136th Annual Meeting of the American Neurological Association September 25–27, 2011 Manchester Grand Hyatt, San Diego, CA Poster Listings Derek Denny-Brown New Member Symposium Abstracts Poster Session Abstracts Works in Progress Abstracts Career Development Abstracts Author Index Subject Index 1–3 4–18 19–21 22 112–123 124–126 BLANK PAGE J_ID: ANA Customer A_ID: SUPP11-2 Cadmus Art: 22574 Date: 31-August-11 Stage: Page: 1 Poster Listings Sunday, September 25, 2011 Posters Poster Listing Pages Topic 101–144 3–5; 19 23–32; 99–100 Movement Disorders 201–240 5–7; 19 32–41; 100–101 Sleep Disorders and Circadian Rhythm 301–303 7 42 Education 401–408 7–8 42–44 Career Development 515–531 22 111 Poster Listing Pages Abstract Pages Posters Behavioral Neurology 601–622 8–9; 19 44–49; 102 Epilepsy 701–732 9–10; 19–20 49–55; 102–104 Neuromuscular Disease 801–841 10–11; 20 55–63; 104–105 Neurogenetics 1001–1013 11–12; 20 63–65; 105–106 Trauma/Injury 1101–1107 12 65–66 Neurology Critical Care 1201–1206 12; 20 66–67; 106 Pediatric Neurology 1301–1304 12–13 67–68 Rehabilitation and Regeneration 1401–1403 13 68–69 Poster Listing Pages Abstract Pages Tuesday, September 27, 2011 Topic I Posters Dementia and Aging 1501–1542 13–15; 20 69–79; 107–108 Headache and Pain 1601–1623 15–16; 21 79–84; 108 Neuroimmunology and Demyelinating Disease 1701–1747 16–28; 21 84–94; 108–110 Neurooncology 1801–1809 18 94–96 Neurovirology 1901–1908 18 96–98 Black Lining: [ON] I Time: 07:59 I Path: //xinchnasjn/01Journals/Wiley/3b2/ANA#/Vol00000/110240/APPFile/JW-ANA#110240 Poster Listings Cerebrovascular Disease Monday, September 26, 2011 Topic ID: senthilk Abstract Pages BLANK PAGE J_ID: ZAY Customer A_ID: SUPP11-1 Cadmus Art: 22576 Date: 31-August-11 136th Annual Meeting Tuesday, September 27, 2011 Derek Denny-Brown New Member Symposium Abstracts Stage: Page: 1 new work using olfactory intracranial EEG techniques in patients with medically refractory epilepsy. By recording directly from olfactory limbic brain regions, we have begun to gain direct insights into the electrophysiological organization of the human olfactory system. Preliminary results suggest that the emotional content of a smell modulates piriform activity in the gamma-band range, and that cortical stimulation at piriform cortex elicits short-latency (<15 ms) orbitofrontal responses. Findings from this work will be instrumental in confirming (or refuting) long-accepted basic notions about the neurobiology of human olfaction and may help inform clinical translational models of neurodegenerative disorders, such as Alzheimer’s and Parkinson’s diseases, in which olfactory impairments often arise prior to the onset of overt symptoms. Derek Denny-Brown Neurological Scholar Award: Can We Detect Alzheimer’s Disease a Decade Before Dementia, and Why Would We Want To? Reisa Sperling, M.D. Center for Alzheimer Research and Treatment, Brigham and Women’s Hospital, Massachusetts General Hospital, Harvard Medical School Poster Session Abstracts The pathophysiological process of Alzheimer’s disease (AD) is thought to begin years, if not decades, prior to the onset of clinical dementia. Converging data from PET amyloid imaging, cerebrospinal fluid studies, and large autopsy series suggest that approximately one-third of clinically normal older individuals harbor a substantial burden of cerebral amyloid-b deposition. Recent multi-modality imaging studies, using PET amyloid imaging and functional MRI, have demonstrated that amyloid-b deposition in normal elderly is associated with aberrant fMRI activity in the default network, in a pattern strongly resembling that seen in AD dementia. AD-like patterns of atrophy have also been detected in amyloid-positive normal older individuals, and recent evidence suggests that specific patterns of cortical thinning are predictive of who will develop dementia a decade later. A small number of studies have reported an association between higher amyloid burden and lower memory performance even among the range of clinically normal older individuals, particularly those studies employing more challenging neuropsychological measures. These findings provide support for the hypothesis that amyloid-b accumulation is linked to synaptic dysfunction in the networks supporting memory processes, and that brain dysfunction is detectable prior to the emergence of significant cognitive impairment. It is likely, however, that many additional factors modulate the likelihood of subsequent clinical decline. Longitudinal studies are ongoing to determine if these amyloid-positive older individuals are indeed in the preclinical stages of AD, and to elucidate the endophenotype that best predicts those who will progress to AD dementia. In parallel with these natural history studies, we must begin secondary prevention trials to determine if altering amyloid burden can delay the emergence of clinical symptoms. It is likely that, similar to cancer, diabetes, cardiovascular and most other chronic diseases, many therapies for AD will be most efficacious in the early stages of the pathophysiological process. M701. Controlled Cortical Impact in Adult Rats and Posttraumatic Seizures and Epilepsy Kevin M. Kelly, Elena A. Kharlamov, Eric R. Miller, Bo Lu and Zakaria Mtchedlishvili; Pittsburgh, PA and Philadelphia, PA The CCI model of TBI has been used in mice and immature rats to model posttraumatic epilepsy. We used young adult rats and long-term video and video-EEG with cortical and hippocampal electrodes to investigate posttraumatic epileptogenesis and associated neuropathological changes. A total of 28,956 hours of monitoring was obtained from 128 CCI-injured and 15 sham-operated animals. Class 3–5 provoked seizures occurred in 7/72 (9.7%) animals video-monitored for 1 week immediately after CCI. Epileptic seizures occurred in 26/118 (22%) animals monitored beyond 1 week post-CCI. Class 3–5 seizures occurred in 19 animals; ictal discharges appeared generalized at onset or from the contralateral frontal cortex. Nonconvulsive seizures occurred in 7 animals characterized by motor arrest or no behavioral change associated with continuous 1–2 Hz high amplitude spikes or spike-waves averaging 26.262.8 seconds. No control animal had seizures. CCI resulted in severe cortical and subcortical injury and alterations in NeuN and GFAP staining. Timm staining showed mossy fiber sprouting in the inner molecular layer of the dentate gyrus of epileptic and nonepileptic animals. These results indicate that the CCI model can be used in adult animals to investigate mechanisms underlying posttraumatic epileptogenesis. Study supported by: Pennsylvania Department of Health Research Formula Fund RFA 01-07-26 and Epilepsy Foundation Research Grant (ZM) M704. Gray Matter Heterotopia in an Epileptic Brain Malformation Are Functionally Connected to Overlying Cortex Joanna A. Christodoulou, Linsey M. Walker, Stephanie N. Del Tufo, Tami Katzir, Susan Whitfield-Gabrieli, John D.E. Gabrieli and Bernard S. Chang; Cambridge, MA; Boston, MA and Haifa, Israel Derek Denny-Brown Neurological Scholar Award: The Human Sense of Smell at Millisecond Speed Jay A. Gottfried, MD, PhD, Northwestern University, Chicago, IL Objective: Periventricular nodular heterotopia (PNH) are associated with epilepsy and dyslexia. Evidence suggests that heterotopia have a functional role and connectivity defects may be important in this disorder. We investigated the restingstate functional connectivity of heterotopic nodules in PNH. Methods: Eleven subjects were studied using functional connectivity MRI with bold oxygenation level-dependent (BOLD) imaging acquired during rest. The functional correlation between heterotopic nodules and other brain voxels was systematically identified and relationships to clinical measures analyzed. Very little is known about the basic anatomy, connectivity, and physiology of the human olfactory system. What we do know is largely inferential, derived from non-human animal studies that may hold scant relevance for the human sense of smell. Although functional imaging studies have expanded our general understanding of human olfactory neurobiology, these techniques have poor temporal resolution and provide only correlative information. Thus even the most basic assumptions about human olfaction have not been systematically tested. In this presentation I will discuss 1 ID: senthilk I Black Lining: [ON] I Time: 08:03 I Path: //xinchnasjn/01Journals/Wiley/3b2/ANA#/Vol00000/110239/APPFile/JW-ANA#110239 J_ID: ZAY Customer A_ID: SUPP11-1 Cadmus Art: 22576 Date: 31-August-11 Stage: Page: 2 Results: Forty-three of 45 heterotopia (96%) showed functional correlation with discrete regions of overlying cortex (mean peak coefficient 0.61). Nodules also demonstrated correlation with contralateral cortex (62%), other nodules (51%), ipsilateral nonoverlying cortex (42%), and basal ganglia/cerebellum (13%). The peak degree of connectivity between heterotopia and other gray matter regions was significantly related to epilepsy duration. Interpretation: Nearly all heterotopia in PNH are functionally connected to overlying cortex, and the strength of aberrant connectivity increases with duration of epilepsy. Along with prior evidence that cortico-cortical tract defects underlie dyslexia in this disorder, these results suggest that altered connections are a critical substrate for neurological dysfunction in brain malformations. Study supported by: NIH/NINDS, Epilepsy Foundation, William F. Milton Fund Amyloid-beta clearance rate is decreased by 30% in AD compared to controls. Changes in clinical, cognitive, MRI, PET, CSF, and blood biomarkers in autosomal dominant AD indicate the pathophysiologic cascade begins up to 20 years before the expected age of onset. The pathophysiologic changes of AD can be specifically measured and targeted for clinical trials. Autosomal dominant AD prevention trials offer a unique opportunity to lead the way to effective treatments for all AD. Study supported by: NIH K-23-AG03094601, NIH R-01NS065667, NIH 3P-01-AG02627603S1 (FACS), NIH 1U01-AG03243801 (DIAN), ADRC (P50 AG05681-22), HASD (P01 AG03991-22), WU CTSA award (UL1 RR024992), Mass Spectrometry Resource (NIH RR000954), Eli Lilly research collaboration R.J.B. is a co-founder of a company (C2N Diagnostics) that has licensed a Washington University patent on some of the technology described in this abstract. M810. Evaluating Mechanoreceptors in Glabrous Skin in Diabetic Neuropathy Iliza Myers, Kay Artibee, Jun Li and Amanda C. Peltier; Nashville, TN T1505. Components of Blood Pressure and Progression of Cerebral Leukoaraiosis: The ARIC Study Rebecca F. Gottesman, Diane J. Catellier, Laura H. Coker, Josef Coresh, Clifford R. Jack, Jr., David S. Knopman, Kathryn M. Rose, A. Richey Sharrett, Dean K. Shibata and Thomas H. Mosley; Baltimore, MD; Chapel Hill, NC; Winston-Salem, NC; Rochester, MN; Durham, NC; Seattle, WA and Jackson, MS Meissner corpuscles (MCs) and their myelinated afferents are found only in glabrous skin. We hypothesized that alterations in MCs occur in diabetic neuropathy and correlate with other measures of axonal loss. Immunohistochemistry was performed on 2 and 3 mm skin punches from the index finger and distal leg, respectively. Four diabetic patients (ages 45–75), with neuropathy confirmed by exam and nerve conduction studies and four control patients (aged 35–50), were studied. Average Meissner corpuscle density (MCD) in control patients was 15.3 6 7.1 MCs/ mm2 with significant reductions observed in two patients (3.3, 6.2 MCs/ mm2) with near normal or higher density in two other patients (11.1, 28.1 MCs/mm2), suggestive of proliferation. MCs in diabetics often displayed abnormal morphology. Density of intrapapillary myelinated endings (IME) correlated with MCD in all patients (r ¼ 0.97). Diabetic patients’ intraepidermal nerve fiber density (IENFD) in the distal leg was 4.2 6 5.9 fibers/mm, compared to 13.7 6 1.3 in controls. IME density did not correlate with IENFD, suggesting that these populations of fibers are independently affected by hyperglycemia. Glabrous skin biopsies afford evaluation of mechanoreceptors which are important in studying pathophysiology of diabetic neuropathy. Study supported by: Supported by NINDS K23 NS056009 (A.C. P.), NINDS R01NS066927-01(J.L.), Vanderbilt CTSA grant 1 UL1 RR024975. Background The contribution of blood pressure (BP) components to the burden and progression of cerebral white matter hyperintensity (WMH) is poorly understood. We evaluated these associations in the population-based Atherosclerosis Risk in Communities (ARIC) cohort. Methods 983 participants each underwent 2 brain MRIs 10 years apart. Systolic (SBP) and diastolic BP (DBP) were measured at 4 study visits. Four BP components were examined as predictors of WMH progression: 1) mean arterial pressure (MAP); 2) pulse pressure (PP); 3) orthostatic hypotension (OH); and 4) 10-year change in BP. Results Baseline (preceding MRI #1) MAP value predicted WMH progression (OR 1.39 (1.20–1.62), per 10 mm Hg increase), but PP did not. Presence of OH did not predict WMH progression, but OH severity did (OR 1.21 (1.02–1.42) per 10 mm Hg SBP decrease). Change in DBP over 10 years had a U-shaped relationship with WMH progression: extreme increases and decreases, independent of antihypertensive use, were both associated with greater WMH progression (p¼0.007). Discussion WMH progression is significantly predicted by MAP and extent of orthostatic SBP reduction. Significant changes over time in DBP, whether positive or negative, predict WMH progression, cautioning against simplified interpretations of blood pressure associations. Study supported by: The Atherosclerosis Risk in Communities Study is carried out as a collaborative study supported by National Heart, Lung, and Blood Institute contracts (HHSN26820 1100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN26820 11000010C, HHSN2682011000011C, HHSN2682011000012C). T1501. Amyloid-Beta Dynamics and Prevention Trials in Dominantly Inherited Alzheimer’s Disease Randall J. Bateman and on behalf of the Dominantly Inherited Alzheimer Network; St. Louis, MO Amyloid-beta is a key pathologic protein in Alzheimer’s disease(AD) and extensive research has started an era of clinical trials targeting amyloid-beta. Understanding the dynamics of amyloid-beta formation and clearance in the human CNS and the processes that lead to clinical disease are essential to design better clinical trials. Developing efforts to prevent AD in autosomal dominant mutation carriers may test the amyloid hypothesis, determine the timing of treatment, and lead the way to AD prevention. Amyloid-beta production and clearance rates were measured with stable isotope labeling kinetics. The Dominantly Inherited Alzheimer’s Network interim findings of clinical, cognitive, MRI, PET, CSF, and blood biomarkers were analyzed with respect to the expected age of onset. Works in Progress Abstracts M839. Virtual Demyelination in pmp22 Deficiency Jiasong Guo, Qing Yan, Gina Sosinsky, Mark Elisman, Cameron McIntyre, Lily Wang, Ueli Suter and Jun Li; Nashville; San Diego; Cleveland; Zurich, Swaziland and Nashville, TN Safety factor for action potential propagation in pmp22þ/À nerves appears impaired (Bai et al, J Neurosci 2010). The 2 ID: senthilk I Black Lining: [ON] I Time: 08:03 I Path: //xinchnasjn/01Journals/Wiley/3b2/ANA#/Vol00000/110239/APPFile/JW-ANA#110239 J_ID: ZAY Customer A_ID: SUPP11-1 Cadmus Art: 22576 Date: 31-August-11 present study investigates mechanisms responsible for the impairment. Fluorescent dyes with different molecular sizes were injected into sciatic nerves. After 4-hour incubation, sciatic nerves were teased into individual nerve fibers, and examined under fluorescence microscopy. Fluorescence was of strong intensity in about a half of paranodal tomacula of pmp22þ/À nerves (15 mice), but absent or minimal in the paranodes of wild-type nerves (11 mice). This finding suggests that myelin is abnormaly leaky, and may result in excessive outward current. Application of potassium channel blocker, 4AP, to reduce outward current improved the amplitude of motor response during nerve stimulation. Western blot and immunohistochemistry revealed alterations of tight junction protein assembly, a potential molecular mechanism for the myelin leakage. Conclusions: Our results show excessive leakage in pmp22þ/À myelin in the absence of demyelination. This leakage is functionally similar to demyelination. These findings not only reveal novel mechanism for conduction block but also establish new therapeutic approach for this disease. Study supported by: NIH Stage: Page: 3 43 Canadian families with 4 or more individuals with MS. Genetic linkage analysis and genotyping of candidate genes in these families has not fully explained familial disease clustering although alleles of GWAS genes are overrepresented. Methods: Whole exome sequencing was performed to further understand heightened prevalence of MS in these families. Findings: Forty-three individuals with MS (one/family) were sequenced. On average over 58000 variants were identified in each individual. Searching for rare variants in known or candidate MS susceptibility genes led to identification of a rare loss-of- function variant in the CYP27B1 gene. This variant in 2716 parent-affected child trios showed significant association to MS P¼6Â10À5. Further genotyping of other variants in over 11,000 individuals showed that rare CYP27B1 variants conferred significant risk of MS, Peto odds ratio ¼ 4.1 (95% confidence interval 1.5–11.1). Interpretation: Causative role for CYP27B1 in MS risk is supported. CYP27B1 encodes the vitamin D activating 1alpha hydroxylase enzyme. A role for vitamin D in MS pathogenesis is strongly implicated. We show the utility of using extreme multicase families to identify rare variants. Study supported by: This study was supported by grant funding from the MS Society of the United Kingdom and the Scientific Foundation of the Canadian MS Society. M1012. Exome Sequencing Identifies a Rare Variant in the CYP27B1 Gene Associated with Multiple Sclerosis George C. Ebers and Sreeram V. Ramagopalan; Oxford, Oxfordshire, United Kingdom Background: Multiple sclerosis (MS) is a complex neurological disease. We previously described the ascertainment of 3 ID: senthilk I Black Lining: [ON] I Time: 08:03 I Path: //xinchnasjn/01Journals/Wiley/3b2/ANA#/Vol00000/110239/APPFile/JW-ANA#110239 J_ID: ZAY Customer A_ID: SUPP11-3 Cadmus Art: 22575 Date: 31-August-11 136th Annual Meeting Sunday, September 25, 2011 Poster Session Stage: Page: 4 S109 Incidence of Nocturnal Blood Pressure Dipping during Hospital Admission and Discharge among African American Stroke Patients Lien Diep, John Kwagyan, Joseph Kurantsin-Mills, Janaki Kalyanam, Amy Wong, Kermit Crowder, Bonnie Davis, Leia Harbour, Jean Edson and Annapurni Jayam-Trouth; Washington, DC and Baltimore, MD Posters will be displayed in Elizabeth A-E of the Manchester Grand Hyatt from 10:00 am – 7:00 pm, with authors present from 6:00 pm – 7:00 pm. NOTE: An asterisk designates a resident/fellow travel award winner. Two asterisks represent a medical student travel award winner. S110 Preoperative Factors Associated with In-Hospital Mortality Following Minimally Invasive Hematoma Aspiration and Thrombolysis for Intracerebral Hemorrhage Feng Xu, Zhouping Tang, Huicong Kang, Dengji Pan, Suiqiang Zhu and Wei Wang; Wuhan, China Cerebrovascular Disease S111 Does Incidental Micro-Hemorrhage, Detected by Gradient Echo Sequence MRI, Predict Hemorrhagic Transformation of an Ischemic Stroke? Konark Malhotra and Yousef M. Mohammad; Chicago, IL S101 Duration of Diabetes and Ischemic Stroke Risk: The Northern Manhattan Study Julio R. Vieira*, Chirantan Banerjee, Yeseon P. Moon, Myunghee C. Paik, Tatjana Rundek, Ralph L. Sacco and Mitchell S.V. Elkind; New York, NY and Miami, FL S112 Younger Patients Have Lower Quality of Life after Intracranial Aneurysm Diagnosis Nerissa Ko, Richard Hornung, Charles Moomaw, Laura Sauerbeck and Joseph Broderick; San Francisco, CA and Cincinnati, OH S102 Functional Outcomes in CREST among Patients with Periprocedural Stroke and Myocardial Infarction Bart M. Demaerschalk, Robert J. Hye, O.W. Brown, Donald V. Heck, Irfan Altafullah, Jenifer H. Voeks, George Howard, James F. Meschia and Thomas G. Brott; Phoenix, AZ; San Diego, CA; Royal Oak, MI; Winston Salem, NC; Robbinsdale, MN; Birmingham, AL and Jacksonville, FL S113 Aggressive Medical Management of Primary Intracerebral Hemorrhage: Cost/Benefit Analysis Luis Cava, Diane C. Andress-Rothrock and John F. Rothrock; Birmingham, AL S103 Inhibition and Scavenging of Complement as Therapeutic Targets in the Mouse Model of Acute Ischemic Stroke Xinzhi Chen, Mark P. Mattson and Milan Basta; Baltimore, MD and Potomac, MD S114 Withdrawn. S115 Genetic Analysis of Strain-Specific Stroke Sesceptibility in Mice: How To Classify C57BL/6? Amy K. Guzik, Sean S. Li, Ira M. Hall, Charles R. Farber, Brian H. Annex and Bradford B. Worrall; Charlottesville, VA S104 Does ACE (rs4646994) and a ADDUCIN (rs4961) Gene Polymorphisms Predicts the Recurrence of Hypertensive Intracerebral Hemorrhage Usha K. Misra, Jayantee Kalita, Bindu I. Somarajan, Bishwanath Kumar, Moromi Das and Balraj Mittal; Lucknow, Uttar Pradesh, India S116 Risk Factor Control in a Phase 3 Carotid Revascularization Trial James F. Meschia, Pierre P. Leimgruber, Vito A. Mantese, Carlos H. Timaran, David Chiu, Bart M. Demaerschalk, Mary E. Longbottom, Jenifer H. Voeks, George Howard and Thomas G. Brott; Jacksonville, FL; Spokane, WA; St. Louis, MO; Dallas, TX; Houston, TX; Phoenix, AZ and Birmingham, AL S105 Risk of Intracerebral Hemorrhage in t-PA Treated Patients with Elevated INR William P. Neil, Rema Raman, Ernstrom Karin and Thomas M. Hemmen; San Diego, CA S106 Toward a Further Clinical Physiological Elucidation: Immediate Regression of Leukoaraiosis after Carotid Artery Revascularization and Yu-Ming Chuang; New Taipei City, Taiwan S117 Radiologic Analysis of Thrombolysis-Induced Intracerebral Hemorrhage and the Role of Early Blood Pressure Management Maxim Mokin, Tareq Kass-Hout, Omar Kass-Hout, Robert Zivadinov and Bijal Mehta; Buffalo, NY S107 Ischemic Stroke Exome Pilot Study John W. Cole, Xinyeu Liu, Luke J. Tallon, Lisa K. Sadzewicz, Oscar C. Stine, Nicole Dueker, Yuching Cheng, Marcella A. Wozniak, Barney J. Stern, James F. Mitchell, Braxton D. Mitchell, Steven J. Kittner and Jeffrey R. O’Connell; Baltimore, MD and Jacksonville, FL S118 Anterior Circulation Stroke Causing Dizziness or Vertigo: A Systematic Review Yun Zhou, Seung-hun Lee, Ali S. Saber Tehrani, Karen A. Robinson and David E. Newman-Toker; Baltimore, MD and Gwangju, Korea S108 Phosphodiesterase Inhibitors Modulate Human Brain Microvascular Endothelial Cell Barrier Properties and Response to Injury Shuo Liu, Fan Yang, Chuanhui Yu, Annlia Paganini-Hill and Mark Fisher; Irvine, CA S119 The Presence of Intracranial Vascular Calcification May Protect Against Vasospasm Following Subarachnoid Hemorrhage Joya Paul, Mohamed Zghouzi, Yousef Mohammad, Shyam Prabhakaran, Sudeep Bhabad and Bichun Ouyang; Chicago, IL 4 ID: srinivasanv I Black Lining: [ON] I Time: 21:55 I Path: //xinchnasjn/01Journals/Wiley/3b2/ANA#/Vol00000/110241/APPFile/JW-ANA#110241 J_ID: ZAY Customer A_ID: SUPP11-3 Cadmus Art: 22575 Date: 31-August-11 Stage: Page: 5 S120 Stroke Knowledge: A Nation-Wide, Internet-Based Survey of 11,121 Inhabitants in Japan Hisanao Akiyama, Kanako Shimizu, Yoshiaki Tokuyama and Yasuhiro Hasegawa; Kawasaki, Kanagawa, Japan S132 Size Matters: Predictors of Intracranial Hemorrhage in Stroke Patients on Anticoagulation Elisabeth B. Marsh, Argye E. Hillis, Rafael H. Llinas and Rebecca F. Gottesman; Baltimore, MD S121 Is Anti Epileptic Drug Necessary in Cortical Venous Thrombosis? Velmurugendran Cannigaiper Uthamaroyan, Kaushik Sundar, Meenakshisundaram Umaiorubahan and Shankar Venkatasubramaniam; Chennai, Tamilnadu, India S133 A Rare Presentation of Anterior and Posterior Spinal Arteries Ischemia during Dilaysis Noor Yono, Adrian Marchidann and Rabih Kashouty; Manhasset, NY and New York, NY S122 Race and Insurance Disparities in Cardiovascular Risk Factors Control in Patients with Acute Stroke Anna M. Cervantes, Jose R. Romero, Helena Lau, Feliks Koyfman, Aleksandra Pikula, Thanh N. Nguyen, Carlos S. Kase and Viken L. Babikian; Boston, MA S134 Neurosarcoidosis: A Case Presentation Amtul Farheen, Nancy Gadallah, Rony Dekermenjian, Michael Rosenberg and Sushanth Bhat; Edison, NJ S135 Stroke Outcomes Based on MERCI/PENUMBRA Intervention and Hemodynamics Jay-Ming Wang**, Zahid I. Choudary, Shazia Z. Choudhary, Michael Sloan, Harry R. Van Loveren, Karen R. Wilson and David A. Decker; Tampa, FL S123 A Population-Based Verbal Autopsy Study of 1250 Stroke Deaths in Bangladesh Farrah J. Mateen, Nurul Alam, Marco Carone and Robert E. Black; Baltimore, MD; Dhaka, Bangladesh and Berkeley, CA S136 Migraine-Related ICH – A Case Study and Review Shivani Ghoshal**, Sankalp Gokhale and Louis Caplan; Boston, MA S124 Heparin-Induced Thrombocytopenia Associated with Cerebral Venous Sinus Thrombosis Following Postoperative Enoxaparin Administration in a 64 YearOld Female Robert A. Fishman and Ashis Tayal; Pittsburgh, PA S137 Stroke as a Complication of Tuberculous Meningitis Amtul Farheen, Sumaiya Salim, Zoha Fasih, Rony Dekermenjian and Sushanth Bhat; Edison, NJ S125 Renal Failure Increases Risk for Intracranial Hemorrhage Following Stroke Elisabeth B. Marsh, Argye E. Hillis, Rafael H. Llinas and Rebecca F. Gottesman; Baltimore, MD S138 Patterns and Mechanisms of Head-Shaking Nystagmus in Anterior Inferior Cerebellar Artery Infarction Young Eun Huh and Ji Soo Kim; Seongnam-si, Gyeonggi-do, Korea S126 Dominant Vertebral Artery Occlusion during Ipsilateral Head Tilt In Soo Moon, Jae-Hwan Choi and Kwang-Dong Choi; Busan, Korea S139 Co-Complaints Influence Odds of Stroke Diagnosis in ED Dizziness Ali S. Saber Tehrani, Yu-Hsiang Hsieh, Jonathan A. Edlow, Carlos A. Camargo and David E. Newman-Toker; Baltimore, MD and Boston, MA S127 A Novel Presentation of Mesodiencephalic Ischemic Stroke: Case Report and Literature Review Khalid S. Alqadi, Tariq Alfahad and Kathleen Burger; Washington, DC S128 Fatal Postpartum Cerebral Vasoconstriction Syndrome Jennifer E. Fugate, Eelco F.M. Wijdicks, Kelly D. Flemming and Alejandro A. Rabinstein; Rochester, MN S140 Eclamptic Versus Non-Eclamptic PRES (Posterior Reversible Encephalopathy Syndrome): Comparison of Clinical Features and Response to Treatment Pavan Bhargava, Fazeel Siddiqui, Vivek Patel, Rodger J. Elble and Srikanth Vallurupalli; Springfield, IL S129 Racial Disparities in Secondary Stroke Prevention Practices Pratik Bhattacharya, Seemant Chaturvedi, Flicia Mada, Leeza Salowich-Palm, Sabrina Hinton, Scott Millis, Sam Watson and Kumar Rajamani; Detroit, MI and Lansing, MI Movement Disorders S201 Allele Specific RNAi Against Triplet Repeat Disease-Causing Alleles in Huntington Disease Hirokazu Furuya, Masaki Takahashi, Shoko Watanabe, Miho Murata, Ichiro Kanazawa, Keiji Wada and Hirohiko Hohjoh; Omuta, Fukuoka, Japan and Kodaira, Tokyo, Japan S130 Predicting Ischemic Stroke Outcomes Based on Volume of Lesion Shazia Z. Choudhary, Jay-Ming Wang, Zahid Choudary, Michael Sloan, Harry R. Van Loveren, Karen R. Wilson, Morgan Wang and David A. Decker; Tampa, FL and Orlando, FL S202 Antigen-Sensitized Dendritic Cell Vaccine Against Human a-Synuclein: A Potential Cell-Based Therapy Against Parkinson’s Disease Chuanhai Cao, Xiaoyang Lin, Wang Li, Cai Jianfeng, Li Kunyu, Song Shijie and Juan Sanchez-Ramos; Tampa S131 Treatment Outside the NINDS Stroke Study Exclusion Criteria: A Case Report Nhu T. Bruce and Brett C. Meyer; San Diego, CA 5 ID: srinivasanv I Black Lining: [ON] I Time: 21:55 I Path: //xinchnasjn/01Journals/Wiley/3b2/ANA#/Vol00000/110241/APPFile/JW-ANA#110241 J_ID: ZAY Customer A_ID: SUPP11-3 Cadmus Art: 22575 Date: 31-August-11 S203 Depressive Symptoms and Neurodegeneration in the Locus Coeruleus: The Honolulu-Asia Aging Study Ross Webster, Robert D. Abbott, Helen Petrovitch, Kamal H. Masaki, Caroline M. Tanner, Jane H. Uyehara-Lock and Lon R. White; Honolulu, HI; Hiroshima, Japan and Sunnyvale, CA Stage: Page: 6 S212 Loss of Cortical Gray Matter in Parkinson’s Disease Suman Sen, Paul J. Eslinger, Daymond Wagner, Guangwei Du, Mechelle M. Lewis, Michel L. Shaffer and Xuemei Huang; Hershey, PA S213 Association of PSP with Chemical Occupational Exposure Factors Irene Litvan, Christopher R. Cunningham, Peter Lees, Leila Jackson, Jorge Juncos, David Riley, Yvette Bordelon, David Standaert, Stephen Reich, Alex C. Cambon, Joseph Jankovic, Deborah A. Hall, Richard Dubinsky, Cassandra Shepherd, Claire Henchcliffe, Ryan Uitti, Benzi Kluger, David Shprecher, Connie Marras, Eliza Gallin, James Leverenz and Shesh N. Rai; Louisville, KY; Baltimore, MD; Cleveland, OH; Atlanta, GA; Los Angeles, CA; Birmingham, AL; Houston, TX; Chicago, IL; Kansas City, KS; New York, NY; Jacksonville, Fl; Boulder, CO; Salt Lake City, UT; Toronto, Canada and Seattle, WA S204 MRI in HDLS Shows a Unique Mechanism of Neuroaxonal Degeneration C. Sundal*, C. Wider, J.A. Van Gerpen, J. Lash, J.Y. Garbern, K.J. Schweitzer, J. Aasly, B. Goodman, B.K. Woodruff, C.W. Christine, M. Baker, J.E. Parisi, S. Roeber, S. DeArmond, R. Rademakers, D.W. Dickson, D.F. Broderick, O. Andersen and Z.K. Wszolek; Gothenburg, Sweden; Jacksonville, FL; Rochester, NY; Trondheim, Norway; Scottsdale, AZ; San Francisco, CA; Rochester, MN and Munchen, Germany S205 Appropriate Outcome Measures for Cognitive Trials in Huntington’s Disease Jody Corey-Bloom, Jody Goldstein, Shea Gluhm, Charles Van Liew, Stephanie Lessig, Jagan Pillai and Steven D. Edland; La Jolla, CA S214 Psychiatric Co-Morbidities and Mortality among Hospitalized Parkinson Disease Patients Nicte Mejia and Zeina Chemali; Boston, MA S215 Comparison of Subthalamic (STN) and Pallidal (GPi) Deep Brain Stimulation (DBS) on Gait and Balance in Patients with Parkinson’s Disease (PD) Jyhgong Gabriel Hou, Minn Thant, Aliya Sarwar, Linda Fincher, Monthaporn S. Bryant, Farrah Atassi and Eugene C. Lai; Houston, TX and Galveston, TX S206 Distinctive Neurocognitive Profiles Associated with Right and Left Motor Symptom Onset in Parkinson’s Disease Paul J. Eslinger, Daymond Wagner, Suman Sen, Mechelle M. Lewis, Guangwei Du, Michele L. Shaffer and Xuemei Huang; Hershey, PA S216 Reliability of Self-Reported Parkinson’s Disease (PD) Features Caroline M. Tanner, Cheryl Meng, Ira Shoulson, Anthony E. Lang, David Oakes, Roger Kurlan, Alberto Ascherio, Flint Beal, Emily Flagg, Jennifer Harman, Michael Schwarzchild, James Beck, Bernard Ravina, Kenneth Marek, Shirley Eberly, Karen Marder and Robin Elliott; Sunnyvale, CA; Washington, DC; Toronto, ON, Canada; Rochester, NJ; Summit, NJ; Boston, MA; New York, NY; Cambridge, MA and New Haven, CT S207 The Clinical and Pathological Features of Familial Parkinsonism with EIF4G1Gene Mutation Shinsuke Fujioka, Owen A. Ross, Rosa Rademakers, Matthew J. Farrer, Dennis W. Dickson and Zbigniew K. Wszolek; Jacksonville, FL and Vancouver, BC, Canada S208 Alcohol Consumption and Risk of Parkinson Disease Rui Liu, Yikyung Park, Xuemei Huang, Xuguang Guo, Albert Hollenbeck, Aaron Blair and Honglei Chen; Research Triangle Park, NC; Rockville, MD; Hershey, PA and Washington, DC S217 First Neurological Examination Can Predict Course of Parkinson’s Disease (PD) Ali H. Rajput, Michele L. Rajput and Alex H. Rajput; Saskatoon, SK, Canada S209 Hereditary Diffuse Leukoencephalopathy with Spheroids: An Under-Diagnosed Disease C. Sundal, C. Wider, J.A. Van Gerpen, J. Lash, J.Y. Garbern, E.A. Shuster, K.J. Schweitzer, J. Aasly, B. Goodman, B.K. Woodruff, W. Kupsky, A. Tselis, C.W. Christine, M. Baker, J.E. Parisi, S. Roeber, S. DeArmond, R. Rademakers, D.W. Dickson, O. Andersen and Z.K. Wszolek; Gothenburg, Sweden; Jacksonville, FL; Rochester, NY; Trondheim, Norway; Scottsdale, AZ; Detroit, MI; San Francisco, CA; Rochester, MN and Munchen, Germany S218 Difficulty with Balance Occurs Early in PD: It Isn’t Appreciated Because It’s Not Asked about Nor Tested For Abraham N. Lieberman, Samea Husain, Naomi Salins and Anthony Santiago; Phoenix, AZ S219 Poor Dementia Screening with Mattis Dementia Rating Scale Cutoffs in Highly Educated Parkinson’s Disease Patients Travis H. Turner and Vanessa Hinson; Charleston, SC S210 Co-Existing HTT and ATXN8OS Repeat Expansions and a �Face of the Giant Panda’ Sign on MRI in a Patient with a Complex Movement Disorder Shin C. Beh, Cherian A. Karunapuzha and Shilpa Chitnis; Dallas, TX S220 Impaired Social Problem-Solving in Huntington’s Disease Charles Van Liew, Jody Goldstein, Shea Gluhm, Jagan Pillai and Jody Corey-Bloom; San Diego, CA S221 Association of Psychological Symptoms with Impulse-Control Behaviors after Dopamine Agonist Therapy for Parkinson’s Disease: A Longitudinal Study S211 Clinical Differences among PD-MCI Subtypes Jennifer G. Goldman, Glenn T. Stebbins, Bryan Bernard and Christopher G. Goetz; Chicago, IL 6 ID: srinivasanv I Black Lining: [ON] I Time: 21:55 I Path: //xinchnasjn/01Journals/Wiley/3b2/ANA#/Vol00000/110241/APPFile/JW-ANA#110241 J_ID: ZAY Customer A_ID: SUPP11-3 Cadmus Art: 22575 Date: 31-August-11 Stage: Page: 7 S233 Gender Differences in the Interleukin-6 G-174C Polymorphism and the Risk of Parkinson’s Disease Marta San Luciano, Laurie J. Ozelius, Richard B.. Lipton, Deborah Raymond, Kaili M. Stanley, Susan B. Bressman and Rachel Saunders-Pullman; New York, NY and Bronx, NY Jennifer S. Hui, Steven Cen, Megan Gomez and Lauice Yang; Los Angeles, CA and Pasadena, CA S222 Balance Difficulty in PD Correlates with Step Length and Velocity Abraham Lieberman, Naomi Salins, Tiki Hussain, Di Pan and Anthony Santiago; Phoenix, AZ S234 Serum Cholesterol Is Linked with Nigrostriatal Iron Deposition in Parkinson’s Disease Guangwei Du, Mechelle M. Lewis, Michele L. Shaffer, Honglei Chen, Richard B. Mailman and Xuemei Huang; Hershey, PA and Research Triangle Park, NC S223 Motor Asymmetry in SCAs Mitra Assadi, Bhavpreet Dham, Gazelle Zerafati, Jon Veloski and Paola Leone; Camden, NJ and Philadelphia, PA S235 Balance Difficulty Differs from Gait Difficulty in PD Abraham Lieberman, Naomi Salins, Tiki Hussain, Di Pan and Anthony Santiago; Phoenix, AZ S224 Neurotoxin Injection for Treatment of Cervical Dystonia Chandler E. Gill, Anna L. Molinari, Neil D. Manus, Michael W. Pelster, Jason A. Cook, Wallace Title and David Charles; Maywood, IL; Nashville, TN; Minneapolis, MN and New Orleans, LA S236 Adult Onset Dopamine Responsive Dystonia (DRD): Is There a New Gene? Hossein Ansari, Ludwig Gutmann and Laurie Gutmann; Morgantown, WV S237 Dystonia Induced Mechanical Stress as a Cause of DBS Extension Fracture and Expulsion Massimo Mondani, Elisa Petacchi, Roberto Eleopra, Silvia Molteni, Sabrina Gualdi, Miran Skrap and Andrea Martinuzzi; Udine, UD, Italy; Conegliano, TV, Italy and Sesto San Giovanni, MI, Italy S225 The Association between Mediterranean-Type Diet Adherence and Parkinson’s Disease Roy N. Alcalay, Yian Gu, Helen Mehia-Santana, Lucien Cote, Karen S. Marder and Nicholas Scarmeas; New York, NY S226 Autonomic Dysfunction in Early Parkinson’s Disease Anna L. Molinari, Fenna T. Phibbs, Lily Wang, Yanna Song and P. David Charles; Nashville, TN Sleep Disorders and Circadian Rhythm S301 Endogenous GABAA Receptor Enhancement Modulates Vigilance in the Primary Hypersomnias David B. Rye, Kathy Parker, Lynn Marie Trotti, Paul S. Garcia, James C. Ritchie, Michael J. Owens, Leslie Morrow, Donald L. Bliwise and Andrew Jenkins; Atlanta, GA; Rochester, NY and Chapel Hill, NC S227 Balance Difficulty in PD Correlates with the BNI Balance Scale Abraham Lieberman, Naomi Salins, Tiki Hussain, Di Pan and Anthony Santiago; Phoenix, AZ S228 STEADY-PD. Safety and Tolerability of Isradipine CR in Early Parkinson’s Disease. Interim Tolerability Data Analysis Tanya Simuni, Kevin Biglan, David Oakes, Cheryl Deeley, Irenita Gardiner, Parkinson Study Group and STEADY PD Investigators; Chicago, IL and Rochester, NY S302 Frequency of Parsaomnias in Patients with NonEpileptic Seizures Mitchell G. Miglis, Michael Boffa, Sujata Thawani, Alcibiades Rodriguez and Anuradha Singh; New York, NY S303 Endothelial Function in Patients with Obstructive Sleep Apnea Kanika Bagai, James Muldowney, Yanna Song, Lily Wang, Douglas E. Vaughan and Beth A. Malow; Nashville, TN and Chicago, IL S229 Nigella sativa Oil Controls Astrogliosis and Reduces Haloperidol-Induced Deficit in Rats Tafheem Malik**, Darakhshan Jabeen Haleem, Shema Husan, Shahid Pervez and Tasneem Fatima; Karachi, Sind, Pakistan and Karachi, Pakistan Education S230 Cost-Benefit Assessment of Two Forms of Botulinum Toxin Type-A in Different Pathologies Humberto Juarez, Santamaria Salvador, Leticia Hernandez and Enrique Molina; Mexico City, Mexico, Mexico S401 The Effectiveness of Education Intervention on Health Knowledge among Neurological Patients Mercedes Jacobson and Polina Pomerants; Philadelphia, PA S231 Weight and Height Distribution in Children with Tourette Syndrome Katie Kompoliti, Glenn T. Stebbins and Christopher G. Goetz; Chicago, IL S402 Teleneurology in Leading U.S. Medical Institutions Benjamin P. George**, Nicholas J. Scoglio, Jason I. Reminick, Kevin M. Biglan and E. Ray Dorsey; Rochester, NY and Baltimore, MD S232 Motor Deterioration after Medication Withdrawal in Early Parkinson’s Disease Chandler E. Gill**, Anna L. Molinari, Thomas L. Davis, Mark Bliton, Stuart G. Finder, Michael G. Tramontana, Peter E. Konrad and David Charles; Maywood, IL; Nashville, TN and Los Angeles, CA S403 Standardized Sign-Out Improves Communication Skills Brian D. Moseley, Jonathan H. Smith, Gloria E. DiazMedina, Mateo Paz Soldan, Meredith Wicklund, Radhika Dhamija, Haatem Reda, Michael F. Presti and Jeffrey W. Britton; Rochester, MN 7 ID: srinivasanv I Black Lining: [ON] I Time: 21:55 I Path: //xinchnasjn/01Journals/Wiley/3b2/ANA#/Vol00000/110241/APPFile/JW-ANA#110241 J_ID: ZAY Customer A_ID: SUPP11-3 Cadmus Art: 22575 Date: 31-August-11 S404 Improved Scores on the AAN Resident Inservice Training Examination (RITE) after Lecture Curriculum Intervention L. John Greenfield, Vicki Ramsey-Williams, Theresa Marshall and Boyd Koffmann; Toledo, OH and Little Rock, AR Stage: Page: 8 M605 Areas of Ischemia Associated with ��Frontal Lobe’’ Task Failure Yessenia Gomez and Argye E. Hillis; Baltimore, MD M606 Thalamic Atrophy in Gastric Bypass Patients with Cognitive Complaints Jonathan Graff-Radford, Jennifer Whitwell, Max R. Trenerry, J.E. Ahlskog, Michael D. Jensen, Clifford R. Jack, Jr. and Keith A. Josephs; Rochester, MN nd S405 Evidence Based Medicine(EBM) in the 2 Year Neurosciences Curriculum Michael J. Schneck and Edward Neafsey; Maywood, IL S406 Adapting a Teaching Hospital Inpatient Neurology Service to New Duty Hour Requirements: The Washington University Adult Neurology Experience Robert Bucelli and Barbara J. Snider; Saint Louis, MO M607 Parietal Lobe Lesions Affect the Generation of Antisaccades James A. Sharpe, Ping Cheng and Moshe Eizenamn; Toronto, ON, Canada S407 Translational Research in Neuro-AIDS and Mental Health Amanda Brown, Valerie Wojna, Bruce Shiramizu, Avindra Nath and Justin C. McArthur; Baltimore, MD; San Juan, PR and Honolulu, HI M608 Cognitive Ability Correlates of Psychiatric and Social Behaviors in Williams Syndrome Rowena Ng, Anna Ja¨rvinen-Pasley and Ursula Bellugi; San Diego, CA M609 Human Brain Mapping at the Single Cellular Level: Neuronal and Area Specific Differences in Health and Diseases Ryan P. Moore, Irisa Mahaparn, Eliezer Masliah and Pavel V. Belichenko; La Jolla, CA S408 Relationship between Medical Student Feedback and Grading and James M. Stankiewicz; Boston, MA 136th Annual Meeting Monday, September 26, 2011 Poster Session M610 Cognitive and Behavioral Differences between ADHD Populations (Inattentive Type Versus ADHD Plus) Using Neuropsychological Testing and Self-Reported Symptoms in Diagnosed Population from Years 1991–2008 Barbara C. Fisher, Danielle M. Garges and Stephany Fulda; Shelby Township, MI and Munich, Germany Posters will be displayed in Elizabeth A-E of the Manchester Grand Hyatt from 10:00 am – 7:00 pm, with authors present from 6:00 pm – 7:00 pm. NOTE: An asterisk designates a resident/fellow travel award winner. Two asterisks represent a medical student travel award winner. M611 The Use of Quetiapine in Agitated Patients with Acquired Brain Injury: A Case Control Study Sara Piccoli, Gabriella Paparella, Alec Vestri and Andrea Martinuzzi; Pieve di Soligo, TV, Italy Behavioral Neurology M601 Behaviorally-Driven Anatomical Mapping of Hemispatial Neglect Alex R. Carter, Mark P. Mcavoy, Serguei V. Astafiev, Jennifer Rengachary, Daniel L.W. Pope, Abraham Z. Snyder, Kristi Zinn, Nick Metcalf, Gordon L. Shulman and Maurizio Corbetta; Saint Louis, MO M612 On-Line Lexical-Semantics in the Semantic Variant of Primary Progressive Aphasia David S. Race and Argye E. Hillis; Baltimore, MD M613 Differences in Time Interval Distributions Reveal Controlled and Automatic Contributions to Cued Word Retrieval Kyongje Sung, Erin J. Pickett, Kerry Ledoux, Tracy D. Vannorsdall, Mohammad Elsayed, Nia M. Billings, Jessica Silva, David J. Schretlen and Barry Gordon; Baltimore, MD M602 Markers of Celiac Disease and Gluten Sensitivity in Patients with Cerebellar Ataxia Caroline Tan, Peter H. Green, Khalaf O. Bushara, Donald D. Kasarda, Ejaz Shamim, Norman Latov, Mark Hallett and Armin Alaedini; New York, NY; Minneapolis, MN; Albany, CA and Bethesda, MD M614 Gender Differences across the Lifespan in Neuropsychological Testing Performance in ADHD Population from the Years 1991–2008 Barbara C. Fisher, Danielle M. Garges and Stephany Fulda; Shelby Township, MI and Munich, Germany M603 Early Signs of Cognitive Impairment among Multiple Sclerosis Patients with Clinically Isolated Syndrome Theodora Panou, Vasileios Mastorodemos, Efrosyni Papadaki, Panagiotis G. Simos and Andreas Plaitakis; Heraklion, Greece and Rethymnon, Greece M615 Hazard Perception in Cognitively Impaired Older Drivers Nazan Aksan, Monica Lees, John D. Lee, Shaun Vecera and Matthew Rizzo; Mountain View, CA; Madison, WI and Iowa City, IA M604 Motor Chunking Is Correlated with Sensorimotor Cortex and Striatum Activation Nicholas Wymbs and Scott T. Grafton; Santa Barbara, CA 8 ID: srinivasanv I Black Lining: [ON] I Time: 21:55 I Path: //xinchnasjn/01Journals/Wiley/3b2/ANA#/Vol00000/110241/APPFile/JW-ANA#110241 J_ID: ZAY Customer A_ID: SUPP11-3 Cadmus Art: 22575 Date: 31-August-11 Stage: Page: 9 M616 Differentiation of Alzheimer’s Disease and Depression with Standard Cognitive Measures Meredith C. Frederick**, Stefan Sillau, David B. Arciniegas, C. Alan Anderson, Katherine L. Howard and Christopher M. Filley; Aurora, CO and Denver, CO M705 JAK/STAT Inhibition Slows the Progression of Temporal Lobe Epilepsy in an Animal Model Heidi L. Grabenstatter, Yasmin Cruz Del Angel, Marco I. Gonzalez, Yogendra H. Raol, Shelley J. Russek and Amy R. Brooks-Kayal; Aurora, CO and Boston, MA M617 Attention Deficit Hyperactivity Disorder in Depressed Adults Ildefonso Rodrı´guez Leyva, Rube´n Haro SIlva and Ana A. Renterı´a Palomo; San Luis Potosi, San Luis Potosi, Mexico M706 Long-Term Changes in mGluR-Mediated LongTerm Depression Following a Single Episode of Early Life Seizures in Rats Paul B. Bernard, Anna Castano and Tim A. Benke; Aurora, CO M618 Cognition and EEG Abnormalities in NonEpileptic AD(H)D/LD Patients with and without AntiEpileptic Drug/Stimulant Therapy Brittany M. DiVito, Heather A. Koch, Spencer A. Leblang, Erik C. Bakken and Drake D. Duane; Scottsdale, AZ and Tempe, AZ M707 Heterozygous Loss of the Epilepsy-Associated GABAA Receptor a1 Subunit Causes Spontaneous EEG Spike Discharges in Two Mouse Strains Fazal M. Arain and Martin J. Gallagher; Nashville, TN M708 Regional Network Disruption in Temporal Lobe Epilepsy Luigi Maccotta* and Edward Hogan; St. Louis, MO M619 Evolution of EEG Abnormalities in Non-Epileptic AD(H)D/LD Patients with and without Anti-Epileptic Drug/Stimulant Therapy Heather A. Koch, Brittany M. DiVito, Spencer A. Leblang, Erik C Bakken and Drake D. Duane; Scottsdale, AZ and Tempe, AZ M709 Mice Deficient in SNAREs/SNARE Regulators Predict Kindling Phenotype John T. Slevin, Elena E. Matveeva, Sidney W. Whiteheart, Greg A. Gerhardt and Thomas C. Vanaman; Lexington, KY M620 Transection of CA3 Does Not Affect Memory in Rats Mohamad Z. Koubeissi, Saifur Rashid, Gemma Casadesus, Joseph LaManna, Kui Xu, Hans Luders and Dominique Durand; Cleveland, OH M710 Pharmacokinetic Equivalence between ImmediateRelease and Extended-Release Topiramate Lawrence J. Lambrecht, Wesley M. Todd and Mark B. Halvorsen; Maple Grove, MN M711 Cingulate Epilepsy, Reporting 3 Clinical and Electrophysiologic Subtypes with Surgical Outcomes Mhd Rafeed Alkawadri, Norman K. So, Paul C. Van Ness and Andreas V. Alexopoulos; Cleveland, OH and Dallas, TX M621 Cruetzfeldt-Jakob Disease Presenting as a Rapidly Progressing Dementia with Non-Convulsive Status Epilepticus Natasha Tilluckdharry, Megan McGarry and Dipak P. Pandya; Paterson, NJ M712 GABAB Receptor Antagonists Reduce ProEpileptic Activity in Hippocampal Slices of Ts65Dn Mice, a Genetic Model of Down Syndrome Alexander M. Kleschevnikov, Brett Rasmuss, Pavel V. Belichenko and William Mobley; La Jolla, CA Epilepsy M701 Controlled Cortical Impact in Adult Rats and Posttraumatic Seizures and Epilepsy Kevin M. Kelly, Elena A. Kharlamov, Eric R. Miller, Bo Lu and Zakaria Mtchedlishvili; Pittsburgh, PA and Philadelphia, PA M713 Lacosamide: Long-Term Safety and Efficacy in Partial-Onset Seizures William Rosenfeld, Nathan B. Fountain, Gintaras Kaubrys, Elinor Ben-Menachem, Cindy McShea, Jouko Isojarvi and Pamela Doty; St. Louis; Charlottesville; Vilnius, Lithuania; Go¨teborg, Sweden and Raleigh M702 Serotonin 1A Receptors and Memory in Temporal Lobe Epilepsy William H. Theodore, Edythe Wiggs, Ashley Martinez, Irene Dustin, Omar Khan, Shmuel Appel, Patricia Reeves-Tyer and Susumu Sato; Bethesda M714 Lacosamide: Long-Term Safety in Partial-Onset Seizures Robert F. LeRoy, Gregory Krauss, Nathan B.. Fountain, Deanne Dilley, O’Neill D’Cruz and Pamela Doty; Dallas, TX; Baltimore, MD; Charlottesville, VA and Raleigh, NC M703 Ictal Hypoxemia Is Associated with Cardiac Repolarization Abnormalities Lisa M. Bateman, Franchette Pascual, Michael Lee, ChinShang Li and Masud Seyal; Sacramento, CA and Los Angeles, CA M715 Withdrawn. M716 Computational Models of Ligand-Gated Receptor Function Characterize Anticonvulsant Drug Actions at GABAergic and Glutamatergic Synapses and David E. Naylor; Torrance, CA M704 Gray Matter Heterotopia in an Epileptic Brain Malformation Are Functionally Connected to Overlying Cortex Joanna A. Christodoulou, Linsey M. Walker, Stephanie N. Del Tufo, Tami Katzir, Susan Whitfield-Gabrieli, John D.E. Gabrieli and Bernard S. Chang; Cambridge, MA; Boston, MA and Haifa, Israel M717 Status Epilepticus: An Independent Predictor of Poor Survival after Anoxic Brain Injury 9 ID: srinivasanv I Black Lining: [ON] I Time: 21:55 I Path: //xinchnasjn/01Journals/Wiley/3b2/ANA#/Vol00000/110241/APPFile/JW-ANA#110241 J_ID: ZAY Customer A_ID: SUPP11-3 Cadmus Art: 22575 Date: 31-August-11 Stage: Page: 10 M806 Reevaluating Disease Progression in Facioscapulohumeral Dystrophy Jeffrey M. Statland*, William B. Martens, Kathryn R. Wagner, John Kissel, Shree Pandya, Michael P. McDermott and Rabi Tawil; Rochester, NY; Baltimore, MD and Columbus, OH Jennie Luna, Nelly Awkar, Megan McGarry, Deepthi Karanam and Dipak P. Pandya; Paterson, NJ M718 Periodic Lateralized Epileptiform Discharges (PLEDs)-Rhythmic Discharges (RDs) in Anoxic Encephalopathy Sushanth Bhat, Sombabu Maganti, Eli S. Neiman, Divya Gupta and Sudhansu Chokroverty; Edison, NJ M807 Dysferlin (DYSF) Is Absent from the Muscle-Fiber Sarcolemma in Various Neuromuscular Diseases, and in Sporadic Inclusion-Body Myositis (s-IBM) It Forms Cytoplasmic Inclusions Colocalizing with Amyloid-b42 (Ab42) Mafalda Cacciottolo, Anna Nogalska, Carla D’Agostino, W King Engel and Valerie Askanas; Los Angeles, CA M719 Periodic Lateralizing Epileptiform Discharges (PLEDs) Causing Persistent Magnetic Resonance Imaging (MRI) Changes in Ipsilateral Thalamus Umang Shah, Umer Akber and Chunyang Wang; Camden, NJ M808 Novel Demonstration of ConformationallyModified Tau in Sporadic Inclusion-Body Myositis (s-IBM) Muscle Fibers. Possible Importance to s-IBM Pathogenesis Anna Nogalska, Carla D’Agostino, King W. Engel and Valerie Askanas; Los Angeles, CA M720 Ammoniacal Encephalopathy Presenting as Complex Partial Seizure-Like Episodes: A Case Series Darine Kassar and Stanley Iyadurai; Saint Louis, MO M721 Status Epilepticus as an Initial Manifestation of Sneddon’s Syndrome Anish Shah, Saurav Sen, Jennie Luna and Dipak P. Pandya; Paterson, NJ M809 Anti-Ganglioside Antibodies Mimic CNS Inhibitors of Axon Regeneration Kazim Sheikh and Gang Zhang; Houston, TX M722 Status Epilepticus Secondary to Milk Alkali Syndrome Induced by Hypercalcemia (Oral Antacids) Rabih Kashouty, Noor Yono and Mershed Al Samara; Manhattan, NY; Manhasset, NY and Southfield, MI M810 Evaluating Mechanoreceptors in Glabrous Skin in Diabetic Neuropathy Iliza Myers, Kay Artibee, Jun Li and Amanda C. Peltier; Nashville, TN M723 A Case of Magnesium-Responsive Paraneoplastic Non-Convulsive Status Epilepticus Robert K. Shin, Anna V. Rosenbaum and Nicholas Frost; Baltimore, MD M811 Amiodarone Associated Myopathy. A Report of 4 Cases Eoin P. Flanagan, Charles M. Harper, Erik K. St. Louis, Michael H. Silber, Ronald C. Petersen and Keith A. Josephs; Rochester, MN M724 Withdrawn. Neuromuscular Disease M812 Cervical Cord 1H-Magnetic Resonance Spectroscopy (1H-MRS) in Amyotrophic Lateral Sclerosis (ALS): Relationship to Clinoco- Electrophysiological Dysfunction Ken Ikeda, Yasuhiro Yoshii, Kiyoko Murata, Riya Nagata, Kiyokazu Kawabe, Osamu Kano and Yasuo Iwasaki; Tokyo, Japan M801 Nicotinamide Mononucleotide (NMN) Treatment of Diabetic Neuropathy Ankit Sura, Mitch Onken, Krish Chandrasekaran, Helen Chen and James W. Russell; Baltimore, MD M813 Localization of FIG4 in the Nervous System Jiasong Guo, Qing Yan and Jun Li; Nashville, TN M802 Defining Outcome Measures in Sporadic IBM for a Follistatin Gene Transfer Clinical Trial Linda P. Lowes, Lindsay N. Alfano, Laurence ViolletCallendret, Xiomara Q. Rosales, Brian Kaspar, K. Reed Clark, Zarife Sahenk, Kevin M. Flanigan and Jerry R. Mendell; Columbus, OH M814 High Frequency Chest Wall Oscillation (HFCWO) in Amyotrophic Lateral Sclerosis (ALS) Patients Decreases Respiratory Infections Requiring Antibiotics and/or Hospitalization: A Pre-Post Observational Study Benjamin R. Brooks, Velma L. Langford, Amber L. Ward, Nicole M. Williams, Mindy S. Nichols, Elena Bravver and Scott C. Lindblom; Charlotte, NC M803 Tomaculous Formation in HNPP Jun Li, Zahara M. Jaffer, Xuebao Zhang, Qing Yan, Michael E. Shy, Ueli Suter, Jonathan Chernoff and Jiasong Guo; Nashville, TN; Philadelphia; Nashville; Detroit and Zurich, Swaziland M815 Dominant Cardiomyopathy and Very Distal Myopathy with Rod, Myofibrillar and AVSF Myopathology Stanley J. Iyadurai, Chris Weihl, Bob Baloh and Alan Pestronk; St. Louis, MO M804 Zebrafish Models of Amyotrophic Lateral Sclerosis Stacey A. Sakowski, J. Simon Lunn, Angela S. Busta, Carey Backus, Sang Su Oh, James J. Dowling and Eva L. Feldman; Ann Arbor, MI M816 Adult-Onset Rod Myopathy Syndrome (AORMS): Sustained Benefit from IVIG Plus Rituximab Shalini Mahajan, King W. Engel, Valerie Askanas, Indermohan Luthra and Varun Gupta; Los Angeles, CA and Rancho Mirage, CA M805 ALS-Like Spinal Cord Pathology in Transgenic Mice with a Mutation in the Valosin-Containing Protein Gene Hong Z. Yin, Tahseen Mozaffar, Virginia E. Kimonis and John H. Weiss; Irvine, CA 10 ID: srinivasanv I Black Lining: [ON] I Time: 21:55 I Path: //xinchnasjn/01Journals/Wiley/3b2/ANA#/Vol00000/110241/APPFile/JW-ANA#110241 J_ID: ZAY Customer A_ID: SUPP11-3 Cadmus Art: 22575 Date: 31-August-11 M817 Geographic Trends of ALS in Minnesota Eric J. Sorenson and Lisa Kronk; Rochester, MN and Minneapolis, MN Stage: Page: 11 M827 Subacute Paraneoplastic Motor Neuronopathy with Ri Immunoeactivity and Breast Cancer: A Clinicopathologically Studied Patient and David S. Younger; New York, NY M818 Clinical Features Associated with Fine Specificity of IgG Anti-GQ1b Antibodies Susumu Kusunoki, Seiko Suzuki, Masami Ueda and Motoi Kuwahara; Osaka-Sayama, Osaka, Japan M828 Magnetic Resonance Neurography Versus Electromyography for the Diagnosis of Radigulopathy Youssef A. Dakka, Andrew Biondo, John Corrigan, Shehanaz Ellik and Ximena Arcilla-Londono; Detroit, MI M819 Amyotrophic Lateral Sclerosis [ALS] Dashboard: Cognitive, Behavioral, Bulbar, Respiratory, Arm, Leg Domain-Specific Disease Staging – Statistically Significant Larger Proportion of !Stage 3 Behavioral, Bulbar, Arm and Leg, but Not Cognitive or Re Benjamin R. Brooks, Mohammed S. Sanjak, Elena Bravver, William L. Bockenek, Urvi G. Desai, Scott C. Lindblom, Thomas J. Paccico, Nicole M. Williams, Mindy S. Nichols, Amber L. Ward, Kathryn A. Wright, Mifflin O’Neill, Velma L. Langford, Kristy Walgren, Priscilla Russo, Anne Blythe and Heather Oplinger; Charlotte, NC M829 Denervation Causes Lower Expression of Heat Shock Protein 27 in Regenerating Skeletal Muscle Takahiro Jimi, Yoshihiro Wakayama and Hajime Hara; Yokohama, Japan M830 Rapid Magnetic Stimulation Versus Conventional Physiotherapy in Bell’s Palsy Devathasan Gobinathan and Lea Dosado; Singapore, Singapore M820 A New Phenotype in Neurodegeneration: Trigeminal Sensory Deficits Preceding Rostro-Caudal Progressive Motor and Sensory Neuronopathy, Chorea and Dementia Camilo Toro, Justin Y. Kwan, Tanya J. Lehky, Bryan J. Traynor, Catherine A. Groden, Rena A. Godfrey, Michele E. Nehrebecky, Wiggs A. Edythe and Gahl William; Bethesda, MD M831 Establishing a Rare Disease Center in China: The Periodic Paralysis Program Qing Ke, Benyan Luo, Ming Ming, Michael Hanna, Jacob Levitt, Barbara Herr and Robert C. Griggs; Hang Zhou, Zhe Jiang, China; Rochester, NY; London, United Kingdom and New York, NY M821 Update on a Phase 1 Study of ISIS 333611 in Familial ALS Due to SOD1 Mutations Timothy M. Miller, Richard Smith, Swati Aggarwal, Alan Pestronk, William David, Jeffrey Rothstein, Ericka Simpson, Benjamin Brooks, Isaac Bakst, Patricia Andres, Peggy Allred, Katie Alexander, Kathie Bishop, C.F. Bennett and Merit Cudkowicz; St. Louis, MO; La Jolla, CA; Boston, MA; Baltimore, MD; Houston, TX; Charlotte, NC and Carlsbad, CA M832 Effect of Fatigue on Pulmonary Function Studies in ALS Patients Kathleen S. Alfuth, Ericka P. Simpson and Aparajitha K. Verma; Houston, TX M833 Monomelic Amyotrophy – A Rare Case Presentation Amtul Farheen, Manpreet Multani, Aiesha Ahmed, Raji Grewal and Raji Grewal; Edison, NJ M822 Retrospective Analysis of a Cohort of Non Systemic Vasculitic Neuropathy Raghav Govindarajan, Jagadish B. Agadi, Anita Mahadevan and S.K. Shankar; Weston, FL and Bangalore, India M834 Botulism: A Case Report Peter Struck, Amtul Farheen and Sushanth Bhat; New Brunswick and Edison, NJ M835 A Novel Pentameric Thiophene Derivative (p-FTAA) Strongly Highlights Clusters of Paired Helical Filaments Containing Phosphorylated Tau in Sporadic Inclusion-Body Myositis (s-IBM) Muscle Fibers There´se Klingstedt, Anna Nogalska, Cristiane Blechschmidt, Stefan Prokop, Frank L. Heppner, King W. Engel, Valerie Askanas and Peter K.R. Nilsson; Linko¨ping, Sweden; Los Angeles and Berlin, Germany M823 Optimizing a Hospital Discharge Database for Passive Surveillance of Guillain-Barre Syndrome (GBS) Christopher D. Lee and Timothy F. Jones; Nashville, TN M824 Gene Expression Analysis in Patients with Amyotrophic Lateral Sclerosis and Multifocal Motor Neuropathy Alexander Shtilbans, Soon Gang Choi, Mary E. Fowkes, Greg Khitrov, Mona Shahbazi, Jess Ting, Stuart C. Sealfon and Dale J. Lange; New York, NY Neurogenetics M1001 Withdrawn. M825 Small-Fiber Polyneuropathy (SFPN) Can Cause Chronic Pain and Somatic Complaints in Youth and Anne Louise Oaklander; Boston, MA M1002 Clinico-Genetic Characterization of a Large Italian Cohort with Primary Spastic Paraplegia Andrea Martinuzzi, Mariateresa Bassi, Grazia D’Angelo, Sara Bonato, Gabriella Paparella, Olimpia Musumeci, Mariagiovanna Rossetto, Marianna Fantin, Francesca Peruch, Alessia Arnoldi, Claudia Crimella, Erika Tenderini, Paolo M826 Median Nerve Ultrasound in Diabetic PN with and without Carpal Tunnel Syndrome Anhar Hassan, Andrea Leep Hunderford, James Watson, Andrea Boon and Eric Sorenson; Rochester, MN 11 ID: srinivasanv I Black Lining: [ON] I Time: 21:55 I Path: //xinchnasjn/01Journals/Wiley/3b2/ANA#/Vol00000/110241/APPFile/JW-ANA#110241 J_ID: ZAY Customer A_ID: SUPP11-3 Cadmus Art: 22575 Date: 31-August-11 Stage: Page: 12 M1102 Computed Tomography Characteristics of Pediatric Traumatic Brain Injury Korak Sarkar and Kia Shahlaie; Sacramento Bonanni, Vanessa Casanova, Giovanni Meola, Giacomo Comi, Antonio Toscano and Nereo Bresolin; Conegliano, TV, Italy; Bosisio Parini, LC, Italy; Messina, Italy and Milano, Italy M1103 Neurological Outcome Scale for Traumatic Brain Injury: Predictive Validity and Sensitivity to Change Paolo Moretti, Stephen R. McCauley, Elisabeth A. Wilde, James N. Scott and Guy L. Clifton; Houston, TX and Calgary, AB, Canada M1003 A Study of ACE and ADD1 Gene Polymorphism in Extra and Intracranial Atherosclerosis in Patients with Ischemic Stroke Jayantee Kalita, Usha K. Misra, Sunil Kumar, Bishwanath Kumar, Bindu I. Somarajan and Balraj Mittal; Lucknow, Uttar Pradesh, India M1104 Determination of Awareness in Patients with Severe Brain Injury Using EEG Spectral Analysis Andrew M. Goldfine, Jonathan D. Victor, Mary M. Conte, Jonathan C. Bardin and Nicholas C. Schiff; New York, NY and White Plains, NY M1004 Generation and Characterization of MeCP2_270 Mutant Mice Chiranjeevi Bodda, Karolina Can, Liakath Ali Kifayathulla, Hope Yao Agbemenyah and Ashraf U. Mannan; Goettingen, Germany M1105 Orthopedic Injuries in Multiple Sclerosis Patients: Analysis of the Incidence of Injury in This Vulnerable Population Daniel Mandell** and William Tosches; Worcester, MA M1005 Identification of Epigenomic Modifications as Biomarkers for Amyotrophic Lateral Sclerosis Claudia Figueroa-Romero, Junguk Hur, Yu Hong, John S. Lunn, Crystal Pacut, Colin E. Delaney, Raymond Yung, Brian Callaghan and Eva L. Feldman; Ann Arbor, MI M1106 Raising the Dead: Barriers to Therapeutic Hypothermia Post Cardiac Arrest and Mark Andrews; Palo Alto, CA M1006 A Drosophila Model of Williams Syndrome Ralph J. Greenspan and Jenee Wagner; La Jolla, CA M1107 Abnormal Oculomotor Function among BlastInjured Combat Veterans Bruce P. Capehart, Adam Mehlenbacher, Carol SmithHammond, Dale Bass and James Burke; Durham, NC M1007 Clinical and Pathological Features of Progressive Supranuclear Palsy with Family History Shinsuke Fujioka, Avi Algom, Audrey Strongosky, Dennis W. Dickson and Zbigniew K. Wszolek; Jacksonville, FL Neurology Critical Care M1201 Withdrawn. M1008 Aberrant Methylation by Mutations of DNA Methyltransferase 1 Cause Peripheral and Central Axonal Degeneration Christopher J. Klein, Maria V. Botuyan, Yanhong Wu, Christopher J. Ward, Garth A. Nicholson, Simon Hammans, Hiromitch Yamanishi, Adam R. Karpf, Douglas C. Wallace, Mariella Simon, Cecilie Lander, Julie M. Cunningham, Glenn E. Smith, William J. Litchy, Benjamin Boes, Elizabeth J. Atkinson, Sumit Middha, P. James Dyck, Joseph E. Parisi, Georges Mer, David I. Smith and Peter J. Dyck; Rochester, MN; Sydney, Australia; Southampton, United Kingdom; Hyogo, Japan; Buffalo, NY; Irvine, CA; Herston, Australia and Indianapolis, IN M1202 Predictors of Outcome in Prolonged Refractory Status Epilepticus Sara Hocker, Jeffrey W. Britton, Jay Mandrekar, Eelco F.M. Wijdicks and Alejandro A. Rabinstein; Rochester, MN M1203 Refractory Status Epilepticus and Heart Damage – A Warning for Neurologists Sara Hocker, Jeffrey W. Britton, Jay Mandrekar, Eelco F.M. Wijdicks and Alejandro A. Rabinstein; Rochester, MN M1204 Safety and Feasibility of Intrathecal Nicardipine for Vasospasm after Subarachnoid Hemorrhage William D. Freeman, Sothear Luke, Christina Campbell, Dan Jackson and James F. Meschia; Jacksonville, FL M1009 Common and Distinct Associations of HLA-DRB1 and -DPB1 Alleles with Neuromyelitis Optica and Multiple Sclerosis in Japanese Satoshi Yoshimura, Noriko Isobe, Takuya Matsushita, Tomomi Yonekawa, Katsuhisa Masaki and Jun-ichi Kira; Fukuoka, Japan M1205 Acute Bacterial Meningitis as a Possible Cause of Severe Dysautonomia Leading to Death Yadira Velazquez-Rodriguez, Umer Akbar and Evren Burakgazi-Dalkili; Camden, NJ M1010 Computer Simulations of Striatal Atrophy and Age at Onset of Huntington’s Disease Steven D. Edland and Jagan Pillai; La Jolla, CA Pediatric Neurology M1301 Diffusion Tensor MRI Tractography Reveals Altered Brainstem Fiber Connections Accompanying Agenesis of the Corpus Callosum Juebin Huang, Jian Chen, Haipeng Cai, Robert P. Friedland, Mohamad Z. Koubeissi, David H. Laidlaw and Alexander P. Auchus; Jackson, MS; Hattiesburg, MS; Louisville, KY; Cleveland, OH and Providence, RI Trauma/Injury M1101 A Human Natural IgM Drives Axon Outgrowth Xiaohua Xu, Arthur Warrington, Brent Wright, Allan Bieber, Virginia Van Keulen, Larry Pease and Moses Rodriguez; Rochester, MN 12 ID: srinivasanv I Black Lining: [ON] I Time: 21:55 I Path: //xinchnasjn/01Journals/Wiley/3b2/ANA#/Vol00000/110241/APPFile/JW-ANA#110241 J_ID: ZAY Customer A_ID: SUPP11-3 Cadmus Art: 22575 Date: 31-August-11 M1302 Neurofibromatosis 1 (NF1) Vasculopathy in Children – An Emerging Entity Partha S. Ghosh, A.D. Rothner and Manikum Moodley; Cleveland, OH Stage: Page: 13 Mariet Allen, Minerva M. Carrasquillo, Christopher N. Rowley, Otto Pedraza, Morad Ansari, Caroline Hayward, Igor Rudan, Harry Campbell, Ozren Polasek, Nicholas D. Hastie, Asha A. Nair, Sumit Middha, Sooraj Maharjan, Thuy Nguyen, Li Ma, Kimberly G. Malphrus, Ryan Palusak, Sarah Lincoln, Gina Bisceglio, Constantin Georgescu, Christopher P. Kolbert, Jin Jen, Zbigniew Wszolek, Maria Barcikowska, Sigrid B. Sando, Jan Aasly, Kevin Morgan, Clifford Jack, Ronald C. Petersen, Neill R. Graff-Radford, Alan Wright, Dennis W. Dickson and Steven G. Younkin; Jacksonville, FL; Rochester, MN; Edinburgh, United Kingdom; Split, Croatia; Zagreb, Croatia; Warsaw, Poland; Trondheim, Norway and Nottingham, United Kingdom M1303 Macro CK-1 a Cause of Spuriously Elevated CK Associated with Leukoencephalopathy in an Infant and John B. Bodensteiner; Phoenix, AZ M1304 Pharmaceuticals in the Environment: A Focus on Neurological Medications and Ilene Ruhoy; Seattle, WA Rehabilitation and Regeneration T1504 Insulin-Like Growth Factor 1 (IGF-1) and Risk of Alzheimer’s Disease: The Framingham Study Andrew J. Westwood*, Alexa S. Baiser, Ramachandran S. Vasan, Tamara B. Harris, Ronenn Roubenoff, Aleksandra Pikula, Rhoda Au, Charles DeCarli, Philip A. Wolf and Sudha Seshadri; Boston, MA; Framingham, MA; Bethesda, MD and Sacremento, CA M1401 Human Induced Pluripotent Stem Cell-Derived Neural Progenitor Grafting into Rat Hippomcapus Alison L. Althaus, Yu Liu, Duriel Hardy and Jack M. Parent; Ann Arbor, MI M1402 Local Molecular Manipulation and Peripheral Nerve Regeneration Douglas W. Zochodne, Kimberly J. Christie, Christine A. Webber, Chu Cheng and Jose A. Martinez; Calgary, AB, Canada and Edmonton, AB, Canada T1505 Components of Blood Pressure and Progression of Cerebral Leukoaraiosis: The ARIC Study Rebecca F. Gottesman, Diane J. Catellier, Laura H. Coker, Josef Coresh, Clifford R. Jack, Jr., David S. Knopman, Kathryn M. Rose, A. Richey Sharrett, Dean K. Shibata and Thomas H. Mosley; Baltimore, MD; Chapel Hill, NC; Winston-Salem, NC; Rochester, MN; Durham, NC; Seattle, WA and Jackson, MS M1403 Very Early Gait Training after Acute Stroke; a Dose-Escalation Study Randolph S. Marshall, Ying K. Cheung, Clare Bassile, Laura A. Evensen, Roujie Chen, Veronica Perez, Ronald M. Lazar and Bernadette Boden-Albala; New York T1506 Therapeutic and Preventive Effects of a Novel AD Vaccine Carmen Vigo, Ivan Cuevas, Lucia Fernandez, Valter Lombardi, Richard Manivanh and Ramon Cacabelos; Sunnyvale, CA and Bergondo, La Coruna, Spain th 136 Annual Meeting Tuesday, September 27, 2011 Poster Session T1507 MoCA vs. MMSE: Patterns of Cognitive Performance across Adult Lifespan in a Non-Clinical Sample Shea Gluhm, Charles Van Liew, Jody Goldstein, Guerry Peavy, Mark Jacobson, Stephanie Lessig and Jody Corey-Bloom; La Jolla, CA and San Diego, CA Posters will be displayed in Elizabeth A-E of the Manchester Grand Hyatt from 10:00 am – 7:00 pm, with authors present from 6:00 pm – 7:00 pm. NOTE: An asterisk designates a resident/fellow travel award winner. Two asterisks represent a medical student travel award winner. T1508 Amyloid Imaging with Florbetapir-PET Correlates with Cognitive Performance in NonDemented Oldest-Old Maria M. Corrada, Dana E. Greenia, Chris M. Clark, Carrie B. Peltz, Mark A. Mintun, Michael J. Pontecorvo, Abhinay D. Joshi and Claudia H. Kawas; Irvine, CA; Philadelphia, PA and St. Louis, MI Dementia and Aging T1501 Amyloid-Beta Dynamics and Prevention Trials in Dominantly Inherited Alzheimer’s Disease Randall J. Bateman and on behalf of the Dominantly Inherited Alzheimer Network; St. Louis, MO T1502 Integrating Genome-Wide Association and Functional Validation To Understand Susceptibility for Alzheimer’s Pathology Joshua M. Shulman, Portia I. Chipendo, Lori B. Chibnik, Brendan T. Keenan, Dong Tran, Matthew A. Huentelman, Julie A. Schneider, Eric M. Reiman, Denis A. Evans, David A. Bennett, Mel B. Feany and Philip L. De Jager; Boston, MA; Chicago, IL and Phoenix, AZ T1509 FRET Measurements of Ab-Induced Glutamate Release from Astrocytes Sara Sanz-Blasco, Juan C. Pin˜a-Crespo, Maria V. Talantova and Stuart A. Lipton; La Jolla, CA T1510 Is Poststroke Dementia Related to Amyloid Deposition and Microglia Activation? Wolf-Dieter Heiss, Basia Radlinska, Jean-Paul Soucy, Ralf Schirrmacher, Alexander Thiel and Vladimir Hachinski; Cologne, Germany; Montreal, QC, Canada and London, ON, Canada T1503 Brain Expression Genome-Wide Association Study (eGWAS) and Alzheimer’s Disease Nilufer Ertekin-Taner, Fanggeng Zou, High Seng Chai, Curtis S. Younkin, Julia Crook, V Shane Pankratz, 13 ID: srinivasanv I Black Lining: [ON] I Time: 21:55 I Path: //xinchnasjn/01Journals/Wiley/3b2/ANA#/Vol00000/110241/APPFile/JW-ANA#110241 J_ID: ZAY Customer A_ID: SUPP11-3 Cadmus Art: 22575 Date: 31-August-11 T1511 Cycad Methylazoxymethanol Linked to DNA Damage, Cancer and Neurodegeneration Glen E. Kisby, Rebecca C. Fry, Michael R. Lasarev, Theodor K. Bammler, Richard P. Beyer, Mona I. Churchwell, Daniel R. Doerge, Lisiane B. Meira, Valerie S. Palmer, Ana-Luisa Ramos-Crawford, Xuefeng Ren, Robert S. Sullivan, Terrance J. Kavanagh, Leona D. Samson, Helmut Zarbl and Peter S. Spencer; Portland, OR; Seattle, WA; Cambridge, MA; Jefferson, AR; Guildford, Kent, United Kingdom; Buffalo, NY; Piscataway, NJ and Chapel Hill, NC Stage: Page: 14 T1520 The First Nationwide Survey of Bardet-Biedl Syndrome in Japan Makito Hirano, Toshihide Yamashita, Yasushi Ikuno, Hiromi Iwahashi, Mitsuru Ohishi, Toshiyuki Mano, Ryu Ishihara, Ichiro Tanaka, Keiko Yanagihara, Yusaku Nakamura and Susumu Kusunoki; Sakai, Osaka, Japan; Suita, Japan; Izumi, Japan; Osaka, Japan; Kashihara, Japan and Osaka Sayama, Japan T1521 P600 Word Repetition Effect Amplitude Correlates with Left Hippocampal Volume John M. Olichney, Rawi Nanakul, Alireza K. Javan, Patrick E. Adams, Andrea Schneider, Andreea Seritan, Randi J. Hagerman, Paul J. Hagerman and Susan M. Rivera; Davis, CA and Sacramento, CA T1512 Genetic Associations between VPS10 Receptor Genes and Late-Onset Alzheimer’s Disease Christiane Reitz, Joseph Lee, Lindsay Farrer, Margaret PericakVance, Jonathan Haines, Ekaterina Rogaeva, Peter St. GeorgeHyslop and Richard Mayeux; New York; Boston; Miami; Nashville and Toronto, Canada T1522 Visuospatial Construction Measures and Their Utility in Identifying Dementia of the Alzheimer’s Type Bonnie M. Scott, G. Duncan, H. Carlson, Matthew Nance, Michele K. York, Angela Larery, Josephine Stouter and Adriana M. Strutt; Houston, TX T1513 Cardiac Ejection Fraction, Cognitive Function and Leukoaraiosis in an Elderly Cohort: The Cardiovascular Health Study Rebecca F. Gottesman, Salvador Cruz-Flores, Annette Fitzpatrick, John Gottdiener, Traci Bartz, Richard Kronmal and W.T. Longstreth, Jr.; Baltimore, MD; St. Louis, MO and Seattle, WA T1523 Responder Analysis in a Trial of Once-Daily, Extended-Release Memantine (28 mg) in Patients with Moderate to Severe Alzheimer’s Disease Stephen M. Graham, Suzanne Hendrix, Michael L. Miller, Vojislav Pejovic and Michael Tocco; Jersey City, NJ; Salt Lake City, UT and Chicago, IL T1514 Predicting MCI Outcome with Clinically Available MRI and CSF Biomarkers David S. Heister, James B. Brewer, Sebastian Magda, Kaj Blennow and Linda K. McEvoy; La Jolla, CA and Mo¨lndal, Sweden T1524 Rates of Cognitive Decline and Alzheimer’s Disease (AD) Neuropathology in Oldest-Old Archana B. Balasubramanian, Claudia H. Kawas, Daniel J. Berlau, Carrie B. Peltz and Marı´a M. Corrada; Irvine, CA T1515 Light and Electron Microscopic Analysis of FUS Immunoreactivity in 3 Variants of Tau and TDP-43 Negative Frontotemporal Lobar Degeneration Keith A. Josephs, Wen-Lang Lin, Joseph E. Parisi, Neil GraffRadford, Ronald C. Petersen and Dennis W. Dickson; Rochester, MN and Jacksonville, FL T1525 Cortical Thickness on MR Imaging: Relation to Cognitive Reserve in Normal Aging and Mild Cognitive Impairment Jagan A. Pillai, Linda K. McEvoy, Donald J. Hagler, Jr, Dominic Holland, Anders M. Dale, David P. Salmon, Douglas Galasko and Christine Fennema-Notestine; San Diego, CA T1516 Effects of Once-Daily, Extended-Release Memantine (28 mg/day) on Cognitive Domains in Patients with Moderate to Severe Alzheimer’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 T1526 Effects of Once-Daily, Extended-Release Memantine on Individual Activities of Daily Living in Patients with Moderate to Severe Alzheimer’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 T1517 Efficacy of Memantine by Baseline Disease Severity: A Pooled Post-Hoc Analysis of Trials in Mild to Moderate Alzheimer’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 T1527 Neurophysiologic Markers of Aging-Related Muscle Weakness Ela B. Plow, Dina Gohar, Mehmed B. Bayram, Jing Hou, Alexandria Wyant, Yin Fang, Vlodek Siemionow and Guang H. Yue; Cleveland, OH T1518 Clinical Gait Abnormalities and Hippocampal Morphometry in MCI: Preliminary Results from the ADNI Study Vincent S. DeOrchis and Joe Verghese; Bronx, NY T1528 The Purkinje Cell of the Cerebellar Cortex in Alzheimer’s Disease and Stavros J. Baloyannis; Thessaloniki, Greece T1519 Topography of Cortical Thinning in PIB-Negative Subcortical Vascular Dementia Versus Alzheimer’s Disease Chi Hun Kim, Sang Won Seo, Sung Tae Kim, Jae-Hong Lee, Jae Seung Kim, Seung Jun Oh, Suk-Hui Kim, Hae Kwan Cheong, Jong-Min Lee, Seun Jeon and Duk L. Na; Seoul, Korea and Suwon, Korea T1529 A Translational Program of BDNF Gene Delivery for Alzheimer’s Disease Mark H. Tuszynski, Alan Nagahara, Adrian P. Kells, J. Bringas, John Forsayeth and Krystopf S. Bankiewicz; La Jolla, CA and San Francisco, CA 14 ID: srinivasanv I Black Lining: [ON] I Time: 21:55 I Path: //xinchnasjn/01Journals/Wiley/3b2/ANA#/Vol00000/110241/APPFile/JW-ANA#110241 J_ID: ZAY Customer A_ID: SUPP11-3 Cadmus Art: 22575 Date: 31-August-11 T1530 Imaging Signatures of Pathology in Behavioral Variant Frontotemporal Dementia Jennifer L. Whitwell, Clifford R. Jack, David S. Knopman, Bradley F. Boeve, Ronald C. Petersen, Joseph E. Parisi, Dennis W. Dickson and Keith A. Josephs; Rochester, MN and Jacksonville, FL Stage: Page: 15 T1605 Heavily T2-Weighted Magnetic Resonance Myelography for Post-Lumbar Puncture Headache: A Pilot Study Yen-Feng Wang, Jong-Ling Fuh, Jiing-Feng Lirng and Shuu-Jiun Wang; Taipei, Taiwan T1531 Improved Statistical Power To Detect Treatment Effects on Functional Outcomes in Alzheimer’s Disease (AD) Clinical Trials by Item-Response Theory (IRT) M. Colin Ard, Douglas R. Galasko and Steven D. Edland; La Jolla, CA T1606 Angioplasty and Stenting for the Treatment of Idiopathic Intracranial Hypertension Associated with Dural Venous Sinus Stenosis Parisa P. Javedani**, Jeremy D. Fields, Kenneth C. Liu, Stanley L. Barnwell and Bryan Petersen; Portland, OR and Charlottesville, VA T1532 Neuropathologic Basis of Age-Associated Brain Atrophy Deniz Erten-Lyons, Randy Woltjer, Hiroko Dodge, Lisa Silbert and Kaye Jeffrey; Portland, OR T1607 Adrenal Insufficiency Presenting as Postural Tachycardia Syndrome Darine Kassar and Stanley Iyadurai; Saint Louis, MO T1608 Prevalence of Chronic Migraine (CM), HeadacheRelated Disability and Sociodemographic Factors in the US Population: Results from the American Migraine Prevalence and Prevention (AMPP) Study Dawn C. Buse, Michael L. Reed, Kristina Fanning, Aubrey N. Manack, Catherine C. Turkel and Richard B. Lipton; Bronx, NY; Chapel Hill, NC and Irvine, CA T1533 A Long-Term, Open-Label Extension Study Evaluating the Safety of Extended-Release Memantine (28 mg) in Patients with Moderate to Severe Alzheimer’s Disease Stephen M. Graham and James Perhach; Jersey City, NJ T1534 A Retrospective Analysis Using Data-Monitoring Algorithms: What Are the Logical Relationships between the ADAS-Cog and MMSE? Christian Yavorsky, Guillermo DiClemente, Mark Opler, Sofija Jovic, Brian Rothman and Ashleigh DeFries; New York, NY T1609 Chronic Low Dose Methadone for the Suppression of Treatment-Refractory Chronic Migraine Keyvani Madjid and John F. Rothrock; San Diego, CA and Birmingham, AL T1535 Withdrawn. T1536 Case of Bimodal Charles Bonnet Syndrome and Dementia Mirret El-Hagrassy and Gokhan Akfirat; New York, NY T1610 Relationship between High Frequency Nausea and Treatment Satisfaction in Episodic Migraine (EM): Results of the American Migraine Prevalence and Prevention (AMPP) Study Richard B. Lipton, Michael L. Reed, Kristina M. Fanning and Dawn C. Buse; Bronx, NY and Chapel Hill, NC T1537 Lead Exposure Up-Regulated Autophagy Response in Neuroblastoma SH-SY5Y Cells Via mTOR Kinase Signaling Pathway Shun-Sheng Chen, Chueh-Tan Chen and Jiin-Tsuey Cheng; Kaohsiung, Taiwan T1611 Frequent Nausea in Episodic Migraine (EM) Is Common and Associated with Increased Burden: Results from the American Migraine Prevalence and Prevention (AMPP) Study Dawn C. Buse, Michael L. Reed, Kristina M. Fanning and Richard B. Lipton; Bronx, NY and Chapel Hill, NC Headache and Pain T1601 Withdrawn. T1602 OnbotulinumtoxinA for the Treatment of Chronic Migraine: Long-Term Outcome Hanlon T. Christopher, Silvia M. Weibelt, Diane C. Andress-Rothrock and John F. Rothrock; Birmingham, AL T1612 Medical Consultation and Headache-Impact among Persons with Chronic Migraine (CM) and Episodic Migraine (EM): Results from the American Migraine Prevalence and Prevention (AMPP) Study Aubrey N. Manack, Dawn C. Buse, Daniel Serrano, Sepideh F. Varon, Catherine C. Turkel and Richard B. Lipton; Irvine, CA; Bronx, NY and Chapel Hill, NC T1603 Utility of Orally-Inhaled Dihydroergotamine When Early Intervention Is Impractical Shashidhar Kori, Stewart Tepper, Peter J. Goadsby, Paul Winner, Min Wang and Stephen Silberstein; Mountain View; Cleveland; San Francisco; West Palm Beach and Philadelphia T1613 Unmet Treatment Needs among Episodic Migraineurs (EM): Results of the American Migraine Prevalence and Prevention Study (AMPP) Richard B. Lipton, Dawn C. Buse, Daniel Serrano, Daisy S. Ng-Mak, Starr H. Pearlman and Michael Reed; Bronx, NY; Chapel Hill, NC; West Point, PA and Savannah, GA T1604 Characterization of Intraepidermal Nerve Fiber Morphology in Pain Associated with Diabetic Neuropathy and Impaired Glucose Tolerance Hsinlin T. Cheng, Jacqueline R. Dauch, Gordon A. Smith, Robinson J. Singleton, Brandon M. Yanik and Eva L. Feldman; Ann Arbor, MI and Salt Lake City, UT T1614 Association between Triptan Use and Cardiac Contraindications in Migraine Daisy S. Ng-Mak, Valerie P. Pracilio, Stephen Silberstein, Joseph Couto, Cary Sennett, Mary Hopkins, Jon Bumbaugh 15 ID: srinivasanv I Black Lining: [ON] I Time: 21:55 I Path: //xinchnasjn/01Journals/Wiley/3b2/ANA#/Vol00000/110241/APPFile/JW-ANA#110241 J_ID: ZAY Customer A_ID: SUPP11-3 Cadmus Art: 22575 Date: 31-August-11 Stage: Page: 16 and Neil Goldfarb; West Point, PA; Philadelphia, PA and Bowie, MD Chicago, IL; Oxford, United Kingdom; Birmingham, AL; London, ON, Canada; Vancouver, BC, Canada; Wayne, NJ; Berlin, Germany and Montville, NJ T1615 ��Let-Down Headache’’: Reductions in Stress and Improvement in Mood Predict Headaches in Persons with Migraine Dawn C. Buse, Sheryl R. Haut, Charles Hall, Howard Tennen, Tiffani DeFreitas, Thomas M. Borkowski and Richard B. Lipton; Bronx, NY and Storrs, CT T1703 A Recombinant Human Neuron-Binding IgM Protects Spinal Cord Axons and Improves Motor Function in a Murine Model of Multiple Sclerosis Aleksandar Denic*, Slobodan Macura, Arthur E. Warrington, Istvan Pirko, Brandon R. Grossardt, Larry R. Pease and Moses Rodriguez; Rochester, MN T1616 Assessing the Consistency of LEVADEXTM (MAP0004, Orally Inhaled Dihydroergotamine) Pharmacokinetic Parameters in Healthy Volunteers: Results from 3 Clinical Studies Amy Forst, Julie Iwashita, Don Kellerman, Shashidhar Kori, Tracy Thomas and Glyn Taylor; Mountain View; Merthyr Tydfil, United Kingdom and Radyr, United Kingdom T1704 Neuroprotection Mediated through Estrogen Receptor Alpha in Astrocytes Rory Spence, Mary Hamby, Elizabeth Umeda, Noriko Itoh, Sienmi Du, Galyna Bondar, Michael Sofroniew and Rhonda Voskuhl; Los Angeles, CA T1705 Genesis of Astrogliosis in an Autoimmune Model of Multiple Sclerosis Fuzheng Guo, Yoshiko Maeda, Joyce Ma, Monica Delgado and David Pleasure; Sacramento, CA T1617 Migraine Recurrence Rates with Acute Treatment: Case for Standardizing the Definition Stewart Tepper, Shashidhar Kori, Peter J. Goadsby, Michel Ferrari, Richard Lipton, Scott Borland, Min Wang and David Dodick; Cleveland; Mountain View; San Francisco; Leiden, Netherlands; Bronx and Scottsdale T1706 Distinct Features of Neuromyelitis Optica According to Anti-Aquaporin-4 Antibody IgG Subclass Noriko Isobe, Tomomi Yonekawa, Takuya Matsushita, Yuji Kawano, Katsuhisa Masaki, Satoshi Yoshimura and Jun-ichi Kira; Fukuoka, Japan and Matsuyama, Japan T1618 Transdermal Sumatriptan for Acute Treatment of Migraine and Jerome Goldstein; San Francisco, CA T1707 Effect of Fingolimod on Relapse Rate by Prior Treatment Status and Reason for Discontinuation: FREEDOMS Subgroup Analyses Marcelo Kremenchutzky, Paul O’Connor, Reinhard Hohlfeld, Ernst-Wilhelm Radue, Ludwig Kappos, Lixin Zhang-Auberson, Dieter A. Ha¨ring, Philipp von Rosenstiel, Xiangyi Meng and Augusto Grinspan; London, ON, Canada; Toronto, ON, Canada; Munich, Germany; Basel, Switzerland and East Hanover, NJ T1619 Dejerine Roussy Syndrome in a Patient with Sneddon’s Syndrome as an Initial Manifestation Jennie Luna, Anish Shah, Sourav Sen and Dipak P. Pandya; Paterson, NJ T1620 Valproate-Responsive Subclinical Rhythmic Electrographic Disharges (SREDA) in a Migraineur Umer Akbar, Bhavpreet Dham, Evren Burakgazi and John Kelly; Camden, NJ and Washington T1708 Effect of Fingolimod on Relapse Rate by Prior Treatment Status and Reason for Discontinuation: TRANSFORMS Subgroup Analyses Bhupendra O. Khatri, Jean Pelletier, Ludwig Kappos, HansPeters Hartung, Giancarlo Comi, Frederik Barkhof, Jeffrey Cohen, Tracy Stites, Xiangyi Meng and Augusto Grinspan; Milwaukee, WI; Marseille, France; Basel, Switzerland; Dusseldorf, Germany; San Raffaele, Milan, Italy; Amsterdam, Netherlands; Cleveland, OH and East Hanover, NJ T1621 Utriculo-Ocular Counterroll Reflex Disruption in Skew Deviation James A. Sharpe, Manokaraananthan Chandrakumar, Alan Blakeman, Herbert C. Goltz and Agnes M. Wong; Toronto, ON, Canada T1622 Superior Semicircular Canal Dehiscence (SSCD) and Osteoporosis in Elderly Asian Women Alexander Yu, Douglas L. Teich and Eric T. Wong; Boston, MA T1709 Safety Overview of Fingolimod in Relapsing Multiple Sclerosis: Phase 2 and 3 Studies Jeffrey A. Cohen, Ludwig Kappos, Gordon Francis, William Collins, Lixin Zhang-Auberson and Dejun Tang; Cleveland, OH; Basel, Switzerland and East Hanover, NJ Neuroimmunology and Demyelinating Disease T1710 Fingolimod Mechanism of Action (MOA) in Multiple Sclerosis (MS) Jerold Chun and Jeffery A. Cohen; La Jolla, CA and Cleveland, OH T1701 Antibodies to Metabotropic Glutamate Receptors in Ophelia Syndrome and Cerebellitis Eric Lancaster, Eugenia Martinez-Hernandez, Maarten J. Titulaer, Sarah Wong, Jian Xu, Anis Contractor, Rita BaliceGordon and Josep Dalmau; Philadelphia, PA and Chicago, IL T1711 Antibodies to the VGKC-Complex Proteins LGI1 and CASPR2 in Acquired Neuromyotonia Camilla Buckley, Philippa Pettingill, Rosie Pettingill, Matthew Kiernan, Osamu Watanabe, Sarosh Irani, Patrick Waters and Angela Vincent; Oxford, United Kingdom; Sydney, Australia and Kagoshima, Japan T1702 Mortality Outcomes for Interferon Beta-1b Versus Placebo 21 Years Following Randomization Douglas S. Goodin, Anthony T. Reder, George Ebers, Gary Cutter, Marcelo Kremenchutzky, Joel Oger, Mark Rametta, Karola Beckmann and Volker Knappertz; San Francisco, CA; 16 ID: srinivasanv I Black Lining: [ON] I Time: 21:55 I Path: //xinchnasjn/01Journals/Wiley/3b2/ANA#/Vol00000/110241/APPFile/JW-ANA#110241 J_ID: ZAY Customer A_ID: SUPP11-3 Cadmus Art: 22575 Date: 31-August-11 T1712 Withdrawn. Stage: Page: 17 T1725 Regulation of IL-12 by IL-23 in Bone Marrow Dendritic Cells Farinaz Safavi, Patricia Gonnella, Bogojub Ciric, Abdolmohamad Rostami and Farinaz Safavi; Philadelphia, PA T1713 Association of MS Susceptibility Variants and Early Attack Location Ellen M. Mowry, Jean Pelletier, Maria R. Blasco, Pierre Duquette, Pablo Villoslada, Pierre-Antoine Gourraud, Irina Malikova, Christophe Picard, Jamie McDonald, Elaine Roger, Stacy Caillier and Emmanuelle Waubant; San Francisco; Marseille, France; Madrid, Spain; Montreal, Canada and Pamplona, Spain T1726 Clinically Apparent MRI Activity Predicts 2-Year Outcomes in Patients with RRMS Thomas Scott, Xiaojun You and Pamela Foulds; Pittsburgh, PA and Weston, MA T1727 The Correlation of Brain MRI Lesion Load with Functional Outcome in Animal Models of MS Istvan Pirko, Jeffrey Gamez, Moses Rodriguez, Mihajlo Babovic and Slobodan I. Macura; Rochester, MN and Northfield, MN T1714 Osmotic Demyelination Syndrome: Lack of Association between Outcome and Severity of Hyponatremia Jennifer E. Fugate*, Jonathan Graff-Radford and Alejandro A. Rabinstein; Rochester, MN T1728 Comparison of CIDP Patients with Normal and Elevated CSF Protein YuanYuan Xue and Ericka P. Simpson; Houston, TX T1715 Correlation of Brain Atrophy, Disability and Spinal Cord Atrophy in a Murine Model of MS M Mateo Paz Soldan, Jeffrey D. Gamez, Aaron J. Johnson, Anne K. Lohrey, Yi Chen and Istvan Pirko; Rochester, MN and Cincinnati, OH T1729 Are Anti-TAG-1 Autoantibodies Markers in Autoimmune Demyelinating Disorders of the PNS and CNS? Harry Alexopoulos, Pantelis P. Pavlakis, Domna Karagogeos, Clementine E. Karageorgiou and Marinos C. Dalakas; Athens, Greece and Heraklion, Greece T1716 Anti-NMDA-Receptor Encephalitis: Clinical Analysis of 457 Patients Maarten J. Titulaer, Eugenia Martinez-Hernandez, Lindsey McCracken, Rita Balice-Gordon and Josep Dalmau; Philadelphia, PA and Barcelona, Spain T1730 Introduction and Diffusion of Multiple Sclerosis in the United States Mitchell T. Wallin and John F. Kurtzke; Washington, DC T1717 Cigarette Smoke Induces Inflammation and Oxidative Stress in Brains of Lewis Rats Ashwani Khanna and Walter Royal, III; Baltimore, MD T1731 Withdrawn. T1732 Withdrawn. T1718 Withdrawn. T1733 The Relationship between Conduction Block and Clinical Characteristics in Guillain-Barre´ Syndrome with Anti-GM1/GalNAc-GD1a Antibodies Go Ogawa, Ken-ichi Kaida, Susumu Kusunoki, Motoi Kuwabara, Fumihiko Kimura and Keiko Kamakura; Tokorozawa, Saitama, Japan and Osaka-Sayama, Osaka, Japan T1719 Differential Sensitivity of Human PBMC Subsets to Alemtuzumab-Mediated Cytotoxicity William Siders, Sambasiva Rao, Juanita Campos-Rivera, Jose Sancho, Paula Boutin, Peter Severy, Johanne Kaplan, Bruce Roberts and Srinivas Shankara; Framingham, MA T1720 Transcriptional Profiles Uncover Population Structure among Multiple Sclerosis Patients Linda Ottoboni, David Hafler, Howard Weiner and Philip De Jager; Boston, MA and New Haven, CT T1734 Withdrawn. T1735 Randomized, Open-Label Study To Evaluate Patient-Reported Outcomes (PRO) with Fingolimod after Changing from Prior Disease-Modifying Therapy (DMT) for Relapsing Multiple Sclerosis (MS): EPOC Study Rationale and Design Luigi M. Barbato, Lesley Schofield, Kevin McCague, Linda Pestreich, Kathy Tobias and Manoj Malhotra; East Hanover, NJ T1721 Analysis of Immune Competence Following Alemtuzumab Treatment in huCD52transgenic Mice William Siders, Nathalie Chretien, Michael LaMorte, Bruce Roberts and Johanne Kaplan; Framingham, MA T1722 Withdrawn. T1736 Novel Diagnostic Tool for MS Nancy L. Monson, Ann J. Ligocki, William H. Rounds, Diane Xiang, Lindsay G. Cowell, Doug Bigwood, Eric Eastman, Jeffrey L. Bennett, Scott D. Boyd, Andrew Z. Fire, Elliot M. Frohman and Benjamin M. Greenberg; Dallas, TX; Gaithersburg, MD; Denver, CO and Palo Alto, CA T1723 Withdrawn. T1724 A Single Dose Escalation Study of the Safety, Pharmacokinetics, and Pharmacodynamics of Subcutaneous Pegylated Interferon-Beta in Healthy Volunteers Kenneth Grabstein, Aijun Wang, Natalie Winblade Nairn and Daniel J. Burge; Seattle, WA T1737 Efficacy of Combination Therapy in Marburg Variant Type of Multiple Sclerosis Jennifer Gabbard, Yasmin Bilal and Dipak Pandya; Paterson, NJ 17 ID: srinivasanv I Black Lining: [ON] I Time: 21:55 I Path: //xinchnasjn/01Journals/Wiley/3b2/ANA#/Vol00000/110241/APPFile/JW-ANA#110241 J_ID: ZAY Customer A_ID: SUPP11-3 Cadmus Art: 22575 Date: 31-August-11 T1738 Coma as an Inital Manifestation of Acute Disseminated Encephalomyelitis Megan McGarry, Natasha Tilluckdharry and Dipak P. Pandya; Paterson, NJ Stage: Page: 18 T1809 Benign-Histology Meningioma with Extracranial Metastasis Umer Akbar, Bhavpreet Dham and Melissa Carran; Camden, NJ Neurovirology T1739 NMO-IgG in a Patient with Neurosarcoidosis Lena Derani** and Elham Bayat; Washington, DC T1901 HIV Associated Neurocognitive Disorder (HAND) Is Not Associated with Increased Fibrillar Amyloid Deposits Using 11C-PiB in Middle-Aged HIVþ Participants Beau Ances, Jewell Thomas, Tammie Benzinger, Jon Christensen, Mengesha Teshome, Patricia Aldea, Anne Fagan, David Holtzman, John Morris and David Clifford; Saint Louis, MO T1740 Correlates of Dietary Intake in Individuals with Multiple Sclerosis Matthew A. Plow, Marcia Finlayson and Chi Cho; Cleveland, OH and Chicago, IL Neurooncology T1801 Comparative Uptake and Cytotoxicity of Anti-Hu and Anti-Ri Antibodies in Rat Cerebellar Slice Cultures John E. Greenlee, Susan A. Clawson, Blair Wood, Kenneth E. Hill and Noel G. Carlson; Salt Lake City, UT T1902 Modulation of HIV-Tat Neurotoxicity by Potassium Channel Blockers Srikant Rangaraju* and Jeffrey A. Rumbaugh; Atlanta, GA T1802 Cerebrospinal Fluid Chemokine/Cytokine Biomarkers for Melanoma Brain Metastasis Edwin Lok, Amy S. Chung, Szexian Lee, Tamar Melman, Kenneth D. Swanson and Eric T. Wong; Boston, MA T1903 Varicella Zoster Encephalitis – Relationship between Viral Load, Time and Outcome Benedict D. Michael, Mike Griffiths, Anna Stewart, Charlotte Buckley, Mark Hopkins, Ian J. Hart, Alistair Miller, Sareen Galbraith and Tom Solomon; Liverpool, Merseyside, United Kingdom T1803 Role of p75NTR and Its Signaling Pathways in Fenretinide (4-hydroxyphenyl Retinamide – 4HPR) Induced Apoptosis in Neuroblastoma Cells Veena R. Ganeshan and Nina F. Schor; Rochester, NY T1904 Acute Varicella Zoster Virus Encephalitis in Adults – Relationship between Viral Load, Time, Clinical Features and Outcome Benedict D. Michael, Michael Griffiths, Anna Stewart, Charlotte Buckley, Mark Hopkins, Ian J. Hart, Alistair Miller, Sareen E. Galbraith and Tom Solomon; Liverpool, United Kingdom T1804 Relationship between Brain MRI Imaging Parameters and Molecular Biomarkers as Prognostic Indicators in Glioblastoma Multiforme Xiao-Tang Kong, Senxi Du, Beverly D. Fu, Mark E. Linskey and Daniela Bota; Orange, CA and Irvine, CA T1905 TLR4 Expression Is Upregulated in HIV-Associated Neurocognitive Disorder (HAND) Amir H. Sabouri, Gursharan Chana, Amol Shah, Critian L. Achim, Ronald J. Ellis, Ian P. Everall and HNRC Group; La Jolla, CA; Melbourne, Australia and San Diego, CA T1805 Secondary Intramedullary Spinal Cord NonHodgkin’s Lymphoma Eoin P. Flanagan, Brian P. O’Neill, Thomas M. Habermann and B. Mark Keegan; Rochester, MN T1906 Revisiting Reactivation of Calcified Neurocysticercosis: Report of Three Recent Cases Sanjna M. John** and Maria del Pilar Cortes Nino; Kingston, ON, Canada and Montreal, QC, Canada T1806 Case Report: Optic Neuropathy in a Patient with Glioblastoma Receiving Bevacizumab Robert A. Fishman, Lara Kunschner and Erik Happ; Pittsburgh, PA T1807 Anti-Ri-Associated Paraneoplastic Brainstem Cerebellar Syndrome with Medically-Intractable Nausea in a Patient with Large Cell Neuroendocrine Lung Carcinoma: A Case Report Amber N. Mitchell, Jessica Levesque and Earl Zimmerman; Albany, NY T1907 Clinical Features at Admission in Patients with Meningeal Cryptococcosis in a Third Level Hospital in Mexico Jesus F. Mendoza, Gilberto Vazquez, Jeronimo Rodriguez and Ildefonso Rodriguez; San Luis Potosı´, San Luis Potosı´, Mexico T1808 Glioblastoma Multiforme: A Rare Presentation of Pineal Tumor with Leptomeningeal Seeding and Future Directions Noor Yono, Tulika Ranjan and Rabih Kashouty; Manhasset, NY, United States Minor Outlying Islands and New York, NY T1908 The Diagnosis of Tuberculous Meningitis: A Current Review of the Clinical and Laboratory Methods Brian Chisulo, Shan H. Jiang and Yue S. Pan; Guangzhou, GZ, China 18 ID: srinivasanv I Black Lining: [ON] I Time: 21:55 I Path: //xinchnasjn/01Journals/Wiley/3b2/ANA#/Vol00000/110241/APPFile/JW-ANA#110241 J_ID: ZAY Customer A_ID: SUPP11-4 Cadmus Art: 22577 Date: 26-August-11 Stage: Page: 19 136th Annual Meeting Sunday, September 25, 2011 Works in Progress Poster Session 136th Annual Meeting Monday, September 26, 2011 Works in Progress Poster Session WIP posters will be displayed in Elizabeth A-E of the Manchester Grand Hyatt from 10:00 am – 7:00 pm, with authors present from 6:00 pm – 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. WIP posters will be displayed in Elizabeth A-E of the Manchester Grand Hyatt from 10:00 am – 7:00 pm, with authors present from 6:00 pm – 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. Behavioral Neurology Cerebrovascular Disease M622 New Approaches to Unraveling the Multi-Scale Neuroanatomical Changes in Williams Syndrome Ann Lam and Elan L. Ohayon; La Jolla S141 Polymorphism of Ninjurin2 in Korean Atherothrombotic Stroke Patients Dae-il Chang, Sung Hyuk Heo and Hye Ok Kim; Seoul, Korea Epilepsy S142 NMDA Receptor Biomarker for Acute Stroke Kerstin Bettermann and Svetlana Dambinova; Hershey, PA and Kennesaw, GA M725 HLA-B*1502 Genotyping in Carbamazepine and Phenytoin Induced Stevens-Johnson Syndrome Sivakumar M. Rajappa and Srinivasan A. Venkatesan; Chennai, Tamil Nadu, India S143 Initial Transcranial Doppler Velocity Predicts Development of Symptomatic Vasospasm in Aneurysmal Subarachnoid Hemorrhage Shyam Prabhakaran, Konark Malhotra, Rajeev Garg, Sayona John, Richard Temes and Viven Lee; Chicago, IL M726 Filamin A Regulates Neural Progenitor Proliferation and Brain Size through wee1-Dependent cdk1 Phosphorylation Gewei Lian and Volney Sheen; Boston, MA S144 Relative Change in Transcranial Doppler Velocities Is Inferior to Absolute Thresholds in Prediction of Vasospasm after Subarachnoid Hemorrhage Konark Malhotra, James Connors, Viven Lee and Shyam Prabhakaran; Chicago, IL M727 A Moderate-Throughput Screen for Antiepileptogenic Compounds Yevgeny Berdichevsky, Yero Saponjian, Michelle Mail and Kevin J. Staley; Boston, MA Movement Disorder M728 Network Structure and Sensitivity to the Geometry of Stimuli in Epilepsy and Cognition Elan L. Ohayon, Ann Lam and Terrence J. Sejnowski; La Jolla, CA S238 Dopamine Transporter Imaging Predicts Long Term Outcomes in Parkinson’s Disease Bernard M. Ravina, Kenneth Marek, Shirley Eberly, David Oakes and Ira Shoulson; Rochester and New Haven M729 Hypoglycemia Induced NMDA Receptor-Dependent Epileptiform Activity in the Hippocampal CA3 Area Causes Damage in CA1 Carlos M. Florez, Jane Zhang, Peter Abdemalik, Liang Zhang and Peter L. Carlen; Toronto, ON, Canada S239 Time to First Levodopa-Induced Motor Complication: Results from the STRIDE-PD Study C. Warren Olanow, Karl Kieburtz, Olivier Rascol, Werner Poewe, Anthony Schapira, Helena Nissinen, Mika Leinonen and Fabrizio Stocchi; New York, NY; Rochester, NY; Toulouse, France; Innsbruck, Austria; London, United Kingdom; Espoo, Finland; Kista, Sweden and Rome, Italy M730 Alzheimer Disease in Lafora Epilepsy Jesus Machado-Salas, Maria Rosa Avila-Costa, Patricia Guevara, Jorge Guevara, Reyna M. Duron, Dongsheng Bai, Miyabi Tanaka and Antonio V. Delgado-Escueta; Los Angeles, CA and Mexico, Mexico S240 Acute Effects of Preladenant, a Selective Adenosine A2A Antagonist, on Dyskinesia and Parkinsonism in Levodopa-Treated Subjects Penelope Hogarth, Matthew D. Troyer, Byung S. Park, Igor D. Grachev, Tatanisha Laguerre, Fengjuan Xuan, Amol Tendolkar and John G Nutt; Portland, OR and Whitehouse Station, NJ M731 Antiepileptic Activity of Intrapulmonary Midazolam Ashish Dhir, Dorota Zolkowska and Michael A. Rogawski; Sacramento and Davis 19 ID: kannanb I Black Lining: [ON] I Time: 16:18 I Path: N:/3b2/ANA#/Vol00000/110242/APPFile/JW-ANA#110242 J_ID: ZAY Customer A_ID: SUPP11-4 Cadmus Art: 22577 Date: 26-August-11 Stage: Page: 20 M732 Do Brain Volumes in JME (juvenile myoclonic epilepsy) differ from normal controls? Neurology Critical Care John T. Spitz, Long Vu, Lydia Su, Mark A. Mandelkern, Barbara E. Swartz; Berkely, CA, Irvine, CA, Los Angeles, CA, Irvine,CA and Newport Beach, CA M1206 Imaging Biomarkers of Cerebral Edema in Malignant Infarction Kevin N. Sheth, Albert J. Yoo, R. G. Gonzalez, W. T. Kimberly, Zeshan A. Chaudhry, Jordan J. Elm, Sven Jacobson, Stephen M. Davis, Geoffrey A. Donnan, Gregory W. Albers and Barney J. Stern; Baltimore, MD; Boston, MA; Charleston, SC; New York, NY; Carlton South, Victoria, Australia and Stanford, CA Neuromuscular Disease M836 Disrupted Expression of Myogenin in Inclusion Body Myositis Akatsuki Kubota, Jun Shimizu, Atsushi Iwata and Shoji Tsuji; Tokyo, Japan 136th Annual Meeting Tuesday, September 27, 2011 Works in Progress Poster Session M837 Abnormalities of a Novel Autophagy-Associated Protein, NBR1, in Muscle Fibers of Sporadic InclusionBody Myositis (s-IBM) Carla D’Agostino, Anna Nogalska, Mafalda Cacciottolo, W.King Engel and Valerie Askanas; Los Angeles, CA WIP posters will be displayed in Elizabeth A-E of the Manchester Grand Hyatt from 10:00 am – 7:00 pm, with authors present from 6:00 pm – 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. M838 Atrophy and Autophagy in Limb Girdle Muscular Dystrophy and Glycogen Storage Disease Type 2 Corrado I. Angelini, Annachiara Nascimbeni, Marina Fanin and Marco Sandri; Padova, Italy M839 Virtual Demyelination in pmp22 Deficiency Jiasong Guo, Qing Yan, Gina Sosinsky, Mark Elisman, Cameron McIntyre, Lily Wang, Ueli Suter and Jun Li; Nashville; San Diego; Cleveland; Zurich, Swaziland and Nashville, TN Dementia and Aging T1538 Proneurogenic Compound Reduces Synaptic Ab42 Oligomer Levels and Shows Cognitive Benefit in Alzheimer’s Mouse Model Sam Gandy, John W. Steele, Charles Glabe, Kai Treuner, Todd Albert, Carrolee Barlow, Michelle E. Ehrlich and Soong Ho Kim; New York, NY; Irvine, CA and San Diego, CA M840 First in Human Phase 1 Trial of Neural Progenitor Cells in ALS: Results in the First 12 Patients Jonathan D. Glass, Nicholas Boulis, Meraida Polak, Crystal Kelly, Thais Federici, Jane Bordeau, Seward Rutkove, Karl Johe, Tom Hazel and Eva Feldman; Atlanta, GA; Boston, MA; Rockville, MD and Ann Arbor, MI M841 Clinical Development of an Antisense Therapy for the Treatment of Transthyretin Amyloidosis Shuling Guo, Elizabeth Ackermann, Sheri Booten, Luis Alvarado andrew Siwkowski, Merrill Benson, Steve Hughes and Brett Monia; Carlsbad, CA and Indianapolis, IN T1539 Alzheimer Risk Variant Clusterin (CLU) and Brain Function during Aging Madhav Thambisetty, Lori Beason-Held, Michael Kraut, Michael Nalls, Andrew Singleton, Luigi Ferrucci, Simon Lovestone and Susan Resnick; Baltimore and London, United Kingdom Neurogenetics T1540 Association of High Density Lipoprotein to Alzheimer Disease Ramin Ebrahimi, Naser Ahmahi, Fereshteh Hajsadeghi and Hormoz Babaei; LA, CA M1011 EPI-A0001: New Potential Therapy for Friedreich Ataxia David R. Lynch, Steve M. Willi, Robert B. Wilson, Karlla W. Brigatti, Olena Kucheruck, Eric C. Deutsch, William D. Shrader, Patrice Rioux, Guy Miller, Amale Hawi and Thomas Sciascia; Philadelphia, PA; Patterson, NY and Mountain View, CA T1541 Amyloid-b 42:40 Metabolism Is Altered in Autosomal Dominant Alzheimer’s Disease (ADAD) Rachel E. Potter, Vitaliy Ovid, Tom Kasten, Wendy Sigurdson, Kwasi Mawuenyega, Bruce Patterson, Don Elbert, Scot Fague, Sumi Chakraverty, Alison Goate, Kevin Yarasheski, John C. Morris, Tammie Benzinger and Randall J. Bateman; St. Louis, MO M1012 Exome Sequencing Identifies a Rare Variant in the CYP27B1 Gene Associated with Multiple Sclerosis George C. Ebers and Sreeram V. Ramagopalan; Oxford, Oxfordshire, United Kingdom T1542 Acetylated Tau, a Novel Pathological Signature in Alzheimer’s Disease and Other Tauopathies David J. Irwin, Todd Cohen, Murray Grossman, Steven E. Arnold, Sharon X. Xie, Virginia M.Y. Lee and John Q. Trojanowski; Philadelphia, PA M1013 Whole Genome Sequencing in Twins Discordant for 27 Diseases George C. Ebers and Sreeram V. Ramagopalan; Oxford, Oxfordshire, United Kingdom 20 ID: kannanb I Black Lining: [ON] I Time: 16:18 I Path: N:/3b2/ANA#/Vol00000/110242/APPFile/JW-ANA#110242 J_ID: ZAY Customer A_ID: SUPP11-4 Cadmus Art: 22577 Date: 26-August-11 Stage: Page: 21 Headache and Pain Rizzuto, Hunter R. Underhill, Kenneth R. Maravilla and Lily K. Jung-Henson; Seattle, WA T1623 Retrospective Analysis of Major Congenital Malformations (MCMs) and Oral Clefts (OC) Associated with In-Utero Topiramate Exposure Mark W. Green and Arun Bhattachuria; New York, NY and Yardley, PA T1744 Skull Is Skull and Not Simply Another Bony Structure Tsutomu Nakada, Yuji Suzuki, Yukihiro Nakayama, Vincent J. Huber and Ingrid L. Kwee; Niigata, Niigata, Japan and Martinez, CA Neuroimmunology and Demyelinating Disease T1745 Characteristics of the Long Latency Vestibular Electrical Evoked Potential in Control Human Subjects Benn E. Smith, Michael J. Cevette, Jan Stepanek, Daniela Cocco, Gaurav Pradhan, Kenneth H. Brookler, Lindsay Wagner, Sarah Oakley, David A. Zapala and Mark A. Ross; Scottsdale, AZ and Jacksoville, FL T1741 Comparison of MRI Techniques for Monitoring of Multiple Sclerosis Manuela Vaneckova, Jan Krasensky, Tomas Kalincik, Dana Horakova, Eva Havrdova and Zdenek Seidl; Prague, Czech Republic T1746 Regulatory T Cells Play Contrasting Roles in a Viral Model for Multiple Sclerosis Nicholas E. Martinez, Fridrik Karlsson, Fumitaka Sato, Seiichi Omura, Alireza Minagar, Mathew B. Grisham, and Ikuo Tsunoda; Shreveport, LA T1742 Effects of Rituximab on T-Cells in MS Uma Vinayagasundaram, Ellen M. Mowry, Ian R. Matthews, Julia Marino and Emmanuelle Waubant; San Francisco, CA T1743 Fast Macromolecular Proton Fraction (MPF) Mapping in Multiple Sclerosis (MS) Vasily L. Yarnykh, James D. Bowen, Bart P. Keogh, Pavle Repovic, Angeli Mayadev, Beena Gangadharan, Daniel S. T1747 Idiopathic Relapsing Conus Myelitis Raghav Govindarajan and Efrain Salgado; Weston, FL 21 ID: kannanb I Black Lining: [ON] I Time: 16:18 I Path: N:/3b2/ANA#/Vol00000/110242/APPFile/JW-ANA#110242 J_ID: ZAY Customer A_ID: SUPP11-5 Cadmus Art: 22578 Date: 26-August-11 136th Annual Meeting Sunday, September 25, 2011 Career Development Poster Session Stage: Page: 22 Neuroimmunology and Demyelinating Disease CD531 TLR9 Processing in Multiple Sclerosis: A New Immunomodulatory Effect of Interferon-beta Konstantin E. Balashov, Suhayl Dhib-Jalbut, and Latt Aung; New Brunswick, NJ Posters will be displayed in Elizabeth A-E of the Manchester Grand Hyatt from 10:00 am – 7:00 pm, with authors present from 6:00 pm – 7:00 pm. Neurogenetics CD522 Aberrant Channel Subunit Trafficking in the Neurodegenerative KCNC3R420H SCA13 Phenotype Michael F. Waters; Gainesville, FL Epilepsy CD515 Non-Convulsive Status Epilepticus Is Associated with Mortality and Worse Short-Term Outcome in Critically Ill Children Nicholas S. Abend, Alexis A. Topjian, and Dennis J. Dlugos; Philadelphia, PA 22 ID: kannanb I Black Lining: [ON] I Time: 17:23 I Path: N:/3b2/ANA#/Vol00000/110243/APPFile/JW-ANA#110243 J_ID: ZAY Customer A_ID: SUPP11-6 Cadmus Art: 22579 Date: 31-August-11 136th Annual Meeting Sunday, September 25, 2011 Poster Session Abstracts Stage: Page: 23 Dr. Elkind serves as Resident and Fellow Section Editor for Neurology, for which he receives compensation from the AAN. S102. Functional Outcomes in CREST among Patients with Periprocedural Stroke and Myocardial Infarction Bart M. Demaerschalk, Robert J. Hye, O.W. Brown, Donald V. Heck, Irfan Altafullah, Jenifer H. Voeks, George Howard, James F. Meschia and Thomas G. Brott; Phoenix, AZ; San Diego, CA; Royal Oak, MI; Winston Salem, NC; Robbinsdale, MN; Birmingham, AL and Jacksonville, FL Posters will be displayed in Elizabeth A-E of the Manchester Grand Hyatt from 10:00 am – 7:00 pm, with authors present from 6:00 pm – 7:00 pm. NOTE: An asterisk designates a resident/fellow travel award winner. Two asterisks represent a medical student travel award winner. Background: Stroke more frequently complicated stenting, and myocardial infarction (MI) more frequently complicated endarterectomy in the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST). Purpose: To inform debate on importance of these components of the CREST primary endpoint. Methods: The modified Rankin Scale (mRS), a measure of function, was assessed at one year, and scales were available for 72 (89%) of the stroke patients and 34 (81%) of the MI patients. Results: There was no evidence of a difference in the distribution of mRS (pCMH ¼ 0.61). Complete or nearly complete recovery (mRS 0-1) was achieved for 43 (60%) of the stroke patients and 23 (68%) of the MI patients. Slight to severe disability (mRS 2–5) was achieved for 16 (22%) of the stroke patients and 5 (15%) of the MI patients. Death occurred in 13 (18%) of the stroke patients and in 6 (18%) of the MI patients. Disability and death were more frequent for both the stroke and MI patients compared to those with neither (p<0.001). Conclusion: Periprocedural stroke and MI had adverse and similar outcomes at one-year in CREST. Each is an important complication of carotid revascularization. Study supported by: The study was funded by the National Institute of Neurological Disorders and Stroke of the National Institutes of Health (NS038384) with supplemental funding provided by Abbott Vascular Solutions (formerly Guidant). Dr. George Howard reports receiving compensation for activities with Bayer Healthcare and research support from Amgen and Bayer Healthcare. He is also a consultant to Abbott for preparation of FDA materials. Cerebrovascular Disease S101. Duration of Diabetes and Ischemic Stroke Risk: The Northern Manhattan Study Julio R. Vieira*, Chirantan Banerjee, Yeseon P. Moon, Myunghee C. Paik, Tatjana Rundek, Ralph L. Sacco and Mitchell S.V. Elkind; New York, NY and Miami, FL Background: Diabetes increases stroke risk, but whether time-dependent analyses improve estimates of effect, and whether duration is important, is less clear. We hypothesized that diabetes duration independently predicts ischemic stroke. Methods: Among 3,298 stroke-free participants, baseline diabetes and age at diagnosis were determined. Incident diabetes was assessed annually (median ¼ 9 years). We fit Cox proportional hazards models to examine associations between diabetes duration and ischemic stroke (IS) risk. Results: Mean age was 69 6 10 years (52% Hispanic, 21% white, and 24% black); 22% were diabetic at baseline and 11% developed new diabetes. Diabetes at baseline was associated with IS (adjusted HR ¼ 2.5, 95% CI ¼ 1.9– 3.3), and the magnitude was similar when analyzed as a time-varying covariate (adjusted HR ¼ 2.4, 95% CI ¼ 1.8– 3.2). Duration of diabetes was associated with IS (adjusted HR ¼ 1.03 per year with diabetes, 95% CI ¼ 1.02–1.05). Compared to non-diabetics, those with diabetes for 0–5 years (adjusted HR ¼ 1.7, 95% CI ¼ 1.1–2.7), 5–10 years (adjusted HR ¼ 1.8, 95% CI ¼ 1.1–3.0), and !10 years (adjusted HR ¼ 3.3, 95% CI ¼ 2.4–4.5) were at increased risk. There was a duration threshold effect at !10 years (p ¼ 0.012). Conclusion: Duration of diabetes is independently associated with ischemic stroke. The risk triples in those with diabetes !10 years. Study supported by: This study was supported by NIH/ NINDS (#R37 29993). Dr. Vieira reports no disclosures. Dr. Banerjee reports no disclosures. Ms. Moon reports no disclosures. Dr. Paik reports no disclosures. Dr. Rundek reports no disclosures. Dr. Sacco discloses receiving research support from the NIH/NINDS over the last 12 months. Dr. Elkind serves as a consultant to Bristol-Myers Squibb and Tethys Bioscience, Inc.; serves on an event adjudication committee for Jarvik Heart; and serves on speakers’ bureaus for Boehringer-Ingelheim, Inc., Bristol-Myers Squibb/Sanofi Pharmaceuticals Partnership, and Genentech; and receives research support from diaDexus, Inc., Bristol-Myers Squibb/Sanofi Pharmaceuticals Partnership, and the NIH/NINDS [# R01 NS050724 (PI), #NS048134 (PI), # P50 NS049060 (Project PI), # R37 NS029993 (Co-PI), #R01 NS55809 (Co-I) and #R01 NS062820 (Co-I)]; and has given expert testimony on behalf of Novartis (ZelnormV and stroke litigation) and GlaxoSmithKline (AvandiaV and stroke litigation). S103. Inhibition and Scavenging of Complement as Therapeutic Targets in the Mouse Model of Acute Ischemic Stroke Xinzhi Chen, Mark P. Mattson and Milan Basta; Baltimore, MD and Potomac, MD Complement activation and subsequent generation of harmful fragments plays and important role in the pathogenesis of acute ischemic stroke (AIS). We investigated the effect of high dose intravenous immunoglobulin (IVIG), a potent scavenger of active complement fragments and C1-INH, an inhibitor of complement pathway cascades in the mouse model of AIS. Brain injury was induced by 1 hour occlusion of middle cerebral artery followed by a 72-hour reperfusion. Both IVIG (Privigen, CSL Behring) and C1-INH (Berinert, CSL Behring) significantly and in a dose responsive manner reduced brain infarction size, neurological deficit score and deposition of C3b fragments at the site of injury when given 30 minutes before or 1 hour after ischemia. Optimal dose of IVIG exerted more neuroprotection than the corresponding C1-INH counterpart (85% vs. 48% reduction of R R 23 ID: senthilk I Black Lining: [ON] I Time: 08:46 I Path: //xinchnasjn/01Journals/Wiley/3b2/ANA#/Vol00000/110244/APPFile/JW-ANA#110244 J_ID: ZAY Customer A_ID: SUPP11-6 Cadmus Art: 22579 Date: 31-August-11 brain infarction volume and 35% vs. 22% inhibition of neurological deficit, respectively). Treatment with human serum albumin and vehicles (stabilizing solutions) for IVIG and C1-INH did not improve the magnitude of brain injury observed in non-treated controls. Our data suggest that complement attenuation could be considered as a novel interventional therapy for AIS. Study supported by: CSL Behring Salary and consulting fees. Stage: Page: 24 210 (1.9%) in group 1, and 2/12 (16.67%) in group 2 (p ¼ 0.036). At 90 days, 44/144 (30.56%) in group 1 had mRS 0-1, and in group 2, 1/8 (12.5%, p ¼ 0.437). We found no difference in sICH or clinical outcome in patients with high INR after IV t-PA. The data is limited to few patients. Larger prospective studies are needed to prove safety and efficacy of IV t-PA in those with higher INR. S106. Toward a Further Clinical Physiological Elucidation: Immediate Regression of Leukoaraiosis after Carotid Artery Revascularization and Yu-Ming Chuang; New Taipei City, Taiwan S104. Does ACE (rs4646994) and a ADDUCIN (rs4961) Gene Polymorphisms Predicts the Recurrence of Hypertensive Intracerebral Hemorrhage Usha K. Misra, Jayantee Kalita, Bindu I. Somarajan, Bishwanath Kumar, Moromi Das and Balraj Mittal; Lucknow, Uttar Pradesh, India Background: To correlate leukoaraiosis, cerebral perfusion and circle of Willis (CoW) flow patterns after carotid artery revascularization. Methods: Leukoaraiosis (LA) on fluid attenuation inversion recovery (FLAIR) magnetic resonance (MR) images at the levels of the centrum semiovale and those of the frontal horns at both cerebral hemispheres were scored in 62 contiguous patients (men/women ¼ 38/24, mean age ¼ 63.2 þ- 8.4 years, range 44–82) before and after unilateral carotid artery revascularization (CAS). The pre-and post-stenting difference of LA scores, CoW flow pattern on MR angiography and MR perfusion parameters was analyzed. Results: Post-stenting sum of leukoaraiosis score on FLAIR imaging was regressed from 9.87þÀ0.65 to 8.33þÀ0.72 (P ¼ 0.03). Subjects were assigned to the complete CoW group (N ¼ 21) vs. the incomplete CoW group (N ¼ 41). Incomplete CoW group had a higher preoperative LA load and higher interhemispheric asymmetry index of relative cerebral blood volume (rCBV) which could be significantly regressed post-operatively. Conclusions: A perfusion related remodeling of the leukoaraiosis, regarding the factor of CoW configuration was observed. Study supported by: CGMH Objectives: To evaluate ACE and aADDUCIN gene polymorphisms in patients with nonrecurrent and recurrent HICH. Methods: Out of 350 HICH, 33 (9.4%) patients had recurrence. ACE (rs4646994) and aADDUCIN (rs4961) gene polymorphisms was done in patients and 198 controls. Risk factors, clinical, CT, ACE (rs4646994) and aADDUCIN (rs4961) findings between recurrent and nonrecurrent HICH were compared. Results: The stroke risk factors and drug compliance were similar between the groups. Ganglionic-ganglionic recurrence was commonest(75.6%) and all had at least one ICH in hypertensive location. DD genotype (OR6.18,95%CI2.9313.02) and D allele (OR2.43,95%CI1.70-3.47) of ACE was associated with nonrecurrent ICH compared to controls. In patients with recurrent ICH, DD genotype (OR7.46,95% CI2.8-19.4) and D allele (OR3.16, 95%CI1.83-5.46) of ACE and GW (OR3.49,95%CI 1.47-8.28) and WW (OR 2.9, 95%CI 1.40-4.30) genotype and W allele (OR7.46,95%CI2.80-19.40) of aADDUCIN were more frequent compared to controls. Recurrent ICH also had higher frequency of WW genotype (OR9.43,95%CI1.49-59.50) and W allele (OR2.19,95%CI1.11-4.03) compared to nonrecurrent ICH. Higher frequency of DDþWW (P ¼ 0.008) and DD/WWþID/GW (P ¼ 0.0001) genotypes were found in recurrent compared to nonrecurrent ICH. Conclusion: Variant genotype combinations of ACE and aADDUCIN render the hypertensive patient vulnerable for recurrent ICH. Study supported by: Study is financially suppoerted by Indian Council of Medical Research, Government of India. S107. Ischemic Stroke Exome Pilot Study John W. Cole, Xinyeu Liu, Luke J. Tallon, Lisa K. Sadzewicz, Oscar C. Stine, Nicole Dueker, Yuching Cheng, Marcella A. Wozniak, Barney J. Stern, James F. Mitchell, Braxton D. Mitchell, Steven J. Kittner and Jeffrey R. O’Connell; Baltimore, MD and Jacksonville, FL Background: The genetic architecture of ischemic stroke is complex and likely to include rare or low frequency variants with high penetrance and large effect sizes. Because a significant portion of human functional variation may derive from the protein-coding portion of genes we undertook a pilot study to identify variation across the human exome. Methods: Ten ischemic stroke cases including 8 AfricanAmericans and 2 Caucasians, consisting of 2 dissections, 5 lacunar, and 3 cryptogenic strokes underwent exome capture and sequencing implementing Illumina and Agilent technology. Whole-genome alignments of the sequence reads were performed using Burrows-Wheeler Aligner against NCBI build 36.1 with the resultant exome data evaluated for capture efficiency and rare variants as associated with stroke. Results: Sequencing generated an average of 25.5 million read pairs (75bp x 2) and 3.8Gbp per sample. After passing quality filters, screening the exomes against dbSNP S105. Risk of Intracerebral Hemorrhage in t-PA Treated Patients with Elevated INR William P. Neil, Rema Raman, Ernstrom Karin and Thomas M. Hemmen; San Diego, CA Use of Intravenous tissue Plasminogen Activator (IV t-PA) for stroke is limited to patients with an INR of less than 1.7. Initial guidelines recommended against use of IV t-PA in patients with an INR >1.4. This was later revised to >1.7. We analyzed our database for safety and outcome in patients with acute ischemic stroke treated with IV t-PA from 2004–2010. We separated patients into two groups: those with INR 0.8–1.3, N ¼ 210 (group 1) and those with INR 1.4 - 1.7, N ¼ 12 (group 2). Intracerebral hemorrhage occurred in 19/210 (9.05%) in group 1 and 2/12 (16.67%) in group 2 (p ¼ 0.316). Symptomatic intracerebral hemorrhage (sICH) was found in 4/ 24 ID: senthilk I Black Lining: [ON] I Time: 08:46 I Path: //xinchnasjn/01Journals/Wiley/3b2/ANA#/Vol00000/110244/APPFile/JW-ANA#110244 J_ID: ZAY Customer A_ID: SUPP11-6 Cadmus Art: 22579 Date: 31-August-11 demonstrated an average of 2839 novel SNPs among African-Americans and 1105 among Caucasians. Nine gene isoforms demonstrated compound heterozygosity across all ten samples. Additional analyses are ongoing. Conclusions: We propose that rare coding variants predispose to the risk of ischemic stroke and that exomic-based analyses are a viable method to identify such variants. Study supported by: Department of Veterans Affairs Stage: Page: 25 Results: At admission, the rate of ND was 37.7%, and RD was 51.9%. The rates of RD were higher among women on admission than men, 62% versus 37% respectively (p ¼ 0.036). At discharge the rate for ND, and RD reduced significantly to 44.2%, and 33.7% respectively (p<0.006). Conclusion: Treatment and care at the hospital improved the dipping status. Significant deviation from normal diurnal dipping is a risk for target organ damage and therefore BP control needs emphasis. S108. Phosphodiesterase Inhibitors Modulate Human Brain Microvascular Endothelial Cell Barrier Properties and Response to Injury Shuo Liu, Fan Yang, Chuanhui Yu, Annlia Paganini-Hill and Mark Fisher; Irvine, CA S110. Preoperative Factors Associated with In-Hospital Mortality Following Minimally Invasive Hematoma Aspiration and Thrombolysis for Intracerebral Hemorrhage Feng Xu, Zhouping Tang, Huicong Kang, Dengji Pan, Suiqiang Zhu and Wei Wang; Wuhan, China Brain microvascular disorders have high prevalence but few treatment options. To develop new strategies for these disorders, we analyzed effects of phosphodiesterase inhibitors on human brain microvascular endothelial cells (HBEC). We modified barrier properties and response to injury of HBEC with three phosphodiesterase (PDE) inhibitors: cilostazol (PDE-3 inhibitor), rolipram (PDE-4 inhibitor), and dipyridamole (non-specific PDE inhibitor). Cilostazol and dipyridamole altered distribution of endothelial Factin. Cilostazol increased expression of tight junction protein claudin-5 by 118 % compared to control (p<.001). Permeability to albumin was decreased by cilostazol (21% vs control, p<.05), and permeability to dextran (70Kd) was decreased by both cilostazol (37% vs control, p<.001) and dipyridamole (44% vs control, p<.0001). Cilostazol increased trans-endothelial electrical resistance (TEER) by 111% compared to control after 12 hours (p<.0001). Protein kinase A (PKA) inhibitors H89 and KT5720 attenuated the TEER increase by cilostazol. Using histamine as standard injury for endothelial monolayers pretreated with PDE inhibitors, cilostazol maintained higher TEER during histamine injury. These findings demonstrate distinctive effects of PDE inhibitors on HBEC. These in vitro findings suggest therapeutic potential of PDE inhibitors in human brain microvascular disorders. Study supported by: NIH NS20989 and Otsuka Pharmaceutical Company. Dr. Fisher has received support from Boehringer-Ingelheim (honoraria, speakers’ bureau, research grant) and Otsuka Pharmaceutical Company (honoraria, research grant). Background and Purpose: Intracerebral hemorrhage (ICH) is the most fatal and disabling stroke subtype. The minimally invasive hematoma aspiration and thrombolysis has the most evidence for beneficial effect on the ICH treatment in the presence of mass-effect. The purpose of this study is to define reliable predictors of in-hospital risk of death following this promising therapeutic modality. Method: All consecutive ICH cases treated with the minimally invasive hematoma aspiration and thrombolysis were prospectively characterized preoperatively from 2007 to 2010 in our division. Mortality was analyzed in relation to CT findings (hematoma location and volume and ventricular extension) and clinical parameters (age and sex, preoperative level of consciousness and hematoma growth) by the multiple linear regression statistical method. Results: One hundred and twenty-nine ICH patients were enrolled. The overall mortality rate was 13.17%. Multiple linear regression analysis revealed initial level of consciousness (B ¼ À0.035, p ¼ 0.002) and intraventricular hematoma (B ¼ 0.176, p ¼ 0.002) were the independent preoperative prognostic factors associated with in-hospital mortality. Conclusion: The level of consciousness along with neuroimaging features can help the clinicians to develop the prognosis of ICH patients treated with the minimally invasive hematoma aspiration and thrombolysis. Study supported by: Management position S111. Does Incidental Micro-Hemorrhage, Detected by Gradient Echo Sequence MRI, Predict Hemorrhagic Transformation of an Ischemic Stroke? Konark Malhotra and Yousef M. Mohammad; Chicago, IL S109. Incidence of Nocturnal Blood Pressure Dipping during Hospital Admission and Discharge among African American Stroke Patients Lien Diep, John Kwagyan, Joseph Kurantsin-Mills, Janaki Kalyanam, Amy Wong, Kermit Crowder, Bonnie Davis, Leia Harbour, Jean Edson and Annapurni Jayam-Trouth; Washington, DC and Baltimore, MD This is a case-control study. We retrieved data on 529 ischemic stroke patients admitted to Rush University. MRI with gradient echo sequence was performed on all of the patients. Using multivariate regression analysis, we assessed the risk of micro hemorrhage(MH) for the development of hemorrhagic transformation(HT) of ischemic stroke after adjusting for age, sex, hypertension, diabetes mellitus, and use of antithrombotics agents prior to the stroke. We had a total of 529 ischemic stroke patients. 81 patients developed HT on the gradient echo sequence MRI. Using multivariate regression analysis, incidental MH was not associated with increased risk of HT of ischemic stroke (11% and 8.9% in the cases and control respectively) (p ¼ 0.53). Interestingly, the intake of anti platelet agents prior to the stroke was associated with decreased risk of HT (33% and 47% in the cases and controls respectively (p ¼ 0.02). Background: Absence of nocturnal dipping in blood pressure (BP) is associated with risk of stroke, and incidence of target-organ damage. Study examined prevalence of nondipping(ND) and reverse dipping (RD) among African American acute stroke inpatients. Methods: We studied 204 patients, 45% males, average age 56 (610.7) years at Howard University Hospital. Daytime BP was defined as average from 10am to 6pm and nighttime from 10pm to 6am. Nocturnal BP dipping refers to !10% fall in average nighttime BP compared to daytime. Non-dipping, and reverse dipping during admission were compared to that at discharge. 25 ID: senthilk I Black Lining: [ON] I Time: 08:46 I Path: //xinchnasjn/01Journals/Wiley/3b2/ANA#/Vol00000/110244/APPFile/JW-ANA#110244 J_ID: ZAY Customer A_ID: SUPP11-6 Cadmus Art: 22579 Date: 31-August-11 In this small sample size study, incidental MH as detected by Gradient Echo Sequence MRI was not associated with increased risk for HT of ischemic stroke. However, prior intake of anti-platelet agents was associated with decreased risk for HT of ischemic stroke. Stage: Page: 26 S115. Genetic Analysis of Strain-Specific Stroke Sesceptibility in Mice: How To Classify C57BL/6? Amy K. Guzik, Sean S. Li, Ira M. Hall, Charles R. Farber, Brian H. Annex and Bradford B. Worrall; Charlottesville, VA Preclinical genetic research can identify potential mechanisms and therapeutic targets for ischemic stroke. Many inbred mouse strains show consistent ischemic susceptibility. Comparing C57BL/6 to susceptible strains, others have identifed a chromosome 7 locus. However, we found no differentially expressed genes at this locus when comparing multiple resistant to susceptible strains. Additionally, in our literature review, C57BL/6 demonstrate variable vulnerability to MCA occlusion. Thus, we analyzed genomic differences between mouse strains with distinct stroke susceptibilities classifying C57BL/6 as susceptible, resistant, or neither. Methods: Utilizing the mouse phenome database and literature-derived phenotypes, we compared resistant (129S1/ SvlmJ, DBA/2J, FVB/HJ, NOD/ShiLtJ) and susceptible (AKR/J, BALB/cByJ, C3H/HeJ) strains. C57BL/6J was added to resistant and susceptible groupings in separate comparisons. Results: Comparisons excluding C57BL/6J demonstrated higher density and percent difference in genomic regions. Within specific loci of genomic differences, C57BL/6J share some patterns with resistant strains and others with susceptible strains. Conclusion: These genetic results mirror conflicting MCAO data, and therefore suggest uncertain classification of C57BL/6. Among newly identified regions, a chromosome 4 locus encompases 100þ genes, many we previously implicated in gene expression experiments, providing promising targets for further research. Study supported by: NIH R25 resident training grant, University of Virginia Internal CTSA pilot grant. S112. Younger Patients Have Lower Quality of Life after Intracranial Aneurysm Diagnosis Nerissa Ko, Richard Hornung, Charles Moomaw, Laura Sauerbeck and Joseph Broderick; San Francisco, CA and Cincinnati, OH Objective: Quality of life (QOL) is an important outcome in patients with intracranial aneurysm (IA). EuroQol EQ5D is a validated preference-based survey that incorporates functional, physical, and mental status into a single QOL value. We measured EQ-5D in subjects with and without IA in the Familial Intracranial Aneurysm (FIA) Study. Methods: Within FIA families, subjects with IA were identified after review of clinical and imaging data. Family members free of IA entered the study as non-cases. Subjects who completed the EQ-5D survey 365 6 60 days after diagnosis (75 cases) or study entry (885 non-cases) were included in the present analysis. Multivariable logistic regression was performed using the EQ-5D index adjusted for variables known to affect QOL. Results: EQ-5D index was significantly lower in subjects with IA than in those without IA (mean 6 SD 0.84 6 0.19 vs. 0.90 6 0.15, p<0.001), especially within the anxiety/depression component (p<0.001). This difference persisted in the multivariable model, with strong interactions noted with tobacco use and age<50 years (p ¼ 0.02). Interpretation: The lower QOL indices in younger IA patients may reflect the impact of IA diagnosis on mental status rather than physical/functional disability in this subgroup Study supported by: NIH/NINDS R01NS039512 S116. Risk Factor Control in a Phase 3 Carotid Revascularization Trial James F. Meschia, Pierre P. Leimgruber, Vito A. Mantese, Carlos H. Timaran, David Chiu, Bart M. Demaerschalk, Mary E. Longbottom, Jenifer H. Voeks, George Howard and Thomas G. Brott; Jacksonville, FL; Spokane, WA; St. Louis, MO; Dallas, TX; Houston, TX; Phoenix, AZ and Birmingham, AL S113. Aggressive Medical Management of Primary Intracerebral Hemorrhage: Cost/Benefit Analysis Luis Cava, Diane C. Andress-Rothrock and John F. Rothrock; Birmingham, AL Objective: to assess the direct medical cost and clinical outcome associated with aggressive medical management of supratentorial primary intracerebral hemorrhage (PICH). Methods: We evaluated 150 consecutive cases of supratentorial PICH wherein the patient was intubated and mechanically ventilated within 24 hours of admission. Clinical outcome and hospital-related direct medical costs were the primary variables examined. Results: Of the 150 patients, 66(44%) died in the hospital; intraventicular extension of ICH and age >65 each correlated independently with in-hospital mortality (p<.025). Of the 84 survivors, 3(3.5%) were discharged to home and the remainder to an extended care facility. One month following initial admission, 1(.6%) of the 150 patients was independent in routine activities of daily living. The mean direct cost associated with in-patient management exceeded $275,000 (range $24,000-$1.5 million). Conclusion: Aggressive medical management of supratentorial PICH is associated with an unfavorable clinical outcome and represents a particularly poor use of healthcare resources. Background: Success of carotid revascularization in preventing stroke must be seen in the context of the success or failure to control traditional risk factors. Purpose: To describe Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) risk factor control. Methods: Risk factor intervention was not protocoldriven. Investigators and coordinators counseled patients and communicated by form-letter with primary physicians, guided by patient-visit results and Guideline statements, with oversight by the CREST PI and Co-PI. Exploratory analyses were performed at baseline and at 36months. Results: For asymptomatic patients, results at 0- and 36months were 142 and 139mmHg for mean systolic blood pressure (SBP); 73 and 75mmHg for mean diastolic BP (DBP); 120 and 112mg/dL for blood glucose; 92 and 87mg/dl for LDL cholesterol; and 24 and 11% for the active smoking. For symptomatic patients, results were 143 and 136mmHg for SBP; 75 and 74mmHg for DBP; 114 and 114mg/dl for glucose; 102 and 91mg/dl for LDL; and 27 and 12% for active smoking. S114. Withdrawn 26 ID: senthilk I Black Lining: [ON] I Time: 08:46 I Path: //xinchnasjn/01Journals/Wiley/3b2/ANA#/Vol00000/110244/APPFile/JW-ANA#110244 J_ID: ZAY Customer A_ID: SUPP11-6 Cadmus Art: 22579 Date: 31-August-11 Conclusion: Traditional stroke risk factors were comparably controlled for asymptomatic and symptomatic patients, with notable success only in smoking cessation. Protocoldriven approaches merit further study. Study supported by: This study was supported by the National Institute of Neurological Disorders and Stroke (NINDS) and the National Institutes of Health (NIH) (R01 NS 038384) and supplemental funding from Abbott Vascular Solutions (formerly Guidant). Dr. Carlos Timaran reports receiving Speakers’ fees and Honoraria from Abbott Vascular. Dr. George Howard reports receiving compensation for activities with Bayer Healthcare and research support from Amgen and Bayer Healthcare. He is also a consultant to Abbott for preparation of FDA materials. Stage: Page: 27 disease (e.g., carotid stenosis). Two independent reviewers selected studies, with differences adjudicated by a third. Study characteristics, patient symptoms, and lesion locations were abstracted. Results: We identified 414 unique citations, examined 67 full manuscripts, and analyzed 39 studies describing 1214 patients. Principal reasons for abstract exclusion were non-English language, no confirmed cerebrovascular diagnosis, and not anterior circulation (73%). Principal reasons for manuscript exclusion were no reported dizziness and no confirmed cerebrovascular diagnosis (53%). Unbiased studies of dizziness prevalence in anterior circulation stroke (i.e., dizziness not a mandatory symptom) reported a presenting symptom of dizziness in 12% (8.4% non-vertiginous, 3.2% vertiginous), syncope in 6.6% of n ¼ 683. Non-vertiginous symptoms were more commonly reported in right hemispheric lesions (73.9% vs. 26.1%, v2 p<0.001). Typical lesion locations were insula, parietal cortex, and subcortical white matter. Conclusions: Contrary to common wisdom, dizziness and vertigo are presenting symptoms of anterior circulation vascular disease. S117. Radiologic Analysis of Thrombolysis-Induced Intracerebral Hemorrhage and the Role of Early Blood Pressure Management Maxim Mokin, Tareq Kass-Hout, Omar Kass-Hout, Robert Zivadinov and Bijal Mehta; Buffalo, NY Introduction: The radiographic features of thrombolysisinduced intracerebral hemorrhages (ICH) and factors that influence early hematoma expansion are not well described. Methods: We performed volumetric analysis of hematoma volumes in patients who developed ICH from intravenous thrombolysis for acute ischemic stroke. Analysis of covariance was used to evaluate for the effect of baseline blood pressure (BP) on initial hematoma volume and further growth. Results: We found a positive correlation between systolic BP following thrombolysis and initial hematoma volume (r ¼ 0.46, p ¼ 0.03) but not for the diastolic BP (r ¼ 0.07, p ¼ 0.40). There was a significant increase in mean hematoma volume expansion when comparing results between the first and second (median time 9 hours 22 min) CT study (14.9 6 19.6 cm3 to 26.0 6 26.7 cm3, p ¼ 0.04). There was also a negative association between the reduction of systolic BP and hematoma growth (r ¼ À0.67, p ¼ 0.02), but no correlation with change in diastolic BP (r ¼ 0.22, p ¼ 0.28). Conclusion: Thrombolysis-induced ICH undergoes significant early expansion in size. Systolic BP plays a role in both initial hematoma development and early growth. Dr. Robert Zivadinov received personal compensation from Teva Neuroscience, Biogen Idec, EMD Serono and Questcor Pharmaceuticals for speaking and consultant fees, financial support for research activities from Biogen Idec, Teva Neuroscience, Genzyme, Questcor Pharmaceuticals, Greatbatch, EMD Serono and Bracco. Dr. Bijal Mehta received lecturing honoraria from Teva and Biogen Idec. S119. The Presence of Intracranial Vascular Calcification May Protect Against Vasospasm Following Subarachnoid Hemorrhage Joya Paul, Mohamed Zghouzi, Yousef Mohammad, Shyam Prabhakaran, Sudeep Bhabad and Bichun Ouyang; Chicago, IL Vasospasm is a serious complication of subarachnoid hemorrhage (SAH). Intracranial vascular calcification (IVC) is incidentally noted on computerized tomography (CT). Presence of IVC may retard contraction of vascular smooth muscle and inhibit vasospasm. In a retrospective single-center study, we reviewed data on consecutive patients with SAH. Symptomatic vasospasm was defined as clinical deterioration associated with angiographic vasospasm requiring intra-arterial treatment. Brain CT angiogram (CTA) images were evaluated for IVC. Chisquare tests and logistic regression analyses assessed the association between IVC and symptomatic vasospasm and controlled for age, gender, Hunt Hess (HH) score, and Fisher Grade (FG). Among 434 patients with SAH, 313 had complete data (mean age 57; 67% female). IVC was detected in 40% and 20% had symptomatic vasospasm. Only 12.7% of those with IVC had symptomatic vasospasm versus 25.2% in those without IVC (OR ¼ 0.430, p ¼ 0.004). Adjusting for age, gender, HH score, and FG, presence of IVC showed a trend towards decreased odds of symptomatic vasospasm (adj. OR ¼ 0.534, p ¼ 0.075). IVC may have a protective effect on symptomatic vasospasm following SAH. Further study may be warranted. S118. Anterior Circulation Stroke Causing Dizziness or Vertigo: A Systematic Review Yun Zhou, Seung-hun Lee, Ali S. Saber Tehrani, Karen A. Robinson and David E. Newman-Toker; Baltimore, MD and Gwangju, Korea S120. Stroke Knowledge: A Nation-Wide, Internet-Based Survey of 11,121 Inhabitants in Japan Hisanao Akiyama, Kanako Shimizu, Yoshiaki Tokuyama and Yasuhiro Hasegawa; Kawasaki, Kanagawa, Japan Background: Determine frequency, localization of anterior circulation stroke causing dizziness/vertigo. Methods: Systematic review of observational studies. Search—electronic (MEDLINE) and manual search for English-language studies (1966–2011). Inclusions—dizziness/vertigo/syncope due to anterior circulation stroke or vascular Objective: To investigate the difference in stroke knowledge among inhabitants, we performed a nation-wide, internetbased survey. 27 ID: senthilk I Black Lining: [ON] I Time: 08:46 I Path: //xinchnasjn/01Journals/Wiley/3b2/ANA#/Vol00000/110244/APPFile/JW-ANA#110244 J_ID: ZAY Customer A_ID: SUPP11-6 Cadmus Art: 22579 Date: 31-August-11 Method: The survey was conducted from November, 2010 via internet using structured, self-applicable questionnaire addressed stroke knowledge. Results: We have valid responses from 11,121 people aged from 20 to 69 years old throughout all Japanese districts. 66.2% of subjects were no source of informations about stroke. On the other hand, subjects of remaining 33.8% can get the informations of stroke through mainly TV (85.2%). They understood the signs of stroke such as speech disturbance (95.5%). 67% of them request the ambulance and transport to the hospital promptly at the time of stroke onset but only 22.4% on the occasion of TIA. Importance of early diagnosis and treatment within 3 hours of onset was well recognized among all age subjects (75.3%) and significantly associated with calling ambulance quickly when stroke (OR 4.458, 95%CI, 3.897– 5.099, p ¼ 0.000) or TIA (OR 2.331, 95%CI, 1.923– 2.825, p ¼ 0.000) occurred. Conclusions: Our survey demonstrates that it is important to educate stroke knowledges through TV such as judgment of stroke and calling ambulance when stroke or TIA occurred. Stage: Page: 28 hypertension (HTN) are modifiable cardiovascular risk factors with higher prevalence in minorities. Design: We evaluated patients with acute ischemic stroke/TIA presenting to Boston Medical Center from 1/ 2009-12/2010. Patients were stratified by race (Whites, Blacks, Other) and insurance status (Medicaid/no insurance, Medicare, Private). Cardiovascular risk factor control (HTN, hyperlipidemia, diabetes) was evaluated on admission. Results: Among 833 patients (mean age 61yrs, 50.4% women), 34.8% were white, 45.5% black and 19.7% other races; 50.4% were insured and 49.6% uninsured. Compared to white, black and other races were more likely to be uninsured (p<0.001), had higher LDL (p<0.001), HbA1C (p<0.001), and DBP (p<0.001). Compared to insured patients, uninsured patients were younger (p ¼ 0.0001), had higher LDL (p ¼ 0.02), HbA1C (p ¼ 0.02), and DBP (p ¼ 0.02). Conclusions: Our findings suggest that race and insurance disparities may influence the control of cardiovascular risk factors, thereby risk of stroke. S123. A Population-Based Verbal Autopsy Study of 1250 Stroke Deaths in Bangladesh Farrah J. Mateen, Nurul Alam, Marco Carone and Robert E. Black; Baltimore, MD; Dhaka, Bangladesh and Berkeley, CA S121. Is Anti Epileptic Drug Necessary in Cortical Venous Thrombosis? Velmurugendran Cannigaiper Uthamaroyan, Kaushik Sundar, Meenakshisundaram Umaiorubahan and Shankar Venkatasubramaniam; Chennai, Tamilnadu, India Background: Verbal autopsy is an interview-based method to determine the cause of death in resource-poor regions. A health and demographic surveillance system has been maintained in Matlab, Bangladesh since 1966 (average population 223,886 in 142 villages). Methods: All adult deaths (2005–2008) were reviewed and categorized by medical officers. Risk factors for stroke deaths were calculated using all adult injury deaths as controls. Results: 1250 stroke deaths (51% women; mean age 72 years, range 20–101) occurred out of 4955 total deaths (population-attributable mortality 25.2%) and were compared to 274 adult injury deaths (47% women, mean age 55.8 years, range 20–100). Risk of stroke death increased with hypertension (OR ¼ 7.94, 95%CI 4.44-15.54, p<0.001), diabetes (OR ¼ 2.54, 1.21-6.21, p ¼ 0.02), and betel consumption (OR 2.36, 1.45–3.80, p<0.001), but not from heart disease (OR 1.37, 0.45–5.95, p ¼ 0.62), cigarette smoking (OR ¼ 1.41, 0.82–2.45, p ¼ 0.22), tobacco powder (OR ¼ 1.15, 0.30–7.64, p ¼ 0.86), or pipe smoking (OR ¼ 0.94, 0.45–2.18, p ¼ 0.88). Conclusions: There is a high modifiable burden of risk factors for adult stroke deaths in rural Bangladesh which may include betel consumption, a previously unidentified risk factor for stroke. Endemic hypertension and diabetes also represent treatable and preventable risk factors. Study supported by: Dr. Mateen is supported by the American Academy of Neurology Practice Research Fellowship Grant and The Johns Hopkins Bloomberg School of Public Health Sommer Scholars Program. Introduction: Though CVT is associated with seizures,is it necessary to start AEDs in all patients with CVT? Aims To study the clinical profile of patients with CVT and to find out the incidence and etiology of seizures. Materials and methods: Patients who presented with signs and symptoms suggestive of CVT were admitted and brain imaging was done.If CVT was revealed,requisite investigations were done.Patients were then treated and followed up for a period of one year. Results: 50 (28 males/22 females) patients were diagnosed to have CVT.Of these 50 patients 25 of them presented with Seizures and all these 25 had an infarct/haemorrhage/ infarct with haemorrhagic transformation in their MRI. Discussion: We found that 50% of our study patients had seizures and all of them had an infarct/haemorrhage/or infarct with haemorrhagic transformation.The patients who did not have an infarct did not have a seizure and were not started on AEDs and remain seizure free till date. Conclusion: Patients with CVT who have no evidence of parenchymal lesion in the MRI need not be treated with AEDs as a prophylaxis and a wait and watch strategy can be followed. Study supported by: Self S122. Race and Insurance Disparities in Cardiovascular Risk Factors Control in Patients with Acute Stroke Anna M. Cervantes, Jose R. Romero, Helena Lau, Feliks Koyfman, Aleksandra Pikula, Thanh N. Nguyen, Carlos S. Kase and Viken L. Babikian; Boston, MA S124. Heparin-Induced Thrombocytopenia Associated with Cerebral Venous Sinus Thrombosis Following Postoperative Enoxaparin Administration in a 64 Year-Old Female Robert A. Fishman and Ashis Tayal; Pittsburgh, PA Objective: To investigate racial and socioeconomic disparities in cardiovascular risk factor control at the time of acute ischemic stroke at an urban hospital. Background: Racial and socioeconomic inequalities may play a role in the observed higher frequency and severity of stroke in minorities. Hypercholesterolemia, diabetes and Heparin-induced thrombocytopenia (HIT) is a serious platelet dyscrasia that is associated with clinically-significant 28 ID: senthilk I Black Lining: [ON] I Time: 08:46 I Path: //xinchnasjn/01Journals/Wiley/3b2/ANA#/Vol00000/110244/APPFile/JW-ANA#110244 J_ID: ZAY Customer A_ID: SUPP11-6 Cadmus Art: 22579 Date: 31-August-11 arterial and venous thrombosis. The more common, and dangerous form of HIT, HIT II, is caused by prothrombotic anti-heparin/platelet factor PF4 complex antibodies, which activate platelets, induce their aggregation, and trigger coagulation (1). The consequences, especially if not diagnosed early, can be devastating, ranging from deep venous thromboses to myocardial infarctions and strokes. HIT is most commonly associated with the use of heparin after orthopedic procedures, as compared to cardiovascular surgeries and medical conditions requiring admission to an intensive care unit. HIT is much less frequently associated with the use of low molecular weight heparin, such as enoxaparin (3). Here, we present the case of a 64 year-old woman who developed both a lower extremity deep venous thrombosis and cerebral venous sinus thromboses from the administration of enoxaparin after an orthopedic surgery. Our patient is only the second reported case of HIT-induced CVST related to enoxaparin administration. Our poster will include brain imaging, graphs and tables regarding the clinical case. Study supported by: Residency Program Stage: Page: 29 tion. Typical RVAS is known to occur due to compression of the dominant vertebral artery during contralateral head rotation, usually at the atlantoaxial joint. A few reports have described atypical patterns of RVAS, such as compression of bilateral vertebral artery during unilateral head rotation and various compression level. The present case shows that dominant vertebral artery can be also compressed by ipsilateral head tilt in RVAS. A 29-years-old man presented with 8 months history of paroxysmal vertigo induced by head tilt to the left. The patient reported that tinnitus in both ears and visual blurring were accompanied by rotatory vertigo. Leftward head tilt induced mainly downbeat nystagmus with a small left beating horizontal component. MRI of the brain was unremarkable and MR angiography showed a hypoplastic right vertebral artery. Dynamic angiography documented complete occlusion of the left vertebral artery at the atlantoaxial junction during leftward head tilt. S127. A Novel Presentation of Mesodiencephalic Ischemic Stroke: Case Report and Literature Review Khalid S. Alqadi, Tariq Alfahad and Kathleen Burger; Washington, DC S125. Renal Failure Increases Risk for Intracranial Hemorrhage Following Stroke Elisabeth B. Marsh, Argye E. Hillis, Rafael H. Llinas and Rebecca F. Gottesman; Baltimore, MD Objective: To present and discuss the clinical and image findings of a novel mesodiencephalic infarct along with its anatomic and pathophysiologic correlates. Background: Strokes in the mesodiencephalic junction can have different presentations due to its complex neural circuits. Weber’s syndrome from thalamic-midbrain stroke has been described in the literature in association with facial palsy, & vertical gaze palsy. To our knowledge, the combination of Weber’s syndrome, contralateral facial & pseudoabducens palsies with vertical gaze palsy have never been described before. Results: A 45 year old male presented with acute onset of double vision, speech difficulty and left side weakness. Neurological exam showed right oculomotor nerve palsy, left central facial and pseudoabducens palsies with vertical gaze palsy, and left hemiparesis. His NIH stroke scale was 11. MRI revealed right thalamic infarct extending inferiorly into the midbrain. MRA of head and neck, and transthoracic echocardiogram were normal. Conclusions: This case highlights the importance of recognizing the atypical manifestations of strokes in the thalamic midbrain junction. Small vessel stroke at the mesodiencephalic junction can lead to a combination of weber’s syndrome with contralateral facial and pseudoabducens palsies with vertical gaze palsy. Background: Anticoagulation is associated with increased risk of intracranial hemorrhage. Renal failure can lead to platelet dysfunction, which may increase the risk further. We followed patients admitted with acute ischemic stroke who had an indication for anticoagulation, to determine if renal failure was associated with increased risk for intracranial hemorrhage. Methods: 63 patients admitted with acute ischemic stroke and with an indication for anticoagulation were included. Age-adjusted logistic regression was used to evaluate the association between history of renal failure and glomerular filtration rate (GFR) (>60 (normal), 30–60 (mildly reduced), <30 (moderately reduced)), and risk for hemorrhage. Results: Patients with renal failure of any type were much more likely to hemorrhage than individuals without history of renal failure (OR 12.40, 95% CI 1.35–113.36). Worsening GFR was also highly associated with risk of hemorrhage. Compared to individuals with normal GFR, patients with mildly reduced GFR were 1.2 times (OR 1.22, 95% CI 0.09–16.16) and individuals with moderately reduced GFR were 15 times (OR 15.43, 95% CI 1.98– 120.02; p-trend 0.03) more likely to bleed. Conclusions: In patients with acute ischemic stroke who also require anticoagulation, renal insufficiency is associated with increased risk of intracranial hemorrhage. Study supported by: The first author, EB Marsh, is supported in part by a NINDS R25 Research Grant- R25 NS065729. EB Marsh is currently a resident, partially supported by funding from the R25 Research Grant. S128. Fatal Postpartum Cerebral Vasoconstriction Syndrome Jennifer E. Fugate, Eelco F.M. Wijdicks, Kelly D. Flemming and Alejandro A. Rabinstein; Rochester, MN Background: Postpartum cerebral vasoconstriction is typically considered benign and self-limiting. We describe four fulminant and fatal cases seen in a short time period at one institution. Methods: Retrospective case series of patients seen at Mayo Clinic from August 2009 – October 2010. Results: Four women ages 15–33 developed acute neurologic deficits 1–8 days after uncomplicated deliveries. One had history of migraine headaches. Two had uneventful pregnancies while two had pre-eclampsia. Presenting symptoms included severe headache (n ¼ 3), focal deficit (n ¼ 1), seizure (n ¼ 1) and encephalopathy (n ¼ 1). Initial brain imaging demonstrated ischemia and global edema in 2, lobar hemorrhage in 1, and normal findings in 1. All had S126. Dominant Vertebral Artery Occlusion during Ipsilateral Head Tilt In Soo Moon, Jae-Hwan Choi and Kwang-Dong Choi; Busan, Korea Paroxysmal vertigo induced by head rotation occurs in patients with rotational vertebral artery syndrome (RVAS), which is characterized by recurrent attacks of vertigo, nystagmus, and ataxia that are mainly induced by head rota- 29 ID: senthilk I Black Lining: [ON] I Time: 08:46 I Path: //xinchnasjn/01Journals/Wiley/3b2/ANA#/Vol00000/110244/APPFile/JW-ANA#110244 J_ID: ZAY Customer A_ID: SUPP11-6 Cadmus Art: 22579 Date: 31-August-11 rapid deterioration over hours to days with multi-territorial infarctions and global edema on imaging. All had angiographic findings of diffuse, severe, multifocal arterial narrowings. Aggressive treatment was attempted in most, including intravenous magnesium, corticosteroids, calcium channel blockers, balloon angioplasty, vasopressors, and osmotic agents. Despite aggressive measures, all patients suffered fulminant courses ending in death within 8–24 days after delivery. Conclusions: Postpartum vasoconstriction can be fatal with rapid progression of vasoconstriction, ischemia, and brain edema. Postpartum women with acute neurological symptoms deserve close monitoring with consideration of noninvasive cerebrovascular imaging. Stage: Page: 30 Results: A positive correlation between the volume of infarction measured on MRI and NIHSS at presentation was found with an R squared value of .12. NIHSS stroke scale range was 7–32. 11 of 14 patients with infarction volume of < 30 ml had improved outcome with 1 no change and 2 worsening. Of the 6 with infarction volume > ¼ 30ml and < ¼ 100ml, 5 improved and 1 had worse outcome. 4 patients had infarction volume > 100 with one improved and 3 with worse outcome. Conclusion: High ischemic volume have higher NIHSS and worse outcome. Study supported by: USF College of Medicine S131. Treatment Outside the NINDS Stroke Study Exclusion Criteria: A Case Report Nhu T. Bruce and Brett C. Meyer; San Diego, CA S129. Racial Disparities in Secondary Stroke Prevention Practices Pratik Bhattacharya, Seemant Chaturvedi, Flicia Mada, Leeza Salowich-Palm, Sabrina Hinton, Scott Millis, Sam Watson and Kumar Rajamani; Detroit, MI and Lansing, MI Introduction: The original NINDS stroke trial established IV rt-PA as effective and defined treatment parameters. Some exclusions were well founded on data, others were chosen via consensus opinion. Successful use of rt-PA outside of some criteria raises concern over the continued utility of some exclusions. We report an intriguing case where a patient with prolonged PTT was successfully treated with IV rt-PA. Methods: Case report from the University of California, San Diego Results: An 86 year old woman with no hematologic history presented with acute ischemic stroke within the 3 hour window. Given her lack of being on anticoagulants or having hepatic dysfunction, her elevated PTT was felt to be spurious, and she was treated with rt-PA despite not meeting this inclusion criteria. Patient had significant improvement and work up was positive for a diagnosis of anti-phospholipid antibody syndrome. Conclusions: rt-PA treatment is effective, though only a minority of patients is treated. Multiple cohort studies have shown that deviations from the original exclusions may not result in worse outcomes for specific exclusion criteria. Reevaluating the significance and limiting the exclusion criteria may help to increase thrombolytic treatments. Study supported by: NIH SPOTRIAS Racial differences in stroke risk, risk factor prevalence and outcomes are established. We explored racial differences in secondary stroke prevention practices among stroke patients. Methods: A retrospective review was conducted on ischemic stroke patients in 5 JC (Joint Commission) certified and 5 noncertified hospitals. Secondary stroke prevention measures such as antiplatelet use, statin use, antihypertensives and smoking cessation steps were assessed. Results: 574 patients (430 white, 144 African Americans(AA); 47.9% evaluated at JC certified centers) were included. AA were younger (mean age 64.4 vs 72.5; p<0.0001) and more likely to have prior stroke (37.1% vs 27.7%; p ¼ 0.03). More AA were evaluated at JC certified centers(65.3% vs 42.1%; p<0.0001). AA received stroke education materials(89.9% vs 77.8%; p ¼ 0.002) and were discharged on antiplatelets more often (95.8% vs 89.5%; p ¼ 0.02). Compliance with secondary prevention measures was higher in JC certified centers. Racial disparity in antiplatelet use was present in JC certified centers alone(100%in AA, 91.8% in whites; p ¼ 0.005). Patients discharged without antiplatelets from JC centers were older and more likely to be discharged to a nursing home. Conclusions: Racial disparities exist in secondary stroke prevention practices (antiplatelet use and stroke education) even in JC certified centers. Increased awareness of these differences amongst patients, families and caregivers could help narrow the disparities. Study supported by: Blue Cross and Blue Shield Foundation of Michigan. S132. Size Matters: Predictors of Intracranial Hemorrhage in Stroke Patients on Anticoagulation Elisabeth B. Marsh, Argye E. Hillis, Rafael H. Llinas and Rebecca F. Gottesman; Baltimore, MD Background: Anticoagulation is associated with increased risk of intracranial hemorrhage. This may be higher in patients who have had a recent stroke. We followed patients with acute ischemic stroke who had an indication for anticoagulation, to determine what factors were associated with increased risk for hemorrhage. Methods: 63 patients admitted with acute ischemic stroke and with an indication for anticoagulation were included. We evaluated risk of hemorrhage associated with indicators of stroke severity; namely NIH Stroke Scale (NIHSS) score and infarct size (largest lesion and total lesion volume), using age-adjusted logistic regression. Results: Higher NIHSS scores predicted increased risk of hemorrhage. For every 3 point increase, risk for hemorrhage increased 51% (OR 1.51, 95% CI 1.01–2.25). Total volume of the infarct also approached statistical significance (OR 2.6 per larger quartile, 95% CI 0.86–7.56). Conclusions: In patients with acute ischemic stroke who also have an indication for anticoagulation, the severity of S130. Predicting Ischemic Stroke Outcomes Based on Volume of Lesion Shazia Z. Choudhary, Jay-Ming Wang, Zahid Choudary, Michael Sloan, Harry R. Van Loveren, Karen R. Wilson, Morgan Wang and David A. Decker; Tampa, FL and Orlando, FL Hypothesis: Can stroke lesion volume predict ischemic stroke outcome? Background: Imaging to diagnose stroke needs development to maximize its potential. We seek to the use stroke lesion volume to predict ischemic stroke outcome. Methods: We did a retrospective chart review of 24 patients with hospitalization with ischemic stroke. The volume of the infarction was measured by using (A x B x C) / 2 method. Patient outcomes were measured by linear regression model and data segmentation. 30 ID: senthilk I Black Lining: [ON] I Time: 08:46 I Path: //xinchnasjn/01Journals/Wiley/3b2/ANA#/Vol00000/110244/APPFile/JW-ANA#110244 J_ID: ZAY Customer A_ID: SUPP11-6 Cadmus Art: 22579 Date: 31-August-11 their stroke, indicated by their NIHSS score and volume of infarct, is a strong predictor of their risk for hemorrhage. Study supported by: The first author, EB Marsh, is supported in part by a NINDS R25 Research Grant- R25 NS065729. EB Marsh is currently a resident, partially supported by funding from the R25 Research Grant. Stage: Page: 31 Background: Not all guidelines for stroke are well supported by evidence. We seek to retrospectively study the effects of MERCI/PENUMBRA stroke interventions and hemodynamics to see ischemic stroke outcome. Methods: A retrospective chart review of 24 patients with hospitalization with ischemic stroke with age range 18 to 90, mean age 70.6, 13 males, and 11 females. The blood pressure was correlated with ischemic stroke outcome. The patients undergoing MERCI/PENUMBRA intervention were analyzed. Results: We noted a significant positive correlation between higher blood pressures and worse outcomes in patients with large volume lesions. In the 8 patients with MERCI/PENUMBRA intervention, we had 3 with worse outcomes and 5 with improvement at discharge. Of the 3 with worse outcomes, 2 had large lesions and 1 had a small lesion. The 5 improved outcomes had 3 small lesions and 2 medium lesions. Three of the five had received IV tPA prior to interventional therapy. Two did not. Conclusion: MERCI/PENUMBRA intervention has an overall positive outcome on patients suffering from ischemic stroke. Higher blood pressures predict a worse outcome in patients with stroke lesions greater than 100 ml. Study supported by: USF College of Medicine S133. A Rare Presentation of Anterior and Posterior Spinal Arteries Ischemia during Dilaysis Noor Yono, Adrian Marchidann and Rabih Kashouty; Manhasset, NY and New York, NY Spinal cord infarction is considered to be a rare event and usually presents with severe neurological deficits. Multiple etiologies have been described; however, this is the first case report of spinal cord infarction in the territory of the anterior and posterior spinal arteries secondary to hypotension during dialysis. We report a case of a 60 year-old man with past medical history of severe atherosclerosis, coronary artery disease and acute kidney failure, who presented with lower extremity paraplegia during hemodialysis secondary to hypotension. MRI of the spine demonstrated spinal cord infarction starting at the level of T8 and below. Clinical features suggested that the lesion was an ischemic infarct. In addition to paraplegia, he demonstrated absence of sensation to dull touch, pin prick, temperature, proprioception and vibration. Hypotension during dialysis could carry significant risk of spinal cord infarction. This unusual infarction demonstrates the importance of blood pressure control in susceptible patients with severe atherosclerotic disease. Physicians should be aware of such complications. S136. Migraine-Related ICH – A Case Study and Review Shivani Ghoshal**, Sankalp Gokhale and Louis Caplan; Boston, MA 54 year-old right-handed male, with a 25-year history of frequent migraine headache, presented with an episode of severe migraine headache associated with visual changes; imaging revealed new left frontal intracranial hemorrhage. Since then, the patient had two different types of paroxysmal attacks. One consisted of prolonged severe headaches with multisystem sensory deficits, most consistent with migraine with aura. The second consisted of brief visual and auditory perseveration, likely representing focal seizures near the region of ICH. Excluding the initial presentation, the subsequent episodes left no discernible damage on clinical exam or imaging. Migraine is a form of vascular headache, postulated to cause direct vasoconstriction of cerebral vessels. This vasospasm may, in some cases, lead to reperfusion edema, with intracerebral bleeding to follow. Though migraine-related ischemia has been well-documented, there have been few noted cases of migraine-related ICH and none to date in male patients; the association of migraine and ICH is likely under-recognized and hence underreported. Given the dangers for cerebral hemorrhage, future migraine treatment may benefit from weighing the risk of vasoactive agents. We take this opportunity to review the current literature to provide guidance for improvement in care. S134. Neurosarcoidosis: A Case Presentation Amtul Farheen, Nancy Gadallah, Rony Dekermenjian, Michael Rosenberg and Sushanth Bhat; Edison, NJ 27 y/o man with no significant medical history woke up with weakness and parasthesias of his right side. He smoked 1ppd for more than 10yrs. Neurological examination was significant for decreased power on right side. Right upper extremity revealed power of 2/5 deltoid, 3/5 bicep/tricep/ brachio, 1/5 intrinsic hand muscles, Right lower extremity revealed: 4/5 iliopsoas, hams, quads 0/5 dorsi and plantar flexion 0/5. Sensation was mildly decreased on right side. Reflexes were asymmetric and increased with upgoing toe on the right. MRI brain showed small left medullary hyperintensity. Csf had opening Pressure of 23, RBC 222, WBC 7, Prot 57.8, Glucose 65. CSF was negative for gram stain, protein electrophoresis, oligoclonal bands, and infectious work up. Csf ACE 0.1. Serum ACE was 109. CT chest showed mediastinal and bilateral hilar lymphadenopathy. Mediastinal lymph node biopsy revealed noncaseating granulomas diagnostic of neurosarcoidosis. The patient was started on iv steroids and was discharged on oral prednisone. He improved clinically and was later almost back to his baseline. Although sarcoidosis is rarely confined to the nervous system, its neurological features frequently occur early in the course of the disease leading to diagnostic confusion. S137. Stroke as a Complication of Tuberculous Meningitis Amtul Farheen, Sumaiya Salim, Zoha Fasih, Rony Dekermenjian and Sushanth Bhat; Edison, NJ S135. Stroke Outcomes Based on MERCI/PENUMBRA Intervention and Hemodynamics Jay-Ming Wang**, Zahid I. Choudary, Shazia Z. Choudhary, Michael Sloan, Harry R. Van Loveren, Karen R. Wilson and David A. Decker; Tampa, FL A 28 y/o Hispanic man who moved to US from Guatemala four years before presentation, had no significant past medical history presented with 2 days of progressive confusion and headache. He reported weight loss, severe cough for few days with low grade temperatures and night sweats. He smoked occasionally. On examination he was lethargic and cachectic, neck stiffness noted, enlarged lymph nodes of the Hypothesis: What are the effects of MERCI/PENUMBRA and blood pressure on stroke outcome? 31 ID: senthilk I Black Lining: [ON] I Time: 08:46 I Path: //xinchnasjn/01Journals/Wiley/3b2/ANA#/Vol00000/110244/APPFile/JW-ANA#110244 J_ID: ZAY Customer A_ID: SUPP11-6 Cadmus Art: 22579 Date: 31-August-11 neck. He was tachycardic and had diminished breath sounds with bilateral crackles. Neurological examination revealed normal cranial nerve examination. He moved all extremities spontaneously. Initial CT head was normal. Lumbar puncture revealed WBC 53 (neutrophils predominantly), RBC 7, Protein 170, Glucose 7. Sputum was positive for AFB. HIV testing was negative. He was diagnosed with disseminated tuberculosis with tuberculous meningitis and started on antituberculous medications. On the third day of admission he had decreased movement of the left side of his body and a repeat CT of his head showed a new infarct in the right internal capsule. Vasculitis of the vessels of circle of Willis which may present as stroke is one of the most dreaded complications of Tuberculous meningitis. Stage: Page: 32 Results:7,925 dizzy patient complaints (3% of visits, weighted 28.3 million) sampled over 13 years. Dizziness was ��isolated’’ (none, nausea/vomiting, or otologic co-complaints) in 21%; others with dizziness had only neurologic (10%), only medical (15%), or other (54%) co-complaints. Cerebrovascular causes were diagnosed in 4.1% (isolated), 10% (neurologic), 0.9% (medical), 3.8% (other), 1.0% (non-dizzy controls). Neurologic co-symptoms increased odds (2.57, 95%CI 1.85 to 3.58) and medical co-symptoms decreased odds (0.21, 95%CI 0.10–0.41) of a cerebrovascular diagnosis relative to isolated dizziness. Conclusions: ED physicians use associated symptoms to diagnose dizzy patients. While this reflects an appropriate assessment of disease probability, it could increase the risk of stroke misdiagnosis in isolated dizziness or dizziness with medical symptoms. Study supported by: This study was supported principally by the National Institutes of Health, National Center for Research Resources (NCRR) grant K23 RR 17324-01. S138. Patterns and Mechanisms of Head-Shaking Nystagmus in Anterior Inferior Cerebellar Artery Infarction Young Eun Huh and Ji Soo Kim; Seongnam-si, Gyeonggi-do, Korea S140. Eclamptic Versus Non-Eclamptic PRES (Posterior Reversible Encephalopathy Syndrome): Comparison of Clinical Features and Response to Treatment Pavan Bhargava, Fazeel Siddiqui, Vivek Patel, Rodger J. Elble and Srikanth Vallurupalli; Springfield, IL Infarctions involving the anterior inferior cerebellar artery (AICA) territory give rise to unique clinical features of combined peripheral and central vestibulopathies. Evaluation of head-shaking nystagmus (HSN) may provide information on central and peripheral vestibular dysfunction. We analyzed patterns of spontaneous nystagmus (SN) and HSN in 18 patients with acute infarction involving the AICA territory which was confirmed on MRI. Patients also underwent head impulse and bithermal caloric tests, and pure tone audiogram. Twelve patients (12/18, 67%) showed unilateral caloric paresis (n ¼ 11) or abnormal head impulse test (n ¼ 9) on the side of the infarction and most of them (10/ 12, 83%) also had acute hearing loss. Fifteen patients (83%) exhibited HSN, and the horizontal HSN was usually contralesional (10/14, 71%). However, 9 patients also showed patterns of central HSN which included perverted HSN (n ¼ 7), ipsilesional HSN (n ¼ 4), and HSN in the opposite direction of SN (n ¼ 4). Especially, perverted HSN was induced in half of the 6 patients without audiovestibular loss. In AICA infarction, HSN was common with both peripheral and central patterns. Careful evaluation of HSN may provide clues for AICA infarction in patients with acute unilateral audiovestibular loss. Study supported by: This study was supported by grant of the Korea Health 21 R&D Project, Ministry of Health & Welfare, Republic of Korea (A080750) Objective: To examine the hypothesis that eclamptic PRES responds more rapidly to treatment than non-eclamptic PRES. Background: PRES is characterized by reversible vasogenic edema, predominantly in the posterior circulation distribution, and can occur in various clinical settings such as eclampsia and malignant hypertension. It is unknown whether clinical, imaging and EEG features differ in eclamptic versus non-eclamptic PRES. Design/Methods: Retrospective data including clinical, EEG and MRI characteristics was collected on patients diagnosed with PRES between January 2003 and June 2010. Appropriate statistical methods were employed. Results: 45 episodes of PRES occurred in 43 patients(69% women) with a mean age of 44.5 years(range 9–82). The nine patients with eclampsia had significantly lower age(25 6 5 yrs vs. 50 6 20 yrs, p ¼ 0.002), shorter duration of stay following diagnosis(3.1 vs. 7.6 days, p ¼ 0.002), less incidence of renal impairment(0% vs. 39%, p ¼ 0.04) and lower likelihood of abnormal EEG finding(33% vs. 85%, p ¼ 0.07) compared to non-eclamptic PRES. The etiologies of non-eclamptic PRES were hypertension(86%), sepsis(17%), transplant(11%) and connective tissue disorder(17%). Conclusions: Eclamptic PRES appears to respond more rapidly with treatment of the underlying condition than non-eclamptic PRES, which has a more varied etiology. S139. Co-Complaints Influence Odds of Stroke Diagnosis in ED Dizziness Ali S. Saber Tehrani, Yu-Hsiang Hsieh, Jonathan A. Edlow, Carlos A. Camargo and David E. Newman-Toker; Baltimore, MD and Boston, MA Movement Disorders Background: Assess impact of co-complaints on stroke diagnosis in dizziness presentations to US emergency departments (EDs). Methods: Design—Cross-sectional study of ED visits from the National Hospital Ambulatory Medical Care Survey. Setting—Weighted sample of US ED visits (1993– 2005). Participants—!16 years old; reason-for-visit code vertigo/dizziness (1225.0). Measures—co-complaints, ICD-9 diagnoses. Co-complaints grouped as otologic (e.g., tinnitus); neurologic (e.g., weakness); medical (e.g., chest pain); or other (including multiple co-complaint groups). Diagnoses grouped using HCUP categories. S201. Allele Specific RNAi Against Triplet Repeat Disease-Causing Alleles in Huntington Disease Hirokazu Furuya, Masaki Takahashi, Shoko Watanabe, Miho Murata, Ichiro Kanazawa, Keiji Wada and Hirohiko Hohjoh; Omuta, Fukuoka, Japan and Kodaira, Tokyo, Japan Suppression of disease-causing alleles is a potential approach to treatment of intractable diseases caused by dominate-negative alleles, such as triplet repeat diseases. RNAi may be an applicable tool in medical treatment; however, the identification of nucleotide variations and the design of siRNAs 32 ID: senthilk I Black Lining: [ON] I Time: 08:46 I Path: //xinchnasjn/01Journals/Wiley/3b2/ANA#/Vol00000/110244/APPFile/JW-ANA#110244 J_ID: ZAY Customer A_ID: SUPP11-6 Cadmus Art: 22579 Date: 31-August-11 conferring disease allele-specific RNAi are quite difficult. Here we report an innovative procedure that facilitated allele-specific silencing of disease-causing alleles in Huntington disease (HD), a triplet repeat disease. We developed a pull-down method to rapidly identify coding SNP (cSNP) haplotypes of triple repeat, disease-causing alleles, and demonstrated disease allele-specific RNAi that targeted cSNP sites in mutant Huntingtin (HTT) alleles, each of which possessed a different cSNP haplotype. We examined 5 patients with HD, found heterozygous cSNP sites in two patients, and successfully suppressed the disease-causing alleles in lymphoblastoid cells derived from the patients by means of RNAi. Therefore, the methods allow for diseasecausing allele specific silencing targeting disease-linked cSNP haplotypes of triplet repeat diseases. Study supported by: This work was supported by research grants from the Ministry of Health, Labour and Welfare of Japan Stage: Page: 33 modified Center for Epidemiologic Studies Depression Scale at examinations from 1991–1993 in 403 autopsied participants. A score >8 was defined as significant DS. LC neurodegeneration was based on semi-quantitative assessments by a neuropathologist shielded from clinical information. After age-adjustment, significant neurodegeneration was observed in 32.9% of 55 decedents with DS versus 17.8% in 348 without DS (p ¼ 0.010). DS continued to be associated with LC neuron loss after removing 27 PD or dementia with Lewy bodies cases (p ¼ 0.044), and after removing 89 cases with any Lewy pathology (p ¼ 0.010). Findings suggest that DS correlate with LC involvement in PD prior to development of classic motor symptoms as well as in some individuals without Lewy pathology. Study supported by: NIA, NIH; NINDS, NIH; Department of Defense; Office of Research and Developement, Veterans Affairs S204. MRI in HDLS Shows a Unique Mechanism of Neuroaxonal Degeneration C. Sundal*, C. Wider, J.A. Van Gerpen, J. Lash, J.Y. Garbern, K.J. Schweitzer, J. Aasly, B. Goodman, B.K. Woodruff, C.W. Christine, M. Baker, J.E. Parisi, S. Roeber, S. DeArmond, R. Rademakers, D.W. Dickson, D.F. Broderick, O. Andersen and Z.K. Wszolek; Gothenburg, Sweden; Jacksonville, FL; Rochester, NY; Trondheim, Norway; Scottsdale, AZ; San Francisco, CA; Rochester, MN and Munchen, Germany S202. Antigen-Sensitized Dendritic Cell Vaccine Against Human a-Synuclein: A Potential Cell-Based Therapy Against Parkinson’s Disease Chuanhai Cao, Xiaoyang Lin, Wang Li, Cai Jianfeng, Li Kunyu, Song Shijie and Juan Sanchez-Ramos; Tampa The goal of this study was to develop a cell-based vaccine directed against human a-synuclein (hAS). Human recombinant a-synuclein (hrAS) was expressed in BL21 cells and AS peptides were synthesized based on antigen analysis. Mouse bone marrow-derived dendritic cells (DCs) were generated ex vivo, sensitized with hrAS or AS mixed peptides and then delivered i.v. to Tg hAS mice. Mice vaccinated with DCs sensitized with a peptide mixture (DC-ASpep) exhibited detectable anti-AS antibody earlier than mice vaccinated with DC-sensitized with human recombinant protein (DC-hrAS). With repeated treatments, antibody levels in the DC-hrAS was higher than in the DCASpep group. AS levels were significantly decreased at both 3rd and 5th treatment compared to the control group. In behavioral tests, treatment groups performed better on the rotometer than control mice; the DC-ASpep group exhibited the best performance. Among all cytokines measured, only GM-CSF and IL1a were significantly changed after treatment, indicating that this treatment method has no potential to induce inflammation. Conclusions: AS-sensitized dendritic cell vaccination is effective, specific, long-lasting and unlike antigen-based vaccines, does not elicit non-specific activation of the immune system. Study supported by: Parkinson Study Group and Helen Ellis Endowed Chair Fund Background: Hereditary diffuse leukoencephalopathy with spheroids (HDLS) is an autosomal dominant neurodegenerative disorder with symptomatic disease onset usually in adult age and with relatively rapid course leading to death in less than a decade. It is clinically characterized by a constellation of symptoms including personality changes, cognitive dysfunction and motor impairments, often leading to a clinical misdiagnosis. Neuropathology is characterized by axonal spheroids. The disease-causing gene is unknown. Methods: Over the last 7 years, we have collected HDLS families both retrospectively and prospectively. We performed head magnetic resonance imaging (MRI) studies with only neuropathological proven HDLS cases/kindreds. Results: From all 13 families available to us, 14 cases were studied. 4 had repeated examinations. MRI demonstrated unique distribution of changes in the periventricular, deep and subcortical white matter of frontal/parietal lobes and in corpus callosum. Conclusions: MRI is helpful to substantiate the diagnosis of HDLS. It will be an important biomarker for HDLS progression after the gene is identified. It will also be very useful to follow the patients undergoing future experimental treatments if such are developed. Study supported by: C.Sundal supported by research grants through Gothenburg University, Sweden S203. Depressive Symptoms and Neurodegeneration in the Locus Coeruleus: The Honolulu-Asia Aging Study Ross Webster, Robert D. Abbott, Helen Petrovitch, Kamal H. Masaki, Caroline M. Tanner, Jane H. Uyehara-Lock and Lon R. White; Honolulu, HI; Hiroshima, Japan and Sunnyvale, CA S205. Appropriate Outcome Measures for Cognitive Trials in Huntington’s Disease Jody Corey-Bloom, Jody Goldstein, Shea Gluhm, Charles Van Liew, Stephanie Lessig, Jagan Pillai and Steven D. Edland; La Jolla, CA Depression commonly occurs in Parkinson’s disease (PD), often pre-dating diagnosis. Lewy pathology in the locus coeruleus (LC) occurs early in PD and LC neurodegeneration occurs in depressed PD patients. Whether depressive symptoms (DS) are associated with LC neurodegeneration prior to onset of classic PD motor features remains unclear. Our objective is to examine the association of DS and LC neurodegeneration in decedents from the longitudinal Honolulu-Asia Aging Study. DS were assessed using the 11-item Suitable measures are needed for clinical trials of therapeutic agents for cognition in Huntington’s disease (HD). The Montreal Cognitive Assessment (MoCA), Mini-Mental State Examination (MMSE), and Mattis Dementia Rating Scale (DRS) are commonly used cognitive instruments; however, little is known about longitudinal change on these measures in HD. We used mixed effects models to analyze MoCA, MMSE, and DRS scores obtained during 2.5–5 years of 33 ID: senthilk I Black Lining: [ON] I Time: 08:46 I Path: //xinchnasjn/01Journals/Wiley/3b2/ANA#/Vol00000/110244/APPFile/JW-ANA#110244 J_ID: ZAY Customer A_ID: SUPP11-6 Cadmus Art: 22579 Date: 31-August-11 follow-up of up to 153 subjects with HD. Annual rates of decline on the MoCA and MMSE were 1.0 and 0.69 points/year, respectively, over 2.5 years of follow-up. Rate of decline on the DRS was 3.04 points/year in the first 5 years of observation. For cognitive trials in HD, sample size requirements (90% power, critical alpha level 0.05) for a 3year trial to detect 50% reduction in mean rate of decline using the MoCA, MMSE, or DRS would be 106, 173, and 165 subjects/ treatment arm, respectively. We conclude that, although all three measures decline significantly over time in an unselected HD population, the MoCA may be a more efficient instrument for assessing effects of a therapeutic agent for cognition in HD. Study supported by: Huntington’s Disease Society of America and Shiley-Marcos Alzheimer Disease Research Center NIH P50 AG005131. Stage: Page: 34 with hallucinations or depression followed by memory impairment. The younger brother developed levodopa responsive asymmetrical parkinsonism characterized by resting tremor, rigidity, and bradykinesia during the course of his illness. The autopsy showed transitional (limbic) type of Lewy body disease (LBD) in the brother and diffuse LBD in the older sister, with mild to moderate Alzheimer’s disease pathology (Braak stage II-IV) in both. We will present our clinicopathologic review with future genealogical and clinical research planned on this family. Study supported by: ZKW is partially supported by the NIH/NINDS 1RC2NS070276, NS057567, P50NS072187, Mayo Clinic Florida (MCF) Research Committee CR programs (MCF #90052018 and MCF #90052030), and gift from Carl Edw and Bolch, Jr., and Susan Boss Bolch (MCF #90052031/PAU #90052). FS is partially supported by Mayo Clinic Florida (MCF) Research Committee CR programs (MDF #90052018). S206. Distinctive Neurocognitive Profiles Associated with Right and Left Motor Symptom Onset in Parkinson’s Disease Paul J. Eslinger, Daymond Wagner, Suman Sen, Mechelle M. Lewis, Guangwei Du, Michele L. Shaffer and Xuemei Huang; Hershey, PA S208. Alcohol Consumption and Risk of Parkinson Disease Rui Liu, Yikyung Park, Xuemei Huang, Xuguang Guo, Albert Hollenbeck, Aaron Blair and Honglei Chen; Research Triangle Park, NC; Rockville, MD; Hershey, PA and Washington, DC Parkinson’s disease (PD) is commonly diagnosed in patients presenting with asymmetric motor impairments. However, the literature remains mixed with regard to the significance and prognostic value of identifying first-onset motor symptoms particularly for cognitive functioning and progression. We investigated the hypothesis that asymmetric motor impairment and attendant dopamine loss are associated with distinctive right- and left-onset profiles in 36 PD subjects (21 with right-sided,15 with left-sided motor symptom onset) and 44 matched healthy controls recruited for longitudinal cognitive and anatomical studies. Although samples did not differ on screening cognitive measures (Mini-Mental Status Examination, Montreal Cognitive Assessment), contrasting profiles of neurocognitive impairments were detected in PD. Specifically, left-sided motor symptoms were associated with prominent deficits in visuospatial learning and memory, visuospatial speed/accuracy in mirror tracing, and design fluency. In contrast, right-sided motor symptoms were associated with decline in cognitive flexibility and heightened symptoms of depression. Results support the hypothesis that asymmetric motor symptoms in PD are associated with distinctive patterns of early cognitive change that may require different management approaches. Analyses are underway to examine the relationship between such cognitive profiles and cortical changes in PD. Study supported by: National Institutes of Health Objective: To prospectively examine the association between overall and individual types of alcohol consumption and risk of Parkinson disease (PD). Methods: Participants comprised 1,086 PD cases and 299,684 individuals without PD from the NIH-AARP Diet and Health Study. Alcohol consumption was assessed in 1995–1996 and PD was diagnosed in 2000–2006. Results: Total alcohol consumption was not associated with PD. However, moderate beer consumption was associated with lower risk of PD. After controlling for potential confounders and other types of alcohol consumption, the multivariate odds ratio (OR) for beer drinkers was 0.81 (95% confidence interval [CI] 0.70–0.94) for <1 drink/day, 0.76 (0.52–1.11) for 1–1.99 drinks/day, and 0.87 (0.61– 1.24) for !2 drinks/day. For liquor consumption, we found a monotonic increase in PD risk: ORs (95% CI) were 1.05 (0.91–1.23), 1.19 (0.91–1.56), and 1.39 (1.05–1.84) for <1, 1–1.99, and !2 drinks/day; p trend <0.01. Results for wine consumption were less clear, although a lower PD risk was also observed when comparing drinkers of 1–1.99 drinks/day with nondrinkers. Conclusions: Our results suggest that beer and liquor consumption may have opposite associations with PD: moderate beer consumption with lower PD risk and liquor consumption with higher risk. Study supported by: Supported by the intramural research program of the NIH, the National Institute of Environmental Health Sciences (Z01-ES-101986), and the National Cancer Institute (Z01 CP010196-02). S207. The Clinical and Pathological Features of Familial Parkinsonism with EIF4G1Gene Mutation Shinsuke Fujioka, Owen A. Ross, Rosa Rademakers, Matthew J. Farrer, Dennis W. Dickson and Zbigniew K. Wszolek; Jacksonville, FL and Vancouver, BC, Canada S209. Hereditary Diffuse Leukoencephalopathy with Spheroids: An Under-Diagnosed Disease C. Sundal, C. Wider, J.A. Van Gerpen, J. Lash, J.Y. Garbern, E.A. Shuster, K.J. Schweitzer, J. Aasly, B. Goodman, B.K. Woodruff, W. Kupsky, A. Tselis, C.W. Christine, M. Baker, J.E. Parisi, S. Roeber, S. DeArmond, R. Rademakers, D.W. Dickson, O. Andersen and Z.K. Wszolek; Gothenburg, Sweden; Jacksonville, FL; Rochester, NY; Trondheim, Norway; Scottsdale, AZ; Detroit, MI; San Francisco, CA; Rochester, MN and Munchen, Germany Recently, we have performed genome-wide linkage analysis of several families with autosomal-dominant late-onset parkinsonism and identified mutations in a novel susceptibility gene for Parkinson’s disease, eukaryotic translation initiation factor 4-gamma 1 isoform (EIF4G1) on chromosome 3q2627. The missense mutations, EIF4G1 c.2057G>T (p.G686C) and c.3589C>T (p.R1197W) were identified together in two siblings of US 331-95 family. We reviewed available medical records and brain autopsy reports for both siblings. Mean age at symptomatic onset was 79 years and mean disease duration was 5.5 years. Both siblings presented Background: Hereditary diffuse leukoencephalopathy with spheroids (HDLS) was originally described in a Swedish 34 ID: senthilk I Black Lining: [ON] I Time: 08:46 I Path: //xinchnasjn/01Journals/Wiley/3b2/ANA#/Vol00000/110244/APPFile/JW-ANA#110244 J_ID: ZAY Customer A_ID: SUPP11-6 Cadmus Art: 22579 Date: 31-August-11 kindred in 1984. An additional 11 kindreds and 8 sporadic cases have been reported over the years. Inheritance is autosomal dominant. HDLS presents with psychiatric, cognitive and motor symptoms. A definite diagnosis is made pathologically by demonstrating axonal spheroids. The causative gene is unknown. Method: Brains and brain biopsy specimens were collected through world wide collaborations and only those cases/families demonstrated pathological features of HDLS were included in our study. Results: 20 affected individuals were identified in 13 kindreds. During the course of the illness all patients developed parkinsonian signs along with other classic symptoms of HDLS. There was no response to levodopa. The mean age of onset was 45 years (range, 16–68), and mean disease duration was 4 years (range, 1–11). Discussion and Conclusions: HLDS is an under-diagnosed neurodegenerative condition. Cases are misdiagnosed as AD, PD, CBD, MS, FTD, FTDP, and others. Finding the gene for this condition will be of paramount importance in understanding the neurodegeneration associated with white matter abnormalities. Study supported by: C.Sundal supported by research grants through Gothenburg University, Sweden Stage: Page: 35 hoc analyses revealed older PD onset age in aMCI-SD, worse MMSE scores in naMCI-MD, and worse H&Y stage in naMCI-MD. Mean UPDRS motor scores were higher in both MD subtypes. Axial function differed among groups with worse scores in naMCI-MD. Conclusion: Nonamnestic and single domain impairment predominated. Multiple-domain PD-MCI had worse motor function. Increased burden of cognitive dysfunction (multiple-domain), rather than deficit type (amnestic/nonamnestic), may be associated with greater motor impairment and dementia risk. Study supported by: NIH K23060949, Parkinson’s Disease Foundation S212. Loss of Cortical Gray Matter in Parkinson’s Disease Suman Sen, Paul J. Eslinger, Daymond Wagner, Guangwei Du, Mechelle M. Lewis, Michel L. Shaffer and Xuemei Huang; Hershey, PA In addition to classic motor dysfunction, Parkinson’s disease (PD) patients exhibit cognitive deficits that are related to cortical network dysfunction. To investigate PD changes in cortical gray matter, high-resolution T1-weighted magnetic resonance images were acquired from 40 right-handed PD subjects and compared to 40 age-, gender-, education-, and handedness-matched healthy controls. Screening cognitive measures of Mini-Mental Status Examination (p ¼ 0.32) and Montreal Cognitive Assessment (p ¼ 0.81) were also comparable between groups. Imaging data were analyzed using voxel-based morphometry (VBM). Permutation-based, nonparametric testing (5000 permutations) was applied within the framework of a general linear model, adjusting for age and gender within groups. Group differences were considered significant at p<0.05 (FWE corrected), after initial clusterforming thresholding at p 0.01 (uncorrected). Compared to controls, PD subjects showed significant loss of gray matter in the left precentral and paracentral gyri, left superior temporal gyrus, bilateral orbital-frontal cortex, bilateral frontal poles, precuneus, cuneus, and left occipital cortex. Results support the conclusion that PD causes significant loss of cortical gray matter in multiple regions outside motor areas. In addition to confirmation with additional samples, correlation of the cortical alterations with cognitive, behavioral and other functional outcomes warrants further investigation. Study supported by: National Institute of Neurological Disorders and Stroke (NS060722), General Clinical Research Center Grant from National Institutes of Health (M01RR10732), General Clinical Research Center Construction Grant (C06RR016499) S210. Co-Existing HTT and ATXN8OS Repeat Expansions and a �Face of the Giant Panda’ Sign on MRI in a Patient with a Complex Movement Disorder Shin C. Beh, Cherian A. Karunapuzha and Shilpa Chitnis; Dallas, TX We present a 66 year old woman with a complex movement disorder syndrome. The disease began in her mid-fifties with fidgetiness. She later developed progressive gait ataxia and chorea. Unintended weight loss, mild dysphagia, depression and mild memory impairment were also present. Examination revealed square-wave jerks, grimacing, motor impersistence, generalized choreiform movements, hyperreflexia and an ataxic, choreic gait. Her mother had a similar movement disorder. In addition to cortical atrophy, T2-weighted brain MRI demonstrated mesencephalic white matter hyperintensity with areas of hypointensity in the red nuclei, substantia nigra and superior colliculi taking on the appearance of the ��face of the giant panda’’ sign. Genetic testing revealed coexisting huntingtin and ATXN8OS triplet repeat expansions. We discuss phenotype-genotype correlation and the unusually variable phenotypes of spinocerebellar ataxia 8. S211. Clinical Differences among PD-MCI Subtypes Jennifer G. Goldman, Glenn T. Stebbins, Bryan Bernard and Christopher G. Goetz; Chicago, IL S213. Association of PSP with Chemical Occupational Exposure Factors Irene Litvan, Christopher R. Cunningham, Peter Lees, Leila Jackson, Jorge Juncos, David Riley, Yvette Bordelon, David Standaert, Stephen Reich, Alex C. Cambon, Joseph Jankovic, Deborah A. Hall, Richard Dubinsky, Cassandra Shepherd, Claire Henchcliffe, Ryan Uitti, Benzi Kluger, David Shprecher, Connie Marras, Eliza Gallin, James Leverenz and Shesh N. Rai; Louisville, KY; Baltimore, MD; Cleveland, OH; Atlanta, GA; Los Angeles, CA; Birmingham, AL; Houston, TX; Chicago, IL; Kansas City, KS; New York, NY; Jacksonville, Fl; Boulder, CO; Salt Lake City, UT; Toronto, Canada and Seattle, WA Objective: To examine PD-MCI subtypes. Background: Mild cognitive impairment in PD (PDMCI) may represent a pre-dementia state. MCI subtypes distinguish between amnestic (aMCI) and nonamnestic (naMCI) phenotypes and single (SD) or multiple-domain (MD) impairment. Whether PD-MCI subtypes differ in characteristics, progression or neuropathology remains unknown. Methods: 96 PD-MCI patients (not demented but with zscore of < À1.5 on at least 1 of 5 cognitive domains) were classified as: aMCI-SD, naMCI-SD, aMCI-MD, and naMCI-MD. Results: Group demographics included: age 71.8 (9.2), education 14.5 (2.9), PD duration 6.9 (5.2) years; MMSE 26.9 (2.1); UPDRS motor score 31.6 (11.4). In our sample, 25% had aMCI-SD, 44% naMCI-SD, 21% aMCI-MD, and 10% naMCI-MD. Subtypes differed significantly regarding age, PD onset age, MMSE, and H&Y stage. Post- Background: Multicenter case-control study designed to determine if an association exists between occupational chemical exposures and PSP. 35 ID: senthilk I Black Lining: [ON] I Time: 08:46 I Path: //xinchnasjn/01Journals/Wiley/3b2/ANA#/Vol00000/110244/APPFile/JW-ANA#110244 J_ID: ZAY Customer A_ID: SUPP11-6 Cadmus Art: 22579 Date: 31-August-11 Methods: Analysis is based on 199 PSP cases and 129 age-gender and geographically matched controls. Trained interviewers conducted standardized telephone surveys to collect information including demographics, residence history, lifetime occupational history and home pesticide use. An industrial hygienist and toxicologist blinded to whether data were from cases or controls assessed self-reported exposure to chemicals and determined if the subjects had direct, indirect or no exposure based on occupational histories. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using univariable and multivariable logistic regression adjusting for significant covariates. Results: PSP cases were significantly more likely to report exposure to occupational pesticides (OR:2.22; CI:1.15-4.37, p ¼ 0.015) and organic solvents (OR:1.57; CI:1.05-2.34, p ¼ 0.026) than controls. Using assigned exposures, cases were significantly more likely to have direct exposure to any chemical (OR:1.99; CI:1.26-3.16, p ¼ 0.003), and pesticides (OR:2.14; CI:1.06-4.61, p ¼ 0.034). Conclusions: This is the first epidemiological study to find a significant association between occupational chemical exposures and PSP. Future studies should determine which chemicals are associated with the development of this primary tauopathy and whether genetic and environmental risk factors interact. Study supported by: National Institutes of Aging, National Insitutes of Health Stage: Page: 36 Objective: To study if STN-DBS or GPi-DBS has different effects on gait and balance in individuals with PD. Background: Both STN- and GPi-DBS improve motor functions in PD. However, their differential benefits on gait and balance are unclear. Comparison of their effects may help clinical decisions in choosing the target. Method: Composite scores of 5-UPDRS items (arising, posture, gait, postural instability, bradykinesia) and 3-item standwalk-sit test of the STN-DBS (N ¼ 25) and GPi-DBS (N ¼ 23) groups were compared. Variables during ��off-on’’ (medication-off, stimulation-on), ��off-off’’ and ��on-on’’ were measured. Result: During ��off-on’’, the sum of 5-item UPDRS improved by 1.96(p<0.05) in STN-DBS and 1.44(p<0.01) in GPi-DBS from ��off-off ’’. The 3-item stand-walk-sit improved by 2.4%, 2.8%, À1.4% in STN-DBS and 14.7%, 12.6%, 16.7% in GPi-DBS. During ��on-on’’, the sum improved by 4.32(p<0.001) and 3.60(P<0.001); the stand-walk-sit improved by 39.1%, 25.4%, 70.0% in STNDBS; and 46.1%, 34.6%, 68.9% in GPi-DBS, respectively. Discussion: Our results suggest that STN-DBS alone was more beneficial than GPi-DBS on gait performance. After taking levodopa, both groups had much more improvement, particularly for freezing episodes. Levodopa remains a gold standard treatment for PD patients after DBS. Study supported by: Veterans Affairs salaries S216. Reliability of Self-Reported Parkinson’s Disease (PD) Features Caroline M. Tanner, Cheryl Meng, Ira Shoulson, Anthony E. Lang, David Oakes, Roger Kurlan, Alberto Ascherio, Flint Beal, Emily Flagg, Jennifer Harman, Michael Schwarzchild, James Beck, Bernard Ravina, Kenneth Marek, Shirley Eberly, Karen Marder and Robin Elliott; Sunnyvale, CA; Washington, DC; Toronto, ON, Canada; Rochester, NJ; Summit, NJ; Boston, MA; New York, NY; Cambridge, MA and New Haven, CT S214. Psychiatric Co-Morbidities and Mortality among Hospitalized Parkinson Disease Patients Nicte Mejia and Zeina Chemali; Boston, MA Affective and anxiety disorders are determinants of poor quality of life and survival for Parkinson disease (PD) patients. Their impact on in-hospital PD mortality has not been examined. The study evaluates the effect of depression and anxiety on in-hospital PD mortality. PD patients with depression or anxiety would have higher in-hospital mortality compared to PD patients with no psychiatric co-morbidities. Alcohol or drug use would further increase mortality. We sampled 1998–2007 HCUP-NIS for PD, depression, anxiety, alcohol and drug use were identified through ICD-9 codes. All statistical models were adjusted for age, gender, and race/ethnicity. 3,013,346 collected PD discharges-age 77.9 (SD 9.0 years), 52.8% male, 84% white. Depression identified in 10.6%; anxiety in 4.7%, an underestimate to population predicted prevalence for those disorders in same settings. Statistically significant lower mortality was found for PD patients with known depression (OR ¼ 0.64; p< 0.001) or anxiety (OR ¼ 0.50; p< 0.001). Substance and alcohol use were assessed as modifiers. Depression and anxiety are under-diagnosed in hospitalized PD patients. Contrarily when recognized and appropriately treated, depression and anxiety are associated with lower in-hospital PD mortality. Alcohol and illicit substances impact negatively on PD outcome. Study supported by: The authors have no disclosure. Dr. Nicte Mejia was awarded 2010 AAN Foundation Clinical Research Training Fellowships Objective: To determine reliability of self-reported remote assessments of PD. Background: In person visits can be costly and impossible for some. Remote assessment may provide a useful alternative. Subjects: Participants in both the Longitudinal Assessment and Biomarker Study of PD, LABS-PD (in person assessments) and Follow-up of Persons with Neurologic Diseases, FOUND (assessments using mailed self-reported questionnaires.) Methods: Analogous FOUND and LABS-PD assessments occurring within 3 months were compared. Results: During 45.2 months median follow-up, 325/422 subjects completed at least one FOUND assessment within 3 months of a LABS-PD assessment. Exact agreement was ! 80% for diagnosis, disease features (e.g., tremor, dyskinesias) and PD medication type. For the 19 items in the UPDRS parts II & IV, agreement was > 70% (8 items: 70–79%, ICC 0.230–0.594; 11 items ! 80%, ICC 0.230 – 0.676). For the 20 items in the MDS-UPDRS parts I.b. & II, exact agreement was > 60% (2 items:60 – 69%, ICC 0.215–0.353; 11 items: 70–79%, ICC 0.393 - 0.563; 7 items: ! 80%, ICC 0.397 – 0.694). Conclusion: Remote assessment of PD patients using mailed self-reported questionnaires is a reliable way to collect information on disease status. Study supported by: Parkinson’s Disease Foundation; NIH; Cephalon, Inc.; H. Lundbeck A.S. Dr. Beck and Mr Elliott are employed by the Parkinson’s Disease Foundation. S215. Comparison of Subthalamic (STN) and Pallidal (GPi) Deep Brain Stimulation (DBS) on Gait and Balance in Patients with Parkinson’s Disease (PD) Jyhgong Gabriel Hou, Minn Thant, Aliya Sarwar, Linda Fincher, Monthaporn S. Bryant, Farrah Atassi and Eugene C. Lai; Houston, TX and Galveston, TX 36 ID: senthilk I Black Lining: [ON] I Time: 08:46 I Path: //xinchnasjn/01Journals/Wiley/3b2/ANA#/Vol00000/110244/APPFile/JW-ANA#110244 J_ID: ZAY Customer A_ID: SUPP11-6 Cadmus Art: 22579 Date: 31-August-11 S217. First Neurological Examination Can Predict Course of Parkinson’s Disease (PD) Ali H. Rajput, Michele L. Rajput and Alex H. Rajput; Saskatoon, SK, Canada Stage: Page: 37 Parkinson’s disease (PD). In 2008, Llebaria and colleagues reported excellent sensitivity and specificity detecting dementia in PD using a DRS total score cutoff of 123. However, this study used a sample with rather low educational achievement. Methods: Linear discriminant function analysis was used cross-validate the 123 cutoff score in a sample of PD patients with rather high educational. Results: From a sample of 38 PD patients, 12 were diagnosed with dementia following comprehensive neuropsychological evaluation. A total score cutoff of 123 misidentified 9 patients with dementia (25% sensitivity, 100% specificity). Age and education corrected scaled scores did not improve overall classification. Discussion: Results suggest caution in applying DRS-2 total score cutoffs in highly educated patients, and highlight the importance of comprehensive neuropsychological evaluations for clinical diagnosis of dementia in PD. Our previous publications concluded that, when the entire clinical course is considered, the tremor dominant (TD), mixed (MX), and akinetic/rigid (AR) subtypes of PD have different pathology and different outcomes. There are no biological markers or early clinical manifestations to distinguish between those phenotypes. All patients were followed at Movement Disorders Clinic Saskatchewan and autopsied between 1972 and 2006. Those with Lewy body PD and no co-morbidity to modify the motor features were included. Excluded were cases that at baseline had 15 years or longer duration of PD motor symptoms. The patients were assessed in the state as they attended our clinic. We hypothesized that predominant tremor at baseline would evolve into lifelong TD, predominant akinesia/rigidity into AR and those with equal severity into MX subtypes. 156 PD cases in the study, included 39 AR, 106 MX, and 11 TD subtypes. Mean duration of symptoms at baseline was 4.4 years. 133 (85%) of all – 90% of AR, 88% of MX, and 55% of TD could be accurately identified at baseline. These observations are helpful for patient care, drug trials patient selection and for studies of pathophysiology of PD. Study supported by: Have received honorarium for lectures and meeting participation from Novartis. Have received travel support to meeting from Teva. Have been involved in Botulinum toxin study sponsored by Allergan. Research funding from Curling Classic, Parkinson Society Saskatchewan, and Greystone Golf Classic. S220. Impaired Social Problem-Solving in Huntington’s Disease Charles Van Liew, Jody Goldstein, Shea Gluhm, Jagan Pillai and Jody Corey-Bloom; San Diego, CA Huntington’s disease (HD) is a genetic neurodegenerative disorder characterized by motor, cognitive, and psychiatric dysfunction. In HD, the inability to solve problems successfully affects not only disease coping, but also interpersonal relationships, judgment, and independent living. In the current study, we examined social problem-solving (SPS) in well-characterized HD and at-risk (AR) subjects using the Social Problem-Solving Inventory-Revised:Long (SPSIR:L)—a 52-item, well-validated, standardized measure of SPS. Items are aggregated under five subscales (Positive, Negative, and Rational Problem-Solving; Impulsivity/ Carelessness; and Avoidance). Thirty-five subjects, including 12 HD (mean age ¼ 53, mean CAG ¼ 44) and 23 gene-positive AR (mean age ¼ 41, mean CAG ¼ 42), were compared with two-tailed t-tests on SPSI-R:L scores. HD subjects scored significantly worse on Total SPS (p<.05), explained by greater Avoidance (p ¼ .01) and Impulsivity/ Carelessness (p<.0001) than AR subjects. Our findings demonstrate that, as HD progresses, impulsivity and avoidance become more predominant and, inevitably, problematic. We conclude that the SPSI-R provides a promising and novel means of quantifying psychosocial impairments in HD. Further studies will be needed to confirm and extend these findings. Study supported by: UCSD Shiley-Marcos Alzheimer’s Disease Research Center, UCSD Huntington’s Disease Society of America Center of Excellence S218. Difficulty with Balance Occurs Early in PD: It Isn’t Appreciated Because It’s Not Asked about Nor Tested For Abraham N. Lieberman, Samea Husain, Naomi Salins and Anthony Santiago; Phoenix, AZ Objective: Devise a question and tests to assess balance early, before patients fall. Background: Balance difficulty resulting in falls is a wellrecognized feature late in PD. Less well known is that balance difficulty occurs early in PD. Method: In addition to questions and testing of gait on the UPDRS we added a question about balance and 3 simple balance tests. We assessed balance and gait in 102 consecutive non-demented PD patients. The ANOVA analysis was used for continuous variables and a logistic regression analysis was used for categorical variables. Results: Duration of PD in patients who answered ��yes’’ on our balance question was 7.11 (6 4.5) versus 3.95 ( 6 1.79) yrs in patients who answered ��no.’’ This was significant: p< 0.0007. It’s noteworthy that 45% of 62 patients with PD for 1- 5 yrs had balance difficulty separate from gait difficulty. There were statistically significant differences on the tests between patients who complained of balance difficulty and those who did not. Conclusions: the balance question and tests provide a simple way of assessing balance early in PD. Study supported by: Self supported S221. Association of Psychological Symptoms with Impulse-Control Behaviors after Dopamine Agonist Therapy for Parkinson’s Disease: A Longitudinal Study Jennifer S. Hui, Steven Cen, Megan Gomez and Lauice Yang; Los Angeles, CA and Pasadena, CA Recent evidence suggests that dopamine agonist (DA) therapy in Parkinson’s disease (PD) is associated with the development of ICBs, but no previous longitudinal studies have examined psychological symptoms associated with ICBs. Participants (n ¼ 18), recruited from the clinical trial Boehringer Ingelheim Eye Safety study, were randomized to pramipexole (9 subjects) or ropinerole (9 subjects). Participants completed the Symptom Checklist-90 Revised (SCL90 R), and a brief, structured interview assessing for ICBs at baseline, 11 weeks, 6, 12, 18, and 24 months. S219. Poor Dementia Screening with Mattis Dementia Rating Scale Cutoffs in Highly Educated Parkinson’s Disease Patients Travis H. Turner and Vanessa Hinson; Charleston, SC Introduction: The Mattis Dementia Rating Scale (DRS) is widely used to assess cognition and screen for dementia in 37 ID: senthilk I Black Lining: [ON] I Time: 08:46 I Path: //xinchnasjn/01Journals/Wiley/3b2/ANA#/Vol00000/110244/APPFile/JW-ANA#110244 J_ID: ZAY Customer A_ID: SUPP11-6 Cadmus Art: 22579 Date: 31-August-11 8/18 (44%) subjects developed ICBs. Subjects developing ICBs showed a significantly higher rate of progression on the Psychoticism (PSY) (p ¼ 0.004), Paranoid Ideation (PAR) (P ¼ 0.01), Global Severity Index (GSI)(p ¼ 0.03), and Positive Symptom Total (PST) (p ¼ 0.01) subscores. Subjects randomized to pramipexole had a significantly higher rate of progression on the PAR subscore (p ¼ 0.02). Careful monitoring of psychological symptoms after initiation of DA therapy may aid in identifying patients at risk for developing ICBs. Pramipexole may play a role in the manifestation of ICBs by augmenting certain psychological symptoms. Clinicians should consider medication effects when prescribing DA in patients with underlying or progressive psychological distress. Stage: Page: 38 motor asymmetry were accurate and correlated with their 9HPT scores. This conclusion raises intriguing questions regarding the progression of these neurodegenerative disorders, and therefore merits further investigation. Study supported by: Cooper Foundation S224. Neurotoxin Injection for Treatment of Cervical Dystonia Chandler E. Gill, Anna L. Molinari, Neil D. Manus, Michael W. Pelster, Jason A. Cook, Wallace Title and David Charles; Maywood, IL; Nashville, TN; Minneapolis, MN and New Orleans, LA Botulinum toxin is a first-line treatment for cervical dystonia (CD); onabotulinumtoxinA (BoNT-A), rimabotulinumtoxinB (BoNT-B), and abotulinumtoxinA (BoNT-D) are available formulations. We conducted a record review and interview to characterize neurotoxin use and reasons for discontinuation. All patients treated at a university clinic from 1997–2006 were eligible and 70 (54 female) participated. Age at onset was 44.2 6 16.8 and 47.2 6 14.8 at first treatment. Initial treatment: BoNT-A (97%), BoNT-B (1.5%), BoNT-D (1.5%). Following BoNT-A, 33.3% switched to BoNT-B; of those, 47.6% returned to BoNT-A. Average starting dose of BoNT-A was 270.4U which increased by 0.28U per injection (range: 1–39). Average starting dose of BoNT-B was 11,996U which increased by 113.6U per injection (range: 1–18). 21 patients (30%) discontinued BoNT, and 16 (23%) of these no longer received any treatment. The most common reason was inadequate response (primary 4%; secondary 11%); 3 patients developed resistance documented by frontalis or antibody test. Other reasons were inadequate insurance payment (7%), travel distance (3%) and side effects (3%). CD patients typically switch between BoNT formulations before discontinuing treatment, and a significant minority discontinue all care. Efforts to improve treatment of CD should include education and advocacy to facilitate patient access. Study supported by: This study was supported by an unrestricted research grant from Allergan, Inc. Vanderbilt University has received income from grants and contracts from Allergan and Medtronic for research led by Dr. Charles. Dr. Charles has received income from Allergan, Medtronic, and Pfizer for education and consulting services. S222. Balance Difficulty in PD Correlates with Step Length and Velocity Abraham Lieberman, Naomi Salins, Tiki Hussain, Di Pan and Anthony Santiago; Phoenix, AZ Objective: To determine step length and velocity in PD patients. Background: PD patients often report balance difficulty without falls. Method: In 102 consecutive non-demented PD patients, we compared patients with reported imbalance without falls to patients without imbalance as regards age, PD duration, UPDRS/Pull-Test, BNI Balance Scale, Stride Length and Velocity. There were no confounding causes of balance or gait difficulty upon historical review or physical exam. Results: Patients with balance difficulty had a shorter stride: 1.72 (60.47) vs 2.16 (60. 27) feet/ step, p <0.0001, and a slower step velocity of 2.86 (60.93) vs 3.72 (60.75) feet/ second; a longer duration of PD: 7.2 (6 4.6) vs 4.4 (62.4) yrs, p < 0.008; a worse BNI Balance Score: 7.9 (63.8) vs 2.8(6 2.3), p<0.0001; were older: 70.6 (68.8) vs 64. 6 (69.4) yrs, p < 0.01; had a worse motor UPDRS score: 19.6 (67.7) vs 14.3(65.8), p < 0.005. Conclusions: Balance difficulty in PD correlates strongly with PD duration, BNI Balance Score, step length and step velocity. The shortened step and slower velocity may reflect adaptive responses to impaired balance rather than a locomotive dysfunction. S223. Motor Asymmetry in SCAs Mitra Assadi, Bhavpreet Dham, Gazelle Zerafati, Jon Veloski and Paola Leone; Camden, NJ and Philadelphia, PA S225. The Association between Mediterranean-Type Diet Adherence and Parkinson’s Disease Roy N. Alcalay, Yian Gu, Helen Mehia-Santana, Lucien Cote, Karen S. Marder and Nicholas Scarmeas; New York, NY Introduction: The spinocerebellar ataxias (SCA) represent a heterogeneous group of neurodegenerative disorders. Given the genetic nature of these diseases, symmetric involvement of the neuroaxis is to be expected in the phenotype. Methods: 19 right-handed patients with SCA were recruited into the study as described before (Assadi, JNS 2007). Upper extremity motor coordination was measured using a timed nine hole peg test (9-HPT) on 3 separate examinations. The mean scores for the right and left hands were calculated and compared using a t-test. Results: Twelve patients reported experiencing more ataxia on the left side, while one patient perceived the right side as being more severely affected. For these 13 patients, the means for the 9-HPT were significantly different between the right and the left sides (t-test, p< 0.01). In the six subjects who did not report any motor asymmetry, the means of the two sides were approximately equal, and no statistical difference was found. Conclusions: Motor asymmetries are common in SCAs and observed in 68% of our cases. Patients’ self-reports of Objective: Recent studies have investigated the association between a Mediterranean-type diet (MeDi) and Alzheimer’s risk, but explorations in relation to Parkinson’s disease (PD) have been limited. We assessed the association between MeDi and PD status. Methods: 280 PD cases (Columbia University) and 199 controls (recruited mostly by random digit-dialing) completed the Willett semi-quantitative food frequency questionnaire. A MeDi adherence score was calculated using a 9point scale. High scores indicate greater adherence to MeDi. A logistic regression model was computed to assess the association between PD status and MeDi, adjusting for caloric intake (CaI), age, gender, education and ethnicity. Among PD cases, we assessed the association between MeDi adherence and age-at-onset using linear regression, adjusted for CaI, gender, education, ethnicity and disease duration. Results: PD cases were younger (68yrs vs. 72yrs, p< 0.001) and more educated (14yrs vs. 12yrs, p<0.001) than 38 ID: senthilk I Black Lining: [ON] I Time: 08:46 I Path: //xinchnasjn/01Journals/Wiley/3b2/ANA#/Vol00000/110244/APPFile/JW-ANA#110244 J_ID: ZAY Customer A_ID: SUPP11-6 Cadmus Art: 22579 Date: 31-August-11 controls. Lower MeDi adherence was associated with higher odds for PD after adjustment for all covariates (OR per MeDi point ¼ 0.894, 95%CI ¼ 0.800–0.998, p ¼ 0.045). Mean age-at-PD-onset was 61.6yrs. Lower MeDi score was associated with earlier age-at-PD-onset (b ¼ 1.275, p ¼ 0.001). Conclusions: PD patients adhere less than controls to the MeDi. Dietary behavior may relate to PD risk. Study supported by: NIH (NS32527 and KL2 RR024157) and the Parkinson’s Disease Foundation Stage: Page: 39 confounding causes of balance or gait difficulty upon historical review or physical exam.Results: Patients with reported balance difficulty had a longer duration of PD: 7.2 (6 4.6) vs 4.4 (6 2.4) yrs, p < 0.008; a worse BNI Balance Score: 7.9 (6 3.8) vs 2.8 (6 2.3), p<0.0001; were significantly older: 70.6 (6 8.8) vs 64. 6 (6 9.4) yrs, p < 0.01; a worse motor UPDRS score: 19.6 (6 7.7) vs 14.3 (6 5.8), p < 0.005. Conclusions: Balance difficulty in PD strongly correlates with the BNI Balance Score. S228. STEADY-PD. Safety and Tolerability of Isradipine CR in Early Parkinson’s Disease. Interim Tolerability Data Analysis Tanya Simuni, Kevin Biglan, David Oakes, Cheryl Deeley, Irenita Gardiner, Parkinson Study Group and STEADY PD Investigators; Chicago, IL and Rochester, NY S226. Autonomic Dysfunction in Early Parkinson’s Disease Anna L. Molinari, Fenna T. Phibbs, Lily Wang, Yanna Song and P. David Charles; Nashville, TN Background: Orthostatic hypotension (OH) and suppressed heart rate (HR) response to standing are frequent symptoms of autonomic dysfunction (AD) in advanced Parkinson’s Disease (PD), but their incidence in early PD is unknown. Methods: 30 Hoehn & Yahr Stage II idiopathic PD subjects underwent a 7 day medication washout. Seated and standing blood pressure (BP) and HR measurements were recorded daily. Subjects were divided into 2 groups based on medication regimen: Group 1 levodopa only (n ¼ 9), Group 2 dopamine agonist monotherapy or in combination with levodopa (n ¼ 21). Results: HR response to standing improved in all 30 subjects during medication washout with an average increase of 2.9 6 7.7 beats/minute (p ¼ 0.03). No subjects exhibited symptomatic OH. On average, systolic BP (SBP) decreased by 2.60 mmHg and diastolic BP (DBP) decreased by 3.13 6 9.26 mmHg on Day 8, but these differences were not significant. Subjects in Group 1 experienced a smaller difference between seated and standing SBP and DBPs on Day 8, but these differences were also not significant. Conclusions: In early PD, the normal compensatory increase in HR upon standing is diminished while SBP and DBP are unaffected. HR response should be considered when evaluating AD in early PD. Study supported by: The clinical trial from which this case is reported is funded by Medtronic, Inc., by Vanderbilt CTSA grant 1 UL1 RR024975 from the NCRR-NIH, and by private donations. Medtronic representatives did not take part in data collection, management, analysis, or interpretation of the data or in preparation, review, or approval of the manuscript. Dr. Charles has received personal compensation and Vanderbilt University has received grants to support research from Medtronic in excess of $10,000. Dr. Charles has also received funding from Allergan for speaking and consulting services as well as research grants. Background: STEADY PD is a multicenter pilot phase II double blind placebo controlled tolerability and dose finding study of isradipine CR as a disease modifying agent in patients with early PD. Objective: To establish a dosage of isradipine CR that is tolerable and demonstrates preliminary efficacy for future pivotal efficacy studies. We report results of the prespecified interim tolerability data analysis. Methods: Subjects with early PD on no dopaminergic therapy are radomized 1:1:1:1 to receive isradipine CR 5:10:20mg:placebo for 12 months. The primary outcome of the study is tolerability of three doses of isradipine with the tolerability threshold defined as > 30% difference relative to placebo. The interim tolerability analysis was preplanned after 50 subjects (50%) completed 12 week dose titration phase. Results: The 20 mg dose was declared intolerable based on the interim tolerability data reviewed by the Data Safety Monitoring Board in July 2010. Investigators remained blinded to the dose assignment. Conclusion: These results support previously reported data on the dose dependent tolerability of isradipine in PD. Final data analysis and dose choice for the pivotal study will be available Fall 2011. Study supported by: Michael J. Fox Foundation and Northwestern Memorial Foundation Dixon Priority Research Initiative Award S229. Nigella sativa Oil Controls Astrogliosis and Reduces Haloperidol-Induced Deficit in Rats Tafheem Malik**, Darakhshan Jabeen Haleem, Shema Husan, Shahid Pervez and Tasneem Fatima; Karachi, Sind, Pakistan and Karachi, Pakistan The neuropathological status of Haloperidol (HP) induced Extrapyramidal symptoms (EPS) remains unclear.Evidence suggested persistent neuronal alterations in the basal ganglia cause EPS. This study evaluate the possible protective effects of the Nigella sativa (NS) oil on HP induced neuronal alterations and motor symptoms. EPS was monitored in HP treated groups and with NS oil alone and with placebo.HP treated group displayed (p<0.01) high degree of motor impairment with late appearing vacuous chewing movement. Striatum (Str) shown grossly disturbed large fraction of cytoarchitectonic pattern with nerve cell depletion concomitant shrunken cytoplasm, nuclear membrane breakdown and chromatin disorganization. Scarring was prominent feature owing profusion of astrogliosis in the dorso - ventro lateral regions of the caudate putamen and in the core of nucleus accumbens.Halo and pyknotic neurons were moderate(p<0.05). HP induced neuronal changes were almost absent in the HP plus NS treated groups. However minor S227. Balance Difficulty in PD Correlates with the BNI Balance Scale Abraham Lieberman, Naomi Salins, Tiki Hussain, Di Pan and Anthony Santiago; Phoenix, AZ Objective: To compare PD patients with and without reported balance difficulty by several variables to assess the validity of the BNI Balance Scale. Background: Balance difficulty is a late complication of PD. We devised a questionnaire and tested 3 tasks to calculate the BNI Balance Scale. Method: In 102 consecutive non-demented PD patients, we compared patients with reported balance difficulty without falls to patients without imbalance as regards age, PD duration,UPDRS/Pull-Test, BNI Balance Scale (one foot stance, turning 360 degrees, timed-gait). There were no 39 ID: senthilk I Black Lining: [ON] I Time: 08:46 I Path: //xinchnasjn/01Journals/Wiley/3b2/ANA#/Vol00000/110244/APPFile/JW-ANA#110244 J_ID: ZAY Customer A_ID: SUPP11-6 Cadmus Art: 22579 Date: 31-August-11 astrogliosis with no indication of cell loss and 82% normal neuronal densities were observed. We conclude that NS may prevent HP induced neuronal degeneration.We believe that further preclinical research into the utility of NS may indicate its usefulness as a protective agent from irreversible EPS. Study supported by: The University of Karachi, Pakistan. Stage: Page: 40 Without a biomarker of Parkinson’s disease (PD) progression, we rely on clinical ratings to estimate disease progression. Medication washout may be useful in these ratings. We are conducting a prospective, blinded, pilot trial of deep brain stimulation (DBS) in early stage PD subjects aged 50 to 75, Hoehn & Yahr II, without dyskinesias or motor fluctuations, and on PD medications < 4 years. Inpatient medication washout and motor rating is conducted at baseline and every six months for two years. On Day 1, subjects are rated ON medication and then medications are withheld and motor function is rated daily. Thirty subjects were randomized (15 MED; 15 DBSþMED). Participants are 27 males and 3 females aged 60.3 6 6.6 years at study entry and taking medication an average of 2.1 6 1.5 years. UPDRS-III score at baseline Day 1 (ON medication) was 14.9 6 7.9 which increased by 1.7 points per day to 27.0 6 7.9 after one week withdrawal. Median ON Hoehn & Yahr Score was 2 (Range: 1-2) which remained at 2 after one week (Range: 2–2.5). Schwab & England ADL score also did not significantly change (Day 1: 92% 6 5%; Day 8: 89% 6 4%). Study supported by: The clinical trial from which this case is presented is supported by Vanderbilt CTSA grant 1 UL1 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 support from Allergan and Medtronic for research led by Drs. Charles and Medtronic for researcfh led by Dr. Konrad. Drs. Konrad and Davis have received personal compensation in the past from Medtronic for consulting fees or honoraria. Dr. Charles receives income from Allergan, Medtronic, and Pfizer for education and consulting services. S230. Cost-Benefit Assessment of Two Forms of Botulinum Toxin Type-A in Different Pathologies Humberto Juarez, Santamaria Salvador, Leticia Hernandez and Enrique Molina; Mexico City, Mexico, Mexico Botulinum Toxin Type-A has been successfully used since 20 years in the treatment of different movement disorder pathologies.The comparison with Merz PharmaV’s Botulinum Toxin Type A regarding its equivalency has not been trustfully demonstrated.The Social Security Hospitals have a high captive population for each disease group.In 2008, due to administrative restructure, a 150 kD assessment of Botulinum Toxin Type-A was initiated.To effectively compare the potency, efficacy and safety of the new biologic, the same dilution and application standards were maintained. Video and photography were taken for all patients with a standard procedure.From May 2008 to April 2009 the responses of 4 types of 150 kD different batches of the toxin were employed.Comparatively, patients injected with onabotulinumtoxin A from May 2007 to April 2008 were selected.Our surveillance regarding potency, maximum time effect, and maximum duration was that in all parameters the Botulinum Toxin Type A at 150 kD was lower and oscillates at 6 weeks in average for all pathologies. R S231. Weight and Height Distribution in Children with Tourette Syndrome Katie Kompoliti, Glenn T. Stebbins and Christopher G. Goetz; Chicago, IL Objective: To compare height and weight of untreated children with Tourette syndrome (TS) with age and gender matched controls. Background: TS children are reported to have lower height and weight, with normal body mass index (BMI), indicating a possible dopaminergic over-activity. Methods: Weight and height of consecutive TS patients under 20 years were recorded. Patients were considered untreated if they had never taken medications for tics or TS co-morbidities. Age and gender standardized weight z-score and BMI z-scores were compared between the TS group and the CDC normative data from 2000 using one-sample t-test. Results: A total of 195 patients (155 males, 40 females), mean 11.9years (SD 3.5), were included, with 95 never exposed to medications. Untreated patients had higher adjusted average weight compared to the CDC sample’s mean (p ¼ 0.0005), but no difference in height (p ¼ 0.08). Patients with medication exposure had a higher adjusted weight compared to those never treated but no difference in height. Conclusion: Un-medicated TS children are heavier than the general population, arguing against a generalized hyperdopaminergic state. Medication treatment increases weight further, alerting physicians to monitor weight when treating TS children. S233. Gender Differences in the Interleukin-6 G-174C Polymorphism and the Risk of Parkinson’s Disease Marta San Luciano, Laurie J. Ozelius, Richard B.. Lipton, Deborah Raymond, Kaili M. Stanley, Susan B. Bressman and Rachel Saunders-Pullman; New York, NY and Bronx, NY Reports of associations between the -174G>C SNP in the promoter region of the interleukin-6 (IL6) gene and the 1730G>A SNP in the estrogen receptor beta (ESR2) and PD are conflicting. We investigated the association of both SNPs in a sample of 121 unrelated Caucasian Parkinson’s disease (PD) cases and 329 control subjects. The G allele of the G-174C SNP was more common in the group of men with PD when compared to controls (p ¼ 0.022), but not among women with PD or in the overall group. In men, having the GG genotype increased the risk of PD by over two fold (OR ¼ 2.11, 95%CI: 1.14–3.89, p ¼ 0.017). Analysis restricted to young-onset PD cases showed no association. No differences in allele or genotype frequencies were observed between PD patients and controls for the ERBeta G-1730A SNP in the overall group or either gender separately, or between younger onset PD patients and controls. Our data supports a possible inflammatory role in PD for IL6, and concurs with a prior report linking the G allele with PD, although a gender effect was not found. These findings were not replicated in two other samples. The contradictory findings may be explained by ethnic differences in distribution of IL6 polymorphisms, the existence of other polymorphisms in tight linkage disequilibrium with the C/ G SNP differentially influencing IL6 expression, methodological differences and sample size considerations, and inability to capture the complex functional network of S232. Motor Deterioration after Medication Withdrawal in Early Parkinson’s Disease Chandler E. Gill**, Anna L. Molinari, Thomas L. Davis, Mark Bliton, Stuart G. Finder, Michael G. Tramontana, Peter E. Konrad and David Charles; Maywood, IL; Nashville, TN and Los Angeles, CA 40 ID: senthilk I Black Lining: [ON] I Time: 08:46 I Path: //xinchnasjn/01Journals/Wiley/3b2/ANA#/Vol00000/110244/APPFile/JW-ANA#110244 J_ID: ZAY Customer A_ID: SUPP11-6 Cadmus Art: 22579 Date: 31-August-11 cytokines and chemokines from single gene association studies. Analysis of IL6 SNPs in larger and more diverse populations and sequencing of surrounding regions is recommended to further assess a role for this cytokine in PD. Study supported by: Dr. San Luciano is supported by an American Academy of Neurology Foundation Clinical Research Training Fellowship. Dr. Saunders-Pullman is supported by the Pfizer Society for Women’s Health Research Scholar Grant for Faculty Development in Women’s Health. This study was supported by Grant Number K23NS047256 from the National Institute of Neurological Disorders and Stroke (RSP), the Michael J. Fox Foundation (RSP, SBB), the Thomas Hartman Foundation (RSP), and The Einstein Aging Study is funded by the National Institute on Aging (AG03949, Principal Investigator: R.B. Lipton). This publication was made possible by the CTSA Grant UL1 RR025750 and KL2 RR025749 and TL1 RR025748 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research. Stage: Page: 41 ance Scale. There were no confounding causes of balance or gait difficulty upon historical review or physical exam. Results: Patients with reported imbalance without gait challenges demonstrated postural instability to Pull-Test: odds ratio 6.00 (95% CL 1.331, 27.047), and one foot stance instability: odds ratio 5.440 (95% CL 1.217, 24, 321) compared with patients reporting isolated gait difficulty. Conclusions: Most patients with PD report a balance difficulty with a co-morbid gait challenge. We believe there is a subset of patients with subjectively perceived and objectively measurable impaired balance without noticeable gait challenges that may reflect a distinct circuitry aberration impacting balance separate from locomotion. S236. Adult Onset Dopamine Responsive Dystonia (DRD): Is There a New Gene? Hossein Ansari, Ludwig Gutmann and Laurie Gutmann; Morgantown, WV Background: DRD is a type of inherited dystonia typically presenting within the first decade of life. Various genes have been identified for this condition. Late-onset DRD is very rare and its gene has yet to be identified. Case Report: 29 y/o female with severe entire-body and facial dystonic movements. This was associated with occasional myoclonus. Mental status significantly decreased over the course of the patient’s nine-week hospitalization.Trials with different agents (including dopamine depletors) failed. Upon administration of Levopoda, however, the patient dramatically improved. After 2 doses, her mental status completely recovered and abnormal movements significantly decreased. With continued medication, patient normalized. Both the patient’s twin and one older sister have a history of similar movements. Conclusions: The rarity of late-onset DRD contributes to its misdiagnosis. Therefore, adult-onset DRD is probably an under-diagnosed condition with no known gene. We speculate this patient’s sisters also suffer from DRD. This family could be a prime case for genetic study used to identify the potential gene/mutation causing adult DRD. They are set to participate in a study by the NIH Undiagnosed Diseases Program. S234. Serum Cholesterol Is Linked with Nigrostriatal Iron Deposition in Parkinson’s Disease Guangwei Du, Mechelle M. Lewis, Michele L. Shaffer, Honglei Chen, Richard B. Mailman and Xuemei Huang; Hershey, PA and Research Triangle Park, NC Higher nigrostriatal iron content has been related to Parkinson’s disease (PD). Higher serum cholesterol levels also have been suggested to be associated with lower occurrence of PD. To understand the relationship between serum cholesterol and nigrostriatal iron content, 3T MRI (T1-, T2-weighted, T2*) were obtained from 40 PD and 29 matched Controls. Fasting serum lipid profiles were measured in all subjects. The mean R2* values of bilateral substantia nigra (SN), caudate, putamen, globus pallidus (GP), and red nucleus (RN) were calculated, and correlated with serum cholesterol levels after controlling for age, gender, and statin usage. In PD, higher serum cholesterol levels were associated with lower iron content in SN (R ¼ À0.337, and p ¼ 0.048), striatum (R ¼ À0.403, p ¼ 0.017 for caudate; R ¼ À0.366, p ¼ 0.031 for putamen), and RN (R ¼ À0.436, p ¼ 0.009), but not GP (R ¼ À0.250, p ¼ 0.147). In Controls, higher serum cholesterol levels were associated with lower iron content in striatum (R ¼ À0.449, p ¼ 0.032 for caudate; R ¼ À0.451, p ¼ 0.027 for putamen), but not associated with the SN (R ¼ 0.096, p ¼ 0.654), RN (R ¼ À0.136, p ¼ 0.526), or GP (R ¼ À0.191, p ¼ 0.371) iron levels. Thus, higher serum cholesterol concentrations are associated with lower iron content in nigrostriatal structures, warranting further studies. Study supported by: NS060722, and the HMC GCRC (NIH M01RR10732) and GCRC Construction Grant (C06RR016499) S237. Dystonia Induced Mechanical Stress as a Cause of DBS Extension Fracture and Expulsion Massimo Mondani, Elisa Petacchi, Roberto Eleopra, Silvia Molteni, Sabrina Gualdi, Miran Skrap and Andrea Martinuzzi; Udine, UD, Italy; Conegliano, TV, Italy and Sesto San Giovanni, MI, Italy The mechanical failure of the device, especially the most exposed and longest part connecting the electrode to the impulse generator (IPG) is a possible adverse eventa in DBS. We describe a 12 year old child in whom the successful treatment with GPi DBS for secondary generalized dystonia repeatedly failed for malfunction of the IPG-electrode connection including one internal fracture diagnosed by electrophysiology, and two aseptic scar breakage leading to expulsion of a 5 cm long stretch of the left extension and removal of the entire left implant. The study of the pattern of child’s movements and of the extension position along the left mastoid and neck revealed a region of mechanical stress on the left extension which was eluded by the right one thanks to its obliquity in respect to the axis of the prevalent neck movements. When implanting dystonia patients with DBS, especially when they are children and present neck dyskinesias, one S235. Balance Difficulty Differs from Gait Difficulty in PD Abraham Lieberman, Naomi Salins, Tiki Hussain, Di Pan and Anthony Santiago; Phoenix, AZ Objective: To compare reported balance difficulty from gait difficulty in PD. Background: Patients with PD often report imbalance without gait challenges. Method: In 102 consecutive non- demented PD patients, we compared 13 patients with reported imbalance without gait impairment with 22 patients with isolated gait difficulty as regards age, PD duration, UPDRS/Pull-Test, BNI Bal- 41 ID: senthilk I Black Lining: [ON] I Time: 08:46 I Path: //xinchnasjn/01Journals/Wiley/3b2/ANA#/Vol00000/110244/APPFile/JW-ANA#110244 J_ID: ZAY Customer A_ID: SUPP11-6 Cadmus Art: 22579 Date: 31-August-11 should avoid positioning the IPG extension parallel to the major axis of the prevalent movement. A slight obliquity of the extension may suffice in preventing failures leading to suspension of an otherwise efficacious treatment. Stage: Page: 42 Conclusions: Patients with PNES in our study population reported a higher frequency of NREM parasomnias compared to epilepsy patients, and a much higher frequency compared to general prevalence estimates. Parasomnias should always be considered in the differential of paroxysmal nocturnal events in these patients. Study supported by: Self Supported Sleep Disorders and Circadian Rhythm S301. Endogenous GABAA Receptor Enhancement Modulates Vigilance in the Primary Hypersomnias David B. Rye, Kathy Parker, Lynn Marie Trotti, Paul S. Garcia, James C. Ritchie, Michael J. Owens, Leslie Morrow, Donald L. Bliwise and Andrew Jenkins; Atlanta, GA; Rochester, NY and Chapel Hill, NC S303. Endothelial Function in Patients with Obstructive Sleep Apnea Kanika Bagai, James Muldowney, Yanna Song, Lily Wang, Douglas E. Vaughan and Beth A. Malow; Nashville, TN and Chicago, IL Background: Obstructive sleep apnea (OSA) is implicated in the pathogenesis of stroke, although mechanisms need clarification. Methods: Severity of OSA [apnea-hypopnea index (AHI) of 5 or greater] was defined by overnight polysomnography. Endothelial function testing was done using flow mediated dilatation and computerized arterial pulse waveform analysis in 17 patients with OSA and 17 normal controls. Results: The mean AHI (6 standard deviation) in the OSA group was 18.68(25.48) and in the non-OSA group was 0.84 (0.80). Using a linear regression model, with AHI as the main effect, and age as covariates, there was a trend towards greater mean velocity change with higher AHIs (p ¼ 0.06). Conclusions: The severity of OSA selectively affects the percent velocity change after reactive hyperemia as measured by flow mediated dilation. Consistent with prior studies with altered endothelial function in OSA patients, our results show a trend towards significant difference in the markers of endothelial function as measured by brachial artery flow- mediated dilatation testing. One reason for the less dramatic difference noted in our study may be because we included patients with mild OSA, as compared with other studies which included patients with moderate to severe OSA. Study supported by: Supported in part by Vanderbilt CTSA grant 1 UL1 RR024975 from NCRR/NIH. Primary hypersomnias lack an etiology or rational treatments. We investigated biological and neurobehavioral markers in 31 such cases. Plasma and CSF assays ruled out sedative-hypnotic use, neurosteroid or gamma-aminobutryic acid (GABA) excess, pathological amino acid profiles, and hypocretin-1 deficiency. We tested for GABA-ergic activity employing ligand binding assays and electrophysiological recordings of cells expressing recombinant GABAA receptors. CSF from 31 hypersomnolent and 16 control patients all enhanced a1b2c2s GABAA receptors. The magnitude of enhancement in hypersomnolent subjects exceeded that of controls (89% 6 46.5 vs 41.4% 6 5.7, t ¼ 5.39, P < 0.001). Pharmacological profiling suggested that enhancement was due to an allosteric modulator unique to affected versus control CSF. Enhancement did not require a functional BZD binding site, was selective for a 2 > a1 receptors and negligible at a 4 receptors, and was reversible with benzodiazepine antagonist flumazenil. Flumazenil normalized vigilance in seven index cases. Inhibitory GABAA receptor enhancement occurs by way of a positive allosteric modulator unique to patients with a primary hypersomnia. This altered biology is antagonized in vitro and in vivo by flumazenil and identifies a novel pathophysiology to primary hypersomnolence. Study supported by: Woodruff Health Sciences Center Fund and USPHS grants NS055015 and NS055015-03S1 (D.B.R), NS-050595 (D.L.B), and GM073959 (A.J). Education S302. Frequency of Parsaomnias in Patients with Non-Epileptic Seizures Mitchell G. Miglis, Michael Boffa, Sujata Thawani, Alcibiades Rodriguez and Anuradha Singh; New York, NY S401. The Effectiveness of Education Intervention on Health Knowledge among Neurological Patients Mercedes Jacobson and Polina Pomerants; Philadelphia, PA Objective: To assess the impact of education intervention on patient’s health literacy in outpatient neurology setting. Background: Inadequate health knowledge is a strong indicator for higher risk of non-compliance, poor self-management, and negative health outcomes. Methods: A single-blind randomized study was conducted. Designed using Ask Me 3 principles, a questionnaire was administered to study group before and a week after onsite education intervention and to demographically matched control group a week after intervention. Performance was scored on consistency between subjects’ responses and congruence with information from subjects’ medical charts. Results: Control and study group population (N ¼ 118) consisted of unemployed (84%) middle-aged adults (44.2 þ/À 12.4) who are legally disabled (66%) and lack postsecondary education (82%). Study subjects retained more health information (0.19þ/À 0.08, p<0.0001) after education intervention and scored higher in their overall knowledge of medical condition (0. 11þ/À 0.44, p< 0.0001) and medications (0.30þ/À 0.50, p <0.0001) than control subjects. Objective: To assess frequency of parasomnias in patients with Psychogenic Non-Epileptic Seizures (PNES) Background: PNES have been associated with a history of psychosocial stresssors, an association that has also been suggested for some parasomnias. There is little data on frequency of parasomnias in patients with PNES. Design/Methods: We selected a cohort of patients (n ¼ 9) with vEEG-confirmed PNES from our Epilepsy Unit and administered sleep questionnaires (Epworth, Munich Parasomnia Scale) on follow-up visits and phone interviews. An age-matched group of patients with vEEG-confirmed epilepsy (n ¼ 9) were interviewed for comparison. Participants were scored on responses relating to twenty-one parasomnias. Responses of PNES and epilepsy patient were compared (Chi square analysis, SPSS v16). Results: PNES patients reported a higher frequency of NREM parasomnias when compared to epilepsy patients, notably hypnic jerks (77.8% vs. 11.1%, p ¼ 0.004), rhythmic foot movements (55.6% vs. 0%, p ¼ 0.023), exploding head syndrome (44.4% vs. 0% p ¼ 0.023), and bruxism (66.7% vs. 0%, p ¼ 0.003). 42 ID: senthilk I Black Lining: [ON] I Time: 08:46 I Path: //xinchnasjn/01Journals/Wiley/3b2/ANA#/Vol00000/110244/APPFile/JW-ANA#110244 J_ID: ZAY Customer A_ID: SUPP11-6 Cadmus Art: 22579 Date: 31-August-11 Stage: Page: 43 versus 15/20, 75%, p ¼ 0.045). The percentage who felt all important data were being transmitted increased from 49% (16/33) to 80% (16/20, p ¼ 0.041). Overall satisfaction (scale 1–10) increased from 6.2þ/À1.6 to 7.4þ/À1.3 (p ¼ 0.002). Interpretation: Structured sign-out results in improved communication skills, and may improve patient safety and quality of care. Conclusions: Statistically significant improvement in health knowledge resulted from education intervention using Ask Me 3 tool. Patient education with attention to health literacy should be employed in neurology teaching clinics to improve patients’ adherence to treatment and comprehension of health information. S402. Teleneurology in Leading U.S. Medical Institutions Benjamin P. George**, Nicholas J. Scoglio, Jason I. Reminick, Kevin M. Biglan and E. Ray Dorsey; Rochester, NY and Baltimore, MD S404. Improved Scores on the AAN Resident Inservice Training Examination (RITE) after Lecture Curriculum Intervention L. John Greenfield, Vicki Ramsey-Williams, Theresa Marshall and Boyd Koffmann; Toledo, OH and Little Rock, AR Objective: Telemedicine is used for the care of neurological conditions yet little is known about the details of telemedicine use in neurology departments. The study purpose is to determine current teleneurology opinions and practices among neurologists at leading U.S. medical institutions. Methods: A survey on teleneurology was performed among neurologists at the top 50 hospitals in neurology based on U.S. News and World Report. The survey was sent to department chairs, faculty involved in teleneurology, or department administrators. Respondents indicated level of telemedicine use by department, current applications, and opinions of telemedicine. Results: The initial response rate was 32% (16 institutions, 18 responses). 50% of respondents were neurology faculty, the remaining were department chairs (33%) and department administrators (17%). 69% of institutions provide telemedicine; of those, all use telemedicine for stroke, 18% for movement disorders, and 9% for neuroimmunology. 45% of institutions using telemedicine services initiated services within the last year, and 60% of institutions not providing telemedicine have plans to within a year. Additionally, 61% of respondents find telemedicine to be equal to the in-person care model. Conclusions: There is increasing use and acceptance of teleneurology by neurologists at leading U.S. medical institutions. Objective: Determine whether curriculum intervention has a positive impact on resident education as measured by RITE scores. Background: Performance on the RITE predicted scores on the ABPN Part I board examination, and has been used to assess readiness to take ABPN Part I (Goodman et al. 2002). Methods: Retrospective analysis of RITE and USMLE scores for 3 years preceding and following curriculum intervention, which consisted of realigning the didactic syllabus with the subject areas of the ABPN (Neurology) exam, and pre-and post-lecture quizzes. Results: All neurology residents at the Medical College of Ohio/University of Toledo between 2003 and 2010 were included. The mean percent of correct answers on the RITE significantly improved from prior to 2007 (55.561.4, n ¼ 30) to 2007 and after (61.361.6, n ¼ 27, p<0.01). Prior to 2007, resident RITE percentile scores improved more from PGY2 to PGY3 (8.5 6 1.7, n ¼ 8) than from PGY3 to PGY4 (3.0 6 2.2, n ¼ 7), but after 2007 increases were seen at both stages (9.0 6 2.2, n ¼ 8; 8.9 6 0.9, n ¼ 7). USMLE scores were also higher after 2007, and correlated with RITE scores. Conclusions: Our data support curriculum intervention to improve resident education as measured by RITE. S405. Evidence Based Medicine(EBM) in the 2nd Year Neurosciences Curriculum Michael J. Schneck and Edward Neafsey; Maywood, IL S403. Standardized Sign-Out Improves Communication Skills Brian D. Moseley, Jonathan H. Smith, Gloria E. DiazMedina, Mateo Paz Soldan, Meredith Wicklund, Radhika Dhamija, Haatem Reda, Michael F. Presti and Jeffrey W. Britton; Rochester, MN Objective: EBM is an increasingly emphasized part of student education but integration in basic science courses is not common. We attempted to create an EBM module in the Loyola neuroscience course to teach clinical decisionmaking based on neuroanatomical principles. Methods: An introductory lecture on EBM was followed by small group review of the NASCET and ACAS trials and recommendaitons about 3 carotid case scenarios. Students were assessed by small group reports and final exam multiple test questions. Based on initial class experience, module changes were made in subsequent years. We describe our experience for years 2007–2010. Results: Multiple test EBM answers were in line with general neuroscience test results (mean 80%). Small group responses were more variable Additionally,student assessment of the module was less positive (mean 3.5/5). Discussion: Reviewing the limited success of EBM in the neuroscience course, we hypothesized we were less successful because students lacked both general clinical experience and factual information about EBM practice. Based on our observations, EBM modules are more likely to succeed as part of the 3rd & 4th year neuroscience clerkships after a more robust general epidemiology and EBM course in preclinical years. Objective: Unstructured handoffs are vulnerable to communication failures. We implemented standardized sign-out on our inpatient Neurology services and assessed its effect on communication skills. Methods: Residents spent the first half of their rotations utilizing unstructured sign-out. They switched to a structured sign-out system (using the Situation-BackgroundAssessment-Recommendation format) during the second half. We analyzed survey responses before and after implementation to evaluate for an effect. Results: We documented improvements in many variables, including being told: pertinent past medical history (14/33, 42% versus 14/20, 70%, p ¼ 0.088); pending laboratory studies/tests (26/33, 79% versus 19/20, 95%, p ¼ 0.234); recommendations for how to handle nursing/pharmacy calls (12/33, 36% versus 12/20, 60%, p ¼ 0.154); and up-to-date code status (14/33, 42% versus 14/20, 70%, p ¼ 0.088). Residents utilizing structured sign-out were significantly more likely to share test results with patients/family prior to shift changes (22/33, 67% versus 18/20, 90%, p ¼ 0.037) and update our electronic service list (13/33, 39% 43 ID: senthilk I Black Lining: [ON] I Time: 08:46 I Path: //xinchnasjn/01Journals/Wiley/3b2/ANA#/Vol00000/110244/APPFile/JW-ANA#110244 J_ID: ZAY Customer A_ID: SUPP11-6 Cadmus Art: 22579 Date: 31-August-11 S406. Adapting a Teaching Hospital Inpatient Neurology Service to New Duty Hour Requirements: The Washington University Adult Neurology Experience Robert Bucelli and Barbara J. Snider; Saint Louis, MO Stage: Page: 44 ance on the clerkship and grade. Students were surveyed via zoomerang after completing their clerkship. Grades had not been assigned before evaluation, though students had received feedback from attendings and the clerkship director about floor performance. Attitudes towards night call, specific floor attendings, lecturers, and a clinical examination were numerically and qualitatively assessed. Histograms will be presented. Spearman rank correlations will be performed to relate student feedback ratings with their floor performance scores, clinical examination score, shelf performance, and overall grade. A Wilcoxon analysis will compare students assigning either extreme high/low feedback ratings and grades, shelf score, and clinical examination performance. Forty-six evaluations have to date been collected. Collection will continue until shortly before the meeting at which point the data will be analyzed. New duty hour regulations for ACGME accredited residency training programs will go into effect July 1, 2011. The complexity of neurological disorders makes balancing duty hours with educational and patient care goals particularly challenging for inpatient neurology services at teaching hospitals. The Washington University/Barnes Jewish Hospital (WU/BJH) Adult Neurology residency convened a workgroup of residents and faculty to create a rotation system designed to ease compliance with the proposed duty hour rules. This system was instituted July 1, 2010. We used a combination of local and national surveys of residents, patient satisfaction scores, and hospital quality data to assess whether this change altered duty hour compliance, resident satisfaction, patient satisfaction or patient outcomes. Our experience demonstrates the inherent difficulties in monitoring the effects of duty-hour driven changes in resident schedules and suggests that these changes may have unexpected negative effects on other aspects of residency education and patient care. Future adjustments will require resident feedback and patient care metrics to best balance resident education/quality of life and patient care responsibilities while maintaining compliance with program requirements. 136th Annual Meeting Monday, September 26, 2011 Poster Session Posters will be displayed in Elizabeth A-E of the Manchester Grand Hyatt from 10:00 am – 7:00 pm, with authors present from 6:00 pm – 7:00 pm. NOTE: An asterisk designates a resident/fellow travel award winner. Two asterisks represent a medical student travel award winner. S407. Translational Research in Neuro-AIDS and Mental Health Amanda Brown, Valerie Wojna, Bruce Shiramizu, Avindra Nath and Justin C. McArthur; Baltimore, MD; San Juan, PR and Honolulu, HI Behavioral Neurology M601. Behaviorally-Driven Anatomical Mapping of Hemispatial Neglect Alex R. Carter, Mark P. Mcavoy, Serguei V. Astafiev, Jennifer Rengachary, Daniel L.W. Pope, Abraham Z. Snyder, Kristi Zinn, Nick Metcalf, Gordon L. Shulman and Maurizio Corbetta; Saint Louis, MO HIV infection of the CNS frequently results in neuropsychiatric complications and is a major cause of disability. Despite effective antiretroviral treatment, nearly 80% of patients have asymptomatic cognitive impairment. HIV disproportionately affects racial/ethnic minorities and several barriers must be overcome for a significant impact on this illness to be realized. A better understanding of how social, cultural and genetics impact the pathophysiology of disease and the development of new therapies is needed. Another barrier is the dearth of scientists from racial/ethnic minority groups in the field of Neuro-AIDS research. The R25 program was designed to address these barriers by 1) supporting the education and training of minority graduate students, fellows and junior faculty and individuals who are not members of minority groups but are engaged in NeuroAIDS disparity related research through a web-based didactic course; 2) to promote innovative Neuro-AIDS research, through pilot grants and 3) to provide long-term mentoring relationships to further career development. Since program inception 12 university partnerships have formed, 127 trainees have completed the course, 8 trainees were research scholars and/or received pilot grants, 11 independent grants were obtained by trainees, and more than 50 manuscripts have been published. Study supported by: 5R25MH080661, The National Institutes of Mental Health Objective: A wide range of lesions have been associated with hemispatial neglect. Some heterogeneity may be attributable to the use of varying tests. We used a single computerized test with high sensitivity for deficits in both topdown control of attention and reorientation to salient stimuli to predict which brain regions are more likely damaged in subjects with those deficits after right hemispheric stroke. Methods: Reaction times and accuracy were measured in 61 right hemisphere stroke patients using a computerized Posner reaction time task. Stroke lesions were quantified by MRI. Behavioral scores and lesion data were entered into a novel voxel-wise logistic regression analysis. Results: Two distinct patterns were observed. Impaired target detection in the contralesional visual field predicted damage to the subcortical paraventricular white matter underlying the middle frontal and inferior frontal gyri. However, impaired shifting of attention predicted damage to more cortical regions between the inferior parietal lobule and the temporo-parietal junction complex. Interpretation: Lesions of long-range fronto-parietal white matter tracts may be associated with deficits in the maintenance of spatial representations; in contrast ventral parietal lesions may be associated with deficits in phasic reorientation of attention. Study supported by: This study was supported by the National Institute of Mental Health [R01 HD061117-05A2 to M.C.; 1K08NS064365-01A1 to A.R.C.], the Robert S408. Relationship between Medical Student Feedback and Grading and James M. Stankiewicz; Boston, MA It is common for students to be asked for feedback in order to foster clerkship improvement. It is less clear whether medical student feedback is ultimately related to perform- 44 ID: senthilk I Black Lining: [ON] I Time: 08:46 I Path: //xinchnasjn/01Journals/Wiley/3b2/ANA#/Vol00000/110244/APPFile/JW-ANA#110244 J_ID: ZAY Customer A_ID: SUPP11-6 Cadmus Art: 22579 Date: 31-August-11 Wood Johnson Foundation Amos Medical Faculty Development Program [65592 to A.R.C.]. Stage: Page: 45 cal and research activities of the Neurology Department of the University Hospital of Crete. M604. Motor Chunking Is Correlated with Sensorimotor Cortex and Striatum Activation Nicholas Wymbs and Scott T. Grafton; Santa Barbara, CA M602. Markers of Celiac Disease and Gluten Sensitivity in Patients with Cerebellar Ataxia Caroline Tan, Peter H. Green, Khalaf O. Bushara, Donald D. Kasarda, Ejaz Shamim, Norman Latov, Mark Hallett and Armin Alaedini; New York, NY; Minneapolis, MN; Albany, CA and Bethesda, MD Motor chunking facilitates the production of everyday movements by combining discrete motor elements into well-integrated units of behavior. We hypothesized that sensorimotor cortex and corresponding basal ganglia projection areas are essential for chunking. Healthy participants learned a motor sequencing task during fMRI scanning. Instructed to respond as quickly as possible, participants translated sequences from a pseudo-musical tablature displaying a series of twelve �notes’ on a four-lined staff to one of four response keys. Using multislice graph analysis, an unbiased estimator identified chunks on a trial-by-trial basis for a set of three extensively trained sequences (189 trials/sequence) performed over the course of three scanning sessions. A �chunking score’ based on the element-to-element variance within each chunk was used to determine the strength of overall chunking for each trial and then entered as a covariate in the estimation of BOLD. Consistent with our predictions, we found activity in contralateral sensorimotor cortex and posterior putamen correlated with chunking strength, independent of movement speed or reaction time. Disruption of this circuit may result in deficits of concatenating complex serial actions into contiguous behavior and explain some symptoms of subcortical apraxia or Parkinson disease. Study supported by: Supported by PHS grant NS44393 and contract no. W911NF-09-D-0001 from the U. S. Army Research Office. Celiac disease is an autoimmune enteropathy resulting from sensitivity to wheat gliadin and related cereal proteins. A link between celiac disease and cerebellar ataxia has been postulated, based primarily on reports of increased anti-gliadin antibodies among patients with ataxia. Serum specimens from 21 patients with cerebellar ataxia and elevated antigliadin antibody titer, 20 celiac disease patients, and 20 healthy subjects were assessed for antibodies to deamidated gliadin peptides and transglutaminase 2 (TG2) by ELISA. The anti-gluten antibody response was further characterized through examination of reactivity towards chromatographically separated gliadin and glutenin protein fractions by immunoblotting. In contrast to the celiac disease group, there was not a significant association between the anti-gliadin immune response and anti-TG2 or anti-deamidated gliadin antibodies in the ataxia group. Characterization of antibody specificity revealed differential reactivity towards specific gluten protein fractions between ataxia and celiac disease patients. The findings indicate that the mechanism and profile of the elevated antibody response to gluten in patients with cerebellar ataxia is significantly different from those in celiac disease patients. M605. Areas of Ischemia Associated with ��Frontal Lobe’’ Task Failure Yessenia Gomez and Argye E. Hillis; Baltimore, MD M603. Early Signs of Cognitive Impairment among Multiple Sclerosis Patients with Clinically Isolated Syndrome Theodora Panou, Vasileios Mastorodemos, Efrosyni Papadaki, Panagiotis G. Simos and Andreas Plaitakis; Heraklion, Greece and Rethymnon, Greece Hypothesis: Measures of ��frontal lobe function’’ evaluate broad functional networks including left frontal, temporal, and parietal cortex. Methods: We identified acute areas of ischemia associated with impaired performance on Trail Making, Phonemic Word Fluency (word generation in 1 minute), and word span, in 95 patients with acute left hemisphere ischemic stroke within 48 hours of onset. DWI and PWI were evaluated for infarct or hypoperfusion in 14 Brodmann areas (4,6,10,11,44, 45,21,22,38,37,39,40,18,19). ANOVA was used to identify areas where ischemia was associated with mean decrement in performance. Results: Patients with ischemia (DWI or PWI abnormality) in BA 6, 44, 45 (posterior frontal), 21, 22, 37 (temporal), 39 or 40 (inferior parietal) had significantly impaired performance on word span (p ¼ .03-.001). Patients with ischemia in BA 4, 6, 21, 22, 37 and 39 had impaired performance on word fluency. Only patients with ischemia in BA 37 had impaired Trail Making, but many could not complete the task. Lowest word span scores were associated with ischemia in BA 45 (mean 1.0 6 0); lowest word fluency were associated with ischemia in BA 21 (mean 4.7 6 3.9). Conclusion: Word fluency and span tasks are sensitive but not specific for frontal lesions. Study supported by: NIH R01 DC05375 The study investigates primary and secondary verbal memory and motor/executive functions (response inhibition and strategy shifting ability) in multiple sclerosis (MS) patients with clinically isolated syndrome (CIS). We studied 44 CIS patients and compared them to 49 patients with relapsing remitting MS (RR-MS) displaying mild disability and to a large cohort of age- and education level-matched healthy volunteers. Results showed that both CIS and RR-MS patients evidenced a disproportionate impairment in the immediate and delayed recall of the second (as compared to the first) of two short narratives of the Logical Memory WMS-III subtest, and reduced performance on the Memory for Digits-Forward. Performance of either group on the executive tasks was not impaired, showing evidence of a reversed speed-accuracy trade-off. Illness duration emerged as a significant predictor of memory and executive task performance. Clinical, psychoemotional, and brain imaging findings were also examined as potential correlates of cognitive deficits and disease progression among CIS patients. These findings may signify early-onset decline of specific cognitive functions in CIS, which merits regular follow-up assessments and monitoring of psychoemotional adaptation and everyday functioning. Study supported by: This Research Project was partially supported by the Association for Research and Treatment of Neurologic Disorders of Crete (��EY ZHN’’), which is philanthropic (non-profit) organization that supports the clini- M606. Thalamic Atrophy in Gastric Bypass Patients with Cognitive Complaints Jonathan Graff-Radford, Jennifer Whitwell, Max R. Trenerry, J.E. Ahlskog, Michael D. Jensen, Clifford R. Jack, Jr. and Keith A. Josephs; Rochester, MN 45 ID: senthilk I Black Lining: [ON] I Time: 08:46 I Path: //xinchnasjn/01Journals/Wiley/3b2/ANA#/Vol00000/110244/APPFile/JW-ANA#110244 J_ID: ZAY Customer A_ID: SUPP11-6 Cadmus Art: 22579 Date: 31-August-11 Background: Gastric bypass patients are at risk for developing neurological complications, often from nutritional deficiencies. We have noticed a series of patients presenting for cognitive complaints that developed after gastric bypass, without any identifiable etiology. We set out to determine whether such patients have any focal brain atrophy that could account for the complaints. Methods: Retrospective case series to identify patients (n ¼ 10) with cognitive complaints following gastric bypass that had a volumetric MRI. Voxel-based morphometry and atlas-based parcellation were used to assess patterns of grey matter volume loss in all patients compared to a group of 10 age and gender-matched controls, and a group of 10 controls matched by body mass index before surgery. Results: Patients underwent gastric bypass at a median age of 54. Cognitive complaints began at a median age of 57. All were taking multi-vitamins with nine receiving vitamin B12. Formal neuropsychometric testing revealed only minor impairments. No nutritional abnormalities were identified. Focal thalamic atrophy was identified in the gastric bypass patients when compared to controls. Conclusions: Patients with cognitive complaints after gastric bypass surgery have focal thalamic brain atrophy that could account for the cognitive impairment. Study supported by: KAJ is funded by the NIH grant R01 DC010367 (PI), the Dana Foundation (PI) and the Morris K. Udall PD Research Center of Excellence NIH/ NINDS P50 NS40256 (Co-investigator). Stage: Page: 46 with the disorder present a variety of psychiatric symptoms including obsessive compulsion, general anxiety, specific phobia, and depression. However, it is unknown the extent to which these behavioral problems are related to cognitive ability or hypersocial behaviors in WS. Thus, this study aimed to examine the relationships among cognitive ability (Verbal, Performance, Full IQ), psychiatric symptoms, and social behaviors (social-emotionality, social approach) in WS versus typical development (TD). A cognitive battery (WISC, WASI, WAIS), Brief Symptom Inventory and Salk Institute Sociability Questionnaire were administered to 41 WS and 31 TD participants. Results suggest that verbal intelligence is predictive of greater psychiatric symptoms (e.g., somatization, interpersonal sensitivity, paranoid ideation, psychoticism) in WS but not in TD. Interestingly, greater reported psychiatric symptoms in WS were associated with poorer socio-emotionality (i.e., emotion recognition, desire to please) but not with approach behavior, while no significant correlations between social and psychiatric measures were observed in TD. Possible role of cognition in psychiatric ailments and social outcomes of WS will be discussed. Study supported by: Grant P01-HD033113-13 M609. Human Brain Mapping at the Single Cellular Level: Neuronal and Area Specific Differences in Health and Diseases Ryan P. Moore, Irisa Mahaparn, Eliezer Masliah and Pavel V. Belichenko; La Jolla, CA M607. Parietal Lobe Lesions Affect the Generation of Antisaccades James A. Sharpe, Ping Cheng and Moshe Eizenamn; Toronto, ON, Canada The Human Brain Mapping Project is an ongoing effort to characterize neural circuitry at the level of single cells (Belichenko and Dahlstrom, 1994). Lucifer yellow microinjection and high resolution confocal microscopy imaging were employed to reveal disparities in dendritic geometry of von Economo neurons (VENs) vs. pyramidal neurons in the cingular cortex complemented with bilateral analysis of speech areas to find morphological substrates for the speech area asymmetry. For the VENs, significant differences were revealed in spine density (p<0.01), spine head area (p ¼ 0.04), and cell shape. Left and right speech area 44 and 45 were distinguished by bigger neuronal size (p<0.05), by greater synaptophysin immunoreactivity (p<0.05), and by greater density of parvalbumin positive neurons (p<0.05) in the speech dominant hemisphere. The results indicate foci for more myopic biochemical analysis in the hope of expediting further characterization both within cell types (VENs vs. pyramidal neurons) as well as between hemispheres (speech areas 44 and 45 asymmetry). Clinical significance of our data includes autistic spectrum disorder (Rett syndrome), a range of diseases presenting with alexithymia including schizophrenia and agenesis of the corpus callosum. Antisaccades are directed away from visual targets, requiring suppression of reflexive saccades toward a target. Impaired antisaccade generation has been attributed to frontal lobe damage. The role of the parietal lobe is not established. We studied antisaccade generation by magnetic search coil technique in 13 patients (age 45 6 7 years) with unilateral focal parietal lobe lesions (9 tumors; 5 vascular lesions), and in 10 age-matched controls. Patients were instructed to make horizontal antisaccades away from a 100ms target flashed randomly 10 degrees to the right or left of center. The task was to look 10 opposite to the target flash. The patient group made antisaccades in only 49.7 6 32.7% of contraversive trials (visual target flash ipsilateral to lesions) and 49.6 6 38.4% of ipsiversive trials. In the other trials they made reflexive saccade errors toward the target flash. The control group made antisaccades in 82.8 6 13.7% of trials. Eight patients showed subnormal antisaccade generation. Their imaged lesions overlapped in parietal lobe white matter.Generation of voluntary saccades is impaired by parietal lobe lesions. Antisaccades provide a means of measuring voluntary saccade function of the parietal lobes independent of visual guidance. Study supported by: Canadian Institutes of Health Research (CIHR) M610. Cognitive and Behavioral Differences between ADHD Populations (Inattentive Type Versus ADHD Plus) Using Neuropsychological Testing and SelfReported Symptoms in Diagnosed Population from Years 1991–2008 Barbara C. Fisher, Danielle M. Garges and Stephany Fulda; Shelby Township, MI and Munich, Germany M608. Cognitive Ability Correlates of Psychiatric and Social Behaviors in Williams Syndrome Rowena Ng, Anna Ja¨rvinen-Pasley and Ursula Bellugi; San Diego, CA Introduction: Investigate relationship between Inattentive Type ADHD and ADHD Plus using neuropsychological tests, self-reported anxiety and hyperactivity in a clinic population. Method: 1332 adults referred for ADD/ADHD testing (15–50 years, 831 males); 74% with diagnosed ADHD Williams syndrome (WS) is a genetic disorder characterized with cognitive impairment, a gregarious personality and significant anxiety. Research on WS indicates that individuals 46 ID: senthilk I Black Lining: [ON] I Time: 08:46 I Path: //xinchnasjn/01Journals/Wiley/3b2/ANA#/Vol00000/110244/APPFile/JW-ANA#110244 J_ID: ZAY Customer A_ID: SUPP11-6 Cadmus Art: 22579 Date: 31-August-11 (Inattentive Type) and 24% with ADHD plus additional disorder (i.e. sleep apnea; brain dysfunction excluded). Neuropsychological tests included Trail Making Tests (A and B) and SDMT-W. Self-report measures assessed hyperactivity and anxiety (PPCA, PHCA, PBC, PCC). Results: Hyperactivity (> 45%) and anxiety (> 50%) were frequent with no significant difference between ADHD and ADHD plus. We found a significant relationship between hyperactivity and anxiety. Individuals who reported yes to one or both anxiety items had higher hyperactivity scores than those who said no to both items. ADDþ performed worse on all neuropsychological tests (p < 0.001 for all comparisons). Conclusions: Findings indicate ADHD (Inattentive Type) and ADHDþ can be differentiated on cognitive measures, but not on self-reported symptoms of anxiety and hyperactivity as these co-morbid factors are highly prevalent in both populations. Study supported by: Personally funded and donated time Stage: Page: 47 tor and unrelated pictures (p < .05). Controls and PPAnonSV patients had more fixations to the competitor than the unrelated pictures in the Coordinate condition only (p < .05). In contrast, SV patients had more fixations to the competitor in both the coordinate and associative conditions (p < .05). These results suggest that deficits in PPA-SV at least partially stem from increased semantic interference (i.e. coordinate and associative) over the time-course of lexical processing. Study supported by: NIDCD RO1 DC 05375 M613. Differences in Time Interval Distributions Reveal Controlled and Automatic Contributions to Cued Word Retrieval Kyongje Sung, Erin J. Pickett, Kerry Ledoux, Tracy D. Vannorsdall, Mohammad Elsayed, Nia M. Billings, Jessica Silva, David J. Schretlen and Barry Gordon; Baltimore, MD Category-cued word retrieval is generally thought to entail the automatic activation of related concepts, guided by controlled switching among subcategories. The same mechanisms are thought to characterize letter-cued word retrieval, but with greater reliance on controlled than automatic processes. We examined the distributions of time intervals between successively generated words during letter- and category-cued retrieval tasks for evidence of these different mechanisms. Sixty-one healthy adults performed two category-cued word fluency tasks (animals and supermarket items) and two letter-cued word fluency tasks (�p’ and �s’). Word outputs were categorized using the methods described in Ledoux et al. (2009) and the time intervals between words were measured. For category-cued word production, exponential distributions provided excellent fits for time interval distributions. However, for letter-cued words, different types of distributions (e.g., ex-Gaussian) were required in order to fit the time intervals. This discrepancy supports the hypothesis that letter- and category-cued word fluency tasks invoke fundamentally different cognitive mechanisms. This implies that different neuroanatomic structures might subserve lexical retrieval under these constraints, a conclusion that garners some support from disassociations in verbal fluency that characterize various degenerative conditions and focal lesions. Study supported by: This research was supported by the Therapeutic Cognitive Neuroscience Gift Fund and by the NIMH grants MH60504 and MH43775. M611. The Use of Quetiapine in Agitated Patients with Acquired Brain Injury: A Case Control Study Sara Piccoli, Gabriella Paparella, Alec Vestri and Andrea Martinuzzi; Pieve di Soligo, TV, Italy Background: Experimental studies on neurocognitive effects of quetiapine showed improvements of cognitive functions in psychiatric patients. Patients with Acquired Brain Injury (ABI) often present behavioral disturbances (BD) requiring drug treatment which might impair responsiveness and cognition. The use of quetiapine may provide in these patients adequate control of BD without cognitive side effects. Methods: 40 consecutive ABI patients (LCF 4–6) attending intensive neurorehabilitation were recruited, 20 of whom with BD scored by Aggressive Behaviour Scale (ABS) requiring medical treatment, and 20 with ABS score <21 not requiring medication. Patients with BD were treated with quetiapine. The changes after 3 months of neurorehabilitation in cognitive functioning and autonomy in ADL (LCF and FIM) in patients receiving quetiapine were compared with those observed in the patients not treated with it. Results: ABS score was significantly reduced in patients receiving quetiapine LCF and FIM improved at similar extent in both groups. Conclusions: Quetiapine provides effective control of BD in ABI patients without interfering with cognitive and functional aspects. M614. Gender Differences across the Lifespan in Neuropsychological Testing Performance in ADHD Population from the Years 1991–2008 Barbara C. Fisher, Danielle M. Garges and Stephany Fulda; Shelby Township, MI and Munich, Germany M612. On-Line Lexical-Semantics in the Semantic Variant of Primary Progressive Aphasia David S. Race and Argye E. Hillis; Baltimore, MD Patients with the semantic variant of primary progressive aphasia (PPA-SV) have semantic deficits in language. In a word-picture matching study, we used eye-tracking to investigate whether PPA-SV patients suffer from lexical-semantic interference during target selection. Participants selected one of four pictures (target, competitor, two unrelated) upon hearing its name. The target-competitor relation was either: coordinate (bee-mosquito), associative (cow-farm), or linguistic (butter-fly). We measured accuracy and proportion of fixations to each picture (which should increase with its level of semantic activity). PPA-SV performance was compared with PPA-nonSV and controls. Accuracy scores were high for controls (98%), PPAnonSV (93%), and PPA-SV (91%). For each condition, all groups had more fixations to the target than to the competi- Introduction: Explore differences between males and females (adolescents and adults) in neuropsychological testing performance in diagnosed ADHD population. Method: A total of 673 adults and adolescents, from age 15 to 73 years were included (419 males) with diagnosed ADHD (Inattentive Type; brain dysfunction/referrals excluded). Results: Females of all ages performed worse than males on all four trials of PASAT. Significant interaction of depression and gender found with females without depression performing better on Stroop than males without depression and no gender differences for subjects with depression; also depressed females performed worse than non-depressed females, with no difference for males. Males 47 ID: senthilk I Black Lining: [ON] I Time: 08:46 I Path: //xinchnasjn/01Journals/Wiley/3b2/ANA#/Vol00000/110244/APPFile/JW-ANA#110244 J_ID: ZAY Customer A_ID: SUPP11-6 Cadmus Art: 22579 Date: 31-August-11 and females did not differ in performance on SDMT and Trail Making Tests. Conclusions: Gender differences are present across lifespan on tasks of information processing (PASAT). Depression moderates performance on tasks assessing distractibility (Stroop) to a greater degree for females than males. Significant gender differences did not occur systematically on SDMT and Trail Making Tests, which involve speeded performance and whole brain functioning. Study supported by: Personally funded Stage: Page: 48 formance on the FAB compared with the MMSE, consistent with frontal-subcortical dysfunction in depression. Study supported by: University of Colorado Denver School of Medicine. M617. Attention Deficit Hyperactivity Disorder in Depressed Adults Ildefonso Rodrı´guez Leyva, Rube´n Haro SIlva and Ana A. Renterı´a Palomo; San Luis Potosi, San Luis Potosi, Mexico Objective: Attention deficit hyperactivity disorder (ADHD) is now recognized as a common disorder, as well as in children and adults. ADHD has an estimated prevalence of 3–5% in adults. Evidence points to an increased rate of a co-morbidity in adult ADHD patients. The most common are disorders of the affective area, including depression. We investigated the comorbidity between these two conditions. Methods: Two questionnaires were applied, the first is the Hamilton Depression Scale D and the second is the Adult Self-Assessment Scale (EAVA), developed by the working group on adult ADHD, which includes the New York University Medical Center, Harvard Medical School and Massachusetts General Hospital. Results: 50 patients, 42 women and 8 men. 74% had some level of depression. 18% had criteria for ADHD (12% inattentive, 6% impulsive). By correlating the scale of Hamilton with the score of EAVA, results that in patients with ADHD and depression, impulsive symptom severity decreased in proportion to the degree of depression. Conclusions: In patients with ADHD and depression, the intensity of the symptoms of inattention and not those of impulsiveness, are related in proportion to the degree of comorbid depression measured by the Hamilton Scale. M615. Hazard Perception in Cognitively Impaired Older Drivers Nazan Aksan, Monica Lees, John D. Lee, Shaun Vecera and Matthew Rizzo; Mountain View, CA; Madison, WI and Iowa City, IA Aging and neurological impairment reduce situation awareness and increase injury risk as in falls and car crashes. Hazard perception ability (HPA) is important to driver safety and can be indexed by reaction time (RT) to traffic scenarios (Horswill & McKenna, 2004; Horswill et al., 2008). Declines in HPA correlate with reductions in Useful Field of View (UFOV), a measure of spatial area within which individuals can detect visual stimuli (Ball & Rebok, 1994). We examined whether vehicular warning systems can improve RT in HPA paradigms in elderly drivers with and without UFOV deficits. 27 of 51 elderly (67-87yrs without neurodegenerative disease, min MMSE ¼ 25) were randomly assigned to receive auditory/visual warnings in a simulator while watching video scenarios and 10 of those had deficits in UFOV. Warnings improved RTs slightly (300msec) and a large difference of 1sec in RTs were noted between those with and without UFOV deficits. Warnings did not differentially improve RTs of those with deficits. However, they improved sensitivity, d’, of elderly without deficits more than those with deficits. Findings imply warning systems do not provide uniform benefits to elderly drivers. Study supported by: NIH R01 HL091917 M618. Cognition and EEG Abnormalities in NonEpileptic AD(H)D/LD Patients with and without AntiEpileptic Drug/Stimulant Therapy Brittany M. DiVito, Heather A. Koch, Spencer A. Leblang, Erik C. Bakken and Drake D. Duane; Scottsdale, AZ and Tempe, AZ Background: Epileptiform EEG abnormalities of unknown but non-epileptic clinical significance are not rare in developmental disorders of attention and learning (ADD/LD). The fate of these EEG patterns, their correlation with behavioral manifestations and effects of AED therapy is unknown. Methods: Retrospective analysis of 56 non-epileptic ADD/LD with an initial Dysrhythmia Grade II or III EEG (Mayo Clinic classification) and subsequent EEG later for developmental dx, cognitive test profile, noting if stimulant, AED, both or none were employed. Results: Baseline Abnormal EEG-M38/F18, mean age 10 5/12 years, Dx:AD(H)D-47, LD-40, both-32 EEG and cognitive improvement in at least 1 of 5 cognitive tests: F/U EEG Nl-50%; F/U EEG Abn-52% In both, proof reading and verbal learning most apt to improve, rarely computerized attention Rx and cognitive improvement (cumulative score 5 tests): No Rx-11, Stim-20, AED-12, Both-23 Conclusions: In AD(H)D/LD with Abn EEG: M616. Differentiation of Alzheimer’s Disease and Depression with Standard Cognitive Measures Meredith C. Frederick**, Stefan Sillau, David B. Arciniegas, C. Alan Anderson, Katherine L. Howard and Christopher M. Filley; Aurora, CO and Denver, CO Objective: Alzheimer’s disease (AD) and depression can both present with cognitive impairment. To compare the neurobiology of these disorders, we assessed patients with AD and depression using the Mini-Mental State Examination (MMSE) and Frontal Assessment Battery (FAB). Methods: Medical records were reviewed of 475 consecutive patients seen at a behavioral neurology clinic over 34 months. From this group, patients with AD (n ¼ 59) and depression (n ¼ 44) were selected after receiving a consensus diagnosis by three physicians certified in Behavioral Neurology & Neuropsychiatry (DBA, CAA, CMF). MMSE and FAB data were analyzed using Z-score transformation. Results: AD patients performed significantly worse than those with depression on both the MMSE (z-scores À3.93 vs. 0.05, p < 0.0001) and FAB (À3.1 vs. À1.0, p ¼ 0.009). Patients with depression scored significantly worse on the FAB than the MMSE (p ¼ 0.0003). AD patients performed equally poorly on both tests. Conclusions: The MMSE and FAB may assist in the differentiation of AD and depression. Whereas both measures were abnormal in AD, depressed patients had poorer per- -Normalization of EEG has no general correlation with improved cognition. When cognition is improved, it is most often in verbal learning/memory/proof reading not computerized attention tasks. -Irrespective of follow up EEG, cognition is most apt to improve when both an AED and stimulant are employed. 48 ID: senthilk I Black Lining: [ON] I Time: 08:46 I Path: //xinchnasjn/01Journals/Wiley/3b2/ANA#/Vol00000/110244/APPFile/JW-ANA#110244 J_ID: ZAY Customer A_ID: SUPP11-6 Cadmus Art: 22579 Date: 31-August-11 M619. Evolution of EEG Abnormalities in Non-Epileptic AD(H)D/LD Patients with and without Anti-Epileptic Drug/Stimulant Therapy Heather A. Koch, Brittany M. DiVito, Spencer A. Leblang, Erik C Bakken and Drake D. Duane; Scottsdale, AZ and Tempe, AZ Stage: Page: 49 M621. Cruetzfeldt-Jakob Disease Presenting as a Rapidly Progressing Dementia with Non-Convulsive Status Epilepticus Natasha Tilluckdharry, Megan McGarry and Dipak P. Pandya; Paterson, NJ Background Creutzfeldt-Jakob disease (CJD) is a fatal neurodegenerative disease caused by the accumulation of misfolded prion proteins in the brain. Although rare, it is the most common prion body disease. Clinical manifestations include rapidly progressive dementia, behavioral changes, extrapyramidal signs, akinetic mutism and myoclonus. We report a unique case of CJD with nonconvulsive status epilepticus. Case Report: 73 year old woman was admitted with a rapidly progressive dementia of one year. The patient was noted to have intermittent jerky movements, decreased responsiveness and mutism. Physical examination revealed vegetative mental state, whole body stiffness, myoclonic jerks and right sided rigidity. Electroenchephalogram (EEG) demonstrated generalized periodic,rhythmic and lateralized complexes. Magnetic Resonance Imaging (MRI) of the brain revealed global cerebral atrophy. CSF evaluation showed presence of 14-3-3 protein and extremely high levels of Tau protein. The brain biopsy was refused by family. Conclusion The clinical triad of rapid progressive dementia, myoclonus, akinetic mutism in conjunction with EEG and CSF findings are usually conclusive for CJD. Brain biopsy is the diagnostic choice with histopathologic findings of spongiform changes, cortical neuronal loss and abnormal deposition of prion protein. Nonconvulsive status epilepticus is usually a rare finding with CJD. Background: Epileptiform EEG abnormalities of non-epileptic clinical significance are not rare in developmental disorders of attention and learning (ADD/LD). The fate of these EEG patterns and their evolution over time with or without AED therapy is unknown. Methods: Retrospective analysis of 56 non-epileptic ADD/LD with initial Dysrhythmia Grade II or III EEG (Mayo Clinic classification) and subsequent EEG later for developmental dx, noting if stimulant, AED, both or none were employed. Population was contrasted with 56 control ADD/LD with normal EEG. Results: Baseline Nl EEG- M38/F18, mean age 10 9/12 years, Dx: AD(H)D-49, LD-50, Both-43 Baseline Abn EEG- M38/F18, mean age 10 5/12 years, Dx: AD(H)D-47, LD-40, Both-32 Follow Up EEG: interval mean 3 9/12 years (range 8/12 to 15 years) Nl- 25(45%) No Rx-3, Stim-5, AED-8, Both-9 Abn- 31(55%) No Rx-9, Stim-11, AED-4, Both-7 Conclusions: In AD(H)D/LD with abnormal EEG: -Diagnosis distribution is similar to normal EEG. -Whether on or off AED Rx, EEG abnormalities often persist, but less often if AED in use. M620. Transection of CA3 Does Not Affect Memory in Rats Mohamad Z. Koubeissi, Saifur Rashid, Gemma Casadesus, Joseph LaManna, Kui Xu, Hans Luders and Dominique Durand; Cleveland, OH Epilepsy M701. Controlled Cortical Impact in Adult Rats and Posttraumatic Seizures and Epilepsy Kevin M. Kelly, Elena A. Kharlamov, Eric R. Miller, Bo Lu and Zakaria Mtchedlishvili; Pittsburgh, PA and Philadelphia, PA Objective: To investigate the effect of CA3 transections on memory in rats. Rationale: Longitudinal hippocampal pathways are needed for seizure synchronization, and their transection may abolish seizures. However, the effect of such transection on memory is unknown. Methods: Sprague-Dawley Rats (247–285g) were used. A stereotactic knife was implanted 4mm ventrally, 3.3mm posterior and 4.0mm lateral to bregma, targeting CA3. The knife was protruded from its sheath to transect CA3. Sham surgery (n ¼ 4), unilateral (n ¼ 5), and bilateral (n ¼ 5) CA3 transections were made. Novel object recognition (NOR) and Morris water maze (MWM) tests were started 18 days later. Cut locations were confirmed by cresyl-violet staining. Results: For MWM, the ratio of the amount of time spent in the target quadrant to that spent in the other three quadrants showed no difference between groups. For NOR, discrimination scores were also not different between controls and transected animals. Histology confirmed the locations of transections in the CA3 region. Conclusion: Normal performance in NOR and MWM does not appear to require intact transmission throughout the whole length of CA3. Significance: Since CA3 transections do not interfere with memory function, they may be tried for treatment of temporal lobe epilepsy. Study supported by: Dr. Durand is supported by the National Institute of Health (5R01NS032845-13, 5R01NS060757-03, and 5R01NS064157-02) and the COULTER Foundation The CCI model of TBI has been used in mice and immature rats to model posttraumatic epilepsy. We used young adult rats and long-term video and video-EEG with cortical and hippocampal electrodes to investigate posttraumatic epileptogenesis and associated neuropathological changes. A total of 28,956 hours of monitoring was obtained from 128 CCI-injured and 15 sham-operated animals. Class 3–5 provoked seizures occurred in 7/72 (9.7%) animals video-monitored for 1 week immediately after CCI. Epileptic seizures occurred in 26/118 (22%) animals monitored beyond 1 week post-CCI. Class 3–5 seizures occurred in 19 animals; ictal discharges appeared generalized at onset or from the contralateral frontal cortex. Nonconvulsive seizures occurred in 7 animals characterized by motor arrest or no behavioral change associated with continuous 1-2 Hz high amplitude spikes or spike-waves averaging 26.2 6 2.8 seconds. No control animal had seizures. CCI resulted in severe cortical and subcortical injury and alterations in NeuN and GFAP staining. Timm staining showed mossy fiber sprouting in the inner molecular layer of the dentate gyrus of epileptic and nonepileptic animals. These results indicate that the CCI model can be used in adult animals to investigate mechanisms underlying posttraumatic epileptogenesis. Study supported by: Pennsylvania Department of Health Research Formula Fund RFA 01-07-26 and Epilepsy Foundation Research Grant (ZM) 49 ID: senthilk I Black Lining: [ON] I Time: 08:46 I Path: //xinchnasjn/01Journals/Wiley/3b2/ANA#/Vol00000/110244/APPFile/JW-ANA#110244 J_ID: ZAY Customer A_ID: SUPP11-6 Cadmus Art: 22579 Date: 31-August-11 M702. Serotonin 1A Receptors and Memory in Temporal Lobe Epilepsy William H. Theodore, Edythe Wiggs, Ashley Martinez, Irene Dustin, Omar Khan, Shmuel Appel, Patricia Reeves-Tyer and Susumu Sato; Bethesda Stage: Page: 50 Objective: Periventricular nodular heterotopia (PNH) are associated with epilepsy and dyslexia. Evidence suggests that heterotopia have a functional role and connectivity defects may be important in this disorder. We investigated the restingstate functional connectivity of heterotopic nodules in PNH. Methods: Eleven subjects were studied using functional connectivity MRI with bold oxygenation level-dependent (BOLD) imaging acquired during rest. The functional correlation between heterotopic nodules and other brain voxels was systematically identified and relationships to clinical measures analyzed. Results: Forty-three of 45 heterotopia (96%) showed functional correlation with discrete regions of overlying cortex (mean peak coefficient 0.61). Nodules also demonstrated correlation with contralateral cortex (62%), other nodules (51%), ipsilateral nonoverlying cortex (42%), and basal ganglia/cerebellum (13%). The peak degree of connectivity between heterotopia and other gray matter regions was significantly related to epilepsy duration. Interpretation: Nearly all heterotopia in PNH are functionally connected to overlying cortex, and the strength of aberrant connectivity increases with duration of epilepsy. Along with prior evidence that cortico-cortical tract defects underlie dyslexia in this disorder, these results suggest that altered connections are a critical substrate for neurological dysfunction in brain malformations. Study supported by: NIH/NINDS, Epilepsy Foundation, William F. Milton Fund Memory deficits are common in patients with temporal lobe epilepsy (TLE). Previous PET studies have shown reduced mesial temporal 5HT1A receptor binding. We studied 40 patients (24 male; mean age 34.5). Seizure diagnosis and focus localization were based on ictal Video-Electoencephalographic recording. Patients had Weschler Adult Intelligence Score III, Weschler Memory Score III, Beck Depression inventory, and interictal PET with [18F]FCWAY, a highly specific 5HT1A ligand. MRI partial volume correction for hippocampal atrophy and tracer plasma free fraction (f1) measurement were used to obtain [18F]FCWAY volume of distribution (V/f1). V/f1 was significantly lower ipsilateral than contralateral to the epileptic focus (73.7 þ/À 27.3 versus 95.4 þ/À 28. We found a significant relation between left hippocampal FCWAY V/f1 and delayed auditory memory score (r ¼ 0.41; p <0.02). The side of the seizure focus was not significant. There was a significant inverse relation between BDI and FCWAY V/f1 ipsilateral to the epileptic focus (r ¼ 0.38; p<0.02), but no relation between BDI and auditory memory. Reduced left hippocampal 5-HT1A receptor binding may play a role in memory impairment in TLE. Study supported by: NINDS NIH Division of Intramural Research M703. Ictal Hypoxemia Is Associated with Cardiac Repolarization Abnormalities Lisa M. Bateman, Franchette Pascual, Michael Lee, Chin-Shang Li and Masud Seyal; Sacramento, CA and Los Angeles, CA M705. JAK/STAT Inhibition Slows the Progression of Temporal Lobe Epilepsy in an Animal Model Heidi L. Grabenstatter, Yasmin Cruz Del Angel, Marco I. Gonzalez, Yogendra H. Raol, Shelley J. Russek and Amy R. Brooks-Kayal; Aurora, CO and Boston, MA Background: Peri-ictal hypoxemia occurs in 1/3 of patients with intractable localization-related epilepsy. Cardiac repolarization abnormalities also occur during seizures. The relationship between these changes is unknown. Methods: We analyzed 37 seizures with oxygen desaturations (DESAT) and 19 seizures without desaturations (NODESAT) in 17 consecutive patients undergoing videoEEG telemetry. Consecutive QT and RR intervals were measured for 1 minute prior to seizure onset (PRE), during the period of hypoxemia in DESAT and two minutes after seizure onset in NODESAT. QTc was calculated using Hodges formula. QTd was the difference between the longest and shortest QT for PRE and DESAT/NODESAT. Results: Prolonged QTc was more likely during DESAT than PRE (OR 10.64;95% CI 4.75–27.98,p<0.0001), as was shortened QTc (OR 1.65;95% CI 1.42– 1.92,p<0.0001). DESAT QTd was significantly associated with desaturation nadir (p ¼ 0.025) and desaturation duration (p < 0.0001) but not seizure duration (p ¼ 0.079). Prolonged QTc was more likely during DESAT than NODESAT (OR 4.30;95% CI 2.56–7.39,p<0.0001), as was shortened QTc (OR 2.13;95% CI 1.84–2.46,p<0.0001). Conclusions: Peri-ictal shortening and prolongation of QTc and increases in QTd are associated with depth and duration of hypoxemia. These findings may be related to the pathophysiology of SUDEP. In the rat pilocarpine model of Temporal Lobe Epilepsy (TLE), status epilepticus (SE) decreases transcription of the GABA-A receptor a1 subunit (GABARa1) in hippocampal dentate gyrus (DG) and may be critical for epileptogenesis. Decreased transcription of GABARa1 results from JAK/ STAT pathway activation which increases inducible cAMP early repressor, and subsequently downregulates GABARa1. To investigate the utility of JAK/STAT inhibitors to prevent epileptogenesis after SE, a novel inhibitor of STAT3 activation, WP1066, was administered to rats at the onset of SE. WP1066 (50 mg/kg i.p.) administered at onset of and 1 hour into pilocarpine-induced SE reduced STAT3 phosphorylation in DG by $45%. Continuous video-EEG monitoring for two weeks demonstrated that administration of WP1066 significantly reduced the total time spent in SE and impeded the progressive increase in spontaneous seizures over time compared to SE rats treated with vehicle. Latency to first seizure was not affected. Conclusions: Treatment with JAK/STAT inhibitors at the time of SE reduces the severity and duration of SE and slows the progression of epilepsy inherent to post-SE models, suggesting that JAK/ STAT inhibitors may be disease modifying. Study supported by: NIH NS R01051710 (to ABK and SJR), Epilepsy Foundation (to HLG), and CURE (to ABK and SJR) M706. Long-Term Changes in mGluR-Mediated Long-Term Depression Following a Single Episode of Early Life Seizures in Rats Paul B. Bernard, Anna Castano and Tim A. Benke; Aurora, CO M704. Gray Matter Heterotopia in an Epileptic Brain Malformation Are Functionally Connected to Overlying Cortex Joanna A. Christodoulou, Linsey M. Walker, Stephanie N. Del Tufo, Tami Katzir, Susan Whitfield-Gabrieli, John D.E. Gabrieli and Bernard S. Chang; Cambridge, MA; Boston, MA and Haifa, Israel Previous research in our lab has indicated that following a single episode of early life seizures (ELS), rats display 50 ID: senthilk I Black Lining: [ON] I Time: 08:46 I Path: //xinchnasjn/01Journals/Wiley/3b2/ANA#/Vol00000/110244/APPFile/JW-ANA#110244 J_ID: ZAY Customer A_ID: SUPP11-6 Cadmus Art: 22579 Date: 31-August-11 increased LTD (long term depression) and cognitive deficits at maturity (PND 60þ). These changes occur in the absence of pronounced hippocampal injury. We speculate that increased LTD expression may be responsible for the observed learning abnormalities. LTD induction can be mediated by two distinct mechanisms, NMDA receptor (NR) dependent and metabotropic glutamate receptor (mGluR) dependent. The NR-mediated and mGluR-mediated forms are differentiated by the effectiveness of different chemical and electrical LTD inducing stimulation paradigms. Using these paradigms, we found that alterations in LTD following ELS are the result of changes exclusively in mGluR-mediated LTD. Furthermore, we found that ELS results in abnormal signaling consistent with that mediated by the Fragile X Mental Retardation Protein (FMRP) to result in increased mGluR-mediated LTD, with similarities to that found in genetic disruption of FMRP. Expression of proteins associated with mGluR-mediated LTD and FMRP signaling were also altered in a consistent fashion, suggesting a mechanism for the observed changes in LTD and possible targets for therapeutic intervention. Study supported by: NIH-NINDS, Epilepsy Foundation, The Childrens Hospital Research Institute Stage: Page: 51 were defined anatomically a priori and functioned as seeds in a functional connectivity analysis. Results indicate that TLE exerts a complex effect on the functional connections of the medial temporal region. Intrahemispheric coupling between the hippocampal head and entorhinal cortex was surprisingly stronger in TLE patients (p<.05), which may have either compensatory or pathologic significance. While cross-hemispheric coupling between hippocampi was weaker than controls (p<.05), even in patients there was strong interhemispheric connectivity, suggesting partially preserved function in the affected hippocampus. Tracking the amount of preserved connectivity in the individual patient may help predict risk of postsurgical functional decline. Study supported by: NIH/NCRR Washington University ICTS Grant Number UL1 RR024992 M709. Mice Deficient in SNAREs/SNARE Regulators Predict Kindling Phenotype John T. Slevin, Elena E. Matveeva, Sidney W. Whiteheart, Greg A. Gerhardt and Thomas C. Vanaman; Lexington, KY Alterations in neurosecretory machinery may play a role in kindling epileptogenesis. Neurotransmitter (NT) release requires fusion of vesicle and plasma membranes, initiated by the formation of a stable complex (7SC) of SNARE proteins. 7SC is composed of VAMP-2 from the synaptic vesicle and syntaxin 1 & SNAP-25 from the neuronal active zone. There are alterations of SNARE Regulators and permanent accumulation of 7SC in hippocampus ipsilateral to the kindling stimulus. We have begun to characterize epileptogenicity of mice deficient in neurosecretory proteins. To fully kindle, the VAMP-2þ/À mouse requires 150% the AD stimulus and >2.5 as many stimuli as the wild-type animal. One month after full kindling 7SC asymmetry is present in both. VAMP-2 reduction correlates with reduced glutamate release in hippocampal CA3. Tomosyn, as a place-holder for the v-SNARE, may be a negative regulator of NT release; we predicted that tomosynÀ/À mice would be kindling-sensitive. In preliminary studies these mutants required half as many stimuli and 2/3 the AD current to fully kindle, compared to wild type. Transgenics with reduced levels of SNAREs/SNARE Regulators may be useful to determine if alterations in neurosecretory machinery can lead to changes in epileptogenesis. Study supported by: Department of Veterans Affairs M707. Heterozygous Loss of the Epilepsy-Associated GABAA Receptor a1 Subunit Causes Spontaneous EEG Spike Discharges in Two Mouse Strains Fazal M. Arain and Martin J. Gallagher; Nashville, TN Autosomal dominant juvenile myoclonic epilepsy and absence epilepsy are associated with missense (A322D) and frameshift (S326fs328X) mutations in the GABAA receptor a1 subunit. Although both mutations substantially reduce a1 subunit protein expression in vitro, previous studies failed to detect seizures in heterozygous a1 subunit knockout (GABRA1 KO) mice. Here, we performed video-EEG studies in wild type and heterozygous GABRA1 KO mice in the seizure-resistant C57BL/6 and susceptible DBA/2J strains. Consistent with previous results, both strains of wild type mice had a low incidence of spike discharges (SD), and this baseline incidence was greater in DBA/2J (7 6 4 SD/ hr) than C57BL/6 (2 6 1 SD/hr) mice. Heterozygous GABRA1 KO caused an ethosuximide-sensitive increase in SD incidence to 14 6 3 SD/hr in DBA/2J mice and 12 6 3 SD/hr in C57BL/6 mice. The typical SD duration was brief (1–3 seconds) and no definite associated behavior changes were observed. Therefore, heterozygous loss of a1 subunit produces thalamocortical hypersynchrony in vivo and likely represents a principle mechanism by which the A322D and S326fs328X mutations cause seizures. Study supported by: National Institute Of Neurological Disorders And Stroke R01NS064286 M710. Pharmacokinetic Equivalence between Immediate-Release and Extended-Release Topiramate Lawrence J. Lambrecht, Wesley M. Todd and Mark B. Halvorsen; Maple Grove, MN Decreased absorption in the presence of food and plasma fluctuations can negatively affect antiepileptic drug therapy. Food has no effect on the absorption of immediate-release topiramate (TPM-IR) but twice-daily dosing is recommended to minimize fluctuations. Recently, an extendedrelease topiramate formulation (USL255) was developed that displays improved pharmacokinetic (PK) characteristics based on single-dose and modeled steady-state data. Equivalence of exposure between USL255 and TPM-IR, and the effect of food on the USL255 PK profile, were determined in a Phase I, randomized, 3-way crossover study. Equivalence criteria were 90% confidence interval of the ratios of the geometric least-squares means for AUC0-t, AUC0-1, and Cmax within the range 0.8–1.25. Similar criteria were established for determining the food effects. Tmax and t1/2 were also determined for each treatment. M708. Regional Network Disruption in Temporal Lobe Epilepsy Luigi Maccotta* and Edward Hogan; St. Louis, MO Medial temporal cortex forms a network of connections with both the contralateral medial temporal lobe and with extratemporal brain regions. It is unclear how temporal lobe epilepsy (TLE) affects these connections, and whether the effect is pathologic/dysfunctional or compensatory. We investigated the functional connections of the medial temporal region with contralateral temporal and extratemporal brain regions in TLE patients using resting state fMRI. Twenty-three TLE patients underwent resting-state BOLD fMRI. Seizure localization was based on video-EEG. Healthy controls served as comparison. Regions of interest 51 ID: senthilk I Black Lining: [ON] I Time: 08:46 I Path: //xinchnasjn/01Journals/Wiley/3b2/ANA#/Vol00000/110244/APPFile/JW-ANA#110244 J_ID: ZAY Customer A_ID: SUPP11-6 Cadmus Art: 22579 Date: 31-August-11 TPM exposure was equivalent between USL255 and TPM-IR; furthermore, USL255 displayed a lower Cmax and later Tmax than TPM-IR. While bioavailability of USL255 was unaffected by food, Tmax was delayed by 4 hours with food as compared with the fasted condition.Single-dose USL255 demonstrated equivalent TPM exposure and a lack of food effect analogous to TPM-IR dosed twice-daily, suggesting that USL255 may provide a once-daily alternative to TPM-IR. Study supported by: Upsher-Smith Laboratories, Inc. All authors are employees of Upsher-Smith Laboratories, Inc. (study sponsor) Stage: Page: 52 lowing suppression of the GABAB receptors, an effect that may contribute to antiepileptic properties of the drug. Thus, GABAB receptor antagonists reduce pro-epileptic activity in DS model mice. Study supported by: Down syndrome research and treatment foundation (DSRTF); Larry L. Hillblom Foundation M713. Lacosamide: Long-Term Safety and Efficacy in Partial-Onset Seizures William Rosenfeld, Nathan B. Fountain, Gintaras Kaubrys, Elinor Ben-Menachem, Cindy McShea, Jouko Isojarvi and Pamela Doty; St. Louis; Charlottesville; Vilnius, Lithuania; Go¨teborg, Sweden and Raleigh M711. Cingulate Epilepsy, Reporting 3 Clinical and Electrophysiologic Subtypes with Surgical Outcomes Mhd Rafeed Alkawadri, Norman K. So, Paul C. Van Ness and Andreas V. Alexopoulos; Cleveland, OH and Dallas, TX Long-term ( 8 years exposure) safety and efficacy of the antiepileptic drug (AED) lacosamide were evaluated from a completed open-label extension (SP615; NCT00552305) in partial-onset seizures. Patients enrolled following double-blind or open-label lacosamide trials. Dosage adjustment of lacosamide (100800mg/day) and/or concomitant AEDs occurred to optimize tolerability and seizure reduction. Treatment-emergent adverse events (TEAEs), vital signs, body weight, clinical laboratory data, electrocardiograms, and seizure frequency from subject diaries were evaluated. Of 370 enrolled patients, 77%, 51%, and 39% had >1, >3, or >5 years lacosamide exposure, respectively (median modal dose 400mg/day). Common TEAEs (!15%) were dizziness, headache, nausea, diplopia, fatigue, upper respiratory tract infection, nasopharyngitis, contusion, and coordination abnormal. Discontinuations due to TEAEs were 12.7%; only dizziness and convulsion led to discontinuation in !1% of patients. Median 28-day seizure frequency was 12.0 at Baseline of previous trials; median percent reduction from Baseline was 50.8% across Treatment, and was 47.3%, 56.8% and 65.2%, respectively, for 1-year, 3-year and 5year completers. The !50% responder rate was 51.2% across Treatment, and was 48.8%, 57.2% and 63.4% for 1year, 3-year and 5-year completers, respectively. Long-term adjunctive lacosamide treatment was generally well tolerated, reduced seizure frequency and maintained efficacy. Study supported by: UCB Inc. Elinor Ben-Menachem, within the past year, has had contracted research, consulting, speaking, and teaching, relationship with UCB. Cindy McShea and Jouko Isojarvi are employed by UCB BioSciences Inc. Pamela Doty is employed by UCB BioSciences, Inc. as a Principal Clinical Program Director for Lacosamide Epilepsy. As Principal Clinical Program Director, she receives stock option grants. William Rosenfeld is a principal investigator and has received research support from UCB for participating in double-blind and open-label studies. William Rosenfeld is on the UCB speaker’s bureau. Objective: To characterize epilepsy arising from the cingulate gyrus. Design/Methods: We describe 14 cases of lesional cingulate gyrus epilepsy treated surgically. The cases were identified from the Cleveland clinic and the UTSouthwestern epilepsy monitoring unit databases 1992–2009. Results: All 14 cases had cingulate epilepsy confirmed by MRI lesions and remarkable improvement after surgery. They were divided into 3 groups based on the anatomical location and the semiology. In the posterior cingulate group 4 of 4 cases had clinical or electrophysiologic findings suggestive of temporal origin of the epilepsy. The anterior cingulate cases were divided into a ��typical’’ (BANCAUD, 1992) group: 6 cases with hypermotor seizures and infrequent generalization with the presence of fear, laughter, or interictal personality changes; and an ��atypical’’ group: 4 cases presenting with simple motor seizures and a tendency for more frequent generalization and less favorable surgical outcome. The pathology of the atypical cases was astrocytoma. Conclusions: Posterior cingulate gyrus epilepsy presents with electroclinical findings that are suggestive of temporal lobe epilepsy and can be considered an example of ��pseudotemporal epilepsy’’. The electroclinical presentation and surgical outcome of lesional anterior cingulate epilepsy is possibly influenced by the underlying pathology. M712. GABAB Receptor Antagonists Reduce ProEpileptic Activity in Hippocampal Slices of Ts65Dn Mice, a Genetic Model of Down Syndrome Alexander M. Kleschevnikov, Brett Rasmuss, Pavel V. Belichenko and William Mobley; La Jolla, CA Epilepsy is a known co-morbidity of Down syndrome (DS). GABAB receptor antagonists have been proposed recently as medicines for improving memory in DS. We examined effects of GABAB antagonists on pro-epileptic properties in Ts65Dn mouse model of DS. In a high-potassium in vitro model of epilepsy, elevation of extracellular [Kþ] provoked seizures in the dentate gyrus in slices from both Ts65Dn and 2N (control) mice. The frequency of seizures was significantly greater in Ts65Dn (0.47 6 0.03 Hz vs. 0.33 6 0.06 Hz, p ¼ 0.013), while the amplitude did not differ (p ¼ 0.45). GABAB antagonist CGP52432 reduced the amplitude of seizures more considerably in Ts65Dn than in 2N slices (63.5 6 4.6% vs. 80.2 6 8.1%, p ¼ 0.033). The frequency of seizures was not affected (p > 0.4). GABAB antagonists reduced also ratio of amplitudes of population spikes (PSA2/PSA1) evoked by paired stimuli. This result suggests an increase in the feedback inhibitory efficiency fol- M714. Lacosamide: Long-Term Safety in Partial-Onset Seizures Robert F. LeRoy, Gregory Krauss, Nathan B.. Fountain, Deanne Dilley, O’Neill D’Cruz and Pamela Doty; Dallas, TX; Baltimore, MD; Charlottesville, VA and Raleigh, NC Long-term safety of the antiepileptic drug (AED) lacosamide was evaluated in an open-label extension trial SP926 (NCT00655486). Eligible participants were enrolled from IV infusion trial SP925 (NCT00655551). Investigators could adjust lacosamide oral tablet (100–800mg/day) and/or concomitant AED dosage to optimize treatment. Safety assessments included adverse events (AEs), ECGs and clinical laboratory data. 52 ID: senthilk I Black Lining: [ON] I Time: 08:46 I Path: //xinchnasjn/01Journals/Wiley/3b2/ANA#/Vol00000/110244/APPFile/JW-ANA#110244 J_ID: ZAY Customer A_ID: SUPP11-6 Cadmus Art: 22579 Date: 31-August-11 Of the 97 enrolled patients, 58.8% and 38.1% had >12- and >18-months of lacosamide exposure, respectively. The median modal lacosamide dose was 500mg/day. TEAEs (incidence !15%) included dizziness (44.3%), diplopia (17.5%), and vomiting (16.5%); most were mild/ moderate in intensity. Only one serious AEs (SAEs) occurred in >1 patient (convulsion, n ¼ 2). One patient discontinued due to SAEs (arrhythmia supraventricular and atrial fibrillation) and continued commercial lacosamide after treatment of the SAEs. One TEAE led to discontinuation in >1 patient (dizziness, n ¼ 3). Median clinical laboratory values remained within normal range; changes from Baseline were not of clinical relevance. Small increases in mean PR interval and QRS duration were consistent with the known lacosamide safety profile and did not vary with lacosamide exposure. Safety evaluations indicate long-term lacosamide administration (100–800mg/day) is generally well tolerated as adjunctive treatment for patients with partial-onset seizures. Study supported by: UCB Inc. Dr. RF LeRoy has a significant financial relationship with UCB, the sponsor of the study which generated this abstract. He participated in funded research as an investigator in study SP926 and other UCB funded studies as well as a speaker for the Vimpat Speaker ProgramHe has participated in UCB sponsored advisory boards for Vimpat. Dr. G Krauss has received research support from UCB S.A., Johnson & Johnson Inc., SK-Biosciences Corporation, Eisai Inc., Sepracor Inc., and Icagen, Inc., and has served as a paid consultant for Eisai Inc. and UCB S.A. Deanne Dilley: Employee, UCB BioSciences, Inc. O’Neill D’Cruz: Employee, UCB BioSciences, Inc. Pamela Doty is employed by UCB BioSciences, Inc. as Principal Clinical Program Director for Lacosamide Epilepsy. As a Principal Clinical Program Director, she receives stock option grants Stage: Page: 53 M717. Status Epilepticus: An Independent Predictor of Poor Survival after Anoxic Brain Injury Jennie Luna, Nelly Awkar, Megan McGarry, Deepthi Karanam and Dipak P. Pandya; Paterson, NJ Introduction: Evaluation of prognosis in Anoxic brain injury is a very difficult task due to lack of clinical and biological markers. The delay in neurological recovery is a poor prognostic sign. Status epilepticus (SE) may present in up to one third of patients with cardiac arrest. We report the significance of SE and myoclonic status as an independent clinical marker in anoxic brain injury. Methods: After IRB approval, we studied adult patients with SE in anoxic brain injury. Status epilepticus was defined with clinical history and EEG findings. Patients without EEG findings were excluded. Total 48 patients were identified. Results: 20/48(41%) had SE. 16/20(80%) expired and 4/ 20(20%) survived. A 15% of the patients with SE had anoxic myoclonus with 100% mortality. All SE patients were comatose. Patients with SE, 60% reported duration of CPR !10 minutes. The other 40% had unknown duration. All our study patients were resistant to antiepileptic medications. Conclusion: Status epilepticus was present in 41% of patients and anoxic myoclonic status remains a grave prognostic sign for any survival. Overall, comatose mental status with SE or anoxic myoclonus remains an independent clinical marker for poor outcome. M718. Periodic Lateralized Epileptiform Discharges (PLEDs)-Rhythmic Discharges (RDs) in Anoxic Encephalopathy Sushanth Bhat, Sombabu Maganti, Eli S. Neiman, Divya Gupta and Sudhansu Chokroverty; Edison, NJ Objective: To describe an unusual EEG pattern of stereotypical PLEDs coupled with RDs in anoxic encephalopathy. Case Discussion: Following cardiac arrest, a comatose 79 year-old woman had left facial twitching, sluggish pupils, absent corneal’s/Doll’s eyes reflexes and no withdrawal to stimuli. Facial twitching subsided with intravenous levetiracetam. CT scan of the head showed cerebral atrophy. An EEG showed right anterior/midtemporal PLEDs with slowsharp morphology recurring at 0.3–0.5 Hz, coupled with a 9 Hz RD from the same area every 24–29 seconds and lasting 5.5–7 seconds, not evolving into electrographic seizures and unchanged in morphology or frequency. There was no clinical/EEG background change to noxious stimulation. Discussion: PLEDs may be PLEDS-proper or PLEDSplus (associated with RDs). Both may occur with acute cerebral lesions, with PLEDs-plus more likely to be associated with seizures. However, focal and chronic lesions more often produce PLEDs-proper. The presented case is unusual, with no evolution of the PLEDs- RDs complex into electrographic seizures; such a pattern has not been described in acute, diffuse cortical injury such as anoxic encephalopathy, where BiPLEDs would be expected. Our EEG findings are reminiscent of those in isolated cortex in an animal model (Kristiansen, 1949). M715. Withdrawn M716. Computational Models of Ligand-Gated Receptor Function Characterize Anticonvulsant Drug Actions at GABAergic and Glutamatergic Synapses and David E. Naylor; Torrance, CA Many neurological drugs act on inhibitory GABAergic or excitatory glutamatergic receptors. Little is known about the direct effects of endogenous ligand or drug exposure on receptors in situ, and even less about broader pharmacological effects on normal or pathological circuit activity. Here, computational models of receptors characterize drug actions on multiple scales from submillisecond transmitter release, diffusion and uptake at single synapses to near seconds of residual receptor desensitization after multisynaptic synchronized release. GABA-A and NMDA receptor-kinetic models at synaptic and extrasynaptic sites in dentate gyrus granule cells are optimized to fit inhibitory and excitatory postsynaptic currents (PSCs) as well as evoked paired-pulse and tonic current responses after ligand and drug exposure. Synaptic GABA-A receptors over-exposed to GABA paradoxically show rapid downregulation/amplitude reduction from receptor desensitization. Hi-frequency 200Hz pulsatile release of GABA for 400 ms (as with epileptic fast ripples) also degrades synaptic inhibition, and recovery from desensitization is prevented by 0.5 to 2 Hz interictal-like discharges. Subsequent model fits of IPSCs/EPSCs after exposure to anticonvulsant agents quantify and optimize the effects of single and combination agents on receptor properties. M719. Periodic Lateralizing Epileptiform Discharges (PLEDs) Causing Persistent Magnetic Resonance Imaging (MRI) Changes in Ipsilateral Thalamus Umang Shah, Umer Akber and Chunyang Wang; Camden, NJ Objective: To recognize PLEDs as potential cause of persistent MRI changes in ipsilateral thalamus. 53 ID: senthilk I Black Lining: [ON] I Time: 08:46 I Path: //xinchnasjn/01Journals/Wiley/3b2/ANA#/Vol00000/110244/APPFile/JW-ANA#110244 J_ID: ZAY Customer A_ID: SUPP11-6 Cadmus Art: 22579 Date: 31-August-11 Background: Transient diffusion weighted image (DWI) abnormalities in ipsilateral thalamus following status epilepticus are well-recognized, but persistent changes in fluidattenuated inversion recovery (FLAIR) and T2-weighted images (T2WI) are rare. Design/methods: We report a patient who had persistent ipsilateral signal change in thalamus after complex partial status epilepticus and PLEDs. Results: Case: A 56 year-old woman presented with recurrent partial seizures involving the right arm and change in mental status. Electroencephalography revealed PLEDs in the left temporal lobe causing partial status epilepticus. Immediate brain MRI was normal but repeat MRI ten days later showed a focus of increased signal on FLAIR and T2WI in the left posterolateral thalamus. No abnormal enhancement was seen. Follow-up MRI one-month later demonstrated a persistent area of signal abnormality in the left thalamus. Discussion: Thalamic role in ictal events is unclear, but afferent and efferent cortical-interconnections may explain thalamic involvement in epileptic activity, which is generally considered a cortical phenomenon. Although DWI thalamic abnormalities are reported after status epilepticus, persistent FLAIR and T2WI signal is rare. Stage: Page: 54 of the disease. Status epilepticus has not been reported as a clinical manifestation in Sneddon’s Syndrome. Results: A 68 year old man with history of hypertension admitted with confusion, decrease responsivessness and subtle left sided weakness. He had non-itchy skin rash and mild left sided paresis. His laboratory tests showed thrombocytopenia, Hepatitis C, positive antiphospholipid antibodies. MRI showed acute right middle cerebral artery distribution infarct. EEG showed Periodic Lateralized Epileptiform Discharges from right hemisphere with changing morphology and evolving in nature. Patient was treated with antiepileptic medications, intravenous immunoglobulins, antiplatelet agents, statin and ACE inhibitors. His acute condition was improved and he was discharged to rehabilitative facility. Conclusions: Most cases of Sneddon’s syndrome are sporadic. It is unclear whether the status epilepticus is due to acute brain injury, from antiphospholipid antibodies or from inflammatory mediators. M722. Status Epilepticus Secondary to Milk Alkali Syndrome Induced by Hypercalcemia (Oral Antacids) Rabih Kashouty, Noor Yono and Mershed Al Samara; Manhattan, NY; Manhasset, NY and Southfield, MI Milk-alkali syndrome is mainly caused by the ingestion of large amounts of calcium and absorbable alkali. This syndrome can lead to metastatic calcification, renal failure and metabolic alkalosis secondary to hypercalcemia. Hypercalcemia is rarely a cause of seizure activity. Very few case reports have been published linking seizure to hypercalcemia, but only one recent case report about mesial temporal sclerosis relates the seizure activity to Milk-alkali syndrome. This is the first report regarding seizures associated with excess calcium carbonate intake without evidence of mesial temporal sclerosis. The patient described in this article, suffered from status epilepticus most likely secondary to hypercalcemia. Evaluations for malignancy, thyroid, and parathyroid dysfunctions were non conclusive, therefore hypercalcemia in our patient was attributed to milk-alkali syndrome given the history of the prolonged calcium carbonate intake. M720. Ammoniacal Encephalopathy Presenting as Complex Partial Seizure-Like Episodes: A Case Series Darine Kassar and Stanley Iyadurai; Saint Louis, MO Objective: To report a series of cases with hyperammonemia, presenting as seizure-like episodes. Background: Seizures are caused due to several causes.While accumulation of ammonia is a common cause of encephalopathy, it is also known to cause a broad spectrum of neurological manifestations. Seizures have not been reported in association with chronic hyperammonemia. Methods: Case Series Case report: Index case: A 53-year old man with chronic hepatitis C presented with confusional episodes associated with stereo-typed movements. Physical examination revealed psychomotor slowing. Routine serological and CSF evaluations were normal, except elevated ammonia (177 mmol/l). A diagnosis of ammoniacal encephalopathy was made. The patient was started on lactulose therapy with improvement. Four other patients with similar history, presentation, and elevated ammonia levels were seen. Complete resolution of symptoms were observed with treatment of hyperammonemia with lactulose in these patients. Conclusion: Here we present a series of patients with episodes of various neurologic dysfunctions. The only metabolic abnormality that was identified was an elevated ammonia level. We believe that his seizure-like episodes are associated with hyperammonemia. To our knowledge, this is the first report that links complex partial seizure-like episodes to hyperammonemia. M723. A Case of Magnesium-Responsive Paraneoplastic Non-Convulsive Status Epilepticus Robert K. Shin, Anna V. Rosenbaum and Nicholas Frost; Baltimore, MD Objective: We present a case of paraneoplastic non-convulsive status epilepticus resistant to multiple AEDs that resolved with magnesium. Background: Paraneoplastic syndromes affecting the nervous system have been described in association with numerous cancers, some presenting as limbic encephalites associated with seizures, including an encephalitis in young women with ovarian teratoma associated with anti-NMDA receptor antibodies. Results: A 57-year old female with clear cell ovarian cancer became unresponsive following a one week prodrome of increasing confusion and forgetfulness. EEG demonstrated non-convulsive status epilepticus. Imaging, serum and CSF studies were non-diagnostic. Over a course of two weeks, she did not respond to multiple anti-epileptic medications and continued to have up to 30 seizures daily. IV magnesium was administered, and the following morning she was alert, oriented and able to converse with her husband. Conclusions: While magnesium is routinely used to treat seizures in obstetrics, its use in neurology is uncommon. Given that it is a known NDMA inhibitor, it may represent M721. Status Epilepticus as an Initial Manifestation of Sneddon’s Syndrome Anish Shah, Saurav Sen, Jennie Luna and Dipak P. Pandya; Paterson, NJ Background: Sneddon’s Syndrome is a rare progressive noninflammatory vasculopathic disease affecting small and medium size arteries in conjunction with ischemic cerebrovascular disease, possibly livedo reticularis in absence of well recognizable connective tissue disease stigmata. It may associate with hepatitis C, thrombocytopenia and positive antiphospholipid antibodies. Seizures are rare during the course 54 ID: senthilk I Black Lining: [ON] I Time: 08:46 I Path: //xinchnasjn/01Journals/Wiley/3b2/ANA#/Vol00000/110244/APPFile/JW-ANA#110244 J_ID: ZAY Customer A_ID: SUPP11-6 Cadmus Art: 22579 Date: 31-August-11 Stage: Page: 55 wild-type nerves (4 mice), and minimal in pmp22þ/À/ pak1À/À nerves (2 mice). Pak1À/À mice developed no phenotype up to 22 month old. Taken together, ablation of PAK1 activity partially suppresses tomaculous formation and myelin leakage in the pmp22þ/À nerves. Reversal of the tomaculous abnormality would improve the security of action potential propagation. Study supported by: NIH a useful treatment option, particularly in cases of paraneoplastic seizures. Study supported by: Study is a case report. There are no sponsors or affilitations associated with it. No individual associated with this case report (or their relatives) has a relevant financial interest relating to the support of the abstract. M724. Withdrawn M804. Zebrafish Models of Amyotrophic Lateral Sclerosis Stacey A. Sakowski, J. Simon Lunn, Angela S. Busta, Carey Backus, Sang Su Oh, James J. Dowling and Eva L. Feldman; Ann Arbor, MI Neuromuscular Disease M801. Nicotinamide Mononucleotide (NMN) Treatment of Diabetic Neuropathy Ankit Sura, Mitch Onken, Krish Chandrasekaran, Helen Chen and James W. Russell; Baltimore, MD Amyotrophic lateral sclerosis (ALS) involves the degeneration and loss of motor neurons (MNs). Zebrafish provide and ideal system to investigate cellular mechanisms and potential treatments for ALS onset and progression. Transient genetic manipulation of zebrafish to express mutant forms of SOD1 associated with familial forms of ALS results in early defects in MN outgrowth and axonal branching. Growth factor signaling, which activates neuroprotective pathways, can be easily upregulated in zebrafish embryos and rescues these early defects, validating the model for therapeutic discovery. Stable transgenic zebrafish lines expressing mutant SOD1 enable further characterization of the consequences of ALS disease progression. Behavioral monitoring reveals late onset muscle weakness and decreased activity in transgenic ALS zebrafish with disease progression. Examination of MNs and zebrafish morphology reveals a loss of neuromuscular junctions and alterations in MN innervations patterns with ALS progression. Finally, MN cell loss is evident later in the course of disease. This sequence of events provides insight into the mechanisms of MN degeneration in transgenic ALS zebrafish, and validates the zebrafish as a novel model for mechanistic discovery and therapeutic development for ALS. Study supported by: Study supported by the A. Alfred Taubman Medical Research Institute and the Program for Neurology Research & Discovery. SAS supported by the NIH (T32 NS007222-28). Nicotinamide adenine dinucleotide (NAD) is a critical metabolite in energy metabolism and mitochondrial (Mt) electron transfer. Nicotinamide mononucleotide (NMN) is a direct substrate for generation of NAD. A decreased NAD level in diabetes may increase the severity of diabetic neuropathy. We determined if NMN prevented the development of diabetic neuropathy. Adult rats were made diabetic with streptozotocin. NMN was injected every second day. There were 4 treatment groups: (1) non-diabetic control with vehicle (2) diabetic (3) diabetic þ 50 mg/kg NMN (4) diabetic þ 100 mg/kg NMN. The Von Frey monofilament sensory withdrawal threshold was normalized in diabetic rats treated with 50 mg/kg or 100 mg/kg NMN for a period of 2 months from the onset of diabetes (n ¼ 6 rats/group, P<0.05 for 100 mg/kg NMN treated compared to diabetic rats). NMN treatment also prevented sciatic motor conduction velocity slowing and diabetic loss of skin Intraepidermal nerve fibers in the hind-limb paw (P<0.01). Addition of NMN to adult mouse DRG dissociated cultures also reduced glucose-induced generation of reactive oxygen species (ROS). NMN effectively reduces the severity of experimental diabetic neuropathy and reduces generation of ROS. Study supported by: Juvenile Diabetes Foundation, Department of Veterans Affairs, NIH M802. Withdrawn M805. ALS-Like Spinal Cord Pathology in Transgenic Mice with a Mutation in the Valosin-Containing Protein Gene Hong Z. Yin, Tahseen Mozaffar, Virginia E. Kimonis and John H. Weiss; Irvine, CA M803. Tomaculous Formation in HNPP Jun Li, Zahara M. Jaffer, Xuebao Zhang, Qing Yan, Michael E. Shy, Ueli Suter, Jonathan Chernoff and Jiasong Guo; Nashville, TN; Philadelphia; Nashville; Detroit and Zurich, Swaziland Kimonis et al. identified a human genetic syndrome, Inclusion Body Myopathy associated with Paget’s disease of the bone and frontotemporal dementia (IBMPFD), and subsequently found it to be associated with mutations in the valosin-containing protein (VCP) gene (Watts, Nature genetics 2004). A knock-in VCP mouse model of IBMPFD (R155H) developed by this group exhibited muscle, bone and brain pathology characteristic of the human disease, including TDP-43 positive inclusions (Badadani, PLoS One. 2010). Recent studies have extended the list of diseases associated with VCP mutations to include ALS (Johnson, Neuron 2010). We have thus undertaken studies of spinal cord pathology in heterozygous R155H mice. Preliminary examinations of 18–24 month old R155H mice show degenerative changes in ventral horn motor neurons (MNs), and increased astrocyte activation. In addition, we find evidence for TDP-43 positive cytosolic inclusions in many damaged MNs. These studies suggest that the R155H VCP mouse may provide a valuable new animal model for ALS, Heterozygous deletion of PMP22 causes hereditary neuropathy with liability to pressure palsies (HNPP) with a pathological hallmark of tomacula. Because p21-activated kinase (PAK1) regulates polarized membrane extension of cells, we have tested a hypothesis whether the PAK1 plays a role in the formation of tomacula. The pmp22þ/À mouse of HNPP was crossbred with pak1 knockout mice (pak1À/À) to generate double-knockouts. The sciatic nerves at the age of one month were analyzed by teased nerve fiber study. The percentages of paranodes with tomacula was 29 6 19% in pak1þ/þ/pmp22þ/À mice (n ¼ 6) vs 9 6 10% in pak1À/À/pmp22þ/À mice (n ¼ 8), which was statistically significant (p<0.05). Moreover, we tested permeability of tomaculous membrane by incubating sciatic nerves (total 10 mice) with a fluorescent dye (wt ¼ 332kd; Sigma). Fluorescence was visible in about a half of paranodal tomacula of pmp22þ/À nerves (4 mice), but absent in all paranodes of 55 ID: senthilk I Black Lining: [ON] I Time: 08:46 I Path: //xinchnasjn/01Journals/Wiley/3b2/ANA#/Vol00000/110244/APPFile/JW-ANA#110244 J_ID: ZAY Customer A_ID: SUPP11-6 Cadmus Art: 22579 Date: 31-August-11 Stage: Page: 56 which reproduces key aspects of human disease, including the presence of MN cytosolic aaggregates, and pronounced astrocytic as well as MN pathology. Study supported by: NIH grant NS36548 M808. Novel Demonstration of ConformationallyModified Tau in Sporadic Inclusion-Body Myositis (sIBM) Muscle Fibers. Possible Importance to s-IBM Pathogenesis Anna Nogalska, Carla D’Agostino, King W. Engel and Valerie Askanas; Los Angeles, CA M806. Reevaluating Disease Progression in Facioscapulohumeral Dystrophy Jeffrey M. Statland*, William B. Martens, Kathryn R. Wagner, John Kissel, Shree Pandya, Michael P. McDermott and Rabi Tawil; Rochester, NY; Baltimore, MD and Columbus, OH Molecular phenotype of s-IBM muscle fibers, the most common myopathy of older persons, has similarities to Alzheimer-disease (AD) brain, including intra-muscle-fiber accumulations of Ab42 and its oligomers, and large clusters of paired-helical filaments (PHFs) immunoreactive with various antibodies recognizing phosphorylated tau (p-tau). In AD brain, conformational changes of tau, including its modifications detectable with specific antibodies TG3, Alz50 and MC1, are early and important modifications leading to tau’s abnormal folding and assembly into PHFs. We have now identified conformationally modified tau (ctau) in 13 s-IBM muscle biopsies by a) light-and electronmicroscopic immunohistochemistry, b) immunoblots, and c) dot-immunoblots, using TG3, Alz50 and MC1 antibodies. Interestingly, in the very atrophic degenerating fibers, TG3 co-localized with PHF-1 antibody recognizing p-tau, considered a later change in the PHFs formation; however, most of TG3-positive inclusions in non-atrophic fibers were PHF-1 immunonegative. None of the 12 disease- and normal-control muscle biopsies contained c-tau or PHF-1 immunoreactive tau. This first demonstration of c-tau in sIBM suggests that, because of its abundance in non-atrophic muscle fibers, c-tau might play an early role in s-IBM PHF formation and thus be pathogenically important. Study supported by: MDA Background: Recent breakthroughs in the molecular pathophysiology of Facioscapulohumeral dystrophy (FSHD) have identified potential therapeutic targets. Consequently, an accurate understanding of disease progression in FSHD is crucial for the design of future clinical trials. Methods: Data from 164 subjects in 2 negative clinical trials and 1 natural history study were combined to examine disease progression in FSHD. All studies utilized the same techniques for manual muscle testing (MMT) and quantitative myometry (QMT). Both techniques yield a total strength score that can be followed over time as an indicator of disease progression. Results: Whereas, natural history data showed a statistically significant decrease in strength by both QMT and MMT at 1 year, combined data from all 3 studies demonstrated a reduced estimate of loss of strength for both techniques at 1 year, which was no longer significant for QMT. Comparing natural history to combined clinical trial data suggested this reduced estimate of disease progression was due to a placebo effect, most noticeable at 6 months. Conclusions: Contrary to estimates based only on natural history data, treatment durations of longer than 1 year will be required to demonstrate arrest of disease progression in future FSHD therapeutic trials. M809. Anti-Ganglioside Antibodies Mimic CNS Inhibitors of Axon Regeneration Kazim Sheikh and Gang Zhang; Houston, TX Anti-ganglioside antibodies (Abs) are strongly associated with axonal forms of Guillain Barre´ syndrome (GBS). Several studies indicate that GBS patients with anti-ganglioside Abs directed against GM1, GD1a, or ganglioside complexes have poor prognosis and/or incomplete recovery. We recently demonstrated that experimental monoclonal and GBS patient derived anti-ganglioside Abs can inhibit regeneration of injured axons in an animal model suggesting that Ab-mediated inhibition of nerve repair is one mechanism of delayed recovery. We have now established motor and sensory primary neuronal culture models to examine the cellular and molecular mechanisms of this Ab-mediated inhibition of axon regeneration. We found that GBS patient’s anti-ganglioside Abs can inhibit neurite outgrowth in primary neuronal cultures. This Ab-mediated inhibition of neurite outgrowth involves the activation of small GTPase RhoA and downstream effector ROCK pathway and this activation is through the engagement of specific cell surface gangliosides by Abs. In summary, these studies directly link patient autoantibodies to an intracellular inhibitory signaling pathway that is also central to inhibitory signaling induced by almost all CNS inhibitors of axon regeneration. Our results support the hypothesis that specific anti-ganglioside Abs mimic intracellular signaling induced CNS inhibitors of axon regeneration. Study supported by: NIH/NINDS M807. Dysferlin (DYSF) Is Absent from the Muscle-Fiber Sarcolemma in Various Neuromuscular Diseases, and in Sporadic Inclusion-Body Myositis (s-IBM) It Forms Cytoplasmic Inclusions Colocalizing with Amyloid-b42 (Ab42) Mafalda Cacciottolo, Anna Nogalska, Carla D’Agostino, W King Engel and Valerie Askanas; Los Angeles, CA DYSF is a transmembrane protein participating in muscle plasmalemma repair. In normal human biopsies, DYSF is present at the muscle-fiber sarcolemma. In dysferlinopathies – autosomal-recessive muscle diseases caused by mutations in the DYSF gene – DYSF is immunohistochemically absent from the sarcolemma, and is absent or prominently decreased by immunoblots. Immunohistochemically-absent DYSF at the sarcolemma is sometimes considered ��diagnostic’’ of dysferlinopathies. However, sarcolemmal absence of DYSF, and a cytoplasmic ��neolocalization’’, was previously reported in some sarcoglyconopathies and DMD patients. We now report absence of DYSF at the sarcolemma of virtually all muscle fibers of 4 ALS, 4 peripheral neuropathy, 5 s-IBM, and 1 polymyositis biopsies. In s-IBM, vacuolated, very abnormal muscle fibers often had DYSF-immunoreactive cytoplasmic inclusions that colocalized with Ab42. Four age-matched controls had normal sarcolemmal DYSF distribution. By immunoblots, DYSF levels were comparable in all biopsies. Thus: a) immunolocalization of DYSF cannot be a diagnostic criterion of dysferlinopathy; b) Ab42 might be a novel binding partner of DYSF, and in that complex DYSF might contribute to the s-IBM pathogenesis. Study supported by: MDA M810. Evaluating Mechanoreceptors in Glabrous Skin in Diabetic Neuropathy Iliza Myers, Kay Artibee, Jun Li and Amanda C. Peltier; Nashville, TN 56 ID: senthilk I Black Lining: [ON] I Time: 08:46 I Path: //xinchnasjn/01Journals/Wiley/3b2/ANA#/Vol00000/110244/APPFile/JW-ANA#110244 J_ID: ZAY Customer A_ID: SUPP11-6 Cadmus Art: 22579 Date: 31-August-11 Meissner corpuscles (MCs) and their myelinated afferents are found only in glabrous skin. We hypothesized that alterations in MCs occur in diabetic neuropathy and correlate with other measures of axonal loss. Immunohistochemistry was performed on 2 and 3 mm skin punches from the index finger and distal leg, respectively. Four diabetic patients (ages 45–75), with neuropathy confirmed by exam and nerve conduction studies and four control patients (aged 35–50), were studied. Average Meissner corpuscle density (MCD) in control patients was 15.3 6 7.1 MCs/ mm2 with significant reductions observed in two patients (3.3, 6.2 MCs/ mm2) with near normal or higher density in two other patients (11.1, 28.1 MCs/mm2), suggestive of proliferation. MCs in diabetics often displayed abnormal morphology. Density of intrapapillary myelinated endings (IME) correlated with MCD in all patients (r ¼ 0.97). Diabetic patients’ intraepidermal nerve fiber density (IENFD) in the distal leg was 4.2 6 5.9 fibers/mm, compared to 13.7 6 1.3 in controls. IME density did not correlate with IENFD, suggesting that these populations of fibers are independently affected by hyperglycemia. Glabrous skin biopsies afford evaluation of mechanoreceptors which are important in studying pathophysiology of diabetic neuropathy. Study supported by: Supported by NINDS K23 NS056009 (A.C. P.), NINDS R01NS066927-01(J.L.), Vanderbilt CTSA grant 1 UL1 RR024975. Stage: Page: 57 ALS patients. Methods: Fifteen patients with definite or probable ALS fulfilled the El Escorial revised criteria, and 15 age- and sex-matched controls underwent cervical cord 1HMRS. A volume of interest with dimensions of approximately 6.0Â8.0Â40.0 mm (19.2 mL) was located along the main axis of C1-C3 cord on T2-weighted images. N-acetyl-aspartate (NAA), choline-containing compounds (Cho), creatine plus phosphocreatine (Cr) and myo-Inositol (m-Ins) were determined. ALS functional rating scale (FRS) and forced vital capacity (FVC) were assessed monthly. Electromyography was performed. Results: NAA/Cr was decreased significantly (p<0.05) and m-Ins/Cr was increased significantly (p<0.05) in ALS patients compared to controls. NAA/m-Ins was associated with decline of FRS score and FVC, and electromyogram, including ongoing denervation and reduced amplitudes of compound muscle action potential in the limb muscles. Conclusion: Our data indicated significant changes of NAA/Cr and m-Ins/Cr in the cervical cord. Significant relationships were found between NAA/m-Ins, clinico-respiratory deterioration and axonal damages on electromyography. Thus, cervical cord 1H-MRS could have benefits for a predictive marker of disease progression in ALS patients. M813. Localization of FIG4 in the Nervous System Jiasong Guo, Qing Yan and Jun Li; Nashville, TN Recessive mutations of FIG4 cause CMT4J with a phenotype resemble amyotrophic lateral sclerosis. Localization of FIG4 in the nervous system remains unknown. We have investigated this issue in rats. FIG4 expression in the CNS was robust embryonically by western blot but low in the adulthood. Using immunohistochemistry at P7-20, FIG4 was localized in cortical/spinal neurons, but hardly detectable in astrocytes. By P30, FIG4 immunoreactivity declined to a minimal level; however, was still conspicuous in the myelin (oligodendrocytes and Schwann cells) and sensory neurons of dorsal root ganglion. For the sub-cellular localization, FIG4 signals appeared to be partially overlapped with late-endosomes/lysosomes, but not overlapped with mitochondria, Golgi complex, early endosome or endoplasmic reticulum. Taken together, these findings are in line with our recent study that has demonstrated prominent vacuolated endo-/lysosomes in the sensory neurons and abnormal lysosomal storage in the spinal motor and cortical neurons in FIG4 null mice (Katona et al, EJN 2011). Study supported by: MDA and VA RR&D M811. Amiodarone Associated Myopathy. A Report of 4 Cases Eoin P. Flanagan, Charles M. Harper, Erik K. St. Louis, Michael H. Silber, Ronald C. Petersen and Keith A. Josephs; Rochester, MN Myopathy is a known side effect of amiodarone. However, the characteristic features and outcome are not widely known. We identified 4 patients from 1996 – 2010 at our institution with electrophysiologically confirmed myopathy and a final diagnosis of presumed amiodarone induced myopathy. The median age was 71 years (range, 67–75) and all had an insidious onset. Initial presenting symptoms included: lower extremity weakness, 3; and swallowing difficulty, 1. Amiodarone was begun a median time of 20.5 months (range, 1–36) before symptom onset. Laboratory features included elevations in: creatine kinase, 2; myoglobin, 2; and aldolase, 1. EMG demonstrated short duration motor unit potentials in proximal muscles in all four patients and features of myonecrosis were seen in two. Muscle biopsies performed in two patients demonstrated severe necrotic myopathy with tubular aggregates in one and vacuolated atrophic fibers in the other. All 3 patients with follow up available improved after discontinuation of amiodarone, but in two the recovery was prolonged (>6 months) and incomplete. Amiodarone induced myopathy appears to affect mostly proximal muscles with variable electrophysiological and pathological findings. Discontinuation of amiodarone is associated with improvement, but recovery may be prolonged and incomplete. M814. High Frequency Chest Wall Oscillation (HFCWO) in Amyotrophic Lateral Sclerosis (ALS) Patients Decreases Respiratory Infections Requiring Antibiotics and/or Hospitalization: A Pre-Post Observational Study Benjamin R. Brooks, Velma L. Langford, Amber L. Ward, Nicole M. Williams, Mindy S. Nichols, Elena Bravver and Scott C. Lindblom; Charlotte, NC Background: Respiratory care in ALS patients with increasing restricted pulmonary function requires attention to clearing pulmonary secretions. Lange, et al., 2006 demonstrated respiratory function improvement but did not show an effect of HFCWO on infection rate. Objective: To evaluate in an ALS Clinic setting whether there is a decrease in the prevalence of infections requiring antibiotics and/or hospitalization following HFCWO. Methods: The prevalence of infections was calculated retrospectively for the period from ALS diagnosis to and prospectively from the point of initiating HFCWO in ALS patients based on vital capacity and clinical respiratory M812. Cervical Cord 1H-Magnetic Resonance Spectroscopy (1H-MRS) in Amyotrophic Lateral Sclerosis (ALS): Relationship to Clinoco- Electrophysiological Dysfunction Ken Ikeda, Yasuhiro Yoshii, Kiyoko Murata, Riya Nagata, Kiyokazu Kawabe, Osamu Kano and Yasuo Iwasaki; Tokyo, Japan Background: To examine whether clinico-electrophysiological aspects are related to spinal cord dysfunction on 1H-MRS in 57 ID: senthilk I Black Lining: [ON] I Time: 08:46 I Path: //xinchnasjn/01Journals/Wiley/3b2/ANA#/Vol00000/110244/APPFile/JW-ANA#110244 J_ID: ZAY Customer A_ID: SUPP11-6 Cadmus Art: 22579 Date: 31-August-11 parameters. Mean infection rate 6 standard deviation(SD)before and after HFCWO was compared with paired, unpaired two-tailed t-tests and Wilcoxan rank tests. Results: ALS patients[36]patients pre-HFCWO had 0.07 6 0.13(SD)infections/month which reduced to 0.02 6 0.06 infections/[t test p ¼ 0.0638; Wilcoxon ranked test p ¼ 0.0415]. Compliance in each patient compared well with the mean national compliance assessed by Hill-Rom in neuromuscular disease. Conclusion: HFCWO significantly reduces the perpatient infection rate in ALS patients. Observational studies employing pre-post-intervention design can provide important clinically meaningful information supporting certain respiratory interventions in ALS patients. Study supported by: Carolinas ALS Research Fund of the Carolinas Healthcare Foundation and Hill-Rom Stage: Page: 58 weekly, continuing for 6 yrs, arrested progression and sustained partially-improved strength, breathing and swallowing. In 3/10, added rituximab, 375mg/m2 q2wksx4 loading, plus q12-6wks maintenance, produced further increased strength, regained ability to walk independently 150ft, climb stairs, turn in bed, shower standing, and drive a car. This benefit from the continuing IVIG-plus-rituximab therapy emphasizes treatability of the AORMS and suggests a dysimmune pathogenesis. His concurrent CIDP-like aspect may be relevant to his beneficial response. (Interestingly, experimentally, tenotomy can produce rods (Engel et al, �66).) M817. Geographic Trends of ALS in Minnesota Eric J. Sorenson and Lisa Kronk; Rochester, MN and Minneapolis, MN Background: This study examined geographic trends of ALS across Minnesota and assessed the completeness of ALS case ascertainment within the ALS association’s database (Minnesota/North Dakota chapter). Methods: The ALS association’s database was queried for deaths during 2009 in Minnesota with the county of residence recorded for each. 2009 census data was recorded for each Minnesota county with an incidence rate calculated for each county and for Minnesota overall. A chi-squared analysis compared incidence rates among the 88 counties. Results: 97 deaths occurred from a population of 5,266,203, giving an incident rate of 1.8 cases per 100,000 person-years (95% CI from 1.5 to 2.2). This agreed with incidence rates from Olmsted County of 1.7 per 100,000 person-years suggesting that the ALS Association’s database has near complete case ascertainment throughout Minnesota. County incidence rates varied from 0 to 12.7 per 100,000 person-years. However, comparison across counties failed to demonstrate any significant differences (p ¼ 0.42). Conclusions: No significant geographic trends were identified among the counties in Minnesota suggesting the clustering of cases in some counties is likely due to random case aggregation. The ALS association’s database proved effective at near complete case ascertainment in the state of Minnesota. Study supported by: ALS Association M815. Dominant Cardiomyopathy and Very Distal Myopathy with Rod, Myofibrillar and AVSF Myopathology Stanley J. Iyadurai, Chris Weihl, Bob Baloh and Alan Pestronk; St. Louis, MO We describe a multigenerational family with a distal myopathy with unusual features. The syndrome segregated by history as a dominantly-inherited disorder with affected family members of both sexes. Four affected patients without cardiac pacing died before age 40. Two affected patients with cardiac pacing were examined in their fifth decade. Symmetric weakness was most severe in intrinsic muscles of the hands and feet, averaging less than 10% of normal. Intrinsic muscles of the hands and feet were severely atrophic. Proximal muscle strength was normal. Tendon reflexes and sensation were normal. Serum CK was less than 250. EMG revealed a distal-predominant, irritable myopathy. Nerve conduction studies were normal. Muscle ultrasound showed a distal myopathy involving the hands and legs. Muscle biopsy showed varied fiber size, splitting, rods, desmin aggregates, and vacuoles containing granular debris with rims staining for sarcolemmal proteins, including dystrophin, sarcoglycans and caveolin. Distinctive features include very distal weakness and wasting, early sudden death, and myopathology with rods, myofibrillar changes in addition to AVSFs. Genotyping will be required to further define the identity of this distal myopathy syndrome. Study supported by: Department of Neurology and Psychiatry, Saint Louis University, St. Louis, MO. M818. Clinical Features Associated with Fine Specificity of IgG Anti-GQ1b Antibodies Susumu Kusunoki, Seiko Suzuki, Masami Ueda and Motoi Kuwahara; Osaka-Sayama, Osaka, Japan M816. Adult-Onset Rod Myopathy Syndrome (AORMS): Sustained Benefit from IVIG Plus Rituximab Shalini Mahajan, King W. Engel, Valerie Askanas, Indermohan Luthra and Varun Gupta; Los Angeles, CA and Rancho Mirage, CA Anti-GQ1b IgG antibodies are present in most cases of Fisher syndrome (FS), Bickerstaff brainstem encephalitis (BBE), and Guillain-Barre´ syndrome (GBS) with ophthalmoplegia. Anti-GQ1b antibodies frequently bind to GT1a, but the relative binding activities with the GQ1b and GT1a antigens vary. Some anti-GQ1b antibodies have higher activity against a mixture of GQ1b and phosphatidic acid (GQ1b/PA). We investigated anti-GQ1b IgG-positive cases including FS (n ¼ 197), BBE (n ¼ 20), GBS (n ¼ 78) and atypical FS (n ¼ 52) to see whether diversity in the fine specificity of IgG anti-GQ1b antibodies is related with variations in clinical features. Higher antibody activity with GQ1b compared to GT1a (GQ1b>GT1a) was significantly more frequent in BBE and FS than in GBS (p<0.01), and higher antibody activity with GQ1b compared to GQ1b/PA (GQ1b>GQ1b/PA) was significantly more frequent in BBE than in FS (p<0.01). A significantly higher anti-GT1a antibody titer and rate of GT1a>GQ1b were found in patients with bulbar palsy (p<0.01). The anti-GQ1b/PA antibody AORMS (Engel WK,’66), is a rare, progressive, myopathy associated with intrafiber rods, often monoclonal gammopathy (MG), 6 dysschwannian neuropathy, and often fatal. Patients were unresponsive to anti-dysimmune therapies, including rituximab (Keller CE,’06). We report successful treatment of a 55yr old AORMS patient. Before treatment, he had for 1yr, sub-acute, progressively severe proximal limb and neck weakness, and dysphagia. Tendon reflexes were absent, vibratory and pinprick sensations decreased. Serum: IgG-kappa MG, normal CK. CSF: protein elevated, 59/45. NCVs: dyschwannian (demyelinating) neuropathy. EMG: fibrillations and brief small abundant motor-units. Muscle biopsy: groups of trichrome-red intrafiber rods, and a few small angular fibers. Rx: IVIG, 0.4 gm/kg infusions twice- 58 ID: senthilk I Black Lining: [ON] I Time: 08:46 I Path: //xinchnasjn/01Journals/Wiley/3b2/ANA#/Vol00000/110244/APPFile/JW-ANA#110244 J_ID: ZAY Customer A_ID: SUPP11-6 Cadmus Art: 22579 Date: 31-August-11 titer was significantly higher in patients with ophthalmoplegia (p<0.01) and in those with ataxia (p<0.01). Thus, the fine specificity of IgG anti-GQ1b antibodies may be associated with clinical features in each patient. Stage: Page: 59 screening (including Sjogren’s and anti-ganglioside antibodies) was uninformative. Electrophysiology revealed motor neuronopathy involving 3–4 body segments and sensory neuropathy. Blink reflexes in four and autonomic testing in two were abnormal. In 3 patients, nerve biopsies showed non-specific axonal degeneration/regeneration. Four patients failed immunotherapy. One autopsy examination revealed loss of spinal motor neurons. This disorder, distinct from sporadic bulbar-onset ALS resembles FOSMN, but with dementia and/or chorea. We are applying new genomics tools to study this unique patient group. Study supported by: National Institues of Health (NIH)Intramural Program M819. Amyotrophic Lateral Sclerosis [ALS] Dashboard: Cognitive, Behavioral, Bulbar, Respiratory, Arm, Leg Domain-Specific Disease Staging – Statistically Significant Larger Proportion of !Stage 3 Behavioral, Bulbar, Arm and Leg, but Not Cognitive or Re Benjamin R. Brooks, Mohammed S. Sanjak, Elena Bravver, William L. Bockenek, Urvi G. Desai, Scott C. Lindblom, Thomas J. Paccico, Nicole M. Williams, Mindy S. Nichols, Amber L. Ward, Kathryn A. Wright, Mifflin O’Neill, Velma L. Langford, Kristy Walgren, Priscilla Russo, Anne Blythe and Heather Oplinger; Charlotte, NC M821. Update on a Phase 1 Study of ISIS 333611 in Familial ALS Due to SOD1 Mutations Timothy M. Miller, Richard Smith, Swati Aggarwal, Alan Pestronk, William David, Jeffrey Rothstein, Ericka Simpson, Benjamin Brooks, Isaac Bakst, Patricia Andres, Peggy Allred, Katie Alexander, Kathie Bishop, C.F. Bennett and Merit Cudkowicz; St. Louis, MO; La Jolla, CA; Boston, MA; Baltimore, MD; Houston, TX; Charlotte, NC and Carlsbad, CA Background: ALS Dashboard is a new tool for analyzing disease severity within a single patient and across different patients defining involvement over 6 domains on a per patient basis. Methods: ALS patients [199/263] at first clinic visit were categorized as El Escorial Criteria clinically definite (EECD) only [90] or Awaji clinically definite only (AwCD) [109] and staged according to the ALS Dashboard criteria. Comparisons of !stage 3 disease in each domain by EECD/ AwCD criteria were conducted by chi-square test with Yates correction and confirmed with Fisher’s exact test. Results: At first clinic visit in EECD/AwCD ALS !stage 3 cognitive disease was similar [8.9%/13.8%; p ¼ 0.3968], ! stage 3 pseudobulbar affect [11.1%/2.8%; p ¼ 0.0369], !stage 3 depression [25.6%/10.0%; p ¼ 0.0070], !stage 3 bulbar dysfunction [45.6%/13.8%; p ¼ 0.0001], !stage 3 arm dysfunction [35.6%/8.3%; p ¼ 0.0001], !stage 3 leg dysfunction [55.6%/33.9%; p ¼ 0.0036]were statistically significantly increased and !stage 3 respiratory dysfunction was identical [7.8%/4.6%; p ¼ 0.5209]. Conclusions: Disease severity in some domains, segregates differently with a higher proportion of !stage 3 disease in EECD ALS. The proportion of !stage 3 disease ranks similarly: leg >arm >bulbar >depression >pseudobulbar affect. Study supported by: Carolinas ALS Research Fund of the Carolinas Healthcare Foundation Objective: To evaluate the safety, tolerability, and pharmacokinetics of intrathecal infusion of ISIS 333611, an antisense oligonucleotide inhibitor of SOD1 mRNA. Background/Methods: Mutations in SOD1 cause 20% of familial ALS. In animal models, ISIS 333611 distributed widely in the brain and spinal cord, decreased SOD1 mRNA, and prolonged survival. A randomized, placebo controlled Phase 1 safety trial of ISIS 333611 is underway. In Cohort 1, ISIS 333611 (0.15 mg) was infused intrathecally over 12 hours in 6 SOD1-positive ALS patients (2 patients received vehicle control). Safety measures and neurological exams were assessed during the infusion and after 1, 8 and 29 days. CSF and plasma drug levels were measured. This completes 1 of 4 cohorts, each with increasing dose and similar active:placebo ratio. Results: No serious adverse events occurred and common adverse events are consistent with procedure-related findings. Changes in neurological exams are consistent with ALS. CSF and plasma drug levels are consistent with levels predicted from preclinical studies. An update on the SOD1 antisense program will be provided. Conclusion: In Cohort 1, ISIS 333611 was well tolerated and CSF drug levels are as predicted. Study supported by: ALS Association, Muscular Dystrophy Association, Isis Pharmaceuticals M820. A New Phenotype in Neurodegeneration: Trigeminal Sensory Deficits Preceding Rostro-Caudal Progressive Motor and Sensory Neuronopathy, Chorea and Dementia Camilo Toro, Justin Y. Kwan, Tanya J. Lehky, Bryan J. Traynor, Catherine A. Groden, Rena A. Godfrey, Michele E. Nehrebecky, Wiggs A. Edythe and Gahl William; Bethesda, MD M822. Retrospective Analysis of a Cohort of Non Systemic Vasculitic Neuropathy Raghav Govindarajan, Jagadish B. Agadi, Anita Mahadevan and S.K. Shankar; Weston, FL and Bangalore, India We describe five adults with a slowly progressive bulbaronset ALS like phenotype but preceded by trigeminal sensory symptoms, with or without late development of chorea and dementia. Age of onset was 53–69 years; disease duration was 5–12 years. Three women and two men experienced facial/oral sensory disturbance involving the unilateral infra-orbital area (3), tongue, or lips 6–18 months before bulbar motor deficits. At evaluation, all had impaired cornea reflexes, facial/ oral hypoesthesia or anesthesia extending to posterior scalp plus truncal and shoulder weakness, while lower limb strength was relatively preserved. Three patients had frontotemporal dysfunction and two had chorea. Neuroimaging, CSF examinations, metabolic, toxic and immunological Background: Nonsystemic vasculitic neuropathy (NSVN) is an infrequent neuropathy without systemic manifestations. Only few studies have reported the clinicopathologic spectrum. Fewer have looked into the treatment aspects. Methods: Nerve biopsies done over 10 years were reviewed. Patients who met criteria for NSVN at time of diagnosis and in whom 6 month follow-up was available were included. They were treated with steroid therapy (ST) or with steroids and azathioprine-combination therapy (CT). Independent T-tests were performed for age, duration of symptoms prior to therapy and improvement in Prineas 59 ID: senthilk I Black Lining: [ON] I Time: 08:46 I Path: //xinchnasjn/01Journals/Wiley/3b2/ANA#/Vol00000/110244/APPFile/JW-ANA#110244 J_ID: ZAY Customer A_ID: SUPP11-6 Cadmus Art: 22579 Date: 31-August-11 disability score (PDS) between groups. Differences between pre and post-therapy PDS within groups were analyzed by paired T-tests and Chi-Square. Results: 21 cases were in the series with 12 males and 9 females.Sensori-motor asymmetric axonopathy was seen in 71%. Biopsy showed microvasculitis in 52%. 12 were treated with ST, 7 with CT,2 opted out. CT was superior in improving disability (1.57 vs. 1.08 p < 0.05). CT was 14 times more likely to improve PDS by more >2 units (p ¼ 0.01). The percentage of improvement did not significantly differ between them (paired T-test 50% vs.42% p ¼ 0.37). Conclusion: NSVN is an asymmetric sensory predominant axonopathy. Combination therapy may be superior to steroids alone in improving disability. Stage: Page: 60 gene protein level from ALS muscles showed no obvious difference compared to controls. Conclusions: The up-regulation of the above genes in the muscles of ALS patients relative to MMN and controls discovered previously by our microarray analysis is reproducible and statistically significant. Further studies are necessary to evaluate the identified genes in larger patient groups and different tissues. Study supported by: This work was supported by grants from the Muscular Dystrophy Association and the Horace Havemeyer Neuromuscular Research Fund. M825. Small-Fiber Polyneuropathy (SFPN) Can Cause Chronic Pain and Somatic Complaints in Youth and Anne Louise Oaklander; Boston, MA M823. Optimizing a Hospital Discharge Database for Passive Surveillance of Guillain-Barre Syndrome (GBS) Christopher D. Lee and Timothy F. Jones; Nashville, TN Patients with unexplained diffuse pain and multisomatic complaints are enigmatic and hard to treat, with pediatric cases especially concerning. An index youth with chronic pain from steroid-responsive SFPN prompted record analysis from 41 consecutive young patients with widespread pain and/or multisomatic complaints; age-matched volunteers provided controls. Age of onset averaged 13y; 73% were female. Most were seriously ill; 71% were hospitalized and 1 died. Half reported preceding injuries or infections. 29% had other autoimmune illnesses. 98% had chronic pain and 98% had somatic symptoms, often cardiovascular and/or gastrointestinal. Abnormal fatigue, headaches, and sweating each affected more than half. Sensory abnormalities were present in 71% and erythromelalgia in 28%. 94% of 33 autonomic-function tests were abnormal, 6% borderline, and most skin (25) and 2/2 nerve biopsies implicated SFPN. Etiologic testing spotlighted only immune markers (in 86%). Many symptoms became manageable once explained as neuropathic. Corticosteroids or IVIG helped 70% of 14 treated. This characterizes a disabling illness, juvenile-onset SFPN, sometimes caused by organ-specific autoimmunity. This verifiable and treatable diagnosis merits consideration in youngsters with syndromes of widespread pain and multisystem complaints, eg fibromyalgia, chronic fatigue, POTS, and seronegative Lyme. Study supported by: NINDS, Dept. of Defense, Bradley family foundation, Curvey family foundation The 2009–2010 H1N1 pandemic influenza immunization program prompted a nationwide active surveillance effort to determine the risk of GBS following vaccination. Active surveillance is unsustainable in the long-term. Therefore, we sought to optimize a statewide hospital discharge database to evaluate its utility for GBS surveillance, compared to active surveillance data. We examined data from all patients discharged from Tennessee hospitals with an ICD-9 code for GBS, from 2000– 2010. A total of 2659 cases with Tennessee residency were identified. Of these, 1098 (41%) were excluded due to a prior hospitalization with a GBS diagnosis in the database. Annual incident cases ranged from 143 to 161 (mean adjusted incidence calculated as 1.41 per 100,000 individuals). Variation in annual case tallies was significantly narrowed with this method, compared to aggregate ICD-9 totals. We calculate capability of detecting an increase in GBS cases with an effect size of 1.20. Sensitivity compared to active surveillance was 0.81. Positive predictive value was 0.45. Although incidence calculations are overestimated, an optimized hospital discharge database shows low variation and is capable of detecting small increases in GBS cases. Such a database can be useful for long-term surveillance. M824. Gene Expression Analysis in Patients with Amyotrophic Lateral Sclerosis and Multifocal Motor Neuropathy Alexander Shtilbans, Soon Gang Choi, Mary E. Fowkes, Greg Khitrov, Mona Shahbazi, Jess Ting, Stuart C. Sealfon and Dale J. Lange; New York, NY M826. Median Nerve Ultrasound in Diabetic PN with and without Carpal Tunnel Syndrome Anhar Hassan, Andrea Leep Hunderford, James Watson, Andrea Boon and Eric Sorenson; Rochester, MN Background: Gold standard diagnosis for carpal tunnel syndrome (CTS) is nerve conduction study (NCS). However sensitivity decreases in peripheral neuropathy (PN). Ultrasound detects median nerve enlargement but its utility in coexistent PN is unknown. Methods: Case-control study enrolling diabetic PN patients (NCS-proven) referred to our EMG lab, with or without clinical symptoms of CTS. Demographics, CTS symptom score, median and ulnar NCS are recorded and correlated with blinded median and ulnar nerve ultrasound cross-sectional areas (CSA). Results: Full data to be presented. Six patients (100% male; 2 cases, 4 controls) are enrolled so far: age 50.5 years (range 35–68), with diabetes duration 106.5 months (10– 300) and PN 13.5 months (0–93). Median nerve CSA was significantly larger (p ¼ 0.03) in CTS cases, and median antidromic sensory distal latency was significantly prolonged (p ¼ 0.04). There was no significant difference in diabetes Objectives: To confirm the previously identified gene expression pattern in muscles from patients with Amyotrophic lateral sclerosis (ALS) and multifocal motor neuropathy (MMN) compared to controls. Methods: RNA extracted from skeletal muscles of 3-ALS, 3-MMN and 3-control patients were subjected to RT-PCR confirmation analysis based on the previously published genome-wide microarray gene expression data (Shtilbans et al, Ann Neurol.,2009). Four additional ALS patients and four new controls were also used. Results: Validation analysis of the most significant expression pattern differences confirmed our previous microarray data for leucine-rich repeat kinase-2 (LRRK-2), follistatin, collagen type XIX alpha-1, ceramide kinase-like and sestrin3 which were overexpressed only in the ALS group. CXorf64 was increased in ALS and decreased in MMN compared to controls. Western blot analysis of LRRK-2 60 ID: senthilk I Black Lining: [ON] I Time: 08:46 I Path: //xinchnasjn/01Journals/Wiley/3b2/ANA#/Vol00000/110244/APPFile/JW-ANA#110244 J_ID: ZAY Customer A_ID: SUPP11-6 Cadmus Art: 22579 Date: 31-August-11 (p ¼ 0.13) or PN duration (p ¼ 0.16); neurophysiologic PN severity (p ¼ 0.18); median motor (p ¼ 0.14) or sensory palmar NCS (p ¼ 0.05). Conclusions: In diabetic patients with peripheral neuropathy, median nerve CSA appears significantly enlarged with coexistent clinical CTS. If findings are confirmed, median nerve ultrasound may be a useful addition to NCS. Stage: Page: 61 Conclusion: In our study there were no significant benefits to MRN over EMG in radiculopathy diagnosis. M829. Denervation Causes Lower Expression of Heat Shock Protein 27 in Regenerating Skeletal Muscle Takahiro Jimi, Yoshihiro Wakayama and Hajime Hara; Yokohama, Japan We have studied changes of gene expression in denervated skeletal muscles and found a remarkably increased expression of genes relating to quality control. Denervation results in the incomplete regeneration of skeletal muscles. So we examined the mRNA expression of heat shock protein 27 (HSP 27) in regenerating rat muscles in innervated and denervated conditions. We made rat regenerating muscles by injection of bupivacaine in both extensor digitorum longus (EDL) muscles. At the same time of injection, right sciatic nerve was removed. At 1, 2, 4, and 6 weeks after surgery, both EDL muscles were excised from five rats. The concentrations of HSP 27 mRNA were estimated by real-time PCR analysis. The mRNA level in the innervated condition was rapidly increased (ten times) at 1 week after surgery, and gradually decreased to the original level, whereas the increase in the denervated condition was mild (four times) and delayed (at two weeks). Thus, we speculated that denervation causes some effects on the regeneration of skeletal muscles, and the lower expression of proteins relating to quality control may be involved in the incomplete regeneration under denervation of skeletal muscle. M827. Subacute Paraneoplastic Motor Neuronopathy with Ri Immunoeactivity and Breast Cancer: A Clinicopathologically Studied Patient and David S. Younger; New York, NY A 49 year old woman had fatigue, cramps, and leg twitching in February 2010, four months before noting a breast mass. Lumpectomy in June 2010 showed stage II invasive ductal breast cancer, and estrogen and progesterone receptor positivity. Examination showed leg weakness, atrophy, and widespread twitching. Initial EMG/NCS showed motor predominant polyneuropathy of the legs with demyelinating features and persistent fasciculation. MRI of the brain, spinal cord, and cerebrospinal fluid showed no evidence of metastases. Blood studies showed positive ANNA-2 (Ri) titer 1:7680 from an extensive panel of paraneoplatic autoantibodies. Intravenous immunoglobulin (IVIg) was followed by combination chemotherapy. Followup EMG/NCS showed persistent motor polyneuropathy and fascicuation with resolution of demyelinating features. Prophylactic radiotherapy was well tolerated. She continued to decline whereupon followup EMG/NCS in February 2011showed motor neuropathy with active leg fibrillation and fasciculation. Sural nerve and soleus muscle biopsy were consistent with subacute motor neuronopathy. CSF evidenced Ri immunoreactivity using purified human recombinant antigen and Western blot analysis. Whole body PET/CT showed no evidence of malignancy. This is the first report of subacute motor neuronopathy in association with the Ri (ANNA-2) antibody. M830. Rapid Magnetic Stimulation Versus Conventional Physiotherapy in Bell’s Palsy Devathasan Gobinathan and Lea Dosado; Singapore, Singapore We compared the use of rapid magnetic stimulation (RMS) therapy in 23 subjects with 22 others who elected conventional electrical, muscle stimulation (CS) treatment and acupuncture. All patients had acyclovir for 7 days with varying dose of steroids. After one year the parameters assessed were the strength of frontalis, orbicularis oculis, zygomaticus, orbicularis oris and for autonomic dysfunction–score 2 being normal, 1 partial recovery and 0 no recovery or distressing. Patients did their own scoring. RMS was administered in 1 or 2 sessions ten times or days during the acute phase at 15Hz, 1500 pulses, 5 second pause, 50 in each of 30 trains at strength of 30 to 35A/us. Stimulation sites were at the mastoid and more distally at the facial area over the affected muscles away from the eye globe. Significant difference was noted in favor of RMS ( p < 0.004, t ¼ 7.1, df ¼ 21 mean score RMS ¼ 9.9 and CS ¼ 6.0). High dose steroids may have introduced a bias element in favor of the RMS group as they received much less steroids. Study supported by: NIL M828. Magnetic Resonance Neurography Versus Electromyography for the Diagnosis of Radigulopathy Youssef A. Dakka, Andrew Biondo, John Corrigan, Shehanaz Ellik and Ximena Arcilla-Londono; Detroit, MI Introduction: Evaluation of spinal nerve disorders relies on an accurate history, examination, MRI, MR Neurography and EMG/NCS. The purpose of our study was (a) to determine if MRN could detect radiculopathies earlier than EMG. Methods: Inclusion criteria included adults with cervical radiculopathy, MRN and EMG studies. Exclusion criteria included peripheral neuropathy, muscle disease, diabetes or tumor. Of the 438 patients reviewed, 64 patients were included. Symptoms, time course, MRN/EMG findings and consistency of MRN/EMG results with clinical findings were obtained retrospectively. The patient population was subdivided into males/females and symptom duration < or > 2 months. McNemars test and Generalized Estimating Equation Model were used. Interaction was evaluated at the significance level of 0.10. Results: Differences in agreement between MRN and EMG were 23.5% for females and 6.7% for males. For those with <2 months duration, the difference in agreement between MRN and EMG was 4.7% while for those with > 2 months duration, it was 20.9%. However, because of the small sample size, the power to detect these differences was reduced and they were not statistically significant. M831. Establishing a Rare Disease Center in China: The Periodic Paralysis Program Qing Ke, Benyan Luo, Ming Ming, Michael Hanna, Jacob Levitt, Barbara Herr and Robert C. Griggs; Hang Zhou, Zhe Jiang, China; Rochester, NY; London, United Kingdom and New York, NY Objective: To establish a rare disease referral center in China. Methods: Analyze ways periodic paralysis (PP) patients reached Chinese centers and compare this process with US and UK approaches. 61 ID: senthilk I Black Lining: [ON] I Time: 08:46 I Path: //xinchnasjn/01Journals/Wiley/3b2/ANA#/Vol00000/110244/APPFile/JW-ANA#110244 J_ID: ZAY Customer A_ID: SUPP11-6 Cadmus Art: 22579 Date: 31-August-11 Results: 116 patients were evaluated with PP in two center (Beijing and Hangzhou) from 2003–2009. Only 20% patients were local, the remaining patients traveled distances without referrals from other areas. The deciding factor in seeking care largely depended on patients’ choice. In contrast, at University of Rochester Medical Center, over 90% of patients are referred from physicians throughout the country by virtue of published information concerning physician expertise or on the basis of referrals from a patient advocacy group. In UK, a single center, supported by the National Health Service, provides assessment and genetic testing for all patients in the country. Conclusions: Currently, PP patients in China are practising self-referral to a larger center for medical care. Most of them are evaluated in brief outpatient visits. With the rapid development of computer access and expertise coupled with a website locating one or more centers, patients in the country will be able to identify specific specialty centers. Study supported by: NIH F05NS065682 Stage: Page: 62 signal alteration in left mid anterior spinal cord from C 3C7. Electrodiagnostic testing revealed normal nerve conduction studies. EMG showed positive sharp waves, fibrillation potentials and motor unit action potentials of increased amplitude and duration with reduced recruitment in almost all of the muscles in left upper extremity. Monomelic amyotrophy is a rare disorder presenting with atrophy and weakness restricted to one limb. The benign nature of Monomelic amyotrophy helps distinguish it from other lower motor neuron disorders like ALS. M834. Botulism: A Case Report Peter Struck, Amtul Farheen and Sushanth Bhat; New Brunswick and Edison, NJ A 3 month old boy presented with 15 days of constipation and 5 days of progressive generalized weakness. Parents noted weak cry, poor appetite, lethargy, and generalized muscle weakness. No respiratory or ocular symptoms were reported. No history of sick contacts. The baby was full term, born by c-section but otherwise healthy. On examination facial weakness, weak gag,head lag and diffuse hypotonia were noted. There were no focal motor deficits. Deep tendon reflexes were 1 in bilateral upper extremities and 2þ in lower extremities. Babinski was positive bilaterally. Blood tests including CBC, CMP, UA, Newborn Screen were normal. Motor nerve conduction studies revealed normal conduction velocity, slightly decreased amplitudes. RNS of right median nerve at 3 Hz showed 9 % decrement and at 20 Hz showed 30 % increment. EMG showed fibrillations at rest, short duration low amplitude MUAPs. Stool revealed botulinum toxin. Baby was diagnosed to have botulism and was treated with Baby Botulism Immunoglobulin. After treatment patient was noted to have a stronger cry, improved appetite and improved weakness. The diagnosis of botulism should be considered in infants and children with hypotonia. The detection of toxin in the stool and EMG are diagnostic. M832. Effect of Fatigue on Pulmonary Function Studies in ALS Patients Kathleen S. Alfuth, Ericka P. Simpson and Aparajitha K. Verma; Houston, TX Objective: To measure change in pulmonary function tests (PFTs) as relates to time of day and fatigue in ALS patients. Methods: Cross-sectional cohort study evaluating % change in PFTs from early to late-day and correlation with fatigue severity scale (FSS), disability (ALSFRS-r), bulbar compromise (ALSFRS-r bulbar subscale). PFT measures include forced vital capacity (FVC), maximal inspiratory pressure (MIP), maximal expiratory pressure (MEP) at times T1 and T2 (5–9hrs after T1) in sitting and supine positions. Results: Eight patients were recruited [age 56.9 6 7.9 yrs, 75% female, 25% bulbar onset, FSS 42.3 6 14.7, ALSFRS 35.5 6 8.1, ALSFRS-r bulbar 12.8 6 1.7]. Highest of three recorded attempts were used to calculate average change between T1 and T2. FVCsitting -13% 6 27%; FVCsupine -13% 6 28%; MIPsitting þ7% 6 14%; MIPsupine -9% 6 20%; MEPsitting -3 6 17%; MEPsupine þ7% 6 29%. Correlation analysis showed a trend association with increasing fatigue (FSS) and decrease in MIPsupine (p ¼ 0.13). Conclusion: Preliminary data suggests PFTs in ALS may significantly change from early to late-day and this may correlate with fatigue. This study is ongoing to determine significance of the results and possible impact upon management. Study supported by: Methodist Neurological Institute Employment M835. A Novel Pentameric Thiophene Derivative (pFTAA) Strongly Highlights Clusters of Paired Helical Filaments Containing Phosphorylated Tau in Sporadic Inclusion-Body Myositis (s-IBM) Muscle Fibers There´se Klingstedt, Anna Nogalska, Cristiane Blechschmidt, Stefan Prokop, Frank L. Heppner, King W. Engel, Valerie Askanas and Peter K.R. Nilsson; Linko¨ping, Sweden; Los Angeles and Berlin, Germany p-FTAA is a fluorescent amyloid-specific ligand that can be used for the detection of protein aggregates in vivo as well as pre-fibrillar and fibrillar species in vitro. The probe spectrally discriminate amyloid-beta (Ab) plaques and phosphorylated tau (p-tau)-containing neurofibrillary tangles in Alzheimer’s disease (AD) brain. Muscle biopsies of s-IBM, the most common muscle disease of older persons, have several pathologic similarities with the AD brain, including intra-muscle fiber accumulations of Ab and p-tau-containing clusters of paired helical filaments (PHFs). We now report that in all 6 s-IBM muscle biopsies studied, fluorescence evaluation of p-FTAA staining, using excitation 450–490 nm and emission 520 nm, revealed a strong and specific signal from inclusions positive with AT100 antibody recognizing p-tau and p62 antibody indicating clusters of PHFs. All 12 normal and disease-control muscle biopsies were negative. Our study demonstrates a novel staining method for detection of p-tau inclusions in s-IBM muscle fibers. The quick staining protocol together with the high signal-to- M833. Monomelic Amyotrophy – A Rare Case Presentation Amtul Farheen, Manpreet Multani, Aiesha Ahmed, Raji Grewal and Raji Grewal; Edison, NJ A 26 year-old right handed Indian man presented with weakness and atrophy of the left upper extremity over seven years. He denied pain, numbness, diplopia, dysphagia, ptosis, muscle cramps, fasciculations and neck pain. There was no history of febrile illness, poliomyelitis, and exposure to toxins or heavy metals. On examination there was atrophy of entire left upper extremity and weakness (power of 4/5) of left deltoid, biceps, triceps, and wrist flexion and extension, and hand muscles. Motor exam was normal in other extremities. Sensation and cranialnerve examination were normal. Serum electrolytes, thyroid panel, ESR, CPK, HIV were normal. MRI of C-spine showed vertically oriented 62 ID: senthilk I Black Lining: [ON] I Time: 08:46 I Path: //xinchnasjn/01Journals/Wiley/3b2/ANA#/Vol00000/110244/APPFile/JW-ANA#110244 J_ID: ZAY Customer A_ID: SUPP11-6 Cadmus Art: 22579 Date: 31-August-11 noise ratio makes this probe an excellent tool for the diagnosis of s-IBM. Stage: Page: 63 Both genotype and allele frequency of ACE and aADDUCIN however were not different between patients with and without ECMRA or ICMRA abnormality after adjustment of putative stroke risk factors. Conclusions: ACE DD genotype and D allele and aADDUCIN GW genotype and W allele were associated with IS compared to controls but not related to IC or ECMRA abnormalities. Study supported by: Study financially supported by Indian council of medical research, Governmernt of India Neurogenetics M1001. Withdrawn M1002. Clinico-Genetic Characterization of a Large Italian Cohort with Primary Spastic Paraplegia Andrea Martinuzzi, Mariateresa Bassi, Grazia D’Angelo, Sara Bonato, Gabriella Paparella, Olimpia Musumeci, Mariagiovanna Rossetto, Marianna Fantin, Francesca Peruch, Alessia Arnoldi, Claudia Crimella, Erika Tenderini, Paolo Bonanni, Vanessa Casanova, Giovanni Meola, Giacomo Comi, Antonio Toscano and Nereo Bresolin; Conegliano, TV, Italy; Bosisio Parini, LC, Italy; Messina, Italy and Milano, Italy M1004. Generation and Characterization of MeCP2_270 Mutant Mice Chiranjeevi Bodda, Karolina Can, Liakath Ali Kifayathulla, Hope Yao Agbemenyah and Ashraf U. Mannan; Goettingen, Germany MeCP2 is a transcription factor that binds to methylated target DNA sequence. Loss-of-function mutations in MECP2 gene is the main cause for Rett syndrome (RTT). The R270X is one of the most frequent recurrent MECP2 mutations among RTT cohorts. The R270X mutation resides within the TRD-NLS region of MeCP2 and causes a severe clinical phenotype with increased mortality as compared to other mutations. To evaluate the functional role of R270X mutation, we first generated a transgenic mouse model expressing MeCP2_270 (human mutation equivalent) by BAC recombineering. The generated transgenic mice were crossed with Mecp2 knockout mice to produce Mecp2_R270X knockin mice. The expression pattern of MeCP2_270 was similar to that of endogenous MeCP2. Strikingly, MeCP2_270 localizes in the nucleus, contrary to the conjecture that the R270X could cause disruption of the NLS. Quantitative expression analysis of MeCP2 target genes revealed a similar trend in gene regulation pattern as observed in knock-out mice, however the level of differential regulation was variable. At the present, we are performing behavioral analysis to characterize the phenotype of the mice. Also, we are evaluating neuronal parameters to determine impairment in neuron development/differentiation and synaptic network dysfunction. Study supported by: DFG-Research Center Molecular Physiology of the Brain. Germany Background: Diagnostic definition of hereditary spastic paraplegias (HSPs) is complicated by the wide genetic heterogeneity. Objectives: Establish in a large cohort of Italian HSP patients the relative frequency of the various forms, providing indications for an efficient diagnostic algorhythm. Methods: 478 index cases (72 familial, 98 pure, 380 complicated) HSP were clinically and molecularly assessed. Results: 80 cases were molecularly defined. SPG4 was the most frequent form (55%), followed by SPG11 (16.6%) SPG7 (9%), SPG10 (8,8% ) and 5 (5.1%). SPG3a and SPG31 were rarer (2.5%). No mutations were identified in SPG6, 8, 13, 20, 21, 35, 48. There was wide inter and intrafamilial variation. Neurophysiology showed invariably increased central conduction time at lower limbs. Axonal polyneuropathy was detected in some SPG3a, 5, 10, 11, 17 and SPG4 (15%). MRI showed abnormalities in SPG 5, 10, 11 and 15. Conclusion: Frequency of SPG forms within this cohort of Italian HSPs confirms the prevalence of SPG4, reveals the recurrence of SPG11 and 7 and the low frequency of SPG3a and 31. Once SPG4 and SPG11 are excluded, family history, neurophysiology and neuroimaging may direct the choice of genetic testing. Study supported by: Italian Ministry of Health M1003. A Study of ACE and ADD1 Gene Polymorphism in Extra and Intracranial Atherosclerosis in Patients with Ischemic Stroke Jayantee Kalita, Usha K. Misra, Sunil Kumar, Bishwanath Kumar, Bindu I. Somarajan and Balraj Mittal; Lucknow, Uttar Pradesh, India M1005. Identification of Epigenomic Modifications as Biomarkers for Amyotrophic Lateral Sclerosis Claudia Figueroa-Romero, Junguk Hur, Yu Hong, John S. Lunn, Crystal Pacut, Colin E. Delaney, Raymond Yung, Brian Callaghan and Eva L. Feldman; Ann Arbor, MI ALS is a progressive and terminal neurodegenerative disease leading to irreversible motor neuron degeneration. The high incidence of sporadic ALS (sALS) suggests that long-term influences of environmental factors on the genome may have a major impact in disease development. We hypothesize that epigenetic modifications play a key role in the pathogenesis of sALS. DNA from postmortem spinal cord (SC) tissue from sALS patients/controls was subjected to an epigene discovery phase. We identified 4,080 autosomal CpG sites with a significantly different methylation status in sALS compared to control (False Discovery Rate < 5%). The biological functions of �extracellular region’, �defense response’ and �immune response’ were highly associated with these differentially methylated sites. Furthermore, differential expression of six genes involved in human cytokine activity was observed in ALS/control human lymphocytes and/or SC. We have identified methylation profiles in diseased tissue, which might parallel those in blood as Objective: To evaluate the hypertensive gene (ACE and aADDUCIN) and MR angiography (MRA) abnormality in patients with ischemic stroke (IS). Method: 151 patients with MRI proven IS were subjected to clinical and biochemical stroke risk factors evaluation. Both intra(IC) and extracranial(EC) MRA were done and more than 50% stenosis was considered significant. ACE and aADDUCIN gene polymorphism was done in patients and 188 controls. Results: The patients’ median was 60years and 26.5% were females. MRA was abnormal in 77.5%; ECMRA in 58.3% and ICMRA in 66.7%. The conventional risk factors were not different between the patients with and without MRA abnormalities. Presence of DD genotype (OR3.86,95%CI0.78-2.28,P ¼ 0.0001) and aADDUCIN GW genotype (OR2.05, 95%CI1.28-3.27,P ¼ 0.003) increased the risk of IS significantly compared to controls. 63 ID: senthilk I Black Lining: [ON] I Time: 08:46 I Path: //xinchnasjn/01Journals/Wiley/3b2/ANA#/Vol00000/110244/APPFile/JW-ANA#110244 J_ID: ZAY Customer A_ID: SUPP11-6 Cadmus Art: 22579 Date: 31-August-11 epigenetic biomarkers of sALS. This could enable early-stage diagnosis and therapeutic interventions to increase survival outcomes in sALS patients. Study supported by: The A. Alfred Taubman Medical Research Institute. Stage: Page: 64 Mayo Clinic Florida (MCF) Research Committee CR programs (MDF #90052018). M1008. Aberrant Methylation by Mutations of DNA Methyltransferase 1 Cause Peripheral and Central Axonal Degeneration Christopher J. Klein, Maria V. Botuyan, Yanhong Wu, Christopher J. Ward, Garth A. Nicholson, Simon Hammans, Hiromitch Yamanishi, Adam R. Karpf, Douglas C. Wallace, Mariella Simon, Cecilie Lander, Julie M. Cunningham, Glenn E. Smith, William J. Litchy, Benjamin Boes, Elizabeth J. Atkinson, Sumit Middha, P. James Dyck, Joseph E. Parisi, Georges Mer, David I. Smith and Peter J. Dyck; Rochester, MN; Sydney, Australia; Southampton, United Kingdom; Hyogo, Japan; Buffalo, NY; Irvine, CA; Herston, Australia and Indianapolis, IN M1006. A Drosophila Model of Williams Syndrome Ralph J. Greenspan and Jenee Wagner; La Jolla, CA Social cognition is a major frontier in neuroscience, and Williams Syndrome (WS) is a condition affecting social cognition associated with hemizygous deletions of $28 genes on human chromosome 7. The genetics of WS is apparently simple, consisting of a deletion of a defined chromosome segment, but complex because the deletions remove a block of genes, thus obscuring the contributions of interactions among subsets of the genes. These interactions are directly addressable in Drosophila, where ten of the genes in WS deletions have bona fide homologs in Drosophila, and one more has a more distant homolog, and all have extant mutant alleles. We are mapping the gene network interactions affected by different combinations of WS homologs in the fruit fly, capitalizing on the extensive conservation with humans of their genes and gene networks. Results from these experiments indicate that fly homologs of LIMK1 and CLIP190, among others, have substantial effects on behavior individually, but their contributions are not additive in combination with other WS genes. This non-linearity is reflected in the effects of these manipulations on gene network activities. Supported by NSF IOS-0840717 and NIH 1R21EY020629-01 grants to R.J.G. Study supported by: NIH, NSF DNA methyltransferase 1 (DNMT1) is an essential component of genomic methylation. Neural gene expression, DNA mismatch repair and cell cycle regulation are all influenced by DNA methylation. Here we show mutations in DNMT1 cause both central and peripheral axonal degeneration in one form of hereditary sensory and autonomic neuropathy with dementia and hearing loss. Two American, one European and one Japanese kindreds were studied. Next generation sequencing was utilized to identify two DNMT1 mutations, c.A1484G(p.Y495C) in American and Japanese kindreds and c.1470TCC-1472ATA(p.D490E-P491Y) in a European kindred. All mutations are within the DNA targeting sequence domain of DNMT1. Functional analysis shows premature degradation and reduced methyltransferase activity. Mutant proteins lost heterochromatin binding ability during the G2 cell cycle, leading to global hypomethylation measured by mass spectrometry analysis. Methylation of satellite 2 repetitive elements is preferentially decreased. Global hypomethylation and regional hypermethylation is shown in affected persons, a pattern commonly seen in unregulated cancer cells, suggesting post mitotic neural cells may undergo axonal degeneration by loss of cell cycle arrest. The discovered mutations in DNMT1 provide a new framework for the study of neurodegenerative diseases. Study supported by: NINDS K08 award M1007. Clinical and Pathological Features of Progressive Supranuclear Palsy with Family History Shinsuke Fujioka, Avi Algom, Audrey Strongosky, Dennis W. Dickson and Zbigniew K. Wszolek; Jacksonville, FL Objective: To compare the clinical and pathological characteristics of progressive supranuclear palsy (PSP) patients with and without a family history of parkinsonism or PSP. Methods: We reviewed autopsy case records from Mayo Clinic Florida Brain Bank to retrieve PSP cases with positive family history of neurodegenerative disease, defined as PSP or parkinsonism, as well as PSP cases without a family history of neurologic disease. Results: This study was based on 375 pathologically confirmed PSP cases, of which 56 had a family history of PSP or parkinsonism. Among these, 19 patients had multiple affected family members with PSP, parkinsonism, or other neurodegenerative conditions, such as dementia or tremor. There was a trend (p ¼ 0.128) for PSP with a positive family history to have more atypical clinical features and diagnoses other than PSP, such as corticobasal syndrome or frontotemporal dementia. They also tended (p ¼ 0.131) to have more frequent atypical PSP pathology. Conclusion: PSP patients with a positive family history share many clinical and pathologic features with PSP patients without family history, but in general they tend to be atypical in clinical presentation and in final pathology. Study supported by: ZKW is partially supported by the NIH/NINDS 1RC2NS070276, NS057567, P50NS072187, Mayo Clinic Florida (MCF) Research Committee CR programs (MCF #90052018 and MCF #90052030), and gift from Carl Edw and Bolch, Jr., and Susan Boss Bolch (MCF #90052031/PAU #90052). FS is partially supported by M1009. Common and Distinct Associations of HLADRB1 and -DPB1 Alleles with Neuromyelitis Optica and Multiple Sclerosis in Japanese Satoshi Yoshimura, Noriko Isobe, Takuya Matsushita, Tomomi Yonekawa, Katsuhisa Masaki and Jun-ichi Kira; Fukuoka, Japan Background: A distinctive association between human leukocyte antigen (HLA) gene alleles and each clinical subtype, opticospinal multiple sclerosis (OSMS) and conventional MS (CMS), has been reported in Asians. However, patients’ sample sizes were relatively small in the previous studies. OSMS is now suggested to be the same as a relapsing form of neuromyelitis optica (NMO) in Westerners. Objective: To clarify the association of HLA-DRB1 and DPB1 alleles with NMO and non-NMO MS phenotypes in a large series of Japanese patients. Methods: Genotyping of HLA-DRB1 and -DPB1 alleles was performed in 288 MS patients including 83 who fulfilled the NMO criteria, and 367 healthy controls (HCs). Results: DRB1*0901 frequency was significantly lower in both NMO (pcorr ¼ 0.0003, OR:0.133, 95%CI:0.048– 0.374) and non-NMO MS patients (pcorr<0.0001, 64 ID: senthilk I Black Lining: [ON] I Time: 08:46 I Path: //xinchnasjn/01Journals/Wiley/3b2/ANA#/Vol00000/110244/APPFile/JW-ANA#110244 J_ID: ZAY Customer A_ID: SUPP11-6 Cadmus Art: 22579 Date: 31-August-11 OR:0.301, 95%CI:0.181–0.499) as compared with HCs. Susceptibility alleles for non-NMO MS are DRB1*0405 (pcorr ¼ 0.0189, OR:1.867, 95%CI:1.300–2.683) and DPB1*0301 (pcorr ¼ 0.0022, OR:3.328, 95%CI:1.747– 6.337) while those for NMO are DRB1*1602 (pcorr ¼ 0.0028, OR:12.942, 95%CI:3.355–49.923) and DPB1*0501 (pcorr ¼ 0.0265, OR:2.608, 95%CI:1.412– 4.816). Conclusion: There is a common resistant DRB1 allele between NMO and non-NMO MS while susceptibility alleles are distinct between the two conditions in Japanese. Study supported by: This work was supported in part by the Health and Labour Sciences Research Grant on Intractable Diseases (H20-Nanchi-Ippan-016) from the Ministry of Health, Labour and Welfare, Japan, and the grant-in-aid (B; no. 22390178) from the Ministry of Education, Culture, Sports, Science and Technology, Japan. Stage: Page: 65 rHIgM12 co-localized with microtubules and was co-immunoprecipitated with b3-tubulin. rHIgM12 promoted tyrosination of a-tubulin. Finally, rHIgM12 enhanced polarized axon outgrowth when presented as substrate. Our results indicate that there exists a repertoire of natural IgMs with the potential to regulate membrane lipid and microtubule dynamics required for axonal outgrowth. These findings also identify a bioactive molecule that may be utilized to treat neurologic diseases. Study supported by: This work was supported by grants from the NIH (R01 GM092993, R01 NS024180, R01 NS03219, R01 NS048357) and the National Multiple Sclerosis Society (CA 1011-A8). We also acknowledge with thanks support from the Applebaum and Hilton Foundations and the Minnesota Partnership Award for Biotechnology and Medical Genomics. M1102. Computed Tomography Characteristics of Pediatric Traumatic Brain Injury Korak Sarkar and Kia Shahlaie; Sacramento M1010. Computer Simulations of Striatal Atrophy and Age at Onset of Huntington’s Disease Steven D. Edland and Jagan Pillai; La Jolla, CA Little is known about the differences in CT findings between adult and pediatric TBI populations. A retrospective analysis of 1206 consecutive non-penetrating TBI patients treated at a Level 1 trauma center from August 2008 to January 2011 was performed. Admission CT scan were evaluated for skull fractures, ICH, midline shift, and basal cistern compression. Of 1206 patients in our registry 349(28.5%) were pediatric. Demographics and injury severity distribution were similar between the two populations (p> 0.05). The distribution of CT findings, however, was significantly different. Pediatric TBI patients were more likely to be associated with skull fractures (57.0% vs 23.4%) and EDH (17.2% vs 9.7%), and less likely to be associated with contusion, SDH, SAH, or basal cisterns compression (p<0.05). Despite similarities in demographic characteristics and clinical severity between adult and pediatric TBI, there were significant differences in the pattern of CT findings. These findings may reflect differences in anatomy (skull fractures), biomechanical forces during injury (ICH patterns), or intracranial compliances (mass effect). These differences may have a significant impact on clinical trial design and treatment strategies for patients in different age groups. Beyond polyglutamine repeat length on the huntingtin gene, little is known about predictors of age at onset of first symptoms of Huntington’s disease (HD). Cajevec et al. (Neurogenetics, 2006) proposed that variability in age at onset given repeat length could be explained by the random nature of striatal cell loss under the ��one-hit’’ model of HD neurodegeneration proposed by Clarke et al. (Nature, 2000). Alternatively, the rate of neuronal loss in HD could vary person to person due to environmental and background genetic influences affecting rate of neuronal loss or affecting susceptibility to the extent of cell loss. To investigate this, we simulated striatal neuron loss in HD as proposed by Cajevec et al. and under these alternative models. We found that stochastic cell death is unlikely to explain an appreciable fraction of variability in age at onset, while models with random rates of neuronal loss and susceptibility recapitulated empirical HD survival distributions perfectly. We conclude, contrary to Cajevec et al., that age at onset is a valuable phenotypic endpoint for investigations of environmental and background genetic factors affecting the expression of HD. Study supported by: NIH/NIA AG00513 and AG034439. M1103. Neurological Outcome Scale for Traumatic Brain Injury: Predictive Validity and Sensitivity to Change Paolo Moretti, Stephen R. McCauley, Elisabeth A. Wilde, James N. Scott and Guy L. Clifton; Houston, TX and Calgary, AB, Canada Trauma/Injury M1101. A Human Natural IgM Drives Axon Outgrowth Xiaohua Xu, Arthur Warrington, Brent Wright, Allan Bieber, Virginia Van Keulen, Larry Pease and Moses Rodriguez; Rochester, MN The Neurological Outcome Scale for Traumatic Brain Injury (NOS-TBI) is a measure assessing neurological functioning in TBI. We hypothesized the NOS-TBI would be more sensitive to change than other well-established measures, demonstrate predictive validity, and relate to initial Marshall CT classification. We analyzed data from the National Acute Brain Injury Study: Hypothermia II trial (n ¼ 98). Patients were 16–45 years with severe TBI assessed at 1, 3 and 6 months post-injury. For analysis of validity, Spearman correlations were performed comparing the NOS-TBI to Glasgow Outcome Scale (GOS) and GOS-Extended (GOS-E), Disability Rating Scale (DRS), and Marshall CT classification. Sensitivity to change was analyzed using the Wilcoxon signed-rank sum test of subsamples demonstrating no We demonstrate that a human natural IgM, HIgM12 promotes axonal outgrowth by mechanisms coupling lipid raft to microtubule dynamics. Serum-derived human IgMs have been shown to support neurite extension of primary cerebellar granule neurons. In the current study with primary hippocampal neurons, we showed that a recombinant form of one of these IgMs, rHIgM12 regulated kinetics of membrane lipids. rHIgM12 bound to neuron surfaces and induced clustering of cholesterol and ganglioside, GM1. Following membrane association, rHIgM12 segregated into two pools, one associated with lipid raft fractions, and the other with detergent insoluble pellet composed of cytoskeletons. Moreover, rHIgM12 affected microtubule dynamics. 65 ID: senthilk I Black Lining: [ON] I Time: 08:46 I Path: //xinchnasjn/01Journals/Wiley/3b2/ANA#/Vol00000/110244/APPFile/JW-ANA#110244 J_ID: ZAY Customer A_ID: SUPP11-6 Cadmus Art: 22579 Date: 31-August-11 change in GOS or GOS-E between 3 and 6 months. The 1- and 3-month NOS-TBI correlated with the 3- and 6month GOS, GOS-E and DRS (all p<.002), and Marshall CT correlated with 6-month NOS-TBI (p<.03). NOS-TBI demonstrated higher sensitivity than GOS or GOSE (p .02). The NOS-TBI demonstrates predictive validity and higher sensitivity to change than existing TBI measures; it may enhance prediction of outcome in clinical practice and measurement of outcome in research. Study supported by: National Institute of Neurological Disorders and Stroke NS043353 Stage: Page: 66 0.033). Patients reported that only 17.4% (19/109) of injuries occurred during exercise. Conclusions: Risk factors for injury include male gender, living longer with MS, being younger and having the diagnosis of primary progressive MS, respectively. Study supported by: University of Massachusetts Medical School M1106. Raising the Dead: Barriers to Therapeutic Hypothermia Post Cardiac Arrest and Mark Andrews; Palo Alto, CA Induction of therapeutic hypothermia (TH) in post cardiac arrest patients has been shown to be neuroprotective and may yield additional therapeutic benefits including decreased mortality. Despite better outcome data, the existence of physician order protocols, and readily available state-of-the-art equipment, early induction of therapeutic hypothermia is often started late in the hospital continuum of care. Unlike other interventions shown to improve postarrest outcomes (early bystander CPR, early defibrillation, and early advanced cardiac life support), early induction of therapeutic hypothermia is a hospital-based strategy requiring the integration and cooperation of multiple practitioners and multiple departments for successful implementation. Approaching the issue from this multidisciplinary perspective led me to survey over a 100 practitioners in a large, university-based hospital setting in order to identify experiences, knowledge, and barriers to inducing therapeutic hypothermia early in the care continuum. Few of the respondents reported experiences with TH and most reported a lack of standardized protocols, unclear orders, and technical difficulties with cooling equipment as the most common barriers to induction. M1104. Determination of Awareness in Patients with Severe Brain Injury Using EEG Spectral Analysis Andrew M. Goldfine, Jonathan D. Victor, Mary M. Conte, Jonathan C. Bardin and Nicholas C. Schiff; New York, NY and White Plains, NY Recent studies using functional MRI (fMRI) and eventrelated potentials (ERP) demonstrate that some severely brain-injured patients retain a range of cognitive functions despite minimal or no behavioral evidence of awareness. However, fMRI is impractical for bedside use and ERPs may fail to detect responses that are delayed or not tightly synchronized to a stimulus. We investigated whether electroencephalographic (EEG) spectral analysis could identify behaviorally covert responses to command in three patients with severe brain injury, ranging from minimally conscious state (MCS) to locked-in-state (LIS). We first demonstrated that EEG spectral analysis could denote performance of a motor and navigation imagery tasks in healthy controls. As patterns of signal change were inconsistent between controls, we defined a positive outcome in patients as consistent spectral changes across task performances. Using this outcome measure, one patient in MCS and one in LIS demonstrated evidence of motor imagery. Patterns of spectral power and cross-channel coherence varied across subjects, representing different local and widespread cortical networks involved in task performance. We conclude that EEG spectral analysis is a promising versatile tool for bedside testing of awareness in patients with severe brain injury. Study supported by: NIH-NICHD 51912, the James S McDonnell Foundation, and Weill-Cornell CTSC UL 1RR02499 M1107. Abnormal Oculomotor Function among BlastInjured Combat Veterans Bruce P. Capehart, Adam Mehlenbacher, Carol SmithHammond, Dale Bass and James Burke; Durham, NC Dysfunctional saccades and smooth pursuit have been reported after blunt traumatic brain injury (TBI). These tests of oculomotor function could assist in the diagnosis of TBI after exposure to significant blast injuries. We report results of saccade and smooth pursuit testing for blastexposed combat veterans who did not have a prior history of blunt TBI. These results show abnormalities in both saccades and smooth pursuit. These tests should be further investigated for use as screening and/or diagnostic assessment when blast-related TBI is a possible diagnosis. M1105. Orthopedic Injuries in Multiple Sclerosis Patients: Analysis of the Incidence of Injury in This Vulnerable Population Daniel Mandell** and William Tosches; Worcester, MA Background: Because of the high degree of disability in multiple sclerosis (MS) patients, minimizing injury occurrence is essential for preserving quality of life. Objectives: By establishing relative risks of particular injuries in different subsets of MS patients and analyzing when the injuries occurred following diagnosis, we aim to provide information to encourage injury prevention. Methods: A questionnaire of 40 fill in the blank or multiple choice questions was administered to previously diagnosed MS patients. Results: The years following MS diagnosis with the highest injury rates (injuries/people years lived) were 25 years or more (.0594 injuries/year, 95% CI [0.0771 - 0.0449]). People below the age of 40 have nearly a doubled risk of injury compared to people above the age of 40 (p ¼ .0331). Primary progressive MS patients had the greatest past incidence of fractures, 55.6% (5/9) (FFH p ¼ Neurology Critical Care M1201. Withdrawn M1202. Predictors of Outcome in Prolonged Refractory Status Epilepticus Sara Hocker, Jeffrey W. Britton, Jay Mandrekar, Eelco F.M. Wijdicks and Alejandro A. Rabinstein; Rochester, MN To determine predictors of outcome in refractory status epilepticus (RSE) we retrospectively analyzed all episodes of RSE treated between 1999 and 2011 at Mayo Clinic. RSE was defined as generalized convulsive or non-convulsive status epilepticus that continued clinically or electrographically despite initial first and second line therapies. We identified 55 episodes of RSE in 46 patients aged 50 6 17.9 years. 66 ID: senthilk I Black Lining: [ON] I Time: 08:46 I Path: //xinchnasjn/01Journals/Wiley/3b2/ANA#/Vol00000/110244/APPFile/JW-ANA#110244 J_ID: ZAY Customer A_ID: SUPP11-6 Cadmus Art: 22579 Date: 31-August-11 Stage: Page: 67 IT injections were given to all patients (mean ¼ 6.4, range 1–14), median dose 4mg (range 1.2mg-4mg). No intracranial complications were observed by neuroimaging. No patient developed infectious ventriculitis. 2 patients had CSF cloudiness immediately after injection, but no infection occurred. 1 patient had yellow nicardipine crystals that came out of external ventricular drain after repeated injections. Conclusion: IT-nicardipine at dose ranges of 1.2mg to 4mg may be safe for treating vasospasm after aSAH. Further study is needed for dose-finding and assessing efficacy. Induction of anesthetic coma was necessary in 49/53 SE incidents. Patients required anesthetic agents for 9.6 (4, 0– 60) days. Eighteen died, withdrawal of support preceded death in 13. Compared to a pre-morbid modified Rankin scale (MRS) of (2.09 6 1.6) 27 patients alive at 3–6 months following hospital discharge had a MRS of (3.81 6 1.52) (p<0.0001) and 20 patients alive at 9–12 months had a MRS of (3.3 6 1.83) (p<0.0005). Asystole (p<0.0098), cardiac arrhythmias requiring treatment (p<0.0540), pulmonary edema (p<0.0498) and longer duration of mechanical ventilation (p<0.0492) were associated with in-hospital death. Mortality was similar to other published series of RSE. Despite prolonged anesthetic coma, patients who survive RSE may have acceptable outcomes. In this RSE series, the largest single center series reported thus far, cardiopulmonary complications were the main predictors of mortality. M1205. Acute Bacterial Meningitis as a Possible Cause of Severe Dysautonomia Leading to Death Yadira Velazquez-Rodriguez, Umer Akbar and Evren Burakgazi-Dalkili; Camden, NJ Objective: To recognize the possibility of pneumococcal meningitis causing severe dysautonomia leading to death. Background: Episodes of autonomic instability with dystonia (PAID) are known to result from multiple intracranial processes, however pneumococcal meningitis as a cause is under-recognized. Design/Methods: We describe a case of severe autonomic instability in a patient with acute bacterial meningitis. Results: Case: A 76 year-old woman with fever and altered mental status was diagnosed with acute pneumococcal meningitis. Antibiotic therapy improved her mentation, however few days later, she developed episodes of unresponsiveness with dilated, asymmetric and sluggish pupils, shivering, generalized tremors, hypertension and tachycardia followed by episodes of severe hypotension, bradycardia and asystole eventually leading to her death. These episodes were not responsive to conventional resuscitative measures. Conclusions: The inflammatory reactions that accompany infections have been implicated in autonomic dysfunction. Our case suggests that PAID is a spectrum-disease rather than a syndrome with distinct criteria. PAID was recognized in patients with central nervous system disorders, particularly traumatic brain injury, but to our knowledge, it has never been reported to occur from pneumococcal meningitis and with such severity resulting in patient’s death. M1203. Refractory Status Epilepticus and Heart Damage – A Warning for Neurologists Sara Hocker, Jeffrey W. Britton, Jay Mandrekar, Eelco F.M. Wijdicks and Alejandro A. Rabinstein; Rochester, MN To determine the incidence of neurocardiogenic injury in refractory status epilepticus (RSE) we reviewed all episodes treated between 1999 and 2011 at Mayo Clinic. RSE was defined as generalized convulsive or non-convulsive SE that continued despite initial therapies. We identified 55 episodes in 46 patients aged 50 6 17.9 years. Induction of anesthetic coma was necessary in 49/53 cases. Patients required anesthetic agents for 9.6 (4, 0–60) days. Eighteen patients had troponin levels drawn at onset of SE (mean 0.1 6 0.19 ng/mL). Electrocardiogram findings at onset of SE included: ST elevation (6.98%), ST depression (4.65%), T wave inversion (4.65%), LVH (6.98%), nonspecific ST changes (54.55%). Cardiac arrhythmias included: asystole (11.54%), ventricular tachycardia/fibrillation (7.69%), atrioventricular block (3.85%), atrial fibrillation/flutter (7.69%), paroxysmal supraventricular tachycardia (1.92%), sinus bradycardia (46%), sinus tachycardia (75%). Intervention was required for cardiac arrhythmias in 22.45%. One patient met criteria for non ST elevation myocardial infarction (NSTEMI). Pulmonary edema was present in 35%. Six of 24 patients evaluated with echocardiograms during and after SE had stress-induced cardiomyopathy with resolution after SE. We conclude that adrenergically-driven neurogenic cardiopulmonary injury is common in RSE. These disturbances may require specific treatment and are often reversible. Pediatric Neurology M1301. Diffusion Tensor MRI Tractography Reveals Altered Brainstem Fiber Connections Accompanying Agenesis of the Corpus Callosum Juebin Huang, Jian Chen, Haipeng Cai, Robert P. Friedland, Mohamad Z. Koubeissi, David H. Laidlaw and Alexander P. Auchus; Jackson, MS; Hattiesburg, MS; Louisville, KY; Cleveland, OH and Providence, RI M1204. Safety and Feasibility of Intrathecal Nicardipine for Vasospasm after Subarachnoid Hemorrhage William D. Freeman, Sothear Luke, Christina Campbell, Dan Jackson and James F. Meschia; Jacksonville, FL Introduction: Delayed arterial vasospasm (VSP) is a major cause of ischemic stroke after aneurysmal subarachnoid hemorrhage (aSAH). We hypothesize intra-thecal (IT) nicardipine would be safe and feasible for treating vasospasm. Methods: Retrospective chart review of consecutive aSAH patients admitted to the Neurosciences ICU at Mayo Clinic Florida from January 2009 to March 2011. Data collection included: age, sex, Fisher grade, and IT nicardipine dosing. Assessment of safety included post-injection intracranial bleeding (per CT or MRI) and infectious ventriculitis. Results: 12 patients (11 women; mean age, 49 yrs [range, 27–67 yrs]) with aSAH were treated with IT-nicardipine. 77 Introduction: Agenesis of Corpus Callosum (ACC) is a developmental anomaly wherein interhemispheric cerebral fibers fail to cross into the contralateral hemisphere. Using Diffusion Tensor MRI Tractography (DTT), we report two ACC cases with altered brainstem fiber connections involving middle cerebellum peduncles and transverse pontine fibers. Cases: Case 1: A 22 year-old woman with seizures, mental retardation and behavioral abnormalities. Case 2: A 50 year-old man with syncope, cognitive impairments and bilateral palmomental responses. 67 ID: senthilk I Black Lining: [ON] I Time: 08:46 I Path: //xinchnasjn/01Journals/Wiley/3b2/ANA#/Vol00000/110244/APPFile/JW-ANA#110244 J_ID: ZAY Customer A_ID: SUPP11-6 Cadmus Art: 22579 Date: 31-August-11 Imaging Procedures: Whole brain DTT was performed using streamtube tracing and culling techniques. DTT of a normal subject was obtained as a control. Results: Conventional brain MRI displayed complete absence of the corpus callosum in both cases. Whole brain DTT showed no corpus callosum fibers crossing the midline in either ACC case. Instead, robust fiber bundles passing through middle cerebellum peduncles via transverse pontine fibers were seen. Conclusion: DTT was useful in visualizing expected and unexpected alterations of white matter fiber connections in ACC. Study supported by: National Science Foundation (1017921,1018769, 1016623) Stage: Page: 68 ease. The significance of the Macro-CK in relation to the Leukoencephalopathy in this patient or the frequency of this association is completely unknown. Study supported by: Supported by The William Pilcher Endowment for Pediatric Neurology M1304. Pharmaceuticals in the Environment: A Focus on Neurological Medications and Ilene Ruhoy; Seattle, WA Pharmaceutical residues in the environment have been an issue of increasing interest amongst environmental scientists, toxicologists, and policy makers. Physicians have recently expressed concern regarding the potential ill effects on humans from chronic exposures to these active pharmaceutical residues (APIs). Research has demonstrated the potential for neurological effects from exposure to the multitude of pharmaceutical residues identified in our environment, specifically in our water systems. Studies in aquatic organisms have revealed altered brain size, poor neuronal growth, and neuropathy. In addition, many of the pharmaceuticals that have been identified are centrally acting. Carbamazepine is one drug of significant concern in that it is largely refractory to most treatment technologies and indeed it has been identified in all water sampling studies. Benzodiazepines are another common culprit that are found with increasing frequency and are ubiquitous in its prescription patterns. This presentation will discuss the known and unknown with regards to medications commonly prescribed in the neurological setting and environmental presence. It will correlate research on aquatic wildlife with the potential for human health effects from exposures to these medications and will recommend actions to minimize human exposures. M1302. Neurofibromatosis 1 (NF1) Vasculopathy in Children – An Emerging Entity Partha S. Ghosh, A.D. Rothner and Manikum Moodley; Cleveland, OH Objective: Vasculopathy in children with NF1. Methods: Retrospective review of children with NF1 from 2000- 2010 at Cleveland Clinic. NF1 associated vasculopathy divided into: (1) Cerebrovascular, (2) Cardiovascular (3) Other. Results: Of 398 patients, 26 (6.5%) had vasculopathy. Group1: Ten (2.5%) had cerebrovascular abnormalities (mean age 12.8 years; 5 males). Presentation- headache (4), seizures (1), asymptomatic (5): all had normal neurological examination. MRA brain: Moyamoya disease-4, stenosis/occlusion of Internal carotid artery-3, Middle cerebral artery stenosis-2, Posterior cerebral artery stenosis-1. Ischemic changes noted in 1. On follow-up (mean 5.2 years); 1 died of brain tumor, others did not develop stroke. One had encephaloduromyosynangiosis for moyamoya. Group2: Fifteen (3.7%) had cardiovascular abnormalities (mean age 6.6 years; 8 males). Presentation: hypertension (2), shortness of breath (2), chest pain (1), syncope (1), murmur (6). Cardiac lesions: Pulmonary stenosis-5, Coarctation-4, mitral-valve prolapse-1, supra-valvular aortic stenosis-1, anomalous right coronary artery-1, pulmonary artery hypoplasia-1. On follow-up (mean 4.6 years), 3 had surgical procedures. Group3: Two girls had renal artery stenosis (RAS); 1 with coarctation. Both were hypertensive: 1 underwent RAS repair. Conclusion: Children with NF1 should be carefully screened for vasculopathy. Rehabilitation and Regeneration M1401. Human Induced Pluripotent Stem Cell-Derived Neural Progenitor Grafting into Rat Hippomcapus Alison L. Althaus, Yu Liu, Duriel Hardy and Jack M. Parent; Ann Arbor, MI Induced pluripotent stem cells (iPSCs) offer potential advantages as a neural progenitor cell (NPC) source for regenerative therapy, including readily available supply, vast differentiation potential and autologous grafts that obviate the need for immunosuppression. To begin developing iPSC-based transplantation therapy, we injected human iPSC-derived NPCs into neonatal rat hippocampus to determine their differentiation potential. We also examined how the degree of in vitro differentiation influenced graft behavior. GFP- or mCherry-labeled human iPSCs were neurally differentiated and transplanted (10^5 cells) into postnatal day 4 rat hippocampus either at the primitive neural rosette stage or after 3-day neurosphere differentiation. Grafts were examined after 2, 4 or 8 weeks by immunostaining for human nuclear antigen or GFP/mCherry and neuronal or glial markers. Grafts generated GFAPþ glia and TuJ1þ neurons at all time points. Neural rosette grafts tended to form large neural tube-like structures that deformed host tissue. Neurosphere grafts dispersed more widely and gave rise to mature-appearing neurons, some of which expressed a pyramidal cell marker (Tbr1). These findings suggest that iPSCs autografts may be useful for treating brain disorders. Further work is needed to determine optimal NPC differentiation states for grafting. Study supported by: NIH NS065450 M1303. Macro CK-1 a Cause of Spuriously Elevated CK Associated with Leukoencephalopathy in an Infant and John B. Bodensteiner; Phoenix, AZ Macro CK-1 is a complex formed by the Creatine Kinase isoenzyme BB and monoclonal IgG. The complex is not formed by abnormal CK enzyme but by an autoimmune reaction and occurs in about 1% of patients studied. First identified as a cause of spurious elevation of the total CK in patients suspected of myocardial infarction in the 1970s the test has been largely replaced by the measurement of Troponin levels. We present an infant with delayed milestones and persistently elevated CK measurements ($1000–4000 IU) normal EMG and brisk DTRs. Suspicion that this was not a myopathy prompted the measurement of CK isoenzymes and brain imaging which showed the presence of Macro CK-1 and extensive signal abnormality of the cerebral white matter. Macro CK-1 has been associated with cancer, infection, myositis and heart disease, not described in association with leukoencephalopathy or in infants. Macro CK-1 may be a cause of elevated total CK in patients without primary muscle dis- 68 ID: senthilk I Black Lining: [ON] I Time: 08:46 I Path: //xinchnasjn/01Journals/Wiley/3b2/ANA#/Vol00000/110244/APPFile/JW-ANA#110244 J_ID: ZAY Customer A_ID: SUPP11-6 Cadmus Art: 22579 Date: 31-August-11 Stage: Page: 69 136th Annual Meeting Tuesday, September 27, 2011 Poster Session M1402. Local Molecular Manipulation and Peripheral Nerve Regeneration Douglas W. Zochodne, Kimberly J. Christie, Christine A. Webber, Chu Cheng and Jose A. Martinez; Calgary, AB, Canada and Edmonton, AB, Canada Posters will be displayed in Elizabeth A-E of the Manchester Grand Hyatt from 10:00 am – 7:00 pm, with authors present from 6:00 pm – 7:00 pm. NOTE: An asterisk designates a resident/fellow travel award winner. Two asterisks represent a medical student travel award winner. Regeneration of peripheral neurons following injury or neuropathy is more challenging than usually assumed. We describe new molecular players that may offer insights into early axon outgrowth, the initiating step in regeneration. After complete nerve transection, axon outgrowth requires an intimate molecular exchange with partnering Schwann cells (SCs). Using an accessible conduit to connect the stumps of transected peripheral nerves in rats, we show that several forms of intervention, including local siRNA knock down, can alter regenerative outcome: (i) CGRP, an axonally synthesized peptide, signals local SCs to proliferate in order to support axon growth: knockdown interrupts regeneration. (ii) PTEN, a tumour suppressor molecule, is a regenerative roadblock that attenuates growth factor support of regeneration: knockdown dramatically enhances axon outgrowth. (iii) DCC and Unc5H are netrin facilitatory and inhibitory developmental pathfinding receptors respectively that are re-expressed in regenerating adult SCs: DCC knockdown attenuates adult regeneration whereas Unc5H knockdown enhances it. Local molecular manipulation can have significant impacts on the critical initiating step of peripheral nerve regeneration by eliminating roadblocks or upregulating growth signals. The approach may offer new forms of intervention for irreversible peripheral nerve lesions. Study supported by: Canadian Institutes of Health Research, Alberta Heritage Foundation for Medical Research Dementia and Aging T1501. Amyloid-Beta Dynamics and Prevention Trials in Dominantly Inherited Alzheimer’s Disease Randall J. Bateman and on behalf of the Dominantly Inherited Alzheimer Network; St. Louis, MO Amyloid-beta is a key pathologic protein in Alzheimer’s disease(AD) and extensive research has started an era of clinical trials targeting amyloid-beta. Understanding the dynamics of amyloid-beta formation and clearance in the human CNS and the processes that lead to clinical disease are essential to design better clinical trials. Developing efforts to prevent AD in autosomal dominant mutation carriers may test the amyloid hypothesis, determine the timing of treatment, and lead the way to AD prevention. Amyloid-beta production and clearance rates were measured with stable isotope labeling kinetics. The Dominantly Inherited Alzheimer’s Network interim findings of clinical, cognitive, MRI, PET, CSF, and blood biomarkers were analyzed with respect to the expected age of onset. Amyloid-beta clearance rate is decreased by 30% in AD compared to controls. Changes in clinical, cognitive, MRI, PET, CSF, and blood biomarkers in autosomal dominant AD indicate the pathophysiologic cascade begins up to 20 years before the expected age of onset. The pathophysiologic changes of AD can be specifically measured and targeted for clinical trials. Autosomal dominant AD prevention trials offer a unique opportunity to lead the way to effective treatments for all AD. Study supported by: NIH K-23-AG03094601, NIH R01-NS065667, NIH 3P-01-AG02627603S1 (FACS), NIH 1U-01-AG03243801 (DIAN), ADRC (P50 AG05681-22), HASD (P01 AG03991-22), WU CTSA award (UL1 RR024992), Mass Spectrometry Resource (NIH RR000954), Eli Lilly research collaboration R.J.B. is a co-founder of a company (C2N Diagnostics) that has licensed a Washington University patent on some of the technology described in this abstract. M1403. Very Early Gait Training after Acute Stroke; a Dose-Escalation Study Randolph S. Marshall, Ying K. Cheung, Clare Bassile, Laura A. Evensen, Roujie Chen, Veronica Perez, Ronald M. Lazar and Bernadette Boden-Albala; New York Intensive rehabilitation within days of stroke may benefit from an altered inhibition/disinhibition environment which promotes neuroplasticity. Conversely, early rehab may be impeded by excitotoxicity, medical co-morbidities, logistics of diagnostic testing, and low motivation. We used a stepwise sequential probability ratio test (sSPRT) with 6 tiers to determine the maximal tolerated dose of standard gait training at 24–96 hours after ischemic or hemorrhagic stroke. A multidisciplinary acute stroke/ rehab team assessed cardiac and neurological safety outcomes. Inclusion criteria: NIHSS leg motor or ataxia !1 and prestroke Rankin 3. After 28 patients the study met the sSPRT algorithm requirements of dose-escalation to the highest tier, with 5 of 6 patients completing 60 min/day at 24–96 hours. Safety outcomes included 3 cardiac withdrawals (2 patients at tier 3, 1 at tier 6), and 3 fatigue withdrawals (1 at tier 4, 1 at tier 5, 1 at tier 6). One patient failed to complete his assigned dose because of sedation for diagnostic testing. These preliminary data suggest that very early rehabilitation with gait training is safe and feasible beginning 24–48 hours after stroke. Further study is required to establish efficacy of early rehabilitation intervention in acute stroke. Study supported by: This work was supported by a Pilot Grant Award through Columbia University’s CTSA. T1502. Integrating Genome-Wide Association and Functional Validation To Understand Susceptibility for Alzheimer’s Pathology Joshua M. Shulman, Portia I. Chipendo, Lori B. Chibnik, Brendan T. Keenan, Dong Tran, Matthew A. Huentelman, Julie A. Schneider, Eric M. Reiman, Denis A. Evans, David A. Bennett, Mel B. Feany and Philip L. De Jager; Boston, MA; Chicago, IL and Phoenix, AZ Gene discovery in Alzheimer’s disease (AD) is limited by etiologic heterogeneity of dementia in cases and subclinical disease in controls. We have implemented a novel strategy using quantitative AD pathology as an outcome for genome-wide association (GWA) analysis. Candidate susceptibility genes were subsequently tested for functional 69 ID: senthilk I Black Lining: [ON] I Time: 08:46 I Path: //xinchnasjn/01Journals/Wiley/3b2/ANA#/Vol00000/110244/APPFile/JW-ANA#110244 J_ID: ZAY Customer A_ID: SUPP11-6 Cadmus Art: 22579 Date: 31-August-11 validation in a Drosophila model, based on transgenic expression of human Tau. In a pilot study of 227 subjects, 6 out of 15 genomic regions associated with AD pathology contained genes showing interactions with Tau neurotoxicity in vivo. In the full cohort of 651 autopsies, GWA identified a variant in PFTK1 (rs11563839) associated with neurofibrillary tangle burden (p ¼ 6Â10À6), and this polymorphism was also related to episodic memory decline (p ¼ 0.004) in 1600 prospectively-followed, elderly subjects. Significantly, in Drosophila, we find that both gain- and lossof-function of the PFTK1 ortholog, Eip63E, is associated with suppression and enhancement of Tau toxicity, respectively. Interestingly, PFTK1 encodes a cell cycle-related kinase strongly expressed in adult brain. Our strategy of integrating a GWA scan for pathologic phenotypes with functional validation in a model organism is likely to be a powerful approach for gene discovery in AD. Study supported by: National Institutes of Health/National Institute on Aging, Massachusetts Alzheimer’s Disease Research Center, the Harvard NeuroDiscovery Center, and the Clinical Investigator Training Program: Beth Israel Deaconess Medical Center–Harvard/MIT Health Sciences and Technology, in collaboration with Pfizer Inc. and Merck & Co. Stage: Page: 70 T1504. Insulin-Like Growth Factor 1 (IGF-1) and Risk of Alzheimer’s Disease: The Framingham Study Andrew J. Westwood*, Alexa S. Baiser, Ramachandran S. Vasan, Tamara B. Harris, Ronenn Roubenoff, Aleksandra Pikula, Rhoda Au, Charles DeCarli, Philip A. Wolf and Sudha Seshadri; Boston, MA; Framingham, MA; Bethesda, MD and Sacremento, CA Objective: To relate serum IGF1 to risk of Alzheimer’s disease (AD) and to brain volumes in a dementia-free community sample. Background: IGF1 may be a biological link between lifestyle and risk of AD; exercise elevates and hyperinsulinemia depresses circulating IGF1. IGF1 levels correlate positively with cognition in older men and lower levels are reported in mouse models of AD. Method: Framingham participants (N ¼ 648, mean age 79 6 4 yrs, 63% women) who had serum IGF1 measured (radioimmunoassay, coefficient of variation 4%) in 1990-94 were followed prospectively for incident AD. Dementia-free survivors (N ¼ 161) underwent brain MRI in 1999–2005. Results: Mean IGF1 levels were 143 6 60lg/L. We observed 105 cases of incident AD over a mean follow-up of 9 6 4 years. In multivariable models adjusted for age-, sex-, APOE, plasma homocysteine and waist-hip ratio, each standard deviation increase in baseline IGF1 was associated with a 23% lower risk of AD (HR ¼ 0.77,95%CI:0.620.96;p ¼ 0.019). Persons with IGF1 levels in the lowest quartile had lower brain volumes (b 6 SD ¼ À0.6 6 0.28; p ¼ 0.033) cross-sectionally, and a 80% greater risk of developing AD (HR ¼ 1.80,95%CI:1.19–2.71;p ¼ 0.005) compared to others. Conclusions: Higher IGF1 levels may protect from clinical AD and subclinical brain atrophy. Study supported by: This work was supported by the Framingham Heart Study’s National Heart, Lung, and Blood Institute contract (N01-HC-25195) and by grants from the National Institute of Neurological Disorders and Stroke (R01 NS17950 to P.A.W.) and from the National Institute on Aging (R01 AG16495 to P.A.W., AG08122 to P.A.W., AG033193 to S.S., AG031287 to S.S., AG033040 to P.A.W., P30AG013846 to S.S.). Dr. Roubenoff is an employee of Biogen Idec, Inc, but reports no conflict of interest with the subject of this paper T1503. Brain Expression Genome-Wide Association Study (eGWAS) and Alzheimer’s Disease Nilufer Ertekin-Taner, Fanggeng Zou, High Seng Chai, Curtis S. Younkin, Julia Crook, V Shane Pankratz, Mariet Allen, Minerva M. Carrasquillo, Christopher N. Rowley, Otto Pedraza, Morad Ansari, Caroline Hayward, Igor Rudan, Harry Campbell, Ozren Polasek, Nicholas D. Hastie, Asha A. Nair, Sumit Middha, Sooraj Maharjan, Thuy Nguyen, Li Ma, Kimberly G. Malphrus, Ryan Palusak, Sarah Lincoln, Gina Bisceglio, Constantin Georgescu, Christopher P. Kolbert, Jin Jen, Zbigniew Wszolek, Maria Barcikowska, Sigrid B. Sando, Jan Aasly, Kevin Morgan, Clifford Jack, Ronald C. Petersen, Neill R. Graff-Radford, Alan Wright, Dennis W. Dickson and Steven G. Younkin; Jacksonville, FL; Rochester, MN; Edinburgh, United Kingdom; Split, Croatia; Zagreb, Croatia; Warsaw, Poland; Trondheim, Norway and Nottingham, United Kingdom Genetic variants that modify brain gene expression may also influence risk for CNS diseases, including Alzheimer’s disease (AD). We performed an eGWAS of 24,526 transcript levels measured in the cerebella of 197 ADs and 177 nonADs with 313,330 SNP genotypes. After elimination of probes with a known SNP within their sequence, cis-SNP/ transcript level associations were sought. Corrections were made for technical and biological variables. Significant cerebellar associations were also tested in the temporal cortex of 198 ADs and 193 non-ADs. Cerebellar expression was detectable for $69% of all transcripts. After accounting for technical variance, cis-SNPs explained 5–85% of the variance of >1,600 transcripts. There was an excess of significant associations. Substantial number of cis-SNP/transcript associations were significant in both ADs and non-ADs with similar direction and magnitude of effects. Many top cerebellar cis-SNPs were also detectable in the temporal cortex with similar effect sizes. We demonstrate that genetic factors influence brain expression for many genes, replicably across disease pathologies and tissue regions. eGWAS may be an excellent approach to identify candidate functional genetic variants implicated in AD. Top cis-SNPs are investigated for association with AD and its endophenotypes including plasma amyloid-b. Study supported by: R01 AG018023, P50 AG016574 T1505. Components of Blood Pressure and Progression of Cerebral Leukoaraiosis: The ARIC Study Rebecca F. Gottesman, Diane J. Catellier, Laura H. Coker, Josef Coresh, Clifford R. Jack, Jr., David S. Knopman, Kathryn M. Rose, A. Richey Sharrett, Dean K. Shibata and Thomas H. Mosley; Baltimore, MD; Chapel Hill, NC; Winston-Salem, NC; Rochester, MN; Durham, NC; Seattle, WA and Jackson, MS Background: The contribution of blood pressure (BP) components to the burden and progression of cerebral white matter hyperintensity (WMH) is poorly understood. We evaluated these associations in the population-based Atherosclerosis Risk in Communities (ARIC) cohort. Methods: 983 participants each underwent 2 brain MRIs 10 years apart. Systolic (SBP) and diastolic BP (DBP) were measured at 4 study visits. Four BP components were examined as predictors of WMH progression: 1) mean arterial pressure (MAP); 2) pulse pressure (PP); 3) orthostatic hypotension (OH); and 4) 10-year change in BP. Results: Baseline (preceding MRI #1) MAP value predicted WMH progression (OR 1.39 (1.20–1.62), per 10 mm Hg increase), but PP did not. Presence of OH did not 70 ID: senthilk I Black Lining: [ON] I Time: 08:46 I Path: //xinchnasjn/01Journals/Wiley/3b2/ANA#/Vol00000/110244/APPFile/JW-ANA#110244 J_ID: ZAY Customer A_ID: SUPP11-6 Cadmus Art: 22579 Date: 31-August-11 predict WMH progression, but OH severity did (OR 1.21 (1.02–1.42) per 10 mm Hg SBP decrease). Change in DBP over 10 years had a U-shaped relationship with WMH progression: extreme increases and decreases, independent of antihypertensive use, were both associated with greater WMH progression (p ¼ 0.007). Discussion: WMH progression is significantly predicted by MAP and extent of orthostatic SBP reduction. Significant changes over time in DBP, whether positive or negative, predict WMH progression, cautioning against simplified interpretations of blood pressure associations. Study supported by: The Atherosclerosis Risk in Communities Study is carried out as a collaborative study supported by National Heart, Lung, and Blood Institute contracts (HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN2 68201100009C, HHSN2682011000010C, HHSN2682011 000011C, HHSN2682011000012C). Stage: Page: 71 Wilcoxon Signed Ranks Tests. We found that, for the total sample, there were significant differences between MoCA and MMSE with regard to total score (p<0.001), in addition to visuospatial (p ¼ 0.002), language (p<0.001), and memory (p<0.001) domains. Although mean MMSE scores declined only modestly across the decades, the decline in mean MoCA scores was more dramatic. There were no consistent domain differences between the MoCA and MMSE during the 3rd, 4th and 5th decades; however, significant differences with regard to memory and language (p<0.01– p<0.001) emerged in the 6th through 9th decades. We conclude that the MoCA may be more sensitive than the MMSE at detecting age-related decrements in cognitive performance, even in non-clinical adult populations. Study supported by: Huntington’s Disease Society of America (HDSA) and Shiley Marcos Alzheimer’s Disease Research Center NIH P50 AG005131 T1508. Amyloid Imaging with Florbetapir-PET Correlates with Cognitive Performance in Non-Demented Oldest-Old Maria M. Corrada, Dana E. Greenia, Chris M. Clark, Carrie B. Peltz, Mark A. Mintun, Michael J. Pontecorvo, Abhinay D. Joshi and Claudia H. Kawas; Irvine, CA; Philadelphia, PA and St. Louis, MI T1506. Therapeutic and Preventive Effects of a Novel AD Vaccine Carmen Vigo, Ivan Cuevas, Lucia Fernandez, Valter Lombardi, Richard Manivanh and Ramon Cacabelos; Sunnyvale, CA and Bergondo, La Coruna, Spain A vaccine consisting of b-amyloid peptide (Ab) delivered in a liposomal matrix composed of phosphatidylcholine: phosphatidylglycerol: cholesterol: sphingosine-1-phosphate (EB101) was administered intraperitoneally for seven months to double transgenic mice (B6C3-Tg (APPswe,PSEN1dE9)), before or after the AD pathology was developed. Ab plaques and neurofibrillary tangles were quantified by ELISAs and brain histology using specific antibodies. Basal immunological interaction between the T-cells in the affected hippocampal area and other immune activation markers, including glial fibrillary acidic protein (GFAP) (astroglia) and CD-45 (B-cells) were also studied. Both preventive and therapeutic vaccination with EB101 resulted in a marked inhibition of Ab deposits (from 60 to 90%), a reduction of neurofibrillary tangles (70 to 90%) and almost completely suppression of reactive gliosis as measured by GFAP immunoreactivity, consistent with a marked decrease in amyloidosis-induced inflammation. No external neurological deficits were observed as a result of EB101 immunization (limb paralysis or brain atrophy). Cognitive tests in these animals treated with EB101 also show a dramatic improvement in learning and psychomotor activity. The present results indicate that the immunization with EB101 prevents and reverses AD neuropathology and underlined inflammation, thus warranting further studies. Study supported by: Euroespes Foundation We examined the association between amyloid imaging with florbetapir F18 positron emission tomography (PET) and cognitive performance in non-demented oldest-old. Thirteen non-demented oldest-old subjects received a florbetapir-PET scan within 3 months of neuropsychological testing, which included the Modified Mini-Mental State Exam (3MS), California Verbal Learning Test (CVLT) 10minute delay, Boston Naming Test, and Trails A and B. Scans were analyzed with a semiautomated quantitative analysis of the cortical to cerebellar signal ratio (SUVr) on the average of 6 cortical brain regions (frontal, temporal, parietal, anterior and posterior cingulate, and precuneus). Participants were 9 women and 4 men with an average age of 94.2 years (range:90–99). Eight participants were diagnosed as cognitively normal and 5 had cognitive impairment but did not meet dementia criteria. CVLT scores correlated significantly with the average SUVr (Pearson corr ¼ À0.64, p ¼ 0.03) and 3MS scores trended towards a significant correlation with the average SUVr (Pearson corr ¼ À0.54, p ¼ 0.07). This preliminary study suggests that greater amyloid burden is associated with poorer cognition, especially memory, in non-demented oldest-old participants. Amyloid imaging may identify oldest-old individuals at increased risk of developing Alzheimer’s disease. Study supported by: NIH grant RO1AG21055 and Avid Radiopharmaceuticals, Inc. Dr. Kawas and Ms. Grenia received a grant from Avid Radiopharmaceuticals (awarded to UCI) for their participation in this study. Dr. Clark, Dr. Mintun, Dr. Pontecorvo, and Mr. Joshi are employees of Avid Radiopharmaceuticals, a wholly owned subsidiary of Eli Lilly. T1507. MoCA vs. MMSE: Patterns of Cognitive Performance across Adult Lifespan in a Non-Clinical Sample Shea Gluhm, Charles Van Liew, Jody Goldstein, Guerry Peavy, Mark Jacobson, Stephanie Lessig and Jody Corey-Bloom; La Jolla, CA and San Diego, CA T1509. FRET Measurements of Ab-Induced Glutamate Release from Astrocytes Sara Sanz-Blasco, Juan C. Pin˜a-Crespo, Maria V. Talantova and Stuart A. Lipton; La Jolla, CA The Mini Mental State Examination (MMSE) is the most commonly used brief cognitive screening instrument; however, the Montreal Cognitive Assessment (MoCA) may be more sensitive to early cognitive dysfunction. The present study sought to compare age-related decline on these measures across the adult lifespan in a non-clinical sample. Performance on the MMSE and MoCA of 202, presumably normal, community-dwelling participants ranging in age from 20–89, divided by decade, were compared with Recent failures of clinical trials for Alzheimer’s disease (AD) using anti-amyloid b-peptide (Ab) approaches suggest that it may be necessary to attack downstream targets in the Ab cascade. To elucidate such targets, we studied the effect of Ab on astrocytes. Astrocytes are known to modulate 71 ID: senthilk I Black Lining: [ON] I Time: 08:46 I Path: //xinchnasjn/01Journals/Wiley/3b2/ANA#/Vol00000/110244/APPFile/JW-ANA#110244 J_ID: ZAY Customer A_ID: SUPP11-6 Cadmus Art: 22579 Date: 31-August-11 neuronal excitability and synaptic transmission. Here, we used the glutamate sensing fluorescent reporter (SuperGluSnFR) developed by Roger Tsien’s laboratory to perform sensitive optical measurements of glutamate release in response to Ab. This probe provides both a temporal and quantitative fluorescent readout of glutamate concentration by imaging FRET-dependent changes. We transfected HEK293T cells with SuperGluSnFr, and then co-cultured these �glutamate-sensing cells’ with astrocytes. Nanomolar concentrations of oligomerized (but not non-oligomerized) Ab induced release of several hundred-micromolar glutamate from astrocytes. These levels of glutamate can cause synaptic loss and excitotoxic damage to neurons. Taken together with prior studies, our work suggests that the neurotoxic effects of Ab may be mediated at least in part by local release of glutamate from astrocytes. Additionally, we found that newer congeners of memantine (called NitroMemantines) are able to prevent toxic glutamatergic effects of Ab to a greater degree than memantine itself. Study supported by: NIH and ADAMAS Pharmaceuticals, Inc. Stuart Lipton is the named inventor on patents for memantine and NitroMemantine for neurodegenerative disorders that are licensed to Forest Laboratories, Inc. and ADAMAS Pharmaceuticals, Inc., respectively. Concerning memantine, Dr. Lipton participates in a Royalty Sharing Agreement administered by his former institution, Harvard Medical School/Children’s Hospital, Boston. Stage: Page: 72 Guam ALS-PD Complex (tauopathy) is linked epidemiologically to cycasin, methylazoxymethanol (MAM) glucoside, a neurotoxin, carcinogen and genotoxin. MAM produces O6methylguanine (O6-mG) DNA lesions that are repaired by O6-mG methyltransferase (MGMT). We asked whether MAM-induced DNA damage in MGMT-deficient (MgmtÀ/À) mouse brain (a model of the young adult human brain) activates signal transduction pathways perturbed in neurodegenerative disease. Brain transcriptional profiles of young adult MgmtÀ/Àand wild-type mice were determined at intervals after a single systemic dose of MAM or vehicle. MgmtÀ/À mice treated with MAM vs. vehicle showed 362 differentially expressed genes, of which 57 were highly correlated with O6-mG levels. Sixty of 153 modulated genes correlated with O6-mG when the response of wild-type vs. MgmtÀ/À mice to MAM vs. vehicle was determined. Top associations were with neurological disease, psychological disorders, cancer, and genetic disorders. Prominent MAM-modulated brain KEGG pathways included Wnt-beta-catenin, which is perturbed in Alzheimer Disease (AD) and in MAM-induced colorectal carcinoma. Thus, MAM modulates pathways common to cancer (in cycling cells) and cell degeneration (in non-cycling neurons). Exposure to environmental MAM-like genotoxins (e.g., nitrosamines) may have relevance to the etiology of other tauopathies, notably AD. Study supported by: National Institutes of Environmental Health Sciences: ES11384, ES11399, ES011387 and ES07033. T1510. Is Poststroke Dementia Related to Amyloid Deposition and Microglia Activation? Wolf-Dieter Heiss, Basia Radlinska, Jean-Paul Soucy, Ralf Schirrmacher, Alexander Thiel and Vladimir Hachinski; Cologne, Germany; Montreal, QC, Canada and London, ON, Canada T1512. Genetic Associations between VPS10 Receptor Genes and Late-Onset Alzheimer’s Disease Christiane Reitz, Joseph Lee, Lindsay Farrer, Margaret PericakVance, Jonathan Haines, Ekaterina Rogaeva, Peter St. GeorgeHyslop and Richard Mayeux; New York; Boston; Miami; Nashville and Toronto, Canada Amyloid deposition typical for Alzheimer’s Disease might be a predisposing factor for poststroke dementia and might be aggravated by inflammation accompanying ischemic changes. The relationship between amyloid deposition, inflammatory reaction and development of poststroke dementia is studied in 5 patients with first supratentorial ischemic stroke by MRI (at 2 weeks and 5 – 7 months) and PET with 11C-PIB for amyloid imaging and with 11C-PK 11195 for inflammation at 6 months, the clinical course is followed for 12 months. Preliminary results indicate a significant increase in global PIB uptake (SUVR > 1.5) in the entire cortex compared to cerebellum. This amyloid deposition usually was asymmetric with peak values in prefrontal (SUVR ¼ 2.29 6 0.325) or parieto-temporal areas (SUVR ¼ 2.02 6 0.202). Increased PK-uptake as a marker of microglia activation was found in areas around the infarct, but also in connecting fiber tracts and distant from the ischemic lesion. These preliminary data demonstrate amyloid deposition and increased microglia activation in patients after stroke. The relationship between these two pathological processes and their impact on the development and progression of cognitive impairment will be further investigated. Background: Genetic and functional studies showed that genetic variation in SORL1 and SORCS1 is associated with LOAD risk by modulating secretase processing of APP. Consequently, underexpression of SORL1 or SORCS1 leads to Ab overexpression and increased LOAD risk. We hypothesized that also genetic variation in the homologs SORCS2 and SORC3 is associated with LOAD. Methods: First, we analyzed associations between genetic variation in SORCS2 and SORCS3 and LOAD risk in several independent datasets. Then, we compared SORCS2 and SORCS3 expression levels in brain regions from LOAD cases and controls, and performed cell biological experiments exploring the effect of both genes on APP processing. Results: Consistent with SORL1 and SORCS1, inherited variants in SORCS2 and SORCS3 were associated with LOAD risk. In addition, both genes were underexpressed in amygdala tissue from LOAD brains compared to control brains. Finally, we found evidence that - similar to SORL1 and SORCS1- both SORCS2 and SORCS3 may influence APP processing by modulating gamma secretase processing of APP. Conclusions: In addition to SORL1 and SORCS1, also variants in SORCS2 and SORCS3 may play a role in the pathogenesis of LOAD through an effect on APP processing. Study supported by: R37-AG15473 (Mayeux), P01AG07232 (Mayeux), R01-AG09029 (Farrer), R01AG025259 (Farrer), P30-AG13846 (Boston University Alzheimer’s Disease Research Center grant), K23AG034550 (Reitz). R01-AG027944 (Pericak-Vance), R01-AG019757 (Pericak-Vance) T1511. Cycad Methylazoxymethanol Linked to DNA Damage, Cancer and Neurodegeneration Glen E. Kisby, Rebecca C. Fry, Michael R. Lasarev, Theodor K. Bammler, Richard P. Beyer, Mona I. Churchwell, Daniel R. Doerge, Lisiane B. Meira, Valerie S. Palmer, Ana-Luisa Ramos-Crawford, Xuefeng Ren, Robert S. Sullivan, Terrance J. Kavanagh, Leona D. Samson, Helmut Zarbl and Peter S. Spencer; Portland, OR; Seattle, WA; Cambridge, MA; Jefferson, AR; Guildford, Kent, United Kingdom; Buffalo, NY; Piscataway, NJ and Chapel Hill, NC 72 ID: senthilk I Black Lining: [ON] I Time: 08:46 I Path: //xinchnasjn/01Journals/Wiley/3b2/ANA#/Vol00000/110244/APPFile/JW-ANA#110244 J_ID: ZAY Customer A_ID: SUPP11-6 Cadmus Art: 22579 Date: 31-August-11 T1513. Cardiac Ejection Fraction, Cognitive Function and Leukoaraiosis in an Elderly Cohort: The Cardiovascular Health Study Rebecca F. Gottesman, Salvador Cruz-Flores, Annette Fitzpatrick, John Gottdiener, Traci Bartz, Richard Kronmal and W.T. Longstreth, Jr.; Baltimore, MD; St. Louis, MO and Seattle, WA Stage: Page: 73 AG024904). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: Abbott, AstraZeneca AB, Bayer Schering PharmaAG,Bristol-Myers Squibb, Eisai Global Clinical Development, Elan Corporation, Genentech, GE Healthcare, GlaxoSmithKline, Innogenetics, Johnson and Johnson, Eli Lilly and Co., Medpace, Inc., Merck and Co., Inc., Novartis AG, Pfizer Inc, F. Hoffman-La Roche, Schering-Plough, Synarc, Inc., and Wyeth, as well as non-profit partners the Alzheimer’s Association and Alzheimer’s Drug Discovery Foundation, withparticipation from the U.S. Food and Drug Administration. Private sector contributions to ADNI are facilitated by the Foundation for the National Institutes of Health (www.fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer’s Disease Cooperative Study at the University of California, San Diego. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of California, Los Angeles. This research was also supported by NIH grants P30 AG010129, K01 AG030514, and the Dana Foundation. None of the study sponsors had any role in the design and conduct of the current study, nor in data analysis, interpretation, preparation, review or approval of the manuscript. L. McEvoy’s spouse is President, CorTechs Labs, Inc. La Jolla, CA; Sebastian Magda is an employee of CorTechs Labs, Inc. Background: Heart failure has been associated with cognitive dysfunction. To explore mechanism, we examined associations among ejection fraction (EF), cognition, and MRIdefined white matter hyperintensity (WMH) in the Cardiovascular Health Study (CHS), a longitudinal cohort study of participants !65 years old. Methods: We included 1972 CHS participants who underwent echocardiography, 2 brain MRIs 5 years apart, and cognitive assessments concurrent with the MRIs. Linear regression models including vascular risk factors, demographics, and EF (normal or impaired) were used to evaluate these outcomes: WMH grade on a 10-point scale, progression of WMH by !1 grade, and change in cognitive performance on the 100point modified Mini-Mental State examination (3MS) and Digit Symbol Substitution test (DSST). Results: EF independently predicted WMH grade at the second MRI (p ¼ 0.05) and WMH progression (OR 1.61, 95% CI 1.07–2.43). Worse EF independently predicted more decline in 3MS (p ¼ 0.02) and DSST (p ¼ 0.02), but these relationships were partially attenuated with WMH grade as a covariate. Conclusions: In an elderly population, EF predicts volume and progression of WMH. EF also predicts cognitive performance, but this may be partially mediated through effects on the white matter. Study supported by: NIH/ NHLBI (not to the first / corresponding author directly) T1515. Light and Electron Microscopic Analysis of FUS Immunoreactivity in 3 Variants of Tau and TDP-43 Negative Frontotemporal Lobar Degeneration Keith A. Josephs, Wen-Lang Lin, Joseph E. Parisi, Neil GraffRadford, Ronald C. Petersen and Dennis W. Dickson; Rochester, MN and Jacksonville, FL Background: The majority of frontotemporal lobar degenerations (FTLD) can be classified as tau or TDP-43 immunoreactive. Three rare variants were unclassified until recent evidence demonstrated FUS immunoreactivity: neuronal intermediate filament inclusion disease (NIFID), atypical FTLD with ubiquitin-immunoreactive inclusions (aFTLDU) and basophilic inclusion body disease (BIBD). Aim: To assess the immunohistochemical profile of NIFID, aFTLD-U and BIBD. Methods: Light, electron and immunoelectron microscopic analysis of 15 cases of NIFID (n ¼ 5), aFTLD-U (n ¼ 8) and BIBD (n ¼ 2). Results: All aFTLD-U and BIBD, and 3/5 NIFID cases were FUS immunoreactive. One FUS-negative NIFID case showed TDP-43 immunoreactivity. Electron microscopic examinations revealed FUS-immunoreactive granulofilament cytoplasmic inclusions in all aFTLD-U and BIBD cases, and in the FUS-positive NIFID cases. Granulofilament inclusions in the TDP-43 positive NIFID case were FUS negative, yet TDP-43-immunoreactive. Compact hyaline inclusions in all 5 NIFID cases were FUS-negative. Conclusions: Unlike in aFTLD-U and BIBD, FUS immunoreactivity in NIFID is variable and is limited to only certain types of inclusions, arguing against the notion that FUS is the primary pathological process in NIFID. Furthermore, TDP43 immunoreactivity and NIFID are not mutually exclusive. Study supported by: NIH R01-AG037491 T1514. Predicting MCI Outcome with Clinically Available MRI and CSF Biomarkers David S. Heister, James B. Brewer, Sebastian Magda, Kaj Blennow and Linda K. McEvoy; La Jolla, CA and Mo¨lndal, Sweden Cerebrospinal fluid (CSF) measures and medial temporal lobe atrophy (MTLA) on structural magnetic resonance images (MRIs) each predict decline to Alzheimer’s disease (AD), but how such measures can be used clinically to improve predictive prognosis is unclear.193 MCI participants were separated into risk groups (high/low) based on MTLA, quantified from FDA-approved software for volumetric imaging of MRIs, or based on cerebrospinal fluid (CSF) levels of total tau and Ab 1–42. Participants were also stratified into groups based on the combination of MTLA and CSF risk measures. Cox hazards models were used to assess group hazard ratios (HR) of converting to AD. MCI individuals with high atrophy or high CSF risk showed significantly greater hazard of AD conversion than those with low risk for each measure (HR: 3.52–4.20). Combining atrophy and CSF risk information substantially improved predictive ability. Individuals with both risk factors showed a significantly higher HR (13.68) than those with neither risk factor. Using both measures, 80% of high-risk individuals developed AD in 3 years compared to 10% of low-risk individuals. Clinically available CSF and MRI measures can be combined to significantly improve predictive prognosis in MCI. Study supported by: L.K.M. is supported by NIA K01AG029218; J. B.B. is supported by NINDS K02NS067427. Data collection and sharing for this project was funded by the Alzheimer’s Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 T1516. Effects of Once-Daily, Extended-Release Memantine (28 mg/day) on Cognitive Domains in Patients with Moderate to Severe Alzheimer’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 73 ID: senthilk I Black Lining: [ON] I Time: 08:46 I Path: //xinchnasjn/01Journals/Wiley/3b2/ANA#/Vol00000/110244/APPFile/JW-ANA#110244 J_ID: ZAY Customer A_ID: SUPP11-6 Cadmus Art: 22579 Date: 31-August-11 In this post hoc analysis of a 24-week, randomized, placebocontrolled trial (MEM-MD-50, NCT00322153) in ChEItreated patients with moderate to severe Alzheimer’s disease (AD), we examined the effects of a new, extended-release (ER) formulation of memantine (28 mg, once daily) on individual SIB domains, as well as on aggregated domains defined previously (Schmitt, 2006). Treatment groups were compared in terms of mean change from Baseline at Endpoint for nine SIB domains (Social Interaction, Memory, Orientation, Language, Attention, Praxis, Visuospatial Ability, Construction, and Orienting to Name) and combinations of domains aggregated using a face-valid approach into three higher-order subscales: MEMORY, LANGUAGE, and PRAXIS. Significant advantage of memantine ER over placebo was observed for the domains of Memory (OC, P ¼ 0.021; LOCF, P ¼ 0.016), Language (OC, P ¼ 0.003; LOCF, P ¼ 0.004), Attention (OC, P ¼ 0.014; LOCF, P ¼ 0.003), Praxis (OC, P ¼ 0.015; LOCF, P ¼ 0.002), Orientation (LOCF, P ¼ 0.043), and Construction (OC, P ¼ 0.042), and for all three higher-order subscales (MEMORY: OC, P ¼ 0.002; LOCF, P ¼ 0.003; LANGUAGE: OC, LOCF, P ¼ 0.003; PRAXIS: OC, P ¼ 0.012; LOCF, P ¼ 0.004). In conclusion, memantine ER treatment may be associated with significant improvements on several cognitive domains, including memory, language, praxis, and attention. Study supported by: Forest Research Institute Michael Tocco and Stephen M. Graham are employees of Forest Research Institute, Inc. Suzanne Hendrix is an employee of Pentara Corporation, an independent contractor to several pharmaceutical companies, including Forest Research Institute, Inc. Michael L. Miller and Vojislav Pejovic are employees of Prescott Medical Communications Group, an independent contractor to several pharmaceutical companies, including Forest Research Institute, Inc. Stage: Page: 74 Drs. Stephen Graham and Michael Tocco are employed by Forest Research Institute. Dr. Suzanne Hendrix is an employee of Pentara Corporation, an independent contractor to several pharmaceutical companies, including Forest Research Institute, Inc. Drs. Michael L. Miller and Vojislav Pejovic are employees of Prescott Medical Communications Group, an independent contractor to several pharmaceutical companies, including Forest Research Institute, Inc. T1518. Clinical Gait Abnormalities and Hippocampal Morphometry in MCI: Preliminary Results from the ADNI Study Vincent S. DeOrchis and Joe Verghese; Bronx, NY Objective: To examine whether clinical gait abnormalities could identify aMCI subjects with reduced hippocampal volume and increased risk of cognitive decline. Methods: The population for this study included subjects with aMCI diagnosed using established criteria and with neuroimaging enrolled in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) study. Hippocampal volume was assessed in 370 aMCI subjects using semiautomated voxel based morphometry available on the ADNI website. The association of gait abnormalities, as diagnosed by study clinicians, with hippocampal volume was assessed using linear regression adjusted for age, gender, education and total brain volume. Results: Subjects mean age was 72.8 years, average education was 15.4 years and 62.3% were women. The mean hippocampal volume was 3188.77 þ/À 562.27mm3 on the right and 3145.28 þ/À 549.78mm3 on the left. Clinical gait abnormalities were diagnosed in 35 (9.3%) subjects and were associated with right hippocampal volume (estimate À264.646, 95% CI: À443.4 to À85.8, p ¼ 0.004), but not the left (p ¼ 0.053). Adding MMSE or memory test scores to the final model did not change the significance of association. Conclusions: Our preliminary study supports gait abnormalities as a clinical marker of worse hippocampal morphology in aMCI. T1517. Efficacy of Memantine by Baseline Disease Severity: A Pooled Post-Hoc Analysis of Trials in Mild to Moderate Alzheimer’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 T1519. Topography of Cortical Thinning in PIBNegative Subcortical Vascular Dementia Versus Alzheimer’s Disease Chi Hun Kim, Sang Won Seo, Sung Tae Kim, Jae-Hong Lee, Jae Seung Kim, Seung Jun Oh, Suk-Hui Kim, Hae Kwan Cheong, Jong-Min Lee, Seun Jeon and Duk L. Na; Seoul, Korea and Suwon, Korea Several randomized, placebo-controlled trials have demonstrated benefits of memantine in patients with moderate to severe Alzheimer’s disease (AD); trials in mild to moderate AD have yielded less consistent results. The dementia severity range in which memantine may provide benefits should be determined with greater precision. In this post-hoc analysis, we pooled 713 memantine-treated (20 mg/day) and 559 placebo-treated patients from three randomized trials in mild to moderate AD (MMSE range: 10–23). For each baseline MMSE value, mean change from baseline was estimated for measures of cognition (ADAS-cog), function (ADCS-ADL23), global status (CIBIC-Plus), and behavior (NPI). Furthermore, data (intent-to-treat population, observed cases) were analyzed by means of a mixed model with quadratic terms for time and baseline MMSE. Memantine treatment was associated with significant benefits versus placebo within the MMSE range of 12–20 for the ADAScog, 15–18 for the ADCS-ADL, and 10–17 for the CIBICPlus; no significant differences between groups were observed for the NPI. In conclusion, memantine treatment may be associated with significant cognitive, functional, and global benefits in patients with MMSE scores corresponding to the early moderate stage of AD. Study supported by: Forest Research Institute Objective: To determine the existence of cortical atrophy in Subcortical Vascular Dementia (SVaD) with negative 11CPittsburgh compound B (PIB) PET scan and to compare the topography of cortical thinning between PIB (-) SVaD and Alzheimer’s disease (AD). Methods: Cortical thickness in 24 patients with PIB (-) SVaD, 81 clinically probable AD subjects with minimal ischemia, and 72 normal cognitive controls (NC) was measured using a surface-based morphometric method. The results were compared and mapped onto a 3D brain surface. Results: Compared with NC, significant cortical thinning of PIB (-) SVaD was noted in a widespread area including frontal, temporoparietal, medial frontal, posterior cingulate cortices, and ligual gyri. Compared with AD, PIB (-) SVaD demonstrated cortical thinning in bilateral perisylvian area, ligual gyri, and right medial frontal lobe. Compared with PIB (-) SVaD, AD showed significant cortical atrophy in bilateral medial temporal lobes and precuneus. 74 ID: senthilk I Black Lining: [ON] I Time: 08:46 I Path: //xinchnasjn/01Journals/Wiley/3b2/ANA#/Vol00000/110244/APPFile/JW-ANA#110244 J_ID: ZAY Customer A_ID: SUPP11-6 Cadmus Art: 22579 Date: 31-August-11 Stage: Page: 75 Results: Across our mixed sample of subjects (n ¼ 33; 21 with Fragile X-associated Tremor Ataxia Syndrome, 12 normal controls, mean age ¼ 65, mean MMSE ¼ 27), a significant correlation (r ¼ 0.38, p ¼ 0.029) was present between P600 repetition effect amplitude and left, but not right, hippocampal volume. Linear regression models found that subsequent cued recall was predicted by left hippocampal volume and age. In contrast, free recall correlated with P600 repetition effect amplitude (rho ¼ .49, p ¼ 0.004) only. Conclusion: P600 word repetition effect correlates with left hippocampal volume. These two measures appear complementary and predict different aspects of memory performance. Study supported by: National Institutes of Health Roadmap Interdisciplinary Research Consortium Grant [Grant Numbers UL1DE019583 (NIDCR), RL1AG032115], NIH Grant R01-AG18442, California Alzheimer’s Disease Program Randi Hagerman receives research support from Neuropharm, Seaside therapeutics, Forest, Johnson and Johnson and Roche and consultation with Novartis for fragile X research studies. Interpretation: Small vessel disease without amyloid burden may lead to substantial cortical atrophy. PIB (-) SVaD demonstrated characteristic cortical thinning in bilateral perisylvian area, ligual gyri, and the right medial frontal lobe. Study supported by: The Korea Healthcare Technology R&D Project, Ministry for Health, Welfare & Family Affairs, Republic of Korea (A050079), grants from the Asan Institute for Life Sciences (2006-159), and the Conversing Research Center Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2009-0081959) T1520. The First Nationwide Survey of Bardet-Biedl Syndrome in Japan Makito Hirano, Toshihide Yamashita, Yasushi Ikuno, Hiromi Iwahashi, Mitsuru Ohishi, Toshiyuki Mano, Ryu Ishihara, Ichiro Tanaka, Keiko Yanagihara, Yusaku Nakamura and Susumu Kusunoki; Sakai, Osaka, Japan; Suita, Japan; Izumi, Japan; Osaka, Japan; Kashihara, Japan and Osaka Sayama, Japan Bardet-Biedl syndrome (BBS) is an autosomal recessive disorder characterized by mental impairment, rod-cone dystrophy, polydactyly, central obesity, hypogonadism, and renal abnormalities. The causative genes have been identified as BBS1-14 genes encoding proteins that maintain cilia function, but more than 20% of patients have no mutations identified. This disease is extremely rare in Japan, where only a few patients have been reported. We conducted the first nationwide survey of this disease in 2010. We summarized clinical and genetic information of newly identified patients and previously reported patients. We found that rare liver fibrosis was detected in 20% of patients, while only 30% of patients had apparent renal abnormalities, thought to be a universal symptom. DNA array analysis (BBS1-10,12) was performed in 9 patients with clinically definite or possible BBS, but no known mutations were identified. However, cultured fibroblasts from two patients had reduced protein levels of BBS6 without any coding mutations, suggesting abnormalities in transcription/translation or protein instabilities affected by other regulatory proteins. In conclusion, we speculate that clinical symptoms and genetic background of BBS in Japan may differ from those in the Western countries. Study supported by: Health and Labour Science Research Grants in Japan (Research in intractable diseases) T1522. Visuospatial Construction Measures and Their Utility in Identifying Dementia of the Alzheimer’s Type Bonnie M. Scott, G. Duncan, H. Carlson, Matthew Nance, Michele K. York, Angela Larery, Josephine Stouter and Adriana M. Strutt; Houston, TX Objectives: To examine the psychometric properties and clinical utility of three visuospatial-construction (VC) measures in differentiating Mild Cognitive Impairment (MCI) and Alzheimer’s disease (AD). Background: Assessment of VC deficits aid clinicians in distinguishing AD from other forms of dementia and determining the patient’s functional status. However, there is currently no research comparing the psychometric properties of commonly employed VC measures with MCI subtypes and varying stages of AD. Methods: 37 MCI and 126 AD patients completed the Beery-Buktenica Developmental Test of Visual Motor Integration (Beery), Rey-Osterrieth Complex Figure Test (ReyO), and the Block Design subtest of the WAIS-III. Results: Age and education significantly differed between groups, and were therefore utilized as covariates. ANCOVAs revealed significant between group differences (p<0.001) across the three outcome measures. While the Rey-O demonstrated the highest sensitivity (76.2%), the Beery yielded a greater specificity (94.6%). Additional statistics will be presented for the VC measures by subgroups (e.g. amnestic vs non-amnestic; mild and moderate AD). Discussion: Considering the significant differences between the VC capacities of patients with and without neurodegenerative conditions, identification of the most statistically sound instrument in assessing VC is warranted. T1521. P600 Word Repetition Effect Amplitude Correlates with Left Hippocampal Volume John M. Olichney, Rawi Nanakul, Alireza K. Javan, Patrick E. Adams, Andrea Schneider, Andreea Seritan, Randi J. Hagerman, Paul J. Hagerman and Susan M. Rivera; Davis, CA and Sacramento, CA Background: Prior work has shown that hippocampal volume and certain ERP components (e.g. P600 repetition effect) can be predictors of memory ability. However, the relationship between hippocampal volume and electrophysiological measures of human memory remains unclear. Objective: To define the relationship between P600 word repetition effect amplitude and hippocampal volume. We hypothesized they would be moderately correlated, with each variable independently predicting verbal memory. Methods: 32 channel ERP data was recorded during a category decision task. Structural 3T MRI was acquired (Siemens Trio) and hippocampal volumes measured on 3D MPRAGE sequences. T1523. Responder Analysis in a Trial of Once-Daily, Extended-Release Memantine (28 mg) in Patients with Moderate to Severe Alzheimer’s Disease 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 therapeutic responses 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. For each efficacy 75 ID: senthilk I Black Lining: [ON] I Time: 08:46 I Path: //xinchnasjn/01Journals/Wiley/3b2/ANA#/Vol00000/110244/APPFile/JW-ANA#110244 J_ID: ZAY Customer A_ID: SUPP11-6 Cadmus Art: 22579 Date: 31-August-11 measure (SIB, ADCS-ADL19, NPI, CIBIC-Plus), 5 response levels were defined, based on change scores attained at Endpoint by the 10th, 25th, 50th, 75th, and 90th percentile of placebo-treated patients. The proportions of memantineand placebo-treated patients attaining each response level (or better) were compared using Fisher’s exact test. For each outcome measure, the proportion of memantine-treated patients numerically exceeded that of placebo-treated patients at all response levels. On the SIB, the memantine group was significantly superior at the 90th percentile level (improvement >11 points; P ¼ 0.003), on the NPI at the 90th percentile level (improvement !17 points; P ¼ 0.018) and the 75th percentile level (improvement !8 points; P ¼ 0.016), and on the CIBIC-Plus at the 75th percentile level (score <3: P ¼ 0.023). No significant between-group differences were observed on the ADCS-ADL19. In conclusion, memantine ER provided consistent benefits on the SIB, NPI, and CIBIC-Plus, particularly among patients who experienced relatively high levels of improvement. Study supported by: Forest Research Institute Michael Tocco and Stephen M. Graham are employees of Forest Research Institute, Inc. Suzanne Hendrix is an employee of Pentara Corporation, an independent contractor to several pharmaceutical companies, including Forest Research Institute, Inc. Michael L. Miller and Vojislav Pejovic are employees of Prescott Medical Communications Group, an independent contractor to several pharmaceutical companies, including Forest Research Institute, Inc. Stage: Page: 76 Resistance to cognitive decline from neuropathology is postulated to occur due to cognitive reserve (CR). We examined whether baseline regional cortical thickness and rate of regional atrophy are structural markers for CR. We hypothesized that higher education, a proxy for CR, would be related to greater cortical thickness in areas related to literacy or intellectual ability in healthy controls and individuals with mild cognitive impairment (MCI) from the Alzheimer’s Disease Neuroimaging Initiative. Cortical thickness in these regions was compared between high (>18 yrs) and low education (<13 yrs) subgroups among controls and MCI individuals separately. Unexpectedly, high education was related to thinner cortices at baseline for controls in lateral occipital and temporal regions and for MCI in the left inferior parietal region after controlling for age and sex. In MCI, the difference in cortical thickness persisted after controlling for disease severity. Pre-existing thinner cortex in the high education group was not associated with a higher atrophy rate than that observed in the low education group. Cortical thickness in areas related to intellectual ability or literacy therefore may not be a persistent marker of CR. Study supported by: Supported by grants from the National Institute of Aging (AG031224; K01AG029218) and the National Center for Research Resources (#U24 RR021382). A.M.D. is a founder of and holds equity interest in CorTechs Labs, Inc, La Jolla, Calif, and serves on its Scientific Advisory Board. The terms of this arrangement have been reviewed and approved by the University of California, San Diego, Calif, in accordance with its conflict of interest policies. The spouse of L.K.M. is president of CorTechs Labs, Inc, La Jolla, Calif. T1524. Rates of Cognitive Decline and Alzheimer’s Disease (AD) Neuropathology in Oldest-Old Archana B. Balasubramanian, Claudia H. Kawas, Daniel J. Berlau, Carrie B. Peltz and Marı´a M. Corrada; Irvine, CA Objective: To examine if rates of cognitive decline vary by level of AD neuropathology in oldest-old. Methods: Participants were 68 autopsied individuals from The 90þ Autopsy Study, a population-based longitudinal study of people aged 90 and older. Participants were non-demented at baseline and had 3 or more visits. Global cognition was assessed using the Mini-Mental State Exam (MMSE). Participants were categorized as having low or high AD neuropathology based on plaques (CERAD staging: Low ¼ 0-A, High ¼ B-C) and tangles (Braak staging: Low ¼ 0-III, High ¼ IV-VI). Random effects models were used to estimate rates of cognitive decline in people with low or high AD neuropathology. Results: Rates of cognitive decline did not differ by level of AD neuropathology. Individuals with low plaques declined 0.63 points/year on the MMSE, whereas individuals with high plaques declined 0.50 points/year (p ¼ 0.43). Individuals with low tangles declined 0.66 points/year on the MMSE, whereas individuals with high tangles declined 0.48 points/year (p ¼ 0.26). Conclusion: AD neuropathology is not associated with differing rates of cognitive decline in the oldest-old. Other factors such as health, lifestyle or other brain pathology may contribute to rates of cognitive decline in the oldest-old. Study supported by: NIH grants R01AG21055 and P50AG16573 T1526. Effects of Once-Daily, Extended-Release Memantine on Individual Activities of Daily Living in Patients with Moderate to Severe Alzheimer’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 study of a 24-week, randomized, placebocontrolled trial (MEM-MD-50, NCT00322153) in ChEItreated patients with moderate to severe Alzheimer’s disease (AD), we examined the effects of a new, extended-release (ER) memantine formulation (28 mg, once daily) on individual items and on factor-derived subscales from the 19item AD Cooperative Study Activities of Daily Living scale (ADCS-ADL19). A significant advantage of memantine ER over placebo was observed at study Endpoint (OC analysis) for ADL items of eating (P ¼ 0.024), clearing the table (P ¼ 0.010) and finding belongings (P ¼ 0.029); no other items demonstrated significant between-group differences. A factor analysis yielded 4 subscales: Basic ADLs (eating, walking, toileting, bathing, grooming, dressing), Higher-Level Functions (using telephone, conversing, clearing the table, finding belongings, obtaining beverage, disposing of litter), Praxis (turning faucet on, off, turning light on, off ), and Autonomy (watching TV, travelling, being left alone). At study Endpoint, the memantine ER group significantly outperformed the placebo group on the Higher-Level Functions subscale (OC, P ¼ 0.011; LOCF, P ¼ 0.026; MMRM, P ¼ 0.008). In conclusion, treatment with memantine ER may be associated with improvements in ADLs related to higher cognitive processing. Study supported by: Forest Research Institute Michael Tocco and Stephen M. Graham are employees of Forest Research Institute, Inc. Suzanne Hendrix is an T1525. Cortical Thickness on MR Imaging: Relation to Cognitive Reserve in Normal Aging and Mild Cognitive Impairment Jagan A. Pillai, Linda K. McEvoy, Donald J. Hagler, Jr, Dominic Holland, Anders M. Dale, David P. Salmon, Douglas Galasko and Christine Fennema-Notestine; San Diego, CA 76 ID: senthilk I Black Lining: [ON] I Time: 08:46 I Path: //xinchnasjn/01Journals/Wiley/3b2/ANA#/Vol00000/110244/APPFile/JW-ANA#110244 J_ID: ZAY Customer A_ID: SUPP11-6 Cadmus Art: 22579 Date: 31-August-11 employee of Pentara Corporation, an independent contractor to several pharmaceutical companies, including Forest Research Institute, Inc. Michael L. Miller and Vojislav Pejovic are employees of Prescott Medical Communications Group, an independent contractor to several pharmaceutical companies, including Forest Research Institute, Inc. Stage: Page: 77 T1529. A Translational Program of BDNF Gene Delivery for Alzheimer’s Disease Mark H. Tuszynski, Alan Nagahara, Adrian P. Kells, J. Bringas, John Forsayeth and Krystopf S. Bankiewicz; La Jolla, CA and San Francisco, CA Nervous system growth factors have extensive effects on neuronal function and survival. Nerve growth factor (NGF) prevents the death and stimulates the function of basal forebrain cholinergic neurons in correlational models of Alzheimer’s disease (AD), and is in a Phase 2 multi-center clinical trial using AAV2 gene delivery. Separately, Brain-Derived Neurotrophic Factor (BDNF) influences the survival and function of entorhinal cortical and hippocampal neurons in several animal models of AD, including transgenic mutant APP-expressing mice; aged rats and lesioned rats; and aged and lesioned primates. These effects occur independent of beta amyloid load. We are examining the safety and tolerability of BDNF gene delivery to the entorhinal cortex in rodent and primate dose escalation, safety and tolerability studies. Successful completion of these studies will lead to a Phase I trial of AAV2BDNF gene delivery to target short term memory loss in Alzheimer’s disease. The translation of this clinical program will require development and utilization of real-time, MRI-guided AAV2 vector delivery with gadoteridol co-infusion to track and confirm vector distribution to the intended target. Study supported by: NIH, VA, Alz Assoc, Shiley Family Foundation T1527. Neurophysiologic Markers of Aging-Related Muscle Weakness Ela B. Plow, Dina Gohar, Mehmed B. Bayram, Jing Hou, Alexandria Wyant, Yin Fang, Vlodek Siemionow and Guang H. Yue; Cleveland, OH Age-related muscle weakness is usually ascribed to peripheral factors, such as loss and change of muscle fibers. Recent evidence demonstrates that central neural drive diminishes with age, but its relation to strength remains unclear. We investigated the cortical neurophysiologic markers of agerelated muscle weakness using Transcranial Magnetic Stimulation (TMS). Ten healthy elderly (76.3 6 2.6yrs) and 15 young individuals (22.3 6 0.9yrs) were enrolled. Measures included left elbow flexion strength, size of muscle evoked potential (MEP) following suprathreshold TMS delivered to Right Motor Cortex (RM1), size of RM1 map of left biceps brachii (BB) muscle, and inter-hemispheric inhibition (IHI) exerted upon RM1. Results demonstrate that elderly, compared to the young, were weaker (83.4 6 8.4N vs.105.9 6 8.3N, p ¼ 0.04), possessed smaller RM1 map of BB (717.8 6 150.8sq. mm vs.1034.4 6 116.1sq. mm, p ¼ 0.05) and showed stronger IHI (79.9 6 6.3% vs. 63.5 6 6.2%, p ¼ 0.04), although their size of MEP was larger (1.1 6 0.2mV vs. 0.4 6 0.1mV, p ¼ 0.02). Stronger IHI was associated with smaller RM1 map of BB (r ¼ À0.38, p ¼ 0.05) and poor strength (r ¼ À0.36, p ¼ 0.06). Thus, although compensatory processes ensue in the muscle, age-related weakness persists. Reduced motor cortical maps and stronger inhibition from ipsilateral motor areas may explain weakness in the elderly; interventions modulating these cortical factors may improve strength. Study supported by: National Institutes of Health R01 NS035130 T1530. Imaging Signatures of Pathology in Behavioral Variant Frontotemporal Dementia Jennifer L. Whitwell, Clifford R. Jack, David S. Knopman, Bradley F. Boeve, Ronald C. Petersen, Joseph E. Parisi, Dennis W. Dickson and Keith A. Josephs; Rochester, MN and Jacksonville, FL Background: Behavioral variant frontotemporal dementia (bvFTD) is pathologically heterogeneous. The most common pathologies underlying bvFTD are Pick’s disease (PiD), corticobasal degeneration (CBD), and FTLD-TDP type 1. We aimed to determine whether patterns of atrophy on imaging differed across these pathologies in bvFTD. Methods: We identified 15 bvFTD subjects that had a volumetric MRI and a pathological diagnosis of PiD (n ¼ 5), CBD (n ¼ 5) or FTLD-TDP type 1 (n ¼ 5). Voxelbased morphometry was used to assess patterns of atrophy in each group compared to 20 controls. Results: All groups showed frontal grey matter loss, although specific patterns of atrophy differed across groups. The PiD group showed widespread frontal loss with involvement of the anterior temporal lobes. The CBD group showed less severe loss predominantly involving posterior lateral and medial superior frontal lobe. The FTLD-TDP group showed widespread loss in frontal, temporal and parietal lobes. Greater parietal loss was observed in FTLD-TDP compared to both other groups, and greater anterior temporal loss was observed in PiD compared to CBD. Conclusions: Atrophy patterns in bvFTD vary according to pathology and may therefore be helpful in predicting these underlying pathologies. Study supported by: NIH grants R01 DC10367, R01 AG037491, R21 AG38736, R01 AG11378 and P50 AG16574. T1528. The Purkinje Cell of the Cerebellar Cortex in Alzheimer’s Disease and Stavros J. Baloyannis; Thessaloniki, Greece Alzheimer’s disease is a heterogeneous neurodegenerative disorder, characterized by progressive memory loss, affective and behavioural changes.We studied the morphological findings of the cerebellar cortex, in twenty early cases of Alzheimer’s disease using electron microscopy and silver impregnation techniques. The Purkinje cells showed morphological alterations concerning dendritic profiles and axonic collaterals. Loss of dendritic branches was marked in Purkinje cells of the vermis. Large number of spines was lost in most of Purkinje cells. Axonic collaterals were also lost. The thick axonic network around the initial part of Purkinje cell axons, disappeard. The electron microscopy revealed morphological alterations of the mitochondria in the perikaryon, the dendritic processes and the axon of Purkinje cells. Fragmentation of the cisternae of Golgi apparatus was prominent.The loss of dendritic spines resulted in a dramatic decrease of the synapses in the molecular layer. However a tendency for regeneration of the spines was noticed, through a limited number of unattached spines. The synaptic alteration of the Purkinje cell emphasizes the importance of synaptic loss for the clinical and pathological profile of the disease, T1531. Improved Statistical Power To Detect Treatment Effects on Functional Outcomes in Alzheimer’s Disease (AD) Clinical Trials by Item-Response Theory (IRT) M. Colin Ard, Douglas R. Galasko and Steven D. Edland; La Jolla, CA 77 ID: senthilk I Black Lining: [ON] I Time: 08:46 I Path: //xinchnasjn/01Journals/Wiley/3b2/ANA#/Vol00000/110244/APPFile/JW-ANA#110244 J_ID: ZAY Customer A_ID: SUPP11-6 Cadmus Art: 22579 Date: 31-August-11 Stage: Page: 78 patients with AD (MMSE 3–18; N ¼ 166) who were titrated or switched immediately to memantine ER, and MEM-MD-54, a 28-week OLEX of a pivotal, 24-week, randomized, placebo-controlled trial of memantine ER (MEM-MD-50; NCT00322153) in patients with AD (MMSE 3–14; N ¼ 677). All patients from Study MEMMD-54 and most patients from MEM-MD-51 were taking a ChEI at Baseline, which continued throughout this study. Sixty-six patients received memantine during this trial; 44 (66.7%) completed the study, and 8 (12.1%) discontinued due to an AE. A total of 50 (75.8%) patients experienced a treatment-emergent AE, including UTI (13.6%), agitation (12.1%), aggression (10.6%), exacerbation of AD (9.1%), and anemia, constipation, weight decrease, and back pain (7.6% each); 17 (25.8%) experienced a serious AE. In conclusion, treatment with once-daily, memantine ER (28 mg) for up to two years is well tolerated in patients with moderate to severe Alzheimer’s disease. Study supported by: Forest Laboratories, Inc. Drs. Stephen Graham and James Perhach are employed by Forest Research Institute. The Alzheimer’s Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) scale assesses an individual’s ability to perform a range of everyday tasks and is frequently used as an endpoint in clinical trials for AD. While the ADCS-ADL has excellent face validity as a measure of the functional impact of AD, the manner in which it is constructed presents several challenges for longitudinal data analysis, including the use of different rating scales across items, item-specific gender and/or lifestyle biases, differences in the complexity or difficulty of indicated activities, and missing data at the item level. IRT constitutes a family of quantitative models that assume that responses on specific items are jointly probabilistically determined by item characteristics and underlying subject-level trait(s), and are well suited to handling item heterogeneity and missing data. Using data from an ADCS clinical trial of 409 mild to moderate AD patients we found that ADCS-ADL scores constructed from IRT-based re-weighted item scores displayed increased sensitivity to change and improved statistical power as an outcome measure in clinical trials. Study supported by: NIH/NIA AG010483 (SDE), AG005131 (SDE, DG), and AG034439 (MCA, SDE). T1534. A Retrospective Analysis Using Data-Monitoring Algorithms: What Are the Logical Relationships between the ADAS-Cog and MMSE? Christian Yavorsky, Guillermo DiClemente, Mark Opler, Sofija Jovic, Brian Rothman and Ashleigh DeFries; New York, NY T1532. Neuropathologic Basis of Age-Associated Brain Atrophy Deniz Erten-Lyons, Randy Woltjer, Hiroko Dodge, Lisa Silbert and Kaye Jeffrey; Portland, OR Background: The ADAS-Cog and MMSE are standard instruments in Alzheimer’s disease trials. The Critical Path Institute Online Data Repository (CODR) includes results of AD trials submitted by 11 sponsors. However, reliability and validity problems exist with clinician administered measures. Data-monitoring uses relationships between instruments to address this. We assessed the likelihood of error in assessments if they fell outside expected correlations between the ADAS-Cog and MMSE, and examined whether errors could have been detected by data-monitoring. Methods: Correlations of total ADAS-Cog and MMSE scores from AD patients in 11 trials were compared with known correlations. Assessments that fell out of previously reported ranges were evaluated using data-monitoring algorithms. Results: The correlation between MMSE and ADAS-Cog was .780 (p<.01), agreeing with the literature and used to establish an expected range. Nearly half (47%) of the sample fell out of the expected range. 90% of these contained one or more potential errors. Conclusions: The ADAS-Cog and MMSE scores that fell out of range were more likely to contain error that those that did not. Because these contained one or more item-level inconsistencies, data-monitoring would have detected this in-study. Study supported by: ProPhase LLC One or more authors are employed by ProPhase LLC. Objective: To examine the association between postmortem neuropathologic measures and antemortem brain atrophy in aging. Background: Better understanding of the neuropathologic basis of age-related brain atrophy is needed to differentiate disease processes from normal aging, and to optimize use of brain volume as an outcome in Alzheimer disease prevention studies. Methods: Seventy-three participants of a longitudinal aging study were followed until death. All subjects had ! 2 MRI scans, with the last scan within 36 months of death, and cognitive evaluations within 24 months of death. The association between antemortem rate of ventricular volume expansion over time and three postmortem measures:neurofibrillary tangles (NFTs), neuritic plaques (NPs) and infarcts (large vessel and lacunar) was examined using a mixed-effects model adjusting for age at death, APOE e4 presence and cognitive status. Results: Presence of infarcts, high NFT and NP scores were significantly associated with higher rate of ventricular enlargement regardless of cognitive status. e4 carriers also had a significantly higher rate of ventricular enlargement. Conclusion: These results suggest that brain atrophy, as indexed by ventricular enlargement, is a marker of accruing age-associated neuropathology independent of presence of cognitive impairment. Study supported by: Merit Review Grant & Research Career Development Award, Office of Research and Development, Department of Veterans Affairs, National Institutes of Health (AG08017, MO1 RR000334) T1535. Withdrawn T1536. Case of Bimodal Charles Bonnet Syndrome and Dementia Mirret El-Hagrassy and Gokhan Akfirat; New York, NY T1533. A Long-Term, Open-Label Extension Study Evaluating the Safety of Extended-Release Memantine (28 mg) in Patients with Moderate to Severe Alzheimer’s Disease Stephen M. Graham and James Perhach; Jersey City, NJ Case: 72 year old hearing impaired male with glaucoma, aggression toward hallucinations. Visual hallucinations followed blindness. He saw silent children, animals for months, recently heard familiar music. Sometimes had insight. Was admitted to Medicine after trying to fight with images for first time. Positive findings: disorientation, impaired short term memory, calculation. Anemia, prerenal acute kidney injury. No history of This study (MEM-MD-82) was a 52-week, multicenter, open-label extension (OLEX) of two previous trials of a 28mg, once-daily, memantine extended-release (ER) formulation: MEM-MD-51, a 52-week, open-label dosing trial in 78 ID: senthilk I Black Lining: [ON] I Time: 08:46 I Path: //xinchnasjn/01Journals/Wiley/3b2/ANA#/Vol00000/110244/APPFile/JW-ANA#110244 J_ID: ZAY Customer A_ID: SUPP11-6 Cadmus Art: 22579 Date: 31-August-11 dementia. Denied images, mentioned spirits, paranoid about witchcraft to make him look mad and get him locked up, implying pension would be stolen. He was hydrated, given Aricept, Seroquel, became calmer. He was discharged with diagnosis of Alzheimer’s dementia, bimodal CBS (Charles Bonnet Syndrome), possible resolved delirium and dehydration. Discussion: CBS involves complex visual hallucinations with partial or full insight; auditory variant rarely reported with visual, both associated with sensory deprivation. Patients often hide hallucinations, as our patient did. Management includes anticonvulsant, antipsychotic, and antidepressant trials, also reassurance, increasing sensory stimulation and socialization. CBS was suggested as early marker for dementia, particularly Alzheimer’s and Lewy Body dementias. Conclusion: Suggest screening blind or deaf patients for CBS; closely follow for signs of dementia if positive. Further studies to ascertain positive predictive value and if earlier diagnosis leads to improved outcomes. Stage: Page: 79 in headache days/month, we continued to treat and follow 123 consecutive patients for at least 2 years (mean 2.76 years; range 24 months-61 months). Results: Ten subjects (8%) eventually worsened despite continued treatment and relapsed to CM. Thirty-one subjects (25%) were able to stop onabotA therapy and remain largely free of headache for >6 months (mean sets of injections required: 4.8; range 2–8). Eighty-two (67%) remained responders but required ongoing injection therapy throughout the study period (at intervals ranging from 3 months to 6 months; mean 3.4 months). Out of 1,142 sets of injections, there was one serious adverse event (status migrainosus, requiring brief hospitalization). Conclusion: Most CM patients who initially respond to treatment with onabotA will maintain that response for at least 2 years, and a substantial minority will be able to discontinue treatment and do well without prophylactic therapy. Long-term therapy with onabotA for CM is associated with a very low incidence of SAEs. Member, Allergan Physician Advisory Board; Consultant, Allergan T1537. Lead Exposure Up-Regulated Autophagy Response in Neuroblastoma SH-SY5Y Cells Via mTOR Kinase Signaling Pathway Shun-Sheng Chen, Chueh-Tan Chen and Jiin-Tsuey Cheng; Kaohsiung, Taiwan T1603. Utility of Orally-Inhaled Dihydroergotamine When Early Intervention Is Impractical Shashidhar Kori, Stewart Tepper, Peter J. Goadsby, Paul Winner, Min Wang and Stephen Silberstein; Mountain View; Cleveland; San Francisco; West Palm Beach and Philadelphia Objective: To study the signal transduced interaction between b-amyloid accumulation and autophagy response of lead exposured neuroblastoma SH-SY5Y cells. Background: Cellular necrosis, apoptosis, and b-amyloid deposition frequently occur after chronic lead exposure, resulted in the amyloid-b formed during autophagic turnover of APPrich organelles supplied by both autophagy and endocytosis. Therefore, the new perspective was tried to prove the role of autophagy on amyloidogensis disorders of lead exposure. Methods: SH-SY5Y neurons were exposed with low concentration lead, and enhanced autophagy process was observed by western blot. The APP-mRNA levels, intracellular and secreted isoforms of APP, the mRNA levels, cell viability and b-amyloid production were also measured. Results: After lead exposure, SH-SY5Y cells were enhanced by their autophagy responses through increased LC3II from LC3I cleavage. Lead exposure also induced neuronal death by b-amyloid deposition. During autophagy process, neuronal death was accompanied with other autophagic characteristics as accumulation of the autophagosome and protein degradation regulated negatively by the mTOR kinase signaling. Conclusion: The autophagy processes have shown that enhancing chronic lead exposure in neurons is accompanied by accumulation of the autophagosome and protein degradation which regulated negatively via mTOR kinase signaling. Study supported by: National Science Council, Taiwan Background: Well-controlled studies have demonstrated substantial reductions in triptan efficacy with delayed migraine treatment, and surveys have revealed some patient reluctance to treat migraines early, leading to treatment failure and dissatisfaction. Methods: This post-hoc analysis of a randomized, double-blind, placebo-controlled phase 3 study of orally-inhaled DHE compared 2-hour pain-relief(PR) and pain-free(PF) rates among patients treating migraine within 1 hour, 1–4 hours, 4–8 hours, or >8 hours of its start. Results: Of 903 patients randomized, 771 treating a single attack were included in the efficacy analysis. Two-hour PF and PF rates were: 66% and 38% (inhaled DHE) and 41% and 13% (placebo) when treated within 1 hour of migraine start; 60% and 28% (inhaled DHE) and 35% and 10% (placebo) when treated within 1–4 hours; 53% and 22% (inhaled DHE) and 30% and 8% (placebo) when treated within 4–8 hours; and 49% and 19% (inhaled DHE) and 24% and 9% (placebo) when treated >8 hours after start. Conclusions: This analysis demonstrated the efficacy of orally inhaled DHE in moderate/severe acute migraine, even when administered >8 hours after migraine start. Inhaled DHE may help many migraineurs who are unable to treat migraine early. Study supported by: This study was sponsored by MAP Pharmaceuticals. Dr Kori is a full-time employee of MAP Pharmaceuticals. Dr Tepper, Dr Goadsby, Dr Winner and Dr Silberstein have consulted for MAP Pharmaceuticals. Shashi Kori, MD is a full-time employee of MAP Pharmaceuticals. Headache and Pain T1601. Withdrawn T1602. OnbotulinumtoxinA for the Treatment of Chronic Migraine: Long-Term Outcome Hanlon T. Christopher, Silvia M. Weibelt, Diane C. AndressRothrock and John F. Rothrock; Birmingham, AL T1604. Characterization of Intraepidermal Nerve Fiber Morphology in Pain Associated with Diabetic Neuropathy and Impaired Glucose Tolerance Hsinlin T. Cheng, Jacqueline R. Dauch, Gordon A. Smith, Robinson J. Singleton, Brandon M. Yanik and Eva L. Feldman; Ann Arbor, MI and Salt Lake City, UT Background: The long-term clinical outcomederived from treatment of chronic migraine (CM) with onabotulinumtoxinA (onabotA) is unknown. Methods: From a series of CM patients treated twice with onabotA who experienced a 50% or greater reduction Neuropathic pain is a common symptom associated with diabetes and. Measurement of intraepidermal nerve fiber 79 ID: senthilk I Black Lining: [ON] I Time: 08:46 I Path: //xinchnasjn/01Journals/Wiley/3b2/ANA#/Vol00000/110244/APPFile/JW-ANA#110244 J_ID: ZAY Customer A_ID: SUPP11-6 Cadmus Art: 22579 Date: 31-August-11 density (IENFD) in distal skin samples is a standard method for the diagnosis of diabetic neuropathy (DN). IENFD, however, is not considered a good indicator for the diagnosis of painful diabetic neuropathy (PDN). To evaluate the use of skin biopsy to study neuropathic pain in PDN, we studied the IENFD and nerve morphology in skin samples from: normal control, diabetic control, PDN, and DN. Skin samples from both the distal leg and proximal thigh were examined. Quantification of IENFD demonstrated no significant difference between PDN and DN. Morphological studies on these skin samples demonstrated the presence of axonal swellings or microneuromas, round shape nerve segments in PDN. The microneuroma densities in the proximal thigh of PDN are significantly higher than that of the DN. In summary, IENFD does not have a diagnostic value for PDN. In contrast, the microneuroma densities in proximal skin samples could be used as an indicator for PDN. Study supported by: NIH Stage: Page: 80 dural venous sinus stenosis of the dominant venous outflow system (gradient !10 mmHg). Results: Thirteen cases were identified (all female; mean 39 years); all failed medical therapy and 5/13 failed surgical intervention. Technical success was achieved in 13/13 without major peri-procedural complications. The mean pre-procedural gradient across the venous stenosis was reduced from 23mmHg to 4mmHg post-procedure. Headache resolved or improved in 9/13. Papilledema resolved in 12/13 and improved in 1/13. Among the 9 patients with angiographic follow-up, there were no instances of restenosis. Conclusions: Venous sinus stenting can achieve a high degree of technical success and safety with excellent clinical outcomes. Our series suggests that angioplasty and stenting may be considered as an alternative to current surgical therapies in patients with IIH and dural venous sinus stenosis. Study supported by: This study was unfunded and no individuals other than the authors have contributed to the preparation of this manuscript. T1605. Heavily T2-Weighted Magnetic Resonance Myelography for Post-Lumbar Puncture Headache: A Pilot Study Yen-Feng Wang, Jong-Ling Fuh, Jiing-Feng Lirng and Shuu-Jiun Wang; Taipei, Taiwan T1607. Adrenal Insufficiency Presenting as Postural Tachycardia Syndrome Darine Kassar and Stanley Iyadurai; Saint Louis, MO Objectives: To report a case of adrenal insufficiency presenting as Postural Tachycardia Syndrome (POTS). Background: POTS is a disorder of unknown etiology characterized by orthostatic intolerance and excessive tachycardia. POTS is believed to be caused by central hypovolemia. Adrenal insufficiency has not been described before as an etiology for POTS. Methods: Case report Case report: We report a case of a 20 year-old woman who presented for migraine headache. Headaches improved after hydration and treatment. She returned to emergency room 2 weeks after discharge, with dizziness and recurrent falls associated with loss of consciousness that occurred while she attempted to stand. Physical examination showed orthostatic tachycardia. Tilt table test was positive. A diagnosis of POTS was made. No major improvement was noticed with fluid hydration and treatment with fludrocortisone. Additional work up showed low morning cortisol level. A diagnosis of adrenal insufficiency was made and patient was placed on prednisone with relief of her symptoms. Conclusion: POTS remains a diagnosis of exclusion. Here we report the first case of POTS associated with adrenal insufficiency, which was successfully treated with prednisone. Given the right clinical setting, checking cortisol level should be a consideration in evaluation for an etiology for POTS. Objective: To investigate the utility of heavily T2-weighted magnetic resonance myelography (HT2W MRM) in postlumbar puncture (LP) headache (PLPH). Background: PLPH occurs in about one third of patients receiving diagnostic LPs. HT2W MRM was proved comparable to computed tomographic myelography in localizing CSF leaks in spontaneous intracranial hypotension. Methods: We prospectively enrolled inpatients with indications for diagnostic LPs. Whole-spine axial HT2W MRMs were carried out after LPs. PLPH was diagnosed according to the ICHD-2 criteria. Results: Sixteen patients (3M/13F, age 45.9 6 14.6 years, range 24–82) were recruited. Five patients (31.3%) (1M/4F) developed PLPH. Twelve patients (75%) had postLP CSF leakage, and all of them had CSF leaks along the nerve roots. Of these patients, four (33.3%) had epidural CSF collections, and five (41.7%) had lumbosacral retrospinal CSF collections. All of the patients with PLPH had CSF leaks along the nerve roots, but only 41.7% of the patients with CSF leakage developed PLPH. Conclusion: HT2W MRM was sensitive in detecting CSF leaks after LP. Although CSF leakage after LPs was common, it was not the only determinant in the development of PLPH. Study supported by: Taipei Veterans General Hospital The authors are employees of Taipei Veterans General Hospital. T1606. Angioplasty and Stenting for the Treatment of Idiopathic Intracranial Hypertension Associated with Dural Venous Sinus Stenosis Parisa P. Javedani**, Jeremy D. Fields, Kenneth C. Liu, Stanley L. Barnwell and Bryan Petersen; Portland, OR and Charlottesville, VA T1608. Prevalence of Chronic Migraine (CM), Headache-Related Disability and Sociodemographic Factors in the US Population: Results from the American Migraine Prevalence and Prevention (AMPP) Study Dawn C. Buse, Michael L. Reed, Kristina Fanning, Aubrey N. Manack, Catherine C. Turkel and Richard B. Lipton; Bronx, NY; Chapel Hill, NC and Irvine, CA Introduction: Lumboperitoneal shunt, ventriculoperitoneal shunt, and optic nerve sheath fenestration are accepted surgical therapies for medically refractory idiopathic intracranial hypertension (IIH). Stenting of stenotic venous sinuses has emerged as a potential therapy. Methods: We retrospectively reviewed all cases of dural stents for IIH at our institution. Eligibility criteria included medically refractory IIH with documented papilledema and Objective: Estimate the prevalence of CM in the US population by sociodemographics and headache-related disability. Methods: In 2004 surveys were mailed to 120,000 US households; 162,756 individuals aged !12 returned surveys; 28,621 reported severe headache. CM was defined as ICHD-2 migraine with headache frequency !15 headache days/month. Crude and sociodemographically adjusted prevalence ratios (PRs) were generated. 80 ID: senthilk I Black Lining: [ON] I Time: 08:46 I Path: //xinchnasjn/01Journals/Wiley/3b2/ANA#/Vol00000/110244/APPFile/JW-ANA#110244 J_ID: ZAY Customer A_ID: SUPP11-6 Cadmus Art: 22579 Date: 31-August-11 Results: 19,189 individuals (11.8%) met ICHD-2 criteria for migraine (17.3% of females; 5.3% of males); 0.9% met criteria for CM (1.3% of females; 0.5% of males). Prevalence was highest in males and females aged 40–49. When compared with persons aged 12–17, adjusted PRs in the 40–49 age group were as follows: females 4.71 (95% CI 3.24–6.83), males 3.31 (95% CI 1.99 ¼ 5.49.) Rates of CM were inversely correlated with annual household income. Severe-headache related disability was reported by 38.0% of CM vs. 9.5% of EM respondents. Conclusions: Prevalence of CM in the US was 0.9%, and was highest in adjusted models among females, in midlife, and households with the lowest income. Severe headache-related disability was most common among persons with CM. Study supported by: The AMPP was funded through a grant to the National Headache Foundation by OrthoMcNeil Neurologics, Inc., Titusville, New Jersey with supplemental funding by Allergan Inc., Irvine, CA. Drs. Buse, Lipton, Serrano, and Reed have received consulting funds and/or research support from Allergan. Drs. Manack and Turkel are full time employees of Allergan. Stage: Page: 81 Results: Among 6,559 respondents with EM, 49.7% reported nausea ! half the time with headache, which was associated with greater symptomology including unilateral pain, pulsating pain, pain worsened by activity, photophobia, phonophobia, osmophobia, loss of appetite, neck pain and sinus pain (all p<.001). Respondents with frequent nausea reported greater dissatisfaction with medication effectiveness, side effects and overall satisfaction, and were more likely to report that headache medication(s) interfered with work, household work, and family social and leisure activities (all p<.001). Conclusions: Persons who frequently experience nausea with headache also have greater odds of experiencing other headache symptoms as well as more dissatisfaction with several aspects of their current medication(s). Study supported by: The AMPP is funded through a research grant to NHF from Ortho-McNeil Neurologics, Inc., Titusville, NJ. Supplemental funding provided by NuPathe, Inc. Conshohoken, PA. Drs. Buse, Reed, Fanning and Lipton have received research support from NuPathe, Inc. T1611. Frequent Nausea in Episodic Migraine (EM) Is Common and Associated with Increased Burden: Results from the American Migraine Prevalence and Prevention (AMPP) Study Dawn C. Buse, Michael L. Reed, Kristina M. Fanning and Richard B. Lipton; Bronx, NY and Chapel Hill, NC T1609. Chronic Low Dose Methadone for the Suppression of Treatment-Refractory Chronic Migraine Keyvani Madjid and John F. Rothrock; San Diego, CA and Birmingham, AL Objective: to determine the safety and effectiveness of methadone administered chronically to patients with treatment-refractory chronic migraine (TRCM). Methods: We administered low dose (range 2.5–10 mg TID) methadone to a series of patients with TRCM. A positive treatment response was defined as a 50% or greater reduction in headache days/month during the 3rd treatment month relative to the baseline pre-treatment month, with that response maintained for at least 6 months. At 6 months we attempted to taper all responders off methadone. Results: We treated 130 subjects, and 57 (44%) achieved a positive response. We followed all responders for a mean of 27 months (range 13–57 months). Only 5 patients (4% of the total and 7% of responders) eventually were able to discontinue methadone without relapsing to CM within 30 days. There was one serious adverse event (death due to overdose of oxycodone and alprazolam). Conclusions: While chronic administration of low dose methadone may achieve remission of TRCM to episodic migraine in a significant minority of patients so treated, discontinuation of treatment typically is associated with rapid relapse to CM. Objective: To characterize headache-burden and sociodemographics by nausea status among persons with EM. Methods: Respondents to the 2009 AMPP survey who met criteria for EM (ICHD-2 criteria and <15 headache days/month) rated nausea occurring with severe headache: none of the time, rarely, < half the time, or ! half the time. Chi-square was used to compare sociodemographics. Ordinal logistic regression adjusting for sociodemographics yielded odds ratios (OR) and 95% confidence internals (CI) for headache-related disability (MIDAS) and headacheimpact (HIT-6). Results: Among 6,559 respondents with EM, 49.7% reported nausea ! half the time with severe headache, with higher frequency in females (52.6%) vs. males (39.3%, p<.001), and among persons on occupational ��disability’’/ medical leave (62.5%) vs. persons employed full-time (46.7%, p<.001). Individuals with frequent nausea were almost twice as likely to experience greater headache-related disability (OR ¼ 1.94, CI 1.68–2.24), almost four times more likely to report ��severe pain’’ with headache (OR ¼ 3.71, CI 3.28–4.18), greater impairment in daily activities, desire to lie down, tiredness, irritability and difficulty concentrating (all p<.001). Conclusion: Frequent nausea was strongly associated greater headache-related disability and headache-impact. Study supported by: The AMPP is funded through a research grant to NHF from Ortho-McNeil Neurologics, Inc., Titusville, NJ. Supplemental funding provided by NuPathe, Inc. Conshohoken, PA. Drs. Buse, Reed, Fanning and Lipton have received research support from NuPathe, Inc. T1610. Relationship between High Frequency Nausea and Treatment Satisfaction in Episodic Migraine (EM): Results of the American Migraine Prevalence and Prevention (AMPP) Study Richard B. Lipton, Michael L. Reed, Kristina M. Fanning and Dawn C. Buse; Bronx, NY and Chapel Hill, NC Objective: Report headache symptomology and satisfaction with medications among persons with EM by headacherelated nausea status. Methods: Respondents to the 2009 AMPP survey who met criteria for EM (ICHD-2 criteria and <15 headache days/month) reported nausea occurring with severe headache: none of the time, rarely, < half the time, or ! half the time. Ordinal logistic regression was used adjusting for sociodemographics, and odds ratios with 95% confidence internals were generated. T1612. Medical Consultation and Headache-Impact among Persons with Chronic Migraine (CM) and Episodic Migraine (EM): Results from the American Migraine Prevalence and Prevention (AMPP) Study Aubrey N. Manack, Dawn C. Buse, Daniel Serrano, Sepideh F. Varon, Catherine C. Turkel and Richard B. Lipton; Irvine, CA; Bronx, NY and Chapel Hill, NC 81 ID: senthilk I Black Lining: [ON] I Time: 08:46 I Path: //xinchnasjn/01Journals/Wiley/3b2/ANA#/Vol00000/110244/APPFile/JW-ANA#110244 J_ID: ZAY Customer A_ID: SUPP11-6 Cadmus Art: 22579 Date: 31-August-11 Objective: Compare patterns of medical consultation and headache-impact in persons with migraine in the general population. Methods: The AMPP study is a longitudinal, population study of persons with severe headache. 2009 survey respondents who met ICHD-2 criteria for migraine (CM [!15 headache days/month] or EM [<15 headache days/month]) were compared on self-reported visits to healthcare professionals (HCPs) and/or facilities for headache in the preceding 12 months and headache-impact (HIT-6). Descriptive statistics summarize data and t-tests were utilized to compare HIT-6 scores. Results: 27,253 questionnaires were fielded; 20,107 were returned. 373 respondents met criteria for CM and 6,796 for EM. 48.5% of CM and 24.5% of EM respondents reported !1 visit to a HCP/facility for headache. CM suffers were more likely to consult both PCPs (CM ¼ 34.1%, EM ¼ 15.8%) and specialists (CM ¼ 15.8%, EM ¼ 5.6%). Among both groups, headache-impact was greater among those who consulted neurologists/headache specialists (CM mean HIT-6 score: 66.7 vs. 64.5; p <0.001; EM Mean HIT-6 score: 63.6 vs. 57.3, p<0.001). Discussion: Persons with CM consult HCPs more frequently, particularly specialists. Specialist visits are related to greater headache-impact. Study supported by: The AMPP Study is funded through a research grant to the NHF from Ortho-McNeil Neurologics, Inc., Titusville, NJ Additional analyses and abstract preparation were supported by Allergan Inc., Irvine, CA. Drs. Buse, Lipton, Serrano, and Reed have received consulting funds and/or research support from Allergan. Drs. Manack and Turkel are full-time employees of Allergan. Stage: Page: 82 the National Headache Foundation from Ortho-McNeil Neurologics, Inc., Titusville, NJ. Additional analyses and manuscript preparation were supported by Merck Sharp & Dohme Corp., West Point, PA. Dr. Ng-Mak is an employee of Merck Sharp & Dohme Corp. T1614. Association between Triptan Use and Cardiac Contraindications in Migraine Daisy S. Ng-Mak, Valerie P. Pracilio, Stephen Silberstein, Joseph Couto, Cary Sennett, Mary Hopkins, Jon Bumbaugh and Neil Goldfarb; West Point, PA; Philadelphia, PA and Bowie, MD Objectives: This study assessed the association between triptan use and the presence of cardiac contraindications within an insured migraine population. Background: Migraine is associated with cardiovascular diseases. The vasoconstrictive mechanism of triptans poses safety concerns for migraine patients with cardiovascular diseases and/or risk factors. Methods: Ten representative health plans were randomly selected from the MedAssurant MORE2 RegistryTM. Approximately 2.5 million lives (ages 18–64) were covered during the measurement year (2009). Migraine patients were identified by a visit with a migraine diagnosis found in claim/encounter data, or if they had ! 2 episodes of headache seven or more days apart, or had at least one prescription for a migraine drug or migraine analgesic. Cardiac contraindications for triptans were defined as at least one prescription or medical claim indicating a cardiac contraindication. Results: 121,286 (4.9%) migraineurs were identified. Of the migraineurs in the sample, 38% had one or more prescriptions for a triptan and 8% had a cardiac contraindication. Twenty-two percent of those with a cardiac contraindication had a triptan prescription during 2009 (24% of those 18–49 and 21% 50–64 years of age). Conclusion: This study demonstrates potential concerns regarding pharmacotherapy for migraine. More than 20% of migraine patients with cardiac contraindications had prescriptions for triptans filled in 2009. While we recognize that triptans remain the gold standard for acute migraine treatment, their high utilization (21%) especially among the 50–64 year old population with cardiac contraindications and who may be exposed to other risks, is concerning and deserves further study. Study supported by: This study was sponsored by Merck Sharp & Dohom Corp. Dr. Ng-Mak is an employee of Merck Sharp & Dohme Corp. T1613. Unmet Treatment Needs among Episodic Migraineurs (EM): Results of the American Migraine Prevalence and Prevention Study (AMPP) Richard B. Lipton, Dawn C. Buse, Daniel Serrano, Daisy S. Ng-Mak, Starr H. Pearlman and Michael Reed; Bronx, NY; Chapel Hill, NC; West Point, PA and Savannah, GA Background: Low triptan persistency and low-moderate satisfaction with migraine therapy suggest that there are unmet treatment needs. Objectives: To define ��unmet treatment needs’’ and examine the prevalence and characteristics of EM in the general population having the unmet needs. Methods: The AMPP is a longitudinal population-based study. EM were assessed based on 5 categories of unmet needs: 1. Dissatisfaction with current treatment; 2. Moderate/severe headache-related disability; 3. Excessive use of opioids/barbiturates; 4. Recurrent use of the emergency department (ED) or urgent care clinic (UCC) for headache; and 5. Use of triptans despite a history of cardiovascular (CVD) events. Results: Of 5,591 EM, 2,274 (40.7%) demonstrated at least one unmet needs. 1,467 (26.2%) had 1 unmet need, while 807 (14.4%) had !2 unmet needs. Among those with !1 unmet need, 851(37.4%) were dissatisfied with treatment, 1,069(47.0%) had moderate/severe headacherelated disability, 728 (32.0%) excessively used opioid or barbiturate, 129 (5.7%) had ! 2 visits/year to the ED/ UCC for headache, and 595 (26.2%) were using triptans despite a history of CVD events. Conclusions: These results demonstrated that unmet needs in migraine exist despite available therapies for EM. Study supported by: The American Migraine Prevalence and Prevention Study is funded through a research grant to T1615. ��Let-Down Headache’’: Reductions in Stress and Improvement in Mood Predict Headaches in Persons with Migraine Dawn C. Buse, Sheryl R. Haut, Charles Hall, Howard Tennen, Tiffani DeFreitas, Thomas M. Borkowski and Richard B. Lipton; Bronx, NY and Storrs, CT Objective: To examine if relaxation following stress increases the probability of headache in persons with migraine (i.e., ��let-down headache’’). Methods: 20 headache clinic patients (ICHD-2 diagnoses of migraine, age !18, 3–10 migraine attacks and <15 headache days/month) entered data using a palm-pilot at multiple pre-set and random times daily. The 4-item Perceived Stress Scale (PSS, range 4–20) and mood (ratings of happy, sad, relaxed, nervous, lively and bored from 0–100) were assessed. Logit-normal random effects models taking account withinperson correlation were used to estimate odds of headache. 82 ID: senthilk I Black Lining: [ON] I Time: 08:46 I Path: //xinchnasjn/01Journals/Wiley/3b2/ANA#/Vol00000/110244/APPFile/JW-ANA#110244 J_ID: ZAY Customer A_ID: SUPP11-6 Cadmus Art: 22579 Date: 31-August-11 Results: 17 patients entered !30 days of data (192 headache attacks [mean ¼ 5.5]). Lower PSS was associated with higher odds ratios (ORs) for headache within 12 hours (OR [95% CI] ¼ 1.81 [1.13, 2.91] per 4-unit difference on PSS). Improvement in mood was significantly associated with headache occurrence within 12, 18, and 24 hours for happy (ORs ¼ 1.20, 1.20, and 1.18, and relaxed ORs ¼ 1.26, 1.17, and 1.14. Increases of >10 points were associated with headache occurrence within 12 hours for happy OR ¼ 2.73 and relaxed OR ¼ 2.31. Conclusions: Reduced perceived stress and increased feelings of happiness and relaxation were associated with increased odds of headache. Study supported by: This study was supported by an investigator initiated grant from ENDO Pharmaceuticals, Chadds Ford, PA. Drs. Buse and Lipton have acted as consultants and/or received research support from Endo Pharmaceuticals. Stage: Page: 83 Background: Recurrence-rates highlight an important clinical problem in acute treatment of migraine, although endpoint definitions differ widely. Methods: A phase 3 study post-hoc analysis comparing orally-inhaled dihydroergotamine (DHE) with placebo using four published recurrence-rate definitions. These were: (a) numerator ¼ subjects with 2-hour pain relief (PR) and moderate/severe pain during 2–24 or 2–48 hours, denominator ¼ subjects with 2-hour PR; (b) numerator ¼ same as a plus subjects with PR using rescue medication during 2– 24 or 2–48 hours, denominator ¼ same as a; (c) numerator ¼ same as a, denominator ¼ subjects in mITT population; and (d) numerator ¼ same as b, denominator ¼ same as c. Results: Of 903 subjects randomized, 792 experiencing/ treating a qualifying migraine comprised the efficacy analysis. Recurrence-rates during 2–24 hours were 6.5%, 22.4%, 3.8%, and 13.2% with DHE and 15.3%, 39.4%, 5.3%, and 13.6% with placebo for definitions a, b, c, and d. Recurrence-rates during 2–48 hours were 10.3%, 30.2%, 6.1%, and 17.7% with DHE and 18.2 %, 41.6%, 6.3%, and 14.4% with placebo for definitions a, b, c, and d. Conclusions: Migraine recurrence-rates vary widely in definition, which can be misleading. A standardized definition would help facilitate clinical discussions. In this analysis, DHE recurrence-rates were low, regardless of definition. Study supported by: This study was sponsored by MAP Pharmaceuticals. Dr Kori is a full time employee of MAP Pharmaceuticals. Dr Tepper, Dr Goadsby, Dr Lipton and Dr Dodick have consulted for MAP Pharmaceuticals. Shashi Kori, MD is a full-time employee of MAP Pharmaceuticals. T1616. Assessing the Consistency of LEVADEXTM (MAP0004, Orally Inhaled Dihydroergotamine) Pharmacokinetic Parameters in Healthy Volunteers: Results from 3 Clinical Studies Amy Forst, Julie Iwashita, Don Kellerman, Shashidhar Kori, Tracy Thomas and Glyn Taylor; Mountain View; Merthyr Tydfil, United Kingdom and Radyr, United Kingdom Background: Rapid, consistent drug absorption is important for effectively treating migraine acutely. MAP0004, a novel, orally inhaled dihydroergotamine (DHE), has shown efficacy in treating migraine acutely. Data from pharmacokinetic studies were analyzed for consistency, adequacy, and speed of DHE absorption through inhalation. Methods: Three studies compared MAP0004 1.0mg nominal with 1.0mg of intravenous (IV) DHE, assessing pharmacokinetic differences between smokers and nonsmokers, effect of co-administration of ketoconazole on MAP0004, and acute effects of MAP0004 on pulmonary artery pressure. Results: MAP0004 delivered DHE rapidly in all studies (mean Tmax, 7–11 minutes). Peak plasma concentrations of DHE were consistent across studies in non-smokers (Cmax geometric mean, 2475–2551 pg/mL). MAP0004 Cmax values were substantially lower than IV values (average, $45,000pg/mL) but higher than intranasal (1,004pg/mL). Cmax and clearance did not vary significantly based on lung function, age, or weight across studies. Co-administration of ketoconazole did not significantly impact DHE pharmacokinetics after MAP0004 administration. 80 -hydroxy-dihydroergotamine concentrations after MAP0004 administration were low (average Cmax, <100pg/mL). No unique MAP0004 tolerability issues were observed. Conclusions: Across studies, MAP0004 administration showed consistent DHE pharmacokinetics and rapid absorption via pulmonary administration. Study supported by: This study was sponsored by MAP Pharmaceuticals. Amy Forst, Don Kellerman and Shashidhar Kori are full-time employees of MAP Pharmaceuticals. Glyn Taylor is a consultant for MAP Pharmaceuticals. Amy Forst, Don Kellerman and Shashidhar Kori are fulltime employees of MAP Pharmaceuticals. T1618. Transdermal Sumatriptan for Acute Treatment of Migraine and Jerome Goldstein; San Francisco, CA Migraine is a widespread neurologic disorder characterized by episodes of headache accompanied by photophobia, phonophobia, gastrointestinal symptoms and, often, cutaneous allodynia. Symptoms can vary considerably, but gastrointestinal disturbances are common. Current pharmacotherapy for migraine includes analgesics, nonsteroidal anti-inflammatory drugs, and 5HT-agonists in various oral, nasal spray, and subcutaneous formulations. Among the 5HT-agonists, sumatriptan is the most frequently prescribed, but its therapeutic limitations (ie, poor absorption, low bioavailability, adverse events) cause some migraineurs to delay or avoid treatment and may lead to suboptimal outcomes. Transdermal sumatriptan (ZelrixV) is a new, single-use, disposable patch that delivers sumatriptan via iontophoresis, a less invasive method for systemic delivery. Pharmacokinetic data indicate that transdermal sumatriptan delivery is fast, consistent, and predictable. Results from well-controlled clinical studies demonstrate significant superiority versus placebo within 1 hour post-activation for pain relief (P ¼ 0.0135) and nausea-free (P ¼ 0.0251); at 2 hours post-activation, transdermal sumatriptan significantly outperformed placebo for pain-free (P ¼ 0.009), pain relief (P ¼ 0.0135), photophobia-free (P ¼ 0.0028), phonophobia-free (P ¼ 0.0002), and migraine-free (P ¼ 0.0135). Transdermal sumatriptan is well tolerated, and reported adverse events are mostly mild, transient application site reactions. This article reviews the evidence supporting the efficacy and safety of transdermal sumatriptan for acute treatment of migraine. R T1617. Migraine Recurrence Rates with Acute Treatment: Case for Standardizing the Definition Stewart Tepper, Shashidhar Kori, Peter J. Goadsby, Michel Ferrari, Richard Lipton, Scott Borland, Min Wang and David Dodick; Cleveland; Mountain View; San Francisco; Leiden, Netherlands; Bronx and Scottsdale T1619. Dejerine Roussy Syndrome in a Patient with Sneddon’s Syndrome as an Initial Manifestation Jennie Luna, Anish Shah, Sourav Sen and Dipak P. Pandya; Paterson, NJ 83 ID: senthilk I Black Lining: [ON] I Time: 08:46 I Path: //xinchnasjn/01Journals/Wiley/3b2/ANA#/Vol00000/110244/APPFile/JW-ANA#110244 J_ID: ZAY Customer A_ID: SUPP11-6 Cadmus Art: 22579 Date: 31-August-11 Introduction: Dejerine Roussy Syndrome(DRS) usually results from damage to sensory pathways from thalamus to spinal cord. It may occur after stroke, multiple sclerosis, after trauma or in brain tumor involving thalamus. Occurrence of DRS in a patient with Sneddon’s syndrome has not been reported. We report a patient diagnosed with Sneddon’s syndrome presenting with central pain syndrome. Case Report: 69 year-old man with hypertension, hepatitis C, right posterior cerebral artery stroke presented with left hemi body severe pain. He was diagnosed with Sneddon’s syndrome nine months ago. His pain was severe, burning in nature, tearing and excruciating deep pressure pain involving left face, and left hemibody. He had left sided spastic hemiparesis and hyperesthesia and tenderness to touch. He was treated with all neuropathic medications and narcotic medications without significant success. Conclusion: DRS can be long lasting or even life long occurs immediately or years after a stroke. The exact pathogenesis is unknown, it could be related with inflammatory mediators and pain peptides by denervated nerves. To the best of our knowledge, occurrence of DRS in Sneddon’s syndrome has not been reported in the literature. Stage: Page: 84 skew from brainstem or cerebellar lesions, and 18 controls. Patient group mean OCR gain was significantly reduced in both torsional directions. OCR gains were asymmetric between eyes and between directions in 16 patients. The hypotropic eye incyclotorting gain was lower than the hypertropic eye excyclotorting gain after head roll toward the hypotropic eye in 17 patients. The reduced static OCR gain and interocular and directional gain asymmetries provide evidence of disruption of utriculo-ocular pathways in the pathogenesis skew deviation. Study supported by: Canadian Institutes of Health Research (CIHR) T1622. Superior Semicircular Canal Dehiscence (SSCD) and Osteoporosis in Elderly Asian Women Alexander Yu, Douglas L. Teich and Eric T. Wong; Boston, MA SSCD is associated with vertigo caused by the absence of bone overlying the SSC. This opening acts as a third window for the vestibular system, resulting in vertigo that is triggered by sound (Tullio phenomenon) or external pressure exerted on the canal (Hennebert sign). Four elderly Asian women were evaluated for dizziness/vertigo in a community health clinic. Their age, 57–85, was significantly older than the median age of 40 originally reported for SSCD. They all complained of motion-induced vertigo without nausea or vomiting. Their cerebellar examinations were normal. Only one had inducible vertigo on Dix-Hallpike maneuver, and none had Tullio phenomenon or Hennebert sign. SSCD was confirmed in all cases by high-resolution CT, with longitudinal areas of dehiscence along the long axis of SSC, ranging from 0.4 to 3.0 mm, as seen on Poschl view. They also suffered from osteopenia or osteoporosis in the axial skeleton, as confirmed by bone density tests. SSCD may be associated with osteoporosis in elderly Asian woman without Tullio phenomenon or Hennebert sign. Further research is needed to determine the relationship of age, race, osteoporosis risk, and the development of SSCD. Study supported by: Chinese Center of Long Island T1620. Valproate-Responsive Subclinical Rhythmic Electrographic Disharges (SREDA) in a Migraineur Umer Akbar, Bhavpreet Dham, Evren Burakgazi and John Kelly; Camden, NJ and Washington Objective: To report SREDA and its response to valproate in a patient with migraine headache. Background: The electroencephalogram (EEG) findings in migraine are typically non-specific, such as ictal and inter-ictal diffuse and focal slowing. More specific EEG findings in migraine are diffuse and focal slowing in theta and delta frequencies and decreased alpha activity with increased response to photic stimulation. Design: We report the case of SREDA during a migraine headache, improving after valproate administration. Case: A 45 year-old Caucasian female with catamenial migraines was admitted for dizziness, fogginess, and refractory migraines. Magnetic resonance imaging revealed deep white matter changes consistent with history of recurrent migraines. An otherwise unremarkable EEG showed intermittent episodes of SREDA in wakefulness and drowsiness. Valproate was initiated and repeat EEG two-weeks later showed no evidence of SREDA. Discussion: SREDA is an infrequent EEG pattern which occurs predominantly in adults after hyperventilation. It is generally thought to be benign with little clinical significance and has been noted in conditions as diverse as vascular events, syncope, transient global amnesia and epilepsy. Response to valproate confirms the electrical mechanism of migraines and suggests SREDA’s potential causal relationship with migraines. Neuroimmunology and Demyelinating Disease T1701. Antibodies to Metabotropic Glutamate Receptors in Ophelia Syndrome and Cerebellitis Eric Lancaster, Eugenia Martinez-Hernandez, Maarten J. Titulaer, Sarah Wong, Jian Xu, Anis Contractor, Rita BaliceGordon and Josep Dalmau; Philadelphia, PA and Chicago, IL Objective: The Ophelia syndrome is a presumed autoimmune disorder characterized by severe but treatment-responsive limbic encephalitis, in association with Hodgkin’s lymphoma. We aimed to determine the target autoantigen. Methods: Imunohistochemistry on brain tissue and cultures of rat hippocampal neurons was used to demonstrate antibodies. Immunoprecipitation, mass spectrometry, and mGluR5 knock outs served to identify the antigen. Results: Patient’s serum had antibodies that reacted with the hippocampus and cell surface of live, cultured neurons, immunoprecipitated mGluR5, and specifically labeled cells transfected with mGluR5. Reactivity of patient’s serum, but not control individuals, was abrogated in brain of mGluR5null mice, further confirming the specificity of the antibodies. Parallel studies with mGluR1, a receptor closely related to mGluR5, lead us to identify a case with cerebellar ataxia and mGluR1 antibodies. Despite the high homology of these receptors, each patient’s antibodies were specific for one type of receptor and a distinct syndrome, resembling the phenotype of genetic deletion of each receptor. T1621. Utriculo-Ocular Counterroll Reflex Disruption in Skew Deviation James A. Sharpe, Manokaraananthan Chandrakumar, Alan Blakeman, Herbert C. Goltz and Agnes M. Wong; Toronto, ON, Canada Lateral head tilt activates the utricles to evoke a static ocular counterroll reflex (OCR) of torsional eye motion. Damage to utriculo-ocular reflex pathways with an abnormal static OCR might be the mechanism of skew deviation, a vertical strabismus caused by supranuclear lesions. OCR gains, the change in torsional eye position/change in head position after sustained passive lateral head tilt of $20 , were recorded using search coils in 18 patients with 84 ID: senthilk I Black Lining: [ON] I Time: 08:46 I Path: //xinchnasjn/01Journals/Wiley/3b2/ANA#/Vol00000/110244/APPFile/JW-ANA#110244 J_ID: ZAY Customer A_ID: SUPP11-6 Cadmus Art: 22579 Date: 31-August-11 Conclusions: Antibodies to mGluR1 and mGluR5 should be considered in patients with cerebellitis and the Ophelia syndrome. Recognition is important because these disorders respond to immunotherapy. Our findings facilitate this diagnosis. Study supported by: Dr. Lancaster has a training grant from Talecris; his contribution to the current work was supported by a Dana Foundation Neuro-immunology Award. Dr. Martinez-Hernandez has a grant from the Fondo de Investigaciones Sanitarias, FIS, Spain (FI08/00285). Dr. Titulaer is supported by a KWF fellowship 2009–4451 of the Dutch Cancer Society. 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 has received a research grant from Euroimmun, and his contribution to the current work was supported in part by grants from the National Institutes of Health and National Cancer Institute (grant RO1CA89054). Drs. Dalmau and Balice-Gordon were supported by 1RC1NS06820401, and a McKnight Neuroscience of Brain Disorders award. Stage: Page: 85 outgrowth. We generated a recombinant form, rHIgM12, with identical properties. Intracerebral infection with Theiler’s Murine Encephalomyelitis Virus (TMEV) of susceptible mouse strains causes chronic demyelinating disease with progressive axonal loss and neurologic dysfunction similar to progressive forms of multiple sclerosis. We studied the effects of rHIgM12 on motor function of TMEV-infected mice by recording spontaneous nocturnal activity continuously over several weeks using AccuScan activity boxes. Compared to control IgM- and salinetreated mice, rHIgM12-treated mice showed improved motor function which became statistically significant at 9 days post treatment (p ¼ 0.038 and p ¼ 0.043, respectively) until the end of experiment (56 days). To assess axonal integrity we performed retrograde-labeling, a technique that relies on anatomically continuous and functionally preserved axons. rHIgM12treated mice had more retrograde-labeled brainstem neurons, as compared to saline-treated controls. This study supports the hypothesis that peripheral treatment with a neuron-binding IgM not only protects spinal cord axons in vivo but also influences functional motor improvement. Study supported by: This work was supported by grants from the NIH (R01 GM092993, R01 NS024180, R01 NS03219, R01 NS048357) and the National Multiple Sclerosis Society (CA 1011-A8). We also acknowledge with thanks support from the Applebaum and Hilton Foundations and the Minnesota Partnership Award for Biotechnology and Medical Genomics. A patent for the use of rHIgM12 antibody has been issued to the Mayo Clinic and Foundation. Therefore some of the authors may receive financial compensation in the future. T1702. Mortality Outcomes for Interferon Beta-1b Versus Placebo 21 Years Following Randomization Douglas S. Goodin, Anthony T. Reder, George Ebers, Gary Cutter, Marcelo Kremenchutzky, Joel Oger, Mark Rametta, Karola Beckmann and Volker Knappertz; San Francisco, CA; Chicago, IL; Oxford, United Kingdom; Birmingham, AL; London, ON, Canada; Vancouver, BC, Canada; Wayne, NJ; Berlin, Germany and Montville, NJ Objective: To assess the effect of interferon beta-1b (IFNB1b) 250 lg on mortality outcomes in multiple sclerosis (MS). Methods: Originally 372 patients were randomized to either IFNB-1b 50 lg (n ¼ 125), IFNB-1b 250 lg (n ¼ 124), or placebo (n ¼ 123), and remained on assigned treatment for a median 3.8 years (maximum 5.1 years), before licensed treatment became available. The primary outcome variable in this 21 year follow-up study was allcause mortality and the secondary cause-specific mortality. Results: At 21.1 years (median), vital status information was available for 366/372 (98.4%) of patients; of whom, 81 (22.1%, 81/366) were deceased. Original randomization to IFNB-1b 250 lg showed a significant reduction in all-cause mortality versus placebo (log-rank test, P ¼ 0.0272) and risk of death was reduced by 39.3%. Cause of death data was assessed for 75% of deaths; of which, 50/61 (82%) were MS-related. Most of the excess mortality rate in placebo was MS-related. Conclusions: With near-complete ascertainment and over 21 years of observation time, a substantial survival advantage was seen for patients receiving early IFNB-1b treatment versus placebo. Most of this striking difference appears to be due to MS-related deaths. Study supported by: Bayer HealthCare Pharmaceuticals, Montville, NJ, USA. Prof Douglas Goodin has received honoraria from Bayer HealthCare Pharmaceuticals for consulting fees and honoraria for speaking. T1704. Neuroprotection Mediated through Estrogen Receptor Alpha in Astrocytes Rory Spence, Mary Hamby, Elizabeth Umeda, Noriko Itoh, Sienmi Du, Galyna Bondar, Michael Sofroniew and Rhonda Voskuhl; Los Angeles, CA Estrogen has well documented neuroprotective effects in central nervous system (CNS) disorders such autoimmune inflammation, traumatic injury, stroke, and neurodegenerative diseases, but the underlying mechanisms are uncertain, because diverse cell types express estrogen receptors in the immune system and CNS. We selectively deleted estrogen receptor alpha (ERa) from either astrocytes or neurons using well-characterized Cre-loxP systems for conditional gene knockout in mice. We found that signaling through ERa in astrocytes, but not in neurons, is essential for the neuroprotective effects of systemic treatment with ERa ligand on clinical function, CNS inflammation and axonal loss during experimental autoimmune encephalomyelitis. Our findings reveal a novel cellular mechanism for estrogen-mediated neuroprotective effects by signaling through astrocytes and have implications for understanding the pathophysiology of sex hormone effects in diverse CNS disorders. Study supported by: National Multiple Sclerosis Society (RRV), Adelson Medical Research Foundation (RRV and MVS), NIH NINDS grants NS 062117 (RRV) and NS057624 (MVS), Skirball Foundation, Hilton Foundation, and Sherak Family Foundation. T1705. Genesis of Astrogliosis in an Autoimmune Model of Multiple Sclerosis Fuzheng Guo, Yoshiko Maeda, Joyce Ma, Monica Delgado and David Pleasure; Sacramento, CA T1703. A Recombinant Human Neuron-Binding IgM Protects Spinal Cord Axons and Improves Motor Function in a Murine Model of Multiple Sclerosis Aleksandar Denic*, Slobodan Macura, Arthur E. Warrington, Istvan Pirko, Brandon R. Grossardt, Larry R. Pease and Moses Rodriguez; Rochester, MN Astrogliosis is a prominent feature of multiple sclerosis (MS). We employed genetic fate-mapping and bromodeoxyuridine (BrdU) labeling to evaluate the cellular origins of reactive astroglia in spinal cords of mice with experimental Our laboratory demonstrated that a natural human serum antibody, sHIgM12, binds to neurons in vitro and promotes neurite 85 ID: senthilk I Black Lining: [ON] I Time: 08:46 I Path: //xinchnasjn/01Journals/Wiley/3b2/ANA#/Vol00000/110244/APPFile/JW-ANA#110244 J_ID: ZAY Customer A_ID: SUPP11-6 Cadmus Art: 22579 Date: 31-August-11 autoimmune encephalomyelitis (EAE) induced by immunization with myelin oligodendrocyte glycoprotein peptide 35–55 (MOG peptide). We found that oligodendroglial progenitor cells (OPCs) were stimulated to proliferate early in the course of MOG peptide EAE, and that many of these OPCs differentiated to oligodendroglia, but that OPC generation of astroglia was a rare event. Spinal cord ependymal cells, which have been reported to give rise to astroglia following spinal cord trauma, did not generate either OPCs or astroglia during MOG peptide EAE. Instead, virtually all reactive astroglia, identifiable by their expressions of nestin and vimentin in addition to glial fibrillary acidic protein, arose from resident spinal cord astroglia. In spinal cord white matter, astroglial proliferation increased overall astroglial numbers. In gray matter, in contrast, reactive astrogliosis was not accompanied by astroglial hyperplasia. Our study provides the first comprehensive view of the cellular origins of astrogliosis during an autoimmune demyelinative disorder. Study supported by: This work was supported by the Shriners Hospitals for Children, the California Institute for Regenerative Medicine (CIRM), NMSS and NINDS Stage: Page: 86 Fingolimod (FTY720) is a sphingosine-1-phosphate receptor modulator for the treatment of relapsing-remitting multiple sclerosis. In the phase 3 FREEDOMS study, fingolimod 0.5-mg once daily reduced annualized relapse rate (ARR) by 56% vs. placebo at 24 months (p<0.001). The effect of fingolimod on ARR in patient subgroups was evaluated in the intent-to-treat population using a negative binomial regression model adjusting for treatment (overall results), or treatment and subgroup (subgroup results). In the overall population, the ARR treatment ratio (fingolimod 0.5 mg [ARR ¼ 0.21] vs. placebo [ARR ¼ 0.48]) was 0.44 (95% confidence interval [CI]: 0.36–0.55). Likewise, ARR ratios were 0.36 (CI: 0.27–0.49) for treatment-naı¨ve (n ¼ 244, fingolimod 0.5 mg; n ¼ 249, placebo) and 0.54 (CI: 0.39–0.73) for previously treated (n ¼ 181, fingolimod; n ¼ 169, placebo) subgroups. Additionally, the ARR ratio favored fingolimod regardless of prior treatment with interferon (yes: ARR ratio ¼ 0.53, CI: 0.37–0.77 [n ¼ 127, fingolimod; n ¼ 115, placebo]; no: ARR ratio ¼ 0.39, CI: 0.30–0.51 [n ¼ 298, fingolimod; n ¼ 303, placebo]) and discontinuation due to lack of efficacy (yes: ARR ratio ¼ 0.31, CI: 0.16– 0.60 [n ¼ 41, fingolimod; n ¼ 38, placebo]; no: ARR ratio ¼ 0.46, CI: 0.37–0.58 [n ¼ 384, fingolimod; n ¼ 380, placebo]). Fingolimod consistently reduced the ARR vs. placebo in all subgroups. Study supported by: Novartis Pharma AG, Basel, Switzerland Dr. Kremenchutzky and the London MS Clinic have received operational funding from the MS Society of Canada, and research support as well as consulting/speaker’s fees from many sources including the endMS research and training network, the Research Scientific Foundation of the MS Society of Canada, Bayer, Berles, Bio-MS, Biogen Idec, Boehringer-Ingelheim, Bristol-Myers Squibb, Elan, EMD Serono, Eli Lilly, Genzyme, GSK, GW, Novartis, PDL, Parexel, Quintiles, Roche, sanofi-aventis, Schering, Teva, and UCB Pharma. Dr. O’Connor has received consulting fees from Novartis, sanofi-aventis, Roche, Biogen Idec, Bayer, EMD Serono, Teva Neurosciences, Eli Lilly, Opexa Therapeutics, Celgene, Glemark, and Actelion. He has received honoraria from Biogen Idec, EMD Serono, and Novartis. Dr. Hohlfeld has recieved consulting fees, honoraria and grant support from Novartis, Biogen-Idec, Merck-Serono, Teva, sanofi-aventis, and Bayer. Dr. Radue has received lecuture fees from Actelion, Bayer Schering, Biogen Idec, and others, and have been exclusively used for research funding at the Medical Image Analysis Center Basel. Dr. Kappos has participated as principal investigator, member or chair of planning and steering committees or advisory boards in corporate-sponsored clinical trials in multiple sclerosis and other neurological diseases. The sponsoring pharmaceutical companies for these trials include Actelion, Advancell, Allozyne, BaroFold, Bayer Health Care Pharmaceuticals, Bayer Schering Pharma, Bayhill, Biogen Idec, BioMarin, CLC Behring, Elan, Genmab, Genmark, GeNeuro SA, GlaxoSmithKline, Lilly, Merck Serono, MediciNova, Novartis, Novonordisk, Peptimmune, sanofi-aventis, Santhera, Roche, Teva, UCB and Wyeth. He has also lectured at medical conferences or in public on various aspects of the diagnosis and management of multiple sclerosis. In many cases these talks have been sponsored by non-restricted educational grants from one or another of the above listed companies. Honoraria and other payments for all these activities have been exclusively used for funding of research of his department. Research and the clinical operations (nursing and patient care services) of the MS Center in Basel have been supported by non-restricted grants from one or more of these T1706. Distinct Features of Neuromyelitis Optica According to Anti-Aquaporin-4 Antibody IgG Subclass Noriko Isobe, Tomomi Yonekawa, Takuya Matsushita, Yuji Kawano, Katsuhisa Masaki, Satoshi Yoshimura and Jun-ichi Kira; Fukuoka, Japan and Matsuyama, Japan Objective: To clarify the clinical features of neuromyelitis optica (NMO) according to anti-aquaporin-4 (AQP4) antibody IgG subclass. Methods: We developed a quantitative flow cytometric assay for each anti-AQP4 antibody IgG subclass, and assessed 142 patients with multiple sclerosis (MS), 29 with neuromyelitis optica (NMO) fulfilling the 1999 criteria, 19 with recurrent/longitudinally extensive myelitis, 86 with other inflammatory or non-inflammatory neurological diseases, and 28 healthy controls. Results: Anti-AQP4 antibody IgG was detected in 46 patients, among whom 35 fulfilled either the 1999 or 2006 NMO criteria, 9 had recurrent/longitudinally extensive spinal cord lesions, and two showed MS-like features. IgG1, 2, 3 and 4 anti-AQP4 antibodies were detected in 97.8, 39.1, 13.0 and 8.7% of patients, respectively. In patients not receiving corticosteroids, the levels of IgG1 anti-AQP4 antibody correlated positively with disease duration, while those of IgG2 antibodies correlated negatively with maximum spinal cord lesion length. IgG2 anti-AQP4 antibody carriers showed a younger age of onset, longer disease duration and lower Progression Index than those of other subclasses. Conclusion: IgG1 anti-AQP4 antibody levels increase with disease duration, while IgG2 antibodies are seen in relatively benign cases with a younger onset age. Study supported by: The Health and Labour Sciences Research Grant on Intractable Diseases (H20-Nanchi-Ippan016) from the Ministry of Health, Labour and Welfare, Japan, and the grant-in-aid (B; no. 22390178) from the Ministry of Education, Culture, Sports, Science and Technology, Japan. T1707. Effect of Fingolimod on Relapse Rate by Prior Treatment Status and Reason for Discontinuation: FREEDOMS Subgroup Analyses Marcelo Kremenchutzky, Paul O’Connor, Reinhard Hohlfeld, Ernst-Wilhelm Radue, Ludwig Kappos, Lixin Zhang-Auberson, Dieter A. Ha¨ring, Philipp von Rosenstiel, Xiangyi Meng and Augusto Grinspan; London, ON, Canada; Toronto, ON, Canada; Munich, Germany; Basel, Switzerland and East Hanover, NJ 86 ID: senthilk I Black Lining: [ON] I Time: 08:46 I Path: //xinchnasjn/01Journals/Wiley/3b2/ANA#/Vol00000/110244/APPFile/JW-ANA#110244 J_ID: ZAY Customer A_ID: SUPP11-6 Cadmus Art: 22579 Date: 31-August-11 companies and by grants from the Swiss MS Society, the Swiss National Research Foundation, the European Union, the Gianni Rubatto, Novartis and Roche Research Foundations. Dr. Zhang-Auberson, Dr. Ha¨ring, Dr. von Rosenstiel, Dr. Meng, and Dr. Grinspan are employees of Novartis. Stage: Page: 87 care services) of the MS Center in Basel have been supported by non-restricted grants from one or more of these companies and by grants from the Swiss MS Society, the Swiss National Research Foundation, the European Union, the Gianni Rubatto, Novartis and Roche Research Foundations. Dr. Hartung has received consulting fees Bayer HealthCare, Biogen Idec, Genzyme, Merck Serono, Novartis, Teva, and Sanofi-Aventis. He has received honoraria from Bayer HealthCare, Biogen Idec, Genzyme, Merck Serono, Novartis, Roche, Teva, and sanofi-aventis. Dr. Comi has received honoraria from Teva, Novartis, Biogen, Lilly, Merck Serono, and Bayer-Schering. Dr. Barkhof have received consulting fees from Bayer-Schering, Merck Serono, Synthon, Novartis, UCB, Biogen Idec, and Roche. He has received honoraria from sanofi-aventis, Genzyme, and Serono Symposia. Dr. Cohen has received consulting fees from Biogen Idec, Elan, Lilly, Novartis, and Teva. Dr. Stites, Dr. Meng, and Dr. Grinspan are employees of Novartis. T1708. Effect of Fingolimod on Relapse Rate by Prior Treatment Status and Reason for Discontinuation: TRANSFORMS Subgroup Analyses Bhupendra O. Khatri, Jean Pelletier, Ludwig Kappos, HansPeters Hartung, Giancarlo Comi, Frederik Barkhof, Jeffrey Cohen, Tracy Stites, Xiangyi Meng and Augusto Grinspan; Milwaukee, WI; Marseille, France; Basel, Switzerland; Dusseldorf, Germany; San Raffaele, Milan, Italy; Amsterdam, Netherlands; Cleveland, OH and East Hanover, NJ In the phase 3 TRANSFORMS study of relapsing–remitting multiple sclerosis patients, fingolimod (FTY720) 0.5-mg once-daily significantly reduced annualized relapse rate (ARR) vs. once-weekly intramuscular interferon (IFN)b-1a 30 lg by 52% at 1 year (p<0.001). Using a negative binomial regression model, effects of fingolimod on ARR were evaluated in various patient subgroups (intent-to-treat population). ARR was lower with fingolimod 0.5 mg than with IFNb-1a in both treatment-naive (ARR ratio ¼ 0.14, fingolimod [n ¼ 183] vs. 0.31, IFNb-1a [n ¼ 183]) and previously treated (ARR ratio ¼ 0.26, fingolimod [n ¼ 246] vs. 0.52, IFNb-1a [n ¼ 248]) patient subgroups. ARR treatment ratios (fingolimod 0.5 mg vs. IFNb-1a) favored fingolimod regardless of prior treatment with IFN (yes: ARR ratio ¼ 0.42, confidence interval [CI]: 0.29–0.62 [n ¼ 218, fingolimod; n ¼ 206, IFNb-1a]; no: ARR ratio ¼ 0.57, CI: 0.37–0.87 [n ¼ 211, fingolimod; n ¼ 225, IFNb-1a]) or glatiramer acetate (yes: ARR ratio ¼ 0.72, CI: 0.40–1.30 [n ¼ 56, fingolimod; n ¼ 66, IFNb-1a]; no: ARR ratio ¼ 0.44, CI: 0.32–0.60 [n ¼ 373, fingolimod; n ¼ 365, IFNb-1a]) and regardless of whether patients discontinued study for lack of efficacy (yes: ARR ratio ¼ 0.43, CI: 0.19– 0.95 [n ¼ 41, fingolimod; n ¼ 45, IFNb-1a]; no: ARR ratio ¼ 0.50, CI: 0.37–0.67 [n ¼ 388, fingolimod; n ¼ 386, IFNb-1a]). In TRANSFORMS, fingolimod improved ARR in the subgroups analyzed. Study supported by: Novartis Pharma AG, Basel, Switzerland Dr. Khatri is a consultant or does speaking for Teva, Bayer, Pfizer, Medtronics, Biogen Idec, Serono, and Novartis. He does receive compensation from them. Dr. Pelletier has received consulting fees from Novartis, Bayer Schering, Merck Serono, sanofi-aventis, and Teva. Dr. Kappos has participated as principal investigator, member or chair of planning and steering committees or advisory boards in corporate-sponsored clinical trials in multiple sclerosis and other neurological diseases. The sponsoring pharmaceutical companies for these trials include Actelion, Advancell, Allozyne, BaroFold, Bayer Health Care Pharmaceuticals, Bayer Schering Pharma, Bayhill, Biogen Idec, BioMarin, CLC Behring, Elan, Genmab, Genmark, GeNeuro SA, GlaxoSmithKline, Lilly, Merck Serono, MediciNova, Novartis, Novonordisk, Peptimmune, sanofi-aventis, Santhera, Roche, Teva, UCB and Wyeth. He has also lectured at medical conferences or in public on various aspects of the diagnosis and management of multiple sclerosis. In many cases these talks have been sponsored by non-restricted educational grants from one or another of the above listed companies. Honoraria and other payments for all these activities have been exclusively used for funding of research of his department. Research and the clinical operations (nursing and patient T1709. Safety Overview of Fingolimod in Relapsing Multiple Sclerosis: Phase 2 and 3 Studies Jeffrey A. Cohen, Ludwig Kappos, Gordon Francis, William Collins, Lixin Zhang-Auberson and Dejun Tang; Cleveland, OH; Basel, Switzerland and East Hanover, NJ Fingolimod (FTY720) is a sphingosine-1-phosphate receptor modulator approved in the US for relapsing multiple sclerosis. Safety data from phase 2 and 3 studies were assessed using 2 analysis groups: Group A (FREEDOMS; n ¼ 1272) included patients receiving fingolimod 1.25-mg or 0.5-mg once-daily, or placebo; Group B (all studies; N ¼ 2615) included patients receiving fingolimod in phase 2 and 3 (TRANSFORMS/FREEDOMS) studies and ongoing extensions. In Group A, serious adverse event (AE) rates were 10.1% with fingolimod 0.5 mg, 11.9% with 1.25 mg, and 13.4% with placebo; corresponding rates of AEs leading to discontinuation were 7.5%, 14.2%, and 7.7%. Group B results were similar, with higher rates of AEs leading to discontinuation with fingolimod 1.25 mg. Overall infection rates were 68.5–71.5% in the fingolimod groups vs. 72% with placebo (Group A). Malignancy rates were 0.9% in both fingolimod groups vs. 2.4% with placebo in Group A and 1.4% with fingolimod 0.5 mg and 1.1% with 1.25 mg in Group B. Macular edema was uncommon, dose-dependent, and generally resolved upon treatment discontinuation. The safety profile of fingolimod has been well characterized, with a better benefit-risk profile observed with the 0.5-mg dose. Study supported by: Novartis Pharma AG, Basel, Switzerland Dr. Cohen has received consulting fees from Biogen Idec, Elan, Lilly, Novartis, and Teva. Dr. Kappos has participated as principal investigator, member or chair of planning and steering committees or advisory boards in corporate-sponsored clinical trials in multiple sclerosis and other neurological diseases. The sponsoring pharmaceutical companies for these trials include Actelion, Advancell, Allozyne, BaroFold, Bayer Health Care Pharmaceuticals, Bayer Schering Pharma, Bayhill, Biogen Idec, BioMarin, CLC Behring, Elan, Genmab, Genmark, GeNeuro SA, GlaxoSmithKline, Lilly, Merck Serono, MediciNova, Novartis, Novonordisk, Peptimmune, sanofi-aventis, Santhera, Roche, Teva, UCB and Wyeth. He has also lectured at medical conferences or in public on various aspects of the diagnosis and management of multiple sclerosis. In many cases these talks have been sponsored by non-restricted educational grants from one or another of the above listed companies. Honoraria and other 87 ID: senthilk I Black Lining: [ON] I Time: 08:46 I Path: //xinchnasjn/01Journals/Wiley/3b2/ANA#/Vol00000/110244/APPFile/JW-ANA#110244 J_ID: ZAY Customer A_ID: SUPP11-6 Cadmus Art: 22579 Date: 31-August-11 payments for all these activities have been exclusively used for funding of research of his department. Research and the clinical operations (nursing and patient care services) of the MS Center in Basel have been supported by non-restricted grants from one or more of these companies and by grants from the Swiss MS Society, the Swiss National Research Foundation, the European Union, the Gianni Rubatto, Novartis and Roche Research Foundations. Dr. Francis, Dr. Collins, Dr. Zhang-Auberson, and Dr. Tang are employees of Novartis. Stage: Page: 88 itive with the cell based assays: eight for both CASPR2-Abs and LGI1-Abs, four only for CASPR2-Abs, two only for LGI1-Abs. In addition, ten of the 48 VGKC-complex-Ab negative sera had CASPR2-Abs. These results indicate that patients with neuromyotonia can have both CASPR2 and LGI1 antibodies. Moreover, the presence of CASPR2 antibodies in 20% of the patients negative for VGKC-Abs by radioimmunoassay suggests that the cell-based assays may make a useful addition to the investigation of neuromyotonia. Study supported by: Medical Research Council of Great Britain and NIHR Oxford Biomedical Research Centre Angela Vincent, Sarosh Irani and Patrick Waters may in the future receive royalties from use of the LGI1 and CASPR2 antibodies for diagnosis of neuromyotonia and other diseases T1710. Fingolimod Mechanism of Action (MOA) in Multiple Sclerosis (MS) Jerold Chun and Jeffery A. Cohen; La Jolla, CA and Cleveland, OH Fingolimod, the first oral MS therapy, is thought to mediate its effects through actions of its metabolite, fingolimodphosphate, on sphingosine-1-phosphate (S1P) receptors on T-lymphocytes. This interaction produces ��functional antagonism’’ of the receptor subtype S1P1 on CCR7-positive Tcells (naı¨ve, activated, central memory), whereby S1P1 is internalized and degraded, receptor signalling is lost, and egress from lymphoid organs is inhibited. Fingolimod exposure leaves CCR7-negative effector memory T-cells comparatively unaffected. In MS, the net effect is a relative preservation of immune surveillance, while proinflammatory subsets are prevented from reaching the CNS. Additionally, accumulating data support a distinct, nonmutually exclusive mechanism involving direct S1P-receptor modulation on CNS cells. To address this issue, studies in EAE-challenged mice have been pursued using a conditional-null mutation resulting in a lack of S1P1 in neurons and glia. This mutant demonstrated attenuated disease severity and loss of fingolimod efficacy despite maintaining immunologic effects on peripheral blood lymphocytes. Loss of fingolimod efficacy was apparent in astrocyte, but not neuronal, S1P1-null mutants. Additional data in this model will be discussed towards considering fingolimod as having a dual MOA involving S1P-receptor modulation in not only the immune system but also the CNS. Study supported by: NIH and Novartis Pharma AG, Basel, Switzerland Dr. Chun has received consulting fees from Novartis and Ono; lecture fees from Novartis; and research support from Novartis and Pfizer. Dr. Cohen has received consulting fees from Biogen Idec, Elan, Lilly, Novartis, and Teva. T1712. Withdrawn T1713. Association of MS Susceptibility Variants and Early Attack Location Ellen M. Mowry, Jean Pelletier, Maria R. Blasco, Pierre Duquette, Pablo Villoslada, Pierre-Antoine Gourraud, Irina Malikova, Christophe Picard, Jamie McDonald, Elaine Roger, Stacy Caillier and Emmanuelle Waubant; San Francisco; Marseille, France; Madrid, Spain; Montreal, Canada and Pamplona, Spain Background: The anatomic location of early MS relapses within the central nervous system is predicted by the first attack location. We sought to determine if genetic polymorphisms associated with multiple sclerosis (MS) susceptibility are associated with attack location. Methods: 17 well-documented MS susceptibility polymorphisms were genotyped in 354 white, non-Hispanic patients seen within a year of MS onset. Their association with the CNS location of the first two MS attacks was assessed. Results: The IL12A polymorphism was associated with increased odds of both attacks involving the spinal cord (OR ¼ 2.4, 95% CI 1.3, 4.3, p ¼ 0.003). The IL7R polymorphism was associated with reduced odds of both attacks involving the brainstem/cerebellum (OR ¼ 0.2, 95% CI 0.0, 0.9, p ¼ 0.042). There was a strong trend for an association of EVI5 with reduced odds of both attacks featuring optic neuritis. Several other genes showed trends for association with attack locations. Conclusions: Some of the MS susceptibility genes predict MS attack location. This finding may lead to improved understanding of MS pathogenesis and treatment. Study supported by: National Multiple Sclerosis Society T1711. Antibodies to the VGKC-Complex Proteins LGI1 and CASPR2 in Acquired Neuromyotonia Camilla Buckley, Philippa Pettingill, Rosie Pettingill, Matthew Kiernan, Osamu Watanabe, Sarosh Irani, Patrick Waters and Angela Vincent; Oxford, United Kingdom; Sydney, Australia and Kagoshima, Japan T1714. Osmotic Demyelination Syndrome: Lack of Association between Outcome and Severity of Hyponatremia Jennifer E. Fugate*, Jonathan Graff-Radford and Alejandro A. Rabinstein; Rochester, MN VGKC-complex-Abs are found in neuromyotonia, Morvan’s syndrome, or limbic encephalitis. It is now clear that VGKC-complex-Abs are mainly directed against proteins that are complexed with VGKCs in the brain, particularly LGI1 (mainly limbic encephalitis) and CASPR2 (mainly Morvans syndrome and neuromyotonia), but these antibodies have not been studied in detail in neuromyotonia patients. 68 sera from patients with neuromyotonia from centers in Kagoshima and Sydney (29 females, 39 males,12 to 85 years) were assayed using cell-based assays for antibodies to LGI1 and CASPR2. 20/68 (30%) sera were positive for VGKC-complex-Abs (106–1560 pM) including three of the four with Morvans syndrome. 14 of these sera were pos- Objective: Little is known about outcome predictors in osmotic demyelination syndrome (ODS), though one study identified that severity of hyponatremia is an independent predictor. We aimed to characterize clinical and radiographic features of patients with ODS and identify variables that predict outcome. Methods: A retrospective study of patients with ODS identified by a search of Mayo Clinic medical records from 1999–2010. Patients were diagnosed by clinical and 88 ID: senthilk I Black Lining: [ON] I Time: 08:46 I Path: //xinchnasjn/01Journals/Wiley/3b2/ANA#/Vol00000/110244/APPFile/JW-ANA#110244 J_ID: ZAY Customer A_ID: SUPP11-6 Cadmus Art: 22579 Date: 31-August-11 Stage: Page: 89 of patients had !3 of the following: psychiatric symptoms, speech disorder, seizures, dyskinesias, decreased consciousness, autonomic instability, or hypoventilation. Treatment included tumor removal when appropriate, and immunotherapy (91%). At the time of analysis, full recovery/minimal symptoms (back to all activities) have occurred in 57.3% of the patients, mainly in those with teratoma (66.7% vs 48.8%); 6% died. The frequency of relapses varied according to the response to initial immunotherapy; 87% of relapses occurred in patients without teratoma. Conclusions: Anti-NMDA-receptor encephalitis is a severe but treatable disorder of predominantly young individuals. Prompt diagnosis and treatment are important to improve outcome. In addition to the above, detailed analysis of the frequency of relapses, immunotherapy, timing of recovery, and prognostic factors will be provided. Study supported by: The current work is supported in part by grants from the National Institutes of Health and National Cancer Institute RO1CA89054 (Dalmau), 1RC1NS068204-01 (Balice-Gordon and Dalmau), and a McKnight Neuroscience of Brain Disorders award (BaliceGordon and Dalmau). Dr. Titulaer is supported by a KWF fellowship 2009– 4451 of the Dutch Cancer Society; Dr. Martinez-Hernandez has a grant from the Fondo de Investigaciones Sanitarias, FIS, Spain (FI08/00285); 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. radiographic features. Medical charts were reviewed. Favorable outcome was defined by Modified Rankin Scale (mRS) 2. Results: Of 24 patients, 14 (48%) had central pontine myelinolysis and 10 (42%) extrapontine myelinolysis. Hyponatremia was documented in 18 (75%) with mean sodium nadir of 114 mmol/L. Favorable outcome was seen in 15 (63%) at mean follow-up 3 years. Initial brain MRI was normal in 21%. The following variables were assessed: age (p ¼ 0.40), gender (0.68), sodium level (p ¼ 0.30), albumin (p ¼ 0.12), extrapontine involvement (p ¼ 1.00), GCS (p ¼ 0.33), alcoholism (p ¼ 1.00), and sepsis (p ¼ 0.17). None were predictive of outcome. Conclusions: Functional outcome in ODS is not associated with severity of hyponatremia. Serial brain imaging is of value as a substantial proportion of patients have normal initial MRIs. T1715. Correlation of Brain Atrophy, Disability and Spinal Cord Atrophy in a Murine Model of MS M Mateo Paz Soldan, Jeffrey D. Gamez, Aaron J. Johnson, Anne K. Lohrey, Yi Chen and Istvan Pirko; Rochester, MN and Cincinnati, OH Disability progression in MS remains incompletely understood. Unlike lesional measures, CNS atrophy has strong correlation with disability. TMEV infection in SJL mice is an established model of progressive MS. We utilized in vivo MRI to quantify brain and spinal cord atrophy in this model and analyzed the temporal relationship between atrophy and disability. Infected and control mice were followed for 12 months. Disability was assessed monthly using rotarod assay. Volumetric MRI datasets were acquired at 7 Tesla. Ventricular volume and C4-5 cord cross-sectional area measurements were performed using Analyze 10. At three months, brain atrophy reached statistical significance (p ¼ 0.009). In contrast, disability did not differ until four months post infection (p ¼ 0.0032). Cord atrophy reached significance by eight months (p ¼ 0.0088). By 12 months, brain atrophy resulted in 111.8% increased ventricular volume (p ¼ 0.000031), while spinal cord cross-sectional area was 25% reduced (p ¼ 0.0013) in cases. Our results suggest that significant brain atrophy precedes and predicts the development of disability, while spinal cord atrophy occurs late and correlates with severe disability. The observed temporal relationship establishes a framework for mechanisms of disability progression and enables further investigations of their underlying substrate. Study supported by: National MS Society Pilot Project Grant, NIH/NINDS R01 NS 058698 T1717. Cigarette Smoke Induces Inflammation and Oxidative Stress in Brains of Lewis Rats Ashwani Khanna and Walter Royal, III; Baltimore, MD Cigarette smoke (CS) exposure is a risk factor for developing multiple sclerosis. We examined this effect by analyzing brains from Lewis rats exposed to CS from 4 cigarettes / day for 30 days using a system developed to simulate human smoking behavior. Using quantitative PCR, we observed an increase in IFN-c, TNF-a, TGF-b, IL-10, IL6, IL-17, IL-18 and IL-23 and in MCP-1/CCL2, MIP-1a/ CXCR3 and SDF-1a/CXCL12 gene expression in the rat brains. Also gene expression for p22phox, NOX-4, dual oxidase and Nfr2 was increased whereas thioredoxin gene expression was decreased. Immunocytochemical analysis of the brains from the rats showed, compared to rats not exposed to CS, increased staining for CD4, TNF-a, IFNc, class II MHC, ED1, Nrf2 and GFAP. Double immunofluorescence staining demonstrated cytoplasmic localization of Nrf2 in astrocytes from rats exposed to CS whereas nuclear localization was observed for non-exposed rats. These studies, therefore, demonstrate that CS exposure can result in increased brain immune cell trafficking, pro-inflammatory responses and oxidative stress. This model may be useful for elucidating mechanisms related to the link between CS and MS and for developing effective treatment strategies for the diseases. T1716. Anti-NMDA-Receptor Encephalitis: Clinical Analysis of 457 Patients Maarten J. Titulaer, Eugenia Martinez-Hernandez, Lindsey McCracken, Rita Balice-Gordon and Josep Dalmau; Philadelphia, PA and Barcelona, Spain Introduction: Anti-NMDA-receptor encephalitis is the most common and best characterized antibody-mediated encephalitis. We provide the clinical features and follow-up of 457 patients. Methods: Analysis of demographics, onset, syndrome, treatment, and outcome at 24 months. Results: 84% were female. Median age was 21 years (range 1–85; 39% 18 and 4.3% !45 years). 45% had a tumor (94% teratomas, 5.7% other). 62% of females >18 years had ovarian teratoma(s), versus 35% 18 years. 84% T1718. Withdrawn T1719. Differential Sensitivity of Human PBMC Subsets to Alemtuzumab-Mediated Cytotoxicity William Siders, Sambasiva Rao, Juanita Campos-Rivera, Jose Sancho, Paula Boutin, Peter Severy, Johanne Kaplan, Bruce Roberts and Srinivas Shankara; Framingham, MA 89 ID: senthilk I Black Lining: [ON] I Time: 08:46 I Path: //xinchnasjn/01Journals/Wiley/3b2/ANA#/Vol00000/110244/APPFile/JW-ANA#110244 J_ID: ZAY Customer A_ID: SUPP11-6 Cadmus Art: 22579 Date: 31-August-11 Alemtuzumab(monoclonal antibody)currently in clinical trials for treatment of MS,recognizes CD52antigen expressed on lymphocytes&most myeloid cells. Its cytotoxic effects are reportedly influenced by density ofCD52antigen on target cells. Using alemtuzumab in polychromatic flow cytometry assay,we examined levels ofCD52expression on 20distinct subsets of lymphoid &myeloid cells in peripheral blood mononuclear cells(PBMCs)from 11 healthy donors. Data demonstrated subsets of PBMCs express differing levels ofCD52. Quantitative analysis showed memory B-cells&myeloid dendritic cells(mDCs)display highest number while natural killer (NK) cells&plasmacytoid DCs have lowest number of CD52 molecules per cell amongst lymphoid&myeloid cell populations,respectively. To test significance of differential CD52expression on sensitivity of PBMC subsets to alemtuzumabmediated cytotoxicity, we developed flow cytometry-based, complement-dependent cytotoxicity(CDC) assay allowing for simultaneous assessment of total number of dead cells&identification of phenotypes of surviving cells amongst PBMCs. Results from 4donors indicated, amongst lymphocytes, alemtuzumab-mediated profound cytotoxic effects on B-and Tcells with minimal effect on NKcells, correlating with density ofCD52 on these cells. Despite CD52 levels comparable to lymphocyte subsets, mDCs&monocytes were less susceptible to alemtuzumab-mediated CDC indicating antigen density alone doesn’t define susceptibility. Additionally, mDCs&monocytes expressed significantly higher levels of complement inhibitory proteins(CIPs) compared to lymphocyte subsets which may contribute to their resistance to alemtuzumabmediated CDC. Overall, results show while density of CD52 antigen can influence cell susceptibility to alemtuzumabmediated CDC, factors such as, level of CIP expression, may also have an impact. Study supported by: Genzyme All authors received financial compensation (including stock) as employees of Genzyme. Stage: Page: 90 T1721. Analysis of Immune Competence Following Alemtuzumab Treatment in huCD52transgenic Mice William Siders, Nathalie Chretien, Michael LaMorte, Bruce Roberts and Johanne Kaplan; Framingham, MA Alemtuzumab (humanized monoclonal antibody) currently in clinical trials for treatment of MS, results in the overall depletion of lymphocyte subsets followed by extended period of repopulation. The goal, to evaluate functionality of lymphocytes following treatment, was accomplished by treating human CD52 (huCD52) transgenic mice w/alemtuzumab & evaluating ability of remaining T-lymphocytes to respond to polyclonal stimulation. While lymphocytes from animals treated with alemtuzumab are present in lower numbers, they retain ability to proliferate in response to T-cell receptor (TCR) ligation & produce similarTh1, Th2, & Th17 family cytokines compared to lymphocytes from untreated animals. Comparison of TCR Vbeta families represented in alemtuzumab-treated & untreated animals demonstrated no differences in diversity of T-cell repertoire. We next evaluated ability of alemtuzumab-treated animals to generate de novo & recall immune responses to adenovirus serotype2( Ad2). Animals were injected with Ad2 at various timepoints relative to treatment &evaluated for Ad2-specificT-cell frequency by IFNgamma ELIspot & development of antibodies to Ad2. This demonstrated animals immunized as early as 7 days developed detectable frequencies of antigen specific T-cells. Recall responses were unaffected in animals which memory responses were allowed to develop prior to treatment. These studies demonstrate alemtuzumab therapy doesn’t impact functional activity of remaining T-cells &doesn’t severely affect ability of host to generate functional T- and B-cell responses to foreign antigen. Study supported by: Genzyme All authors receive financial compensation from Genzyme (including stock) as employees. T1722. Withdrawn T1720. Transcriptional Profiles Uncover Population Structure among Multiple Sclerosis Patients Linda Ottoboni, David Hafler, Howard Weiner and Philip De Jager; Boston, MA and New Haven, CT T1723. Withdrawn There is extensive heterogeneity among subjects with multiple sclerosis (MS) in terms of their disease course and treatment response. Here, we explore the structure of the MS subject population using RNA expression profiles derived from peripheral blood mononuclear cells of 398 subjects. These subjects were untreated (n ¼ 148), treated with glatiramer acetate (GA) (n ¼ 101) or treated with interferon beta (IFNb) (n ¼ 143). We find the expected expression profile associated with IFNb treatment but find no significant difference in gene expression with GA treatment. Using unsupervised clustering, we define 2 subsets of untreated subjects, with enhanced type I interferon response gene expression in the smaller group and enhanced lymphocyte activation pathway gene expression in the larger group. This population structure is preserved in the GA subjects (Kappa coefficient ¼ 0.83) and IFNb subjects (Kappa ¼ 0.82). Retrospective data suggest that the smaller group is more likely to have an clinical or MRI event after sampling (p ¼ 0.02). We therefore report the identification of a gene expression profile discriminating 2 subsets of MS subjects and further report that this architecture captures a previously reported T cell gene expression signature associated with high-risk CIS subjects (Corvol et al. PNAS 2008). Study supported by: Affymetrix Inc. - donation of microarrays and processing T1724. A Single Dose Escalation Study of the Safety, Pharmacokinetics, and Pharmacodynamics of Subcutaneous Pegylated Interferon-Beta in Healthy Volunteers Kenneth Grabstein, Aijun Wang, Natalie Winblade Nairn and Daniel J. Burge; Seattle, WA Purpose: A single-ascending dose study was conducted in healthy volunteers (HV) to establish the safety, tolerability, pharmacokinetic (PK) and pharmacodynamic (PD) profile of AZ01 (PEGylated interferon-beta). Methods: Eight HV in each of 5 escalation cohorts received one subcutaneous dose of AZ01 or placebo (6:2) at doses from 100mg to 10mg. Safety, PK and PD parameters were evaluated. Results: The AE profile of AZ01 was consistent with that expected with IFN-beta therapy, especially in the 10mg group. Events included injection site reactions, headache, myalgia, chills, fatigue, nausea, and fever. No SAEs or AEs leading to discontinuation occurred. No laboratory parameter, vital sign measurement, or ECG was determined by the Investigator to be clinically significant. PK and PD analyses indicate a sustained exposure and response to single doses of AZ01, lasting about 14 days. Conclusion: Single subcutaneous AZ01 doses of up to 10mg were well tolerated by HV. 90 ID: senthilk I Black Lining: [ON] I Time: 08:46 I Path: //xinchnasjn/01Journals/Wiley/3b2/ANA#/Vol00000/110244/APPFile/JW-ANA#110244 J_ID: ZAY Customer A_ID: SUPP11-6 Cadmus Art: 22579 Date: 31-August-11 The prolonged PK and PD may allow dosing at greater intervals than with currently available interferon therapies. Less frequent injections are likely to decrease injection site reactions and flu-like symptoms and improve compliance. Study supported by: Allozyne Inc. Salaries, stock options, consulting fees Stage: Page: 91 nir; research support from Biogen Idec, Teva, Novartis, the National MS Society, Pittsburgh Foundation, and Allegheny-Singer Research Foundation. XY and PF: employees of Biogen Idec. T1727. The Correlation of Brain MRI Lesion Load with Functional Outcome in Animal Models of MS Istvan Pirko, Jeffrey Gamez, Moses Rodriguez, Mihajlo Babovic and Slobodan I. Macura; Rochester, MN and Northfield, MN T1725. Regulation of IL-12 by IL-23 in Bone Marrow Dendritic Cells Farinaz Safavi, Patricia Gonnella, Bogojub Ciric, Abdolmohamad Rostami and Farinaz Safavi; Philadelphia, PA We previously demonstrated MS-related MRI features including brain atrophy, spinal cord atrophy, lesional T1 hypointensity and gray matter T2 hypointensity in Theiler’s Murine Encephalitis Virus-based MS models. A common characteristic of most MS models is the relative paucity of brain compared to spinal cord lesions. In MS, brain lesion load and disability correlation remains controversial, with most studies demonstrating weak but some showing moderate to strong correlation. We hereby describe two different models of brain lesion development and their correlation with rotarod detectable disability. In interferon-c receptor deficient mice of 129 (A) or C57BL6/J (B) background, we observed different patterns of lesion formation: in model (A) lesion development was close to linear and showed strong correlation with disability (r ¼ À0.96, p ¼ 0.00002). In model (B), biphasic lesion development was demonstrated: early (<4weeks) and unusually large periventricular lesion formation was followed by lesion development similar to the pattern in model (A), and only beyond week 4 was a strong MRI-disability correlation observed in this model (r ¼ À0.92, p ¼ 0.02).These models demonstrate different patterns of lesion formation and correlation with disability and may allow for investigations of the MRIclinical paradox. Study supported by: NIH NINDS R01 NS58698, Mayo Clinic Department of Neurology Intramural Research Funds Th1 and Th17 cells play important roles in the pathogenesis of Experimental Autoimmune Encephalomyelitis and other autoimmune models. IL-12 and IL-23 are heterodimeric cytokines produced mostly by dendritic cells (DCs) that promote development of Th1 and Th17 cells, respectively. Understanding the mechanisms that regulate production of these cytokines should advance our knowledge of the pathogenesis of Multiple Sclerosis (MS) and could lead to novel treatments for this disease. To test the effect of IL-23 on IL12 production, Bone Marrow Dendritic cells(BMDCs) from IL-23p19 KO and WT mice were used. BMDCs were stimulated with LPS and mouse recombinant IL-23 (5 ng/ ml) and IL-12p70 and IL-12p35 expression were measured after 6 and 24 hrs. WT DCs stimulated with both LPS and LPSþIL-23 secreted significantly larger quantities of IL12p70 (p< 0.01) compared to IL-23p19 KO cells. RT-PCR analysis also showed significantly higher expression of IL12p35 mRNA in WT DCs treated with either LPSþIL-23 or LPS (p < 0.01 ). Our observations indicate that the expression of IL-12 is regulated by IL-23 in vitro.Finding similar regulatory mechanisms in vivo should increase our understanding of the role of these cytokines in the pathogenesis of autoimmunity. Study supported by: NIH grant number RO1NS046782 T1726. Clinically Apparent MRI Activity Predicts 2-Year Outcomes in Patients with RRMS Thomas Scott, Xiaojun You and Pamela Foulds; Pittsburgh, PA and Weston, MA T1728. Comparison of CIDP Patients with Normal and Elevated CSF Protein YuanYuan Xue and Ericka P. Simpson; Houston, TX Background: Several studies report clinically apparent and clinically silent MRI lesions predict disease worsening in patients on IFNb-1a. The magnitude of risk, especially with clinically silent activity, remains uncertain. Methods: SENTINEL enrolled patients with > ¼ 12 months of prior IFNb-1a treatment who continued with or without addition of natalizumab. MRI scans at baseline and year 1 were compared for new lesions. New lesions as a risk for clinical activity (relapses or progression) between years 1 and 2 were examined. Results: New MRI and clinical activity in year 1 was associated with increased risk for relapse or progression in year 2 (P<0.0001 and P ¼ 0.0016). Clinical activity in year 1, even without new MRI activity, showed increased risk for the same outcomes (P<0.0004). From a logistic regression, patients with > ¼ 2 new MRI lesions and no clinical activity in year 1 demonstrated a trend to be more likely to have clinical activity in year 2 compared with similar patients with <2 new lesions in year 1 (OR ¼ 1.562, CI 0.889, 2.743), P ¼ 0.1208). Conclusion: Clinically apparent but not clinically silent MRI activity predicted disease worsening over 2 years. Longer studies are needed to confirm results. Study supported by: Biogen Idec Inc. TS: consultant fees and honoraria from Biogen Idec, Teva, Novartis, Pfizer, Athena Diagnostics, Acorda, and Ave- Background: Elevated CSF protein with leukocyte count <10/mm3 is a supportive criterion of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). However, protein content can be normal in a part of these patients. Objective: To analysis the difference of electrophysiological patterns and clinical features in CIDP patients with or without protein elevation. Methods: Detailed electrophysiological findings, clinical features and CSF changes were reviewed in patients with CIDP. Result: Of 35 patients, 26 had elevated CSF protein and 9 were unchanged. There was no statistical difference between these groups for age (Pearson corr: 0.179), gender (Pearson corr: 0.065), response to therapy, comorbdity, and outcome (Pearson correlation 0.197). Of the 9 patients with normal CSF protein, there was a strong correlation with an axonal pattern on electrophysiological examination (Pearson correlation 0.692; pvalue). Conclusion: CIDP patients with normal CSF protein are indistinguishable from CIDP with elevated protein with the exception of an axonal pattern on EMG/NCV. Although these patients had an equal response to therapy, further data will be collected to determine whether other factors are associated with normal CSF protein and treatment outcomes. Study supported by: The Methodist Hospital Neurological Institute Salaries 91 ID: senthilk I Black Lining: [ON] I Time: 08:46 I Path: //xinchnasjn/01Journals/Wiley/3b2/ANA#/Vol00000/110244/APPFile/JW-ANA#110244 J_ID: ZAY Customer A_ID: SUPP11-6 Cadmus Art: 22579 Date: 31-August-11 T1729. Are Anti-TAG-1 Autoantibodies Markers in Autoimmune Demyelinating Disorders of the PNS and CNS? Harry Alexopoulos, Pantelis P. Pavlakis, Domna Karagogeos, Clementine E. Karageorgiou and Marinos C. Dalakas; Athens, Greece and Heraklion, Greece Stage: Page: 92 T1733. The Relationship between Conduction Block and Clinical Characteristics in Guillain-Barre´ Syndrome with Anti-GM1/GalNAc-GD1a Antibodies Go Ogawa, Ken-ichi Kaida, Susumu Kusunoki, Motoi Kuwabara, Fumihiko Kimura and Keiko Kamakura; Tokorozawa, Saitama, Japan and Osaka-Sayama, Osaka, Japan There is evidence of anti-TAG-1 autoantibodies (TAG-1 is involved in the development of axonal connections), being associated with autoimmune syndromes of the CNS. Anti-TAG-1 antibodies have been found both in multiple sclerosis and in autoimmune limbic encephalitis. Also, polymorphisms in the TAG-1 gene influence treatment response in chronic inflammatory demyelinating polyradiculoneuropathy. We wanted to investigate whether anti-TAG-1 autoantibodies are present in CIDP. We tested serum samples from 12 patients with autoimmune demyelinating neuropathy (8 with CIDP, 2 with CIDP and CNS demyelination, 2 with MMN), 9 with Sjo¨gren’s syndrome-associated axonal polyneuropathy and 50 with relapsing–remitting MS. We established a cell-based assay previously used to detect anti-TAG-1 autoantibodies in LE. Briefly, either the FNIII or the IgC2 domains of TAG-1 were expressed in HEK cells and were incubated with patient sera. Antibody binding was visualized using a secondary anti-human fluorescent antibody. No positive staining was detected in any of the patients with autoimmune peripheral neuropathies or with RRMS. Our results suggest that neither anti-TAG-1 autoantibodies are a marker for demyelination in PNS or CNS nor TAG-1 is a candidate autoantigen in CIDP or MS. Study supported by: Special Research Account, National and Kapodistrian University of Athens Patients with Guillain-Barre´ syndrome (GBS) with antibodies to a ganglioside complex GM1/GalNAc-GD1a frequently show motor conduction block (CB) at the intermediate portion of peripheral nerves. Clinical data of 57 patients with anti-GM1/GalNAc-GD1a-IgG were studied to elucidate the association between CB and clinical and electrophysiological characteristics. Thirty patients (male/female, 19/11) had CB, classified as CB(þ) (mean age, 43.1 6 17.7 y/o), and 27 patients (male/female, 10/17) did not, classified as CB(-) (mean age, 46.8 6 16.5 y/o). Males are significantly more in the CB(þ). Both groups presented frequent preceding respiratory infection, infrequent cranial and sensory nerve disturbances, and were equal in the disability at the nadir. Twenty of 25 non-ambulatory patients could walk within three months, with no difference between both groups. The 17 CB(þ) patients were electrodiagnostically classified into acute inflammatory demyelinating polyneuropathy, one of whom changed to acute motor axonal neuropathy later. Serial electrophysiological results suggested Wallerian degeneration only in one and no evident remyelination. In view of the rapid recovery and lack of remyelination, axonal conduction failure with little pathological changes may be major mechanism in anti-GM1/GalNAcGD1a antibody-associated nerve dysfunction. T1734. Withdrawn T1730. Introduction and Diffusion of Multiple Sclerosis in the United States Mitchell T. Wallin and John F. Kurtzke; Washington, DC T1735. Randomized, Open-Label Study To Evaluate Patient-Reported Outcomes (PRO) with Fingolimod after Changing from Prior Disease-Modifying Therapy (DMT) for Relapsing Multiple Sclerosis (MS): EPOC Study Rationale and Design Luigi M. Barbato, Lesley Schofield, Kevin McCague, Linda Pestreich, Kathy Tobias and Manoj Malhotra; East Hanover, NJ Epidemiological evidence suggests that multiple sclerosis has spread from an origin in northwestern Europe. How and when it came to the US has not been well defined. Nationwide morbidity data here have arisen primarily from the military-veteran populations of our several wars. Prevalence rates for draftees rejected because of MS for military service in World War I provide its earliest distribution. Small numbers of cases required combination of states of residence into 23 areas. Prevalence rates for the 255 cases in these areas showing a strikingly high rate in area P, comprising Wisconsin and Minnesota. These states were settled in the mid-19th century mainly by immigrants from south-central Norway and Sweden. Their original Scandinavian residences were principally in the high-risk areas for MS in both countries. When compared with two later military-veteran series, one from World War II and the Korean Conflict, the other from Vietnam and later service to 1994, a continuing spread from this north mid-western focus was seen. MS appears to have been introduced into the US in the mid-19th by immigrants from Scandinavia to Wisconsin and Minnesota, with later diffusion throughout the land. Study supported by: VA Merit Review Grant Program & National MS Society The efficacy and safety profiles of fingolimod (FTY720) have been well characterized in phase 2 and 3 studies; however, limited data exist on PRO. The EPOC study is evaluating PRO and safety in relapsing–remitting MS patients who have received !6 months’ treatment with a single approved DMT and are randomized 3:1 to receive oncedaily fingolimod 0.5 mg with no washout or to continue standard DMT (interferon-b-1a, interferon-b-1b, or glatiramer acetate) for 6 months, followed by a 3-month openlabel extension, in which the DMT group can change to fingolimod with no washout. The primary endpoint is change in patient-reported treatment satisfaction using the global satisfaction subscale of the Treatment Satisfaction Questionnaire for Medication (TSQM). Secondary endpoints are safety/tolerability, changes in physician-reported Clinical Global Impression-Improvement, and changes in the following PRO: Fatigue Severity Scale; Beck Depression Inventory-II; activities of daily living using the Multiple Sclerosis Activities Scale (PRIMUS-Activities); effectiveness, side effects, and convenience subscales of the TSQM; and the Short-Form 36 Health Survey-v2-acute. The study is enrolling at approximately 175 US centers. T1731. Withdrawn T1732. Withdrawn 92 ID: senthilk I Black Lining: [ON] I Time: 08:46 I Path: //xinchnasjn/01Journals/Wiley/3b2/ANA#/Vol00000/110244/APPFile/JW-ANA#110244 J_ID: ZAY Customer A_ID: SUPP11-6 Cadmus Art: 22579 Date: 31-August-11 Study supported by: Novartis Pharma AG, Basel, Switzerland Dr. Barbato, Dr. Schofield, Dr. McCague, Dr. Pestreich, Dr. Tobias, and Dr. Malhotra are employees of Novartis. Stage: Page: 93 T1738. Coma as an Inital Manifestation of Acute Disseminated Encephalomyelitis Megan McGarry, Natasha Tilluckdharry and Dipak P. Pandya; Paterson, NJ Background: Acute Disseminated Encephalomyelitis (ADEM) is a monophasic autoimmune demyelinating disease. Clinical manifestations include an altered behavior, headache, seizures and coma. We report a unique case which was presented as a coma an initial manifestation of ADEM. Case Report 21 year old woman was found unconscious with severe metabolic acidosis, renal failure requiring urgent dialysis and ventilatory support. Magnetic Resonance Imaging (MRI) of the brain showed extensive T2 signal in the periventricular area, deep white matter and bilaterally in the basal ganglia and hippocampus with enhancement. Her CSF studies were unremarkable. She was treated with pulse dose of solumedrol. Because of lack of initial response, she was treated with eight cycles of plasmapheresis. She recovered completely from illness. She had several follow up MRIs with significant improvement. Her neuropsychological evaluations showed significant improvement and currently she is pursuing higher studies without any difficulties. Conclusion: Based on our literature, this is the first case of coma patient as an initial manifestation of ADEM. Our patient has complete recovery of physical and neurcognitive symptoms which make onliest clinical features and outcome. We think that prompt and aggressive management may improve outcome from catastrophic neurological sequel. T1736. Novel Diagnostic Tool for MS Nancy L. Monson, Ann J. Ligocki, William H. Rounds, Diane Xiang, Lindsay G. Cowell, Doug Bigwood, Eric Eastman, Jeffrey L. Bennett, Scott D. Boyd, Andrew Z. Fire, Elliot M. Frohman and Benjamin M. Greenberg; Dallas, TX; Gaithersburg, MD; Denver, CO and Palo Alto, CA Multiple Sclerosis (MS) is the leading disease of the central nervous system and a significant, costly cause of disability in young adults. Patients at risk for MS often present with a single demyelinating event, typically called a ��clinically isolated syndrome’’ (CIS) and present a challenging diagnostic and therapeutic dilemma. The community has an urgent need to develop tools that would assist in identifying patients who would develop MS in the future, since treatment with the appropriate immunomodulatory agents early in the disease course can delay long-term disability. Our laboratory has identified a completely novel type of biomarker, based on a pattern of antibody gene mutations (i.e. antibody gene signature or ��AGS’’) that is exclusive to MS patients. In fact, the AGS demonstrated utility as a molecular diagnostic tool in a small cohort of patients who presented with optic neuritis (and were thus at risk to develop MS) with a sensitivity of 100%, specificity of 67%, positive predictive value of 89%, negative predictive value of 100%, and accuracy of 91%. Our current cohort, which includes both patients who presented with optic neuritis and patients that presented with transverse myelitis, has an increased accuracy of 94%. Study supported by: National MS Society T1739. NMO-IgG in a Patient with Neurosarcoidosis Lena Derani** and Elham Bayat; Washington, DC Neurosarcoidosis is a rare manifestation of sarcoidosis in which inflammation and abnormal deposits occur in the nervous system. Neuromyelitis optica (NMO) is an inflammatory demyelinating disease that primarily targets the spinal cord and optic nerves. NMO-IgG (anti-aquaporin-4) is considered to be a sensitive and specific marker for NMO. However, NMO-IgG has also been found in patients with NMO spectrum disorders (NMOSD), paraneoplastic disease and systemic lupus erythematosus. We present the first reported case of NMO-IgG positivity in a patient with neurosarcoidosis but no evidence of NMO. We discuss autoimmunity in neurosarcoidosis, the specificity of NMO-IgG and its likelihood in autoimmune diseases, and the possibility of concomitant neurosarcoidosis and neuromyelitis optica. We suggest the possibility that NMO-IgG is a nonspecific indicator of autoimmunity present in patients with other autoimmune disorders, including neurosarcoidosis. We remind neurologists that patients who test positive for NMO-IgG do not necessarily carry the diagnosis of NMO or NMOSD, despite the documented specificity and sensitivity of NMO-IgG for these diseases. Further studies are needed to investigate the positive predictive value of NMOIgG and the prevalence of positive NMO-IgG in the normal population and in patients with autoimmune diseases. T1737. Efficacy of Combination Therapy in Marburg Variant Type of Multiple Sclerosis Jennifer Gabbard, Yasmin Bilal and Dipak Pandya; Paterson, NJ Background: Marburg variant type of MS is a very rare form of disease which commonly consider fatal after weeks to months. The variant forms of multiple sclerosis are very rare and tend to have a rapid deteriorating course. We report an unusual case of Marburg variant MS, who responded to various combination therapy favourably. Results: 18-year-old male presented with imbalance, wide based gait and dizziness. His physical examination showed nystagmus, no signs of optic neuropathy, dysmetria, hyperreflexia and sustained clonus. The MRI brain showed extensive demyelinating plaques in periventricular white matter, brainstem and various areas of brain. The imaging findings were not consistent with Neuromyelitis optica. The patient was initally treated with pulse doses methylprednisone and plasmapheresis. Because of persisting clinical symptoms and imaging findings, patient was treated with induction doses of mitoxanthrone and interferone beta-1b. The patient had near complete resolution of his clinical symptoms and significant MRI improvement. Conclusions: Combination acute therapies like plasmapheresis and mitoxanthrone may reduce inflammatory cytokins in acute course of disease and may result in improvement. More multicenter clinical trial may help to understand nature of disease and management options. T1740. Correlates of Dietary Intake in Individuals with Multiple Sclerosis Matthew A. Plow, Marcia Finlayson and Chi Cho; Cleveland, OH and Chicago, IL Since the multiple sclerosis (MS) population has a similar life expectancy as the general population and is characterized by impairments that can interfere with healthy eating habits, malnutrition, vitamin deficiencies, and obesity are prevalent problems among MS patients. However, few studies have been conducted to provide clinicians with evidence-based 93 ID: senthilk I Black Lining: [ON] I Time: 08:46 I Path: //xinchnasjn/01Journals/Wiley/3b2/ANA#/Vol00000/110244/APPFile/JW-ANA#110244 J_ID: ZAY Customer A_ID: SUPP11-6 Cadmus Art: 22579 Date: 31-August-11 approaches to support MS patients in developing healthy eating habits. Thus, the purpose of this study was to identify modifiable factors that predict dietary intake. Using data from an on-line validated survey of 271 MS patients, a stepwise multiple regression model was used to determine the relative importance of personal characteristics, symptoms, functional limitations, and coping skills in influencing dietary intake. Over 50% of the sample was overweight/ obese. Four variables made the model: self-efficacy (b ¼ 0.51), physical activity (b ¼ 0.14), pessimism (b ¼ À0.13), age (b ¼ 0.12), and coping skills (b ¼ 0.10), which explained 40.5% of the variance in intake. Neither symptoms nor functional limitations significantly predicted intake. This is the first study to document a relationship between self-efficacy, coping skills, and nutritional habits in a large generalizable sample of MS patients. Future research should examine the effectiveness of efficacy-enhancing nutritional interventions that focus on improving coping skills. Study supported by: This work was supported through the National Multiple Sclerosis Society (NMSS) post-doctoral training grant. The information presented in this abstract does not necessarily reflect the position, ideas, or opinions of the NMSS Stage: Page: 94 CSF with distinct chemokine/cytokine profiles. Cluster 1 had the shortest time from initial melanoma diagnosis to brain metastasis (mean 7.5 months, P ¼ 0.0278). MIP-1b and IP-10 were elevated while GRO-a, IL-8, and Eotaxin were suppressed. Cluster 3 was associated with a shortened time from brain metastasis to death (mean 5.5 months, P ¼ 0.0714). Prior biologics treatment also correlated with the shortest time interval from brain metastasis to death (mean 5.9 months, P ¼ 0.0396). In cluster 3, MIP-1a was elevated, while GRO-a, MPIF-1, MIG, and IL-1b were suppressed. Cluster 4 was associated with a trend for prolonged overall survival (mean 78.0 months, P ¼ 0.0847). This cluster also had the longest survival from date of biologics treatment to death (mean 58.5 months, P ¼ 0.0132). Cluster 4 had elevated MPIF-1 while GRO-a, IL-8, IP-10, MDC, IL5, MIG, and IL-1b were suppressed. Specific cytokine/chemokine profiles measured in the CSF of melanoma patients may have prognostic and predictive value for melanoma brain metastasis. Study supported by: A Reason To Ride research fund. T1803. Role of p75NTR and Its Signaling Pathways in Fenretinide (4-hydroxyphenyl Retinamide – 4HPR) Induced Apoptosis in Neuroblastoma Cells Veena R. Ganeshan and Nina F. Schor; Rochester, NY Neurooncology T1801. Comparative Uptake and Cytotoxicity of AntiHu and Anti-Ri Antibodies in Rat Cerebellar Slice Cultures John E. Greenlee, Susan A. Clawson, Blair Wood, Kenneth E. Hill and Noel G. Carlson; Salt Lake City, UT Objective: To understand the role of p75NTR and its signaling pathways in Fenretinide(4-hydroxyphenyl retinamide4HPR)-induced apoptosis and determine if JNK phosphorylation mediates this effect in neuroblastoma cells. Background: 4HPR is well tolerated in clinical trials and causes apoptosis by increasing oxidative stress(OS) in cancer cells. p75NTR has pro and anti-apoptotic functions depending on the cell milieu and type. Methods: S-type neuroblastoma cells (SH-EP1) transfected with varying amounts of p75NTR are used in the 4HPR-concentration experiments. 4HPR treatment results in changes in JNK phosphorylation and OS, which are recorded using western blotting and fluorescent microscopy. Results: 4HPR treatment reduces viability in SH-EP1 and SK-N-SH cells within 24(15%)-72 hrs(40%) and causes an increase in mitochondrial O2- production. A sustained increase in Akt phosphorylation occurs in SH-EP1 cells with lower p75NTR levels. Within 1hr of 4HPR treatment, JNK phosphorylation increases by 100–150% in SH-EP1 cells with lower levels of p75NTR. Conclusion: JNK phosphorylation appears to be protective against 4HPR-induced apoptosis. This will facilitate the development of combination chemotherapeutics for residual disease treatment and recurrence by increasing OS and enhancing response to conventional chemotherapeutics. Study supported by: Studies presented in this abstract were funded by grants to Nina F. Schor from the National Cancer Institute (CA07429), the National Institute of Neurologic Disorders and Stroke (NS038569), and the William H. Eilinger Endowment for Pediatric Research of the Golisano Children’s Hospital at the University of Rochester Medical Center. These organizations played no role in the interpretation of the data or the substance of the review presented herein. Veena R. Ganeshan is a doctoral student in the Integrated Graduate Program in Neuroscience of the University of Rochester School of Medicine and Dentistry. Neither of the authors have conflicts of interest of relevance for this abstract. No additional individuals played any role in the production of this abstract. Anti-Hu and anti-Ri antibodies label different neuronal antigens in western blots. However, both recognize intracellular antigens present in essentially all neurons. At autopsy, brains of patients with anti-Hu antibody show neuronal destruction. In contrast, anti-Ri antibody is less clearly associated with neuronal death, and patients with anti-Ri antibodies may respond to treatment. To study the effects of these two antibodies on living neurons, we incubated rat cerebellar slice cultures with either anti-Hu or anti-Ri antibodies and followed these cultures over time using TUNEL and FLICA methods to detect apoptosis, and uptake of SYTOX green to detect non-apoptotic cell death. Both anti-Hu and anti-Ri antibodies accumulated in essentially all neurons. Anti-Hu antibodies caused apoptosis within 72–96 hours in neurons throughout the cerebellum. In contrast, cells accumulating anti-Ri antibodies remained viable for over 200 hours, without evidence of apoptosis or necrotic cell death. Neurons in general may be able to internalize antibodies. Anti-Hu appears to be specifically cytotoxic, whereas anti-Ri appears less able to affect neuronal viability and may predominantly cause neuronal dysfunction rather than death. Study supported by: United States Department of Veterans Affairs T1802. Cerebrospinal Fluid Chemokine/Cytokine Biomarkers for Melanoma Brain Metastasis Edwin Lok, Amy S. Chung, Szexian Lee, Tamar Melman, Kenneth D. Swanson and Eric T. Wong; Boston, MA Because immunoregulatory chemokines and cytokines may modulate the biology of melanoma brain metastasis, we measured 26 of them in the CSF from 22 patients using multiplexed ELISA. Clustergram revealed segregation of non-disease controls from 5 identifiable clusters of patient 94 ID: senthilk I Black Lining: [ON] I Time: 08:46 I Path: //xinchnasjn/01Journals/Wiley/3b2/ANA#/Vol00000/110244/APPFile/JW-ANA#110244 J_ID: ZAY Customer A_ID: SUPP11-6 Cadmus Art: 22579 Date: 31-August-11 T1804. Relationship between Brain MRI Imaging Parameters and Molecular Biomarkers as Prognostic Indicators in Glioblastoma Multiforme Xiao-Tang Kong, Senxi Du, Beverly D. Fu, Mark E. Linskey and Daniela Bota; Orange, CA and Irvine, CA Stage: Page: 95 lished Bevacizumab side effects include hypertension, delayed/impaired wound healing, gastrointestinal perforation and proteinuria. Recently a small number of case reports have reported six cases of optic neuropathy following Bevacizumab treatment for GBM. We report here a case of a 24 year old woman with Neurofibromatosis type I (NF-1) and right Thalamic GBM (WHO grade IV), who developed a severe, subacute optic neuropathy during treatment with Bevacizumab and Irinotecan for recurrent GBM following standard initial chemo radiotherapy with temozolamide. Following 4 cycles of salvage chemotherapy using Bevacizumab/Irinotecan, the patient developed diffuse blurring of vision, which progressed over 3-4 weeks-eventually resulting in total blindness. Six weeks following cessation of Bevacizumab the patient’s vision improved with return of light perception, and eventual return of baseline vision. Our completed poster will include a summary of our case, MRI images of the tumor, and results of ophthalmologic examination during and following Bevacizumab treatment. Study supported by: Residency program The purpose of this study is to explore the relationship between the potential MRI prognostic indicators and the molecular biomarkers in order to better evaluate the prognosis of the patients with GBM. Molecular biomarkers were determined using Immunohistochemistry. MIPAV software was used to quantify the volume of MRI parameters. Of the seventeen specimens that eventually included, 10 had high and 6 low levels of MGMT expression; 5 were negative and 11 positive for EGFR wt amplification; 12 negative and 5 positive for EGFRvIII expression; 14 had PTEN loss and 3 had intact PTEN. The vasogenic edema were more significant in the low MGMT expression group (P ¼ 0.04). The necrosis were larger in the group of non EGFR wt amplification (P ¼ 0.03) and the total volume of tumor involvement was significantly more in EGFRvIII variant expression group (P ¼ 0.0072). Our data suggest that the volume of vasogenic edema, necrosis and total tumor involvement are related to low MGMT level, lack of EGFR wt amplification, and increased EGFRvIII expression as prognostic indicators. Definitely, more cases will be added to the study to confirm the findings and to evalute the clinical prognosis. T1807. Anti-Ri-Associated Paraneoplastic Brainstem Cerebellar Syndrome with Medically-Intractable Nausea in a Patient with Large Cell Neuroendocrine Lung Carcinoma: A Case Report Amber N. Mitchell, Jessica Levesque and Earl Zimmerman; Albany, NY T1805. Secondary Intramedullary Spinal Cord NonHodgkin’s Lymphoma Eoin P. Flanagan, Brian P. O’Neill, Thomas M. Habermann and B. Mark Keegan; Rochester, MN Paraneoplastic neurologic syndromes are rarely the first manifestations of occult malignancies, which if left untreated, often lead to significant morbidity and mortality. The presence of onconeural antibodies supports the paraneoplastic diagnosis, but is not absolutely essential. Anti-Ri autoantibodies are commonly associated with breast and small cell lung cancers. There are cases of anti-Ri paraneoplastic cerebellar degeneration reported, but none describe associated severe nausea and emesis as the major presenting and enduring symptoms. Here, we report a case of a 75year-old female with medically-intractable nausea, vomiting, diplopia, and vertigo for three months. Physical exam revealed rotary nystagmus, ocular skew deviation, limb dysmetria, and gait ataxia. After two courses of intravenous immunoglobulin, there was minimal improvement. Serum was Anti-Ri antibody positive. Computed tomography identified a 2.5 cm by 2.2 cm lung mass, and histopathology revealed large cell neuroendocrine carcinoma with smaller portions of adenocarcinoma. Post-lobectomy, the patient clinically improved. This is the first report of paraneoplastic brainstem cerebellar syndrome involving anti-Ri positivity from neuroendocrine tumor of the lung with nausea and vertigo as the major features and with improvement after tumor resection. Intramedullary spinal cord metastases are rare and associated with poor long-term survival. We present the clinical characteristics and outcome of secondary intramedullary spinal cord non-Hodgkin’s lymphoma (NHL) in 7 patients seen at Mayo Clinic from 1996–2010. All patients had myelopathy and imaging evidence of intramedullary spinal cord involvement of pathologically confirmed systemic NHL (B-cell, 6; T-cell, 1). Spinal cord NHL was diagnosed by: CSF cytology, 4; PET hypermetabolism, 2; or MRI features alone, 1. In two, myelopathy was the initial presentation of systemic NHL and in the remainder the median time from NHL diagnosis to intramedullary involvement was 8 months (range, 1–58). Median age was 60 years (range, 41–81) and 4 were wheelchair-dependent at diagnosis. MRI spine lesions (Thoracic, 3; Cervical, 3; or both, 1) were typically gadolinium enhancing, expansile and associated with PET hypermetabolism. Two had leptomeningeal involvement and 4 had coexisting brain lesions. Six of the seven were treated: intravenous methotrexate, 3; radiation, 2; and R-CHOP, 1. Four improved (mild, 3; marked, 1) following treatment. The median survival was 11.5 months (range, 1–28). Secondary intramedullary spinal cord NHL appears to have longer survival than intramedullary metastases from most other cancers. T1808. Glioblastoma Multiforme: A Rare Presentation of Pineal Tumor with Leptomeningeal Seeding and Future Directions Noor Yono, Tulika Ranjan and Rabih Kashouty; Manhasset, NY, United States Minor Outlying Islands and New York, NY T1806. Case Report: Optic Neuropathy in a Patient with Glioblastoma Receiving Bevacizumab Robert A. Fishman, Lara Kunschner and Erik Happ; Pittsburgh, PA Glioblastoma Multiforme (GBM) is the most common primary malignancy of the Central Nervous System. Pineal GBM with leptomeningeal seeding is an exceedingly rare tumor. Only 18 cases have been reported in the literature. We present a case of pineal gland GBM with leptomeningeal disease treated with combination chemotherapy. A 55-yearold man presented with progressive headache, peduncular Bevacizumab is a humanized monoclonal antibody developed to target and subsequently block vascular endothelial growth factor received FDA approval for single agent treatment of recurrent Glioblastoma multiforme in 2009. Estab- 95 ID: senthilk I Black Lining: [ON] I Time: 08:46 I Path: //xinchnasjn/01Journals/Wiley/3b2/ANA#/Vol00000/110244/APPFile/JW-ANA#110244 J_ID: ZAY Customer A_ID: SUPP11-6 Cadmus Art: 22579 Date: 31-August-11 hallucinations and perinaud syndrome. Brain MRI showed a heterogeneously enhancing pineal mass measuring 2.1 cm with hydrocephalus and infiltration into the midbrain and thalamus. The pathology was consistent with GBM with Ki-67 labeling index of 30–50%. Brain and total spine MRI showed diffuse linear leptomeningeal disease. Chemotherapy with Temozolomide was started on day 1st. Two high-volume lumbar punctures with intrathecal Methotrexate were performed. Within 24 hours following the first Methotrexate treatment, the patient showed significant improvement. Initial lumbar puncture showed markedly elevated protein count of 2856. He was further treated with Avastin every 2 weeks and monthly Temozolomide. Recent CSF protein has improved to 315 and the pineal mass size has decreased to 0.9mm after four months of starting treatment. Stage: Page: 96 mographic variables amongst groups. An ANOVA assessed 11 C-PiBregional differences. Results: Symptomatic AD were older (p < 0.001), had lower CSF Ab42 (p < 0.001), and had higher CSF tau levels (p < 0.001). Regardless of degree of impairment, HIVþ participants had no increased 11C-PiB. Mean and regional binding potentials were elevated for symptomatic AD participants (p <0.0001). Conclusions: HIVþ participants, even with HAND, do not exhibit increased 11C-PiB while symptomatic AD individuals have increased fibrillar Ab42 deposition. Observed dissimilarities between HAND and AD may reflect differences in Ab42 metabolism. 11C-PiB may provide a diagnostic biomarker for distinguishing symptomatic AD from HAND. Study supported by: ADRC Pilot Grant (3255 P50AG05681), NIMH (K23MH081786), NINR (R01NR 012657), Dana Foundation (DF10052), ARRS Scholar Award, NIH P01-AG026276, and NIH PO1-AG03991 T1809. Benign-Histology Meningioma with Extracranial Metastasis Umer Akbar, Bhavpreet Dham and Melissa Carran; Camden, NJ T1902. Modulation of HIV-Tat Neurotoxicity by Potassium Channel Blockers Srikant Rangaraju* and Jeffrey A. Rumbaugh; Atlanta, GA Objective: To recognize extracranial dissemination from a meningioma Background: Meningiomas are regarded as benign tumors, as malignant histology is uncommon and extracranial metastasis is an extremely rare occurrence. Design: We report a case of a histologically-benign meningioma with metastasis to the lungs. Case: A 36 year-old male with symptomatic epilepsy presented with a breakthrough seizure. Patient had a meningioma resection in 1998. Few months later, imaging revealed recurrent tumor which was treated with 48 Gy of radiation. Routine chest x-ray followed by computed tomography scan confirmed multiple scattered round nodules, averaging between 1 to 1.5 cm. Fine-needle aspiration showed clusters of meningothelial cells consistent with metastasis from the recurrent intracranial tumor. Discussion: Majority of meningiomas are benign (grade I), while few are atypical (grade II) and malignant (grade III) histology is rare. Aggressive behavior and metastatic potential is mainly seen in atypical and malignant histologic subtypes. With a metastasis rate of 0.1%, meningiomas are seldom seen extracranially. Very rarely, the metastasizing meningioma is of benign histology. Certain tumor tendencies for aggressive behavior have been observed and are discussed. HIV-Tat is released by HIV-infected cells and activates NMDA receptors on neurons leading to calcium influx. As intracellular calcium concentrations rise, the calcium gradient decreases and limits further calcium entry.Voltage-sensitive(Kv) and calcium-activated(SK) potassium channels open in response to depolarization and calcium flux thereby restoring the ionic gradient needed for sustained calcium entry. This dysregulation of calcium homeostasis triggers secondary neurotoxic cascades resulting in cell death. Kv(Kv1.2, 1.3, 2.1) and SK channels are expressed in large numbers by cortical neurons. We hypothesized that blockade of potassium channels may reduce Tat-neurotoxicity by preventing restoration of calcium gradients. Fetal rat cortical neurons were exposed to Tat (400 nM) and potassium channel blockers: Tetraethylammonium (TEA, non-specific Kv blocker), 4-Aminopyridine (4-AP, Kv1 and Kv2 blocker) and Apamin (SK blocker). Neurotoxicity was determined by the MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay after 12 hours. Tat neurotoxicity (p ¼ 0.0005 compared to untreated controls) was abolished by 4AP at 0.5 mM (p ¼ 0.0005) and 1mM (p ¼ 0.0003) and reduced by TEA (100 microM, p ¼ 0.03) and Apamin (50nM, p ¼ 0.01). Our results suggest that potassium channels play a role in Tat-neurotoxicity. Kv and SK potassium channels may represent novel therapeutic targets in HIVneurodegeneration. Study supported by: Emory University Internal funding. Neurovirology T1901. HIV Associated Neurocognitive Disorder (HAND) Is Not Associated with Increased Fibrillar Amyloid Deposits Using 11C-PiB in Middle-Aged HIVþ Participants Beau Ances, Jewell Thomas, Tammie Benzinger, Jon Christensen, Mengesha Teshome, Patricia Aldea, Anne Fagan, David Holtzman, John Morris and David Clifford; Saint Louis, MO T1903. Varicella Zoster Encephalitis – Relationship between Viral Load, Time and Outcome Benedict D. Michael, Mike Griffiths, Anna Stewart, Charlotte Buckley, Mark Hopkins, Ian J. Hart, Alistair Miller, Sareen Galbraith and Tom Solomon; Liverpool, Merseyside, United Kingdom Objectives: Diagnostic challenges exist for differentiating HIV associated dementia (HAD) from Alzheimer disease (AD). Similar abnormalities in brain amyloid-b42 (Ab42) metabolism occur for both. We evaluated if 11C-Pittsburgh compound B (11C-PiB) discriminates AD from HAND. Methods: In this case-control study 16 HIVþ (11 cognitively normal, 5 HAND) and 19 HIV- (8 cognitively normal, 11 symptomatic AD) participants were assessed using 11 C-PiB, clinical exam, and cerebrospinal fluid (CSF) testing. v2 and t-tests investigated differences in clinical and de- Background: Varicella zoster virus (VZV) is a common cause of encephalitis with a wide spectrum of morbidity and mortality. The pathophysiology remains poorly understood and few prognostic markers are available. A few studies have attempted to use the viral load of the cerebrospinal fluid (CSF) to investigate this, with contradictory results. These have not been conducted in context of time. Objectives: To determine the CSF viral load in VZV encephalitis in relation to time and outcome. 96 ID: senthilk I Black Lining: [ON] I Time: 08:46 I Path: //xinchnasjn/01Journals/Wiley/3b2/ANA#/Vol00000/110244/APPFile/JW-ANA#110244 J_ID: ZAY Customer A_ID: SUPP11-6 Cadmus Art: 22579 Date: 31-August-11 Stage: Page: 97 Study Design: The regional virology database was screened to identify VZV positive CSF over 5years. Viral load was determined by quantitative-polymerase chain reaction (qPCR). Results: 608 patients were screened, 36 had VZV qPCR performed, 12 were positive and had encephalitis. There was a strong negative correlation between time to LP and viral load (tau b ¼ À0.59, p ¼ 0.036). There was no significant difference in viral load between those with good and poor outcome. Conclusions: CSF viral load appears to more closely relate to time to LP than outcome. Timing of LP should be included in future studies to investigate the role of the viral load in the pathophysiology and prognosis of encephalitis. Study supported by: Study funded by the National Institute for Health Research (NIHR-UK) Biomedical Research Centre. for lipopolysaccharide (LPS), within post-mortem brain tissue from HIV positive subjects (n ¼ 15) and HIV negative subjects (n ¼ 10) via quantitative real time PCR (qRTPCR) and immunohistochemistry (IHC). We also assessed cognitive brain functions in 7 domains and their correlation with TLR4 mRNA expression. We found TLR4 expression was significantly higher in HIV positive subjects than HIV negative controls (p<0.05). IHC demonstrated that TLR4 expression was upregulated in HAND brains, and TLR4positive cells in the cortex were significantly smaller in HIV positive subjects (p<0.05). Higher TLR4 mRNA expression was associated with impaired motor function among HIV positive subjects (p<0.05). These findings suggest that TLR4 signaling may play a role in HIV neuropathogenesis and suggest new strategies for therapeutic intervention. Study supported by: NIH R21 Grant T1904. Acute Varicella Zoster Virus Encephalitis in Adults – Relationship between Viral Load, Time, Clinical Features and Outcome Benedict D. Michael, Michael Griffiths, Anna Stewart, Charlotte Buckley, Mark Hopkins, Ian J. Hart, Alistair Miller, Sareen E. Galbraith and Tom Solomon; Liverpool, United Kingdom T1906. Revisiting Reactivation of Calcified Neurocysticercosis: Report of Three Recent Cases Sanjna M. John** and Maria del Pilar Cortes Nino; Kingston, ON, Canada and Montreal, QC, Canada Background: Neurocysticercosis (NCC) is a CNS infection with significant associated morbidity in the form of acquired epilepsy. The final stage of disease is cyst calcification, originally thought to represent disease resolution and cessation of active symptoms. Recent studies have suggested that calcified NCC is a chronic condition with intermittent symptom exacerbation and imaging findings during symptom recurrence. Methods: We did a retrospective chart review and imaging analysis of patients seen with reactivation of calcified NCC at the Montreal Neurological Institute between 2007 and 2010. Findings: 2/3 of patients presented with neurological symptoms other than seizures, and 2/3 of patients presented with multiple calcified cysts. All patients had edema and hypodensity on imaging around at least one calcified lesion during symptom exacerbation. Interpretation: Our findings were generally consistent with prior literature, however, seizure was not the predominant clinical presentation as has been reported. Perilesional edema was seen on imaging in all patients and could be used as a reliable sign of symptom recurrence. Background: Varicella zoster virus (VZV) is a common cause of viral encephalitis with a wide spectrum of outcomes. The pathophysiology remains poorly understood and few prognostic markers exist. A few studies have used viral load, determined by quantitative polymerase chain reaction (qPCR) of cerebrospinal fluid (CSF), to investigate this, with contradictory results. However, these have not assessed this in the context of time. Objectives: To determine the viral load in VZV encephalitis in relation to time and outcome. Study Design: The Liverpool Specialist Virology laboratory was screened to identify patients with VZV-positive CSF over 5years. Viral load was determined. Poor outcome was defined as moderate disability-death (Glasgow outcome score [GOS]2-5) and high viral load as (>5Â104GEq/ml). Results: Of 608 screened; 36 had VZV-PCR; 12 were positive. There was a strong negative correlation between time from symptoms to LP and viral load (tau b ¼ À0.59, p ¼ 0.036). There was no difference in viral load between those with good and poor outcome. Conclusions: In VZV encephalitis, viral load appears to better relate to time. Timing should be included in future studies aiming to relate viral load to outcome. Study supported by: This study recieved support from the National Institute for Health Research Biomedical Research Centre on Infectious Diseases. The authors have no other conflicts of interest to declare T1907. Clinical Features at Admission in Patients with Meningeal Cryptococcosis in a Third Level Hospital in Mexico Jesus F. Mendoza, Gilberto Vazquez, Jeronimo Rodriguez and Ildefonso Rodriguez; San Luis Potosı´, San Luis Potosı´, Mexico Introduction: Meningeal cryptococcosis (MC) is caused by Cryptococcus species. In Mexico, treatment is limited because 5-fluocytocine is unavailable. Objectives: To determine the presenting clinical features of patients diagnosed with meningeal cryptococcosis in a third level hospital in Mexico. Methods: Retrospective review of medical records of patients with diagnosis of MC. Results: We found 4 HIV possitive patients. Symptom onset to admision was longer than two weeks in 5 patients. Clinical characteristics: headache 87.5%, cognitive impairment, nausea/vomiting and meningismus 62.5% each, fever and cranial nerve affection 37.5% each, wakefullnes alterations in 25%. CSF findings: Positive india ink 75%, low glucose 75%, linfocytosis 62.5%, high protein level 62.5%, positive culture 50%. T1905. TLR4 Expression Is Upregulated in HIVAssociated Neurocognitive Disorder (HAND) Amir H. Sabouri, Gursharan Chana, Amol Shah, Critian L. Achim, Ronald J. Ellis, Ian P. Everall and HNRC Group; La Jolla, CA; Melbourne, Australia and San Diego, CA Despite the introduction of highly active antiretroviral therapy (HAART), HIV associated neurocognitive disorders (HAND) remain a significant cause of morbidity. In a previous investigation, we have demonstrated that the gene expression of a number of proteins related to the innate immune system toll-like receptor (TLR) signaling pathway correlate strongly with HIV associated neurodegeneration, most significantly TLR3 and À4. In this study, we examined gene expression of TLR4, the major signaling receptor 97 ID: senthilk I Black Lining: [ON] I Time: 08:46 I Path: //xinchnasjn/01Journals/Wiley/3b2/ANA#/Vol00000/110244/APPFile/JW-ANA#110244 J_ID: ZAY Customer A_ID: SUPP11-6 Cadmus Art: 22579 Date: 31-August-11 All patients recieved treatment with Amphotericine B and fluconazole.Only half completed the induction phase as recommended. Discussion: Clinical presentation, CSF findings of patients presenting with MC in our hospital do not differ from what has been reported in the medical literature. This findings confirms the need to mantain a high suspicion index of CM in immunocompromised or immunocompetent patients with suggestive clinical picture. Special attention must be paid to appropiate treatment schemes in the future to achieve better outcomes in this population. Study supported by: The authors declare no conflict of interest. None of the authors recieved any financial benefits from the study. Stage: Page: 98 considered in the diagnosis of tuberculous meningitis (TBM). In compiling this review, we searched electronic data bases in PubMed, Science Direct, Biomedical Central and Google Scholar. Firstly, we evaluate the more traditional diagnostic methods which have been commonly applied in the diagnostics of tuberculosis (TB). The role of direct cerebrospinal fluid (CSF) examination for acid-alcohol fast bacilli, CSF culture for Mycobacterium tuberculosis, and detection of mycobacterial nucleic acid in the CSF is evaluated. We also consider the role of brain imaging and chest X-ray. Secondly, the review evaluates the current evidence on the role of some newly prospective diagnostic techniques and the coverage is given to the role of CSF adenosine deaminase activity, Gen Probe amplified Mycobacterium tuberculosis direct test, microscopic observation drug susceptibility (MODS) culture technique, ex vivo Mycobacterium tuberculosis-specific enzyme-linked immunospot assay (ELISpot assay) and enzyme-linked immunosorbent assay (ELISA) in the diagnosis of TBM. Study supported by: This was a self-financed study. T1908. The Diagnosis of Tuberculous Meningitis: A Current Review of the Clinical and Laboratory Methods Brian Chisulo, Shan H. Jiang and Yue S. Pan; Guangzhou, GZ, China This review traces our understanding of the clinical manifestations and the laboratory methods commonly 98 ID: senthilk I Black Lining: [ON] I Time: 08:46 I Path: //xinchnasjn/01Journals/Wiley/3b2/ANA#/Vol00000/110244/APPFile/JW-ANA#110244 J_ID: ZAY Customer A_ID: SUPP11-7 Cadmus Art: 22580 Date: 26-August-11 136th Annual Meeting Sunday, September 25, 2011 Works in Progress Poster Session Abstracts Stage: Page: 99 predictive value of 78% at a cutoff point of 0.5 lg/l. Preliminary results suggest a significant correlation (rs¼0.8) between NR2 peptide levels and lesion size. Conclusion: The NR2 peptide is a sensitive and specific biomarker for IS. Increased NR2 peptide levels can identify patients with acute IS and correlate with findings on neuroimaging studies. Study supported by: Department of Defense Grant (DM090557: VALIDATION OF AMPA RECEPTOR PEPTIDE ASSAY TO IMPROVE DIAGNOSTIC CERTAINTY OF MILD TRAUMATIC BRAIN INJURY), USAMRAA WIP posters will be displayed in Elizabeth A-E of the Manchester Grand Hyatt from 10:00 am – 7:00 pm, with authors present from 6:00 pm – 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. S143. Initial Transcranial Doppler Velocity Predicts Development of Symptomatic Vasospasm in Aneurysmal Subarachnoid Hemorrhage Shyam Prabhakaran, Konark Malhotra, Rajeev Garg, Sayona John, Richard Temes and Viven Lee; Chicago, IL Cerebrovascular Disease We reviewed 350 consecutive SAH patients with aneurysmal source, who had TCD within 3 days of admission and survived at least 7 days. We recorded initial flow velocity (IFV) of the MCA by TCD. Using survival analysis and Cox proportional hazard models, we evaluated initial TCD velocity at baseline as a predictor of symptomatic MCA vasospasm and calculated hazard ratios (HR). Among 195 patients who met inclusion criteria, 43(22%) developed symptomatic MCA vasospasm. Median values from admission for: TCD monitoring¼1 day, vasospasm ¼ 6 days and initial MCAMFV ¼ 68cm/sec. In multivariable analysis, initial MCAMFV >75 cm/s was strongly predictive of symptomatic MCA vasospasm. The 3, 7, 10, and 14-day risks of symptomatic MCA vasospasm were 0.9%, 9.4%, 14.8%, and 14.8% for those with initial MCA-MFV <75 cm/s compared to 5.1%, 21.8%, 31.2%, and 33.0% for those with initial MCA-MFV >75 cm/s (log-rank test: P ¼ 0.001). Elevated initial TCD velocity may provide a useful marker for those at high-risk for symptomatic vasospasm. The risk of vasospasm in those with elevated MCA velocity > 75 cm/s was significantly higher, occurring earlier and for a longer period, than in those without. S141. Polymorphism of Ninjurin2 in Korean Atherothrombotic Stroke Patients Dae-il Chang, Sung Hyuk Heo and Hye Ok Kim; Seoul, Korea Recently, in a genome-wide association study, the singlenucleotide polymorphisms (SNPs) rs12425791 and rs11833579 of ninjurin2 (NINJ2) were reported to be associated with atherothrombotic stroke. However, this finding has not been validated in Korean population yet. We therefore investigated an association between atherothrombotic stroke and SNPs of NINJ2 in 200 patients and 295 control subjects. Allelic discrimination assay was used. The A allele of rs11833579 increased stroke risk significantly (p ¼ 0.003, 1.50 (95% CI, 1.15 to 1.96), respectively). The A allele frequencies were higher in stroke patients with hypertension than in control subjects with hypertension (p ¼ 0.042 and p ¼ 0.001, respectively) in both SNPs of NINJ2 (rs12425791 and rs11833579). Also, the A allele was more frequent in stroke patients with hyperlipidemia than in control subjects with hyperlipidemia (p ¼ 0.010 and p ¼ 0.005, respectively) in both. In addition, the A allele was more frequent in stroke patients with diabetes than in control subjects with diabetes (p ¼ 0.008, respectively) in SNPs rs11833579. In conclusion, SNPs of NINJ2 (rs12425791 and rs11833579) confer a substantial genetic risk factor for atherothrombotic stroke in our population. S144. Relative Change in Transcranial Doppler Velocities Is Inferior to Absolute Thresholds in Prediction of Vasospasm after Subarachnoid Hemorrhage Konark Malhotra, James Connors, Viven Lee and Shyam Prabhakaran; Chicago, IL S142. NMDA Receptor Biomarker for Acute Stroke Kerstin Bettermann and Svetlana Dambinova; Hershey, PA and Kennesaw, GA We reviewed 350 consecutive SAH patients with aneurysmal source, who underwent serial TCD monitoring and survived at least 7 days. We recorded initial flow velocity(IFV) upto 14 days, maximal flow velocity of middle cerebral artery (MCA), relative flow changes (MFV/IFV) >3, absolute maximal Lindegaard ratio (LR) >6, mean MCA maximum flow velocity (MFV) >175 cm/s, and MFV >200 cm/s. Among 211 patients selected, 48 (23%) developed symptomatic MCA vasospasm. Area under the ROC curve (AUC) was: MCA-MFV >175 ¼ 0.80, MFV >200 ¼ 0.73, LR >6 ¼ 0.71, and MFV/IFV >3 ¼ 0.60. The best characteristics were observed for MFV >175 cm/s or maximal LR >6 as: AUC ¼ 0.81; while sensitivity, specificity and negative predictive value were: 81%, 81% and 94%, respectively; the positive likelihood ratio was 4.1. MFV/IFV >3 performed the worst. MFV >175 cm/s and/or Lindegaard ratio >6 accurately predict symptomatic MCA vasospasm. Presence of either/both abnormalities in first 14 days after SAH increases the likelihood of symptomatic MCA vasospasm by Background: The NR2 peptide, a breakdown product of brain specific NMDA receptors, is released into the bloodstream during cerebral ischemia and can be used as a marker for acute ischemic stroke (IS). Performance characteristics and critical values of the NR2 peptide in acute IS patients presenting within 24h of symptom onset are analyzed. Methods: NR2 peptide levels are correlated with neurological status and results of advanced neuroimaging studies. Plasma NR2 peptide concentrations are determined by plotting their absorbance values on a calibration curve constructed from the absorbance units of each calibrator and their known concentrations. Results: Controls and individuals with vascular risk factors have NR2 peptide concentrations below 0.25 and 0.3 lg/l, respectively. Acute IS patients have significantly higher NR2 peptide levels (>0.5 lg/l) compared to all control groups (p<0.0001). Test sensitivity for IS is 98% with a 99 ID: kannanb I Black Lining: [ON] I Time: 17:25 I Path: N:/3b2/ANA#/Vol00000/110245/APPFile/JW-ANA#110245 J_ID: ZAY Customer A_ID: SUPP11-7 Cadmus Art: 22580 Date: 26-August-11 >4 fold. Other thresholds including relative change from baseline appear inferior to these absolute thresholds. Stage: Page: 100 ing-off in 32.8%. The development of motor complications was predicted by younger age of onset, higher Unified Parkinson’s Disease Rating Scale Part II score, region (North America), and gender in addition to levodopa dose. There was no difference in the LC and LCE groups. Conclusion: The development of levodopa-induced motor complications is dose-related (higher with increasing doses), supporting using the lowest levodopa dose that provides satisfactory clinical control. Study supported by: This analysis was supported by an unrestricted grant from Novartis Pharma AG and Orion Pharma. C. Warren Olanow has served as a consultant for Teva Neuroscience, Lundbeck, Boehringer Ingleheim, Novartis Pharmaceuticals Orion Pharma, Abbot,Solvay, Merck Serono, Ipsen, and the welding defense industry, and has stock options in Ceregene and Clintrex. Karl Kieburtz as received research grants from Amarin, Boehringer-Ingelheim, Medivation and Neurosearch, and received consultancies fees from Abbott, Antipodean, Boehringer-Ingelheim, Ceregene, Eisai, FoldRx, Lilly, Merz, Novartis Pharmaceuticals, Pfizer, Prestwick, Teva, Schering-Plough, Schwarz, UCB, Vernalis and Welding. Olivier Rascol has served as a consultant for Orion Pharma, Novartis Pharmaceuticals, Teva-Lundbeck, and served on scientific advisory board for Bial, Boerhinger Ingelheim Eisai, GSK, Impax, Lundbeck, Merck Serono, Merz Pharmaceutical, Oxford Biomedica, Schering-Plough, Servier, Abbott, Teva, UCB, Xenoport. Werner Poewe has received consultancy and lecture fees from Astra Zeneca, Teva, Novartis Pharmaceuticals, GSK, Boehringer-Ingelheim, UCB, Orion Pharma, Merck Serono and Solvay-Abbott in relation to clinical drug development programmes for PD. Anthony Schapira has served on advisory boards and as a speaker for Orion Pharma and Novartis Pharmaceuticals. He has served as a consultant and speaker for Boehringer Ingelheim, GSK, Teva-Lundbeck and Merck Serono. Helena Nissinen is a full-time employee of Orion Pharma Mika Leinonen is a former employee of Orion Pharma and a full-time employee of 4Pharma AB, which received funding from Orion Pharma to carry out the statistical analysis for the study. Fabrizio Stocchi has received research grants from Novartis Pharmaceuticals, GSK and Vernalis, and has served as a consultant for Novartis Pharmaceuticals, Lundbeck, TEVA, GSK, Vernalis, Serono, Schering Plough and IPX. Movement Disorder S238. Dopamine Transporter Imaging Predicts Long Term Outcomes in Parkinson’s Disease Bernard M. Ravina, Kenneth Marek, Shirley Eberly, David Oakes and Ira Shoulson; Rochester and New Haven Objective: Our objective is to measure the prognostic value of dopamine transporter (DAT) imaging for motor and non-motor outcomes in PD. Methods: We prospectively evaluated a PD cohort after enrollment in a de novo PD clinical trial with motor, cognitive, and behavioral measures. DAT imaging with [123I][b]CIT (b-CIT) and SPECT was performed at baseline and after 22 months. Results: Four hundred and ninety-one (91%) of 537 subjects had evidence of dopamine deficiency consistent with PD. The cohort was followed for 5.5 (0.8) years and had a diagnosis of PD for 6.3 (1.2) years. Lower striatal binding of b-CIT at baseline was independently associated with significantly higher risk for important clinical milestones and measures of PD severity, including motor related disability, falling and postural instability, cognitive impairment, psychosis, and clinically important depressive symptoms. Subjects in the bottom quartile for DAT imaging compared to the top quartile had an odds ratio (95% CI) of 3.5 (1.7, 6.9) for cognitive impairment and 12.8 (2.6, 61.8) for psychosis. Conclusions: Near the time of PD diagnosis, DAT imaging with b-CIT and SPECT is an independent predictor of clinically important motor and non-motor long term outcomes. Study supported by: This study was sponsored by the National Institute of Neurological Disorders and Stroke (NINDS) (5U01NS050095), Department of Defense (DOD) Neurotoxin Exposure Treatment Parkinson’s Research Program (W23RRYX7022N606), Michael J Fox Foundation (MJFF), Parkinson’s Disease Foundation (PDF), Cephalon Inc, and Lundbeck Inc. S239. Time to First Levodopa-Induced Motor Complication: Results from the STRIDE-PD Study C. Warren Olanow, Karl Kieburtz, Olivier Rascol, Werner Poewe, Anthony Schapira, Helena Nissinen, Mika Leinonen and Fabrizio Stocchi; New York, NY; Rochester, NY; Toulouse, France; Innsbruck, Austria; London, United Kingdom; Espoo, Finland; Kista, Sweden and Rome, Italy S240. Acute Effects of Preladenant, a Selective Adenosine A2A Antagonist, on Dyskinesia and Parkinsonism in Levodopa-Treated Subjects Penelope Hogarth, Matthew D. Troyer, Byung S. Park, Igor D. Grachev, Tatanisha Laguerre, Fengjuan Xuan, Amol Tendolkar and John G Nutt; Portland, OR and Whitehouse Station, NJ Introduction: The STRIDE-PD study compared initiation of levodopa/carbidopa (LC) to levodopa/carbidopa/entacapone (LCE) in PD patients. Objective: Determine the effect of levodopa dose on development of motor complications. Methods: A total of 745 patients participated in a 134– 208-week, double-blind trial, with 3-monthly assessments of dyskinesia and wearing-off. Based on nominal levodopa dose per day, patients were divided into four groups: <400 mg (19.7%), 400 mg (46.3%), >400–600 mg (26.6%), and >600 mg (7.4%). Dose response was analyzed using log-rank test. Predictive factors for first motor complication were screened using multivariate analysis. Results: A dose response was observed between levodopa dose and first motor complication (p<0.001); with a frequency of 31.3, 57.1, 65.7 and 81.8% in Groups 1–4, respectively. Dyskinesia developed first in 18.5% and wear- Background/Objective: Selective antagonism of striatal adenosine A2A receptors is proposed to augment the effects of levodopa in Parkinson disease (PD) and may do so without worsening dyskinesia. We investigated the acute effects of preladenant on dyskinesia, parkinsonism and safety in patients with advanced PD. Methods: Design: Single-dose, randomized, double-blind, placebocontrolled, 3-period crossover. Population: PD fluctuators with dyskinesia(n ¼ 12). Intervention: 10mg and 100mg of preladenant and placebo plus two-hour levodopa infusion. 100 ID: kannanb I Black Lining: [ON] I Time: 17:25 I Path: N:/3b2/ANA#/Vol00000/110245/APPFile/JW-ANA#110245 J_ID: ZAY Customer A_ID: SUPP11-7 Cadmus Art: 22580 Date: 26-August-11 Outcome measures: Dyskinesia score(primary); fingertapping and walking speed, tremor score and blood pressure(secondary). Analysis: Area Under Curve statistical paradigm Results: Single doses of 100mg of preladenant increased levodopa-induced dyskinesia compared to placebo(p ¼ 0.003). Single doses of 10mg were not statistically significantly different from placebo(p ¼ 1.00). We found a trend suggesting a dose-response for dyskinesia, and observed dyskinesia in 4 of 12 subjects prior to levodopa infusion. Neither dose significantly improved any measure of parkinsonism. The drug was generally well-tolerated. Stage: Page: 101 Conclusions: This proof of concept study does not support the hypothesis that A2A antagonists augment the effects of levodopa without increasing dyskinesia. Our results suggest that a supratherapeutic dose of preladenant may be pro-dyskinetic, perhaps independently of levodopa, in PD patients with pre-existing dyskinesias. Study supported by: Merck & Co, Inc Presenting author Hogarth and co-authors Nutt & Park received salary support from payments made by the sponsor to OHSU for contracted research design and execution services. Co-authors Troyer, Laguerre, Grachev, Xuan, and Tendolkar are/were employees of the sponsor. 101 ID: kannanb I Black Lining: [ON] I Time: 17:25 I Path: N:/3b2/ANA#/Vol00000/110245/APPFile/JW-ANA#110245 J_ID: ZAY Customer A_ID: SUPP11-7 Cadmus Art: 22580 Date: 26-August-11 136th Annual Meeting Monday, September 26, 2011 Works in Progress Poster Session Stage: Page: 102 phenytoin therapy. Purified DNA were used for HLAB*1502 typing by Sequence Specific Oligopeptide method using Polymerase Cahin Reaction. Results: Out of 136 patients on CBZ, HLA-B*1502 were detected in 22 and 19 developed SJS/TEN. In 50 patients on Phenytoin, HLA-B*1502 were detected in six patients and four had SJS. The mean duration from exposure to SJS was 14 days. Conclusion: There is a high prevalence of HLA-B*1502 in South Indians on Carbamazepine and Phenytoin (18.66%). There was a strong association of HLA-B*1502 allele and the developmment of SJS in South Indians, with the Positive Predictive Value for Carbamazepine and Phenytoin being 86% and 66.67% respectively. WIP posters will be displayed in Elizabeth A-E of the Manchester Grand Hyatt from 10:00 am – 7:00 pm, with authors present from 6:00 pm – 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. M726. Filamin A Regulates Neural Progenitor Proliferation and Brain Size through wee1-Dependent cdk1 Phosphorylation Gewei Lian and Volney Sheen; Boston, MA Behavioral Neurology M622. New Approaches to Unraveling the Multi-Scale Neuroanatomical Changes in Williams Syndrome Ann Lam and Elan L. Ohayon; La Jolla Mutations in the actin binding filamin A (FlnA) gene cause the human disorder periventricular heterotopia (PH). FlnAdependent regulation of cytoskeletal dynamics is thought to direct neural progenitor migration and proliferation. Here we show that late embryonic FlnA null mice exhibit a reduction in brain size, impairments in neural progenitor proliferation, and decline in neural progenitor numbers over time. The drop in the progenitor population is not attributable to changes in cell fate specification through altered asymmetric versus symmetric cell divisions, but to prolonged cell cycle duration. Suppression of FlnA leads to impaired degradation of cyclin b1-related proteins, thereby delaying the onset and progression through mitosis. We find that the cdk1 kinase wee1 binds FlnA, demonstrates increased expressions levels after loss of FlnA function, and is associated with increased phosphorylation of cdk1. Phosphorylation of cdk1 inhibits activation of anaphase promoting complex degradation system, which is responsible for cyclin b1 degradation and progression through mitosis. Collectively, our results demonstrate a molecular mechanism whereby FlnA impairs G2 to M phase entry, leading to cell cycle prolongation, impaired neural progenitor proliferation, and reduced brain size. Study supported by: This work was supported in part by the National Institutes of Health NS063997-01 to VLS. This work was also supported in part by the Empire State Stem Cell Fund through the New York State Department of Health Contract #C024324 to VLS. The opinions expressed here are solely those of the author and do not necessarily reflect those of the Empire State Stem Cell Board, the New York State Department of Health, or the State of New York. VLS is a Doris Duke Clinical Scientist Developmental Award Recipient. In this study we explore novel multi-scale approaches to investigate the role of neuroanatomy in cognitive phenotypes by imaging the distribution of metalloproteins across scales in Williams Syndrome tissue. Synchrotron-based rapid scanning imaging was used at whole hemisphere levels and resolutions of up to 10 microns to co-localize elements in postmortem samples of Williams Syndrome and typicaldeveloping individuals in prefrontal, temporal and occipital cortex. Comparisons between- and within-subjects revealed differences between brain areas in elemental distributions. For example, initial scans showed the expected high levels of iron in nuclei such as the substantia nigra and prominent zinc florescence along white matter tracts. To increase the resolution by a factor of 20, microprobe imaging was then used attaining resolutions as high as 0.5 microns. This microprobe analysis of 50–100 micron thick cortical sections showed the co-localization of iron, zinc and calcium in and around cell-like structures. The combination of these two synchrotron-based techniques thus enables the study of biologically relevant elements in postmortem brain tissue across large areas, while allowing for the co-registering of elements at high resolutions at the cellular level in regions of interest. Study supported by: NIH Epilepsy M725. HLA-B*1502 Genotyping in Carbamazepine and Phenytoin Induced Stevens-Johnson Syndrome Sivakumar M. Rajappa and Srinivasan A. Venkatesan; Chennai, Tamil Nadu, India Objective: To study the association of HLA-B* 1502 allele in epileptic patients with carbamazepine and phenytoininduced Stevens Johnson Syndrome (SJS) in South Indian patients. Background: SJS and Toxic Epidermal Necrolysis (TEN) are severe cutaneous adverse drug reactions caused by carbamazepine (CBZ) and phenytoin. A strong association has been reported between human leucocyte antogen HLAB*1502 and carbamazepine-induced SJS in Han Chinese patients. Design/Methods: Single center, prospective cross sectional study. After an informed consent, 7 ml of EDTA blood were collected from 100 patients on CBZ and 50 on M727. A Moderate-Throughput Screen for Antiepileptogenic Compounds Yevgeny Berdichevsky, Yero Saponjian, Michelle Mail and Kevin J. Staley; Boston, MA Epilepsy is a frequent complication of traumatic, infectious and ischemic brain injury. The time interval between injury and epilepsy provides a tremendous opportunity for diseasemodifying therapies. Development of these therapies is limited by inadequate knowledge of the pathophysiology of epileptogenesis, the long time intervals required to observe changes in experimental epileptogenesis, and difficulties quantifying epileptogenesis. 102 ID: kannanb I Black Lining: [ON] I Time: 17:25 I Path: N:/3b2/ANA#/Vol00000/110245/APPFile/JW-ANA#110245 J_ID: ZAY Customer A_ID: SUPP11-7 Cadmus Art: 22580 Date: 26-August-11 To address these difficulties we have developed a moderate-throughput drug screen for antiepileptogenic agents comprised of arrays of organotypic hippocampal brain slices that develop robust spontaneous electrographic seizure activity within two weeks in vitro. Seizure activity is quantified either electrographically or metabolically as cumulative lactate production over two weeks in vitro. Neuroprotection is quantified as cumulative lactate dehydrogenase release over two weeks in vitro. Using these techniques we have screened 50 compounds from the NINDS Custom Compounds Collection in less than 4 months. Most anticonvulsants demonstrated neither antiepileptogenic nor significant chronic anticonvulsant effects, although acute anticonvulsant effects were readily observable. With other compounds we have resolved chronic anticonvulsant or antiepileptogenic activities (which are indistinguishable in the first-level screen) evidenced by decreased lactate with no increase in LDH, as well as neuroprotective activity, evidence by reduction in LDH. Study supported by: NIH (NINDS) Stage: Page: 103 seizures. It was common to observe spreading depressionlike events (SD) and irreversible synaptic failure in the CA1 region following the seizure activity originated in CA3 (8/ 12). SD also occasionally occurred in the CA3 area (3/12) following a SD event in the CA1 region. Hypoglycemic seizures required glutamatergic activity and NMDA receptor blockade prevented the hypoglycemia-induced seizures and SDs. Conclusions: Hypoglycemia-induced seizures in the hippocampus start in the CA3 region and cause SD and synaptic failure in the CA1 region. Activation of NMDA receptors is the key factor for the initiation of seizures and development of brain failure during severe hypoglycemia. Study supported by: JDRF M730. Alzheimer Disease in Lafora Epilepsy Jesus Machado-Salas, Maria Rosa Avila-Costa, Patricia Guevara, Jorge Guevara, Reyna M. Duron, Dongsheng Bai, Miyabi Tanaka and Antonio V. Delgado-Escueta; Los Angeles, CA and Mexico, Mexico Here we describe temporal progression of tau and amyloid pathology and subtypes of Lafora bodies (LB) in a Laforindeficient (epm2aÀ/À) mice model. Wild type and epm2aÀ/À mice were sacrificed at different ages. Histological and immuonocytochemical techniques were used. We found in epm2aÀ/À mice that neurofibrilary tangles appear at 11 days-old while senile plaques are abundant at 6 months. Type I LB are abundant inside neurons, type II LB are confined to neuron somata. Type I LB appear at 1 month while type II LB with an external rim staining for Neurofilament L, appear at 3 to 5 months. Both types of LB increase in size and number with age but show regional differences. Diencephalon has meager or no LB, cell death and neurofibrillary tangles. All three features are abundant in hippocampus, amygdala, cerebellum, and in greatest amount in pons. Our results indicate that Lafora Disease is both a neurodegenerative disease and a glycogen metabolism disorder. We hypothesize that laforin deficiency upregulates tau protein kinase I/glycogen synthase kinase 3beta forming tau, amyloid and polyglucosan bodies. Our findings are critical for future experiments on disease mechanisms and therapies for both Lafora disease and Alzheimer disease. Study supported by: National Institutes of Health [1RO1NS055057], Chelsea’s Hope Foundation for Lafora Disease and Programa de Apoyo a Proyectos de Investigacio´n e Innovacio´n Tecnolo´gica-DGAPA UNAM [IN214609, and PAPCA 2010-2011] M728. Network Structure and Sensitivity to the Geometry of Stimuli in Epilepsy and Cognition Elan L. Ohayon, Ann Lam and Terrence J. Sejnowski; La Jolla, CA What modulates a brain’s sensitivity to stimuli? This question is central to the study of reflex epilepsies and cognition. Previously we have shown that network structure can affect the persistence of complex activity. Here we use computational models to demonstrate how anatomical changes can modulate sensitivity to initial conditions such as perceptual stimuli. Models consisted of large spatial networks with up to 20,000 spiking units with inhibitory and excitatory populations. Network structure was adjusted by randomly adding or removing cells at 5% increments. Simulations showed that homogeneous networks (density ¼ 1.0) were least likely to maintain activity with either single or distributed stimuli. In contrast, heterogeneous networks became more sensitive to a variety of stimuli (e.g., over 95% persistence at density ¼ 0.6). Interestingly, the self-propagating responses generated in heterogeneous networks could be ��grafted’’ back onto the homogenous networks and continue propagating. These experiments illustrate that changes in anatomy can modulate responses to stimulus geometry thereby helping explain how neurodegeneration and trauma might lead to changes in sensitivity and the lowering of seizure threshold. The findings also illustrate how network structure might modulate responses to stimuli in attention and cognition. Study supported by: NIH M731. Antiepileptic Activity of Intrapulmonary Midazolam Ashish Dhir, Dorota Zolkowska and Michael A. Rogawski; Sacramento and Davis M729. Hypoglycemia Induced NMDA ReceptorDependent Epileptiform Activity in the Hippocampal CA3 Area Causes Damage in CA1 Carlos M. Florez, Jane Zhang, Peter Abdemalik, Liang Zhang and Peter L. Carlen; Toronto, ON, Canada Midazolam is a short-acting central/peripheral benzodiazepine receptor modulator. It is widely used as an intravenous sedative and a fast-acting anticonvulsant to abort status epilepticus. In the present study, we sought to characterize intrapulmonary route to deliver midazolam for providing fast and potent antiepileptic action. Further, we explored the involvement of both central and peripheral benzodiazepine receptors in its mechanism of anticonvulsant action. Intraperitoneal administration of midazolam at 250–5000 lg/kg protected mice against pentylenetetrazol, picrotoxin and kainic acid-induced convulsions. Similarly, the intratracheal route of midazolam administration demonstrated anticonvulsant activity but at much lower doses (25–100 lg/ kg); the maximum anticonvulsant action was observed Seizures are the most common clinical presentation of severe hypoglycemia in neonates. We characterized a new in vitro model for the study of hypoglycemia-induced seizures using mouse hippocampal thick slices. Changing the glucose concentration to 1mM produced seizures in 88% of the preparations. Isolation experiments revealed that CA3, less susceptible for hypoglycemia induced synaptic failure than CA1, is the epileptogenic area. The CA3 network showed decreased interneuronal activity and increased frequency and energy transfer of the pyramidal cell activity prior to the onset of 103 ID: kannanb I Black Lining: [ON] I Time: 17:25 I Path: N:/3b2/ANA#/Vol00000/110245/APPFile/JW-ANA#110245 J_ID: ZAY Customer A_ID: SUPP11-7 Cadmus Art: 22580 Date: 26-August-11 between 5–15 minutes. The anticonvulsant action of intratracheal midazolam (100 lg/kg) in PTZ i.v. seizure model was reversed by pre-administration of flumazenil (5 mg/kg., i.p.), a centrally acting benzodiazepine receptor antagonist. Finasteride (100 mg/kg., i.p.), a 5-alpha reductase inhibitor and neurosteroid synthesis inhibitor partially blocked the anticonvulsant action of midazolam in PTZ seizure threshold model. Furthermore, the anticonvulsant action of intraperitoneal midazolam was reversed by PK-11195, a peripheral benzodiazepine receptor antagonist. In conclusion, the intrapulmonary midazolam provides fast and potent anticonvulsant action and involves both central and peripheral receptors in its mechanism of action. Study supported by: Epilepsy Laboratory Stage: Page: 104 Results: Biopsied samples from IBM patients showed lower expression of myogenin than those from IIM patients, in immunohistochemistry (IBM 4.761.4 cells/100myofibers, IIM 7.363.7, p ¼ 0.0352), Western blot (IBM 0.04860.030 (relative amount to actin), IIM 0.09060.056, p ¼ 0.0297), and real-time RT-PCR (IBM 10.668.5 (relative amount to b-actin), IIM 19.6611.7, p ¼ 0.0344). Immunohistochemistry of biopsied samples from IBM patients also revealed that myogenin was aberrantly expressed within degenerative myofibers, and was aggregated in Ab-positive inclusion bodies. Conclusion: Disrupted expression of myogenin may reflect impaired regeneration in IBM. Study supported by: Grants-in Aid for Scientific Research and Health and Labour Sciences Research Grants for Research on Intractable Diseases from the Ministry of Health, Labour and Welfare of Japan, and Grants-in Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan. M732. Do Brain Volumes in JME (juvenile myoclonic epilepsy) differ from normal controls? John T. Spitz, Long Vu, Lydia Su, Mark A. Mandelkern, Barbara E. Swartz; Berkely, CA, Irvine, CA, Los Angeles, CA, Irvine,CA and Newport Beach, CA M837. Abnormalities of a Novel Autophagy-Associated Protein, NBR1, in Muscle Fibers of Sporadic InclusionBody Myositis (s-IBM) Carla D’Agostino, Anna Nogalska, Mafalda Cacciottolo, W.King Engel and Valerie Askanas; Los Angeles, CA Background: JME is a form of generalized epilepsy that accounts for 7% of all epilepsies. The natural history of JME and its brain morphology is explored in this study. Methods: We compared the volumes of 11 regions of interest (frontal and subcortical) and grey matter density between 17 JME subjects (33.8 þ/À 10.4 years) with sex and age-matched controls (35.4 þ/À 11.7) using automated and manual volumetric procedures and voxel based morphometry (VBM). Regional volumes were normalized to whole brain volumes prior to statistical analyses. Results: Initial analysis of the volumetric data using ttests with Bonferroni correction found no significant differences between the JME and controls. However, individual subjects with JME were more likely to have regions larger than control mean volumes than visa versa using VBM and volumetry (p ¼ .04, Binomial test, VBM). Additionally, both VBM and manual volumetric analysis found the left thalamus larger in JME subjects. These results will be expanded using ANCOVA and/or MANCOVA analyses to control for a number of covariates: duration of epilepsy, sex, seizure control and medications for final presentation. Discussion will emphasize the growing literature in this area. Study Supported By: Veteran’s Administration Merit Review Program 821/103. Intra-muscle fiber accumulation of ubiquitinated protein aggregates containing several conformationally modified proteins, including amyloid-b and phosphorylated tau, is characteristic of the pathologic phenotype of s-IBM, the most common degenerative myopathy of older persons. Impaired protein-degradation, involving both the 26S proteasome and autophagic-lysosomal pathways, we previously demonstrated in s-IBM muscle. NBR1 is a ubiquitin-binding scaffold-protein importantly participating in autophagic degradation of ubiquitinated proteins. Abnormalities of p62, another ubiquitin-binding protein, were previously described in s-IBM. Abnormalities of NBR1 have not been reported in s-IBM. We have now identified in 14 s-IBM muscle biopsies that NBR1, by: a) immunohistochemistry, was strongly accumulated within s-IBM muscle-fiber aggregates, where it closely co-localized with p62 and phosphorylated tau; b) immunoblots, was increased 3x, p< 0.01; and c) immunoprecipitation, was associated with p62. By real-time PCR, NBR1 mRNA was increased 2x, p< 0.01. None of the 15 disease- and normal-control muscle biopsies had any NBR1 abnormality. This first demonstration of NBR1 abnormalities in sIBM: a) further suggests that abnormalities of the autophagic-lysosomal pathway may be critically involved in the sIBM pathogenesis, and b) indicates a potential therapeutic focus. Study supported by: Muscular Dystrophy Association Neuromuscular Disease M836. Disrupted Expression of Myogenin in Inclusion Body Myositis Akatsuki Kubota, Jun Shimizu, Atsushi Iwata and Shoji Tsuji; Tokyo, Japan Background: Inclusion body myositis (IBM) is a chronic progressive inflammatory myopathy, with degenerative pathology. Immunosuppressive therapies are ineffective to IBM, unlike other idiopathic inflammatory myositis (IIM). Muscle regeneration is also impaired in IBM, but the mechanism remains undetermined. Myogenin is one of the myogenic regulatory factors, and plays an essential role in maturation of myogenic cells. Purpose: We evaluated expression of myogenin in biopsied muscles from IBM and IIM patients. Materials and methods. We analyzed biopsied samples from 11 IBM and 19 IIM patients. We quantified myogenin-positive cells by immunohistochemistry, myogenin protein by Western blot, and myogenin mRNA by real-time reverse transcription PCR (RT-PCR). M838. Atrophy and Autophagy in Limb Girdle Muscular Dystrophy and Glycogen Storage Disease Type 2 Corrado I. Angelini, Annachiara Nascimbeni, Marina Fanin and Marco Sandri; Padova, Italy Few studies have investigated atrophy/autophagy gene expression in LGMDs and GSD type 2, to study the fate of misfolded proteins in ubiquitin-proteasome system and recovery in autophagy-lysosome pathway after Enzyme Repacement Therapy (ERT). We investigated gene expression from 40 muscle biopsies of LGMD 2A, 20 LGMD 2B and 12 GSD type 2, both infantile and late onset. We found evidence of activation of molecular pathways with upregulation of autophagy-related 104 ID: kannanb I Black Lining: [ON] I Time: 17:25 I Path: N:/3b2/ANA#/Vol00000/110245/APPFile/JW-ANA#110245 J_ID: ZAY Customer A_ID: SUPP11-7 Cadmus Art: 22580 Date: 26-August-11 genes: BNIP3 and p62 in Pompe, of atrophy-related genes atrogin-1 and MuRF-1 in LGMD 2A (calpainopathy) and in LGMD 2B (dysferlinopathy). In one infantile, one juvenile and one adult GSD type 2 cases a second biopsy was done after ERT and analysed for morphology and gene markers: in the second biopsy we observed after ERT reduced vacuolated fibers and decreased autophagy related markers. Our study in GSD type 2 recognises an important contribution of autophagic process in the development of muscle pathology, after ERT autophagy markers are considerably decreased as well as vacuolisation of muscle fibers. Our observations in LGMDs are new and support future therapeutic interventions to rescue muscle atrophy. Study supported by: Telethon, Eurobobank. Stage: Page: 105 events attributable to the cellular injections. We are using clinical evaluation, strength testing, and electrical impedence myography to monitor progression of disease. Following FDA review and approval of safety data from the first 12 patients we will move to injections into the cervical spinal cord. Study supported by: Neuralstem, Inc. M841. Clinical Development of an Antisense Therapy for the Treatment of Transthyretin Amyloidosis Shuling Guo, Elizabeth Ackermann, Sheri Booten, Luis Alvarado, Andrew Siwkowski, Merrill Benson, Steve Hughes and Brett Monia; Carlsbad, CA and Indianapolis, IN Transthyretin (TTR)-associated amyloidosis is a late-onset autosomal-dominant genetic disease. Mutations in TTR destabilize TTR tetramer thereby inducing the formation of amyloid fibrils. This disease mainly affects peripheral nerves as in familial amyloidotic polyneuropathy (FAP) or heart as in familial amyloid cardiomyopathy (FAC). Circulating TTR is predominantly produced by the liver, and the only available treatment as of June 2011 is orthotopic liver transplantation. Using antisense technology, we identified an antisense oligonucleotide, ISIS-TTRRx, for the treatment of TTR-associated amyloidosis. When tested in a human TTR transgenic mouse model, ISIS-TTRRx showed a dose-dependent reduction of human TTR at both the mRNA and protein levels. In cynomolgus monkeys, ISIS-TTRRx treatment produced a time-dependent reduction in plasma TTR levels. After 12 weeks of treatment, liver TTR mRNA and plasma TTR protein levels were reduced by $80%. We also observed a significant decrease in plasma RBP4 levels correlating with TTR reduction. ISIS-TTRRx treatment was well tolerated in both rodents and monkeys and produced a PK/PD profile consistent with prior experience using this chemistry platform. ISIS-TTRRx is currently under evaluation in a Phase I clinical trial, with the first cohort dosed in May 2011. Study supported by: Isis Pharmaceuticals Shuling Guo, Elizabeth Ackermann, Sheri Booten, Luis Alvarado, Steve Hughes and Brett Monia are all employees at Isis Pharmaceuticals M839. Virtual Demyelination in pmp22 Deficiency Jiasong Guo, Qing Yan, Gina Sosinsky, Mark Elisman, Cameron McIntyre, Lily Wang, Ueli Suter and Jun Li; Nashville; San Diego; Cleveland; Zurich, Swaziland and Nashville, TN Safety factor for action potential propagation in pmp22þ/À nerves appears impaired (Bai et al, J Neurosci 2010). The present study investigates mechanisms responsible for the impairment. Fluorescent dyes with different molecular sizes were injected into sciatic nerves. After 4-hour incubation, sciatic nerves were teased into individual nerve fibers, and examined under fluorescence microscopy. Fluorescence was of strong intensity in about a half of paranodal tomacula of pmp22þ/À nerves (15 mice), but absent or minimal in the paranodes of wild-type nerves (11 mice). This finding suggests that myelin is abnormaly leaky, and may result in excessive outward current. Application of potassium channel blocker, 4AP, to reduce outward current improved the amplitude of motor response during nerve stimulation. Western blot and immunohistochemistry revealed alterations of tight junction protein assembly, a potential molecular mechanism for the myelin leakage. Conclusions: Our results show excessive leakage in pmp22þ/À myelin in the absence of demyelination. This leakage is functionally similar to demyelination. These findings not only reveal novel mechanism for conduction block but also establish new therapeutic approach for this disease. Study supported by: NIH Neurogenetics M1011. EPI-A0001: New Potential Therapy for Friedreich Ataxia David R. Lynch, Steve M. Willi, Robert B. Wilson, Karlla W. Brigatti, Olena Kucheruck, Eric C. Deutsch, William D. Shrader, Patrice Rioux, Guy Miller, Amale Hawi and Thomas Sciascia; Philadelphia, PA; Patterson, NY and Mountain View, CA M840. First in Human Phase 1 Trial of Neural Progenitor Cells in ALS: Results in the First 12 Patients Jonathan D. Glass, Nicholas Boulis, Meraida Polak, Crystal Kelly, Thais Federici, Jane Bordeau, Seward Rutkove, Karl Johe, Tom Hazel and Eva Feldman; Atlanta, GA; Boston, MA; Rockville, MD and Ann Arbor, MI This study tested the ability of EPI-A0001(previously called A0001) (a-tocopherol quinone), to improve in vitro measures, glucose metabolism and neurological function in Friedreich ataxia. We used an in vitro assay of cell rescue followed by a double blind, placebo controlled trial of 2 doses of EPI-A0001 in 30 adults. The primary clinical trial outcome was disposition index, a measure of diabetic tendency, from an IVGTT, evaluated 4 weeks after treatment. Secondary neurologic measures included the Friedreich ataxia rating scale (FARS). EPI-A0001 inhibited cell death in FRDA models in vitro. For the clinical trial, mean GAA repeat length was 699, and mean age was 31. Four weeks after treatment initiation, changes in disposition index between subjects treated with EPI-A0001 and placebo were not statistically significant. In contrast, a dose dependent improvement in FARS score was Twelve patients with ALS were injected into the lumbar spinal cord with fetal-derived neural stem cells. The design is one of ��escalating risk’’, where each group of patients is progressively less impaired. The first 6 patients were nonambulatory, 3 were supported by mechanical ventilation. The first 3 patients received 5 unilateral injections at L2L4, and the next 3 received 5 injections bilaterally. Patients 7–12 were ambulatory and had vital capacities > 60 % predicted. Patients 7–9 received 5 unilateral injections, and patients 10–12 received bilateral injections. Each injection was 10 ll of 10,000 cells/ll; patients received either 500,000 or 1 million cells through 5 or 10 injections, respectively. There have been two deaths, one which was unrelated to either ALS or the clinical trial. The surgical procedure was well tolerated. There have been no adverse 105 ID: kannanb I Black Lining: [ON] I Time: 17:25 I Path: N:/3b2/ANA#/Vol00000/110245/APPFile/JW-ANA#110245 J_ID: ZAY Customer A_ID: SUPP11-7 Cadmus Art: 22580 Date: 26-August-11 found. Patients on placebo improved 2.0 FARS points while patients on low dose EPI-A0001 improved by 4.9 points (p ¼ 0.04) and patients on high dose improved by 6.1 points (p<0.01). Although EPI-A0001 did not alter disposition index, it caused a dose dependent improvement in neurologic function. Longer studies will assess the reproducibility and persistence of neurologic benefit. Study supported by: Penwest/Endo Pharmaceuticals, Edison Pharmaceuticals Drs. Sciascia and Hawi are former employees of Penwest Pharmaceuticals. Drs Miller and Shrader are current employees of Edison pharmaceuticals. Dr Rioux is a former employee of Edison pharmaceuticals Stage: Page: 106 slowly progressive sensory neuropathy and spinal stenosis but also for many degenerative conditions of other organs including osteoarthritis. Their whole genome was sequenced and was found to be identical for all exons. Further studies of whole genome methylation sequencing using two completely different methodologies confirmed 141 sites which were significantly different at a genome-wide level. The results of these studies carried out on CD4 positive T-lymphocytes, were confirmed in epithelial cells from buccal smear, implicating a germ line origin for these changes. There are two common features among the 27 conditions present in one but not in the other monozygotic twin. These findings highlight the importance of epigenetic alterations in the development of the common degenerative diseases of man. Study supported by: This study was supported by grant funding from the MS Society of the UK and the Scientific Foundation of the Canadian MS Society. M1012. Exome Sequencing Identifies a Rare Variant in the CYP27B1 Gene Associated with Multiple Sclerosis George C. Ebers and Sreeram V. Ramagopalan; Oxford, Oxfordshire, United Kingdom Background: Multiple sclerosis (MS) is a complex neurological disease. We previously described the ascertainment of 43 Canadian families with 4 or more individuals with MS. Genetic linkage analysis and genotyping of candidate genes in these families has not fully explained familial disease clustering although alleles of GWAS genes are overrepresented. Methods: Whole exome sequencing was performed to further understand heightened prevalence of MS in these families. Findings: Forty-three individuals with MS (one/family) were sequenced. On average over 58000 variants were identified in each individual. Searching for rare variants in known or candidate MS susceptibility genes led to identification of a rare loss-of- function variant in the CYP27B1 gene. This variant in 2716 parent-affected child trios showed significant association to MS P ¼ 6Â10À5. Further genotyping of other variants in over 11,000 individuals showed that rare CYP27B1 variants conferred significant risk of MS, Peto odds ratio ¼ 4.1 (95% confidence interval 1.5–11.1). Interpretation: Causative role for CYP27B1 in MS risk is supported. CYP27B1 encodes the vitamin D activating 1alpha hydroxylase enzyme. A role for vitamin D in MS pathogenesis is strongly implicated. We show the utility of using extreme multicase families to identify rare variants. Study supported by: This study was supported by grant funding from the MS Society of the United Kingdom and the Scientific Foundation of the Canadian MS Society. Neurology Critical Care M1206. Imaging Biomarkers of Cerebral Edema in Malignant Infarction Kevin N. Sheth, Albert J. Yoo, R. G. Gonzalez, W. T. Kimberly, Zeshan A. Chaudhry, Jordan J. Elm, Sven Jacobson, Stephen M. Davis, Geoffrey A. Donnan, Gregory W. Albers and Barney J. Stern; Baltimore, MD; Boston, MA; Charleston, SC; New York, NY; Carlton South, Victoria, Australia and Stanford, CA Objective: 70% of patients with malignant infarction die secondary to cerebral edema. A fundamental challenge is the lack of a validated imaging marker for brain edema. We hypothesized that MRI hemisphere and ventricle volumes reliably change over the first five days in patients with malignant edema. Methods: We conducted a retrospective analysis of the EPITHET study MRI’s at stroke onset and at 3–5 days. We selected patients with an acute diffusion weighted imaging volume ! 82cc, which is highly predictive for malignant edema. The involved hemisphere and ipsilateral ventricle were manually outlined, and volumes were measured using Analyze software. Results: 12 patients, with a mean age of 71 and mean NIHSS score of 19, were included in the analysis,. The mean (6SD) increase in ipsilateral hemisphere brain volume was 81.5cc (629.0cc) with a corresponding decrease in ventricular volume of 9.2cc (64.7cc) (both p<0.0001). Concordance correlations for baseline and follow-up measurements were 0.9470 (95%CI: 0.8411–0.9830) and 0.9319 (95%CI: 0.7978–0.9782). Conclusions: MRI-based metrics of cerebral edema are responsive to change and have a high inter-rater agreement. These data suggest their potential utility as a biomarker for novel therapies that prevent malignant edema. Study supported by: National Institutes of Health, Remedy Pharmaceuticals Remedy Pharmaceuticals has provided funding for a 10 patient pilot study for intravenous glyburide in malignant infarction. This study is ongoing and a precursor to application for NIH. M1013. Whole Genome Sequencing in Twins Discordant for 27 Diseases George C. Ebers and Sreeram V. Ramagopalan; Oxford, Oxfordshire, United Kingdom An apparently unique pair of monozygous twins was identified. They had long been thought to be fraternal because of striking differences in birthweight, appearance and health. However a history was elicited of their having been told they were born in the same sac. Finally at age 61 suspicions were raised when it was noted their handprints were identical. They were discordant for many neurological conditions including precocious puberty, migraine, essential tremor, 106 ID: kannanb I Black Lining: [ON] I Time: 17:25 I Path: N:/3b2/ANA#/Vol00000/110245/APPFile/JW-ANA#110245 J_ID: ZAY Customer A_ID: SUPP11-7 Cadmus Art: 22580 Date: 26-August-11 136th Annual Meeting Tuesday, September 27, 2011 Works in Progress Poster Session Stage: Page: 107 positron emission tomography measurements of rCBF were available at baseline and up to 7 annual follow-up visits in 88 cognitively normal older individuals in whom genome-wide genotyping data were collected. Cognitively normal carriers of the risk allele of the rs11136000 SNP in CLU show significant and dose-dependent longitudinal increases in resting state rCBF in brain regions intrinsic to memory processes. We propose that these increments in rCBF over time represent compensatory changes in neuronal activity required to maintain normal cognition during aging in at-risk individuals, and that their eventual failure in some may mark the transition from normal aging to Alzheimer’s disease. Study supported by: NIA Intramural Research Program WIP posters will be displayed in Elizabeth A-E of the Manchester Grand Hyatt from 10:00 am – 7:00 pm, with authors present from 6:00 pm – 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. T1540. Association of High Density Lipoprotein to Alzheimer Disease Ramin Ebrahimi, Naser Ahmahi, Fereshteh Hajsadeghi and Hormoz Babaei; LA, CA Dementia and Aging T1538. Proneurogenic Compound Reduces Synaptic Ab-42 Oligomer Levels and Shows Cognitive Benefit in Alzheimer’s Mouse Model Sam Gandy, John W. Steele, Charles Glabe, Kai Treuner, Todd Albert, Carrolee Barlow, Michelle E. Ehrlich and Soong Ho Kim; New York, NY; Irvine, CA and San Diego, CA Background: Alzheimer’s disease (AD) is a devastating progressive neurologic disorder with increasing prevalence. Little data exists regarding association of HDL-c to AD. This study evaluates the association of different HDL-c levels with AD. Methods: This study consists of 2144 Veterans with AD and 16175 without AD. VA electronic medical records from veterans were used to evaluate the presence or absence of AD, HDL levels and risk factors. HDL-c was classified as HDL-c <40 mg/dl, 40–50 mg/dl and >50 mg/dl. Conditional logistic regression analysis was employed to assess the association of lower levels of HDL-c with AD. Results: The mean age was 7966 years. After adjustment for risk factors, odds ratio of AD was 2.20 (95% CI 2.09– 2.31, p ¼ 0.0001) for those with HDL-c of 40–50 mg/dl and 2.89 (95% CI 2.75–3.05, p ¼ 0.0001) for those with HDL-c <40 mg/dl, as compared to subjects with HDL-c>50 mg/dL. Conclusion: There is a strong association between lower levels of HDL-c and AD. Furthermore, population attribution risk of lower levels of HDL-c for new AD is very high; warranting future studies evaluating the role of specific lipid therapy to improve HDL-c levels to potentially decreased future development of AD. Study supported by: Self Group II metabotropic glutamate receptors (Gp II mGluR) trigger production of Ab peptides from isolated synaptic terminals, and synaptic Ab42 generation is selectively suppressed by Gp II mGluR antagonists. Gp II mGluR antagonists also stimulate hippocampal neurogenesis and enhance cognition. Pilot studies were performed in old (18 mo) and young (6 mo) Dutch APP693Q x PS1D Exon 9 bigenic mice. After 3 wk oral BCI-838 treatment of 18 mo-old mice, levels of prefibrillar A11-immunoreactive Ab oligomers were decreased in hippocampi from treated mice (p 0.01). In young Dutch APP693Q x PS1D Exon 9 mice, fibrillar OC-immunoreactive Ab oligomer levels were decreased in the treated young mice (p 0.01). Some Dutch APP693Q and wildtype littermates were given BCI838 p.o. for 3 mo. BCI-838 treatment was associated with improved memory in cued fear conditioning (p ¼ 0.01 TgþVeh vs TgþBCI-838). A trend toward reduced anxiety was also observed (p ¼ 0.086 for TgþVeh vs TgþBCI838). GpII mGluR antagonists are promising compounds for prevention or treatment of AD because of their unique synaptic Ab42- and Ab-oligomer-lowering activity coexisting with pro-cognitive and pro-neurogenic activities. Study supported by: P01 AG10491 Carrolee Barlow is CSO at BrainCells. Todd Albert and Kai Treuner are staff scientists at BrainCells. T1541. Amyloid-b 42:40 Metabolism Is Altered in Autosomal Dominant Alzheimer’s Disease (ADAD) Rachel E. Potter, Vitaliy Ovid, Tom Kasten, Wendy Sigurdson, Kwasi Mawuenyega, Bruce Patterson, Don Elbert, Scot Fague, Sumi Chakraverty, Alison Goate, Kevin Yarasheski, John C. Morris, Tammie Benzinger and Randall J. Bateman; St. Louis, MO T1539. Alzheimer Risk Variant Clusterin (CLU) and Brain Function during Aging Madhav Thambisetty, Lori Beason-Held, Michael Kraut, Michael Nalls, Andrew Singleton, Luigi Ferrucci, Simon Lovestone and Susan Resnick; Baltimore and London, United Kingdom We hypothesized that ADAD is caused by mutations that lead to higher production rates for amyloid-beta (Ab) 42 compared to Ab40. We measured Ab isoform production and clearance rates in ADAD participants to determine the effects of mutations which invariably lead to AD. Presenilin 1 mutation carriers (46.2yrs 6 15.8 (N ¼ 7)), and related non-carriers (52.0yrs 6 20.5 (N ¼ 7)) completed Ab stable isotope labeling 13C6-Leu kinetic studies of cerebrospinal fluid, and PET PIB imaging. Differences in the Ab42 relative to Ab40 labeling curves were specifically altered in mutation carriers versus non-carriers. Newly generated Ab42 was detected before Ab40 or 38, and there were differences in area under the curve analyses. These findings support prior in vitro studies that Ab42 is overproduced relative to other Ab isoforms. Ab isoform production and clearance Recent genome wide association studies have identified common risk variants for Alzheimer’s disease (AD), although these exert small effects and are, by themselves, unlikely to be of clinical utility in risk prediction. However, these genetic risk variants may reveal mechanisms involved in the transition from normal aging to cognitive impairment. We examined the effect of the recently discovered AD risk variant rs11136000 single nucleotide polymorphism in the clusterin gene (CLU) on longitudinal changes in resting state regional cerebral blood flow (rCBF) during normal aging. 15O-water 107 ID: kannanb I Black Lining: [ON] I Time: 17:25 I Path: N:/3b2/ANA#/Vol00000/110245/APPFile/JW-ANA#110245 J_ID: ZAY Customer A_ID: SUPP11-7 Cadmus Art: 22580 Date: 26-August-11 may be used to define the therapeutic effectiveness of treatments which target abnormal Ab metabolism in AD. Study supported by: This work was supported by a grant from NIH (no. P01AG026276), an anonymous foundation, Eli Lilly research, the Knight Initiative for Alzheimer’s Research, and the James and Elizabeth McDonnell Fund for Alzheimer’s Research. R.J.B. is a cofounder of a company (C2N Diagnostics) that has licensed a pending Washington University patent on the technology described in this article. Stage: Page: 108 Results: MCM rates were 4.11%, 4.02% and 4.15% for TPM, migraineurs, and APMD-treated migraineurs, respectively. Relative risks (95% CI) for TPM vs. migraineurs and APMD-treated migraineurs were 1.02 (0.73–1.45) and 0.99 (0.68–1.45), respectively. OC rates were 0.26%, 0.17%, and 0.37% for the TPM, migraineurs, and APMD-treated migraineurs, respectively. Relative risks (95% CI) for TPM vs. migraineurs and APMD-treated migraineurs were 1.50 (0.37–6.19) and 0.69 (0.15–3.12), respectively. Conclusions: TPM exposure did not significantly increase the rates of OC or MCM. Study supported by: Vivus, Inc. T1542. Acetylated Tau, a Novel Pathological Signature in Alzheimer’s Disease and Other Tauopathies David J. Irwin, Todd Cohen, Murray Grossman, Steven E. Arnold, Sharon X. Xie, Virginia M.Y. Lee and John Q. Trojanowski; Philadelphia, PA Neuroimmunology and Demyelinating Disease T1741. Comparison of MRI Techniques for Monitoring of Multiple Sclerosis Manuela Vaneckova, Jan Krasensky, Tomas Kalincik, Dana Horakova, Eva Havrdova and Zdenek Seidl; Prague, Czech Republic The microtubule-binding protein, tau, is the major component of neurofibrillary inclusions characteristic of Alzheimer’s disease (AD) and related tauopathies. Recently, we reported that the acetylation of tau at lysine residue 280 (ac-K280) is a novel, pathological post-translational modification. Here, we performed detailed immunohistochemistry (IHC) to further characterize tau ac-K280 expression in tauopathies. Ac-K280 tau IHC was conducted on 30 postmortem central nervous system (CNS) regions from AD (n ¼ 10), corticobasal degeneration (CBD; n ¼ 5), and progressive supranuclear palsy (PSP; n ¼ 5) patients. Ac-K280-immunoreactive (Ir) tau pathology was compared to multiple well-characterized tau epitopes. All cases showed significant CNS ac-K280-Ir tau pathology in a distribution pattern similar to hyperphosphorylated-tau. In AD cases, the majority of ac-K280-Ir tau pathology was in intracellular, thioflavin-S (ThS) positive tau inclusions, and also ThS negative tau pathology in CBD and PSP. Ac-K280-Ir was present throughout all stages of AD pathology, but more prominent in later stages. Ac-K280-Ir is a pathological modification of tau that may contribute to neurodegeneration by augmenting losses of normal tau properties, as well as toxic gains of function. Thus, inhibiting tau acetylation could be a disease modifying drug discovery target for tauopathies. Study supported by: NIH grants: T32-AG000255 Training in Age-Related Neurodegenerative Diseases and P30 AG010124-20 Alzheimer’s Disease Core Center grant. Goal: To compare contemporary MRI measures for prediction of future clinical disability in multiple sclerosis patients by analysis of our MRI data (brain atrophy, T2 lesion volume, T1 lesion volume and corpus callosum atrophy). Methods: Long term (7-year) longitudinal MRI data of 178 patients were analyzed Area of corpus callosum, T2 lesion volume, T1 lesion volume, brain parenchymal fraction and brain atrophy were measured. Clinical disability was assessed with Expanded Disability Status Scale (EDSS). Patients were divided in two groups: clinically stable and those with sustained progression during seven years. Results: Statistically significant correlation of future clinical disability (as characterized by EDSS score) with brain atrophy and corpus callosum atrophy was found. In this retrospective study, clinically stable patients were distinguished from patients with sustained progression in less than 1 year using the corpus callosum atrophy (probability over 98%) and after 3 years using the brain atrophy (with probability of 96%). Conclusions: We have shown that the corpus callosum atrophy is a superior marker of disease progression compared to the brain atrophy, which was considered to be its most significant marker. Supported by Biogen Idec Inc. and the grants MZOVFN2005, MSM 0021620849. Study supported by: Supported by Biogen Idec Inc. and the grants MZOVFN2005 and MSM 0021620849. Headache and Pain T1742. Effects of Rituximab on T-Cells in MS Uma Vinayagasundaram, Ellen M. Mowry, Ian R. Matthews, Julia Marino and Emmanuelle Waubant; San Francisco, CA T1623. Retrospective Analysis of Major Congenital Malformations (MCMs) and Oral Clefts (OC) Associated with In-Utero Topiramate Exposure Mark W. Green and Arun Bhattachuria; New York, NY and Yardley, PA Objective: To examine rituximab effect on T-cell subsets. Background: Rituximab, an anti-CD20 antibody, profoundly depletes circulating B-cells. It is unclear how it impacts T-cells. Methods: In a retrospective study of patients who received >1 rituximab infusions at UCSF MS center, within-patient pre- and post-infusion (mean duration ¼ 7 months) lymphocyte counts for the first rituximab course were compared. Results: Of 119 patients who received rituximab, 56 (45 MS, 10 NMO, 1 other indication) had both pre- and post-infusion labs. The mean (þ SD) absolute count of CD19þ B-cells dropped from 273 (þ 25) pre- vs. 59 (þ17) post-rituximab (p <0.0001). The overall (CD3þ; 1322 þ 104 vs. 1047 þ 62; p ¼ 0.009), CD4þ (907 þ 75 vs. 717 þ 44; p ¼ 0.0124), and CD8þ (409 þ 39 vs. 313 þ 23; p ¼ 0.004) T-cell counts dropped after rituximab. At follow-up, 15 of 67 (22%) had a CD4 Purpose: To analyze the prevalence of malformations among infants born to women exposed to topiramate. Methods: This study used retrospective data from Wolters-Kluwer Pharma Solutions that followed patients’ Pharmacy and Medical Claims (1/2003–12/2010) to identify infants exposed to topiramate during pregnancy (n ¼ 778). Probable exposure during pregnancy was refined using data on script fill date/supply, infant birth date, and ICD-9 codes for birth term. Control cohorts included women with diagnosis of migraine without epilepsy (n ¼ 26,920) and a subset exposed to acute-preventive migraine drugs (APMD) during pregnancy (n ¼ 2,964). Topiramate was excluded from both groups. All cohorts excluded known or suspected teratogens. 108 ID: kannanb I Black Lining: [ON] I Time: 17:25 I Path: N:/3b2/ANA#/Vol00000/110245/APPFile/JW-ANA#110245 J_ID: ZAY Customer A_ID: SUPP11-7 Cadmus Art: 22580 Date: 26-August-11 count below 500, and 4 (6%) had a CD4 count below 200. NK cell number (CD56þ, CD16-) tended to increase postinfusion (182 þ 13 vs. 199 þ 14; p ¼ 0.2). Impact of retreatment is being analyzed. Conclusions: Rituximab induces long-term T-cell reduction, whose impact is unclear. Study supported by: Research grant from Roche Stage: Page: 109 marrow space of the skull involves aquaporin water channels. Study supported by: Grants from the Ministry of Education, Culture, Sports, Science, and Technology (Japan) and University of Niigata. T1743. Fast Macromolecular Proton Fraction (MPF) Mapping in Multiple Sclerosis (MS) Vasily L. Yarnykh, James D. Bowen, Bart P. Keogh, Pavle Repovic, Angeli Mayadev, Beena Gangadharan, Daniel S. Rizzuto, Hunter R. Underhill, Kenneth R. Maravilla and Lily K. Jung-Henson; Seattle, WA T1745. Characteristics of the Long Latency Vestibular Electrical Evoked Potential in Control Human Subjects Benn E. Smith, Michael J. Cevette, Jan Stepanek, Daniela Cocco, Gaurav Pradhan, Kenneth H. Brookler, Lindsay Wagner, Sarah Oakley, David A. Zapala and Mark A. Ross; Scottsdale, AZ and Jacksoville, FL MPF mapping is a new quantitative imaging method, which determines relative concentration of macromolecular protons involved into the magnetization transfer effect. Literature suggests strong correlations between MPF and myelin content in neural tissues. We recently developed a fast 3D MPF mapping technique for clinical applications, which utilizes two images (with and without off-resonance saturation), and complimentary T1, B0, and B1 maps, providing whole-brain coverage, 1.5Â1.5Â4mm3 resolution, and <15 min total acquisition time on a 3T MRI scanner. In this ongoing study, MPF maps were obtained from 9 healthy controls, 18 relapsing-remitting (RRMS) patients, and 3 secondary-progressive (SPMS) patients. Whole-brain MPF histogram analysis was performed to quantitatively characterize individual MPF distributions in white matter (WM) and gray matter (GM). Group comparisons (independent t-test) revealed significant decreases of mean MPF in MS vs. controls and in SPMS vs. RRMS for both WM (P<0.001) and GM (P<0.04). Mean MPF in WM and GM demonstrated significant correlations with EDSS (r ¼ À0.55 and À0.56, P<0.01) and MSFC (r ¼ 0.78 and 0.68, P<0.001) scores. In summary, MPF can be used as a prospective quantitative imaging biomarker of demyelination, which captures pathological changes in both WM and GM. Study supported by: National Institutes of Health: NIH R21EB009908 Dr. Yarnykh is the PI of the above NIH grant, and his salary is funded in part by this award. Introduction: A human vestibular electrical evoked potential (VEEP) technique has recently been reported. Objective: To report a unique long latency waveform associated with the human VEEP which has novel electrical properties. Methods: Control ears (n ¼ 23) were studied with bipolar mastoid electrical stimulation. Evoked potentials were produced using currents from 1 to 25mA, recording over Cz-A1/2. Results: In neurologically normal controls, mastoid stimulation at 2.5mA yielded Cz-A1/2 late responses of median amplitude 61lV (range 1.6–104; SD 25) and median latency 10.2ms (range 6.0–13.3; SD 4.9). These responses progressively increased in latency from 8.6 to 22.6ms (mean latency increase of 1.3ms/mA) as current strength was increased in 10 steps (1mA/step) from threshold current levels in all 5 subjects studied in this way. Conclusions: (1) The VEEP technique produces late responses in neurologically normal adults, (2) these response latencies increase with increasing current strength as reported in animals, (3) the current strength-response pattern of human VEEP late responses may reflect inhibition of descending vestibular efferent pathways or alternative as yet undiscovered mechanism(s), and (4) future studies are needed to define the nature and origin of the VEEP in health and disease. Study supported by: Mayo Foundation T1744. Skull Is Skull, and Not Simply Another Bony Structure Tsutomu Nakada, Yuji Suzuki, Yukihiro Nakayama, Vincent J. Huber and Ingrid L. Kwee; Niigata, Niigata, Japan and Martinez, CA T1746 Regulatory T Cells Play Contrasting Roles in a Viral Model for Multiple Sclerosis Nicholas E. Martinez, Fridrik Karlsson, Fumitaka Sato, Seiichi Omura, Alireza Minagar, Mathew B. Grisham, and Ikuo Tsunoda; Shreveport, LA Theiler’s murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD) is a viral model for multiple sclerosis (MS). Regulatory T cells (Tregs) can suppress experimental autoimmune encephalomyelitis, an autoimmune model for MS by modulating pathogenic Th1 and Th17 immune responses. While these findings imply that Tregs could also be beneficial in MS, we hypothesized that Tregs can be a double-edged sword in TMEV-IDD. In viral infections, although Tregs can prevent immune-mediated pathology, Tregs can suppress anti-viral immune responses, leading to more active viral replication and/or viral persistence. We injected TGF-b induced Tregs (iTregs) into TMEV-infected SJL/J mice on days 0 (early) or 35 (late). The early iTreg injection group developed more severe motor disturbances 1 week post infection (p.i.). The exacerbation of acute disease is most likely due to suppression of anti-viral immune responses in the central nervous system, facilitating viral replication. In contrast, late iTreg injection reduced inflammatory demyelination during the chronic phase of infection (2 months p.i.), which could be due to suppression of Aquaporin-4 (AQP-4) is a membrane protein in the aquaporin family of water transporters. It is widely expressed in the astrocyte system of the brain. Evidence continues to accumulate that AQP-4 is actively involved not only in vital physiological brain functions such as neural-flow coupling, but also in the pathophysiology of various brain diseases. In the process of developing clinical AQP-4 positron emission tomography (PET) for the brain, we identified various AQP-4 inhibitors. Among these, TGN-020 (2-nicotinamido-1,3,4-thiadiazole), was found to be suitable for AQP-4 PET in spite of its partial co-affinity for aquaporin-1. Subsequent human PET images obtained utilizing 11C-TGN-020 appropriately demonstrated specific distribution of AQP-4 within human brain in vivo. The study, however, unexpectedly exhibited very strong uptake of 11C-TGN-020 within the diploic space of the skull. Other bony structures, by contrast, showed virtually no uptake. Aeration represents a unique characteristic of the skull of ��heavy brain’’ animals. The study strongly suggests that drying of the 109 ID: kannanb I Black Lining: [ON] I Time: 17:25 I Path: N:/3b2/ANA#/Vol00000/110245/APPFile/JW-ANA#110245 J_ID: ZAY Customer A_ID: SUPP11-7 Cadmus Art: 22580 Date: 26-August-11 immunopathology. Therefore, iTregs could play contrasting roles depending upon the stage of virus-mediated demyelinating diseases. Study supported by: National Center for Research Resources of the National Institutes of Health. Stage: Page: 110 tially with repeat imaging 5 days from symptom onset revealing a conus myelitis (CM). Case report: A 42-year-old female woke up with UR, which progressed to an ascending FP without a sensory level. MRI of spinal axis w/wo was normal. Lumbar puncture revealed 0 WBC, 1 RBC, normal protein, glucose and negative immune markers (IgG Index and oligoclonal bands). EMG was normal. MRI of the lumbar spine repeated 5 days later revealed CM. Extensive infectious, inflammatory and autoimmune work up including NMO was negative. Brain MRI w/wo was normal as were VEPs. She had a relapse 3 months after the initial bout. Conclusion: Idiopathic CM appears to be a rare clinical entity, which can have protean manifestations requiring a high index of clinical suspicion and a thorough systematic workup. Study supported by: None T1747 Idiopathic Relapsing Conus Myelitis Raghav Govindarajan and Efrain Salgado; Weston, FL Background: Idiopathic acute transverse myelitis (TM) involves the thoracic cord. In rare cases conus might be the only site involved. Bladder symptoms can be a presenting feature without an obvious sensory level. Imaging studies might remain inconclusive thus posing a diagnostic challenge. Relapses in TM are rare and even more so restricted to the conus. We report a case of a 42 year-old female who presented with urinary retention (UR) that progressed to a flaccid paraplegia (FP). Imaging studies were negative ini- 110 ID: kannanb I Black Lining: [ON] I Time: 17:25 I Path: N:/3b2/ANA#/Vol00000/110245/APPFile/JW-ANA#110245 J_ID: ZAY Customer A_ID: SUPP11-8 Cadmus Art: 22581 Date: 26-August-11 136th Annual Meeting Sunday, September 25, 2011 Career Development Poster Session Abstracts Stage: Page: 111 in gene expression, differential display microarray data was analyzed. Results: Immunocytochemistry of KCNC3R420H mutant allele revealed perinuclear clumping and aggregation. Evidence for precise trans-Golgi localization was obtained by high FRET efficiency in the KCNC3R420H cells co-stained for 58K and KCNC3. Immunogold EM revealed KCNC3R420H failed to be delivered to the plasma membrane, though intracellular accumulation of KCNC3R420H was observed in swollen, distorted Golgi depleted of Golgi-derived vesicles. Microarray data revealed significant expression differences between the mutant and wildtype cultures in genes involved in Golgi processing and ubiquitination pathways. Conclusions: Our results establish the likelihood of protein aggregation and aberrant intracellular trafficking localized to the trans-Golgi network as a pathogenic mechanism in the neurodegenerative form of SCA13. KCNC3 channels are expressed in Purkinje cells and the hippocampus and are critical for the properties of bursting neurons. Study supported by: K23; American Academy of Neurology clinical research training fellowship Posters will be displayed in Elizabeth A-E of the Manchester Grand Hyatt from 10:00 am – 7:00 pm, with authors present from 6:00 pm – 7:00 pm. CD515. Non-Convulsive Status Epilepticus Is Associated with Mortality and Worse Short-Term Outcome in Critically Ill Children Nicholas S. Abend, Alexis A. Topjian and Dennis J. Dlugos; Philadelphia, PA Objective: Determine whether non-convulsive seizures (NCS) and non-convulsive status epilepticus (NCSE) were associated with higher mortality and worse short-term outcome. Methods: Critically ill children with acute encephalopathy underwent EEG monitoring. EEGs scored as no seizures, NCS, or NCSE. Co-variates included age, etiology of acute encephalopathy, and EEG background. Outcomes were mortality and change in Glasgow Outcome Scale (GOS) from admission to ICU discharge. Chi-squared analysis and multi-variable logistic regression were used to evaluate for associations. Results: 200 children underwent cEEG. NCS occurred in 84 (42%) of which 43 (22%) had NCSE. 83 (41%) had a decrease in GOS of which 36 (18%) died. In multi-variate analysis NCSE was associated with mortality (OR 3.05, p¼0.04) and change in GOS (OR 15.5, P<0.001) while NCS was not associated with mortality (OR 1.2, p¼0.76) or change in GOS (OR 1.5, p¼0.45). Conclusions: NCSE, but not NCS, is associated with worse short-term outcomes in critically ill children with acute encephalopathy. Further investigation is needed to determine whether this association is causal, persists in the long-term, and whether identification and management of NCS improves outcome. Study supported by: NIH K12-NS049453 CD531. TLR9 Processing in Multiple Sclerosis: A New Immunomodulatory Effect of Interferon-beta Konstantin E. Balashov, Suhayl Dhib-Jalbut and Latt Aung; New Brunswick, NJ Background: Viral pathogens, e.g., Epstein-Barr DNA virus have been implicated in the pathogenesis of multiple sclerosis(MS). Toll-like receptor(TLR)9 is the only TLR able to recognize viral DNA. TLR9 protein has to be cleaved from the N-terminal to become functional(processed TLR9). TLR9 is highly expressed in plasmacytoid dendritic cells(pDCs). Methods: pDCs were separated from healthy donors and MS patients. TLR9 gene expression was assessed by oligonucleotide microarrays. Unprocessed(135kDa) and processed(65kDa) TLR9 protein expression were studied by Western blot. Cytokine production by activated pDCs was measured by Multi-Analyte Profiling. Results: After treatment with IFN-beta, pDCs developed decreased ability to produce IFN-alpha, IL-6 and TNFalpha in response to TLR9 agonists as compared to the same patients prior to treatment. IFN-beta treated patients had levels of both TLR9 gene expression and the fulllength(unprocessed) TLR9 protein similar to untreated patients and healthy donors. However, pDCs separated from IFN-beta treated patients(n¼11), had significantly reduced levels of the processed TLR9 protein (0.89760.0639 relative units) as compared to untreated patients(1.44560.106, n¼14, p¼0.0004). Conclusion: Our findings suggest a novel immunomodulatory mechanism of IFN-beta. Modulation of TLR9 protein processing may contribute to decreased frequency of clinical exacerbations in IFN-beta treated MS patients. Study supported by: NIH, NMSS, Bayer Healthcare Dr. Balashov and Dr. Dhib-Jalbut served as consultants for Bayer Healthcare in the past. CD522. Aberrant Channel Subunit Trafficking in the Neurodegenerative KCNC3R420H SCA13 Phenotype Michael F. Waters; Gainesville, FL Background: Potassium channels influence many aspects of electrical excitability and mutations in their genes have been described in neurological diseases. We previously reported that the KCNC3R420H mutation leads to a neurodegenerative phenotype. Methods: Cell were transfected with constructs expressing wild-type and mutant KCNC3 alleles. Localization experiments were performed utilizing immunocytochemistry and electron microscopy. To assess mutant-mediated alterations 111 ID: kannanb I Black Lining: [ON] I Time: 17:25 I Path: N:/3b2/ANA#/Vol00000/110246/APPFile/JW-ANA#110246 J_ID: ZAY Customer A_ID: SUPP11-9 Cadmus Art: 22582 Date: 26-August-11 Stage: Page: 112 ABSTRACT AUTHOR INDEX Arnoldi, Alessia M1002 Artibee, Kay M810 Asadollahi, Marjan T1732 Ascherio, Alberto S216 Askanas, Valerie M807, M808, M816, M835 Assadi, Mitra S223 Astafiev, Serguei V. M601 Atassi, Farrah S215 Atkinson, Elizabeth J. M1008 Au, Rhoda T1504 Auchus, Alexander P. M1301 Awkar, Nelly M717 Azimi, Amirreza T1722 Babikian, Viken L. S122 Babovic, Mihajlo T1727 Backus, Carey M804 Bagai, Kanika S303 Baiser, Alexa S. T1504 Baker, M. S204, S209 Bakken, Erik C. M618, M619 Bakst, Isaac M821 Balasubramanian, Archana B. T1524 Balice-Gordon, Rita T1701, T1716 Baloh, Bob M815 Baloyannis, Stavros J. T1528 Bammler, Theodor K. T1511 Banerjee, Chirantan S101 Bankiewicz, Krystopf S. T1529 Barbato, Luigi M. T1735 Barcikowska, Maria T1503 Bardin, Jonathan C. M1104 Barkhof, Frederik T1708 Barnwell, Stanley L. T1606 Bartz, Traci T1513 Bass, Dale M1107 Bassi, Mariateresa M1002 Bassile, Clare M1403 Basta, Milan S103 Bateman, Lisa M. M703 Bateman, Randall J. T1501 Bayat, Elham T1739 Bayram, Mehmed B. T1527 Beal, Flint S216 Beck, James S216 Beckmann, Karola T1702 Beh, Shin C. S210 Belichenko, Pavel V. M609, M712 Bellugi, Ursula M608 Benke, Tim A. M706 Aasly, J. S204, S209 Aasly, Jan T1503 Abbott, Robert D. S203 Abolfazlee, R. S114, T1732 Achim, Critian L. T1905 Adams, Patrick E. T1521 Agadi, Jagadish B. M822 Agbemenyah, Hope Yao M1004 Aggarwal, Swati M821 Ahlskog, J.E. M606 Ahmed, Aiesha M833 Akbar, Umer M1205, T1620, T1809 Akber, Umer M719 Akfirat, Gokhan T1536 Akiyama, Hisanao S120 Aksan, Nazan M615 Al Samara, Mershed M722 Alaedini, Armin M602 Alam, Nurul S123 Alcalay, Roy N. S225 Aldea, Patricia T1901 Alexander, Katie M821 Alexopoulos, Andreas V. M711 Alexopoulos, Harry T1729 Alfahad, Tariq S127 Alfano, Lindsay N. M802 Alfuth, Kathleen S. M832 Algom, Avi M1007 Alkawadri, Mhd Rafeed M711 Allen, Mariet T1503 Allred, Peggy M821 Alqadi, Khalid S. S127 Altafullah, Irfan S102 Althaus, Alison L. M1401 Amini Harandi, Ali S114, T1712, T1718, T1722, T1723, T1731, T1732, T1734 Ances, Beau T1901 Andersen, O. S204, S209 Anderson, C. Alan M616 Andres, Patricia M821 Andress-Rothrock, Diane C. S113, T1602 Andrews, Mark M1106 Annex, Brian H. S115 Ansari, Hossein S236 Ansari, Morad T1503 Appel, Shmuel M702 Arain, Fazal M. M707 Arcilla-Londono, Ximena M828 Arciniegas, David B. M616 Ard, M. Colin T1531 Ben-Menachem, Elinor M713 Bennett, C.F. M821 Bennett, David A. T1502 Bennett, Jeffrey L. T1736 Benzinger, Tammie T1901 Berlau, Daniel J. T1524 Bernard, Bryan S211 Bernard, Paul B. M706 Beyer, Richard P. T1511 Bhabad, Sudeep S119 Bhargava, Pavan S140 Bhat, Sushanth M718, M834, S134, S137 Bhattacharya, Pratik S129 Bieber, Allan M1101 Biglan, Kevin S228 Biglan, Kevin M. S402 Bigwood, Doug T1736 Bilal, Yasmin T1737 Billings, Nia M. M613 Biondo, Andrew M828 Bisceglio, Gina T1503 Bishop, Kathie M821 Black, Robert E. S123 Blair, Aaron S208 Blakeman, Alan T1621 Blasco, Maria R. T1713 Blechschmidt, Cristiane M835 Blennow, Kaj T1514 Bliton, Mark S232 Bliwise, Donald L. S301 Blythe, Anne M819 Bockenek, William L. M819 Bodda, Chiranjeevi M1004 Boden-Albala, Bernadette M1403 Bodensteiner, John B. M1303 Boes, Benjamin M1008 Boeve, Bradley F. T1530 Boffa, Michael S302 Bonanni, Paolo M1002 Bonato, Sara M1002 Bondar, Galyna T1704 Boon, Andrea M826 Bordelon, Yvette S213 Borkowski, Thomas M. T1615 Borland, Scott T1617 Bota, Daniela T1804 Botuyan, Maria V. M1008 Boutin, Paula T1719 Boyd, Scott D. T1736 Bravver, Elena M814, M819 Brennan, K.C. T1601 Bresolin, Nereo M1002 112 ID: kannanb I Black Lining: [ON] I Time: 17:26 I Path: N:/3b2/ANA#/Vol00000/110247/APPFile/JW-ANA#110247 J_ID: ZAY Customer A_ID: SUPP11-9 Cadmus Art: 22582 Date: 26-August-11 Catellier, Diane J. T1505 Cava, Luis S113 Cen, Steven S221 Cervantes, Anna M. S122 Chai, High Seng T1503 Chana, Gursharan T1905 Chandrakumar, Manokaraananthan T1621 Chandrasekaran, Krish M801 Chang, Bernard S. M704 Charles, David S224, S232 Charles, P. David S226 Chaturvedi, Seemant S129 Chemali, Zeina S214 Chen, Chueh-Tan T1537 Chen, Helen M801 Chen, Honglei S208, S234 Chen, Jian M1301 Chen, Roujie M1403 Chen, Shun-Sheng T1537 Chen, Xinzhi S103 Chen, Yi T1715 Cheng, Chu M1402 Cheng, Hsinlin T. T1604 Cheng, Jiin-Tsuey T1537 Cheng, Ping M607 Cheng, Yuching S107 Cheong, Hae Kwan T1519 Chernoff, Jonathan M803 Cheung, Ying K. M1403 Chibnik, Lori B. T1502 Chipendo, Portia I. T1502 Chisulo, Brian T1908 Chitnis, Shilpa S210 Chiu, David S116 Cho, Chi T1740 Choi, Jae-Hwan S126 Choi, Kwang-Dong S126 Choi, Soon Gang M824 Chokroverty, Sudhansu M718 Choudary, Zahid S130 Choudary, Zahid I. S135 Choudhary, Shazia Z. S130, S135 Chretien, Nathalie T1721 Christensen, Jon T1901 Christie, Kimberly J. M1402 Christine, C.W. S204, S209 Christodoulou, Joanna A. M704 Christopher, Hanlon T. T1602 Chuang, Yu-Ming S106 Chun, Jerold T1710 Chung, Amy S. T1802 Churchwell, Mona I. T1511 Ciric, Bogojub T1725 Bressman, Susan B. Brewer, James B. Bringas, J. Britton, Jeffrey W. S233 T1514 T1529 M1202, M1203, S403 Broderick, D.F. S204 Broderick, Joseph S112 Brooks, Benjamin M821 Brooks, Benjamin R. M814, M819 Brooks-Kayal, Amy R. M705 Brott, Thomas G. S102, S116 Brown, Amanda S407 Brown, O.W. S102 Bruce, Nhu T. S131 Bryant, Monthaporn S. S215 Bucelli, Robert S406 Buckley, Camilla T1711 Buckley, Charlotte T1903, T1904 Bumbaugh, Jon T1614 Burakgazi, Evren T1620 Burakgazi-Dalkili, Evren M1205 Burge, Daniel J. T1724 Burger, Kathleen S127 Burke, James M1107 Buse, Dawn C. T1608, T1610, T1611, T1612, T1613, T1615 Bushara, Khalaf O. M602 Busta, Angela S. M804 Cacabelos, Ramon T1506 Cacciottolo, Mafalda M807 Cai, Haipeng M1301 Caillier, Stacy T1713 Callaghan, Brian M1005 Camargo, Carlos A. S139 Cambon, Alex C. S213 Campbell, Christina M1204 Campbell, Harry T1503 Campos-Rivera, Juanita T1719 Can, Karolina M1004 Cannigaiper Uthamaroyan, Velmurugendran S121 Cao, Chuanhai S202 Capehart, Bruce P. M1107 Caplan, Louis S136 Carlson, H. T1522 Carlson, Noel G. T1801 Carone, Marco S123 Carran, Melissa T1809 Carrasquillo, Minerva M. T1503 Carter, Alex R. M601 Casadesus, Gemma M620 Casanova, Vanessa M1002 Case, Amanda M1001 Castano, Anna M706 Stage: Page: 113 Clark, Chris M. Clark, K. Reed Clawson, Susan A. Clifford, David Clifton, Guy L. Cohen, Jeffery A. Cohen, Jeffrey Cohen, Jeffrey A. Coker, Laura H. Cole, John W. Collins, William Comi, Giacomo Comi, Giancarlo Conte, Mary M. Contractor, Anis Cook, Jason A. Corbetta, Maurizio Coresh, Josef Corey-Bloom, Jody T1508 M802 T1801 T1901 M1103 T1710 T1708 T1709 T1505 S107 T1709 M1002 T1708 M1104 T1701 S224 M601 T1505 S205, S220, T1507 Corrada, Maria M. T1508, T1524 Corrigan, John M828 Cote, Lucien S225 Couto, Joseph T1614 Cowell, Lindsay G. T1736 Crimella, Claudia M1002 Crook, Julia T1503 Crowder, Kermit S109 Cruz Del Angel, Yasmin M705 Cruz-Flores, Salvador T1513 Cudkowicz, Merit M821 Cuevas, Ivan T1506 Cunningham, Christopher R. S213 Cunningham, Julie M. M1008 Cutter, Gary T1702 D’Agostino, Carla M807, M808 Dakka, Youssef A. M828 Dalakas, Marinos C. T1729 Dale, Anders M. T1525 Dalmau, Josep T1701, T1716 D’Angelo, Grazia M1002 Das, Moromi S104 Dauch, Jacqueline R. T1604 David, William M821 Davis, Bonnie S109 Davis, Thomas L. S232 D’Cruz, O’Neill M714 De Jager, Philip T1720 De Jager, Philip L. T1502 DeArmond, S. S204, S209 DeCarli, Charles T1504 Decker, David A. S130, S135 Deeley, Cheryl S228 DeFreitas, Tiffani T1615 113 ID: kannanb I Black Lining: [ON] I Time: 17:26 I Path: N:/3b2/ANA#/Vol00000/110247/APPFile/JW-ANA#110247 J_ID: ZAY Customer A_ID: SUPP11-9 Cadmus Art: 22582 Date: 26-August-11 Elble, Rodger J. Eleopra, Roberto El-Hagrassy, Mirret Elkind, Mitchell S.V. Ellik, Shehanaz Elliott, Robin Ellis, Ronald J. Elsayed, Mohammad Engel, King W. M808, S140 S237 T1536 S101 M828 S216 T1905 M613 M816, M835 Engel, W. King M807 Ertekin-Taner, Nilufer T1503 Erten-Lyons, Deniz T1532 Eslinger, Paul J. S206, S212 Etemadifar, Masoud T1732 Evans, Denis A. T1502 Evensen, Laura A. M1403 Everall, Ian P. T1905 Faezi, Sholeh T1731 Fagan, Anne T1901 Fallah, A. T1712, T1723 Fang, Yin T1527 Fanning, Kristina T1608 Fanning, Kristina M. T1610, T1611 Fantin, Marianna M1002 Farber, Charles R. S115 Farheen, Amtul M833, M834, S134, S137 Farrer, Lindsay T1512 Farrer, Matthew J. S207 Fasih, Zoha S137 Fatima, Tasneem S229 Feany, Mel B. T1502 Feldman, Eva L. M804, M1005, T1604 Fennema-Notestine, Christine T1525 Fernandez, Lucia T1506 Ferrari, Michel T1617 Fields, Jeremy D. T1606 Figueroa-Romero, Claudia M1005 Filley, Christopher M. M616 Fincher, Linda S215 Finder, Stuart G. S232 Finlayson, Marcia T1740 Fire, Andrew Z. T1736 Fisher, Barbara C. M610, M614 Fisher, Mark S108 Fishman, Robert A. S124, T1806 Fitzpatrick, Annette T1513 Flagg, Emily S216 Flanagan, Eoin P. M811, T1805 Flanigan, Kevin M. M802 Flemming, Kelly D. S128 Forsayeth, John T1529 DeFries, Ashleigh T1534 Dekermenjian, Rony S134, S137 del Pilar Cortes Nino, Maria T1906 Del Tufo, Stephanie N. M704 Delaney, Colin E. M1005 Delgado, Monica T1705 Demaerschalk, Bart M. S102, S116 Denic, Aleksandar T1703 DeOrchis, Vincent S. T1518 Derani, Lena T1739 Desai, Urvi G. M819 Dham, Bhavpreet S223, T1620, T1809 Dhamija, Radhika S403 Diaz-Medina, Gloria E. S403 Dickson, D.W. S204, S209 Dickson, Dennis W. M1007, S207, T1503, T1515, T1530 DiClemente, Guillermo T1534 Diep, Lien S109 Dilley, Deanne M714 DiVito, Brittany M. M618, M619 Dodge, Hiroko T1532 Dodick, David T1617 Doerge, Daniel R. T1511 Dominantly Inherited Alzheimer Network T1501 Dorsey, E. Ray S402 Dosado, Lea M830 Doty, Pamela M713, M714 Dowling, James J. M804 Du, Guangwei S206, S212, S234 Du, Senxi T1804 Du, Sienmi T1704 Duane, Drake D. M618, M619 Dubinsky, Richard S213 Dueker, Nicole S107 Duncan, G. T1522 Duquette, Pierre T1713 Durand, Dominique M620 Dustin, Irene M702 Dyck, P. James M1008 Dyck, Peter J. M1008 Eastman, Alison J. M1001 Eastman, Eric T1736 Eberly, Shirley S216 Ebers, George T1702 Edland, Steven D. M1010, S205, T1531 Edlow, Jonathan A. S139 Edson, Jean S109 Edythe, Wiggs A. M820 Eizenamn, Moshe M607 Stage: Page: 114 Forst, Amy Foulds, Pamela Fountain, Nathan B. T1616 T1726 M713, M714 Fowkes, Mary E. M824 Francis, Gordon T1709 Frederick, Meredith C. M616 Freeman, William D. M1204 Friedland, Robert P. M1301 Frohman, Elliot M. T1736 Frost, Nicholas M723 Fry, Rebecca C. T1511 Fu, Beverly D. T1804 Fugate, Jennifer E. S128, T1714 Fuh, Jong-Ling T1605 Fujioka, Shinsuke M1007, S207 Fulda, Stephany M610, M614 Furuya, Hirokazu S201 Gabbard, Jennifer T1737 Gabrieli, John D.E. M704 Gadallah, Nancy S134 Galasko, Douglas T1525 Galasko, Douglas R. T1531 Galbraith, Sareen T1903 Galbraith, Sareen E. T1904 Gallagher, Martin J. M707 Gallin, Eliza S213 Gamez, Jeffrey T1727 Gamez, Jeffrey D. T1715 Ganeshan, Veena R. T1803 Garbern, J.Y. S204, S209 Garcia, Paul S. S301 Garden, Gwenn A. M1001 Gardiner, Irenita S228 Garges, Danielle M. M610, M614 George, Benjamin P. S402 Georgescu, Constantin T1503 Gerhardt, Greg A. M709 Ghaffarpour, Majid T1732 Ghaffar-Pour, Majid S114 Gharagozli, Kourosh T1731 Ghareghozli, Kourosh T1718 Ghargozlee, Kourosh T1732 Ghosh, Partha S. M1302 Ghoshal, Shivani S136 Ghragozlee, Kourosh S114 Gill, Chandler E. S224, S232 Gluhm, Shea S205, S220, T1507 Goadsby, Peter J. T1603, T1617 Gobinathan, Devathasan M830 Godfrey, Rena A. M820 Goetz, Christopher G. S211, S231 Gohar, Dina T1527 Gokhale, Sankalp S136 114 ID: kannanb I Black Lining: [ON] I Time: 17:26 I Path: N:/3b2/ANA#/Vol00000/110247/APPFile/JW-ANA#110247 J_ID: ZAY Customer A_ID: SUPP11-9 Cadmus Art: 22582 Date: 26-August-11 Hafler, David T1720 Hagerman, Paul J. T1521 Hagerman, Randi J. T1521 Hagler, Jr, Donald J. T1525 Haines, Jonathan T1512 Haleem, Darakhshan Jabeen S229 Hall, Charles T1615 Hall, Deborah A. S213 Hall, Ira M. S115 Hallett, Mark M602 Halvorsen, Mark B. M710 Hamby, Mary T1704 Hammans, Simon M1008 Hanna, Michael M831 Happ, Erik T1806 Hara, Hajime M829 Harbour, Leia S109 Hardy, Duriel M1401 Ha¨ring, Dieter A. T1707 Harman, Jennifer S216 Haro SIlva, Rube´n M617 Harper, Charles M. M811 Harris, Tamara B. T1504 Hart, Ian J. T1903, T1904 Hartung, Hans-Peters T1708 Hasegawa, Yasuhiro S120 Hassan, Anhar M826 Hastie, Nicholas D. T1503 Hatemian, A. S114 Haut, Sheryl R. T1615 Hayward, Caroline T1503 Heck, Donald V. S102 Heiss, Wolf-Dieter T1510 Heister, David S. T1514 Hemmen, Thomas M. S105 Henchcliffe, Claire S213 Hendrix, Suzanne T1516, T1517, T1523, T1526 Heppner, Frank L. M835 Hernandez, Leticia S230 Herr, Barbara M831 Heshmat, Ramin T1722 Hill, Kenneth E. T1801 Hillis, Argye E. M605, M612, S125, S132 Hinson, Vanessa S219 Hinton, Sabrina S129 Hirano, Makito T1520 HNRC Group T1905 Hocker, Sara M1202, M1203 Hogan, Edward M708 Hohjoh, Hirohiko S201 Hohlfeld, Reinhard T1707 Holland, Dominic T1525 Hollenbeck, Albert S208 Goldfarb, Neil T1614 Goldfine, Andrew M. M1104 Goldman, Jennifer G. S211 Goldstein, Jerome T1618 Goldstein, Jody S205, S220, T1507 Goltz, Herbert C. T1621 Gomez, Megan S221 Gomez, Yessenia M605 Gonnella, Patricia T1725 Gonzalez, Marco I. M705 Goodin, Douglas S. T1702 Goodman, B. S204, S209 Gordon, Barry M613 Gottdiener, John T1513 Gottesman, Rebecca F. S125, S132, T1505, T1513 Gourraud, Pierre-Antoine T1713 Govindarajan, Raghav M822 Grabenstatter, Heidi L. M705 Grabstein, Kenneth T1724 Graff-Radford, Jonathan M606, T1714 Graff-Radford, Neil T1515 Graff-Radford, Neill R. T1503 Grafton, Scott T. M604 Graham, Stephen M. T1516, T1517, T1523, T1526, T1533 Green, Peter H. M602 Greenberg, Benjamin M. T1736 Greenfield, L. John S404 Greenia, Dana E. T1508 Greenlee, John E. T1801 Greenspan, Ralph J. M1006 Grewal, Raji M833 Griffiths, Michael T1904 Griffiths, Mike T1903 Griggs, Robert C. M831 Grinspan, Augusto T1707, T1708 Groden, Catherine A. M820 Grossardt, Brandon R. T1703 Gu, Yian S225 Gualdi, Sabrina S237 Guo, Fuzheng T1705 Guo, Jiasong M803, M813 Guo, Xuguang S208 Gupta, Divya M718 Gupta, Varun M816 Gutmann, Laurie S236 Gutmann, Ludwig S236 Guzik, Amy K. S115 Habermann, Thomas M. T1805 Hachinski, Vladimir T1510 Stage: Page: 115 Holtzman, David T1901 Hong, Yu M1005 Hopkins, Mark T1903, T1904 Hopkins, Mary T1614 Hornung, Richard S112 Hou, Jing T1527 Hou, Jyhgong Gabriel S215 Howard, George S102, S116 Howard, Katherine L. M616 Hsieh, Yu-Hsiang S139 Huang, Juebin M1301 Huang, Xuemei S206, S208, S212, S234 Huentelman, Matthew A. T1502 Huh, Young Eun S138 Hui, Jennifer S. S221 Hur, Junguk M1005 Husain, Samea S218 Husan, Shema S229 Hussain, Tiki S222, S227, S235 Hye, Robert J. S102 Ikeda, Ken M812 Ikuno, Yasushi T1520 Irani, Sarosh T1711 Ishihara, Ryu T1520 Isobe, Noriko M1009, T1706 Isojarvi, Jouko M713 Itoh, Noriko T1704 Iwahashi, Hiromi T1520 Iwasaki, Yasuo M812 Iwashita, Julie T1616 Iyadurai, Stanley M720, T1607 Iyadurai, Stanley J. M815 Jack, Clifford T1503 Jack, Clifford R. T1530 Jack, Jr., Clifford R. M606, T1505 Jackson, Dan M1204 Jackson, Leila S213 Jacobson, Mark T1507 Jacobson, Mercedes S401 Jaffer, Zahara M. M803 Jankovic, Joseph S213 Ja¨rvinen-Pasley, Anna M608 Javan, Alireza K. T1521 Javedani, Parisa P. T1606 Jayadev, Suman M1001 Jayam-Trouth, Annapurni S109 Jeffrey, Kaye T1532 Jen, Jin T1503 Jenkins, Andrew S301 Jensen, Michael D. M606 Jeon, Seun T1519 Jianfeng, Cai S202 Jiang, Shan H. T1908 Jimi, Takahiro M829 115 ID: kannanb I Black Lining: [ON] I Time: 17:26 I Path: N:/3b2/ANA#/Vol00000/110247/APPFile/JW-ANA#110247 J_ID: ZAY Customer A_ID: SUPP11-9 Cadmus Art: 22582 Date: 26-August-11 Kim, Chi Hun T1519 Kim, Jae Seung T1519 Kim, Ji Soo S138 Kim, Suk-Hui T1519 Kim, Sung Tae T1519 Kimonis, Virginia E. M805 Kimura, Fumihiko T1733 Kira, Jun-ichi M1009, T1706 Kisby, Glen E. T1511 Kissel, John M806 Kittner, Steven J. S107 Klein, Christopher J. M1008 Kleschevnikov, Alexander M. M712 Klingstedt, There´se M835 Kluger, Benzi S213 Knappertz, Volker T1702 Knopman, David S. T1505, T1530 Ko, Nerissa S112 Koch, Heather A. M618, M619 Koffmann, Boyd S404 Kolbert, Christopher P. T1503 Kompoliti, Katie S231 Kong, Xiao-Tang T1804 Konrad, Peter E. S232 Korczyn, Amos D. T1535 Kori, Shashidhar T1603, T1616, T1617 Koubeissi, Mohamad Z. M620, M1301 Koyfman, Feliks S122 Krauss, Gregory M714 Kremenchutzky, Marcelo T1702, T1707 Kronk, Lisa M817 Kronmal, Richard T1513 Kumar, Bishwanath M1003, S104 Kumar, Sunil M1003 Kunschner, Lara T1806 Kunyu, Li S202 Kupsky, W. S209 Kurantsin-Mills, Joseph S109 Kurlan, Roger S216 Kurtzke, John F. T1730 Kusunoki, Susumu M818, T1520, T1733 Kuwabara, Motoi T1733 Kuwahara, Motoi M818 Kwagyan, John S109 Kwan, Justin Y. M820 Lai, Eugene C. S215 Laidlaw, David H. M1301 LaManna, Joseph M620 Lambrecht, Lawrence J. M710 LaMorte, Michael T1721 John, Sanjna M. Johnson, Aaron J. Jones, Timothy F. Josephs, Keith A. T1906 T1715 M823 M606, M811, T1515, T1530 Joshi, Abhinay D. T1508 Jovic, Sofija T1534 Ju, Y. Sungtaek T1601 Juarez, Humberto S230 Juncos, Jorge S213 Kaida, Ken-ichi T1733 Kalita, Jayantee M1003, S104 Kalyanam, Janaki S109 Kamakura, Keiko T1733 Kanazawa, Ichiro S201 Kang, Huicong S110 Kano, Osamu M812 Kaplan, Johanne T1719, T1721 Kappos, Ludwig T1707, T1708, T1709 Karageorgiou, Clementine E. T1729 Karagogeos, Domna T1729 Karanam, Deepthi M717 Karimi, Mehdi S114 Karin, Ernstrom S105 Karpf, Adam R. M1008 Karunapuzha, Cherian A. S210 Kasarda, Donald D. M602 Kase, Carlos S. S122 Kashouty, Rabih M722, S133, T1808 Kaspar, Brian M802 Kassar, Darine M720, T1607 Kass-Hout, Omar S117 Kass-Hout, Tareq S117 Katzir, Tami M704 Kaubrys, Gintaras M713 Kavanagh, Terrance J. T1511 Kawabe, Kiyokazu M812 Kawano, Yuji T1706 Kawas, Claudia H. T1508, T1524 Ke, Qing M831 Keegan, B. Mark T1805 Keenan, Brendan T. T1502 Kellerman, Don T1616 Kells, Adrian P. T1529 Kelly, John T1620 Kelly, Kevin M. M701 Khan, Omar M702 Khanna, Ashwani T1717 Kharlamov, Elena A. M701 Khatri, Bhupendra O. T1708 Khitrov, Greg M824 Kiernan, Matthew T1711 Kifayathulla, Liakath Ali M1004 Stage: Page: 116 Lancaster, Eric T1701 Lander, Cecilie M1008 Lang, Anthony E. S216 Lange, Dale J. M824 Langford, Velma L. M814, M819 Larery, Angela T1522 Lasarev, Michael R. T1511 Lash, J. S204, S209 Latov, Norman M602 Lau, Helena S122 Lazar, Ronald M. M1403 Leblang, Spencer A. M618, M619 Ledoux, Kerry M613 Lee, Christopher D. M823 Lee, Jae-Hong T1519 Lee, John D. M615 Lee, Jong-Min T1519 Lee, Joseph T1512 Lee, Michael M703 Lee, Seung-hun S118 Lee, Szexian T1802 Leep Hunderford, Andrea M826 Lees, Monica M615 Lees, Peter S213 Lehky, Tanya J. M820 Leimgruber, Pierre P. S116 Leone, Paola S223 LeRoy, Robert F. M714 Lessig, Stephanie S205, T1507 Leverenz, James S213 Levesque, Jessica T1807 Levitt, Jacob M831 Lewis, Mechelle M. S206, S212, S234 Li, Chin-Shang M703 Li, Jun M803, M810, M813 Li, Sean S. S115 Li, Wang S202 Lieberman, Abraham S222, S227, S235 Lieberman, Abraham N. S218 Ligocki, Ann J. T1736 Lin, Wen-Lang T1515 Lin, Xiaoyang S202 Lincoln, Sarah T1503 Lindblom, Scott C. M814, M819 Linskey, Mark E. T1804 Lipton, Richard T1617 Lipton, Richard B. S233, T1608, T1610, T1611, T1612, T1613, T1615 Lipton, Stuart A. T1509 Lirng, Jiing-Feng T1605 Litchy, William J. M1008 Litvan, Irene S213 Liu, Kenneth C. T1606 116 ID: kannanb I Black Lining: [ON] I Time: 17:26 I Path: N:/3b2/ANA#/Vol00000/110247/APPFile/JW-ANA#110247 J_ID: ZAY Customer A_ID: SUPP11-9 Cadmus Art: 22582 Date: 26-August-11 Marsh, Elisabeth B. S125, S132 Marshall, Randolph S. M1403 Marshall, Theresa S404 Martens, William B. M806 Martinez, Ashley M702 Martinez, Jose A. M1402 Martinez-Hernandez, Eugenia T1701, T1716 Martinuzzi, Andrea M611, M1002, S237 Masaki, Kamal H. S203 Masaki, Katsuhisa M1009, T1706 Masliah, Eliezer M609 Mastorodemos, Vasileios M603 Mateen, Farrah J. S123 Matsushita, Takuya M1009, T1706 Mattson, Mark P. S103 Matveeva, Elena E. M709 Matyushov, Alexei M1201 Mayeux, Richard T1512 McArthur, Justin C. S407 Mcavoy, Mark P. M601 McCague, Kevin T1735 McCauley, Stephen R. M1103 McCracken, Lindsey T1716 McDermott, Michael P. M806 McDonald, Jamie T1713 McEvoy, Linda K. T1514, T1525 McGarry, Megan M621, M717, T1738 McShea, Cindy M713 Mehia-Santana, Helen S225 Mehlenbacher, Adam M1107 Mehta, Bijal S117 Meira, Lisiane B. T1511 Mejia, Nicte S214 Melman, Tamar T1802 Mendell, Jerry R. M802 Mendoza, Jesus F. T1907 Meng, Cheryl S216 Meng, Xiangyi T1707, T1708 Meola, Giovanni M1002 Mer, Georges M1008 Meschia, James F. M1204, S102, S116 Metcalf, Nick M601 Meyer, Brett C. S131 Meysamie, A. T1712 Michael, Benedict D. T1903, T1904 Middha, Sumit M1008, T1503 Miglis, Mitchell G. S302 Miller, Alistair T1903, T1904 Miller, Eric R. M701 Liu, Rui S208 Liu, Shuo S108 Liu, Xinyeu S107 Liu, Yu M1401 Llinas, Rafael H. S125, S132 Lohrey, Anne K. T1715 Lok, Edwin T1802 Lombardi, Valter T1506 Longbottom, Mary E. S116 Longstreth, Jr., W.T. T1513 Lowes, Linda P. M802 Lu, Bo M701 Luders, Hans M620 Luke, Sothear M1204 Luna, Jennie M717, M721, T1619 Lunn, J. Simon M804 Lunn, John S. M1005 Luo, Benyan M831 Luthra, Indermohan M816 Ma, Joyce T1705 Ma, Li T1503 Maccotta, Luigi M708 Macura, Slobodan T1703 Macura, Slobodan I. T1727 Mada, Flicia S129 Madjid, Keyvani T1609 Maeda, Yoshiko T1705 Maganti, Sombabu M718 Magda, Sebastian T1514 Maghzi, Amir Hadi T1732 Mahadevan, Anita M822 Mahajan, Shalini M816 Mahaparn, Irisa M609 Maharjan, Sooraj T1503 Mailman, Richard B. S234 Malhotra, Konark S111 Malhotra, Manoj T1735 Malik, Tafheem S229 Malikova, Irina T1713 Malow, Beth A. S303 Malphrus, Kimberly G. T1503 Manack, Aubrey N. T1608, T1612 Mandell, Daniel M1105 Mandrekar, Jay M1202, M1203 Manivanh, Richard T1506 Mannan, Ashraf U. M1004 Mano, Toshiyuki T1520 Mantese, Vito A. S116 Manus, Neil D. S224 Marchidann, Adrian S133 Marder, Karen S216 Marder, Karen S. S225 Marek, Kenneth S216 Marras, Connie S213 Stage: Page: 117 Miller, Michael L. T1516, T1517, T1523, T1526 Miller, Timothy M. M821 Millis, Scott S129 Ming, Ming M831 Mintun, Mark A. T1508 Misra, Usha K. M1003, S104 Mitchell, Amber N. T1807 Mitchell, Braxton D. S107 Mitchell, James F. S107 Mittal, Balraj M1003, S104 Mobley, William M712 Moeller, Thomas M1001 Mohammad, Yousef S119 Mohammad, Yousef M. S111 Mokin, Maxim S117 Molina, Enrique S230 Molinari, Anna L. S224, S226, S232 Molteni, Silvia S237 Mondani, Massimo S237 Monson, Nancy L. T1736 Moodley, Manikum M1302 Moomaw, Charles S112 Moon, In Soo S126 Moon, Yeseon P. S101 Moore, Ryan P. M609 Moretti, Paolo M1103 Morgan, Kevin T1503 Morris, John T1901 Morrison, Richard S. M1001 Morrow, Leslie S301 Moseley, Brian D. S403 Moshirzadeh, Sasan T1718 Mosley, Thomas H. T1505 Mowry, Ellen M. T1713 Mozaffar, Tahseen M805 Mtchedlishvili, Zakaria M701 Muldowney, James S303 Multani, Manpreet M833 Murata, Kiyoko M812 Murata, Miho S201 Musumeci, Olimpia M1002 Myers, Iliza M810 Na, Duk L. T1519 Nafissi, Shahriar T1722 Nagahara, Alan T1529 Nagata, Riya M812 Nair, Asha A. T1503 Nakamura, Yusaku T1520 Nanakul, Rawi T1521 Nance, Matthew T1522 Nath, Avindra S407 Naylor, David E. M716 Neafsey, Edward S405 Nehrebecky, Michele E. M820 117 ID: kannanb I Black Lining: [ON] I Time: 17:26 I Path: N:/3b2/ANA#/Vol00000/110247/APPFile/JW-ANA#110247 J_ID: ZAY Customer A_ID: SUPP11-9 Cadmus Art: 22582 Date: 26-August-11 Parent, Jack M. M1401 Parisi, J.E. S204, S209 Parisi, Joseph E. M1008, T1515, T1530 Park, Yikyung S208 Parker, Kathy S301 Parkinson Study Group S228 Pascual, Franchette M703 Patel, Vivek S140 Pati, Sandipan M715, M1201 Paul, Joya S119 Pavlakis, Pantelis P. T1729 Paz Soldan, M Mateo T1715 Paz Soldan, Mateo S403 Pazdera, Ladislav M724 Pearlman, Starr H. T1613 Pease, Larry M1101 Pease, Larry R. T1703 Peavy, Guerry T1507 Pedraza, Otto T1503 Pejovic, Vojislav T1516, T1517, T1523, T1526 Pelletier, Jean T1708, T1713 Pelster, Michael W. S224 Peltier, Amanda C. M810 Peltz, Carrie B. T1508, T1524 Perez, Veronica M1403 Perhach, James T1533 Pericak-Vance, Margaret T1512 Peruch, Francesca M1002 Pervez, Shahid S229 Pestreich, Linda T1735 Pestronk, Alan M815, M821 Petacchi, Elisa S237 Petersen, Bryan T1606 Petersen, Ronald C. M811, T1503, T1515, T1530 Petrovitch, Helen S203 Pettingill, Philippa T1711 Pettingill, Rosie T1711 Phibbs, Fenna T. S226 Picard, Christophe T1713 Piccoli, Sara M611 Pickett, Erin J. M613 Pikula, Aleksandra S122, T1504 Pillai, Jagan M1010, S205, S220 Pillai, Jagan A. T1525 Pin˜a-Crespo, Juan C. T1509 Pirko, Istvan T1703, T1715, T1727 Plaitakis, Andreas M603 Pleasure, David T1705 Plow, Ela B. T1527 Plow, Matthew A. T1740 Polasek, Ozren T1503 Pomerants, Polina S401 Neil, William P. Neiman, Eli S. Newman-Toker, David E. S105 M718 S118, S139 Ng, Rowena M608 Ng-Mak, Daisy S. T1613, T1614 Nguyen, Thanh N. S122 Nguyen, Thuy T1503 Nichols, Mindy S. M814, M819 Nicholson, Garth A. M1008 Nilsson, Peter K.R. M835 Nogalska, Anna M807, M808, M835 Nourian, A. S114, T1732 Oakes, David S216, S228 Oaklander, Anne Louise M825 O’Connell, Jeffrey R. S107 O’Connor, Paul T1707 Ogawa, Go T1733 Oger, Joel T1702 Oh, Sang Su M804 Oh, Seung Jun T1519 Ohishi, Mitsuru T1520 Olichney, John M. T1521 O’Neill, Brian P. T1805 O’Neill, Mifflin M819 Onken, Mitch M801 Opler, Mark T1534 Oplinger, Heather M819 Ottoboni, Linda T1720 Ouyang, Bichun S119 Owens, Michael J. S301 Ozelius, Laurie J. S233 Paccico, Thomas J. M819 Pacut, Crystal M1005 Paganini-Hill, Annlia S108 Paik, Myunghee C. S101 Pakdaman, Hosein T1734 Pakdaman, Hossein S114, T1712, T1722, T1723, T1731, T1732 Pakdaman, Hossien T1718 Pakdaman, Reza T1712, T1723 Palmer, Valerie S. T1511 Palusak, Ryan T1503 Pan, Dengji S110 Pan, Di S222, S227, S235 Pan, Yue S. T1908 Pandya, Dipak T1737 Pandya, Dipak P. M621, M717, M721, T1619, T1738 Pandya, Shree M806 Pankratz, V. Shane T1503 Panou, Theodora M603 Papadaki, Efrosyni M603 Paparella, Gabriella M611, M1002 Stage: Page: 118 Pontecorvo, Michael J. T1508 Pope, Daniel L.W. M601 Prabhakaran, Shyam S119 Pracilio, Valerie P. T1614 Prakash, Neal T1601 Presti, Michael F. S403 Prokop, Stefan M835 Rabinstein, Alejandro A. M1202, M1203, S128, T1714 Race, David S. M612 Rademakers, R. S204, S209 Rademakers, Rosa S207 Radlinska, Basia T1510 Radue, Ernst-Wilhelm T1707 Rahimian, E. T1723 Rai, Shesh N. S213 Rajamani, Kumar S129 Rajput, Alex H. S217 Rajput, Ali H. S217 Rajput, Michele L. S217 Raman, Rema S105 Rametta, Mark T1702 Ramos-Crawford, Ana-Luisa T1511 Ramsey-Williams, Vicki S404 Rangaraju, Srikant T1902 Ranjan, Tulika T1808 Rao, Sambasiva T1719 Raol, Yogendra H. M705 Rashid, Saifur M620 Rasmuss, Brett M712 Ravina, Bernard S216 Raymond, Deborah S233 Reda, Haatem S403 Reder, Anthony T. T1702 Reed, Michael T1613 Reed, Michael L. T1608, T1610, T1611 Reeves-Tyer, Patricia M702 Reich, Stephen S213 Reiman, Eric M. T1502 Reitz, Christiane T1512 Reminick, Jason I. S402 Ren, Xuefeng T1511 Rengachary, Jennifer M601 Renterı´a Palomo, Ana A. M617 Riley, David S213 Ritchie, James C. S301 Rivera, Susan M. T1521 Rizzo, Matthew M615 Roberts, Bruce T1719, T1721 Robinson, Karen A. S118 Rodriguez, Alcibiades S302 Rodriguez, Ildefonso T1907 Rodriguez, Jeronimo T1907 118 ID: kannanb I Black Lining: [ON] I Time: 17:26 I Path: N:/3b2/ANA#/Vol00000/110247/APPFile/JW-ANA#110247 J_ID: ZAY Customer A_ID: SUPP11-9 Cadmus Art: 22582 Date: 26-August-11 Santiago, Anthony S218, S222, S227, S235 Sanz-Blasco, Sara T1509 Sarkar, Korak M1102 Sarwar, Aliya S215 Sato, Susumu M702 Sauerbeck, Laura S112 Saunders-Pullman, Rachel S233 Scarmeas, Nicholas S225 Schiff, Nicholas C. M1104 Schirrmacher, Ralf T1510 Schneck, Michael J. S405 Schneider, Andrea T1521 Schneider, Julie A. T1502 Schofield, Lesley T1735 Schor, Nina F. T1803 Schretlen, David J. M613 Schwarzchild, Michael S216 Schweitzer, K.J. S204, S209 Scoglio, Nicholas J. S402 Scott, Bonnie M. T1522 Scott, James N. M1103 Scott, Thomas T1726 Sealfon, Stuart C. M824 Sen, Saurav M721 Sen, Sourav T1619 Sen, Suman S206, S212 Sennett, Cary T1614 Seo, Sang Won T1519 Seritan, Andreea T1521 Serrano, Daniel T1612, T1613 Seshadri, Sudha T1504 Severy, Peter T1719 Seyal, Masud M703 Shaffer, Michel L. S212 Shaffer, Michele L. S206, S234 Shah, Amol T1905 Shah, Anish M721, T1619 Shah, Umang M719 Shahbazi, Mona M824 Shahbegi, Said S114 Shahbeigi, Saeed T1734 Shahkarami, Mohammad Amir T1722 Shahlaie, Kia M1102 Shamim, Ejaz M602 Shankar, S.K. M822 Shankara, Srinivas T1719 Sharpe, James A. M607, T1621 Sharrett, A. Richey T1505 Sheikh, Kazim M809 Shepherd, Cassandra S213 Shibata, Dean K. T1505 Shijie, Song S202 Shimizu, Kanako S120 Shin, Robert K. M723 Rodriguez, Moses M1101, T1703, T1727 Rodrı´guez Leyva, Ildefonso M617 Roeber, S. S204, S209 Rogaeva, Ekaterina T1512 Roger, Elaine T1713 Romero, Jose R. S122 Rosales, Xiomara Q. M802 Rose, Kathryn M. T1505 Rosenbaum, Anna V. M723 Rosenberg, Michael S134 Rosenfeld, William M713 Ross, Owen A. S207 Rossetto, Mariagiovanna M1002 Rostami, Abdolmohamad T1725 Rothman, Brian T1534 Rothner, A.D. M1302 Rothrock, John F.S113, T1602, T1609 Rothstein, Jeffrey M821 Roubenoff, Ronenn T1504 Rounds, William H. T1736 Rowley, Christopher N. T1503 Royal, III, Walter T1717 Rudan, Igor T1503 Ruhoy, Ilene M1304 Rumbaugh, Jeffrey A. T1902 Rundek, Tatjana S101 Russek, Shelley J. M705 Russell, James W. M801 Russo, Priscilla M819 Rye, David B. S301 Saber Tehrani, Ali S. S118, S139 Sabouri, Amir H. T1905 Sacco, Ralph L. S101 Sadzewicz, Lisa K. S107 Safavi, Farinaz T1725 Sahenk, Zarife M802 Sahraian, Mohammad T1732 Sahraian, Mohammad Ali T1712, T1723 Sakowski, Stacey A. M804 Salami, Shiva T1722 Salim, Sumaiya S137 Salins, Naomi S218, S222, S227, S235 Salmon, David P. T1525 Salowich-Palm, Leeza S129 Salvador, Santamaria S230 Samadpour, Reza T1731 Samson, Leona D. T1511 San Luciano, Marta S233 Sanchez-Ramos, Juan S202 Sancho, Jose T1719 Sando, Sigrid B. T1503 Sanjak, Mohammed S. M819 Stage: Page: 119 Shiramizu, Bruce S407 Shojaee, Maziar T1731 Shojaei, Maziar T1718 Shoulson, Ira S216 Shprecher, David S213 Shtilbans, Alexander M824 Shulman, Gordon L. M601 Shulman, Joshua M. T1502 Shuster, E.A. S209 Shy, Michael E. M803 Siddiqui, Fazeel S140 Siders, William T1719, T1721 Siemionow, Vlodek T1527 Silber, Michael H. M811 Silberstein, Stephen T1603, T1614 Silbert, Lisa T1532 Sillau, Stefan M616 Silva, Jessica M613 Simon, Mariella M1008 Simos, Panagiotis G. M603 Simpson, Ericka M821 Simpson, Ericka P. M832, T1728 Simuni, Tanya S228 Singh, Anuradha S302 Singleton, Robinson J. T1604 Skrap, Miran S237 Slevin, John T. M709 Sloan, Michael S130, S135 Smith, David I. M1008 Smith, Glenn E. M1008 Smith, Gordon A. T1604 Smith, Jonathan H. S403 Smith, Richard M821 Smith-Hammond, Carol M1107 Snider, Barbara J. S406 Snyder, Abraham Z. M601 So, Norman K. M711 Sofroniew, Michael T1704 Solomon, Tom T1903, T1904 Somarajan, Bindu I. M1003, S104 Song, Yanna S226, S303 Sorenson, Eric M826 Sorenson, Eric J. M817 Soucy, Jean-Paul T1510 Spence, Rory T1704 Spencer, Peter S. T1511 St. George-Hyslop, Peter T1512 St. Louis, Erik K. M811 Standaert, David S213 Stankiewicz, James M. S408 Stanley, Kaili M. S233 Statland, Jeffrey M. M806 STEADY PD Investigators S228 119 ID: kannanb I Black Lining: [ON] I Time: 17:26 I Path: N:/3b2/ANA#/Vol00000/110247/APPFile/JW-ANA#110247 J_ID: ZAY Customer A_ID: SUPP11-9 Cadmus Art: 22582 Date: 26-August-11 Toscano, Antonio Tosches, William Tramontana, Michael G. Tran, Dong Traynor, Bryan J. Trenerry, Max R. Trotti, Lynn Marie Tselis, A. Tufail, Yusuf M715, Turkel, Catherine C. M1002 M1105 S232 T1502 M820 M606 S301 S209 M1201 T1608, T1612 Turner, Travis H. S219 Tuszynski, Mark H. T1529 Tyler, William J. M715, M1201 Ueda, Masami M818 Uitti, Ryan S213 Umaiorubahan, Meenakshisundaram S121 Umeda, Elizabeth T1704 Uyehara-Lock, Jane H. S203 Vallurupalli, Srikanth S140 Van Gerpen, J.A. S204, S209 Van Keulen, Virginia M1101 Van Liew, Charles S205, S220, T1507 Van Loveren, Harry R. S130, S135 Van Ness, Paul C. M711 Vanaman, Thomas C. M709 Vannorsdall, Tracy D. M613 Varon, Sepideh F. T1612 Vasan, Ramachandran S. T1504 Vaughan, Douglas E. S303 Vazquez, Gilberto T1907 Vecera, Shaun M615 Velazquez-Rodriguez, Yadira M1205 Veloski, Jon S223 Venkatasubramaniam, Shankar S121 Verghese, Joe T1518 Verma, Aparajitha K. M832 Vestri, Alec M611 Victor, Jonathan D. M1104 Vieira, Julio R. S101 Vigo, Carmen T1506 Villoslada, Pablo T1713 Vincent, Angela T1711 Viollet-Callendret, Laurence M802 Voeks, Jenifer H. S102, S116 von Rosenstiel, Philipp T1707 Voskuhl, Rhonda T1704 Vysata, Oldrich M724 Wada, Keiji S201 Wagner, Daymond S206, S212 Stebbins, Glenn T. S211, S231 Stern, Barney J. S107 Stewart, Anna T1903, T1904 Stine, Oscar C. S107 Stites, Tracy T1708 Stouter, Josephine T1522 Strongosky, Audrey M1007 Struck, Peter M834 Strutt, Adriana M. T1522 Sullivan, Robert S. T1511 Sundal, C. S204, S209 Sundar, Kaushik S121 Sung, Kyongje M613 Sura, Ankit M801 Suter, Ueli M803 Suzuki, Seiko M818 Swanson, Kenneth D. T1802 Tabasi, M. S114 Tabatabae, Al S114 Takahashi, Masaki S201 Talantova, Maria V. T1509 Tallon, Luke J. S107 Tan, Caroline M602 Tanaka, Ichiro T1520 Tang, Dejun T1709 Tang, Zhouping S110 Tanner, Caroline M. S203, S216 Tawil, Rabi M806 Tayal, Ashis S124 Taylor, Glyn T1616 Teich, Douglas L. T1622 Tenderini, Erika M1002 Tennen, Howard T1615 Tepper, Stewart T1603, T1617 Teshome, Mengesha T1901 Thant, Minn S215 Thawani, Sujata S302 Theodore, William H. M702 Theriot, Jeremy J. T1601 Thiel, Alexander T1510 Thomas, Jewell T1901 Thomas, Tracy T1616 Tilluckdharry, Natasha M621, T1738 Timaran, Carlos H. S116 Ting, Jess M824 Title, Wallace S224 Titulaer, Maarten J. T1701, T1716 Tobias, Kathy T1735 Tocco, Michael T1516, T1517, T1523, T1526 Todd, Wesley M. M710 Toga, Arthur W. T1601 Tokuyama, Yoshiaki S120 Toro, Camilo M820 Stage: Page: 120 Wagner, Jenee M1006 Wagner, Kathryn R. M806 Wakayama, Yoshihiro M829 Walgren, Kristy M819 Walker, Linsey M. M704 Wallace, Douglas C. M1008 Wallin, Mitchell T. T1730 Wang, Aijun T1724 Wang, Chunyang M719 Wang, Jay-Ming S130, S135 Wang, Lily S226, S303 Wang, Min T1603, T1617 Wang, Morgan S130 Wang, Shuu-Jiun T1605 Wang, Wei S110 Wang, Yen-Feng T1605 Ward, Amber L. M814, M819 Ward, Christopher J. M1008 Warrington, Arthur M1101 Warrington, Arthur E. T1703 Watanabe, Osamu T1711 Watanabe, Shoko S201 Waters, Patrick T1711 Watson, James M826 Watson, Sam S129 Waubant, Emmanuelle T1713 Webber, Christine A. M1402 Webster, Ross S203 Weibelt, Silvia M. T1602 Weihl, Chris M815 Weiner, Howard T1720 Weiss, John H. M805 Werner, Perla T1535 Westwood, Andrew J. T1504 White, Lon R. S203 Whiteheart, Sidney W. M709 Whitfield-Gabrieli, Susan M704 Whitwell, Jennifer M606 Whitwell, Jennifer L. T1530 Wicklund, Meredith S403 Wider, C. S204, S209 Wiggs, Edythe M702 Wijdicks, Eelco F.M. M1202, M1203, S128 Wilde, Elisabeth A. M1103 William, Gahl M820 Williams, Nicole M. M814, M819 Wilson, Karen R. S130, S135 Winblade Nairn, Natalie T1724 Winner, Paul T1603 Wojna, Valerie S407 Wolf, Philip A. T1504 Woltjer, Randy T1532 Wong, Agnes M. T1621 Wong, Amy S109 120 ID: kannanb I Black Lining: [ON] I Time: 17:26 I Path: N:/3b2/ANA#/Vol00000/110247/APPFile/JW-ANA#110247 J_ID: ZAY Customer A_ID: SUPP11-9 Cadmus Art: 22582 Date: 26-August-11 Xu, Xiaohua M1101 Xue, YuanYuan T1728 Yamanishi, Hiromitch M1008 Yamashita, Toshihide T1520 Yan, Qing M803, M813 Yanagihara, Keiko T1520 Yang, Fan S108 Yang, Lauice S221 Yanik, Brandon M. T1604 Yavorsky, Christian T1534 Yin, Hong Z. M805 Yonekawa, Tomomi M1009, T1706 Yono, Noor M722, S133, T1808 York, Michele K. T1522 Yoshihiro, Anna M715, M1201 Yoshii, Yasuhiro M812 Yoshimura, Satoshi M1009, T1706 You, Xiaojun T1726 Younger, David S. M827 Wong, Eric T. T1622, T1802 Wong, Sarah T1701 Wood, Blair T1801 Woodruff, B.K. S204, S209 Worrall, Bradford B. S115 Wozniak, Marcella A. S107 Wright, Alan T1503 Wright, Brent M1101 Wright, Kathryn A. M819 Wszolek, Z.K. S204, S209 Wszolek, Zbigniew T1503 Wszolek, Zbigniew K. M1007, S207 Wu, Yanhong M1008 Wyant, Alexandria T1527 Wymbs, Nicholas M604 Xiang, Diane T1736 Xu, Feng S110 Xu, Jian T1701 Xu, Kui M620 Stage: Page: 121 Younkin, Curtis S. Younkin, Steven G. Yu, Alexander Yu, Chuanhui Yue, Guang H. Yung, Raymond Zarbl, Helmut Zerafati, Gazelle Zghouzi, Mohamed Zhang, Gang Zhang, Xuebao Zhang-Auberson, Lixin Zhou, Yun Zhu, Suiqiang Zimmerman, Earl Zinn, Kristi Zivadinov, Robert Zochodne, Douglas W. Zou, Fanggeng 121 ID: kannanb I Black Lining: [ON] I Time: 17:26 I Path: N:/3b2/ANA#/Vol00000/110247/APPFile/JW-ANA#110247 T1503 T1503 T1622 S108 T1527 M1005 T1511 S223 S119 M809 M803 T1707, T1709 S118 S110 T1807 M601 S117 M1402 T1503 J_ID: ZAY Customer A_ID: SUPP11-10 Cadmus Art: 22584 Date: 31-August-11 Stage: Page: 122 WIP AUTHOR INDEX Fanin, Marina M838 Federici, Thais M840 Feldman, Eva M840 Ferrucci, Luigi T1539 Florez, Carlos M. M729 Gandy, Sam T1538 Gangadharan, Beena T1743 Garg, Rajeev S143 Glabe, Charles T1538 Glass, Jonathan D. M840 Goate, Alison T1541 Gonzalez, R. G. M1206 Govindarajan, Raghav T1747 Grachev, Igor D. S240 Green, Mark W. T1623 Grisham, Mathew B. T1746 Grossman, Murray T1542 Guevara, Jorge M730 Guevara, Patricia M730 Guo, Jiasong M839 Guo, Shuling M841 Hajsadeghi, Fereshteh T1540 Havrdova, Eva T1741 Hawi, Amale M1011 Hazel, Tom M840 Heo, Sung Hyuk S141 Hogarth, Penelope S240 Horakova, Dana T1741 Huber, Vincent J. T1744 Hughes, Steve M841 Irwin, David J. T1542 Iwata, Atsushi M836 Jacobson, Sven M1206 Johe, Karl M840 John, Sayona S143 Jung-Henson, Lily K. T1743 Kalincik, Tomas T1741 Karlsson, Fridrik T1746 Kasten, Tom T1541 Kelly, Crystal M840 Keogh, Bart P. T1743 Kieburtz, Karl S239 Kim, Hye Ok S141 Kim, Soong Ho T1538 Kimberly, W. T. M1206 Krasensky, Jan T1741 Kraut, Michael T1539 Kubota, Akatsuki M836 Kucheruck, Olena M1011 Kwee, Ingrid L. T1744 Laguerre, Tatanisha S240 Lam, Ann M622, M728 Lee, Virginia M.Y. T1542 Abdemalik, Peter Ackermann, Elizabeth Ahmahi, Naser Albers, Gregory W. Albert, Todd Alvarado, Luis Angelini, Corrado I. Arnold, Steven E. Askanas, Valerie Avila-Costa, Maria Rosa Babaei, Hormoz Bai, Dongsheng Barlow, Carrolee Bateman, Randall J. Beason-Held, Lori Benson, Merrill Benzinger, Tammie Berdichevsky, Yevgeny Bettermann, Kerstin Bhattachuria, Arun Booten, Sheri Bordeau, Jane Boulis, Nicholas Bowen, James D. Brigatti, Karlla W. Brookler, Kenneth H. Cacciottolo, Mafalda Carlen, Peter L. Cevette, Michael J. Chakraverty, Sumi Chang, Dae-il Chaudhry, Zeshan A. Cocco, Daniela Cohen, Todd Connors, James D’Agostino, Carla Dambinova, Svetlana Davis, Stephen M. Delgado-Escueta, Antonio M729 M841 T1540 M1206 T1538 M841 M838 T1542 M837 M730 T1540 M730 T1538 T1541 T1539 M841 T1541 M727 S142 T1623 M841 M840 M840 T1743 M1011 T1745 M837 M729 T1745 T1541 S141 M1206 T1745 T1542 S144 M837 S142 M1206 V. M730 Deutsch, Eric C. M1011 Dhir, Ashish M731 Donnan, Geoffrey A. M1206 Duron, Reyna M. M730 Eberly, Shirley S238 Ebers, George C. M1012, M1013 Ebrahimi, Ramin T1540 Ehrlich, Michelle E. T1538 Elbert, Don T1541 Elisman, Mark M839 Elm, Jordan J. M1206 Engel, W.King M837 Fague, Scot T1541 Lee, Viven S143, S144 Leinonen, Mika S239 Li, Jun M839 Lian, Gewei M726 Lovestone, Simon T1539 Lynch, David R. M1011 Machado-Salas, Jesus M730 Mail, Michelle M727 Malhotra, Konark S143, S144 Maravilla, Kenneth R. T1743 Marek, Kenneth S238 Marino, Julia T1742 Martinez, Nicholas E. T1746 Matthews, Ian R. T1742 Mawuenyega, Kwasi T1541 Mayadev, Angeli T1743 McIntyre, Cameron M839 Miller, Guy M1011 Minagar, Alireza T1746 Monia, Brett M841 Morris, John C. T1541 Mowry, Ellen M. T1742 Nakada, Tsutomu T1744 Nakayama, Yukihiro T1744 Nalls, Michael T1539 Nascimbeni, Annachiara M838 Nissinen, Helena S239 Nogalska, Anna M837 Nutt, John G S240 Oakes, David S238 Oakley, Sarah T1745 Ohayon, Elan L. M622, M728 Olanow, C. Warren S239 Omura, Seiichi T1746 Ovid, Vitaliy T1541 Park, Byung S. S240 Patterson, Bruce T1541 Poewe, Werner S239 Polak, Meraida M840 Potter, Rachel E. T1541 Prabhakaran, Shyam S143, S144 Pradhan, Gaurav T1745 Rajappa, Sivakumar M. M725 Ramagopalan, Sreeram V. M1012, M1013 Rascol, Olivier S239 Ravina, Bernard M. S238 Repovic, Pavle T1743 Resnick, Susan T1539 Rioux, Patrice M1011 Rizzuto, Daniel S. T1743 Rogawski, Michael A. M731 Ross, Mark A. T1745 122 ID: srinivasanv I Black Lining: [ON] I Time: 22:03 I Path: //xinchnasjn/01Journals/Wiley/3b2/ANA#/Vol00000/110248/APPFile/JW-ANA#110248 J_ID: ZAY Customer A_ID: SUPP11-10 Cadmus Art: 22584 Date: 31-August-11 Rutkove, Seward Salgado, Efrain Sandri, Marco Saponjian, Yero Sato, Fumitaka Schapira, Anthony Sciascia, Thomas Seidl, Zdenek Sejnowski, Terrence J. Sheen, Volney Sheth, Kevin N. Shimizu, Jun Shoulson, Ira Shrader, William D. Sigurdson, Wendy Singleton, Andrew Siwkowski, Andrew Smith, Benn E. Sosinsky, Gina Spitz, John T. Staley, Kevin J. Steele, John W. Stepanek, Jan Stern, Barney J. Stocchi, Fabrizio Suter, Ueli Suzuki, Yuji Tanaka, Miyabi Temes, Richard Tendolkar, Amol Thambisetty, Madhav Treuner, Kai Trojanowski, John Q. Troyer, Matthew D. Tsuji, Shoji Tsunoda, Ikuo M840 T1747 M838 M727 T1746 S239 M1011 T1741 M728 M726 M1206 M836 S238 M1011 T1541 T1539 M841 T1745 M839 M732 M727 T1538 T1745 M1206 S239 M839 T1744 M730 S143 S240 T1539 T1538 T1542 S240 M836 T1746 Stage: Page: 123 Underhill, Hunter R. T1743 Vaneckova, Manuela T1741 Venkatesan, Srinivasan A. M725 Vinayagasundaram, Uma T1742 Wagner, Lindsay T1745 Wang, Lily M839 Waubant, Emmanuelle T1742 Willi, Steve M. M1011 Wilson, Robert B. M1011 Xie, Sharon X. T1542 Xuan, Fengjuan S240 Yan, Qing M839 Yarasheski, Kevin T1541 Yarnykh, Vasily L. T1743 Yoo, Albert J. M1206 Zapala, David A. T1745 Zhang, Jane M729 Zhang, Liang M729 123 ID: srinivasanv I Black Lining: [ON] I Time: 22:04 I Path: //xinchnasjn/01Journals/Wiley/3b2/ANA#/Vol00000/110248/APPFile/JW-ANA#110248 J_ID: ZAY Customer A_ID: SUPP11-12 Cadmus Art: 22585 Date: 26-August-11 Stage: Page: 124<?tbend ABSTRACT SUBJECT INDEX A Cortical Dysplasia (CD) M704 Cytokines M1005, S202, T1717, T1725, T1802, T1908 Cytotoxicity T1509, T1737, T1902 Acute Cerebral Ischemia M721, S102, S105, S109, S116, S118, S120, S121, S128, S136, T1619 Acute Ischemic Stroke S102, S103, S105, S109, S114, S116, S117, S120, S122, S124, S125, S127, S129, S130, S131, S132, S135 Acute Neuropathies M818, M822, M823, M825, M827, M830, T1733 Affective Functioning M608, M617, M819, S203 Alzheimer’s Disease (AD) M616, M808, M1001, T1501, T1502, T1503, T1504, T1506, T1508, T1509, T1512, T1514, T1516, T1517, T1518, T1521, T1522, T1523, T1524, T1525, T1526, T1528, T1529, T1531, T1532, T1533, T1534, T1535, T1901 Amyotrophic Lateral Sclerosis (ALS) M804, M805, M807, M813, M817, M821, M824, M829, M1005 Antibodies M602, M809, M818, M822, M825, M1101, S202, T1506, T1701, T1703, T1706, T1711, T1716, T1719, T1721, T1729, T1733, T1736, T1739, T1801, T1908 Apoptotic Cell Death T1537, T1801, T1803 Astrocytes M1004, T1506, T1509, T1704, T1705, T1710 Atherosclerosis M1003 Attention-Deficit/Hyperactivity Disorder M610, M614, M617, M618, M619 Autoimmune Demyelination M1105, M1303, T1704, T1713, T1729, T1731, T1732, T1734, T1738 D Deep Brain Stimulation M1201, S215, S232, S237 Delirium T1536 Dementia M621, M820, M1008, S201, S219, T1504, T1510, T1518, T1519, T1521, T1521, T1522, T1525, T1531, T1536 Demyelination M822, T1705, T1712, T1713, T1714, T1715, T1718, T1722, T1723, T1727 Diabetic Neuropathy M801, M810, M822, M826, T1604 Down Syndrome (DS) M712 Drosophila M1006, T1502 E Epilepsy M620, M701, M702, M703, M704, M707, M708, M710, M711, M713, M714, M715, M716, M717, M718, M719, M722, S302, T1906 Epilepsy Model M701, M705, M706, M707, M709, M712, M716, M720 Epileptic Seizures M621, M701, M711, M716, M717, M719, M721, M722, M723, M1202, M1203 Epileptogenesis M618, M619, M701, M705, M707, M709, M712, M716, M718 Experimental Autoimmune Encephalomyelitis (EAE) T1704, T1705, T1725 B Brain Imaging M601, M606, M704, M719, M1103, M1104, M1301, S117, S119, S125, S128, S132, S140, S204, S212, T1510, T1513, T1514, T1518, T1525, T1527, T1532, T1601, T1619, T1714, T1715, T1804, T1906, T1908 Brain Ischemia M605, M1201, M1204, S103, S106, S114, S115, S126, T1519 Brain Mapping M601, M604, M605, M609, M708, M724, S109, T1527, T1601 F fMRI Frontotemporal Dementia (FTD) M604, M708 M612, M819, T1515, T1530 G Gene Expression M705, M707, M824, M829, M1003, M1004, S104, S115, T1503, T1511, T1512, T1520, T1720, T1804 Gene Regulation M705, M821, M1001, M1004, M1008 Gene Therapy S201, T1529 Genetic Mutations M709, M803, M813, M815, M1002, M1004, M1006, M1007, M1008, S107, S115, S201, S207, S233, T1502, T1512, T1520, T1713, T1736 Gilles de la Tourette Syndrome (GTS) S231 Glioblastoma Multiforme T1804, T1806, T1806, T1808 C Cell Death M717, M812, M1106, S114, T1528, T1537, T1801 Cerebrospinal Fluid (CSF) M821, S134, S301, T1501, T1514, T1738, T1802, T1903, T1904, T1907, T1908 Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP) T1728, T1729 Cognitive and Neurobehavioral Status Examination (CNS) M607, M613, M617 Cognitive Dysfunction M601, M603, M604, M605, M606, M609, M611, M612, M613, M620, M621, M706, M712, M720, M1006, S204, S205, S206, S209, S211, S214, S219, S407, T1507, T1520, T1522, T1536, T1901 Cognitive Outcomes M603, M613, M615, M618, M619, M702, M819, M1103, S205, S212, S301, S401, S406, T1507, T1508, T1513, T1524, T1534, T1738 Consciousness M721, M1104, S110, S140, S301 H Headache M825, T1601, T1603, T1605, T1606, T1607, T1608, T1610, T1611, T1612, T1613, T1614, T1615, T1616, T1617, T1618, T1619 HIV S407, T1901, T1902, T1905 Huntington’s Disease M1010, S201, S205, S210, S220 124 ID: kannanb I Black Lining: [ON] I Time: 17:28 I Path: N:/3b2/ANA#/Vol00000/110250/APPFile/JW-ANA#110250 J_ID: ZAY Customer A_ID: SUPP11-12 Cadmus Art: 22585 Date: 26-August-11 Stage: Page: 125<?tbend I O Interferon Treatments T1702, T1722, T1724 Interferons M1001, T1722, T1726 Intracerebral Haemorrhage (ICH) M1003, S104, S105, S110, S111, S113, S117, S124, S125, S128, S132, S136 Ischemia S124, S126, S133 Oligodendrocyte T1705, T1710 Other M608, M608, M608, M616, M617, M618, M619, M710, M715, M722, M723, M723, M724, M806, M809, M811, M811, M820, M823, M823, M824, M825, M826, M834, M1005, M1007, M1102, M1102, M1102, M1104, M1107, M1107, M1205, M1301, M1302, M1303, M1304, M1401, M1402, M1402, M1402, S101, S102, S110, S112, S113, S116, S118, S118, S123, S125, S128, S129, S132, S133, S133, S134, S138, S139, S139, S139, S140, S140, S202, S210, S210, S214, S217, S217, S217, S223, S223, S224, S224, S224, S224, S225, S226, S226, S229, S232, S236, S236, S236, S401, S401, S403, S404, S405, S405, S408, T1501, T1501, T1503, T1504, T1508, T1515, T1537, T1537, T1602, T1606, T1607, T1609, T1619, T1620, T1622, T1701, T1701, T1714, T1716, T1716, T1716, T1724, T1725, T1727, T1730, T1739, T1739, T1802, T1803, T1805, T1805, T1805, T1805, T1807, T1807, T1807, T1807, T1808, T1808, T1808, T1809, T1809, T1809, T1902, T1903, T1903, T1904, T1906, T1906, T1907, T1907 L L-Dopa Therapy Levodopa Lewy Bodies (LB) Limbic Encephalitis S215 S232, S236 S207 T1701 M Magnetic Resonance Imaging (MRI) M612, M719, M721, M828, M1301, S106, S204, S212, S234, T1504, T1505, T1514, T1519, T1521, T1525, T1530, T1532, T1605, T1726, T1727, T1737, T1738 Magnetic Resonance Spectroscopy (H-MRS) M812 Migraine S136, T1601, T1602, T1603, T1608, T1609, T1610, T1611, T1612, T1613, T1614, T1615, T1616, T1617, T1618, T1620 Morvan Syndrome T1711 Motoneuron Disease M804, M805, M812, M813, M814, M817, M819, M820, M832, M833, M1002, T1511 Multiple Sclerosis (MS) M603, M1009, M1105, T1621, T1702, T1703, T1704, T1707, T1708, T1709, T1710, T1712, T1713, T1715, T1717, T1718, T1719, T1720, T1721, T1722, T1723, T1724, T1725, T1726, T1727, T1729, T1730, T1731, T1732, T1734, T1735, T1736, T1737, T1740 Muscular Dystrophies M806, M807 Myelin M803 Myelin Oligodendrocyte Glycoprotein (MOG) T1737 Myoclonus M621, M717 Myopathic Syndrome M815, M816 Myopathy M802, M806, M807, M808, M811, M815, M816, M829, M835 P Parkinson’s Disease (PD) M604, S202, S203, S206, S207, S208, S211, S212, S214, S215, S216, S217, S218, S219, S221, S222, S225, S226, S227, S228, S232, S233, S234, S235, T1511, T1535 Periodic Paralysis M831 PET M702, T1508, T1510, T1519, T1901 Pharmacokinetics M710, S230, T1724 R Reactive Oxygen Species (ROS) M801, T1803 S Sleep Disorders and Circadian Rhythm S301, S302, S303 Stroke M601, M1003, M1101, M1204, M1403, S101, S102, S103, S105, S107, S108, S109, S110, S115, S116, S122, S123, S124, S127, S130, S131, S133, S135, S137, S402, T1510, T1621 Subarachnoid Hemorrhage M1102, M1204, S119 Subthalamic Nucleus (STN) Stimulation S215 N Neurodegenerative Diseases M805, M808, M812, M813, M817, M820, M821, M832, M1005, M1007, M1008, M1101, S203, S204, S207, S209, S210, S213, S214, S220, S223, S229, S234, T1503, T1511, T1515, T1530, T1532, T1740 Neurofibromatosis Type1 M1302, T1806 Neurogenesis M803, M1401 Neuroleptics (NLs) M611, S229 Neuromyelitis Optica (NMO) M1009, T1706, T1739 Neuroprotection M801, M803, M829, S114, S229, T1509, T1529, T1902 Neurotrophin T1529, T1803 T Tau M808, M1007, T1502, T1530 Temporal Lobe Epilepsy (TLE) M702, M708, M709, M711 Triptans T1613, T1614, T1618 V Visual Cortex Visual Function M607 M607, M615, M1107, T1536, T1806 125 ID: kannanb I Black Lining: [ON] I Time: 17:28 I Path: N:/3b2/ANA#/Vol00000/110250/APPFile/JW-ANA#110250 J_ID: ZAY Customer A_ID: SUPP11-13 Cadmus Art: 22586 Date: 26-August-11 Stage: Page: 126 WIP SUBJECT INDEX L A Acute Cerebral Ischemia Acute Ischemic Stroke Affective Functioning Alzheimer’s Disease (AD) Lafora Disease L-Dopa Therapy S142 M1206, S142 M622, T1745 M730, T1538, T1539, T1540, T1541, T1542 T1541 T1744 S141 T1742 Alzheimer’s Disease Mutants Astrocytes Atherosclerosis Autoimmune Demyelination M Magnetic Resonance Imaging (MRI) Migraine Multiple Sclerosis (MS) Muscular Dystrophies Myelin Myoclonus Myopathy B Brain Imaging M622, M1206, S143, S144, S238, T1539, T1741, T1743, T1744 M1206, S142 M622, T1745 M727, M729, T1539, T1541 Brain Ischemia Brain Mapping Brain Metabolism M730 S240 M1206, T1741, T1743 T1623 M1012, T1741, T1742, T1743 M838 M839, T1745 M730 M836, M837, M838 N Neurodegenerative Diseases M840, M841, T1538, T1542 Neurogenesis M726, M839, T1538, T1744 Neuromyelitis Optica (NMO) T1742 Neuroprotection M727, M1011 C Cell Death Cerebrospinal Fluid (CSF) Cognitive Outcomes M728, M1011 T1541 M728, S238 O D Other Dementia Demyelination T1538 M839, T1741, T1742, T1743 M622, M725, M731, M836, M837, M840, M841, M1011, M1012, M1013, S141, S239, S240, T1540, T1623, T1745 P E Epilepsy Epilepsy Model Epileptic Seizures Epileptogenesis Parkinson’s Disease (PD) PET Pharmacokinetics Pompe Disease M726, M727, M731, M732 M728, M729, M730, M731 M729 M727, M728, M729 S238, S239, S240 T1539, T1744 M841, S240 M838 R F Frontotemporal Dementia (FTD) Reactive Oxygen Species (ROS) T1542 M1011 S G Gene Expression Gene Regulation Genetic Mutations Single Photon Emission Computed Tomography S238 Stroke S141, S142, S143, S144 Subarachnoid Hemorrhage S143, S144 M838, S141 M726, M1013 M726, M839, M841 H T Headache Tau S143, S144, T1623 M837, T1542 126 ID: kannanb I Black Lining: [ON] I Time: 17:29 I Path: N:/3b2/ANA#/Vol00000/110251/APPFile/JW-ANA#110251 COVER 3 = BLANK PAGE COVER 4 = BLANK PAGE
© Copyright 2024 Paperzz