Together, these studies indicate that administration of MIS416, which initially targets innate cells, reshapes autoimmune T cell responses and in an IFN-c-dependent manner leads to a reduction in CNS inflammation and disease. Study supported by: This work has been supported by Victoria University of Wellington, the Great New Zealand Trek, and Innate Immunotherapeutics. GW and Innate Immunotherapeutics have financial and commercial interest in MIS416. GW may have financial benefit from MIS416. ACL, DO, MW, and SS have no financial interest or benefit. Stage: Page: 146 T1821. Phase Imaging in Marmoset EAE at 7T Demonstrates Heterogeneity within Focal Lesions Pietro Maggi, Pascal Sati, Emily Leibovitch, Maria I. GaitaВґn, Jillian Wholer, Sheila Macri, Luca Massacesi, Susan Westmoreland, Steve Jacobson, Afonso Silva and Daniel S. Reich; Bethesda, MD and Boston, MA вЂ�вЂ�PhaseвЂ™вЂ™ imaging at 7T demonstrates that MS lesions appearing similar on conventional вЂ�вЂ�magnitudeвЂ™вЂ™ images are often remarkably heterogeneous (Hammond et al., Ann Neurol 2008; Yao et al., Radiology 2012). In the marmoset EAE model, induced with human white matter homogenate (n Вј 4), we investigated the biological origin of intralesional phase variations. A multi-gradient-echo sequence performed at 7T generated magnitude T2*-weighted (T2*w) and phase images. Animals were scanned prior to and every two weeks after immunization, and then weekly after the first lesion appeared. We observed two lesion patterns: (1) Lesions that appeared similar on magnitude and phase (homogeneous hyperintense T2*w signal and hypointense phase signal); (2) Lesions that appeared different on magnitude and phase (homogeneous hyperintense T2*w signal but heterogeneous phase signal with areas of hypointensity and isointensity). We conclude that phase imaging in marmoset EAE might provide more specific information about the pathology underlying tissue damage within lesions. Possible sources of phase heterogeneity include variations in water content, myelination, and iron deposition; histopathology is underway to investigate these possibilities. Study supported by: Intramural Research Program of NINDS/NIH; National Center for Research Resources and the Office of Research Infrastructure Programs/NIH T1819. Treatment of MS with ACTHar Gel вЂ“ Clinical Experience and Case Presentation Gerard M. Lehrer; New York, NY ACTH has been known to be effective in treating MS exacerbations after the study by Rose et al. The half life after IV administration is less than 8 hours, and it had to be repeated twice daily. The presumed effect was via glucocorticoid from the adrenal cortex. Because ACTHar prepared first by Armour as a porcine anterior pituitary extract in a gelatin base was to have extended activity, I began using it as a single, subcutaneous injection of 80-120u. Surprisingly a single injection often resulted in almost total reversal of symptoms, lasting 4-6 days, with no or few repeats for complete return to usual function. Patients will be examples in whom total loss of vision, documented by loss of VEP, returned to 20/20 within 24 hours. It appeared that other components of the gene product, pro-opiomelanocortin, e.g. melanocortin, MSH, lipotropin, and 39 aminoacid ACTH might be responsible for a direct effect on immune and inflammatory processes. Colleagues confirmed this impression. Synthetic ACTH prepared similarly was only minimally effective. Data from approximately 600 patients will be reviewed. Study supported by: Questcor T1822. Cognitive Function and Visual outcome Measures in Patients with Early MS Amir H. Maghzi, Laura Julian, Jackie Marcus, Jennifer Graves, Ellen M. Mowry, Rebecca Spain, Ari Green, Michelle K. Mass, Daniel Pelletier and Emmanuelle Waubant; San Francisco, CA; Baltimore; Prtland and New Haven T1820. Blood Brain Barrier Changes Prior to Lesion Formation in a Primate Model of Multiple Sclerosis Pietro Maggi, Emily Leibovitch, Maria I. GaitaВґn, Jillian Wholer, Govind Nair, Luca Massacesi, Steve Jacobson, Afonso Silva and Daniel S. Reich; Bethesda, MD Objectives: In search of the best outcome to measure neuroprotection,we aimed to study the correlation of cognitive function with optical coherence tomography(OCT) measurements in a cohort of patients with early MS. Methods: Patients with relapsing-remitting MS or clinically isolated syndromes seen within 12 months of onset and naive to disease-modifying therapies were enrolled in a trial of neuroprotection with riluzole vs. placebo. Baseline clinical, demographic, OCT, MRI and neuropsychological data were obtained at least four weeks after corticosteroid treatment. Linear regression analysis with adjustment for age and educational level were performed. Results: Baseline OCT and neuropsychological evaluations were available for 31 patients (77.4% females; mean age 37.02; median EDSS 2.0; mean disease duration 7.4 months). 32% of patients had impairment on at least one cognitive test. Mean retinal nerve fiber layer thickness (96.63Гѕ/-12.04 microns, normal 88.5-111.7) and mean macular volume (6.59Гѕ/-0.39 mm3, normal 6.1-7.0) for both eyes were not correlated with information processing speed, learning and memory, executive functioning, attention, working memory, and visuospatial capacities. Conclusion: Although based on small numbers, OCT measurements do not seem to be associated with cognitive deficits in early MS.Correlations with measures of brain atrophy and interocular differences are ongoing. Changes in BBB permeability are associated with inflammation in MS and EAE. We used quantitative MRI to investigate processes associated with lesion formation in marmoset EAE induced with human white matter homogenate (n Вј 4). Animals underwent brain MRI on a 7T scanner, including T1 maps before and after gadolinium injection. Animals were scanned prior to and every two weeks after immunization, then weekly after the first lesion appearance. Prolongation of the longitudinal relaxation rate (R1 Вј 1/T1) following gadolinium injection was used to estimate BBB changes at each time point. In areas that later became focal lesions, we found that DR1 increased over time (p Вј 0.0024), 4.461.3 (mean6standard error) fold over baseline in the 10 days prior to lesion appearance. Slight further increases in DR1 at the time of and shortly after lesion appearance were also observed. There was no change in DR1 in the cortex or extralesional white matter. We conclude that focal BBB changes occur during the initial stages of lesion development in marmoset EAE. This suggests that inflammation in this MS model is primarily a multifocal process rather than a diffuse one. Study supported by: Intramural Research Program of NINDS/NIH; 146 ID: guganp I Black Lining: [ON] I Time: 09:25 I Path: N:/3b2/ANA#/Vol00000/120255/APPFile/JW-ANA#120255 J_ID: ZAY Customer A_ID: BKLT2012_Abstracts Cadmus Art: ANA12 Date: 18-September-12 Study supported by: This study was supported by the national MS Society (RG3932-A-2). Biogen Idec and Sanofi Aventis have provided free medication for this trial. Dr. Maghzi was supported through a McDonaldвЂ™s Fellowship from MSIF. Dr. Marcus was supported by a fellowship from national MS society and Biogen Idec. Dr. Waubant has received has received honorarium for educational presentations from Biogen Idec. She is ad hoc consultant for Sanofi Aventis. She has received free study medication from Biogen Idec and Sanofi Aventis. She has received an educational grant from Biogen Idec. Dr. Green served as ad hoc consultant for Novartis and Biogen Idec. All other authors have nothing to disclose regarding this study. Stage: Page: 147 Results: In all BD cases, Cx43, Cx32 and Cx47 were extensively diminished. In the leading edge of BaloВґвЂ™s lesions, Cx43 and AQP4 loss preceded Cx47 loss. Two cases with MS and six with NMO showed preferential Cx43 and AQP4 loss far beyond the demyelinated areas, and vasculocentric deposition of immunoglobulin or complement was observed in four of the six NMO cases. The other cases showed AQP4 and Cx43 preservation, even in actively demyelinating lesions. Some NMO cases showed preferential MAG loss in AQP4and Cx43-diminished active lesions. Conclusion: Our findings indicate that antibody-independent astrocytopathy can occur in MS, BD and NMO, and could be a common denominator. Study supported by: This work was supported in part by a Health and Labour Sciences Research Grant on Intractable Diseases (H22-Nanchi-Ippan-130 and H23Nanchi-Ippan-017) from the Ministry of Health, Labour, and Welfare, Japan, by a Scientific Research B Grant (No. 22390178) and a Challenging Exploratory Research Grant (No. 23659459) from the Ministry of Education, Culture, Sports, Science, and Technology (Japan), by the Kaibara Morikazu Medical Science Promotion Foundation (Japan), and by the Japanese Multiple Sclerosis Society. T1823. Clinical Information of Four Men with Anti-NMethyl D-Aspartate Receptor Encephalitis Makoto Samukawa, Makito Hirano, Hikaru Sakamoto, Shuichi Ueno, Toshiharu Maekura, Harutoshi Fujimura, Susumu Kusunoki and Yusaku Nakamura; Osaka-Sayama, Osaka, Japan; Sakai, Osaka, Japan and Toyonaka, Osaka, Japan Anti-N-methyl D-aspartate receptor (NMDAR) encephalitis is a female-predominant disease often associated with tumors such as ovarian teratoma. Male patients have been also reported but their clinical information is not well-known. Thus, we report four men who had anti-NMDAR encephalitis with characteristic symptoms. All patients had prodromal symptoms such as fever and headache, and then developed psychiatric changes. No patients had tumors. Cerebral spinal fluid in all patients contained NMDAR antibody. Characteristic complications include: venous thrombosis (2/4), hippocamps involvement (2/4), hypersexuality (2/4), and joint contracture (1/4). Venous thrombosis, generally more frequent in men than in women, caused fatal pulmonary embolism in one of our patients. Joint contracture has been found previously in only one man. Hippocampus is consistently affected in this disease, however, one of our patients had atrophy of hippocampus severely progressed on MRI even after recovery of psychiatric problems. Hypersexuality is common in limbic encephalitis, but detail description has not been reported previously. This symptom in men can threaten female nurses. We suggest that these characteristic features are not necessarily male-specific, but should be properly managed in consideration of gender differences. Study supported by: N/A T1825. The Role of Manganese Enhanced MRI (MEMRI) in TheilerвЂ™s Murine Encephalitis Virus (TMEV) Induced CNS Inflammatory Disease Models Istvan Pirko, Jeffrey Gamez, Emily R. Shearier, Mekala Raman, Aaron J. Johnson and Slobodan I. Macura; Rochester, MN MEMRI is a unique tool utilized in CNS tractography. Manganese can be directly microinjected to CNS foci for connectivity studies utilizing its T1 relaxation enhancement properties. When administered systemically, it crosses the BBB at specific locations and visualizes corresponding neuronal structures. While DTI scrutinizes physical connectivity by assessing water diffusion directionality, MEMRI provides вЂ�вЂ�functional tractographyвЂ™вЂ™ by visualizing tract connectivity via transsynaptic uptake. Dose dependent toxicity limits its longterm use. MEMRI has never been utilized in the TMEV model of MS. We studied IP administration in TMEV infected C57BL6/J mice, in uninfected controls, and in a previously reported hemorrhagic demyelination model.Tract enhancement was noted at 24 hours with maximal uptake in hippocampi, olfactory bulbs, and cerebellum. In infected mice, characteristic T1 black holes, thinning and focal disruption of tracts were detected. BBB disruption and resultant Mn uptake were also demonstrated. Manganese also exerted an unexpected therapeutic effect: hemorrhagic demyelination was suppressed with manganese adnimistration, likely as a result of direct effects on infected neurons.We conclude that MEMRI enables unique functional tractography, with a capacity to provide important structural and functional information. Study supported by: NIH NINDS R0 1NS058698 and Mayo Clinic Department of Neurology intramural funds T1824. Connexin Astrocytopathy in Multiple Sclerosis, BaloВґвЂ™s Disease and Neuromyelitis Optica Katsuhisa Masaki, Satoshi O. Suzuki, Takuya Matsushita, Takeshi Matsuoka, Toshihiko Suenaga, Takeshi Tabira, Toru Iwaki and Jun-ichi Kira; Fukuoka, Japan; Nara, Japan and Tokyo, Japan Background: Recently, we reported AQP4 loss without perivascular deposition of either activated complement or immunoglobulin in patients with multiple sclerosis (MS), neuromyelitis optica (NMO) and BaloВґвЂ™s disease (BD). To investigate the relationship between astrocytopathy and demyelination, we examined the expression of connexins (Cx), which form gap junction channels between astrocytes and oligodendrocytes. Methods: We evaluated astrocytic Cx43/Cx30 and oligodendrocytic Cx47/Cx32 expression relative to AQP4 and GFAP expression, and extents of demyelination in 11 autopsied cases with NMO, five with MS, four with BD. T1826. Pilot Clinical Trial of Eculizumab in AQP4-IgG-Positive NMO Sean J. Pittock**, Andrew McKeon, Jay N. Mandrekar, Brian G. Weinshenker, Claudia F. Lucchinetti and Dean M. Wingerchuk; Rochester, MN and Scottsdale, AZ Objective: Investigate safety and efficacy of blocking terminal complement activation in reducing frequency of neuromyelitis optica (NMO) relapses. We conducted an 147 ID: guganp I Black Lining: [ON] I Time: 09:25 I Path: N:/3b2/ANA#/Vol00000/120255/APPFile/JW-ANA#120255 J_ID: ZAY Customer A_ID: BKLT2012_Abstracts Cadmus Art: ANA12 Date: 18-September-12 open-label study of eculizumab, an inhibitor of C5 cleavage, in patients with aggressive NMO. Methods: 14 adults with NMO spectrum disorder (! 2 relapses in the preceding 6 months or 3 in the preceding 12 months) were treated with eculizumab for 1 year. 7 had failed standard immunosuppressant treatments. Results: After 12 months treatment, 12 of 14 were relapse-free. The median annualized attack rate declined from 3 (pre-eculizumab) to 0 (on-eculizumab; p<0.0001). Two subjects had single attacks: one had back pain only (<30 hours after first infusion, without objective clinical/radiological evidence of myelitis) and received corticosteroids for a вЂ�вЂ�possibleвЂ™вЂ™ attack; the other had optic neuritis. At 12 months, no subject had worsened disability by any outcome measure. Median EDSS score declined from 4.3 (pre-eculizumab) to 3.5 (on-eculizumab; p <0.01). One patient was successfully treated for meningococcal meningitis. Otherwise, the treatment was well tolerated. Conclusions: Apparent stabilization of disease activity in this cohort selected for aggressive disease activity supports a central role for complement activation in NMO. Eculizumab warrants further investigation as NMO therapy. Study supported by: Alexion Pharmaceuticals, Inc. Stage: Page: 148 substantial so disabling sequelae are rare. Permanent disability from progressive disease is more common but this usually evolves very slowly. Rare case reports have suggested there may also be a fulminant variant (first proposed by Otto Marburg in 1906) of вЂ�вЂ�unrelenting progressive disease that typically leads to death within a few months to a year.вЂ™вЂ™ To clarify the early course of MS, we analyzed all 1,854 patients who met McDonald diagnostic criteria for MS seen at our MS Center from 1994-2011. None had fulminant disease. Only 4 patients reached an EDSS of 6.0 (requiring assistance to walk) within the first year and all these were alive and stable 10 years later. No patient died within 5 years of onset and fewer than 10% of patients reached an EDSS of 6.0 within 5 years. (Analysis of these patients will be presented.) We conclude that fulminant MS is rare. The low rate of disability in the first few years of MS has important implications for counseling newly diagnosed patients and discussing therapeautic options. Study supported by: No outside support. T1829. Demographic and Clinical Features of Participants in a VA Longitudinal Study of MS Walter Royal, Mitchell Wallin, Terry Lee-Wilk, Heidi Maloni, William J. Culpepper, Joseph Finkelstein, Jong-Chaur Shieh, Michael Levin, Micheline McCarthy, William Tyor, Jonathan Leigh, Min Zhan, Robert Kane and Christopher Bever; Baltimore, MD; Washington, DC; Buffalo, NY; Memphis, TN; Miami, FL; Atlanta, GA and Cleveland, OH T1827. Growth Factors PDGF and FGF-2 Are Required for Human Recombinant IgM-Mediated Stimulation of Oligodendrocyte Proliferation and Survival Jens O. Watzlawik, Arthur E. Warrington and Moses Rodriguez; Rochester, MN Objectives: To describe results of a cross-sectional analysis of clinical and demographic characteristics for military veterans participating in a longitudinal study of MS. Methods: MS patients recruited from 8 VA medical centers were assessed using the Kurtzke EDSS, the Multiple Sclerosis Functional Composite, and questionnaires to obtain demographic information. Results: 96 patients were enrolled, 83% treated with a MS disease modifying therapy. The patient mean age was 47.5 Гѕ 8.7, male: female ratio was 2.6:1, and 59.5% were non-white. 59.4% had relapsing-remitting, 28.1% secondary progressive, 8.3% primary progressive and 4.2% had relapsing progressive MS. Females were younger at the time of their first MS symptom (p Вј 0.005). Non-white patients were younger at enrollment (p Вј 0.008) and borderline younger at their first MS symptom (p Вј 0.06) than white patients. EDSS scores showed a bimodal distribution with peaks at EDSS 2.5 and 6.0. Progressive disease was associated with older age at the time of study enrollment (p Вј 0.018) and a borderline later onset of MS symptoms than relapsing-remitting patients (p Вј 0.05). Conclusions: Some cohort characteristics differ from those of non-VA patient groups, but several features are similar. Ongoing and more detailed studies are underway. Study supported by: Veterans Administration Authors are paid salaries by the VA. RHIgM22 is a recombinant human IgM, which targets myelin and oligodendrocytes (OLs) and promotes remyelination in animal models of MS. Co-factors required for rHIgM22 to promote remyelination are unknown and, it is unclear whether remyelination is driven by stimulation of oligodendrocyte progenitor cell (OPC) proliferation/survival, or by survival of mature OLs. RHIgM22 has completed safety studies in animals and is likely soon being tested in MS patients. We assessed IgM-induced OL proliferation, differentiation, apoptotic and intracellular signaling in vitro by radiolabeling, immunohistochemistry and Western blots. RHIgM22 promotes OPC proliferation in mixed glia cultures, but not in isolated OPCs. Proliferation in mixed glia is blocked by inhibition of PDGFaR kinase. RHIgM22 inhibits apoptotic signaling and differentiation in isolated OPCs in a PDGF-/FGF-2-dependent manner, but does not influence survival in mature OLs. Our findings demonstrate that glial growth factors are necessary for rHIgM22-mediated effects and suggest that astrocytes and microglia play important beneficial roles for IgM-induced in vivo remyelination. Our data support the hypothesis that OPCs are responsible for remyelination following a demyelinating insult such as MS rather than mature oligodendrocytes. Study supported by: This work was supported by grants from the National Institutes of Health (R01s - GM092993, NS024180, NS032129, NS048357, R21 - NS073684), the National Multiple Sclerosis Society (CA1060A11), the Applebaum Foundation, the Hilton Foundation, the Peterson Foundation and the Minnesota Partnership for Biotechnology and Medical Genomics. T1830. Unusual Presentation of Paraneoplastic StiffPerson Syndrome with Underlying Breast Cancer Alvin Shrestha, Tatiana Mihalova, Daniel Burns, Hannah Jennens and Roland Etti; Birmingham, West Midlands, United Kingdom A 46 year old lady presented to the Neurologists with constant itching and burning sensation of the left arm followed by the right. An MRI of the head and neck and nerve conduction study was normal. Five months later, she developed persistent stiffness of the neck and shoulders, and found head movement restrictive. Routine bloods were T1828. Does вЂ�вЂ�FulminantвЂ™вЂ™ Multiple Sclerosis Exist? Loren A. Rolak and Susan Anderson; Marshfield, WI Disability seldom occurs early in the course of MS. Relapses can produce severe deficits but remissions are usually 148 ID: guganp I Black Lining: [ON] I Time: 09:25 I Path: N:/3b2/ANA#/Vol00000/120255/APPFile/JW-ANA#120255 J_ID: ZAY Customer A_ID: BKLT2012_Abstracts Cadmus Art: ANA12 Date: 18-September-12 unremarkable; however anti-amphiphysin antibody was positive. She was given a diagnosis of partial stiff-person syndrome. At 11 months from the initial symptoms, the patient herself reported an abnormal lump in her right axilla. A CT whole body confirmed the lymph node, but did not show any other malignancy or lymphoma. A lumbar puncture showed an acellular CSF with normal CSF/serum glucose ratio, protein level and cytology. She was reviewed in the Breast Clinic, where the node was aspirated. The cytology unfortunately revealed large numbers of malignant cells, ER, PGR and cytokeratin positive, in keeping with metastatic breast cancer. This case describes an unusual initial presentation of burning sensation and itching, before the occurrence of classical stiffness in keeping with stiff-person syndrome, which preceded the detection of the underlying malignancy by several months. Study supported by: Conflict of interest: nil Stage: Page: 149 antibody staining. Using stage specific antisera to monitor differentiation, we observed maturation of OL from Akt1-/mice was arrested prior to differentiation. Staining specific for galactocerebroside (GalC), an early marker of differentiation, was absent. Western blot analysis confirmed the loss Akt1. Akt2-/- and Akt3 -/- mice displayed normal differentiation in vitro. These results suggest that Akt1, the predominant isoform during development, is required for oligodendrocyte maturation in vitro. Study supported by: This work was supported by the Grace R Loeb Endowed Chair in Neuroscience ChildrenвЂ™s Hospital of Philadelphia T1833. Profound Alternating Corticospinal Tract Enhancement in Neuro-BehcetвЂ™s Disease April A. Erwin, Carlo Tornatore and Mark Lin; Washington, DC Introduction: A typical MRI presentation of neuro-BehcetвЂ™s is corticospinal tract T2 hyperintensities. We present a case with profound corticospinal tract enhancement, alternating sides on successive relapses. We also present for comparison a more conventional case of neuro-BehcetвЂ™s with nonenhancing brainstem T2 hyperintensities. Cases: A 30 year old female presented with dysarthria and hemiparesis on three occasions. MRI brain during each event revealed enhancing brainstem and basal ganglia corticospinal tract lesions, alternating right to left on successive exacerbations, and remitting after administration of steroids. CSF oligoclonal bands and rheumatological serum screening tests were negative. Further history-taking revealed patient had recurrent bipolar ulcers and papulopustular skin lesions, qualifying her for a diagnosis of BehcetвЂ™s per International Study Group criteria. In another case, a 42 year old Yemeni male presented with hemisensory loss and bipolar ulcers. His MRI brain showed a more typical pattern of nonenhancing T2 hyperintensities in the right midbrain and pons. Conclusions: Neuro-BehcetвЂ™s is known to cause T2 hyperintensities in the brainstem and basal ganglia which may briefly enhance in the acute phase. However, the degree of enhancement and recurrent, alternating corticospinal tract lesions seen in our patient have not been described. Study supported by: None T1831. The Prevalence of Cardiovascular Risk Factors in Multiple Sclerosis Patients Zohara Sternberg, Christopher Leung, Daniel S. Sternberg and Elad Levy; Buffalo Objectives: This retrospective study examined the prevalence of CV risk factors in patients with multiple sclerosis (MS). Methods: CV risk factors were compared with non-MS patients who were diagnosed with non-autoimmune diseases of the brain. Correlation between CV risk factors and indicators of disease severity were carried out for MS patients. Results: After adjusting for confounding factors, MS patients had significantly higher TC (P Вј 0.01), higher plasma HDL (P <0.001), but lower plasma glucose (P <0.001) and systolic BP (P Вј 0.001) compared to non-MS patients. Gender differences in CV risk factors among MS patients were observed. Multiple regression analysis showed a positive correlation between plasma glucose and the EDSS (P Вј 0.008), and the rate of clinical relapse (P Вј 0.001), while diastolic BP and serum albumin were inversely related to the EDSS and MSSS (Ps < 0.05). Conclusion: MS patients present with low CV risk factors. Lowe plasma glucose and BP may be associated with autonomic nervous dysfunction in MS. Study supported by: Jog for the Jake, a local philanthropic foundation T1834. Anti-CD52 Therapy in Experimental Autoimmune Encephalomyelitis Michael J. Turner, Nathalie Chretien, Evis Havari, Michael LaMorte, Bruce Roberts, Johanne Kaplan and William M. Siders; Framingham, MA T1832. Akt1, Not Ak2 or Akt3, Regulates Oligodendrocyte Maturation In Vitro Jennifer A. Minarcik, Mary V. Reid, Morris J. Birnbaum, Chen Po, Judith B. Grinspan and Gihan I. Tennekoon; Philadelphia, PA and Baltimore, MD Alemtuzumab is a humanized monoclonal antibody that binds to the human CD52 molecule present at high levels on T and B lymphocytes. Administration of alemtuzumab results in lymphocyte depletion thereby altering the circulating lymphocyte pool in RR-MS patients. A recently developed depleting murine CD52 (muCD52)-specific antibody was evaluated in a mouse EAE model to expand our understanding of anti-CD52 therapy. Following immunization to induce EAE mice were treated with anti-muCD52 antibody, characterized with respect to disease severity and mechanism of action of the antibody. Results from these studies demonstrated a profound impact of anti-muCD52 therapy. Specifically, prophylactic treatment effectively prevented the development of disease while therapeutic intervention inhibited disease progression and reversed existing symptoms. Longitudinal flow cytometric evaluation demonstrated a decrease in the number of MOG35-55 specific CD4Гѕ T Myelin formation around axons by oligodendrocytes (OL) enables proper conduction of nerve impulses and ensures axonal integrity. Axonal signals that initiate and maintain myelination require the activation of several signal transduction pathways. The Akt (serine/threonine protein kinase B) pathway contributes to cell survival, proliferation, and lineage specificity of OL, along with the production of myelin through the phosphorylation of the mammalian target of rapamycin (mTOR). We investigated the importance of Akt and its 3 isoforms in the regulation of OL differentiation in cell culture. To study the effects of the specific Akt isoforms, we isolated OL from newborn mice (Akt1-/-, Akt2-/-, Akt3-/-, heterozygote and WT). OL were isolated by differential adhesion and purity was established using A2B5/GFAP 149 ID: guganp I Black Lining: [ON] I Time: 09:25 I Path: N:/3b2/ANA#/Vol00000/120255/APPFile/JW-ANA#120255 J_ID: ZAY Customer A_ID: BKLT2012_Abstracts Cadmus Art: ANA12 Date: 18-September-12 cells as determined by IFNg intracellular cytokine staining. Histological evaluation also showed a reduction in the level of lymphocytic infiltrate in the CNS of anti-muCD52 treated animals compared to control animals that received the vehicle. These results demonstrated the therapeutic efficacy of anti-muCD52 treatment as exhibited by a reduction in MOG-reactive pathogenic T cells and decreased lymphocyte infiltration in the CNS of mice with EAE. Study supported by: Genzyme, a Sanofi Company Dr. Turner and all co-authors receive personal compensation as an employees of Genzyme. Stage: Page: 150 scientific meetings and scientific advisory honorariums from Merck Serono, TEVA, Biogen, Bayer Schering and Novartis, has held MS society grants and is a clinical lead for the UK DOH RSS. T1836. Serum Proteomic Analysis of a Presymptomatic MS Cohort Mitchell Wallin, Unsong Oh, Julius Nyalwidhe, Thomas Kislinger, O. John Semmes, John Kurtzke, Parisa Coffman and Steven Jacobson; Washington, DC; Richmond, VA; Norfolk, VA; Bethesda, MD and Toronto, ON, Canada Objective: Susceptibility to MS is determined by environmental and genetic factors, but the cause remains unknown. Changes to the proteome prior to first symptom onset may reflect the underlying pathophysiology of the disease. Methods: Pre and post-symptomatic serum from 100 US military veterans with MS along with 100 matched healthy veterans and 50 other neurological disease controls were obtained from Department of Defense Serum Repository. Multidimensional protein Identification Technology Liquid Chromatography Tandem Mass Spectrometry analysis was performed on tryptic peptides of lectin-captured glycosylated serum proteins following albumin/IgG depletion. Results: The mean collection interval between MS presymptomatic and post-symptomatic serum was 6.0 and 1.1 years, respectively. Pre-symptomatic proteins from the MS group were differentially regulated compared to that of both control groups indicating that proteomic changes are detected prior to symptom onset. Pathway analysis showed that proteins involved in the complement and coagulation pathways and lipid transport are significantly altered in the serum of subjects with MS compared to healthy donors. Conclusions: Compared with controls, differential proteomic changes were noted in the serum of patients with MS that preceded the onset of symptomatic disease. Study supported by: National MS Society T1835. MOG Antibodies in Adult and Pediatric Demyelinating Diseases Joanna Kitley, Mark Woodhall, Patrick Waters, M. Isabel Leite, Jackie Palace and Angela Vincent; Oxford, United Kingdom Antibodies that bind to extracellular domains of myelin-oligodendrocyte glycoprotein (MOG), expressed on human embryonic kidney cells, have only recently been identified in patients with demyelinating diseases, and have been reported most consistently in children with ADEM. We have started performing MOG-antibody testing as a clinical service, and from 125 patient samples referred, 14 patients were positive for MOG-antibodies; all were negative for aquaporin-4-antibodies. 4/14 were children aged 3-16, 3/4 were male. The remainder were 6 male and 4 female adults. Here we report the clinical phenotypes of 8 of these patients. The presentations varied between ADEM-like (two children), monophasic LETM (two adults) and simultaneous ON and LETM typical of monophasic NMO (four adults). Overall, all the adults had features consistent with a diagnosis of NMO or NMO spectrum disorder. 7/8 patients made excellent recovery with immunotherapies and relapses were uncommon. We conclude that, although the full spectrum and long-term course of MOG-antibody-disease are not entirely established, MOG-antibodies will be helpful in the diagnosis and management of children and adults with demyelinating conditions, and that they might account for some of the aquaporin-4-antibody-вЂ™вЂ™seronegativeвЂ™вЂ™ cases that have previously been described as NMO. Study supported by: JK has received support for scientific meetings from Biogen Idec and is supported by the NHS National Specialised Commissioning Group for Neuromyelitis Optica. MW, PW and MIL are involved in AQP4 and MOG antibody testing, supported by the NHS National Specialised Commissioning Group for Neuromyelitis Optica and by the NIHR Oxford Biomedical Research Centre. AV and the Nuffield Department of Clinical Neurosciences hold patents and receive royalties and payments for antibody tests. JP has received unrestricted grants and support for scientific meetings and scientific advisory honorariums from Merck Serono, TEVA, Biogen, Bayer Schering and Novartis, has held MS society grants and is a clinical lead for the UK DOH RSS. JK has received support for scientific meetings from Biogen Idec and is supported by the NHS National Specialised Commissioning Group for Neuromyelitis Optica. MW, PW and MIL are involved in AQP4 and MOG antibody testing, supported by the NHS National Specialised Commissioning Group for Neuromyelitis Optica and by the NIHR Oxford Biomedical Research Centre. AV and the Nuffield Department of Clinical Neurosciences hold patents and receive royalties and payments for antibody tests. JP has received unrestricted grants and support for T1837. Guillain-BarreВґ Syndrome and Its Association with the 1976 вЂ�вЂ�Swine FluвЂ™вЂ™ Immunisation Programme James N.R. Wyatt; Liverpool, United Kingdom Introduction: In 1976, the US government suspected an influenza pandemic. In response, they set up a national vaccination programme. This was soon disbanded, as a rise in the incidence of Guillain-BarreВґ syndrome was reported. Years after, it is still a matter of debate whether there was a causal relationship. Objective: To use the Bradford-Hill criteria(1) of causality to determine the presence or absence of a causal relationship between GBS and the 1976 вЂ�вЂ�swine fluвЂ™вЂ™ programme. Method: PubMed and Medline were searched using phrases such as вЂ�вЂ�Guillain-Barre syndrome AND influenza vaccineвЂ™вЂ™ or вЂ�вЂ�1976 swine flu AND Guillain-Barre syndromeвЂ™вЂ™. Current and past literature obtained in this way was reviewed and formed the basis for my research. Conclusion: 5 out of 9 of the Bradford-Hill criteria were satisfied. Thus, there is some, but not overwhelming evidence to support a causal relationship. Using present literature it is not possible to reach a definite conclusion. However, there is enough evidence to suggest caution in future mass vaccination programmes. 1.Bradford-Hill A. The environment and disease: Association or causation? Meeting of section of occupational medicine; 1965; 7; 295-300 Study supported by: None 150 ID: guganp I Black Lining: [ON] I Time: 09:25 I Path: N:/3b2/ANA#/Vol00000/120255/APPFile/JW-ANA#120255 J_ID: ZAY Customer A_ID: BKLT2012_Abstracts Cadmus Art: ANA12 Date: 18-September-12 T1838. Leveraging Electronic Health Records for Studying Multiple Sclerosis Zongqi Xia, Tianxi Cai, Suchun Cheng, Raul N.G. Perez, Vivian S. Gainer, Shwan N. Murphy, Pei J. Chen, Guergana K. Savova, Katherine P. Liao, Elizabeth W. Karlson, Ashwin N. Ananthakrishnan, Peter Szolovitis, Susanne E. Churchill, Issac S. Kohane, Robert M. Plenge and Philip L. De Jager; Boston, MA; Cambridge, MA and Charlestown, MA Stage: Page: 151 PR3-ANCA. Serum IgG4 was increased in 7/26 cases measured. The most frequent cause of secondary HP was ANCA-associated vasculitis/Wegener granulomatosis (59.3%). The most frequent initial symptoms were headache (33.4%) and visual disturbance (11.9%), with headache and cranial nerve involvement present in 70.8% and 61.8% of cases during the entire course. Interpretation: ANCA-associated HP is the most common type of HP observed in Japan. Study supported by: This work was supported in part by a Health and Labour Sciences Research Grant on Intractable Diseases (H23- Nanchi-Ippan-086) from the Ministry of Health, Labour, nd Welfare, Japan Electronic Health Records (EHR)-derived virtual cohorts complement conventional cohort studies. We developed an EHR algorithm to identify patients with multiple sclerosis (MS). We built a вЂ�вЂ�data-martвЂ™вЂ™ that includes the complete medical records of 193,895 patients from Partners HealthCare who either underwent a magnetic resonance imaging study (brain, cervical spine) or had a related ICD9 code for MS. The mart contains codified and narrative data extracted using natural language processing. We randomly selected 595 subjects to develop a training set where MS diagnosis was established by neurologist chart review. The LASSO logistic regression model was developed on the training set and selected informative variables for the MS algorithm, which was then applied to the entire mart. The algorithm yielded AUC Вј 0.962, sensitivity Вј 83%, PPV Вј 92% and NPV Вј 89% with specificity set at 95%. In total, the algorithm captures 5,537 MS patients, including 86% of the 1,341 subjects from a gold-standard MS cohort. We are testing the portability of the MS algorithm in other EHR systems and leveraging the EHR-derived MS cohort to study predictors of conversion from the presymptomatic phase to clinical MS, disease activity in MS, and response to disease-modifying therapy. Study supported by: National Institutes of Health Office of the Director, National Library of Medicine and the National Institute of General Medical Sciences (2U54LM008748) T1840. Caspr2 Autoantibodies Target CNS and PNS Axons Eric Lancaster, Josep Dalmau and Steven S. Scherer; Philadelphia, PA and Barcelona, Spain Background: Caspr2 is an axonal protein that localizes voltage gated potassium channels (VGKC) to the juxtaparanodes of myelinated axons. A subset of patients with antibodies to the VGKC complex, Caspr2 is the actual antigen. Caspr2 autoantibodies are associated with acquired peripheral nerve hyperexcitability (IsaacsвЂ™ syndrome) and/or encephalitis. The mechanisms by which Caspr2 antibodies cause disease are unknown. Methods: Peripheral and central nervous system tissues were immunolabeled with patientsвЂ™ Caspr2 antibodies. Results: Caspr2 is expressed in the soma and dendrites of CNS neurons, but surface Caspr2 is expressed only on axons. Accordingly, Caspr2 autoantibodies labeled the axons, but not soma or dendrites, of cultured hippocampal neurons. This labeling did not co-localize with a synaptic marker (Bassoon). In brain slices, stained was observed predominantly in white matter tracts, specifically on the juxtaparanodes of myelinated axons. In the PNS, Caspr2 antibodies labeled the juxtaparanodes of axons of sciatic nerve fibers, and spinal nerve roots, as well as the somata of dorsal root ganglia neurons. Conclusions: While other antibodies to cell surface proteins (e.g. the NMDA receptor) target synapses, Caspr2 antibodies predominately target CNS and PNS axons. Study supported by: This work is supported in part by grants from the National Institutes of Health RO1NS077851, RO1MH094741, and the National Cancer Institute RO1CA089054 (JD); and FundacioВґ la MaratoВґ TV3 and Fondo de Investigaciones Sanitarias (FIS, PI11/ 01780) (JD); and grants from the National Organization for Rare Disorders (EL), NINDS (EL) and the Dana Foundation (EL). Dr. Dalmau has received a research grant from Euroimmun, and receives royalties from patents for the use of Ma2 and NMDAR as autoantibody test. Dr. Dalmau has received a research grant from Euroimmun, and receives royalties from patents for the use of Ma2 and NMDAR as autoantibody test. T1839. The First Nationwide Survey of Hypertrophic Pachymeningitis in Japan Tomomi Yonekawa, Katsuhisa Masaki, Takuya Matsushita, Shinya Sato and Jun-ichi Kira; Fukuoka, Japan Objective: To clarify clinico-epidemiological features of hypertrophic pachymeningitis (HP) in Japan through the first nationwide survey of this disease. Methods: Cases with HP diagnosed from January 1, 2005 through December 31, 2011 were collected nationwide. We excluded HP cases associated with malignancy and those with intracranial hypotension. Results: A preliminary survey reported 330 HP cases (34.8% response rate), with detailed data collated for 184 of these cases. The prevalence of HP was 0.282 per 100,000 people, with a male to female ratio of 1.2:1. Mean age of onset was 58.6615.7 years. Of the 184 detailed cases, 152 had cranial HP, 11 had spinal HP, 9 had both. Idiopathic HP was seen in 103 cases, secondary HP in 67 cases. 45 cases of 117 examined were positive for MPO-ANCA or 151 ID: guganp I Black Lining: [ON] I Time: 09:25 I Path: N:/3b2/ANA#/Vol00000/120255/APPFile/JW-ANA#120255 J_ID: ZAY Customer A_ID: BKLT2012_WIP_Abstracts Cadmus Art: ANA13 Date: 18-September-12 2012 Annual Meeting Works in Progress Poster Session Abstracts Stage: Page: 152 criteria were finally enrolled in this study. The diagnosis of fatty liver was made based on the findings of liver ultrasound, while the presence of ICAD was decided according to the interpretation of MRA data. Results: Of 6146 participants, the prevalence of NAFLD and ICAD was 46.4% (nВј2853)and 4.6% (nВј282), respectively. After the adjustment for atherosclerosis risk factors, NAFLD was independently associated with increased risk of ICAD (OR: 1.89, 95% CI: 1.45-2.46). In addition, NAFLD was still associated with increased risk of ICAD in another multiple regression model adjusting for metabolic syndrome and other risk factors (OR: 1.91, 95% CI: 1.462.50). Conclusions: The present study suggested that the detection of NAFLD was independently associated with the increased risk for ICAD among asymptomatic Korean. Posters will be displayed in Arlington, located on the 3rd floor in the Back Bay Hall of the Marriott Copley Place from 11:30 am вЂ“ 7:00 pm. Authors will be present during the following times: WIP100-WIP1001: Sunday, October 7, 5:30 вЂ“ 7:00 pm WIP1100-WIP1409: Monday, October 8, 5:30 вЂ“ 6:30 pm WIP1500-WIP1804: Tuesday, October 9, 5:30 вЂ“ 7:00 pm The Works in Progress category emphasizes ongoing clinical or basic research of an extraordinary nature, which warrants expediated presentation. These abstracts were selected based on scientific merit, timeliness, and anticipated interest to the membership. Key aspects of research must have been conducted after the regular abstract deadline. NOTE: Two asterisks designates an abstract selected for oral presentation in the Derek Denny-Brown New Member Symposium. WIP103. Hydrogen Sulfide Increases Angiogenesis and Improves Functional Outcome after Stroke Mi-Young Oh, Hyunduk Jang, Wi-Sun Ryu, Seung-Hoon Lee and Byung-Woo Yoon; Seoul, Korea Objective: Hydrogen Sulfide is a potent inducer of angiogenesis. In this study, we investigate whether NaHS (H2S donor) induces angiogenesis and thereby improves functional outcome in rat cerebral ischemic/reperfusion model. Methods: Adult male rats were subjected to middle cerebral artery occlusion and were treated with 5mg/kg of NaHS or normal saline starting 48 hours after middle cerebral artery occlusion and daily for 14 days. Neurological functional tests were performed. The volume of von willebrand factor(vWF)- positive area was measured. Newly proliferated vascular endothelial cell were counted. Angiogenic factor expressions were measured by immunohistochemistry and western blot. In vitro, endothelial tube formation was examined. Results: NaHS significantly promoted vWF-positive area (30.16% vs. vehicle, 12.3 %, p<0.01) and proliferation of vascular endothelial cell (7.3/2*105 um2 vs. vehicle, 3.1/ 2*105um2, p<0.01) in the ischemic brain. and improved functional outcome after stroke. Mechanisms underlying the NaHS-induced vascular remodeling were investigated. NaHS increased the expression of vascular endothelial growth factor (VEGF), angiopoietin-1 (Ang1), angiopoietin2(Ang-2) and phosphorylation of Akt, and ERK-1/2. Conclusion: NaHS promoted angiogenesis, which may contribute to improvement of functional outcome after stroke. The VEGF/VEGF receptor, phosphoinositide 3-kinase/Akt, and ERK-1/2 pathways appear to mediate NaHSinduced angiogenesis. Behavioral Neurology WIP101. The Detrimental Effect of Aging on Leptomeningeal Collaterals in Ischemic Stroke Atay Vural, Murat E. Arsava, Erhan Akpinar, Rahsan Gocmen, Seray Akcalar, Kader K. Oguz and Akif M. Topcuoglu; Ankara, Turkey Background and Purpose: Aging is associated with decreased penumbral salvage in patients with ischemic stroke. Another critical factor that determines the fate of penumbra tissue is the degree of collateral circulation, which decreases significantly with aging in experimental models of stroke. In this study we sought to identify whether these observations could be translated to humans. Methods: Computed tomography angiography (CTA) source images were used to assess the degree of collateral circulation in a retrospective series of patients with proximal middle cerebral artery occlusion. Bivariate and multivariate analyses were used to explore the relationship between patient age and degree of collateral irculation. Results: A total of 70 patients were included into the study. Older age (pВј0.005), history of hypertension (pВј0.036), higher admission NIHSS scores (pВј0.013) and increased time to CTA (pВј0.013) were associated with inadequate collaterals in bivariate analyses. In multivariate analysis, older age (pВј0.008) and higher NIHSS scores (pВј0.032) remained as the only significant independent variables that were associated with inadequate collaterals. A 10-year increment in patient age increased the odds of inadequate collateral circulation by 1.87 (95% CI, 1.18-2.97). Conclusions: Our findings show that there is a significant interplay between patient age and adequacy of leptomeningeal collateral circulation in patients with proximal middle cerebral artery occlusion. WIP104. Retinal Microvascular Abnormalities Predict Brain Microvascular Disease Progression: An ARIC Study Thomas C. Hanff, A. Richey Sharrett, Tom H. Mosley, Dean Shibata, David S. Knopman, Ronald Klein, Barbara Klein and Rebecca F. Gottesman; Baltimore, MD; Jackson, MS; Seattle, WA; Rochester, MN and Madison, WI WIP102. The Association between Non-Alcoholic Fatty Liver Disease and Intracranial Atherosclerotic Disease Hyun-Suk Jung, Byung-Su Kim and Yoon Ho Choi; Seoul, Republic of Korea Background: Brain microvascular disease (BMVD) exists for years before visible on MRI. Retinal microvascular changes may be an even earlier marker of BMVD. We tested this association by 1)using a continuous measure of white matter hyperintensity progression (WMP) and 2)combining WMP and lacunar infarcts into one comprehensive measure of brain microvascular disease. Methods: Participants underwent initial brain MRIs and retinal photography, and 10 year follow-up brain MRIs. Background: The purpose of this study is to examine an association between non-alcoholic fatty liver disease (NAFLD) and intracranial atherosclerotic disease (ICAD). Methods: From January 2008 to December 2010, 6146 asymptomatic study participants met full study inclusion 152 ID: guganp I Black Lining: [ON] I Time: 09:31 I Path: N:/3b2/ANA#/Vol00000/120256/APPFile/JW-ANA#120256 J_ID: ZAY Customer A_ID: BKLT2012_WIP_Abstracts Cadmus Art: ANA13 Date: 18-September-12 Stage: Page: 153 Retinal microvascular changes (e.g., retinopathy and arteriovenous nicking), were evaluated relative to: 1)volume of WMP (change in leukoaraiosis volume) and 2)global microvascular disease (lacunes on follow-up MRI Гѕ WMP). Results were adjusted for vascular risk factors including blood pressure and diabetes. Results: Any retinopathy was associated with 3.06 cc (95% CI 0.39-5.73) more WMP, and arteriovenous nicking was independently associated with 2.98 cc (95% CI 1.134.81) more WMP. Furthermore, combining lacunar infarcts and WMP yielded associations between brain and retinal changes that were stronger than has been previously reported. Discussion: This combined brain vascular score may be useful in efforts to identify early markers of BMVD. graphics, vascular risk factors, comorbidities, trauma severity and trauma mechanism compared to controls. Results: The cohort included a total of 1,173,431 subjects (436,541 TBI), with a mean age of 49.9. Recurrent stroke was identified in 1.1% of the TBI group and 0.9% of the non-TBI trauma group in 2.4 years of mean followup. After adjustment, TBI was independently associated with ischemic stroke (hazard ratio 1.34, 95% CI 1.28-1.39). Conclusions: TBI is associated with ischemic stroke, independently of other major predictors. Study supported by: Dr. Burke is supported by a VA advanced fellowship. WIP105. Racial and Ethnic Differences in Post-Stroke Depression among Community Dwelling Adults Lesli Skolarus, Lynda Lisabeth, Lewis Morgenstern, Deborah Levine and Devin Brown; Ann Arbor WIP201. The Association of Non-Clinical Factors with Head CT Use in Emergency Department Dizziness Visits: A Population-Based Study Kevin A. Kerber, James F. Burke, Lesli E. Skolarus, Brian C. Callaghan, Devin L. Brown, William J. Meurer, Lynda D. Lisabeth, A. Mark Fendrick and Lewis B. Morgenstern; Ann Arbor, MI Education Background: African Americans (AAs) and Hispanics have a higher incidence of stroke than non-Hispanic whites (NHWs). Post-stroke depression (PSD) is associated with greater disability and mortality. We sought to explore racial and ethnic differences in PSD. Methods: National Health Interview Survey (NHIS) data from 2000-2010 were used to identify 8,413 community dwelling adults with self-reported stroke. Depression was identified by the Kessler-6 scale using a standard cut-off of !13. Logistic regression was used to assess racial/ethnic associations with PSD after adjusting for demographics, comorbidities, disability, socioeconomic status (education, insurance) and US nativity. Results: Overall, 9% had PSD. Hispanics (14%) were more likely to have PSD than AAs (9%) and NHWs (9%, p<0.01). After full adjustment, AAs were less likely (ORВј0.76, 95% CI 0.65-0.89) while Hispanics were equally likely to have PSD compared with NHWs (ORВј1.05, 95% CI 0.83-1.33). Age and socioeconomic factors were confounders of the race/ethnicity-PSD association for both AAs and Hispanics. Discussion: Among US stroke survivors, Hispanics had more PSD than NHWs. This ethnic association was driven by age and socioeconomic status suggesting that younger, more disadvantaged Hispanics may be an important target for PSD intervention efforts. Study supported by: NINDS K23 NS073685 Efforts to optimize HCT utilization in emergency department dizziness (ED) visits require understanding the factors that contribute to their use. From a population-based study of dizziness, we aimed to explore associations of non-clinical factors with HCT use. From May 8, 2011 to May 7, 2012, adult patients who presented to EDs in Corpus Christi, Texas, with dizziness, vertigo, or imbalance as a reason for the visit were identified. Clinical and non-clinical information was abstracted from source documents. Adjusting for clinical factors, a hierarchical logistic regression model with provider as a random effect was used to explore the associations of nonclinical factors with use of a head CT. To date, 1,126 visits meeting the study criteria have been abstracted. A HCT was performed in 44.4%. In the hierarchical model (c-statistic, 0.80), significant non-clinical factors included having insurance (OR, 2.2; 95%CI, 1.4-3.4), physician use of a documentation template having a preprinted HCT item (OR 2.4, 95%CI, 1.6-3.6), and provider (intraclass correlation coefficient, 0.07). This ongoing work suggests that non-clinical factors likely have an important role in the use of a HCT in ED dizziness presentations. Study supported by: NIH K23 RR024009. WIP106. Association between TBI and Ischemic Stroke James F. Burke, Jessica L. Stulc, Lesli E. Skolarus, Darin B. Zahuranec and Lewis B. Morgenstern; Ann Arbor, MI WIP202. Quantifying Neurologist Outpatient Test Utilization and Costs James F. Burke, Brian Callaghan, Lesli E. Skolarus and Kevin A. Kerber; Ann Arbor, MI Introduction: A substantial proportion of stroke in the young is unexplained. We explored whether traumatic brain injury (TBI) is a risk factor for subsequent ischemic stroke given that TBI causes vascular changes that augment thrombosis and diffuse hypercoagulability. Methods: Patients with any emergency department visit or hospitalization for TBI (exposed group) or non-TBI related trauma (control) based on statewide emergency department and inpatient databases in California from 2005-2009 were included in a retrospective cohort. TBI was defined using the Center for Disease Control definition. Our primary outcome was subsequent hospitalization for ischemic stroke (ICD-9-CM 433.x1, 434.x1, 436). The association between TBI and stroke was estimated using Cox proportional hazards modeling adjusting for demo- Introduction: Specialty societies are collaborating to limit healthcare expenditures by identifying overutilized services. To inform this process for neurology, we are quantifying utilization and aggregate cost of tests ordered by neurologists. Methods: Serial cross sectional study of the 2009 National Ambulatory Medical Care Survey вЂ“ a nationally representative survey of ambulatory medical care services. Utilization of imaging, lab and electrophysiological tests by neurologists was tabulated across all visits and the visit ICD-9-CM codes were aggregated across primary neurological subspecialties. Costs of care were estimated using average Medicare payments. Results: In 2009, there were an estimated 14,800,000 neurologist visits, resulting in 2,170,000 MRIs, 1,100,000 153 ID: guganp I Black Lining: [ON] I Time: 09:31 I Path: N:/3b2/ANA#/Vol00000/120256/APPFile/JW-ANA#120256 J_ID: ZAY Customer A_ID: BKLT2012_WIP_Abstracts Cadmus Art: ANA13 Date: 18-September-12 EMGs, 570,000 EEGs and 460,000 PSGs. The mean cost of diagnostic tests ordered per visit is $212 (95% CI $177$247). MRI and EMG were the two largest cost centers, accounting for 53% and 32% of total estimated costs. The largest number of MRIs were performed for headache and neuromuscular disorders, while EMG was used most for neuromuscular disorders and pain complaints. Conclusions: MRI and EMG are the largest contributors to diagnostic test costs attributable to neurologists in the outpatient setting. These tests should be carefully scrutinized in efforts to identify overutilization. Study supported by: Dr. Burke is supported by a VA advanced fellowship. Stage: Page: 154 neurofibromas are near-universal in NF1, but tumor-burden can vary greatly. We tested the hypothesis that there are single nucleotide polymorphisms (SNPвЂ™s) or copy number variants (CNVвЂ™s) associated with extremes of cutaneous tumor-burden. Threehundred NF1-subjects were identified for the top or bottom 15% of cutaneous tumor-burden. Subjects were genotyped using the Affymetrix Genome-Wide Human SNP array 6.0, containing 909,622 markers and >946,000 CNV probes. The association analysis shows several SNPвЂ™s with p-values near genome-wide significance. The CNV investigations reveal three deletions in high tumor-burden cases in a region encompassing a gene that may play a role in cell division and growth regulation. We will identify novel genetic variants impacting cutaneous tumor-burden in NF1 by whole-exome-sequencing of those subjects with high and low cutaneous tumor burden. We will test whether each variant identified has an impact on severity of disease by analyzing each SNP for association to the severity of cutaneous tumor-burden. Further processing of variants in whole-exome-sequencing will follow our informatics pipeline to identify potential common or rare modifying variants. Study supported by: Departmental NF-Midwest NF-Northeast K12 CA090354 Training Grant PI: Tracy Batchelor, M.D. Harvard Medical School Center for Neurofibromatosis and Allied Disorders (CNfAD). Neuro-oncology WIP301. Malignant Glioma Genotyping by CSF 2-Hydroxyglutarate Oncometabolite and IDH1 Mutation Analysis Leonora Balaj, Edwin Lok, Kenneth D. Swanson, John M. Asara, Clark C. Chen, Fred Hochberg, Xandra O. Breakefield and Eric T. Wong; Boston, MA and San Diego, CA IDH1 mutation in gliomas results in a gain-of-function for the isocitrate dehydrogenase enzyme causing markedly increased kinetics of NADPH-dependent reduction of a-ketoglutarate to 2-hydroxyglutarate. Glioma cells also secrete small membrane vesicles termed exosomes and exosomederived nucleic acids can be utilized for the detection of tumor-specific biomarker such as the G395A mutation in the IDH1 mRNA. We report a 42-year-old patient with biopsyproven low-grade fibrillary astrocytoma located in left insula, which had 1p and 19q deletions. The tumor had a partial response to neoadjuvant temozolomide lasting 2 years but later progressed and was treated with temozolomide chemoirradiation. CSF was collected at the time of disease progression. Targeted mass spectrometry (LC-MS/MS) detected at least a 4-fold increase in the oncometabolite 2-hydroxyglutarate compared to 10 control samples obtained from patients without malignancy. Exosomes were isolated from the CSF by high-speed centrifugation and highly sensitive BEAMingqRT-PCR detected the G395A mutation commonly found in IDH1-mutated tumors. This is the first documentation of oncometabolite accompanied by the identification of the IDH1 G395A genotype in patient CSF. CSF oncometabolite profiling and IDH1 genotyping of malignant gliomas could potentially facilitate their timely diagnosis and treatment. Study supported by: A Reason To Ride research fund Xandra O Breakefield serves on the Scientific Advisory Board for Exosome Diagnostics, Inc. Leonora Balaj, Edwin Lok, Kenneth D Swanson, John M Asara, Clark C Chen, Fred Hochberg, and Eric T Wong have no conflict of interest. Neurogenetics WIP501. Dark Xavier, Zebrafish Model of MADD Seok-Hyung Kim, Robert Carson, Michael J. Bennett, Sarah A. Scott, H. Alex Brown and Kevin C. Ess; Nashville, TN and Philadelphia, TN Multiple acyl-CoA dehydrogenase deficiency (MADD) is a genetic disease caused by mutations in electron transfer flavoprotein complex (ETFA/ETFB) or ETF dehydrogenase (ETFDH). Impairment of these genes impairs mitochondrial function resulting in accumulation of acyl-CoA esters. Patients with MADD are classified as Type I (neonatal-onset, congenital abnormalities), Type II (neonatal onset without congenital abnormities) and Type III (milder symptoms). Severe neurological manifestations are seen including encephalopathy and leukodystrophy as well as hypoglycemia, metabolic acidosis, heart disease and hepatomegaly. There are no animal models of MADD that recapitulate the clinical spectrum seen in MADD. Using forward genetics, we identified mutant zebrafish with a fatty liver phenotype. These zebrafish (dark xavier, dxa) have a nonsense mutation in Etfa. Homozygous dxa zebrafish have abnormalities of brain, liver, kidneys and heart. Marked accumulation of lipids, acyl-esters and cholesterol in multiple organs was seen. Brain abnormalities include hypomyelination and increased numbers of neural progenitor cells. Interestingly, dxa mutants had increased cell size in multiple organs. This suggests activation of target of rapamycin complex 1 (TORC1) signaling, this was confirmed using biochemical assays. Dxa zebrafish will be invaluable for future in vivo chemical screens to identify therapeutic compounds efficacious for MADD. Study supported by: Dept. of Defense Grant TS093052 WIP302. Genetic Modifiers Affecting Neurofibromatosis (GMAN): Cutaneous Tumor Burden in Neurofibromatosis Type 1 Fawn Leigh, Lan Kluwe, Victor Mautner, Douglas R. Stewart, Conxi Lazaro, Neale Benjamin, Bergen Sarah, Scott R. Plotkin, Alexander Pemov, Jennifer Sloan, Lee Kaplan, Maragaret P. Wallace, Meena Upadhyaya, Ludwine Messiaen, Bruce Korf, Andre Bernards and James Gusella; Boston, IL; Hamburg, Germany; Rockville, MD; Barcelona, Spain; Gainesville, FL; Birmingham, AL and Cardiff, United Kingdom Neurofibromatosis type 1 (NF1) is the most common neuro-cutaneous syndrome, affecting 1 in 3,000. Cutaneous 154 ID: guganp I Black Lining: [ON] I Time: 09:31 I Path: N:/3b2/ANA#/Vol00000/120256/APPFile/JW-ANA#120256 J_ID: ZAY Customer A_ID: BKLT2012_WIP_Abstracts Cadmus Art: ANA13 Date: 18-September-12 WIP502. Driving Selection Against Heteroplasmic Mitochondrial DNA Mutations by Rapamycin Ying Dai, Kangni Zheng, Joanne Clark, Russell H. Swerdlow, Stefan M. Pulst, James P. Sutton, Leslie A. Shinobu and David K. Simon; Boston, MA; Kansas City, KS; Salt Lake City, UT; Oxnard, CA and Fujisawa, Kanagawa, Japan Stage: Page: 155 UDRS scores suggests a possible clinical application. Work is ongoing to correlate results to neuropathology. Study supported by: PFC is an Honorary Consultant Neurologist at Newcastle upon Tyne Foundation Hospitals NHS Trust, is a Wellcome Trust Senior Fellow in Clinical Science (084980/Z/08/Z), and a UK NIHR Senior Investigator. PFC receives additional support from the Wellcome Trust Centre for Mitochondrial Research (096919Z/11/Z), the Medical Research Council (UK) Centre for Translational Muscle Disease research, the Association FrancВёaise contre les Myopathies, EU FP7 TIRCON, and the UK NIHR Biomedical Research Centre for Ageing and Age-related disease award to the Newcastle upon Tyne Foundation Hospitals NHS Trust. Mitochondrial DNA (mtDNA) mutations cause a variety of mitochondrial diseases, and may contribute to aging and neurodegenerative disorders, but there are no effective treatments to counteract the effects of these mutations. Selective degradation of dysfunctional mitochondria through autophagy (mitophagy) plays a critical role in mitochondrial quality control. Rapamycin activates mitophagy by inhibiting mTOR kinase activity. We hypothesized that enhancing mitopahgy would cause the preferential degradation of mitochondria harboring relatively greater levels of mtDNA mutations, thereby driving mutation levels lower over time. We examined the effect of rapamycin on mtDNA mutation levels in human cybrid cell lines carrying a heteroplasmic mtDNA G11778A mutation, the most common cause of LeberвЂ™s hereditary optic neuropathy (LHON). We confirm that chronic rapamycin inhibits mTOR kinase and induces mitophagy, as indicated by colocalization of LC3 positive autophagosomes with mitochondria. This is accompanied by a striking progressive reduction in G11778A mutation levels. The decreased mutational burden is not due to rapamycin-induced cell death, as there is no significant difference in cytotoxicity between rapamycin and vehicle-treated cells. These data suggest that pharmacological induction of mitophagy may have therapeutic potential for the treatment of disorders associated with heteroplasmic mtDNA mutations. Study supported by: This work was supported by the National Institute of Neurological Disorders and Stroke (1R21NS077758; DKS) and the United Mitochondrial Disease Foundation (UMDF11-095; YD). WIP504. Early Neuropsychiatry Features in Neuroferritinopathy Michael J. Keogh, Baldev Singh and Patrick F. Chinnery; Newcastle upon Tyne, Tyne and Wear, United Kingdom Introduction: Neuroferritinopathy is an autosomal dominant movement disorder caused by iron accumulation within the basal ganglia. Early clinical descriptions stressed the absence of neuropsychiatric features until the very late phase, distinguishing the disorder from HuntingtonвЂ™s disease. However, these anecdotal reports have not been substantiated. Methods: Systematic review of 22 neuroferritinopathy patients. Results: 45% (nВј10) had objective measures of an abnormality on AddenbrookeвЂ™s Cognitive Examination (ACER) or neuropsychometric testing. The mean age of onset for neuropsychiatric features was 48.6 years old (sdВј10.3 years), 4.2 years (sdВј3.9 years) after the development of motor symptoms. Mean ACE scores were 74.7 (sd Вј 7.3), with verbal fluency particularly affected. Neuropsychiatric abnormalities were present in 6 patients (60%) at the time of presentation with a movement disorder. During follow up, two patients required anti-psychotic medication and psychiatric institutional care. Significant clinical heterogeneity was noted. Discussion: Contrary to previous reports, neuropsychiatric symptoms are often present on clinical presentation, and usually develop within 5 years of onset. Although there is marked clinical heterogeneity, defects of verbal fluency are most common. These findings redefine the phenotype of neuroferritinopathy. The absence of neuropsychiatric features is not a reliable feature discriminating the disease from other inherited movement disorders. WIP503. Voxel Based Morphometry and Voxel Based Relaxometry in Neuroferritinopathy Michael J. Keogh, Andrew M. Blamire and Patrick F. Chinnery; Newcastle upon Tyne, Tyne and Wear, United Kingdom Neuroferritinopathy is an autosomal dominant movement disorder resulting in iron deposition in the basal ganglia which is visible on MRI imaging. However, MRI changes correlate poorly with clinical features, and the extent of tissue abnormalities outside the basal ganglia is poorly defined. Voxel based morphometry (VBM) and relaxometry (VBR) are quantitative MRI techniques which can assess brain morphology and suggest regional tissue anomalies respectively; they have never been applied in a large cohort of patients with any neurodegeneration with brain iron (NBIA) disorder. Methods: VBM and VBR analysis of 10 patients with neuroferritinopathy were compared with clinical rating scales and age matched controls. Results: VBM detected extensive signal alteration in the basal ganglia, cerebellum, motor cortex and brain stem (threshold p<0.001, uncorrected) compared to controls. Unified Dystonia Rating Scale scores correlated with VBM signal in the caudate, lentiform and globus pallidus. T1 and T2 VBR changes were seen in the cerebellum, brainstem and several deep cortical regions. Conclusions: VBM and VBR suggest that anatomical and tissue abnormalities outside the basal ganglia may be present in neuroferritinopathy. VBM correlation with Pediatric Neurology WIP801. Anti-NMDA Receptor Encephalitis, a Series of 208 Children Maarten J. Titulaer**, Lindsey McCracken, Thais Armangue, Inigo Gabilondo, Eugenia Martinez-Hernandez, Takahiro Iizuka, Lawrence S. Honig, Susanne Benseler, Myrna R. Rosenfeld, Rita Balice-Gordon, Francesc Graus, Carol Glaser and Josep Dalmau; Barcelona, Spain; Philadelphia, PA; Sagamihara, Japan; New York, NY; Toronto, Canada and Richmond, CA Objective: To report the syndrome and suggest treatment guidelines for this disorder. Methods: Cohort study, analysis of symptoms, treatment, and long-term follow-up (24 months). 155 ID: guganp I Black Lining: [ON] I Time: 09:31 I Path: N:/3b2/ANA#/Vol00000/120256/APPFile/JW-ANA#120256 J_ID: ZAY Customer A_ID: BKLT2012_WIP_Abstracts Cadmus Art: ANA13 Date: 18-September-12 Results: 73% were girls. 42% of girls !12 years had ovarian teratoma(s) versus 6% <12; 0% in boys. In patients <12, initial symptoms were seizures, abnormal behavior, and movement disorders (36%-33%-14%), while in patients !12 were abnormal behavior and seizures (57%-23%). Within one month, the syndrome was similar to that reported in adults, although with less frequent autonomic/ breathing dysfunction. Immunotherapy (94%) and tumor removal (when appropriate) resulted in full/good recovery in 79% of the patients; 3% died. Early treatment and no ICU admission associated with better outcome (pВј0.018 and p<0.0005). 52% responded to steroids, IVIg and/or plasmapheresis, 100% with good outcome. If these treatments failed (48%), rituximab/cyclophosphamide (second-line therapy) improved outcome (79% vs 67% without secondline therapy). Relapses occurred in 15%. Conclusions: Pediatric and adult phenotypes of antiNMDAR encephalitis are similar, but tumor association, symptom onset and frequency of some symptoms vary. Prompt treatment improves outcome. If initial immunotherapy fails, second-line treatment is usually effective. 79% of children have good outcome although complete recovery can take >24 months. Study supported by: The current work is supported in part by a KWF fellowship 2009-4451 of the Dutch Cancer Society (MT), the National Institutes of Health RO1NS077851 (JD), RO1MH094741 (RB-G and JD), FundacioВґ la MaratoВґ TV3 (JD), Fondo de Investigaciones Sanitarias (FIS, PI11/01780 to JD, FI08/00285 to EMH, and PS09/0193 to FG), and a McKnight Neuroscience of Brain Disorders award (RB-G and JD). Dr. Dalmau receives royalties from the editorial board of Up-To-Date; from Athena Diagnostics for a patent for the use of Ma2 as autoantibody test. Dr. Dalmau holds a patent application for the use of NMDA receptor as autoantibody test. Dr. Dalmau has received a research grant from Euroimmun. Stage: Page: 156 Trauma/Injury WIP1001. Predicting Return to FunctionalIndependence by 12-15 Months after Severe Traumatic Brain Injury on Discharge from Inpatient-Rehabilitation David S. Kushner, Jasmine Martinez-Barrizonte and Myrlynn Delille; Miami, FL Inpatient rehabilitation (IR) case series to evaluate usefulness of bowel/bladder continence status and improvement in Functional-Independence-Measure (FIM) cognitive score at discharge in predicting return to functional-independence at 12-15months in 7 patients having severe traumatic brain injury (STBI). Patients had initial emergency department Glasgow Coma Scale scores of 3-6, post-traumatic amnesia durations of 18-115 days, time to follow commands of 16100 days, abnormal initial brain CT scans, and initial pupil abnormalities. IR ranged 20-42 days. Outpatient rehabilitation ranged 20days-8months. IR FIM cognitive and sphincter/(bowel/bladder continence) score improvements were compared to national normative STBI FIM data from Uniform Data Systems for Medical Rehabilitation (UDSMR) for 2010 (nВј15,808). All 7 patients resumed ability to live independently/drive by 12-15 months; 4 are now employed as a physician, accountant, lawyer and a banker. CognitiveFIM scores improved an average of 11 points, compared to 5.9 points for UDSMR. Sphincter-FIM scores improved an average of 6.3 points, compared to 3 points for UDSMR. IR FIM cognitive and sphincter score improvements approximately twice the national average are associated with favorable functional outcomes at 12-15months after STBI. Dementia and Aging WIP1101. Dementia Hospital Length-of-Stay and Cost Leslie S. Wilson; San Francisco, CA AlzheimerвЂ™s prevalence is 5.1 million; expected to double by 2050. Medicare spends $160 billion. Objective: Compare care patterns for hospitalized dementia vs non-dementia patients longitudinally in an integrated healthcare system. Methods: 106,283 hospitalized dementia (predominantly Alzheimers) and matched non-dementia patients from Kaiser Northern California. Analysis was random effects GLS regression. Results: Mean age 77 with 31% dementia vs 10% nondementia patients over 85 years. 82% dementia vs 69% non-dementia hospitalizations were urgent. Dementia diagnosis code was primarily the third listed. Dementia diagnosis is a significant predictor of hospital LOS, increasing stay by 0.46 days (CI:0.5403-0.3831;pВј0.000). Alzheimers diagnosis accounted for less LOS increase than cerebral vascular dementia. Pneumonia was the most frequent DRG diagnosis for dementia and second for non-dementia hospitalizations. Costs for the most frequent principal diagnosis were the same, but for the second most frequent ICD9:599.0 (urinary tract infection), dementia patients stayed 1.57 days longer; costing $1,000 more than non-dementia patients. LOS differences are significantly affected by co-morbidities (pВј0.000). Conclusion: Dementia is a significant predictor of LOS but varies by dementia type. Efficient management of hospitalized dementia patients should focus on selected associated co-morbidities. Study supported by: Elan Pharmaceuticals, now Johnson an Johnson gave an unrestricted grant for this work. WIP802. Tolerability and Efficacy of rTMS in Children with ASD Lindsay M. Oberman, Brittany Irish, Lidya Poni, Alvaro Pascual-Leone and Alexander Rotenberg; Boston, MA Autism spectrum disorders (ASD) are the most prevalent developmental disorder. Current interventions offer moderate success in some individuals, though many continue to have life-long impairments. Specific repetitive transcranial magnetic stimulation (rTMS) protocols have recently been developed and in the case of major depression, FDAapproved, for treatment of multiple neuropsychological disorders. However, since most rTMS studies have focused on adults, the tolerability and efficacy in children is unknown. Previous findings from our lab suggest that applying rTMS to suppress right pars opercularis (increasing excitability in left pars opercularis, a region critical to language and socialskills, through transcollosal connections) leads to improvements in these domains in adults with AspergerвЂ™s Syndrome. We have now extended this study to children with ASD (NВј6 at time of submission) and find that rTMS is both tolerable, with only one minor headache, and potentially effective with three of six children showing improvement in pragmatic language and social-skills on both standardized measures and subjective reports after a single session of rTMS. Future studies should explore rTMS in pediatric disorders as a novel, well-tolerated, nonpharmacologic and potentially efficacious avenue for therapeutic interventions. Study supported by: Harvard Catalyst KL2 mentored award to L.M.O., A.P-L. Mentor. 156 ID: guganp I Black Lining: [ON] I Time: 09:31 I Path: N:/3b2/ANA#/Vol00000/120256/APPFile/JW-ANA#120256 J_ID: ZAY Customer A_ID: BKLT2012_WIP_Abstracts Cadmus Art: ANA13 Date: 18-September-12 WIP1102. The Auditory Event-Related Oscillations Are Diminished, and Correlate with Hippocampal Volumetry in Mild Cognitive Impairment Gorsev G. Yener, Pinar Kurt, Berrin Cavusoglu, Derya D. Emek, Gulsah Aktas, Emel Ada, Bahar Guntekin and Erol Basar; Izmir, Turkey and Istanbul, Turkey Stage: Page: 157 Study supported by: NIH R01 NS052305, and the UNM Clinical Translational Science Center WIP1104. Behavioral Deficits in APP Transgenic Mice Reversed by mGluR Inhibitor with Pro-Neurogenic, Ab-Reducing, and Anxiolytic Properties Sam Gandy, John W. Steele, Star W. Lee, Dane Clemenson, Reto Gadient, Pam Wedel, Charles Glabe, Carrolee Barlow, Michelle Ehrlich, Fred H. Gage and Soong Ho Kim; New York, NY; La Jolla, CA and Irvine, CA Background: Amnestic mild cognitive impairment (MCI) is a pre-dementia stage in majority. Event-related oscillations (ERO) might be used for detection of cognitive deficits. Our group showed decreased delta target ERO in AD previously. We investigated whether the same prevails for MCI, and ERO correlate to brain volumetry. Method: MCI subjects (nВј22) and age-matched healthy controls (HC) (nВј21) were investigated by auditory ERO. The maximum target delta peak-to-peak amplitudes (0.52.2 Hz) were measured in Гѕ300-800 msec. Volumetric measurements of magnetic resonance images were performed using a semi-automatic lesion annotation and volume measurement tool (LAVA, mimlabs) in 11 MCI and 10 HC subjects. Results: The oddball target delta response was 47-62% lower in MCI over fronto-central-parietal regions. Left hippocampal and total brain volumes were lower in MCI. Left hippocampal volume correlated to C3, Tp8 beta; F3 gamma ERO; and right hippocampal volume to C3 beta ERO. Discussion: The auditory target delta ERO are lower in fronto-central-parietal regions as accordant with our earlier findings in AD. Moreover, correlation of ERO to hippocampal volumetry gives a rise the neurophysiological methods to be searched as a potential biomarker in future. Study supported by: Istanbul Kultur University GoВЁrsev G. Yener was in the advisory boards of Lundbeck and Novartis. She received honorarium from Pfizer for speaking activities. One hallmark of AlzheimerвЂ™s disease is accumulation of neurotoxic amyloid beta (Ab) oligomers in the brain. Activation of Group II metabotropic glutamate receptors (Gp II mGlu receptor: mGlu2, mGlu3) triggers release of Ab peptides from isolated synaptic terminals and is selectively suppressed by antagonist pretreatment. We have assessed the therapeutic potential of chronic pharmacological inhibition of Gp II mGluR in APP (AlzheimerвЂ™s amyloid precursor protein) transgenic mice. To achieve inhibition of Gp II mGluR in the brain, orally bioavailable prodrug BCI-838 was used to deliver its active metabolite BCI632. Chronic (3 month) treatment with BCI-838 was associated with reduction in levels of brain Ab monomers and oligomers, correction of transgene-related behavioral deficits, reduction in transgene-related anxiety behavior, and stimulation of hippocampal neurogenesis. Group II mGluR inhibition may offer a unique package of relevant properties as an AD therapeutic by providing acute symptomatic benefit, attenuation of neuropathology, and stimulation of repair. Study supported by: BCI-838 and BCI-631 were provided by BrainCells Inc. Gadient and Wedel are employees of BrainCells Inc. Gage is a founding scientist of BrainCells Inc. WIP1105. Transcranial Magnetic Stimulation of Deep Brain Regions in AlzheimerвЂ™s Disease: A Pilot Study Elissa L. Ash, Veronika Vakhapova, Irena Bova, Ely Simon, Moran Korem, Moran Eldad, Amos D. Korczyn and Avraham Zangen; Tel Aviv, Israel and Beersheva, Israel WIP1103. Biomarkers of Neuroinflammation in Subcortical Ischemic Vascular Disease Gary A. Rosenberg, Yi Yang, Richard R. Reichard, Jillian Prestopnik and John C. Adair; Albuquerque, NM and Albququerque, NM rTMS is a non-invasive technique using magnetic coils to painlessly stimulate brain regions to influence cortical activity. Deep-rTMS allows for stimulation of deeper and wider brain areas, thereby potentially providing more significant effects on brain activity and function. Basic and clinical rTMS studies suggest that stimulation can produce long term changes in cortical synapses akin to LTP and LTD, and might influence neuronal regulation and network patterns, in addition to other, non-neuronal effects. In a placebo-controlled pilot study we evaluated the safety and feasibility of high frequency and low frequency deep-rTMS to the prefrontal areas of AD patients receiving stable doses of accepted AD medications. Results from this feasibility study demonstrate the safety of the method, as well as a trend toward improvement in cognitive and clinical measures in patients treated with high frequency deep-rTMS that lasted through a 2 month, post-treatment phase; this effect was not evident with low frequency stimulation. Given the small sample size, no conclusions can be drawn regarding efficacy. Further studies are warranted. Study supported by: Brainsway Inc. Prof. Avraham Zangen is an inventor of deep TMS coils that have been patented by the NIH and the Weizmann Institute. He serves as a consultant for and has financial interest in Brainsway Inc. that purchased an exclusive license of these patents. Background: Subcortical ischemic vascular disease (SIVD) is a form of vascular cognitive impairment (VCI) secondary to small vessel arteriolosclerosis. Matrix metalloproteinases (MMPs) are increased in cerebrospinal fluid (CSF) and brain tissue in SIVD. We report an association between CSF MMPs and immunohistochemistry. Methods: Four patients in a long-term study of VCI underwent autopsy. They had neurological and neuropsychological testing and MRI. Albumin index, MMP-2, MMP-3, MMP-9, Ab1-42, phospho Tau (P-Tau) and totaltau (T-tau) were measured in CSF. Brain was immunostained for MMPs and co-localized with astrocytes and microglia/macrophages. Results: Histology showed gliosis in white matter in all patients; three had SIVD and one AD. CSF in SIVD patients showed altered levels of MMPs. Ab1-42/1og (PTau) was reduced in AD. SIVD patients had MMP-2 immunostaining in white matter. In AD, gray matter showed MMP-9 and MMP-3. All brains had Iba-1 immunostaining consistent with an inflammatory response. Conclusions: This is the first report to show an association of MMPs in CSF with immunostaining in brain. This small sample suggests inflammation is important in SIVD, and supports further study of MMPs as biomarkers in VCI. 157 ID: guganp I Black Lining: [ON] I Time: 09:31 I Path: N:/3b2/ANA#/Vol00000/120256/APPFile/JW-ANA#120256 J_ID: ZAY Customer A_ID: BKLT2012_WIP_Abstracts Cadmus Art: ANA13 Date: 18-September-12 Stage: Page: 158 Study supported by: Research on Neurodegenerative Diseases/ALS from Ministry of Health, Labor and Welfare, Japan Neuromuscular Disease WIP1401. Non-Human Primate Model of Amyotrophic Lateral Sclerosis with Cytoplasmic Mislocalization of TDP-43 Takuya Ohkubo, Mio Tajiri, Azusa Uchida, Hiroki Kimura, Nobuyuki Sasaguri, Toshiki Uchihara, Hidehiro Misusawa and Takanori Yokota; Tokyo, Japan and Tsukuba, Japan WIP1403. Miller-Fisher Variant of Guillain-Barre: Is Treatment Cost-Effective? Li Yang, Harrison X. Bai, Li-Ming Tan and Bo Xiao; Changsha, Hunan, China and New Haven, CT Objective: The purpose of the study is to determine whether treatment affects the rate and speed of recovery of Miller Fisher Syndrome. Methods: We identified 44 patients diagnosed with MFS from 10/2004-5/2012. Clinical data were collected from charts. Statistical analysis was performed by using StudentвЂ™s t test and chi-square analysis. Results: Median age 47, 66% male, 66% preceded by prodromal symptoms: 55% respiratory, 5% GI. Patients received no treatment (41%), corticosteroids (39%), IVIg (18%) or plasmapheresis (7%). The average follow up period is 38 months. Patients receiving treatment stayed in the hospital longer than those who did not receive treatment (20.0 vs.12.8 d, pВј0.045), but did not have higher rates of resolution in opthalmoplegia (pВј0.192), ataxia (pВј0.608) or areflexia (pВј0.519). There is no significant difference in duration between neurological onset and beginning of recovery of ataxia (18.2 vs.26.2 d, pВј0.33) or opthalmoplegia (19.1 vs.26.1 d, pВј0.43). Conclusions: Immunomodulating treatment slightly hasten the alleviation of ataxia and opthalmoplegia, but does not affect recovery outcome. Considering the side effect of corticosteroids and the high cost of IVIg, their use would not be necessary for patients with MFS since they have a natural good recovery over time. TDP-43 was found to be a major component of abnormal aggregation in the motoneuron in sporadic ALS. We injected an AAV vector expressing human wild-type TDP43 to the spinal cord in non-human primate, cynomolgus.These monkeys developed progressive motor weakness and muscle atrophy. They also showed regional cytoplasmic TDP-43 mislocalization with loss of nuclear TDP-43 staining in the lateral nuclear group of spinal cord and cystatin C-positive cytoplasmic aggregates, reminiscent of the spinal cord pathology of patients with ALS. TDP-43 mislocalization was an early or presymptomatic event and was later associated with neuron loss. These findings suggest that TDP-43 transactive response deoxyribonucleic acid-binding protein 43 mislocalization leads to a-motoneuron degeneration. Furthermore, truncation of TDP-43 was not a prerequisite for motoneuronal degeneration, and phosphorylation of TDP-43 occurred after degeneration had begun. In contrast, similarly prepared rat models expressed TDP-43 only in the nucleus of motoneurons. There is thus a species difference in TDP-43 pathology, and our monkey model recapitulates ALS pathology to a greater extent than rodent models, providing a valuable tool for studying the pathogenesis of sporadic ALS. Furthermore, we discuss the mechanism of propagation of TDP-43 protein. Study supported by: Grants-in-Aid for Scientific Research (A) (#22240039, to T.Y. and H.M.) and Grant-in-Aid for Young Scientists (A) (#24689039 to T.O.) by the Ministry of Education,Culture,Sports,Science and Technology (MEXT), Japan WIP1404. Completion and Outcomes of a Phase 1 Intraspinal Stem Cell Transplantation Trial for ALS Eva L. Feldman, Nicholas M. Boulis, Karl Johe, Seward B. Rutkove, Thais Federici, Meraida Polak, Crystal Kelly and Jonathan D. Glass; Ann Arbor, MI; Atlanta, GA; Rockville, MD and Boston, MA WIP1402. Regional Spread of ALS Lesion вЂ“ Multifocal Hits and Local Propagation? Teruhiko Sekiguchi, Tadashi Kanouchi, Kazumoto Shibuya, Yuichi Noto, Masanori Nakagawa, Satoshi Kuwabara, Hidehiro Mizusawa and Takanori Yokota; Tokyo, Japan; Chiba, Japan and Kyoto, Japan The FDA-approved trial, вЂ�вЂ�A Phase 1, Open-label, First-inhuman, Feasibility and Safety Study of Human Spinal Cord-derived Neural Stem Cell Transplantation for the Treatment of Amyotrophic Lateral Sclerosis, Protocol Number: NS2008-1,вЂ™вЂ™ has been completed in 18 ALS subjects. Cohorts followed a вЂ�вЂ�risk escalationвЂ™вЂ™ paradigm including unilateral (nВј5) or bilateral (nВј10 total) lumbar or cervical injections. The final 3 subjects receiving cervical injections previously received bilateral lumbar injections. All injections delivered 100,000 cells, for a dosing range up to 1.5 million cells. The procedure utilized a novel spinal-mounted stabilization and injection device that includes a floating cannula to prevent spinal cord shearing. The procedure was well-tolerated with minimal perioperative or postoperative complications. Cervical kyphosis developed in one subject following the multi-level laminectomy. Some subjects did not tolerate immunosuppression. Disease progression continued in all but one subject who exhibited clinical and electrophysiological improvements. Four subject deaths have occurred and postmortem analyses are underway. Results demonstrate that intraspinal transplantation of neural progenitor cells in ALS subjects is feasible and well-tolerated, and supports future trial phases examining therapeutic efficacy. Study supported by: Neuralstem, Inc. Rockville, MD. To investigate whether or not the lesions in sporadic ALS spread contiguously from a focal onset site in rostrocaudal direction along the spinal cord, as in the manner hypothesized by a prion-like propagation from single seed. Thirtytwo sporadic ALS patients with initial symptom in the bulbar or upper limb regions were studied. The presence of abnormal spontaneous activities in needle electromyography (nEMG), were compared among the muscles innervated by different spinal segments, especially between T10 and L5 paraspinal muscles and between vastus medialis and biceps femoris. These paired muscles have almost the same axon length and motoneuronal property. Thirteen of 32 patients showed non-contiguous distribution of nEMG abnormality from the onset site. In 8 (61.5%) of the 13 patients, the non-contiguous pattern was also evident between the paired muscles with same motoneuronal vulnerability. The motoneuron pool with skipped nEMG abnormality seemed to form a cluster in the lumbosacral cord in 4 of the 8 patients. In sporadic ALS, involvement of the lower motoneurons cannot be explained by the вЂ�вЂ�single seed and simple propagationвЂ™вЂ™, and we propose a hypothesis, вЂ�вЂ�multifocal hits and local propagationвЂ™вЂ™. 158 ID: guganp I Black Lining: [ON] I Time: 09:31 I Path: N:/3b2/ANA#/Vol00000/120256/APPFile/JW-ANA#120256 J_ID: ZAY Customer A_ID: BKLT2012_WIP_Abstracts Cadmus Art: ANA13 Date: 18-September-12 Dr. Boulis is the inventor of the intraspinal stabilization and injection device. Neuralstem, Inc. has purchased an exclusive license to this technology. Dr. Boulis received an inventors share of this fee, and has the rights to royalty payments for distribution of this technology. Stage: Page: 159 PMP22 may be more common than previously thought in causing CMT1A. Study supported by: Grant from NINDS R01NS066927. WIP1409. Prevalence of Small-Fiber Polyneuropathy in Fibromyalgia Anne Louise Oaklander, Daniela Herzog, Heather Downs and Siena Napoleon; Boston, MA WIP1405. Congenital Myasthenic Syndrome (CMS), Autophagic Myopathy, and Cognitive Dysfunction Caused by Mutations in DPAGT1 Duygu Selcen**, XinMing Shen, Ying Li, Eric Wieben and Andrew G. Engel; Rochester, MN and Rochester Fibromyalgia is a chronic-pain disorder of unknown pathogenesis which currently can only be symptomatically managed. Small-fiber polyneuropathy (SFPN) can have similar symptoms, but objective diagnostic tests, etiologic causes, and some disease-modifying treatments exist for SFPN. This ongoing study tests the hypothesis that some fibromyalgia patients have undiagnosed SFPN. Twelve diagnosed and screened (American College of Rheumatology-2010 criteria) fibromyalgia patients were studied along with 14 normal controls; neuropathy patients were excluded. The consensusrecommended diagnostic tests for SFPN were applied and blindly analyzed; including PGP9.5-immunolabeled distalleg skin biopsy, autonomic-function testing (AFT) (WR Electronics), and the Utah Early Neuropathy Scale. Intraepidermal nerve-fiber densities (IENF) were normalized to values from 240 normal volunteers. Among fibromyalgia subjects IENF averaged 24 6 0.10% of predicted norm vs. 64 6 0.07% among controls (p 0.01). 50% of fibromyalgia vs. 0% of control skin-biopsies were definitively diagnostic (IENF <5th centile). Among fibromyalgia subjects 22% of AFT were diagnostic of SFPN with 67% borderline vs. 0% diagnostic and 38% borderline among controls. UENS scores averaged 4.3 among fibromyalgia subjects vs. 0.4 among controls (p 0.02). Multiple preliminary results suggest that substantial numbers of fibromyalgia patients meet rigorous diagnostic criteria for SFPN. Study supported by: Funded in part by the Public Health Service NIH-K24NS59892 and a charitable donation from Ms. Jane Cheever Powell. We recently identified two CMS patients with CNS involvement. Patient 1 is a16-year-old mentally retarded girl with severe generalized CMS since infancy. One of her siblings is also affected and has autistic features. Patient 2 is a 14-year-old girl with mild cognitive deficits and progressive limb-girdle CMS since infancy. Both respond poorly to anti-AChE therapy. Intercostal muscle specimens in both show small tubular aggregates in type 2 fibers, type1 fiber atrophy, and a vacuolar myopathy with autophagic features. Endplate studies reveal that quantal release, postsynaptic response to acetylcholine quanta, and endplate AChR content are reduced to $50% of normal. Quantitative EM of 65 endplate regions shows hypoplastic endplates, very small nerve terminals, and poorly differentiated postsynaptic regions. Neither patient harbors mutations in currently recognized CMS disease genes but exome sequencing in each identifies two heteroallelic mutations in DPAGT1 coding for dolichyl-phosphate N-acetylglucosamine phosphotransferase, an enzyme subserving protein N-glycosylation. Immunoblots of muscle extracts probed by two different antibodies demonstrates reduced to absent glycosylation of $70 kDa proteins. We hypothesize that hypoglycosylation of synapse-specific proteins causes defects in motor as well as central synapses. Study supported by: NIH Grant NS6277 and a Research Grant from the MDA. WIP1406. Withdrawn. WIP1407. Withdrawn. Behavioral Neurology WIP1408. DNA Replication, but Not Chromosomal Unequal Exchange, as an Alternative Mechanism That Results in CMT1A Mutation Brett A. Parker, Ryan Alexander, Xingyao Wu, Michael Shy, Nathalie Schnetz-Boutaud, Jonathan Haines, Jun Li and Bryan Burnette; Nashville, TN and Iowa City, IA WIP1501. Cognitive Remediation (CR) Combined with Transcranial Magnetic Stimulation (TMS) in AlzheimerвЂ™s Disease (AD) Lukas Schilberg, Anna-Katharine Brem, Catarina Freitas, Natasha Atkinson, Ilya Vidrin, Leonie Asboth, Daniel Z. Press and Alvaro Pascual-Leone; Boston, MA Charcot-Marie-Tooth disease type-1A (CMT1A) is caused by the trisomy of chromosome 17p12 bearing the PMP22 gene. We have identified a CMT1A family with a proband carrying a tetrasomy of the chromosome 17p12, while the probandвЂ™s mother has the classical trisomy and his father has no mutation. Although, the proband has had difficulties in walking since birth, his two siblings with the trisomy of PMP22 are asymptomatic, and his mother only has a mild sensory loss, supporting a gene-dosage effect. By mapping the high-variant SNPs in the chromosome 17p, we showed that the three copies of the PMP22 in the mother and the four copies of PMP22 in the proband were of identical origin. We then expanded this observation in an additional 39 patients with CMT1A. Single origin of the PMP22 was identified in seven of the 39 patients. 32 patients showed different origins of the PMP22 trisomy as predicted by the traditional вЂ�chromosomal unequal exchange mechanismвЂ™. Our results suggest that in addition to the unequal exchange mechanism, DNA replication producing identical copies of Existing AD treatments show limited benefit and have sideeffects. We are evaluating a novel, non-pharmacologic intervention merging TMS with computer-based CR in mild-moderate AD (MMSE 18-26). To date, we have 12 patients randomized to active or sham TMS-CR. Patients undergo 6 weeks of daily one-hour sessions of TMS-CR as adjunct to their stable pharmacologic therapy (5 sessions/ week, total 30 sessions). A short train of repetitive TMS is applied to a given brain region immediately before CR tailored to engage the targeted brain circuit. Six different brain regions engaged in major cognitive functions affected by AD are targeted, as identified using the patientвЂ™s own brain MRI. Relative to baseline, five patients in the active group who have completed the study have improved by 2.9 points on the AlzheimerвЂ™s Disease Assessment Scale (ADAS-Cog), whereas two who have undergone sham worsened by 2.7 points: mean difference in ADAS-Cog between groups of 5.6 points. Importantly, all patients in the active TMS-CR group to date show an improvement, and none in the sham 159 ID: guganp I Black Lining: [ON] I Time: 09:31 I Path: N:/3b2/ANA#/Vol00000/120256/APPFile/JW-ANA#120256 J_ID: ZAY Customer A_ID: BKLT2012_WIP_Abstracts Cadmus Art: ANA13 Date: 18-September-12 Stage: Page: 160 group. These results are extremely promising, and show markedly greater benefits than reported for existing treatments. Study supported by: Harvard Catalyst | The Harvard Clinical and Translational Science Center (National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health Award #UL1 RR 025758); Berenson-Allen Foundation; Neuronix Ltd. Dr. Pascual-Leone serves as scientific advisor of Neuronix globus pallidus and substantia nigra all had significant connectivity changes with the left parietal lobe. The anterior putaminal change in connectivity correlated with the change in UPDRS-III scores (rВј0.5869). Interpretation: The connectivity change between basal gangliar components and the left parietal lobe in this population could reflect the loss of a compensatory mechanism after levodopa administration, or a pathological hypersynchronicity that improved with levodopa. Study supported by: The Paul Ruby Foundation for ParkinsonвЂ™s Research Movement Disorder WIP1703. Distinct Progressive Genotype-Related Neurodegeneration in Spinocerebellar Ataxia Types 1, 3 and 6 вЂ“ A Longitudinal Study Kathrin Reetz, Shahram Mirzazade, Anna Lehmann, Agnes Juzek, Anna Costa, Till K. Hauser, Heike Jacobi, Thomas Klockgether, Jorg B. Schulz and On Behalf of the Ataxia Study Group; Aachen, Germany; TuВЁbingen, Germany and Bonn, Germany WIP1701. A Diagnostic Questionnaire Discriminates between Psychogenic and Neurogenic Movement Disorders David S. Glosser, Nathan A. Taylor, Lori Sheehan, Daniel Kremens and Tsao-Wei Liang; Philadelphia, PA Introduction: We developed a questionnaire that discriminates neurogenic from psychogenic movement disorders (NMD vs. PMD). PMDs are defined as stereotyped behaviors misattributed to a NMD. PMDs can be regarded as distress displays, or escape/avoidance behaviors, and may trigger invasive therapies and disability. PMDs may mimic disorders of gait, tremor, speech, speed, coordination, & their diagnosis is challenging. Methods: Sixty five sequential movement disorder referrals were administered a 15 minute 7-risk factor interview assessing: 1. movement consistency, onset rate, stereotypy 2. hx of psych treatment, self-injury, abuse, drug/ETOH, somatizations/medicolegal. All subjects were independently diagnosed by 2 movement disorders neurologists as NMD (nВј43) vs. PMD (nВј18). Results: Mean # risks of PMD SвЂ™s Вј 7.83; NMD SвЂ™s Вј 4.69, (tВј4.272; pВј.000). Diagnostic sensitivity @ 4 risks Вј 88%; @ 5 risks Вј 55%. Selectivity @ 4 risks Вј 55%; @ 5 risks Вј 91%. Conclusions: The instrument discriminates between NMD & PMD patients. Its use may facilitate early diagnosis and reduce the social and economic costs of the condition as well as medical and psychiatric morbidity. Study supported by: Departmental funds, Thomas Jefferson U. Hospital, DepвЂ™t of Neurology Background: EUROSCA is a multicentric longitudinal cohort study that examines disease progression in Spinocerebellar Ataxias (SCA) SCA1, SCA3 and SCA6. Methods: In the EUROSCA study sites Belgium, France, Germany, Italy, Poland and Spain clinical and magnetic resonance imaging (MRI) data were collected at baseline and after a two-year follow up for a complementary approach of quantitative three-dimensional (3D) volumetry and observer-independent longitudinal voxel-based morphometry (VBM). Results: 37 SCA1, 19 SCA3 and 7 SCA6 patients completed follow-up and were compared to respective agematched healthy control groups. Overall, volumetric data demonstrated an increase of atrophy in the brainstem, cerebellum and basal ganglia in all genotypes over time. Rate of progression was greatest in SCA1 and SCA3 in pons, in SCA1 in cerebellum and in SCA1 and SCA3 in putamen. Compared to healthy controls longitudinal VBM revealed greatest increase in gray matter atrophy in the cerebellum and brainstem in SCA1, in the putamen and pallidum in SCA3 and to a lesser extent also in the cerebellum in SCA6. Discussion: Quantitative volumetry and VBM imaging demonstrated specific SCA genotype-related neurodegenerative longitudinal progression in SCA1, SCA3 and SCA6. Study supported by: Research Grant from the European Commission (6th Framework) WIP1702. Resting State Functional Connectivity Pharmaco-MRI of ParkinsonвЂ™s Disease Peter S. Pressman, Darren R. Gitelman and Tanya Simuni; San Francisco, CA and Chicago, IL WIP1704. Cerebellar Ataxia with Neuronopathy and Bilateral Vestibular Areflexia Syndrome (CANVAS) David J. Szmulewicz, John A. Waterston, Hamish G. MacDougall, Stuart Mossman, Andrew M. Chancellor, Catriona A. McLean, Saumil Merchant, Peter Patrikios, Leslie Roberts, Elsdon Storey and G. Michael Halmagyi; Melbourne, Australia; Sydney, Australia; Wellington, New Zealand; Boston and Brisbane, Australia Objective: Resting state functional connectivity MRI (fcMRI) has demonstrated significant differences between controls and patients with ParkinsonвЂ™s disease (PD). Few studies have investigated the effects of dopaminergic medication on resting state fcMRI in PD. This study investigated how basal gangliar functional connectivity differed on and off levodopa in this population. Methods: Patients arrived off all prescribed medications, and received standardized testing as well as a resting MRI study. Imaging and testing was repeated one hour after medication administration. A seed-to-voxel analysis from basal gangliar components was performed, and the MRI results compared with the Unified ParkinsonвЂ™s Disease Rating Scale (UPDRS). Results: Our subjects were predominantly symptomatic on the right side. The anterior and posterior putamen, ventral lateral and ventral anterior nuclei of the thalamus, We report a novel cerebellar ataxia with characteristic clinical features and atrophy of the cerebellum and of cranial and spinal nerve sensory ganglia. In 2004 we reported the association of bilateral vestibulopathy with cerebellar ataxia as a distinct syndrome with a characteristic clinical sign - an absent visually-enhanced vestibulo-ocular reflex. Later we showed in 18 patients that a non-length dependent peripheral neuropathy was an integral part of CANVAS (Cerebellar Ataxia Neuropathy bilateral Vestibular Areflexia Syndrome). We now have data from 41 patients with CANVAS, and brain and spine neuropathology from one and 160 ID: guganp I Black Lining: [ON] I Time: 09:31 I Path: N:/3b2/ANA#/Vol00000/120256/APPFile/JW-ANA#120256 J_ID: ZAY Customer A_ID: BKLT2012_WIP_Abstracts Cadmus Art: ANA13 Date: 18-September-12 show that the underlying pathology is in sensory ganglia in other word it is a вЂ�вЂ�neuronopathyвЂ™вЂ™ rather than a вЂ�вЂ�neuropathyвЂ™вЂ™. Brain and temporal bone pathology in another patient showed marked loss of Purkinje cells and of vestibular, trigeminal and facial ganglion cells. All patients had brain MRI and 36/41 had evidence of cerebellar atrophy involving anterior and dorsal vermis, and hemispheric crus I. Clinical presentation may mimic that of SCA 3. There are 5 sets of sibling pairs, inferring CANVAS is a late-onset recessive disorder and identification of the culprit gene is currently a target of investigation. Stage: Page: 161 hybridization using specific oligoprobes and riboprobe for preprodynorphin. Subthalamotomy had beneficial effects on the motor symptoms in the four lesioned monkeys, increased LIDs, increased the duration of antiparkinsonian response to L-DOPA, and allowed a 40% reduction of LDOPA. In the striatum, no change was observed in the dopamine transporter, levels of D2 receptor and its mRNA, as well as in preproenkephalin. The striatal increases of D1 receptor levels, its mRNA, and changes in preprodynorphin mRNA induced by subthalamotomy may explain the potentiation of the response to L-DOPA following surgery. Study supported by: CIHR WIP1705. N-Acetylcysteine Increases Cerebral Glutathione as Measured by 7T Magnetic Resonance Spectroscopy in Patients with Gaucher or ParkinsonвЂ™s Disease Mary J. Holmay, Melissa Terpstra, Lisa Coles, Usha Mishra, Matthew Ahlskog, Gulin Oz, James C. Cloyd and Paul J. Tuite; Minneapolis, MN WIP1707. A Novel Alpha-Synuclein Missense Mutation in ParkinsonвЂ™s Disease Christos Proukakis, Maria Katsianou, Angelika Hummel, Timothy Brier, Henry Houlden, Jonathan Mark Cooper and Anthony H. Schapira; London, United Kingdom and London, United Kingdom Decreased glutathione (GSH) in postmortem ParkinsonвЂ™s disease (PD) brains and increased reactive oxygen species in fibroblasts from individuals with Gaucher disease (GD) have been observed, indicating oxidative stress in both conditions. The objective of this study was to determine if an intravenous dose of N-acetylcysteine (NAC), a GSH precursor, alters blood redox status and brain GSH levels. Patients with PD, GD, and age-matched healthy controls (NВј3 per group) participated. Reduced (GSH) and oxidized glutathione (GSSG) were measured in whole blood by HPLC/MS and brain GSH was measured by MRS as described previously (Oz & Tkac, MRM, 2011) at 7T prior to and up to 120 minutes following the start of a 1-hour infusion of NAC (150mg/kg). Blood GSH/GSSG ratios increased, peaking at 60-75 minutes after the start of infusion with a maximal change from baseline of 502-1624%. Brain GSH peaked at 105-120 minutes with a maximal change from baseline of 20-82%. This pilot study shows that a single, intravenous high NAC dose alters peripheral and brain GSH levels. Further study will help determine dosage regimens of this potentially useful antioxidant for PD and GD. Study supported by: This pilot study was funded by a grant from the Lysosomal Disease Network, protocol #6721. Ms Holmay is an employee of Lundbeck US. However the Company had no involvement in this research. Background: Although alpha-synuclein (SNCA) is crucial in the pathogenesis of ParkinsonвЂ™s disease (PD), only three missense mutations have been reported. The possibility of somatic mutations has not been investigated. Methods: SNCA exons were analysed in DNA from 28 PD patient brains by sequencing and high resolution melting (HRM) analysis. Restriction digests, and subcloning of PCR products were used to confirm a mutation, and determine its phase. Transfection was used to generate a cell model. Results: A novel missense mutation (c.150T>G, p.H50Q) was detected in DNA from one case. This was absent in databases and controls. The mutation changes a highly conserved residue which is within one turn of the a-helix from E46 and A53, and is a copper binding site. The mutant peak appeared lower than the wild type on sequencing, but no evidence of mosaicism was found. HRM analysis, which can detect low level mosaicism, did not reveal mutations in other samples. Stably transfected neuroblastoma cell lines overexpressing HA-tagged mutant SNCA were generated. No colocalisation of mutant SNCA with cellular organelles was found. Conclusions: We propose H50Q as the fourth SNCA missense mutation. The cell lines are being analysed for changes in copper toxicity and mitochondrial function. Study supported by: Royal Free Peter Samuel Fund, Wellcome Trust/MRC joint call in Neurodegeneration award (WT089698), the Kattan Trust, ParkinsonвЂ™s UK WIP1706. Changes in D1 Receptor Are Associated with the Potentiation of Response to Levodopa Following Subthalamotomy in Parkinsonian Monkeys Vincent A. Jourdain, Laurent Gregoire, Marc Morissette, Nicolas Morin, Martin Parent and Therese Di Paolo; Quebec, QC, Canada WIP1708. The Discharge of Striatal Neurons Is Profoundly Altered in Patients with ParkinsonвЂ™s Disease Arun Singh, Lisa F. Potts, Klaus Mewes, Robert Gross, Mahlon R. DeLong and Stella M. Papa; Atlanta, GA Loss of striatal dopaminergic modulation in ParkinsonвЂ™s disease (PD) presumably leads to abnormal discharges of striatal output neurons (medium spiny neurons, MSNs). To examine the MSN firing in PD, we analyzed data obtained during electrophysiologic mapping for DBS treatment including PD, dystonia and essential tremor (ET) patients for comparison. Strict criteria were applied for MSN classification. The mean firing rate of MSNs was significantly higher in PD (30612 Hz) than dystonia (1065 Hz) and ET (<3 Hz). In PD, a larger fraction of striatal neurons also exhibited burst activity. These findings are aligned with recent data from parkinsonian monkeys (Liang, J. Neurosci., 2008), challenging the classic functional model of PD. The less increased frequencies in dystonia highlight the relevance Subthalamotomy is offered to parkinsonian patients presenting disabling L-DOPA-induced dyskinesia. A potentiation of response to L-DOPA is observed following subthalamotomy. We investigated the dopaminergic D1 and D2 systems and associated neuropeptides in four MPTP-treated dyskinetic monkeys receiving a unilateral subthalamotomy and compared these results to four control and four MPTPtreated monkeys. The concentration of dopamine was measured by high-performance liquid chromatography. Dopamine transporter, D1, and D2 receptors levels were quantified by autoradiography using [125I]RTI, [3H]SCH23390 and [3H]raclopride binding, respectively. The D1, D2 and preproenkephalin mRNAs were measured by in situ 161 ID: guganp I Black Lining: [ON] I Time: 09:31 I Path: N:/3b2/ANA#/Vol00000/120256/APPFile/JW-ANA#120256 J_ID: ZAY Customer A_ID: BKLT2012_WIP_Abstracts Cadmus Art: ANA13 Date: 18-September-12 of specifically high MSN activity to PD, but also suggest that there may be grounds for the frequently alluded Dystonia-PD continuum. The very low firing rates in ET resemble MSN activity in normal monkeys, suggesting a parallel with normal humans. These findings demonstrate profound alterations of the MSN discharge in patients with PD, and point to the importance of investigating its molecular basis to develop function-restorative therapies. Study supported by: NS045962 Stage: Page: 162 PatientsвЂ™ antibodies were found specific for DPPX, without reacting with DPP10 or Kv4.2. The unexplained diarrhea led to demonstrate a robust expression of DPPX in the myenteric plexus. The course of neuropsychiatric symptoms was prolonged and often associated with relapses while decreasing immunotherapy. Long-term follow-up showed substantial improvement in 3 patients (1 is lost to follow-up). Interpretation: Antibodies to DPPX associate with a protracted encephalitis characterized by CNS hyperexcitability (agitation, myoclonus, tremor, seizures), pleocytosis, and frequent diarrhea at symptom onset. The disorder is potentially treatable with immunotherapy. Study supported by: Supported in part by a KWF fellowship 2009-4451 of the Dutch Cancer Society (MT), the National Institutes of Health RO1NS077851 (JD), RO1MH094741 (RB-G and JD), FundacioВґ la MaratoВґ TV3 (JD), Fondo de Investigaciones Sanitarias (FIS, PI11/01780 to JD, FI08/00285 to EMH, and PS09/0193 to FG), and a McKnight Neuroscience of Brain Disorders award (RB-G and JD). Dr. Dalmau receives royalties from the editorial board of Up-To-Date; from Athena Diagnostics for a patent for the use of Ma2 as autoantibody test. Dr. Dalmau holds a patent application for the use of NMDA receptor as autoantibody test. Dr. Dalmau has received a research grant from Euroimmun. Autoimmune Neurology WIP1801. Elevated Micro RNAs in Cerebrospinal Fluid of Multiple Sclerosis Patients Contribute to Neuronal Injury Neha Patel, Elliot Choi, Marie Medynets, Scott Newsome, Peter Calabresi, Avindra Nath and Tongguang Wang; Bethesda, MD and Baltimore, MD Neurodegeneration in patients with progressive forms of multiple sclerosis (MS) may continue despite immunomodulatory therapy and its pathophysiology is poorly understood. Since micro RNAs (miR) play a critical role in maintaining cellular homeostasis, levels of 88 miRs in cerebrospinal fluid (CSF) samples from 7 relapsing-remitting, 9 secondary progressive MS (SPMS) patients and 9 controls were determined using PCR array. The levels of 12 miRs were significantly up-regulated and one, miR423-3p, downregulated in SPMS compared to control. Among them, miR150 also increased in relapsing-remitting MS compared to control. Using cellquanti-blue assay and beta-III-tubulin immunostaining, the effects of increased miRs on cultured human fetal neurons were studied with mimics. Among them, miR-16 and miR-29 induced significant neurotoxicity compared to control. These observations indicate that miRs can be detected in CSF from MS patients and are maximally dysregulated in patients with SPMS. Change in miR levels in different categories of MS could be used as biomarkers for the disease diagnosis and prognosis. These miRs may also play a role in the pathogenesis of the progressive forms of MS and could serve as potential targets for the therapy. Study supported by: NIH intramural funding. WIP1803. Human Aquaporin 4 281-300 Is the Immunodominant Linear Determinant in the Context of HLA-DRB1*03:01 вЂ“ Relevance for Diagnosing and Monitoring Patients with Neuromyelitis Optica Benjamin Arellano, Rehana Hussain, Tresa Zacharias, Doris Lambracht-Washington and Olaf Stuve; Dallas, TX Objective: Human aquaporin 4 (hAQP4) is thought to be the autoantigen in patients with neuromyelitis optica (NMO). HLA haplotype analyses in NMO patient cohorts suggest a positive association with HLA-DRB1*03:01. This study aimed to identify immunodominant linear determinants of hAQP4 in the context of HLA-DRB1*03:01. Design: HLA-DRB1*03:01 transgenic mice were immunized with whole-protein hAQP4. To test cellular immune responses, lymph node cells and splenocytes were cultured in vitro with twenty-amino acid-long peptides that overlap by ten amino acids across the entirety of hAQP4. The frequency of Th1, Th17, and Th2 cytokines was determined by ELISPOT assay. Results: Peptide hAQP4281-300 generated a significantly (P-value<0.01) greater Th1 and Th17 immune response than any of the other linear peptides screened. This 20mer peptide contains two dominant immunogenic 15mer peptides. hAQP4281-300 did not interfere with recombinant AQP4 autoantibody binding. Conclusion: hAQP4281-330 is the dominant linear immunogenic determinant of hAQP4 in the context of HLADRB1*03:01. Within hAQP4281-330 are two dominant immunogenic determinants that induce differential Th phenotypes. hAQP4 determinants identified in this study may serve as diagnostic biomarkers in NMO patients. Study supported by: Doris Duke Charitable Foundation with collaborations with lab funded by the Guthy-Jackson Charitable Foundation. WIP1802. Encephalitis and Antibodies to DPPX, a Regulatory Subunit of Kv4.2 Potassium Channels Anna Boronat, Jeffrey M. Gelfand, Nuria Gresa-Arribas, HyoYoung Jeong, Michael Walsh, Kirk Roberts, Eugenia MartinezHernandez, Myrna R. Rosenfeld, Rita Balice-Gordon, Francesc Graus, Bernardo Rudy and Josep Dalmau; Barcelona, Spain; San Francisco; New York; Brisbane, Australia and Philadelphia Objective: To report a novel cell-surface autoantigen in 4 patients that is a critical regulatory subunit of the Kv4.2 potassium channels. Methods: Techniques included immunoprecipitation, mass spectrometry, cell-base experiments with Kv4.2 and several dipeptidyl-peptidase-like protein-6 (DPPX) plasmid constructs, and brain immunostaining of DPPX-null mice. Results: Immunoprecipitation studies identified DPPX as the target autoantigen. Symptoms included agitation, confusion, myoclonus, tremor, and seizures. All patients had pleocytosis, and three severe prodromal diarrhea of unknown etiology. Given that DPPX вЂ�вЂ�tunes upвЂ™вЂ™ the Kv4.2 potassium channels, we determined the epitope distribution in DPPX, DPP10 (a protein homologous to DPPX) and Kv4.2. WIP1804. Treatment Patterns in Co-Occurring Multiple Sclerosis and Sarcoidosis Dorlan J. Kimbrough, Justin C. McArthur and Carlos A. Pardo; Baltimore, MD Recent reports (Carbonelli et al., 2012 and Chakravarty et al., 2012) suggest that interferon (IFN) beta may trigger 162 ID: guganp I Black Lining: [ON] I Time: 09:31 I Path: N:/3b2/ANA#/Vol00000/120256/APPFile/JW-ANA#120256 J_ID: ZAY Customer A_ID: BKLT2012_WIP_Abstracts Cadmus Art: ANA13 Date: 18-September-12 pulmonary sarcoidosis in multiple sclerosis (MS) patients. We retrospectively identified six patients with concurrent or sequential MS/sarcoidosis among 300 patients from the Neurosarcoidosis (NS) and MS clinics at Johns Hopkins Hospital between 2000 and 2011. Medical records were reviewed. All six patients were women, age 39.8 Гѕ/ГЂ 10.8 years at diagnosis. Three had biopsy-proven pulmonary sarcoidosis; in two cases, MS was initially diagnosed (treatments included glatiramer, natalizumab, and mycophenolate mofetil for one case; IFN beta-1a alone for the second). In the third case, pulmonary sarcoidosis was treated with prednisone and preceded neurologic symptoms by twenty years. Among the three cases Stage: Page: 163 without biopsy, one MS patient was treated with IFN beta1b, glatiramer, and IFN beta-1a before developing sarcoidosis. One NS patient used prednisone and mycophenolate mofetil before MS was reconsidered; a third case was diagnostically uncertain and treated with mycophenolate mofetil. Co-occurring MS/sarcoidosis cases are rare in our patient population. IFN therapy preceded sarcoidosis in three cases, but confounding treatments and rarity of cases prevented strong inferences about association. Study supported by: Project RESTORE Bart McLean Fund for Neuroimmunology Research. National Institutes of Health. 163 ID: guganp I Black Lining: [ON] I Time: 09:31 I Path: N:/3b2/ANA#/Vol00000/120256/APPFile/JW-ANA#120256 J_ID: ZAY Customer A_ID: BKLT2012_CD_Abstracts Cadmus Art: ANA13 Date: 18-September-12 NINDS/ANA Career Development Symposium Poster Session Abstracts Stage: Page: 164 (b) 75 BAVMГѕ(with) aneurysm cases vs. 504 controls, and (c) 150 BAVM-(without) aneurysm cases vs. 504 controls. Results: rs10757278-G was marginally associated with BAVM (ORВј1.23, 95% CIВј0.99-1.53, PВј0.064). Compared to controls, the association was stronger in BAVMГѕaneurysm (ORВј1.50, 95% CIВј1.03-1.89, PВј0.035) than in BAVM-aneurysm cases (ORВј1.03, 95% CIВј0.77-1.33, PВј0.832). Similar effects were observed for other SNPs in linkage disequilibrium (r2>0.8) with rs10757278. Conclusion: Common 9p21.3 variants showed similar effect sizes as previously reported for aneurysmal disease. The SNP association with BAVM appears to be explained by known association with aneurysms, suggesting that BAVM associated aneurysms share similar vascular pathology mechanisms. Study supported by: K23 NS058357 (HK), R01 NS034949 (WLY), and P01 NS044155 (WLY) Each year, recipients of K awards are invited to attend the NINDS/ANA Career Development Symposium, designed to provide them with the essential tools to enhance their ability to write successful grant proposals and to obtain grant funding from the NIH and other institutions. The NINDS/ANA Career Development Symposium was set up to foster the success of young members of the faculty who had obtained career development awards (K08, K12, or K23) from the NIH. Career Development posters will be presented during the wine and cheese reception of the Career Development Symposium from 5:00 pm вЂ“ 7:00 pm on Saturday, October 6. The K-awardee participantвЂ™s name is in bold. CD503. Metabolomics Identifies Alterations in the Tricarboxylic Acid Cycle in Acute Ischemic Stroke W. Taylor Kimberly, Yu Wang, Ly Huong Pham and Robert E. Gerszten; Boston, MA CD501. Directional EEG Connectivity Method Demonstrates Complex, Reciprocal Information Flows during Praxis Performance Joshua B. Ewen, Anna Korzeniewska, Balaji M. Lakshmanan, Stewart H. Mostofsky and Nathan E. Crone; Baltimore, MD Background: There is limited information about changes in metabolism during acute ischemic stroke. The identification of circulating plasma metabolites modulated during cerebral infarction may provide insight into pathogenesis and identify novel biomarkers. Methods: We performed filament occlusion of the middle cerebral atery of Wistar rats compared to sham controls, collecting plasma and CSF two hours after onset of ischemia. Samples were analyzed using liquid chromatography followed by tandem mass spectrometry. Polar metabolites including organic acids, sugars and bile acids were quantified using electrospray ionization followed by scheduled multiple reaction monitoring. Results: Several metabolites were altered in the setting of cerebral infarction. We detected a 38% rise in lactate (PВј0.03), and a 41% accumulation of pyruvate (PВј0.04) in the plasma of stroke animals. We also detected increases in several metabolites in the tricarboxylic acid (TCA) cycle, including succinate (47%, PВј0.03), malate (64%, PВј0.03), alpha-ketoglutarate (64%, PВј0.03), fumarate (28%, PВј0.03) and aconitate (61%; PВј0.005) but not in citrate (P>0.20). Conclusions: Taken together, these data highlight alterations in metabolites that are related to the TCA cycle during acute ischemic stroke. Validation in human cohorts may confirm their potential utility as biomarkers of stroke. Study supported by: 1K23NS076597-01; The Clinical Investigator Training Program: Beth Israel Deaconess Medical Center вЂ“ Harvard Medical School, in collaboration with Pfizer Inc. and Merck & Co. Praxis function is known from lesion studies to depend on left parietal and premotor regions. While the typical physiological model suggests that praxis вЂ�вЂ�commandsвЂ™вЂ™ are sent from the left parietal region to left premotor regions and then to primary motor cortex, EEG studies of go/no-go praxis tasks suggest more complex interactions between bilateral anterior and posterior brain regions. Using a high density EEG array, we recorded data from a praxis task and analyzed them with Event Related Causality (ERC; Granger-Causality-based method which estimates dynamical changes in brain activity flow). Because the ERC method has been not previously been applied to scalp EEG, we investigated optimal analysis parameters. Data from the mental rehearsal portion of the task demonstrated activity flows between left and right posterior regions and flows from both posterior regions toward left frontal regions. Data from the initiation of the pantomime portion demonstrated reciprocal flows, suggesting feedback from left anterior regions to bilateral posterior regions. These results demonstrated the utility of ERC in analyzing scalp EEG recordings and suggest generally that systems-level neural complex motor circuits function with reciprocal information flows. Study supported by: NIH/NINDS CD502. Genetic Variants on 9p21.3 Are Associated with Brain Arteriovenous Malformations with Associated Flow-Related Arterial Aneurysms Helen Kim, Nasrine Bendjilali, Jeffrey Nelson, Shantel M. Weinsheimer, Mark Segal, Charles E. McCulloch, Ludmila Pawlikowska and William L. Young; San Francisco, CA CD504. Perception among African Americans towards Calling 911 for Acute Stroke Lesli E. Skolarus, Jillian S. Murphy, Marc A. Zimmerman, Sarah Bailey, Sophronia Fowlkes and Lewis B. Morgenstern; Ann Arbor and Flint Background: The 9p21.3 locus is associated with risk of coronary artery disease and intracranial and abdominal aortic aneurysms (rs10757278). We investigated whether previously reported 9p21.3 SNPs are associated with risk of brain arteriovenous malformations (BAVM), which often have accompanying flow-related arterial aneurysms. Methods: Genotypes for 6 SNPs, including rs10757278, were imputed using 1000 Genomes Phase 1 CEU data (R2>0.9). We tested for association using logistic regression of imputed dosages adjusting for age, sex and top 3 components of ancestry in: (a) 338 BAVM cases vs. 504 controls, Background: African Americans receive acute stroke treatments less often than European Americans. We used a community-based participatory research approach to explore perceptions of emergency stroke care among urban African American youth and adults. Methods: Community partners, church health teams/ leaders identified and recruited focus group participants 164 ID: guganp I Black Lining: [ON] I Time: 09:12 I Path: N:/3b2/ANA#/Vol00000/120257/APPFile/JW-ANA#120257 J_ID: ZAY Customer A_ID: BKLT2012_CD_Abstracts Cadmus Art: ANA13 Date: 18-September-12 from 3 African American churches in Flint, MI. Nine focus groups were conducted from November 2011 to March 2012; we took a grounded theory approach to analysis. Results: Thirty nine youth (64% women) and 38 adults (90% women) participated. Adults and youth endorsed their inability to recognize stroke warning signs. Adult barriers also included finances. Adult facilitators included widespread acceptance of stroke as an emergency and perceived social approval for calling 911for stroke. Youth barriers to calling 911 for stroke included emotional state (fear, liability), lack of empowerment, anxiety about talking to EMS dispatchers and perceptions that the medical community does not care to help them. Youth also identified community factors, including violence and limited city resources as barriers. Conclusion: Designing behavioral interventions to increase 911 calls for acute stroke should be cognizant of and sensitive to barriers specific to the community. Study supported by: NINDS K23 NS073685 Stage: Page: 165 Methods: SPOTRIAS (Specialized Program of Translational Research in Acute Stroke) centers prospectively collected data on all patients treated with IVrtPA or IAT from 1/1/2005 to 12/31/2010. IAT was categorized as bridging therapy (BT: IAT after IVrtPA), and endovascular therapy alone (ETA). In-hospital mortality was compared in (1) patients age 80 versus <80, and (2) IAT/BT/ETA versus IVrtPA only among those age 80 using multivariable logistic regression. Results: 3378 were treated with IVrtPA, 808 with IAT (383 with ETA and 425 with BT). Patients 80 (nВј1182) had a higher risk of in-hospital mortality compared to younger counterparts. Among those age 80, IAT (OR 0.95, 95%CI 0.60-1.49), BT (OR 0.82, 95%CI 0.47-1.45), and ETA (OR 1.15, 95%CI 0.64-2.08) versus IVrtPA were not associated with increased in-hospital mortality. Conclusions: IAT does not appear to increase the risk of in-hospital mortality among those over age 80 compared to intravenous thrombolysis alone Study supported by: SPOTRIAS is funded by the National Institutes of Neurological Diseases and Stroke (NINDS P50 NS049060). JZW was funded by NINDS 1K23 NS 073104-01A1 and the NIH Loan Repayment Program (AG 31009). CD505. High Resolution Magnetic Resonance Imaging (HRMRI) in Intracranial Atherosclerosis Tanya N. Turan, Truman R. Brown, Zoran Rumboldt and Robert J. Adams; Charleston, SC Introduction: HRMRI can identify prognostically important plaque features (intraplaque hemorrhage (IPH), fibrous cap, and lipid core) in extracranial carotid disease, but plaque features in intracranial atherosclerosis (ICAS), a more common cause of stroke worldwide, have not been systematically examined. This study aimed to refine a HRMRI protocol that will consistently visualize the arterial lumen, vessel wall, and atherosclerotic plaque components in patients with ICAS. Methods: 36 patients with 50-99% ICAS underwent a brain MRI using a 3Tesla Siemens scanner with a 32 channel head coil. Stepwise adjustments to the imaging protocol were made to refine the image quality. Images were assessed using a grading scale based on visualization of the vessel wall, lumen, and plaque components. Results: The final imaging protocol was selected from the sequences that provided the best image quality without unacceptable scan duration. The final sequences include 3D acquisition of T1 weighted images (pre- and post-contrast), T2 weighted images, and FLAIR sequences. Summary: HRMRI can be used to identify IPH, fibrous cap, and lipid rich core in ICAS. Further studies are planned using this protocol to determine inter-rater reliability and the prognostic value of these plaque features in ICAS. Study supported by: NIH/NINDS 1K23NS069668 CD507. Induction of Autophagy Protects Against TDP43-Mediated Neurodegeneration Sami Barmada, Aaron Daub, Michael Ando, Andrea Serio, Andrey Tsvetkov, Arpana Arjun, Siddharthan Chandran and Steve Finkbeiner; San Francisco, CA and Edinburgh, United Kingdom TDP43, a nuclear DNA- and RNA-binding protein, plays a prominent role in the pathogenesis of both amyotrophic lateral sclerosis (ALS) and frontote