Life Long Learning in Neurology - part 1 doc

Life Long Learning in Neurology








MULTIPLE-CHOICE QUESTIONS
Prepared By Neurology Residents Team
Medical City Hospitals-Baghdad


© 2008 All rights reserved.

Continuum Contents






Internal medicine 1

Neurogenetics 9
Spinal Cord Disorder 22
Stroke prevention 30
Critical care neurology 41
Infectious disease 49
Muscle disease 61
Neuro-otology 70
Psychiatry for neurologist 79
Headache 88
Movement disorder 99
Dementia 107
Sleep disorder 116
Epilepsy 126
Multiple sclerosis 134
Autonomic Disorders 144
CONTENTS
Continuum Contents




1
INTERNAL MEDICINE Feb. 2005

TYPE A QUESTIONS (ONE BEST ANSWER)
1. Most evidence suggests that the major efferent limb of the inflammatory reflex is carried in:
A. The sympathetic chain
B. The phrenic nerve
C. The vagus nerve
D. Postganglionic sympathetics arising in the stellate ganglia

E. The long thoracic nerve
Correct Answer: The correct answer is C. Evidence suggests that information leaving the central nervous system
regarding regulation of inflammation is carried mainly in the vagus nerve. The sympathetic chain is the origin of
postganglionic fibers for sympathetic innervation of visceral organs. The phrenic nerve carries motor axons for the
diaphragm, and the postganglionic sympathetics are destined to provide sympathetic innervation to the heart, lungs,
and neighboring structures.
2. Autopsy studies in patients with gluten ataxia have demonstrated within the cerebellum lymphocytic infiltration
and loss of:
A. Stellate cells
B. Mossy fibers
C. Granule cells
D. Purkinje cells
E. Basket cells
Correct Answer: The correct answer is D. Hadjivassiliou and colleagues have reported the presence of Purkinje cell
loss and lymphocytic infiltration in the cerebellum and posterior columns of the spinal cord in several individuals
with gluten ataxia, suggesting the presence of an immune-mediated inflammatory process as the mechanism for the
development of gluten ataxia.
Hadjivassiliou M, Boscolo S, Davies-Jones GA, et al. The humoral response in the pathogenesis of gluten ataxia.
Neurology 2002;58:1221-1226.
3. A 25-year-old primigravida is seen in urgent consultation shortly after experiencing a first generalized tonic-
clonic seizure. She is 1 day postpartum after vaginal delivery of a full-term infant. Pregnancy was complicated by
early preterm labor treated successfully with magnesium sulfate. Delivery was uncomplicated with stable vital
signs and no sign of maternal infection. Examination shows a still somnolent woman who has bitten her tongue.
Vital signs show a blood pressure of 150/90 mm Hg. She moves all limbs spontaneously with brisk deep tendon
reflexes throughout; Babinski's sign is present bilaterally. She becomes oriented over the course of the examination
and complains of a headache and blurred vision. Magnetic resonance imaging (MRI) imaging of the brain done
later that day shows large areas of increased signal in the occipital lobes bilaterally on T2-weighted and fluid-
attenuated inversion recovery (FLAIR) sequences. What is the most important causative factor in this patient's
problem?
A. Degree of hypertension

B. Rapid rise of blood pressure
C. Integrity of collateral circulation
D. Postpartum hypercoagulability
E. Amniotic fluid emboli
Correct Answer: The correct answer is B. This patient has eclampsia with primary endothelial cell dysfunction. In
these patients, who were not long-term hypertensives, "rapid rise of blood pressure over time rather than the
absolute blood pressure carries the greatest risk" (see chapter 5, "Hyperperfusion Syndromes," p. 99).Collateral
circulation is irrelevant. Postpartum hypercoagulability or amniotic fluid emboli is unlikely.
4. 4. Which of the following vasculitic syndromes is most likely to be associated with the presence of serum
antineutrophil cytoplasm autoantibodies (ANCA)?
A. Polyarteritis nodosa
B. Giant cell arteritis
C. Takayasu's arteritis
D. Wegener granulomatosis
E. Leukocytoclastic skin vasculitis
Correct Answer: The correct answer is D. ANCA with a diffuse cytoplasmic staining pattern (cANCA) with
specificity for proteinase 3 (PR3) are found in over 90% of patients with untreated Wegener granulomatosis. None
of the other vasculitides listed above are commonly associated with ANCA. Microscopic polyangiitis shows


2
considerable overlap with Wegener granulomatosis and is frequently associated with antimyeloperoxidase ANCA
or anti-PR3-ANCA. Churg-Strauss angiitis is also associated with ANCA.
Seo P, Stone JH. The antineutrophil cytoplasmic antibody-associated vasculitides. Am J Med 2004;117:39-50.
5. The following is a serum marker associated with arterial hypercoagulability:
A. D-dimer
B. High sensitivity C-reactive protein
C. Factor V Leiden mutation
D. Protein C deficiency
E. Protein S deficiency

Correct Answer: The correct answer is A. D-dimer is a marker for both arterial and venous thrombosis. The other
choices are all markers of venous thrombosis only.
6. A 70-year-old man with a history of unstable angina and hypertension undergoes coronary artery bypass grafting
and is transferred postoperatively to the surgical intensive care unit for further care. On the second postoperative
day, he is noted by staff to be disoriented and poorly cooperative with his care. A neurological consultant is called.
The patient is afebrile with stable vital signs. He appears distracted and is unable to state where he is or how long
he has been there. He looks off to various corners of the room; he moves all four limbs normally. Deep tendon
reflexes are symmetric, and plantar responses are flexor. He has been receiving tapering doses of morphine sulfate,
along with other medications. The consultant diagnoses encephalopathy. Which of the following is the most likely
cause of this condition?
A. Microemboli
B. Hypoxemia
C. Drug withdrawal
D. Focal cerebral infarction
E. Infection
Correct Answer: The correct answer is A. Showers of embolic material to the brain are the most likely cause of
postoperative encephalopathy, on the same spectrum as those who suffer definitive strokes after surgery. There is
no evidence for poor oxygenation or infection with stable vital signs; drug withdrawal is unlikely with careful
tapering of doses.
7. The central nervous system (CNS) regulates inflammation via two mechanisms: a humoral system and a neural
system. Stimulation of what nervous structure is known to result in an inhibition of inflammatory cytokine
synthesis in all visceral organs?
A. Cingulate gyrus
B. Amygdala
C. Pontine reticular formation
D. Superior cervical ganglion
E. Vagus nerve
Correct Answer: The correct answer is E. Stimulation of the vagus nerve has been shown to inhibit inflammatory
cytokine synthesis in all visceral organs, including those that belong to the reticuloendothelial system, via release of
acetylcholine, which reacts with macrophage receptors. This direct inhibitory influence does not occur with

stimulation of the other structures.
8. A 67-year-old insurance salesman presents to his physician with complaints of chronic cough, unintentional loss
of 25 lbs over the past 3 months, andthe development of poor balance, numbness on the lateral aspect of the right
leg and foot, and burning in his left foot over the past 2 weeks. Nerve conduction studies/electromyography
demonstrate a predominantly sensory neuronopathy with superimposed mononeuritis multiplex polyneuropathy.
Blood work includes a normal glycosylated hemoglobin level, an elevated anti-Hu antibody titer, and a negative
human immunodeficiency virus serology. Right peroneal nerve biopsy yields pathological evidence of transmural
inflammation of epineurial vessels. Which of the following is the most likely diagnosis?
A. Wegener granulomatosis
B. Polyarteritis nodosa
C. Microscopic polyangiitis
D. Paraneoplastic vasculitis
E. Nonsystemic vasculitic neuropathy
Correct Answer: The correct answer is D. Paraneoplastic vasculitis, most likely due tolung neoplasm, is the most
likely diagnosis. None of the other options is associated with a positive anti-Hu antibody but could present with
weight loss and neuropathy.
9. A 38-year-old male is referred to the neurologist with a 2-year history of gradually progressive deterioration in
balance. His past medical history is significant for chronic diarrhea and difficulty maintaining his weight. His


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examination is remarkable for moderate truncal ataxia, mild dysarthria, and mild intention tremor in the upper
extremities. The antibody test most useful in establishing the diagnosis of gluten ataxia is:
A. Antitissue transglutaminase
B. Antigliadin
C. Antiendomysial
D. Antireticulin
E. Antiglutenin
Correct Answer: The correct answer is B. Hadjivassiliou and colleagues believe that the presence of
immunoglobulin G antigliadin antibodies, even though somewhat nonspecific, is the best marker for gluten ataxia

because it is the most sensitive indicator of gluten sensitivity, which may be present even in the absence of gluten
enteropathy.
Correct Answer: Antitissue transglutaminase, antiendomysial, and antireticulin antibodies are all more specific
markers for gluten enteropathy but are less frequently positive in gluten ataxia. Antiglutenin antibodies are not
typically measured in celiac disease.
Hadjivassiliou M, Grünewald R, Sharrack B, et al. Gluten ataxia in perspective: epidemiology, genetic
suspectibility and clinical characteristics. Brain 2003; 126:685-691.
10. A 65-year-old man with a history of hypertension, hyperlipidemia, and intractable angina undergoes coronary
artery bypass grafting with cardiopulmonary bypass. His immediate postoperative recovery is unremarkable, and he
begins outpatient cardiac rehabilitation. One month after surgery, his therapists note that he seems withdrawn at
times and appears reluctant to participate fully in his treatment. He notes some difficulty falling asleep at night and
tells his wife he feels as though, "I might die in my sleep." He takes a beta-blocker, nitrate, and statin drug but
admits to sometimes missing a pill. Approximately 1 year after surgery, he has not resumed all of his normal
activities and begins to complain of recurrent chest pain. His cardiologist performs an exercise tolerance test, and
no ischemic changes are noted. Which of the following is the most likely explanation for his recurrent symptoms?
A. Poor exercise tolerance
B. Reocclusion of grafts
C. Cognitive impairment
D. Medication noncompliance
E. Depression
Correct Answer: The correct answer is E. No ischemic changes have been demonstrated on testing, and although
we do not have any information on the patient's premorbid mood, "…depression at 3 months is strongly associated
with the return of angina at 1 year and 3 years" (see chapter 2, "Neurological Aspects of Cardiac Surgery With
Emphasis on Coronary Artery Bypass Grafting," page 51).
11. The hallmark of the encephalopathy of fulminant hepatic failure is:
A. Parkinsonism due to manganese deposition in the globus pallidus
B. Nystagmus and ophthalmoplegia
C. Diabetes insipidus
D. Korsakoff's psychosis
E. Cerebral edema with increased intracranial pressure

Correct Answer: The correct answer is E. The hallmark and defining characteristic of the encephalopathy that
develops in fulminant hepatic failure is cerebral edema with consequent increased intracranial pressure, which can
develop very rapidly and can compromise cerebral perfusion. Its pathogenesis is not fully understood.
Correct Answer: Hyperintensity within the globus pallidus on T1-weighted MRI images is often seen in individuals
with chronic hepatic failure and is probably due to manganese deposition. Nystagmus and ophthalmoplegia are
classic features of Wernicke's encephalopathy, which occurs in individuals with thiamine deficiency, often in the
setting of long-standing ethanol abuse. Diabetes insipidus is a consequence of posterior pituitary dysfunction.
Korsakoff's psychosis, characterized by prominent impairment of short-term memory with confabulation, is another
consequence of thiamine deficiency, typically in the context of chronic ethanol abuse.
12. A 70-year-old man with a history of coronary artery disease and bilateral carotid stenosis (last estimated at
between 50% to 69% on both sides) is evaluated for coronary artery bypass grafting. Six months prior to this, he
saw a neurologist for a transient episode of aphasia; at that time, MRI scanning of the brain, including diffusion-
weighted imaging (DWI), showed small vessel disease. He undergoes conventional on-pump surgery with cross-
clamping of the aorta; 1 day postoperatively, he has difficulty expressing himself and mild right pronator drift. A
computed tomography (CT) scan of the brain fails to demonstrate any acute lesion. When he is extubated and
placed in a chair, staff members note that he has difficulty swallowing and moving both arms fully. A neurological
consultant is called and diagnoses a left frontal infarct while suspecting that a more diffuse problem may be


4
present. MRI scan of the brain with DWI and magnetic resonance angiography is obtained. What is the most likely
finding on these studies?
A. Small vessel disease
B. Left carotid occlusion
C. Bilateral watershed infarcts
D. Bilateral middle cerebral artery infarcts
E. Diffuse cerebral edema
Correct Answer: The correct answer is C. As in Case 2-1, this patient likely suffered the consequence of multiple
emboli. Although the focal findings suggest possibly a unilateral left middle cerebral artery infarct, a carotid
occlusion would likely have produced a larger deficit. The patient also has findings (eg, dysphagia) suggestive of

bilateral disease but with a level of consciousness and examination not likely to be as severe as bilateral middle
cerebral artery infarcts.
13. Acute sensorineural hearing loss is associated with:
A. Celiac disease
B. Ulcerative colitis
C. Whipple's disease
D. Hepatic encephalopathy
E. Crohn's disease
Correct Answer: The correct answer is B. Both acute sensorineural hearing loss and chronic subclinical hearing
loss have been reported in the setting of ulcerative colitis. The pathogenesis of the neuronal damage is presumed to
be on an autoimmune basis.
Summers RW, Harker L. Ulcerative colitis and sensorineural hearing loss: is there a relationship? J Clin
Gastroenterol 1982;4:251-252.
14. 14. A 45-year-old woman with a history of metastatic breast cancer is begun on intravenous cyclosporine A
therapy after undergoing bone marrow transplant. Two hours after her first infusion of cyclosporine, she complains
of a headache; within an hour, she is noted to have a generalized tonic-clonic seizure. A neurological consultant is
called later that day and finds visual loss in the right hemifield and left superior quadrant. MRI scanning of the
brain shows confluent areas of enhanced signal intensity in the occipital lobes on T2-weighted and FLAIR imaging;
DWI and gradient-echo imaging are normal, and no enhancing lesions are seen with gadolinium. The consultant
suggests repeating the imaging study in a few weeks. What is most likely to be seen on the repeat study?
A. Resolution of the lesions
B. Bioccipital infarctions
C. Intracerebral metastases
D. Petechial hemorrhage
E. Brain stem compression
Correct Answer: The correct answer is A. The patient's findings on her initial MRI scan are consistent with
vasogenic edema, as seen in cyclosporine A use (p. 102). In most cases, "diffusion-weighted imaging (DWI) has
been used mostly to distinguish the cytotoxic edema of infarction from the vasogenic edema of HTE [hypertensive
encephalopathy]" (p. 102). Although it is possible for this patient to have suffered permanent infarctions, the
normal DWI finding on her initial imaging study argues against this. There is no suggestion of metastases on the

gadolinium-enhanced images, nor of brain stem compression. Petechial hemorrhage is possible but not seen on
gradient-echo imaging.
15. A 42-year-old man presents with a history of recurrent oral and genital ulcerations. He has had episodes of
retinal vasculitis and is followed by a neuro-ophthalmologist. In addition, he has had three episodes of
encephalopathy that brought him to evaluation in the emergency department. During two of these episodes,
cerebrospinal examination showed lymphocytic pleocytosis with elevated protein. He also has had problems with
pseudotumor cerebri in the past. Which of the following diseases does he most likely have?
A. Sjögren syndrome
B. Behçet's disease
C. Rheumatoid arthritis
D. Lymphomatoid granulomatosis
E. CNS borreliosis
Correct Answer: The correct answer is B. Behçet's disease is characterized by a triad of oral and genital ulcers and
uveitis and may be associated with cutaneous, retinal, and CNS vasculitis. Encephalopathy may occur due to direct
inflammation of the CNS. Pseudotumor may also occur from smoldering vasculitis involving the cerebral veins.
Siva A, Altintas A, Saip S. Behçet's syndrome and the nervous system. Curr Opin Neurol 2004;17:347-357.


5
16. A 65-year-old man with a history of hypertension, diabetes mellitus, and depression undergoes coronary artery
bypass grafting for intractable angina. He awakens 10 hours after surgery. Shortly thereafter, staff notes that he is
not following commands and appears to stare off into space. Medications include morphine sulfate, intravenous
beta-blockers, and heparin. He is intubated; vital signs are remarkable for a blood pressure of 110/60 mm Hg and a
regular heart rate. A neurological consultant is called and finds the patient to be awake but attending only to the
right. He moves the right side spontaneously and withdraws the left leg. Laboratory tests show a glucose of 150
mg/dL. What is the most likely mechanism for this patient's problem?
A. Medication-induced delirium
B. Hyperglycemia
C. Prolonged hypotension
D. Atheroembolic event

E. Intracerebral hemorrhage
Correct Answer: The correct answer is D. The patient has a focal ischemic event in a major arterial territory. He has
mild hyperglycemia, although no history of a prior stroke is known. Although he is in a younger age group, the
presence of diabetes and hypertension makes his risk of stroke higher than any other category in his age group
(Table 2-5).
17. A 75-year-old man with a history of coronary artery disease, hypertension, and hyperlipidemia is brought to the
emergency department 1 hour after an episode at home during which he was noted to mumble something, then
shake on the right side, and then fall to the ground. Five days earlier he had undergone left carotid endarterectomy
for a 90% stenosis of the left internal carotid artery. Surgery was uneventful, and he was discharged to home on the
fourth postoperative day. When seen in the emergency department, he has difficulty naming objects and complains
of a headache. Vital signs are significant for a blood pressure of 165/90 mm Hg. Mild right pronator drift is present.
What is the most likely mechanism underlying this patient's neurological event?
A. Defective cerebral autoregulation
B. Intracerebral steal syndrome
C. Focal ischemia
D. Cytotoxic edema
E. Thrombogenesis
Correct Answer: The correct answer is A. There is good evidence for the postulated postendarterectomy
hyperperfusion syndrome to be the result of chronic hypoperfusion in the setting of high-grade carotid stenosis,
leading to a shift of the autoregulatory curve to the left and, hence, an intolerance of the restored perfusion
pressures after revascularization. Focal ischemia and cytotoxic edema might occur as a result of embolization from
the endarterectomy site or from acute thrombosis, but these are less likely than post-carotid endarterectomy
hyperperfusion to cause headache and seizure.
18. An apparently healthy man has a high-sensitivity C-reactive protein level (hsCRP) that falls in the highest
quartile for a large population of similar men. How does his relative risk for myocardial infarction compare to that
of a similar man with an hsCRP level that falls within the lowest quartile?
A. Equivalent
B. One time greater
C. Three times greater
D. Five times greater

E. Ten times greater
Correct Answer: The correct answer is C. In the study by Ridker and colleagues, (1997) in which 22,000 apparently
healthy men were followed for 10 years, the risk of myocardial infarction was 3 times greater in those men whose
hsCRP fell within the top quartile compared to the risk of the men within the lowest quartile.
Hadjivassiliou M, Boscolo S, Davies-Jones GA, et al. The humoral response in the pathogenesis of gluten ataxia.
Neurology 2002;58:1221-1226.
Hadjivassiliou M, Boscolo S, Davies-Jones GA, et al. The humoral response in the pathogenesis of gluten ataxia.
Neurology 2002;58:1221-1226.
Pai JK, Pischon T, Ma J, et al. Inflammatory markers and the risk of coronary heart disease in men and women. N
Engl J Med 2004;351:2599-2610.
Ridker PM, Cushman M, Stampfer MJ, et al. Inflammation, aspirin and the risk of cardiovascular disease in
apparently healthy men. N Engl J Med 1997;336:973-974.
19. A 55-year-old man is seen in follow-up by his physician for hypertension. He has a history of chronic renal
failure due to hypertensive disease. He is maintained on four medications for blood pressure, including clonidine,
metoprolol, hydrochlorothiazide, and lisinopril. His blood pressure in the office is 195/100 mm Hg. Two days later,
he is brought to the emergency department by ambulance after suffering a seizure. Blood pressure is 240/120 mm


6
Hg; papilledema is present. A CT scan of the brain done urgently shows poor differentiation of the gray-white
junction. Damage to which of the following structures can be implicated in this patient's problem?
A. Adventitia
B. Astrocytic podocyte
C. Basal lamina
D. Endothelium
E. Muscularis
Correct Answer: The correct answer is D. The endothelium makes up the major functional component of the blood-
brain barrier to protein tracers, suggesting that it is the major barrier to production of edema.
20. A distinguishing clinical characteristic of Whipple's disease is:
A. Oculomasticatory myorhythmia

B. Myoclonic ataxia
C. Palatal myoclonus
D. Internuclear ophthalmoplegia
E. Myotonia paradoxica
Correct Answer: The correct answer is A. Oculomasticatory myorhythmia consists of the combination of pendular
convergence nystagmus and concurrent slow,rhythmic, synchronous contractions of the masticatory muscles and is
accompanied by supranuclear vertical gaze paresis. Its presence is virtually pathognomonic for Whipple's disease,
although it actually develops in only approximately 20% of patients with the disease.
Correct Answer: Myoclonic ataxia (Ramsay Hunt syndrome) has been reported in the setting of celiac disease.
Palatal myoclonus (now termed palatal tremor) in its secondary, or symptomatic, form is produced by pathological
processes damaging the brain stem and may result in hypertrophy of the inferior olive. Internuclear
ophthalmoplegia is produced by lesions involving the median longitudinal fasciculus and is often associated with
multiple sclerosis. Myotonia paradoxica occurs in the setting of paramyotonia congenita and is characterized by
myotonia that worsens with repeated activity.
Louis ED, Lynch T, Kaufmann P, et al. Diagnostic guidelines in central nervous system Whipple's disease. Ann
Neurol 1996;40:561-568.
Schwartz MA, Selhorst JB, Ochs AL, et al. Oculomasticatory myorhythmia: a unique movement disorder occurring
in Whipple's Disease. Ann Neurol 1986;20:677-683.
21. A 46-year-old male physician is quite worried about his personal risk of stroke despite the fact that he does not
smoke or have hypertension or hyperlipidemia. His father had several strokes in his early 60s despite a lack of
demonstrable risk factors including a negative evaluation for hypercoagulable states. He wonders if a blood test
would help to determine his risk of stroke. Which of the following markers of inflammation is the most predictive
of relative risk of stroke?
A. Tumor necrosis factor-[alpha]
B. High-sensitivity C-reactive protein
C. Interleukin 6
D. Interleukin 10
E. Soluble CD40 ligand
Correct Answer: The correct answer is B. High-sensitivity C-reactive protein is the most reliable and consistent
predictor of arterial thrombosis and the only inflammatory biomarker clinically proven to add predictive

information to both the Framingham Risk Score and to formal definitions of metabolic syndrome. Tumor necrosis
factor-[alpha], interleukin 6, and soluble CD40 ligand are also markers of inflammation but have not been found to
have the predictive value of high-sensitivity C-reactive protein. Interleukin 10 is an anti-inflammatory cytokine.
22. A 5-year-old girl with glomerulonephritis, renal failure, and hypertension who has had three generalized tonic-
clonic seizures in a period of 3 hours is taken to the emergency department. On arrival, her blood pressure is
180/110 mm Hg, and treatment is begun with intravenous sodium nitroprusside. A neurological consultant is called
5 hours later. Blood pressure at that time is 140/90 mm Hg. She is mildly confused and complains of a headache.
Flame hemorrhages are seen in the eyes. An adult patient with a similar presentation was admitted the day before;
his blood pressure on arrival to the emergency department was noted to be 240/140 mm Hg. What is the most likely
explanation for the greater vulnerability of the child than the adult for this problem?
A. Autoregulation in children comprises a broader mean arterial pressure (MAP) range
B. Endothelial cells in children are less developed
C. Renal compensatory mechanisms are less available
D. Childhood hypertension is less aggressively treated
E. The range of autoregulation in children is shifted to lower MAP


7
Correct Answer: The correct answer is E. As a result of the developmentally lower upper threshold of
autoregulation, autoregulatory breakthrough will occur at lower blood pressures in children.
23. Serum C-reactive protein is a biomarker of inflammation. What percentage of the population variance in C-
reactive protein levels appears related to inherited factors?
A. 10%
B. 25%
C. 50%
D. 75%
E. 90%
Correct Answer: The correct answer is C. Approximately 50% of the variance in C-reactive protein levels occurs
on a familial basis. This suggests that low-grade systemic inflammation may be determined in part by several
common gene polymorphisms.

24. A 75-year-old woman with a history of hypertension develops abrupt onset of headache and confusion. On
physical examination, blood pressure is 210/120 mm Hg. Pupils react normally, but she has obvious difficulty
seeing in both hemifields. A CT scan of the brain does not demonstrate a hemorrhage. MRI of the brain with
diffusion-weighted sequences does not demonstrate a stroke, and FLAIR imaging is suggested. What finding is
most likely to be seen on FLAIR imaging?
A. Cytotoxic edema
B. Petechial hemorrhage
C. Major branch occlusion
D. Vasogenic edema
E. Hydrocephalus
Correct Answer: The correct answer is D. Gross hemorrhage and hydrocephalus have been ruled out by CT scan,
and petechial hemorrhage should be seen on conventional MRI. Diffusion-weighted imaging has effectively ruled
out a major branch occlusion. FLAIR imaging clearly demonstrates the vasogenic edema that is the primary
imaging finding in hypertensive encephalopathy.
25. An association with migraine has been reported for:
A. Crohn's disease
B. Viral hepatitis
C. Ulcerative colitis
D. Celiac disease
E. Whipple's disease
Correct Answer: The correct answer is D. In a recent study, Gabrielli and colleagues (2003) discovered the
presence of biopsy-confirmed celiac disease in 4.4% of 90 patients with migraine. A gluten-free diet resulted in
improved control of migraine severity in all affected individuals.
Correct Answer: Migraine has not been specifically associated with inflammatory bowel disease, hepatitis, or
Whipple's disease.
Gabrielli M, Cremonini F, Fiore G, et al. Association between migraine and Celiac disease: results from a
preliminary case-control and therapeutic study. Am J Gastroenterol 2003;98:625-629.
26. A-25 year-old primigravida in her 30th week of pregnancy is seen in the emergency department 2 days after the
onset of headache, confusion, and visual changes. Vital signs include a blood pressure of 160/100 mm Hg. SheC
appears distracted. Tone is increased throughout. Which of the following is the best treatment for her hypertension?

A. Sodium nitroprusside
B. Magnesium sulfate
C. Enalaprilat
D. Furosemide
E. Phentolamine
Correct Answer: The correct answer is A. Lowering the blood pressure with a drug that has rapid onset and short
duration of action is recommended. Magnesium sulfate is used to treat epileptic complications of eclampsia (not
hypertension); enalaprilat is contraindicated in pregnancy while diuretics are generally not used since most patients
are felt to be volume contracted. Phentolamine is used in hypertensive crises induced by monoamine oxidase
inhibitors, as well as in pheochromocytoma.
27. A 70-year-old man with a history of hypertension undergoes coronary artery bypass grafting with conventional
on-pump technique. His immediate recovery is unremarkable, and he is discharged to home on the fifth
postoperative day. He begins outpatient cardiac rehabilitation and is able to increase his exercise tolerance
gradually over the next 2 months. At 2 months postoperatively he resumes driving but has some difficulty
responding quickly in the car. He has not yet resumed responsibility for balancing his checkbook. He is sent for


8
neurological consultation and is found to be distractible but with a Mini-Mental State Examination of 28/30. MRI
scanning of the brain shows deep white matter ischemic changes, unchanged from a scan done 2 years previously
for an episode of transient numbness. What is the best option for the management of this patient regarding his
cognitive status?
A. Start an anticholinesterase medication
B. Reexamine in a few months
C. Repeat the MRI in 6 months
D. Screen the patient for presumed depression
E. Refer the patient for neuropsychological testing
Correct Answer: The correct answer is B. This patient demonstrates a short-term cognitive decline 2 months
postoperatively without MRI evidence of focal ischemic changes and without a history of postoperative
encephalopathy. Current data suggest that these changes will be reversible if the patient is observed for a little

longer period of time.
28. An antitumor necrosis factor monoclonal antibody is:
A. Natalizumab
B. Rituximab
C. Celecoxib
D. Infliximab
E. Homeopathimab
Correct Answer: The correct answer is D. Infliximab is an antitumor necrosis factor monoclonal antibody.
Natalizumab is a monoclonal antiadhesion molecule (alpha
4
) antibody. Rituximab is an anti-CD20 antibody, which
is used in the treatment of non-Hodgkin's lymphoma. Celecoxib is a COX-2 specific nonsteroidal anti-
inflammatory drug. Homeopathimab is a playful neologism.
29. A 65-year-old man with a history of coronary artery disease and aortic stenosis is evaluated for surgery after
medical management for angina fails. Past surgeries include successful repair of an abdominal aortic aneurysm.
The cardiothoracic surgeon tells him that he can undergo valve replacement and coronary artery bypass surgery all
at one time. In terms of risk for stroke in the perioperative period, current data suggest that it is which of the
following?
A. More than double the risk of coronary artery bypassgrafting alone
B. Four times the risk of valve replacement alone
C. Lower than the risk of coronary artery bypass grafting and a carotid endarterectomy
D. Two times greater than the risk of carotid endarterectomy
E. Greater than the risk of aortic aneurysm surgery
Correct Answer: The correct answer is A. See Table 2-2.
30. Aside from lipid-lowering effects, 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors
(statins) have anti-inflammatory actions that reduce atherosclerotic plaque inflammation and rupture. Which of the
following is one of the mechanisms by which statins may reduce inflammation?
A. Inhibition of tumor necrosis factor-[alpha] (TNF-[alpha]) secretion
B. Induction of arterial thrombosis
C. Down-regulation of interleukin 10 elaboration

D. Increase of interleukin 1 release
E. Increased T-cell activation
Correct Answer: The correct answer is A. Statins have been shown to cause in vitro inhibition of TNF-[alpha]
secretion. TNF-[alpha] is one of the most important substances in the acute inflammatory cascade, causing other
mononuclear cells to release inflammatory cytokines. The other choices reflect increased activation of the
inflammatory cascade.
Neuhaus O, Strasser-Fuchs S, Fazekas F, et al. Statins as immunomodulators: comparison with interferon-beta 1b
in MS. Neurology 2002;59:990-997.
31. A 72-year-old woman was in good health until she developed a vesicular rash that involved the right forehead
without corneal involvement. The rash crusted over and healed well. However, 2 weeks later she developed
disorientation and confusion. A week later she developed a moderate left hemiparesis. An MRI scan showed
multiple T2 hyperintensities involving the left basal ganglia and deep white matter; diffusion images were
consistent with infarcts. Cerebrospinal fluid (CSF) contained 88 WBC/mm
3
(98% mononuclear cells) with a
glucose of 56 mg/dL and a protein level of 68 mg/dL. Cerebral angiography demonstrated narrowing and beading
of the right intracranial internal carotid and middle cerebral arteries. Which of the following is the most likely
diagnosis?
A. Granulomatous angiitis of the nervous system


9
B. Wegener granulomatosis
C. Temporal arteritis
D. Herpes zoster ophthalmicus-associated cerebral angiitis
E. Takayasu arteritis
Correct Answer: The correct answer is D. Herpes zoster ophthalmicus may be associated with delayed contralateral
hemiparesis and other neurological deficits referable to angiitis in the distribution of the middle cerebral artery
ipsilateral to the rash. These other arteritides are not associated with vesicular rash.
Hilt DC, Buchholz D, Krumholz A, et al. Herpes zoster ophthalmicus and delayed contralateral hemiparesis caused

by cerebral angiitis: diagnosis and management approaches. Ann Neurol 1983;14:543-553.
Questions 32 and 33 refer to the following case vignette:
A 28-year-old man has been experiencing prominent abdominal pain with waxing and waning diarrhea that has
generally been nonbloody. He has lost 50 lbs in the past year. He has also been treated for renal calculi in the past.
32. Colonoscopy with intestinal biopsy in this individual is likely to show:
A. Diffuse inflammation of the colonic mucosa and superficial submucosa
B. Periodic acid-Schiff 9 (PAS)-positive inclusions in macrophages in the lamina propria
C. Mucosal plaquelike lesions over the colonic surface
D. Normal-appearing colonic mucosa
E. Inflammation extending deeply into the colonic wall with noncaseating granulomas
Correct Answer: The correct answer is E. Crohn's disease is typically characterized by abdominal pain with
diarrhea that is nonbloody and less urgent than the bloody, urgent diarrhea that occurs with ulcerative colitis.
Weight loss frequently occurs in Crohn's disease, and individuals with Crohn's disease are prone to develop both
gallstones and renal calculi. Thus, this individual is suffering from Crohn's disease. Intestinal biopsy in an
individual with Crohn's disease will typically demonstrate patchy, or segmental, involvement of both small
intestine and colon with deep, often transmural, inflammation that is frequently accompanied by noncaseating
granulomas. Diffuse, more superficial inflammation of the colonic mucosa is the pathological hallmark of
ulcerative colitis. The presence of PAS-positive inclusions in macrophages in a colonic biopsy specimen is highly
suggestive of Whipple's disease. Mucosal plaquelike lesions coating the colonic mucosa are seen in patients with
pseudomembranous colitis, which classically develops in the setting of antibiotic treatment of Clostridium difficile
infection. Colonic biopsy is normal in individuals with irritable bowel syndrome.
Podolsky DK. Inflammatory bowel disease. N Engl J Med 2002;347:417-429.
33. The neurological complication that this man has the highest risk of developing is:
A. Peripheral neuropathy
B. Myopathy
C. Stroke
D. Myelopathy
E. Seizures
Correct Answer: The correct answer is A. In the comprehensive survey of Lossos and colleagues, peripheral
neuropathic disease was the site of neurological involvement in 31.5% of patients with neurological complications

of their inflammatory bowel disease. Myopathy accounted for 16% of the cases, cerebrovascular complications
21%, and myelopathy 26%. Seizures are an infrequent complication of inflammatory bowel disease.
Lossos A, River Y, Eliakim A, Steiner I. Neurologic aspects of inflammatory bowel disease. Neurology
1995;45:416-421.
TYPE R QUESTIONS (EXTENDED MATCHING)
For each of the following patients with a fluid or electrolyte abnormality in questions 34 to 37, select the correct
treatment.
A. Free water restriction
B. 0.9 % normal saline with insulin
C. 10% calcium gluconate
D. Intravenous potassium chloride (KCl)
E. 3% saline
34. A 55-year-old man with hypertension and non-insulin-dependent diabetes is admitted to the hospital after he
could not be aroused at home earlier in the morning. He has a history of a prior stroke with residual mild left
hemiparesis. On admission to the hospital, his serum glucose is 650 mg/dL and serum sodium 132 mEq/L. Several
hours later, staff note that he has continuous, rhythmic jerking of the left arm and leg, although he is awake and
talking.


10
Correct Answer: The correct answer is B. Hyperosmolality is associated with hyperglycemia and can produce focal
neurological signs and symptoms, particularly in the face of a prior focal lesion. The treatment is rehydration with
normal saline and intravenous infusion of insulin. It may be necessary to encourage increased water intake or
administer hypotonic saline.
35. A 45-year-old man with a history of alcoholism and cirrhosis is found down on the street and transported to the
emergency department. He appears to be acutely intoxicated and is kept in the emergency department; an
intravenous line is placed, and resuscitation is begun. On examination, he has ascites. Laboratory values include a
sodium of 110 mEq/L and a potassium of 3.4 mEq/L.
Correct Answer: The correct answer is A. He has hypervolemic hypotonic hyponatremia, requiring free water
restriction. However, if he had symptomatic acute hyponatremia accounting for delirium or seizures, hypertonic

saline should be given to raise the sodium concentration to greater than 115 mEq/L.
36. A 25-year-old man presumed to have been in good health previously is found by a rancher in the desert in the
summer where he states he was left without water 2 days before. He is able to speak but cannot move due to
extreme weakness. He is transported to an emergency department where his temperature is 41°C, blood pressure is
80/60 mm Hg, and pulse is 120. Fluid resuscitation is begun with improvement in blood pressure. Initial laboratory
values include a creatine phosphokinase (CPK) of 10,000 IU/L and a potassium of 8.0 mEq/L. Electrocardiogram
shows a bradyarrhythmia with disappearance of P waves.
Correct Answer: The correct answer is C. This is life-threatening hyperkalemia from rhabdomyolysis; to protect the
heart, calcium gluconate is administered followed by insulin and glucose to redistribute potassium back into cells.
37. A 70-year-old man is transferred out of the intensive care unit after a 2-week hospitalization for pneumococcal
meningitis. He was treated with intravenous penicillin and emerged from coma 3 days prior to beingtransferred.
Two days after arriving on the step-down unit, he is noted to be a little more lethargic than when he arrived on the
unit. He is afebrile; vital signs are otherwise normal. Laboratory values include potassium of 3.5 mEq/L and
sodium of 121 mEq/L. Urine sodium is elevated.
Correct Answer: The correct answer is A. This is likely the syndrome of inappropriate antidiuretic hormone
secretion due to the meningitis with resultant isovolemic hyponatremia.
For questions 38 to 40, select the most likely diagnosis.
A. Polyarteritis nodosa
B. Churg-Strauss syndrome
C. Microscopic polyangiitis
D. Giant cell arteritis
E. Henoch-Schönlein purpura
F. Granulomatous angiitis of the nervous system
G. Takayasu's arteritis
38. A 43-year old woman has had a 2-year history of asthma with several flares and had pneumonia and a white
cell differential count showing 25% eosinophils during one of these flares. She has had diffuse arthralgias for
several months. One week ago she developed burning pain and numbness on the lateral aspect of her left leg. She
was admitted after she developed similar numbness and pain in the fourth and fifth fingers of the right hand, fevers,
and right footdrop. Sural nerve biopsy demonstrated fibrinoid necrosis of vessel walls.
Correct Answer: The correct answer is B. The diagnostic criteria for patients with Churg-Strauss syndrome consist

of asthma, peripheral eosinophilia, and histopathology of vasculitis, tissue eosinophil infiltrates, or extravascular
granulomas.
Masi AT, Hunder GG, Lie JT, et al. The American College of Rheumatology 1990 criteria for the classification of
Churg-Strauss syndrome (allergic granulomatosis and angiitis). Arthritis Rheum 1990;33:1094-1100.
39. A 38-year-old man has experienced several months of intermittent fevers and an involuntary weight loss of 10
lbs. He has had problems with swelling and pain in his knees, wrists, and elbows. Antinuclear antibody and
rheumatoid factor tests were negative. He now presents with an eruption of multiple, small, tender papules and
palpable nonblanching purpura on both legs. This morning he woke up with right leg pain and footdrop. Aphthous
ulcers are present on his tongue and buccal mucosa. Nerve conduction study/electromyography shows evidence of
polyneuropathy in a mononeuritis multiplex distribution.
Correct Answer: The correct answer is C. This man's presentation fits best with a diagnosis of microscopic
polyangiitis because of the occurrence of skin papules and purpura and polyneuropathy. Small vessels in the lungs
and kidneys may also be involved.
40. A 39-year-old woman presents to an emergency department with lethargy, confusion, and ataxia. She had
complained of gradually worsening diffuse Cheadache and neck stiffness for several months. Cranial MRI shows
multiple small hyperdense foci in the white matter and cortical white matter junction with leptomeningeal
enhancement. CSF examination shows a predominantly lymphocytic pleocytosis of 45 white cells/cm
3
and protein


11
of 76 mg/dL. Oligoclonal bands are absent. CSF cultures are negative; ANCA test is negative. Over the next few
days the patient's mental status worsens, and she develops a left hemiparesis.
Correct Answer: The correct answer is F. Typical features of granulomatous angiitisof the CNS (isolated CNS
vasculitis) are headache and development of encephalopathy over several months. CSF may show pleocytosis
and/or elevated protein or may be normal. ANCA are generally absent.
Neurogenetics April 2005
TYPE A QUESTIONS (ONE BEST ANSWER)
1. A 57-year-old man presents to his physician with a 6-month history of slowly progressive gait difficulties and

increasing difficulty with tremor of the hands. He is otherwise healthy and takes no medications. There have been
no speech or visual difficulties. His family history is negative for ataxia. His three children (all daughters) are
healthy. One of his grandsons has mental retardation of unknown etiology. On examination, his mental status and
language examinations are normal. He has no nystagmus or dysarthria. Strength is 5/5 throughout, and deep tendon
reflexes are normal. The sensory examination is normal. His gait is broad based, and tandem gait is grossly
impaired. There is an action and static tremor of both upper extremities. Magnetic resonance imaging (MRI) of the
head revealed nonenhancing T2-signal abnormalities in the middle cerebellar peduncles bilaterally. Genetic testing
for which of the following disorders would be most appropriate for this patient?
A. Fragile X syndrome
B. Friedreich ataxia
C. Dentatorubral-pallidoluysian atrophy
D. Spinocerebellar ataxia type 3 (Machado-Joseph disease)
E. Charcot-Marie-Tooth disease
Correct Answer: The correct answer is A. This patient most probably has fragile X-associated tremor ataxia
syndrome (FXTAS). Fragile X syndrome is a repeat expansion mutation of the FMR-1 gene on the X chromosome,
which is the most common inherited form of mental retardation. Approximately 50% of the maternal grandfathers
carrying the premutation-sized repeat expansion will develop a late-life tremor with ataxia. The patient would be
unlikely to have Friedreich ataxia, dentatorubral-pallidoluysian atrophy, or spinocerebellar ataxia type 3 given the
patient's age, absence of other clinical features, and the history of mental retardation in his daughter's son. Patients
with Charcot-Marie-Tooth disease (CMT) may have postural and action tremor but should not have cerebellar
ataxia. Moreover, patients with CMT have longstanding signs and symptoms of peripheral neuropathy.
2. A 10-year-old girl is brought to the office because her parents are concerned about her risk of developing a
seizure disorder. She has no history of staring spells or convulsions. Her monozygotic twin was diagnosed with
childhood absence epilepsy when she was 7 years old. Because of the family history, her primary physician ordered
an electroencephalogram (EEG), which showed generalized 3-Hz spike-and-wave discharges. What is the
likelihood that this patient will develop a seizure disorder?
A. 5%
B. 30%
C. 50%
D. 75%

E. 100%
Correct Answer: The correct answer is B. These numbers are not meant to be precise. However, in clinical practice
the concordance rate of childhood absence epilepsy in monozygotic twins is 100% for the EEG trait but only 30%
for the clinical development of absence seizures.
3. An 18-year-old woman presents because of two generalized tonic-clonic seizures that have occurred over the
past year. Each episode occurred in the morning, and she recalls staying up late the night before each seizure. She
also describes a 2-year history of occasional brief bilateral myoclonic jerks of her arms in the morning. Her
maternal aunt had a history of seizures. Neurological examination is normal. MRI of the brain is normal, and EEG
shows occasional bursts of generalized 3-Hz to 4-Hz spike-and-wave discharges. Which of the following is the
most likely diagnosis?
A. Juvenile myoclonic epilepsy
B. Lafora disease
C. Unverricht-Lundborg disease
D. Myoclonic epilepsy with ragged red fibers
E. Autosomal dominant nocturnal frontal lobe epilepsy
Correct Answer: The correct answer is A. This patient has the typical clinical features of juvenile myoclonic
epilepsy ( JME), including characteristic myoclonic jerks upon awakening and generalized tonic-clonic seizures
that may be precipitated by sleep deprivation. Although there is a strong genetic component to JME, with
concordance in all monozygotic twins, the causative genetic defect is only now becoming better understood. JME is


12
not associated with cognitive dysfunction and usually responds well to appropriate medications for primary
generalized epilepsy; however, patients typically require lifelong therapy. In contrast, Lafora disease (autosomal
recessive), Unverricht-Lundborg disease (autosomal recessive), and myoclonic epilepsy with ragged red fibers
(mitochondrially inherited) cause syndromes of progressive myoclonic epilepsy with neurological deterioration.
Autosomal dominant nocturnal frontal lobe epilepsy causes tonic and hyperkinetic seizures that occur mostly
during nonrapid eye movement sleep rather than upon awakening.
4. A healthy 22-year-old woman gives birth at 38 weeks to an infant with severe facial malformations. The
pregnancy and delivery were uncomplicated. The infant is microcephalic with a single eye located in the midline

and a small protruding noselike appendage above the orbit. A median cleft lip and palate is present. The Apgar
scores are 5 and 6 at 5 and 10 minutes. The child is hypotonic. An MRI reveals a single large ventricular cavity,
absence of the interhemispheric fissure and corpus callosum, an undivided thalamus, and evidence of
subependymal heterotopias. There is no family history of congenital malformations. Maternal use during pregnancy
of which of the following medications is most likely to produce this malformation?
A. Tetracycline
B. Phenytoin
C. Retinoic acid
D. Thalidomide
E. Diazepam
Correct Answer: The correct answer is C. This child has alobar holoprosencephaly, due to a defect of
prosencephalon cleavage at about day 42 of gestation. Sonic Hedgehog is an important protein responsible for
induction of cleavage. Sonic Hedgehog is produced by the notochord, ventral forebrain, and the floor plate of the
neural tube. Retinoic acid can down-regulate Sonic Hedgehog and produce this malformation if taken during early
pregnancy. The other medications listed are not known to produce holoprosencephaly. Other causes of
holoprosencephaly include maternal diabetes, syphilis, cytomegalovirus, toxoplasmosis, rubella, and chromosomal
abnormalities (eg, trisomy 13 and 18; duplications of 3p, 13q, and 18q; deletions of 2p, 7q, 13q, and 18q).
5. A 4-year-old girl presents with a 6-month history of progressive gait unsteadiness and dysarthria. She has
developed bobbing movements of the head, particularly when looking to the right or left. There has been no
weakness or sensory abnormality. Her 3-year-old brother has similar but milder symptoms. Her 15-year-old brother
and both parents have no symptoms. On examination, she has mild dysarthria and ataxic eye movement. She has
difficulty initiating lateral gaze and thrusts her head side to side to accomplish lateral eye movements. Conjunctival
and antecubital telangiectasias are present. Strength is 5/5 throughout. Deep tendon reflexes are mildly and
symmetrically reduced, and Babinski sign is absent. The sensory examination is normal. Genetic testing reveals
that the patient is homozygous for mutations in the ATM gene on chromosome 11q. Which of the following is the
most appropriate counseling for this child's parents?
A. Their 15-year-old son has a 25% chance of developing the disorder
B. The patient's future offspring have a 50% chance of developing the disorder
C. Any of the parents' future offspring have a 50% chance of being carriers of the mutation
D. The fact that neither parent has the disorder implies nonpaternity

E. Stroke is the most common cause of death in affected individuals
Correct Answer: The correct answer is C. This patient has ataxia telangiectasia (AT), an autosomal recessive
disorder resulting from homozygous mutations in the ATM gene on chromosome 11q. In most patients, the onset of
the illness will be in early childhood. Therefore, it is somewhat unlikely that the patient's 15-year-old brother has
the disorder, although he may be a carrier. The pattern of inheritance implies that both parents are unaffected
carriers of the mutation. Nonpaternity is therefore unlikely. Any future offspring of this couple have a 50% chance
of being carriers and a 25% chance of having AT. It is somewhat unlikely that the patient will reproduce given her
shortened life expectancy, future disability, and the likelihood of gonadal failure. If the patient were to reproduce,
all of her children would be carriers of the mutated gene and would only be clinically affected if the father of these
children were also a carrier or had AT. Most patients with AT die in their teens or 20s from bronchopulmonary
infection or neoplasia. Patients with AT are not at increased risk of developing stroke.
6. A 9-month-old girl presents with developmental delay and a 3-month history of infantile spasms. On
examination, she has no dysmorphic features. EEG shows hypsarrhythmia. Which of the following is the most
appropriate next step in establishing a diagnosis?
A. Brain MRI
B. Genetic testing
C. Neuropsychological testing
D. Repeat EEG
E. Magnetic source imaging


13
Correct Answer: The correct answer is A. The developmental delay is concerning for brain malformations. The
results of the imaging study may narrow the list of potential diagnoses for further evaluation by genetic testing.
Repeat EEG, neuropsychological testing, or magnetic source imaging is unlikely to provide further specific
etiological diagnostic information.
7. A 20-year-old man presents with a 5-year history of arm and leg weakness and gait difficulties. He first noted
problems in high school gym class when he could not keep up with his classmates running on the basketball court.
Over time he has noted increasing difficulty with bilateral footdrop and leg stiffness. In the last year, he has noted
fasciculations and wasting in the muscles of his arms and legs. He has had no bowel or bladder difficulties and no

sensory symptoms. He denies problems with swallowing, speech, or breathing. The patient is adopted, and no
biological family history is available. Examination reveals muscle wasting in the proximal and distal muscles of the
arms and legs. Rare fasciculation is present. The cranial nerve examination is normal. Strength is symmetrically
reduced in the arms and legs and is worse distally (3/5). Deep tendon reflexes are absent at the ankle and slightly
increased (3+) at all other sites. Babinski sign is present bilaterally. The sensory examination is normal. His gait is
slightly spastic. Which of the following genes is most likely affected in this patient?A/
A. SETX
B. GJB1
C. PMP22
D. MPZ
E. MTMR2
Correct Answer: The correct answer is A. This patient has an inherited autosomal dominantform of amyotrophic
lateral sclerosis type 4 (ALS4). It is caused by missense mutations in the senataxin gene (SETX) that appear to
cause neuronaldegeneration limited to motor neurons. Generally this disorder has its onset in childhood and a much
more benign clinical course than typical ALS. It may be associated with a normal lifespan. These cases may be
difficult to distinguish from cases of hereditary spastic paraparesis. Normal compound motor action potential
amplitudes may be helpful in distinguishing patients with hereditary spastic paraparesis from those with ALS4.
Mutations or deletions in GJB1, PMP22, MTMR2, and MPZ are associated with inheritedsensorimotor
neuropathies.
8. A 4-month-old boy presents with growth retardation, developmental delay, and seizures. He was the product of a
normal gestation and birth but has had difficulties with feeding since birth and seizures since 6 weeks of age. No
craniofacial dysmorphisms are present. The child's MRI revealssevere lissencephaly, more pronounced in the
frontal lobes than in the occipital lobes. The child's 28-year-old mother has a history of generalized tonic-clonic
seizures since the age of 10. These were well controlled on carbamazepine during pregnancy. She is otherwise
neurologically normal. An MRI of her head done 5 years ago showed a band of heterotopia beneath the cortical
surface but no evidence of lissencephaly. Genetic testing of the child reveals a mutation in the doublecortin gene of
chromosome Xq21-24. Which of the following mechanisms best explains the mother's less severe phenotype
compared with that of her son?
A. Random lyonization of the X chromosome
B. Anticipation

C. De novo mutation in the child
D. Additional mutation of LIS1 gene in the child
E. Balanced translocation in the child's X chromosome
Correct Answer: The correct answer is A. This child has X-linked lissencephaly due to a mutation in the gene
coding for doublecortin, a component of the microtubule cytoskeleton important for the normal migration of
neurons to the cerebral cortex. Because of random lyonization (inactivation of one X chromosome in each cell),
females with the mutation on one X chromosome will only partially express disordered neuronal migration with a
subcortical band heterotopia. Males who inherit the affected X chromosome from their mothers will express the
mutation in all cells and express the full-blown syndrome with lissencephaly, which usually ismost severe in the
frontal lobes. X-linked lissencephaly is not a repeat expansion disorder and, therefore, does not express
anticipation. A balanced translocation of the X chromosome is not possible in a male (who has only one X
chromosome). A second mutation in another gene (LIS1) is possible, although unlikely, and not necessary to
explain the phenotype of the patient in question.
9. A 58-year-old man presents for advice regarding possible apolipoprotein E (Apo E) testing for Alzheimer's
disease. He has no cognitive complaints. His father was diagnosed with Alzheimer's disease at age 78, and this
diagnosis was confirmed at autopsy when he died 4 years later. Neurological examination, including bedside
testing of memory and other cognitive functions, is normal. Which of the following is the most accurate statement
regarding Apo E testing in this patient?


14
A. Testing is recommended because, if he is Apo E4 negative, he has very little risk of developing Alzheimer's
disease.
B. Testing is recommended because, if he is positive for an Apo E4 allele, 50% of his children are at risk of
developing Alzheimer's disease.
C. Testing is recommended because, if he is positive for an Apo E4 allele, he will likely develop Alzheimer's
disease during his lifetime.
D. Testing is not recommended because Apo E4 is a susceptibility gene and is not accurately predictive of the
development of Alzheimer's disease.
E. This test is not recommended since currently no effective preventive treatment is available for Alzheimer's

disease.
Correct Answer: The correct answer is D. Apo E4 testing is an example of genetic risk factor analysis. The Apo E4
allele is a polymorphism, not a mutation; the presence of an Apo E4 allele represents a genetic risk factor for the
development of Alzheimer's disease but is neither necessary nor sufficient to cause the disease. Some persons with
the E4 allele do not develop Alzheimer's disease in a normal life span, and about 40% of patients with Alzheimer's
disease do not have an E4 allele. Since the predictive value of the test is not very high in asymptomatic individuals,
Apo E testing in this scenario is not recommended.
10. A 40-year-old man presents with a 10-year history of progressive symmetrical motor and sensory
abnormalities, first involving the feet and then the hands. He reports that he has had "skinny legs" and high arches
since he was a teenager. He has had no pain or abnormalities of bowel or bladder function. Examination shows
symmetrical weakness and atrophy in the distal extremities. Deep tendon reflexes are absent. Pin, temperature, and
vibration sense are reduced in the hands and feet. Joint position sense is reduced in the toes and fingers. Gait testing
reveals mild steppage gait, and he has difficulty walking on his toes. The nerve conduction velocities are slow.
Genetic testing reveals a duplication in the PMP22 gene. The patient states that neither parent has clinical evidence
of peripheral neuropathy. Which of the following is a potential cause of this patient having the genetic
abnormality?
A. New mutation in the proband
B. Germline mosaicism
C. False paternity
D. None of the above
E. A, B, and C
Correct Answer: The correct answer is E. This patient has Charcot-Marie-Tooth disease type 1A (CMT1A), an
autosomal dominant disorder. In about 10% of patients, this is a de novo mutation and neither parent has the
mutation. Germline mosaicism refers to the development of the mutation within DNA of the sperm cell or ovum.
While this is rarely, if ever, described in CMT1A, it remains a possibility. The patient's father of record may not be
his biological father. This underscores the importance of actually examining family members. Therefore, options A,
B, and C are possibilities in this case.
11. A 4-day-old infant boy has evidence of hypotonia and poor suck. He was the product of a normal gestation and
delivery. He was noted to be "floppy" at birth, and his Apgar scores were 8 and 8 at 5 and 10 minutes, respectively.
Since that time he has been unable to breast-feed and has required a nasogastric feeding tube. His respiratory effort

has been noted to be weak, but he has not required artificial ventilation. He is diffusely hypotonic with a weak
Moro reflex. There is no family history of neuromuscular disease, although his 30-year-old mother states that she is
adopted and unacquainted with her biological parents. The mother has a history of insulin-dependent diabetes
mellitus. She reports that she sometimes has difficulty releasing the handles of a shopping bag or suitcase if she has
been gripping them tightly. She has an angular face with prominent cheekbones and is noted to have mild weakness
and wasting of distal muscles in the hands and feet. Her examination also shows percussion myotonia in the thenar
eminence. On genetic testing, the infant has evidence of 1000 CTG repeats in the 3' untranslated region of the
myotonic dystrophy protein kinase gene. Which of the following best explains the finding that the infant has more
severe disease than the mother?
A. X-linked dominant inheritance pattern
B. Anticipation
C. Germline mosaicism
D. New mutation in the proband
E. Variable penetrance
Correct Answer: The correct answer is B. This infant has congenital myotonic dystrophy (DM) from a repeat
expansion in the DM protein kinase gene. Expanded repeats are highly dynamic mutations and tend to change size
from one generation to the next. They often enlarge further with transmission. Large mutations tend to cause more
severe disease earlier. The mother most certainly has a repeat expansion, although far fewer repeats than her son.


15
This is an example of anticipation. DM is an autosomal dominant disorder, not X-linked. Germline mosaicism may
be an explanation for an affected proband when neither parent appears to carry the affected gene. In this case, only
some of the ova or sperm carries the gene. The mother clearly has signs of the disorder, so the child's disease does
not represent a new mutation. In the case of DM, the disease is virtually fully penetrant with the severity at age of
onset of the disease being determined by the number of CTG repeats.
12. A 21-year-old man presents for an evaluation after he was unable to pass basic training for the army. He had
particular difficulty doing pull-ups; he was able to do this exercise in high school, but for the past 2 years he has
noticed gradual difficulty lifting his arms over his head and lifting heavy objects. There is no family history of
similar problems. On examination, mild bilateral facial weakness is present. He has moderate weakness and

wasting of the right biceps and triceps; the same muscles on the left are normal. He has bilateral scapular winging.
Sensation is intact. Reflexes are 1+ and symmetrical, and toes are downgoing. Serum creatine kinase (CK) is 246
IU/L (normal =<200). Which of the following abnormalities is most likely present in this patient?
A. Deletion of a repeat element on chromosome 4
B. Expansion of a trinucleotide repeat on chromosome 19
C. Mutation of the dystrophin gene
D. Mutation of the lamin A/C gene
E. Mutation of the emerin gene
Correct Answer: The correct answer is A. This patient most likely has facioscapulohumeralmuscular dystrophy
(FSHD). Features typical of FSHD include the age ofonset, facial weakness (although 15% of patients may have
normal facialstrength), and the prominent distribution of weakness around the shouldergirdle, which may be
asymmetrical. Although FSHD is autosomal dominant,the lack of a family history is not unusual since 20% to 30%
of cases arenew mutations. FSHD occurs due to a deletion in a series of 3.3 kb repeatson chromosome 4. However,
because a similar series of repeats is seen onchromosome 10, DNA testing for FSHD is complex and results in a
report ofthe estimate of probability that the patient has an FSHD-associated deletion.This patient's clinical signs
and symptoms are not suggestive of myotonicdystrophy, the most common form of which is associated with
expansion ofa trinucleotide repeat on chromosome 19. The presence of facial weaknessmakes Emery-Dreifuss
muscular dystrophy (associated with mutations of thelamin A/C or emerin genes) and Duchenne-Becker muscular
dystrophy(caused by dystrophin gene mutations) unlikely; Duchenne-Becker musculardystrophy is also ruled out
by the absence of significant CK elevation.
13. A 14-year-old boy presents with a 1-year history of gradually progressive incoordination of gait and limb
movements with dysarthria. He was the product of a normal gestation and delivery, and his early milestones were
reached at the appropriate time. Until age 13, he was a good athlete, running on the school track team. He is an
excellent student academically. The family history reveals no neurological disease. His 50-year-old parents are
third cousins and healthy. He has two healthy sisters, ages 8 and 10. His Mini-Mental Status Examination is 30/30.
He has a mild kyphoscoliosis and high arches. His cranial nerve examination shows ataxic eye movements and an
ataxic dysarthria. His visual acuity is 20/25 in both eyes, and mild optic atrophy is present. He has 5/5 strength
throughout. The deep tendon reflexes are absent, and bilateral Babinski signs are present. There is prominent gait
and limb ataxia. Sensory examination shows impairment of joint position and vibration sense in the fingers and
toes. MRI shows minimal cerebellar atrophy. Genetic testing of the patient shows 1000 GAA repeats in the first

intron in both alleles of the FRDA gene on chromosome 9. Which of the following is the most accurate statement
concerning this patient's disorder?
A. The lack of family history is most suggestive of a new mutation
B. The repeat expansion occurs in a protein-coding region of the gene.
C. His sisters each have a 50% chance of developing this disorder.
D. Cardiomyopathy is the most common cause of death.
E. This disorder exhibits an autosomal dominant pattern of inheritance.
Correct Answer: The correct answer is D. This patient has Friedreich ataxia, an autosomal recessive disorder with a
carrier frequency of about 1 in 120 in European populations. Most affected individuals are homozygous for an
expanded trinucleotide (GAA) repeat in the FRDA gene on the proximal long arm of chromosome 9. The mutation
is in the untranslated region of the gene and produces hypermethylation-silencing of the disease gene. As the
disorder is autosomal recessive, both parents are likely carriers (particularly given their consanguinity). Thus the
patient's sisters each have a 25% of inheriting neither abnormal gene copy, a 50% chance of being carriers of one
gene copy, and a 25% of inheriting both abnormal gene copies and developing Friedreich ataxia. Most patients with
Friedreich ataxia die of associated cardiomyopathy or restrictive lung disease from the kyphoscoliosis. Friedreich
ataxia is one of the few trinucleotide repeat disorders with an autosomal recessive pattern of inheritance.
14. A 16-year-old boy presents with a 2-year history of difficulty walking. He has developed bilateral footdrop and
sensory ataxia. His examination reveals severe loss of vibration and position sense. Pinprick sensation was also


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reduced from the toes to the distal calves. Anterior tibialis strength was 4/5 bilaterally. His nerve conduction
studies reveal severe slowing of motor and sensory conduction velocities (10 m/s). Genetic testing reveals
homozygous mutations in the periaxin (PRX) gene. There are no other affected family members, but both parents
are noted to be heterozygous for the mutation. What is the chance that the patient's clinically unaffected 30-year-old
brother is a carrier of the abnormal gene?
A. One in four
B. One in two
C. Two in three
D. Three in four

E. One in three
Correct Answer: The correct answer is C. This patient has CMT4F, an autosomal recessive disorder caused by
mutations in the periaxin gene (PRX). To be affected, the patient must inherit one defective gene from each parent.
There is a 25% chance of this occurring. There is a 25% chance that a child will not inherit the mutated gene from
either parent and a 50% chance that the child will inherit one copy of the mutation from either the mother or father.
In this case the child would be a carrier. If the brother is truly unaffected, his chance of being a carrier would be
two in three. The mathematics are: chance of being a carrier (1/2) divided by chance of carrier (1/2) + chance of no
mutation (1/4) = 1/2 divided by 3/4 = 2/3.
15. A 6-year-old boy presents for evaluation of learning difficulties. He was the product of a normal gestation and
birth. His Apgar scores were 8 and 10 at 5 and 10 minutes, respectively. His mother says that he was "a little slow"
in learning to walk and did not speak his first words until 18 months. He is having difficulty keeping up
academically with the other children in his first-grade class. Formal psychometrics reveal an IQ of 55. His
examination reveals a mildly dysmorphic face with large ears and mandible. Which of the following statements is
most consistent with this patient's likely diagnosis?
A. The patient's maternal grandfather has an action tremor and gait ataxia.
B. The patient's father has mild mental retardation and large testicles.
C. The patient's 16-year-old sister has choreiform movements.
D. Any future male offspring of the patient will have a 50% risk of mental retardation.
D. Any future male offspring of the patient will have a 50% risk of mental retardation.
Correct Answer: The correct answer is A. This patient has fragile-X syndrome, an X-linked dominant disorder due
to a repeat expansion of the FMR-1 gene. This disorder is maternally transmitted so the patient's father and the
patient's future male offspring would not be expected to inherit the gene. While the patient's sister could be
affected, chorea is not a clinical feature of this disorder. Males who carry the premutation-sized fragile-X repeats
may develop a late-life tremor/ataxia syndrome. Thus, the patient's maternal grandfather would be at risk to
develop these symptoms. Patients with fragile-X syndrome often have T2 signal abnormalities in the middle
cerebellar peduncles and cerebellar white matter.
16. A 35-year-old right-handed man presents with paresthesias in the ulnar aspect of his left hand over the last 3
months. He has noted some grip weakness in the left hand over the same period. His past medical history is
remarkable for bilateral carpal tunnel release surgery and painless right footdrop 3 years ago. The footdrop
gradually resolved after his family physician advised him to stop crossing his legs. His father and one of his sisters

have had carpal tunnel release surgeries. A brother required ulnar nerve transposition surgery. He has another
sister, who is 20 years old, two daughters, and one son who have no neurological symptoms. On examination, he
has wasting and weakness in the interossei and hypothenar muscles of the left hand. There is some mild weakness
of left wrist flexion. There is reduced pinprick and temperature sensation on the ulnar aspect of the palmar and
dorsal left hand. Palpation of the left ulnar nerve at the ulnar groove reproduces his paresthesias. Nerve conduction
studies reveal evidence of conduction block in the left ulnar nerve at the elbow, slowing of peroneal conduction
around the knee, and prolonged median and peroneal distal motor latencies. Genetic testing reveals a deletion in the
PMP22 gene. Which of the following is the most appropriate counseling for this patient?
A. His son is at no risk to develop this neuropathy
B. Each of his children has a 50% chance of developing this neuropathy
C. His daughters have a 25% chance of developing this neuropathy
D. Sons or daughters who inherit the mutation have a 50% chance of Cbeing asymptomatic
E. His asymptomatic 20-year-old sister has not inherited the abnormal gene
Correct Answer: The correct answer is B. The patient has hereditary neuropathy with liability to pressure palsies
(HNPP), an autosomal dominantly inherited neuropathy characterized by episodes of focal weakness and sensory
loss rather than a length-dependent neuropathy. HNPP is caused by a deletion in the PMP22 gene. The autosomal
dominant nature of this disorder indicates that 50% of the patient's biological children will be at risk to develop the
neuropathy. While many people believe that the frequency of HNPP is underreported, the actual percentage of