HOW TO USE THE SLIDE SET
This slide set was created as a supplement for
use in teaching clinical reasoning. Please
feel free to use and modify as needed for
use at your institution.
There are 3 components of this slide set:
1.
2.
3.
A 60-year-old Woman with
Chorea and Weight Loss
Clinical Reasoning Series
A 60-year-old woman was transferred to our
institution for further evaluation of chorea and
weight loss
What are your initial thoughts
about chorea?
Chorea




An uncommon symptom, especially in older
adults
Hyperkinetic movement disorder
Rapid, semi-purposeful, non-patterned
involuntary movements involving distal or
proximal muscle groups
Link to video
http://www.youtube.com/watch?v=OveGZ
dZ_sVs
1.
Most Common Causes of Chorea
Huntington’s Disease
–
–
2.
Look for family history (usually autosomal
dominant, but can be de novo)
Associated with early cognitive decline
Sydenham’s Chorea
–
–
Post-rheumatic fever
Usually in children and young adults
The Dual-Process Theory
Two different approaches used to make
diagnostic decisions developed by cognitive
psychologists
1. Intuitive
2. Analytical
Most physicians use one or the other, but
ideally both should be used because they
complement each other
The Intuitive Approach





Usually used by experienced or expert
clinicians
Relatively quick
Based on pattern recognition
Implicit, uses first impressions
Requires little cognitive effort
The Intuitive Approach
Example:
“Common disorders associated with chorea are
Sydenham’s chorea and Huntington’s
chorea”
The Analytical Approach






Usually used by novice clinicians or by
experienced clinicians when confronted with
difficult cases
Explicit
Based on knowledge and logic
Less susceptible to bias
Slow process
Requires considerable cognitive work
The Intuitive Approach
Example:
“Metabolic disorders, nutritional deficiencies,
infections, autoimmune disorders, vascular
ischemia, toxins and medication side effects
are possible etiologies of chorea”
For the past 6 months:
 Progressive clumsiness and chorea
 Difficulty speaking and eating due to
involuntary movements of the mouth
 Intermittent progressive abdominal pain and
nausea
 Unintentional weight loss (sixty pounds)
What is your differential diagnosis?
Differential Diagnosis

Infectious
- CNS, HIV-associated, neurosyphilis

Malignancy

Toxins/Deficiencies
- Heavy metal toxicity, vitamin B12 deficiency

Wilson’s Disease
Autoimmune
Neuroacanthocytosis
Anti-phospholipid syndrome
Celiac disease
Sarcoidosis
Hepatocerebral degeneration






Which type of reasoning are you
currently using?
Intuitive or Analytical?

Past Medical History
- Atrial fibrillation
- Hypertension
- Hypothyroidism
- Vitamin B12 deficiency



Widowed. No family history of
neurodegenerative disorder or malignancy
30-pack-year history of tobacco use and quit
6 months ago
No alcohol or illegal drug use

Home Medications






Atorvastatin
Digoxin
Furosemide
Levothyroxine
Vitamin B12
Warfarin
Physical Exam
Temp: 98.6 °F, BP: 108/62 mm Hg, HR: 74
General: cachectic, chronically ill appearing, in no
distress. Alert and oriented
Cardiovascular: heart rhythm irregularly irregular
Pulmonary, gastrointestinal and integumentary
unremarkable
Physical Examination
Neurologic:
 Oral dyskinesias and severe dysarthria
 Conjugate gaze and symmetric face
 Choreiform movements in upper extremities
 Motor 4/5 strength in all four extremities
 Moderate generalized muscle atrophy consistent
with cachexia and displayed paratonia in both upper
extremities (involuntary variable resistance during
passive movement)
Physical Examination
Neurologic:
 Reflexes: 1+ in upper extremities, absent in lower
extremities
 Plantar responses: flexor
 Proprioception: decreased at the toes
 Vibratory sensation: decreased below the knees of
bilateral lower extremities
 Diffuse allodynia, more prominent in the abdomen
 Coordination testing: finger-to-nose task was
impaired due to her upper extremity chorea
 Gait: not tested as patient was wheelchair-bound
What tests or studies should be done next?




Complete metabolic panel, blood count, and
thyroid function tests: unremarkable
International normalized ratio (INR): 2.3
Electromyographic study: mild distal motor
neuropathy
Computed tomographic scans of head, chest,
abdomen and pelvis with and without
contrast: unremarkable
MRI brain

Magnetic resonance imaging showed T1
hyperintensities within the basal ganglia with
thalamic sparing and no areas of ischemia or
hemorrhage
What would you do next?
What type of reasoning are you
currently using?
Intuitive or Analytical?
Blood was tested for the presence of
paraneoplastic antibodies and returned
positive for anti-CRMP-5 IgG at a level of
1:3,840 (negative < 1:240)
What do you know about
paraneoplastic syndromes?
Paraneoplastic Syndromes


Manifest as symptoms or findings that are
explained by the presence of a malignancy, but
that are not produced by a local effect from
tumor cells
Examples: hyponatremia from small cell lung
cancer or neurological paraneoplastic
syndromes due to immune responses against a
tumor expressing a certain antigen that crossreacts with neuron antigens
Paraneoplastic Syndromes



Often precede the diagnosis of cancer
The presence of a paraneoplastic antibody in
an individual with a neurological disorder is
not necessarily diagnostic of an underlying
malignancy
Some antibodies are more likely to be
associated with an underlying neoplasm than
others
Paraneoplastic Antibody
Anti-Hu
Anti-Yo
Anti-Ma2 +/- anti-Ma1
Anti-CRMP-5
Predominant Associated
Neoplasm
Small cell lung carcinoma
(93%)
Ovarian (47%), breast (25%),
endometrial (13%)
Testicular (55%), non-small
cell lung carcinoma (21%)
Small cell lung carcinoma,
(77%), thymoma (8%)
Anti-Amphiphysin
Small cell lung carcinoma,
(59%), breast (35%)
Anti-Ri
Breast (43%), small-cell lung
carcinoma (24%) and nonsmall cell lung carcinoma
(24%)
Associated Paraneoplastic
Syndrome
Cerebellar degeneration,
neuropathy
Cerebellar degeneration,
dementia, neuropathy
Brainstem encephalitis,
parkinsonism
Cerebellar degeneration,
chorea, myelopathy,
neuropathy
Cerebellar degeneration, stiff
person syndrome, dementia,
psychiatric symptoms,
myelopathy, neuropathy
Cerebellar degeneration,
opsoclonus-myoclonus
syndrome, brainstem
encephalitis, myelopathy,
neuropathy


The presence of the CRMP-5 antibody with
the patient’s clinical findings supported the
diagnosis of “definite” paraneoplastic
syndrome
Malignancy has been reported in greater than
90% of cases with this antibody




Repeat CT scans of the chest, abdomen, and
pelvis: unrevealing
Mammogram: normal
Colonoscopy had been performed six months
prior with negative results
Three months after the initial panel was sent,
CRMP-5 antibody titer was repeated and
again returned positive
What would you do next?

Referred to Oncology

PET scan: 1.5 cm hypermetabolic lymph
node posterior to the trachea with a
standardized uptake value of 3.4
(normal < 2.5)

Endoscopic ultrasound-guided fine needle
aspiration was positive for malignant cells
that stained for synaptophysin, thyroid
transcription factor 1 (TTF-1), and CD56

This confirmed the diagnosis of small cell
cancer of pulmonary origin



Underwent 4 cycles of chemotherapy, lung
radiation therapy and prophylactic whole
brain radiation therapy
One year following treatment, she had gained
weight, was eating well, and was no longer
wheelchair-bound
Most recent CRMP-5 antibody titer was
negative

Chorea, from the Latin dance or Greek
khoreia, is a specific type of movement
disorder that is characterized by rapid, semipurposeful, non-patterned involuntary
movements

Chorea can be caused by:






Sydenham’s chorea
Genetic disorders: Huntington’s disease, Wilson’s
disease
Metabolic disorders: electrolyte disturbances,
vitamin deficiencies, thyroid disorders
Space-occupying lesions and paraneoplastic
processes
Autoimmune conditions
Toxin ingestions

Paraneoplastic syndromes manifest as
symptoms or findings that are explained by
the presence of a malignancy, but that are
not produced by a local effect from tumor
cells

Patients found to have paraneoplastic
antibodies should be evaluated for an occult
malignancy

The CRMP-5 antibody can produce chorea
and seems to be associated with malignancy
in greater than 90% of cases
References









Bhatnagar D, Morris JL, Rodriguez M, Centor RM, Estrada CA, Willett LL. A middle-age
woman with sudden onset dyspnea. J Gen Intern Med. 2011;26:551-4.
Dhaliwal G. Going with Your Gut. J Gen Intern Med 26:107–109.
Henderson MC, Dhaliwal G, Jones SR, Culbertson C, Bowen JL. Doing what comes
naturally. J Gen Intern Med. 2010;25:84-7.
Croskerry P. A universal model of diagnostic reasoning. Acad Med. 2009; 84:1022–1028.
Norman G. Dual processing and diagnostic errors. Adv Health Sci Educ Theory Pract.
2009. Suppl 1:37-49.
Eva KW, Hatala RM, LeBlanc VR, Brooks LR. Teaching from the clinical reasoning
literature: combined reasoning strategies help novice diagnosticians overcome
misleading information. Med Educa 2007; 41: 1152–1158. 10.1111/j.13652923.2007.02923.x
Bowen, JL. Educational Strategies to Promote Clinical Diagnostic Reasoning. N Engl J
Med 2006;355:2217-2225.
Gozzard P, Maddison P. Which antibody and which cancer in which paraneoplastic
syndromes? Pract Neurol. 2010;10:260-70.
Pellacia T, Tardif J, Triby E, Charlin B. An analysis of clinical reasoning through a recent
and comprehensive approach: the dual process theory. Med Educ Online 2011; 16:5890.
doi: 10.3402/meo.v16i0.5890.
Chorea – Videos

Clinical assessment of chorea severity
(Medscape login required). Available at:
http://www.medscape.com/infosite/xenazine/article1?src=0_nl_sm_0&eguid=MTEyMTM5NzU. Accessed
August 29th, 2011.

YouTube. Available at:
http://www.youtube.com/watch?v=OveGZdZ_sVs.
Accessed August 29th, 2011.