Life Long Learning in Neurology - part 2 pptx

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asymptomatic mutation-positive patients is not known. Without clinical and genetic evaluation, it cannot be known
if the sister has inherited the affected gene. Although the onset is usually in the second decade of life, phenotypes
vary.
17. A 10-year-old boy presents with a 1-year history of difficulties in school, behavioral problems, and unsteady
gait. He was the product of a normal gestation and delivery and reached his early milestones at the appropriate
time. Over the last year he has become more withdrawn and has failed several of his classes at school. Previously
he was a good student. He has been previously healthy and takes no medications. Family history reveals that his
father had some form of a progressive mental illness with "shaking" and committed suicide at age 42. Numerous
relatives on his paternal side were institutionalized in middle age for "mental disease," several of whom died of
suicide. There is no maternal family history of neurological or psychiatric illness. On examination, he is distractible
and scores 20/30 on the Mini-Mental Status Examination. He has a masked face and reduced eye blink. His gait is
bradykinetic. There is diffuse rigidity in the axial musculature and extremities. He has diffuse hyperreflexia and
bilateral Babinski signs. MRI of the head is normal. Genetic testing reveals 110 CAG repeats in a gene on 4p16.3.
In addition to demonstrating anticipation, the inheritance of this patient's disease is also an example of which of the
following?
A. Autosomal recessive inheritance
B. Probable nonpaternity
C. Parent-of-origin effect
D. Expansion of a gene in a noncoding region
E. X-linked dominant inheritance
Correct Answer: The correct answer is C. This patient has the juvenile Westphal variant of Huntington's disease
(HD). This disorder results from increased numbers of CAG repeats (coding for glutamine) in the coding region of
a gene on 4p16.3, coding for the huntingtin protein. The larger the repeat expansion, the earlier and more severe the
disease. With progressive generations, the repeat expansion often enlarges (anticipation). When the disease onset is
in childhood, the gene has almost always been inherited from the father (parent-of-origin effect). This should not be
a case of nonpaternity as the father's "mental illness" and that of numerous paternal family members were almost
certainly HD. HD is inherited in an autosomal dominant pattern.
18. A 44-year-old man presents with a 4-year history of progressive gait difficulties. In recent months he has noted

difficulty with upper extremity incoordination. He reports occasional episodes of horizontal diplopia and notes
difficulty looking up into the rearview mirror when driving. His 65-year-old father has been in a nursing home for
10 years with ataxia and some form of peripheral neuropathy. On examination, he has prominent lid retraction with
mild exophthalmos. Impaired voluntary vertical and horizontal gaze is present, but the oculocephalic reflex is
intact. He has an ataxic dysarthria. Mild tongue wasting and weakness with fasciculation are present. His limb
strength is 5/5 diffusely. The deep tendon reflexes are symmetrically brisk, and the plantar reflexes are flexor. His
gait is broadbased and ataxic. Moderate limb ataxia is present. The remainder of his examination is normal. Which
of the following disorders is the most likely diagnosis in this patient?
A. Dentatorubral-pallidoluysian atrophy
B. Machado-Joseph disease
C. Friedreich ataxia
D. Spinocerebellar ataxia type 10
E. Ataxia telangiectasia
Correct Answer: The correct answer is B. This patient has a cerebellar ataxia with onset in middle age. Associated
symptoms include supranuclear ophthalmoplegia, lid retraction, and tongue fasciculations. The most likely
diagnosis is spinocerebellar ataxia type 3 (Machado-Joseph disease). This disorder is caused by an autosomal
dominant polyglutamine-coding CAG repeat expansion on chromosome 14. The age of onset depends on the repeat
length. Longer repeats present earlier with dystonia and pyramidal signs. Intermediate-length repeats present in
middle age with ataxia, and shorter repeats present in older patients with amyotrophy/neuropathy. Exophthalmos is
characteristic, although not always present. Dentatorubral-pallidoluysian atrophy is a rare progressive ataxia with
cognitive changes, chorea, and seizures. Friedreich ataxia and ataxia telangiectasia are autosomal recessive ataxias
with onset in childhood. Spinocerebellar ataxia type 10 is an ataxic syndrome with seizures primarily seen in
families of Mexican descent.
19. A 13-year-old boy presents with a 1-year history of progressive ataxia and upper extremity incoordination. He
is a good student but has not been able to participate in sports this school year because of difficulty running.
Recently his parents have noted that his speech is slurred. On examination, he has high arches and a mild thoracic
scoliosis. He has a mild ataxic dysarthria. Ataxic visual pursuit and nystagmus are present. The funduscopic
examination is normal. His strength is 5/5 throughout. The deep tendon reflexes are symmetrically reduced.
Babinski sign is present bilaterally. Reduced vibration and joint position sense are present in the feet. Testing for

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metabolic disorders is negative. MRI of the head shows cerebellar atrophy. Genetic testing reveals a large repeat
GAA expansion (500 repeats) of the FRDA gene on chromosome 9q. Which of the following additional tests would
be most appropriate in this patient?
A. Serum immunoglobulins
B. Serum [alpha]-fetoprotein
C. Echocardiogram
D. Blood smear for acanthocytes
E. Ceruloplasmin level
Correct Answer: The correct answer is C. This patient has Friedreich ataxia, an autosomal recessive GAA repeat
expansion disorder of the FRDA gene on chromosome 9q. Hypertrophic cardiomyopathy is common in these
patients. Arrhythmias and cardiac failure are a major cause of morbidity and mortality. Immunoglobulin deficiency
and elevated a-fetoprotein levels are seen in ataxia telangiectasia. Acanthocytosis is a feature of
abetalipoproteinemia. Low ceruloplasmin levels are seen in Wilson's disease, an autosomal recessive disorder due
to a gene defect on chromosome 13.
20. A 5-year-old boy presents with developmental delay and a 3-month history of generalized tonic-clonic seizures.
Examination shows facial angiofibromas and hypomelanotic skin macules. Which of the following is the most
likely diagnosis?
A. Lafora disease
B. Unverricht-Lundborg disease
C. Severe myoclonic epilepsy of infancy
D. Tuberous sclerosis
E. Myoclonic epilepsy with ragged red fibers
Correct Answer: The correct answer is D. Facial angiofibromas and hypomelanotic skinC macules are common
examination findings in tuberous sclerosis; this patient's seizures most likely represent secondary generalization
from a focal cortical hamartoma. Severe myoclonic epilepsy of childhood presents as intractable epilepsy within
the first year of life with developmental delay. Lafora disease and Unverricht-Lundborg disease present as
progressive myoclonic epilepsy with intellectual deterioration, and myoclonic epilepsy with ragged red fibers is
characterized by myoclonic epilepsy and myopathy. None of these other conditions is associated with the

dermatological findings seen in this patient.
21. A 12-year-old boy is brought to the office by his mother because she is concerned about his risk of developing
Huntington's disease (HD). The boy has no neurological or psychiatric symptoms or signs and is doing well in
school. His 36-year-old father was diagnosed with HD 2 years ago. Which of the following is the most accurate
statement regarding HD gene testing in this patient?
A. Testing for the HD gene in the child should proceed as long as written consent is obtained from both parents.
B. Testing for the HD gene in this child should proceed with consent of the parents only if the child appears to fully
understand the ramifications of the test.
C. Testing for the HD gene should occur only if formal neuropsychological testing reveals an abnormality.
D. Testing for the HD gene in this child is not appropriate because no effective preventive treatment of this disease
is currently available.
E. Testing for the HD gene in this child is not appropriate because this test is usually not accurately predictive of
the development of disease.
Correct Answer: The correct answer is D. Whether or not consent is obtained from the family or the patient appears
to understand the significance of the test, presymptomatic testing in a minor is not appropriate for HD or any other
disease for which no preventive intervention is currently available. Likewise, performing neuropsychological
testing to screen for a previously unrecognized problem is not appropriate in this scenario. Although some HD gene
testing may result in the finding of intermediate repeat lengths and an indeterminant risk of disease, the finding of a
clearly abnormal CAG repeat length (ie, greater than 40) is accurately predictive of the development of HD.
Testing in a minor should only occur if the patient is symptomatic (ie, as a diagnostic, but not a predictive, test).
The potential for psychosocial harm (regarding employment, insurance, or personal interactions) as a result of
predictive testing is particularly great for a minor, and at least 90% of those at risk choose not to undergo predictive
testing once they reach adulthood.
22. A 17-year-old boy presents with a 4-year history of generalized tonic-clonic seizures associated with
intermittent myoclonic jerks of the upper extremities. The seizures have been refractory to antiepileptic drugs. His
cognitive function has undergone a gradually progressive decline. EEG shows spike-and-wave discharges of 3-Hz
frequency. Which of the following diagnostic tests is most likely to establish the diagnosis?
A. Brain MRI
B. Genetic testing

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C. Neuropsychological testing
D. Repeat EEG
E. Magnetic source imaging
Correct Answer: The correct answer is B. This patient's clinical history is most consistent with a syndrome of
progressive myoclonic epilepsy. However, no additional information is available to identify the underlying cause.
For such difficult cases, genetic testing is now available for Lafora disease, Unverricht-Lundborg disease, and
myoclonic epilepsy with ragged red fibers. Brain MRI is likely to be unremarkable in each of these conditions, and
neuropsychological testing would not specifically differentiate between the causes of progressive myoclonic
epilepsy. Further EEGs in this patient would not be diagnostically useful since an EEG abnormality consistent with
progressive myoclonic epilepsy has already been found in this patient. Magnetic source imaging is not indicated in
this case. This study is most useful when lateralizing clinical features or interictal spike discharges suggest the
presence of a resectable epileptogenic focus.
23. A 3-year-old boy presents with severe motor developmental delay. He was the product of a normal pregnancy
and vaginal delivery. Postpartum he was noted to have reduced muscle tone. He has had numerous respiratory
illnesses, some requiring hospitalization but none requiring artificial ventilation. He was able to sit unsupported at
10 months and crawl at 11 months. He began to walk at age 2 but has required leg and ankle bracing. Bowel and
bladder function are normal, and cognitive development has been normal. There is no family history of neuropathy,
and the patient has two older siblings who are neurologically normal. Motor testing reveals severe distal weakness
in the upper and lower extremities with marked distal wasting. Pes cavus and scoliosis are present. The deep tendon
reflexes are absent. There is a stocking-glove loss to all sensory modalities. Spirometry reveals evidence of
respiratory muscle weakness. Nerve conduction studies show reduction of sensory and motor amplitudes and
markedly slowed conduction velocities (in the range of 10 m/s). A sural nerve biopsy shows evidence of severe
demyelination and axonal loss. Which of the following is the most accurate statement concerning this patient's
condition?
A. Insufficient data are available to diagnose Dejerine-Sottas neuropathy in this patient.
B. The absence of a family history makes an inherited neuropathy unlikely.
C. The sural nerve biopsy was an essential part of the patient's evaluation.
D. Genetic testing should include a search for missense mutations in PMP and EGR2.

E. Any male siblings of the patient will be at no risk to develop this problem.
Correct Answer: The correct answer is D. This patient meets the clinical criteria for Dejerine-Sottas neuropathy,
which include onset by 2 years of age; severe motor, sensory, and skeletal deficits; markedly abnormal nerve
conduction velocities, and evidence of severe demyelination or axonal loss on nerve biopsy. It is a clinical
designation and includes multiple disorders associated with mutations or deletion of PMP22, MPZ, EGR2, among
others. The absence of family history does not exclude an inherited neuropathy as the disorder may be autosomal
recessive or represent a new mutation. False paternity is also a possibility. Sural nerve biopsies are rarely necessary
to make a diagnosis in patients with a Dejerine-Sottas phenotype or to define the genetic cause. Risk to any other
future children the parents may have cannot be determined until the mutation and pattern of inheritance are
established. This underscores the importance of genetic testing.
24. A woman has two sons who were diagnosed with Duchenne muscular dystrophy in early childhood, both of
whom were found to have a deletion of exons 40 through 52 of the dystrophin gene. The woman herself does not
have a dystrophin deletion, however. Which of the following genetic processes is the most likely explanation for
this woman's normal testing?
A. Anticipation
B. Germline mosaicism
C. Mitochondrial inheritance
D. New mutation
E. Paternal inheritance
Correct Answer: The correct answer is B. This woman is most likely germline mosaic for the dystrophin deletion,
ie, her blood DNA is normal, but her germline carries the mutation that was passed on to her affected sons.
Mitochondrial inheritance (which is always maternally transmitted) is an implausible explanation since the
dystrophin gene is on the X chromosome. Paternal inheritance cannot be an explanation since the gene on the X
chromosome can only be passed from the mother to the children. Since the genetic abnormality here is not a
trinucleotide repeat, anticipation would not explain the patient's normal testing; anticipation refers to the
phenomenon seen in some trinucleotide repeat diseases where abnormal expanded repeats may become larger from
generation to generation, causing earlier symptom onset and more severe disease in successive generations.
25. A 4-year-old boy presents with a 12-month history of weakness and falls. His parents note that he seems
clumsy, has difficulty running and climbing stairs, and tends to walk on his toes. He has a 6-year-old brother and a

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12-year-old sister who are well, and there is no other family history ofsimilar difficulties. Examination shows mild
weakness in deltoids and hip flexors, and hypertrophy of the calves. Sensation appears normal, and reflexes are 1+
and symmetrical, with downgoing toes. Gowers' sign is present. His gait is waddling, and he tends to walk on his
toes. Serum CK is 8784 IU/L. Which of the following is the most appropriate next step in diagnostic evaluation?
A. DNA testing
B. Electromyography
C. MRI of the brain
D. Muscle biopsy
E. Skin biopsy
Correct Answer: The correct answer is A. This patient's signs, symptoms, and CK elevation are typical of
Duchenne muscular dystrophy, which is due to a mutation in the dystrophin gene. Routine DNA analysis of the
dystrophin gene identifies 60% to 70% of dystrophin mutations (deletions and duplications). If DNA testing for a
dystrophin mutation in this patient is normal, then the next step would be to perform a muscle biopsy with
dystrophin immunohistochemistry. Electromyography would not likely add further diagnostic specificity in this
child whose signs and symptoms already are most consistent with a dystrophic muscle process. MRI of the brain
and skin biopsy (for merosin immunostaining) can be helpful in the evaluation of patients with congenital muscular
dystrophy but are not indicated in this scenario.
26. An 8-year-old girl presents because of weakness. Her parents note that she seems to have been weaker than
other children since birth and she was never able to run or jump like others her age. No definite worsening has
occurred. Her family history is notable for a paternal aunt who died at age 18 of malignant hyperthermia during
general anesthesia for an appendectomy; she had no history of weakness. Examination shows 4/5 strength in hip
flexors and deltoids; the remainder of the motor examination is normal. Sensation is normal, and reflexes are 2+
and symmetrical with downgoing toes. Serum CK is 184 IU/L. Which of the following is the most likely diagnosis?
A. Central core disease
B. Duchenne muscular dystrophy
C. Limb-girdle muscular dystrophy
D. Myofibrillar myopathy
E. Nemaline myopathy

Correct Answer: The correct answer is A. This patient's clinical history and examination are most consistent with a
congenital myopathy. Central core disease, an autosomal dominant congenital myopathy, is associated with
susceptibility to malignant hyperthermia under certain forms of general anesthesia and is, therefore, the most likely
diagnosis. Susceptibility to malignant hyperthermia can occur in patients with central core disease even if they do
not have clinical weakness. Myofibrillar myopathy and nemaline myopathy are also forms of congenital myopathy
but are not associated with malignant hyperthermia. Duchenne muscular dystrophy is unlikely given the patient's
sex and the normal CK; limb-girdle muscular dystrophy is also unlikely because of the normal CK. In addition,
neither of these conditions is associated with susceptibility to malignant hyperthermia.
27. A 30-year-old man presents with a 2-year history of progressive gait and limb ataxia, dysarthria, and spasticity
in all four limbs. There is no family history of ataxia or other neurological diseases. The workup for metabolic and
paraneoplastic disorders is negative, and MRI of the head demonstrates only cerebellar and brain stem atrophy.
Despite the negative family history, this patient could still have an inherited form of ataxia for which of the
following reasons?
A. Autosomal recessive inheritance pattern
B. Incomplete penetrance of the mutation in other family members
C. Death of carrier parent before symptom onset
D. New mutation in the proband
E. All of the above are correct
Correct Answer: The correct answer is E. Patients with autosomal recessive ataxias are often the only affected
person in their family, particularly if the proband has few siblings. In autosomal dominant ataxias, one can have an
apparently negative family history due to incomplete penetrance of the mutation, early death of the carrier parent
before symptom onset, false paternity, or the occurrence of a de novo mutation in the proband. An X-linked pattern
of inheritance can also be missed if there are few maternal male relatives, and mitochondrial diseases can be
sporadic.
28. A 20-year-old woman presents with a 5-year history of migraine headaches. More recently, she has developed
vertigo, dysarthria, and unsteady gait with her migraines. These episodes last several hours and then resolve. They
tend to occur during times of stress and after intense exercise. In the last few months she has noted mildly impaired
balance, which makes running on a treadmill difficult. Her father had episodes of ataxia before his death of heart
attack at age 40. She is an only child and has no other affected relatives. Her neurological examination is entirely

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normal save for mild difficulty with tandem gait. Neuroimaging and metabolic workup for cerebellar ataxia are
negative. Genetic testing for repeat expansion ataxic disorders is negative. Which of the following medications is
most likely to be helpful in treating and preventing this patient's episodes?
A. Vitamin E
B. Calcium carbonate
C. Acetazolamide
D. Idebenone
E. Propranolo
Correct Answer: The correct answer is C. This patient most probably has episodic ataxia type 2, an autosomal
dominant disorder due to a mutation in a gene (CACNA1A) coding for a calcium channel protein. Commercial
genetic testing is not yet available for this disorder. Acetazolamide may be very helpful as symptomatic treatment
for this disorder. The other medications listed would not be helpful for this disorder.
29. A 15-year-old boy presents with a 3-year history of progressive weakness. He has no other significant past
medical history. Family history is significant for a brother who also had weakness and died of sudden cardiac death
at the age of 16. There is no history of weakness, syncope, or cardiac problems in his 22-year-old brother, his 10-
and 18-year-old sisters, or his parents. Examination shows contractures of his elbows and ankles, with 4/5
weakness in biceps, triceps, and tibialis anterior muscles. Sensation is normal, and reflexes are 1+ and symmetrical
with downgoing toes. Serum CK is 320 IU/L. Mutations of a gene encoding which of the following proteins is most
likely responsible for this patient's illness?
A. Myotubularin
B. Dystrophin
C. Emerin
D. Fukutin-related protein
E. Merosin
Correct Answer: The correct answer is C. This patient's signs and symptoms are most consistent with X-linked
Emery-Dreifuss muscular dystrophy (EDMD), which is caused by mutations in emerin, a widely expressed protein.
EDMD is characterized by early contractures, progressive limb-girdle weakness, and cardiomyopathy, which may
present as a life-threatening rhythm disturbance. A phenotypically identical but autosomal dominant form of

EDMD is caused by mutations in another nuclear lamina protein, lamin A/C. Mutations in dystrophin are
associated with Duchenne-Becker muscular dystrophy, which is less likely than EDMD in this patient, especially
given this patient's early contractures and the very mildly elevated CK. Mutations in merosin and fukutin-related
protein are implicated in certain forms of congenital muscular dystrophies not suggested by this patient's clinical
history. Mutations in fukutin-related protein are also associated with some of the later-onset limb-girdle muscular
dystrophies, but this diagnosis is also less consistent with this patient's history and examination than EDMD.
Mutations of myotubularin are seen in myotubular myopathy, an X-linked congenital myopathy that usually
presents in infancy with profound hypotonia and respiratory insufficiency.
30. An 8-year-old boy presents with a 6-month history of gait problems and learning difficulties. He was the
product of a normal gestation and delivery. He reached the usual childhood milestones at the appropriate time and
has been a good student in school. This semester, however, he has had behavioral problems and has obtained poor
grades. His parents note that he is clumsier and falls frequently when playing with his friends. He has two healthy
sisters. His mother is adopted and has no knowledge of her biological family. There is no family history of
neurological disorders in his father or his father's family. On examination, the patient is noted to have increased
pigmentation of the oral mucosa and skin folds. He is highly distractible and hyperactive. The cranial nerve
examination reveals mild optic atrophy. Hearing is reduced. His gait is slightly stiff, broad based, and ataxic.
Strength is 5/5 throughout. The deep tendon reflexes are symmetrically increased, and Babinski sign is present
bilaterally. The sensory examination is normal. MRI of the head reveals increased T2 signal in the parieto-occipital
regions bilaterally without contrast or mass effect. Pontocerebellar atrophy is present. Plasma very long chain fatty
acids are increased, and serum cortisol is reduced. Which of the following is the most accurate statement
concerning this patient's neurological disorder?
A. There is a 50% risk that any future male siblings of this patient will be affected.
B. Dietary therapy is effective in reversing neurological deficits in this condition.
C. This disorder is associated with a mutation in mitochondrial DNA.
D. Steroid replacement will reduce neurological disability.
E. The absence of other affected family members suggests false paternity.
Correct Answer: The correct answer is A. This patient has adrenoleukodystrophy, which is due to a mutation in the
X-ALD gene on chromosome Xq28. As the disorder is X-linked, the gene affects male offspring of female carriers.
As the disorder is maternally transmitted, the father's side of the family would not have a history of the disorder.

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Fifty percent of male offspring of female carriers will inherit the mutation. However, because of the broad
phenotypical heterogeneity of the disorder, only about half will develop the illness. Dietary therapy has little effect
on either the progression or preexisting neurological deficits in affected patients. Corticosteroid replacement
therapy may be necessary for other reasons but does not affect neurological disability.
31. An 8-year-old boy presents with seizures and mental retardation since infancy. He was the product of a normal
birth and gestation. He was slow to reach developmental milestones and is able to attend school in special
education classes. He began having infantile spasms at age 6 months but now has generalized tonic-clonic seizures
about once a month. There is no family history of neurological disease. On physical examination he has a nodular
malar rash. Periungual fibromas are present, and a few hypopigmented macules are on the skin of his back when
viewed with a Wood's lamp. No focal abnormalities are found on neurological examination. Computed tomography
and MRI of the head demonstrate multiple, calcified, and minimally enhancing lesions in the subependymal
regions. Genetic testing reveals a mutation in the TSC1 gene on chromosome 9q. Genetic testing of the parents is
negative for the mutation. Which of the following is the most appropriate counseling to the parents of this child?
A. The parents have a 50% chance of having another affected child
B. The absence of genetic abnormality in the parents is most suggestive of false paternity
C. The patient is at increased risk of developing astrocytoma
D. The patient's future offspring will have a 25% chance of being affected by this disorder
E. Other than the skin and nervous system, major organ systems are not affected by this disorder
Correct Answer: The correct answer is C. This patient has tuberous sclerosis, a genetic disorder inherited as an
autosomal dominant trait. Mutations are possible in two genes: TSC1 (chromosome 9) and TSC2 (chromosome
16). Two thirds of patients have sporadic de novo mutations; thus there is no family history. Affected individuals
who reproduce have a 50% chance of having an affected offspring. There is at least a 5% chance of development of
astrocytoma. Subependymal giant cell astrocytomas are most common. In addition to the skin and nervous system,
rhabdomyomas are seen in the heart, and angiomyolipomas may be seen in the kidneys of these patients.
32. A 6-year-old girl presents with a 6-month history of unsteady gait and frequent falls. Over the same time frame
she has developed tremor of the head and upper extremities. She was the product of a normal gestation and
delivery, and her development up to this point has been normal. There is no family history of ataxia or other
neurological disease. On examination, her cognitive function is normal. She has mild dysarthria. The funduscopic

examination reveals pigmentary changes in the retina but no evidence of optic atrophy. There is titubation of the
head. Strength is 5/5 throughout, and deep tendon reflexes are symmetrically reduced. The plantar responses are
flexor. Vibration and joint position sense are reduced in the hands and feet. Her gait is broad based and ataxic.
Romberg's sign is positive. Laboratory testing reveals very low serum vitamin E levels. Vitamin A and D levels are
normal. Which of the following is the most likely cause for this patient's signs and symptoms?
A. Gastrointestinal malabsorption disorder
B. Malnutrition
C. Friedreich ataxia
D. Mutation in [alpha]-TTP gene
E. Ataxia telangiectasia
Correct Answer: The correct answer is D. This patient has a spinocerebellar ataxia due to the vitamin E deficiency.
The fact that her vitamin A and D levels are normal suggests the cause is unlikely to be due to dietary deficiency or
malabsorption. Although many of the clinical features are similar to those of Friedreich ataxia and ataxia
telangiectasia, the very low vitamin E level makes this possibility less likely. She most probably has ataxia with
isolated vitamin E deficiency, an autosomal recessive disorder due to frame-shift mutations in the gene coding for
the [alpha]-tocopherol transfer protein ([alpha]-TTP). Deficiency in this protein causes vitamin E deficiency due to
inadequate recycling of vitamin E. Oral vitamin E supplementation may produce clinical improvement or at least
retard progression.
33. A 30-year-old woman presents to her physician with a 2-year history of paresthesias and sensory loss in her
palms and soles. Over the last year, she has noted weakness in her ankles and a tendency of her toes to trip her
when ascending stairs. She reports that she has always had high arches and difficulty wearing high heels. She had
no difficulty keeping up athletically in school but reports a relatively sedentary lifestyle for the past 10 years. Her
25-year-old brother has high arches and reports some difficulties with his feet. The patient's 55-year-old mother has
had "foot problems" for many years and has worn bilateral ankle-foot orthotics for the last 10 years. The patient's
maternal grandmother and a maternal uncle may have had similar symptoms, but both died in their 60s of heart
disease. No other family members have symptoms of neuropathy. On examination, she has high arches and atrophy
of the intrinsic muscles of the hands and feet. She has a mild steppage gait and particular difficulty walking on her
heels. There is symmetrical 4/5 weakness of muscles of the distal upper and lower extremities but proximal
strength is 5/5. Deep tendon reflexes are absent at the ankle and symmetrically reduced at the knee and elbow. The

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plantar responses are flexor. Sensory examination reveals reduction to all modalities in a stocking-glove
distribution. The remainder of the neurological examination is normal. Nerve conduction studies reveal slowing of
motor and sensory conduction velocities in the 36 m/s range. Based on this patient's family history, which of the
following genetic abnormalities is most likely to be present?
A. Mutation in the GJB1 gene
B. Duplication in the PMP22 gene
C. Deletion in the GARS gene
D. Mutation in the senataxin gene
E. Mutation in the SPTLC1 gene
Correct Answer: The correct answer is A. The pattern of inheritance suggests an X-linked dominant condition (no
male-to-male inheritance), although an autosomal dominant condition remains a possibility. The X-linked form of
CMT, CMTX, is due to a point mutation in the GJB1 gene that codes for the connexin 32 gap junction channel
protein, which is expressed in the Schwann cell. Occasionally women can be affected, although typically the men
in a family are more significantly affected. Duplication in the PMP22 gene produces CMT1A, an autosomal
dominant disorder that usually produces more severe slowing of nerve conduction velocities (in the range of 20
m/s). Mutations in the GARS gene produce an autosomal dominant axonal neuropathy (CMT2D) or a motor
neuropathy, hereditary motor neuropathy type V. Mutations in the senataxin gene produce an autosomal dominant
disorder with both upper and lower motor neuron abnormalities and normal sensory examination (ALS4). Patients
with point mutations in the SPTLC1 gene have hereditary sensory and autonomic neuropathy and develop
difficulties primarily in small fiber nerve function. Nerve conduction velocities are usually normal.
34. A 22-year-old woman presents with a 3-year history of progressive ptosis and diplopia. She carries a diagnosis
of "seronegative ocular myasthenia gravis" but has never responded to pyridostigmine or corticosteroids. She has
had reduced hearing bilaterally since her early teens and was recently noted to have second-degree heart block
when she had a syncopal spell. For the last 6 months she notes unsteady gait. There is no family history of
neurological disease of any sort. On examination, she is of short stature. Mental status is normal. Her cranial nerve
examination reveals bilateral severe ptosis and complete ophthalmoplegia. Mild pigmentary changes are noted in
the retinas. Bilateral sensorineural hearing loss is present. She has mild to moderate proximal weakness in the arms
and legs. The deep tendon reflexes are normal. Her gait is broad based and ataxic. She cannot tandem walk without

falling. Finger-nose and heel-shin testing reveal mild limb ataxia. MRI of the head with contrast reveals mild
cerebellar atrophy. Serum lactate is elevated. Which of the following is the most likely diagnosis?
A. Myoclonic epilepsy with ragged red fibers
B. Mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes (MELAS)
C. Kearns-Sayre syndrome
D. Leigh disease
E. Oculopharyngeal muscular dystrophy
Correct Answer: The correct answer is C. This patient has chronic progressive external ophthalmoplegia, also
known as Kearns-Sayre syndrome (KSS). KSS results from a deletion in mitochondrial DNA. Spontaneous (ie, not
maternally inherited) mutations are present in about 80% of patients. Therefore, there is often no family history of
the disorder. The presence of ophthalmoplegia and ptosis is unique to KSS, which lacks seizures, encephalopathy,
and strokelike events as part of the clinical presentation of MERRF; MELAS, and Leigh's disease.
Oculopharyngeal muscular dystrophy (OPMD) is a repeat expansion disorder with onset in the fifth or sixth
decade. Ptosis, ophthalmoplegia, and dysphagia and proximal weakness are common to both OPMD and KSS.
Hearing loss, cerebellar ataxia, and cardiac conduction defects are not clinical features of OPMD but are seen with
KSS.
35. A 28-year-old recently married woman with a clinical diagnosis of neurofibromatosis type 1 (NF1),
characterized by an optic nerve glioma and multiple cutaneous neurofibromas and café-au-lait spots, comes to the
office seeking reproductive advice. Which of the following is the most appropriate recommendation for this
patient?
A. Examination of her spouse for signs of NF1
B. Genetic testing for an abnormal NF1 gene to confirm the diagnosis
C. Referral to a genetic counselor
D. Tubal ligation or other form of permanent sterilization
E. Therapeutic abortion if she becomes pregnant and prenatal testing is positive
Correct Answer: The correct answer is C. This case underscores the importance of referring a patient with a genetic
disorder to a geneticist or genetic counselor for a detailed discussion of reproductive risks and options. NF1 is
autosomal dominant; this patient has a 50% risk of passing the NF1 gene to each of her children, although disease
severity in an affected patient can be variable. Counseling about reproductive options and the role of possible

24
prenatal testing are best deferred to the genetics professional for this and other hereditable diseases. In addition, the
neurologist should not let his or her personal beliefs interfere with the patient's freedom to reproduce or to access to
prenatal testing and reproductive counseling. Examination of this patient's spouse is unnecessary because this is an
autosomal dominant condition, and genetic testing in the patient is unnecessary presently as the patient already
meets clinical criteria for the disease.
36. A 35-year-old man presents with a 6-month history of progressive dysarthria and mild dysphagia. Over the
same period, he has noted tremor of the hands when he reaches for objects. He has had some nocturnal cramping in
the legs but denies weakness in the limbs. He takes no medications and has been previously healthy. Family history
is negative for neuromuscular disease. His mother died at age 60 of myocardial infarction, but his father is healthy
at age 80. He has two sisters, one daughter, and two sons, all of whom are healthy. On examination, there is mild
gynecomastia. He has evidence of tongue wasting, weakness, and fasciculation. Mild palate weakness is present.
His speech is hoarse and breathy. Perioral fasciculations are present. He has mild upper and lower extremity
weakness with rare fasciculation. The deep tendon reflexes are symmetrically reduced, and Babinski sign is absent
bilaterally. Sensory examination is normal. His electromyography and nerve conduction studies show evidence of
reduced compound motor action potentials with normal conduction velocities. The needle examination shows
widespread fibrillations and large motor units, particularly in the tongue. Genetic testing reveals 55 CAG repeats in
the gene coding for the androgen receptor gene. Which of the following is the most appropriate counseling for this
patient?
A. His life expectancy is about 3 years
B. His sons each have a 25% chance of developing this illness
C. His sister's children are at no risk of developing the disorder
D. His daughters are all carriers of the affected gene
E. The patient's creatine kinase (CK) level will be 10 times the normal value
Correct Answer: The correct answer is D. This patient has spinobulbar muscular atrophy (SBMA or Kennedy's
syndrome) as X-linked polyglutamine-coding CAG repeat expansion disease localized to Xq21-22. This gene codes
for the androgen receptor gene encoding the male steroid receptor. Androgen receptor is expressed in motor
neurons of the spinal cord and brain stem and mediates neurotrophic responses to androgen. Generally, this motor
neuron disorder progresses much more slowly than ALS. Because it is an X-linked disorder, daughters of the male

proband will all be carriers and sons will not inherit the gene. Assuming this patient inherited this gene from his
mother, who was a carrier, his sister has a 50% of being a carrier of the gene. Therefore, her daughters each have a
50% chance of being carriers, and her sons each have a 50% chance of developing Kennedy syndrome. The
patient's sister and his daughters should have genetic testing. His mother is dead and cannot be tested. Patients with
Kennedy syndrome may have a slightly elevated CK, usually less than 5 times the normal value.
37. A 29-year-old woman presents with a 6-month history of progressive balance difficulties and falling. She
reports tingling in her hands and loss of feeling in her feet. She states, "It feels like I'm walking on stumps." She
denies weakness in the arms or legs but notes that she was always a slow runner and poor athlete. There have been
no symptoms in the face and no change in bowel or bladder function. As a child and teenager she never noticed
problems walking. As far as she knows there is no family history of peripheral neuropathy. She thinks her brother
has "flat feet." Her examination reveals mild bilateral pes cavus and early development of hammertoes. There is no
obvious atrophy in the lower legs or hands. She has symmetrical, mild, 4+/5 weakness in toe and ankle
dorsiflexors. Strength is otherwise normal. The ankle reflexes are absent, and the other deep tendon reflexes are
present but markedly reduced. The plantar responses are flexor. Sensory examination reveals reduced vibration
sense to the level of the ankle with intact joint position sense. There is a stocking-glove loss to pin and temperature.
Slight enlargement of ulnar and peroneal nerves is noted bilaterally. Nerve conductions studies reveal symmetrical
reduction in sensory and motor action potential amplitudes and uniform slowing of conduction velocities in the 30
m/s range. Genetic testing reveals a duplication at chromosome 17p11.2 in the region containing the PMP22 gene.
Which of the following features in this patient's presentation is the most helpful in differentiating her condition
from chronic inflammatory demyelinating polyneuropathy?
A. The family history of flat feet
B. The presence of mild pes cavus
C. The presence of nerve enlargement
D. The uniform slowing of conduction velocities
E. Marked reduction in the deep tendon reflexes
Correct Answer: The correct answer is D. This patient has CMT1A, an autosomal dominant disorder due in most
cases to a 1.4 Mb duplication at chromosome 17p11.2 in the PMP22 gene. The absence of a definite family history
does not exclude the diagnosis of inherited neuropathy as there may be phenotypical variability in expression or the
patient may have a new mutation. Pes cavus and planus are nonspecific findings and may be present with any

25
chronic disorder of the central or peripheral nervous system. Both acquired and inherited chronic demyelinating
neuropathies may produce remyelination with nerve enlargement. In most patients with chronic inflammatory
demyelinating polyneuropathy, the slowing seen on nerve conduction studies will be asymmetrical. CMT1A, in
particular, and many inherited demyelinating neuropathies will have uniform conduction slowing. Deep tendon
reflexes are typically reduced in both chronic inflammatory demyelinating polyneuropathy and CMT1A.
38. A 2-year-old boy presents with developmental delay, poor vision, and evidence of hypopituitarism. He was the
product of a normal gestation and delivery. Since birth he has been in the fifth percentile for height, weight, and
head circumference. Motor milestones are delayed, and he is just beginning to walk and use single words. He has
had seizures since age 4 months that have been difficult to control on medications. On examination he is visually
inattentive, the pupillary light response is absent bilaterally, and bilateral optic disc pallor is present. Tone is
increased and diffuse hyperreflexia is present. Blood work reveals evidence of panhypopituitarism. MRI of the
head reveals agenesis of the corpus callosum and septum pellucidum and hypoplasia of the optic nerves and
chiasm. This child's disorder is associated with which of the following factors?
A. Young maternal age
B. Maternal diabetes
C. Maternal alcohol use
D. Mutations in HESX1
E. All of the above
Correct Answer: The correct answer is E. This patient has septo-optic dysplasia (de Morsier syndrome), a disorder
of prosencephalic cleavage and development of anterior telencephalic structures. Clinical features include mental
retardation, visual disturbance, seizures, quadriparesis, and hypothalamic-pituitary dysfunction. There may be
agenesis of the septum pellucidum, corpus callosum, and hypoplasia of the optic nerves and chiasm, and
infundibulum. This disorder may have many causes, including genetic (mutations of HESX1), teratogenic drugs,
and other maternal factors (young maternal age and diabetes).
39. A 3-month-old girl presents with intractable infantile spasms and hypotonia. She is the product of a normal
gestation and birth and is the first child of a 25-year-old healthy woman. The infant was hypotonic at birth, and
Apgar scores were 7 and 9 at 5 and 10 minutes. The child has had feeding difficulties since birth, and seizures
developed at age 2 months. On examination she has a dysmorphic face with low-set ears, temporal hollowing,

hypertelorism, a high forehead, and upturned nostrils. She is hypotonic. An MRI of the head reveals complete
agyria and posterior enlargement of the lateral ventricles. Genetic testing reveals a large deletion in the LIS1 gene
on chromosome 17p. The child's father is found to have a balanced translocation involving 17p. Which of the
following is the most appropriate counseling for the parents of this child?
A. The child will have a normal life expectancy but will be neurologically disabled
B. The seizures will become less frequent as the child develops
C. The likelihood of subsequent offspring of the parents being affected is very small
D. Amniocentesis with fetal karyotyping of subsequent pregnancies is advised
E. This disorder can be identified on fetal ultrasound at 12-weeks gestation
Correct Answer: The correct answer is D. This child has Miller-Dieker syndrome, a disorder in which more than
90% of patients have a large deletion of the short arm of chromosome 17. The deletion usually encompasses the
LIS1 gene as well as adjacent genes. The child has severe lissencephaly with agyria due to a severe disorder of
neuronal migration. A broad heterotopic neuron zone is often beneath the cortical surface. Gyri and sulci do not
form. This disorder cannot be recognized by fetal ultrasound until after the 28th week, as cerebral gyri are not
formed prior to this gestational age. Therefore, amniocentesis with fetal karyotyping is the only reliable antenatal
diagnostic test in the first trimester of pregnancy. In most patients the deletion is a de novo mutation. However, if
one of the parents harbors a balanced translocation of chromosome 17, the recurrence risk is high and the parents
should be counseled accordingly. Affected individuals have severe deficits and usually die in the first few years of
life.
40. A 15-year-old boy presents with clusters of hyperkinetic motor seizures that typically occur at night. There is a
family history of seizures in his father and his paternal grandmother. Neurological examination is normal. Routine
EEG is normal. Which of the following is the most likely diagnosis?
A. Autosomal dominant lateral temporal lobe epilepsy
B. Autosomal dominant nocturnal frontal lobe epilepsy
C. Generalized epilepsy with febrile seizures plus (GEFS+)
D. Myoclonic epilepsy with ragged red fibers
E. Juvenile myoclonic epilepsy
Correct Answer: The correct answer is B. Hyperkinetic seizures occurring predominantly at night suggest a frontal
lobe origin. Additionally, the strong family history argues for autosomal dominant inheritance. Autosomal

26
dominant nocturnal frontal lobe epilepsy (ADNFLE) is a rare but well-characterized condition that fits this
description. Ictal EEG of patients with ADNFLE may demonstrate seizure activity in the frontal lobes, but interictal
recordings are usually nondiagnostic. Autosomal dominant lateral temporal lobe epilepsy causes simple partial
seizures characterzed by acoustic or, less commonly, visual hallucinations unlike the seizures described in this
patient. MERRF is a mitochondrially inherited cause of progressive myoclonic epilepsy and myopathy, not
consistent with this patient's presentation. JME typically causes seizures upon awakening rather than at night,
unlike this patient; in addition, interictal EEGs of patients with JME commonly show generalized spike-and-wave-
discharges.
Spinal Cord Disorder June 2005
TYPE A QUESTIONS (ONE BEST ANSWER)
1. A 39-year-old woman developed low back pain after she slipped and fell on an ice patch outside a restaurant.
The following day, her legs suddenly gave out while she was walking. On examination, she has moderate weakness
of both lower extremities, worse in the flexors than the extensors. She has bilateral Babinski signs and a sensory
level for pain and temperature at about the T10 level with normal position and vibration sensation. A spinal
magnetic resonance image (MRI) is normal except for a Schmorl's node in the T6 vertebral body. Which of the
following is the most likely cause of her weakness?
A. Embolic intervertebral disk material
B. Epidural abscess
C. Epidural hematoma
D. Spinal cord contusion
E. Vertebral artery dissection
Correct Answer: The correct answer is A. The onset of symptoms after mild back trauma and the presence of a
Schmorl's node at a nearby spinal level make it likely that this patient suffered fibrocartilaginous embolism (in
which intervertebral disk material gains access to the vascular system of the spinal cord and causes a spinal cord
infarction). The MRI scan makes epidural abscess or hematoma unlikely. While vertebral artery dissection can
cause spinal cord infarction, this patient had low back pain but no reported neck pain after her fall, and the
Schmorl's node favors fibrocartilaginous embolism. Spinal cord contusion undetectable on MRI is not a recognized
condition.

2. A 60-year-old man underwent repair of a 7-cm thoracoabdominal aortic aneurysm. Upon awakening from the
operation, he noticed inability to move his legs. Examination revealed a flaccid paraplegia with a sensory level at
T10. Examination 3 months later reveals severe lower extremity weakness, absent knee jerks, and bilateral ankle
clonus and Babinski signs. Which of the following findings is to be expected upon his evaluation at this time?
A. Abnormal tibial somatosensory evoked potentials
B. Orthostatic hypotension
C. Fibrillation potentials in the gastrocnemius muscles
D. Bladder detrusor-sphincter dyssynergia
E. Decreased amplitude sural nerve action potential
Correct Answer: The correct answer is D. The patient suffered a spinal cord infarction in the territory of the artery
of Adamkiewicz, which is a prominent anterior spinal artery feeder that originates between T9 and T12 and can be
damaged during aortic repairs in this region. Anterior spinal artery territory infarctions affect the anterior two thirds
of the spinal cord and preserve the dorsal columns. In this case, a sensory level at T10 and the pattern of segmental
reflexes indicate a lesion extending to the L4 spinal segment but sparing the segments below. This will produce,
upon recovery from spinal shock, a spastic bladder with detrusor hyperreflexia and detrusor-sphincter dyssynergia.
Lesions below T9 spare the excitatory input to spinal sympathetic vasoconstrictor neurons and thus do not lead to
orthostatic hypotension. Anterior spinal artery territory infarction typically spares the dorsal column, and, therefore,
tibial sensory evoked potentials are expected to be unaffected.
3. Which of the following tests would be most appropriate in a 50-year-old woman with slowly progressive spastic
paraparesis in whom testing reveals no evidence for structural neurological disease, inflammatory or motor neuron
disease, vitamin B
12
deficiency, or motor neuron disease?
A. Androgen receptor gene
B. Dystrophin
C. Emerin
D. FMR1 gene
E. Very long chain fatty acids
Correct Answer: The correct answer is E. As many as 50% of female carriers of the gene for adrenoleukodystrophy
(an X-linked, recessive disorder) develop myelopathy, although their condition is usually milder and tends to

manifest at an older age than does typical adrenoleukodystrophy or adrenomyeloneuropathy in males. The


27
diagnosis is established by measuring very long chain fatty acids in plasma, especially the C26:0/C22:0 ratio.
Female carriers of spinobulbar muscular atrophy, Duchenne's muscular dystrophy, Emery-Dreifuss muscular
dystrophy, and fragile X syndrome do not develop myelopathy.
4. A 25-year-old man developed a rapidly progressive paraparesis with a sensory level at T8. Which of the
following features would be most suggestive of an etiology other than idiopathic or postinfectious transverse
myelitis?
A. Asymmetrical weakness
B. Cerebrospinal fluid (CSF) pleocytosis
C. Elevated immunoglobulin (IgG) index
D. Enhancing spinal cord lesion on MRI
E. Progression to nadir within 2 hours
Correct Answer: The correct answer is E. Spinal cord inflammation (demonstrated by CSF pleocytosis, elevated
IgG index, or a gadolinium-enhancing spinal cord lesion on MRI) is one of the diagnostic criteria for idiopathic or
postinfectious transverse myelitis. Most patients with idiopathic transverse myelitis have some degree of weakness,
and about 50% lose all voluntary movement in their legs at the peak of their illness. The clinical features can be
symmetrical or asymmetrical; those with asymmetrical clinical findings are more likely to be subsequently
diagnosed with multiple sclerosis. Neurological function usually worsens progressively over the course of 4 to 21
days, with more than 80% of patients reaching their clinical nadir within 10 days of symptom onset. Progression to
nadir within 4 hours of symptom onset is one of the exclusion criteria for idiopathic-postinfectious transverse
myelitis.
5. A 42-year-old woman with acquired immunodeficiency syndrome (AIDS) reports that her gait has been
gradually worsening over the past 3 months and she has also developed urinary incontinence. Examination reveals
spastic paraparesis, with weakness more prominent than spasticity. She has brisk reflexes in both lower extremities
with bilateral Babinski signs. She has reduced sensation to all primary modalities in her lower extremities with a
sensory level to pinprick at about T6. All findings are bilaterally symmetrical. Which of the following provides the
strongest evidence that she has a mass lesion in her spinal cord rather than vacuolar myelopathy?

A. Babinski signs
B. Right-left symmetry
C. Sensory level to pinprick
D. Urinary incontinence
E. Weakness more prominent than spasticity
Correct Answer: The correct answer is C. The vacuolar myelopathy of human immunodeficiency virus (HIV)
infection is characterized by spastic paraparesis with hyperreflexia and Babinski signs. Incontinence is common
(60% of patients in one study). The symptoms and signs are typically symmetrical. Weakness typically exceeds
spasticity. Posterior column sensory modalities are usually more affected than pain and temperature sensation. The
presence of a discrete sensory level to pinprick should suggest an alternate diagnosis.
6. A 40-year-old woman is evaluated for progressive difficulty walking and leg stiffness that began insidiously
approximately 10 years ago. She has one younger brother who had long-standing difficulties participating in sports
because of tendency to stumble and fall easily. She denies sensory loss or bladder difficulties. Her mother is
affected by similar symptoms that began in her 30s and she now requires a cane. Neurological examination reveals
weakness in the iliopsoas, hamstring, and anterior tibialis muscles, hyperreflexia at the knees and ankles, and
decreased vibration sense in the toes. She has pes cavus. The rest of her examination is unremarkable. MRI of the
head and spine and CSF examination are unremarkable. The most likely cause of this patient's condition is a
mutation of a gene encoding which of the following proteins?
A. Proteolipid protein
B. Myelin basic protein
C. Spastin
D. Paraplegin
E. Spartin
Correct Answer: The correct answer is C. The history and findings are consistent with autosomal dominant, pure
hereditary spastic paraplegia (HSP). The most common cause (40% of autosomal dominant HSP) is mutation of the
spastin gene on chromosome 2p22 (SPG4).
7. A 35-year-old man is evaluated for a 2-week history of progressive gait difficulties, leg stiffness, and
paresthesia. He has been a healthy professional and was on no medication except for vitamin and mineral
supplements. Neurological examination reveals a spastic-ataxic gait, moderate and symmetrical weakness and
spasticity in the lower limbs, and bilateral Babinski signs. Severe loss of vibration sense up to the knees and

position sense at the toes and foot are present. The rest of the neurological examination is normal. Laboratory


28
testing reveals elevated homocysteine levels. Which of the following toxins is the most likely cause of this
neurological condition?
A. Vitamin B
6

B. Nitrous oxide
C. Manganese
D. Vitamin E
E. Methyl mercury
Correct Answer: The correct answer is B. The patient has a progressive myelopathy affecting the dorsal and lateral
columns and resembling that seen with vitamin B
12
deficiency. Nitrous oxide is an anesthetic commonly used in
surgery and dentistry, and it is also used as a recreational drug. It irreversibly oxidizes the cobalt moiety of
methylcobalamin, interfering with methylation reaction, including transformation of homocysteine to methionine.
8. A 35-year-old woman is evaluated for onset of back pain and progressive leg weakness and numbness over the
past 2 days and difficulty voiding over the past 18 hours. The first priority in evaluating this patient is determining
whether:
A. The cause is vascular or inflammatory
B. A compressive cause exists
C. Lesions are present in other regions of the nervous system
D. Evidence exists of a primary neoplasm outside the nervous system
E. Evidence exists of systemic inflammatory conditions, such as systemic lupus erythematosus or sarcoidosis
Correct Answer: The correct answer is B. The first priority in evaluating a patient with an acute myelopathy is to
exclude a compressive cause. The patient should have gadolinium-enhanced spine MRI as soon as possible.
9. A 48-year-old man with AIDS developed gait problems that progressed rapidly over several days. A week

earlier, he developed a vesicular rash that extended in a narrow band on his left side from the epigastric area around
to his back. Examination reveals generalized cachexia, a few residual crusted vesicles, and diffuse
lymphadenopathy. He has a spastic paraparesis with a sensory level to pinprick at T6. His myelopathy is most
likely to respond to which of the following medications?
A. Amphotericin
B. Famciclovir
C. Isoniazid
D. Sulfadiazine
E. Zidovudine
Correct Answer: The correct answer is B. The description of this patient's rash is typical of herpes varicella-zoster.
Zoster myelitis most often occurs in immunocompromised individuals and generally responds well to antiviral
therapy with acyclovir or related medications.
10. A 30-year-old woman is evaluated for a 5-year history of progressive difficulty walking due to leg stiffness and
instability. Her parents are unaffected, but, by report, her deceased maternal grandmother had progressive gait
difficulties and became wheelchair bound in her 60s. The patient has a younger brother and an older sister, both
unaffected. Neurological examination reveals spastic paraparesis with exaggerated knee and ankle reflexes and
bilateral Babinski signs. She has optic disk pallor and mild ataxic dysarthria. Her MRI reveals mild cerebellar
atrophy. A quadriceps muscle biopsy reveals ragged red fibers. The most likely cause of this patient's condition is a
mutation of a gene encoding which of the following proteins?
A. Proteolipid protein
B. L1 cell adhesion molecule
C. Frataxin
D. Paraplegin
E. Spastin
Correct Answer: The correct answer is D. The history and findings suggest the diagnosis of an autosomal recessive,
complicated form of HSP. The presence of ragged red fibers indicates mitochondrial dysfunction. Paraplegin is a
chaperone involved in mitochondrial protein editing and folding. Mutation of the paraplegin gene on chromosome
16q (SPG7) produces both pure and complicated forms of autosomal recessive HSP. Heat shock protein 60
(HSP60) is also a mitochondrial chaperone, and mutations of the HSP60 gene on chromosome 2q, have been linked
to autosomal dominant, pure forms of disease (SPG13).

11. A 32-year-old man with AIDS complains of progressive leg weakness, paresthesias, gait unsteadiness, and
urinary incontinence. He is receiving antiretroviral therapy. Examination reveals spastic paraparesis, sensory ataxia,
and loss of joint position and vibration sense in the toes. Tibial somatosensory potentials are absent. Spinal MRI
shows no mass lesion. CSF reveals 10 mononuclear cells, a protein concentration of 50 mg/dL, and a glucose
concentration of 60 mg/dL. Polymerase chain reaction (PCR) for HIV is positive, but PCR and culture for herpes


29
simplex virus types 1 and 2, varicella-zoster virus, cytomegalovirus, Epstein-Barr virus, human T-lymphotropic
virus (HTLV) types 1 and 2, and JC virus are negative. What is the most likely pathological diagnosis?
A. Demyelinating polyradiculopathy
B. Antiretroviral drug-induced myeloradiculopathy
C. Tuberculous meningovasculitis
D. Vacuolar myelopathy
E. Meningeal B-cell lymphomatosis
Correct Answer: The correct answer is D. The history and findings indicate involvement of the posterior and lateral
columns as seen in vacuolar myelopathy, the typical myelopathy in adult patients with AIDS. This is a diagnosis of
exclusion after having considered other causes, including opportunistic infections and lymphoma.
12. A 30-year-old man is evaluated for an 8-month history of fatigue, progressive gait difficulties, and erectile
dysfunction. Neurological examination reveals a spastic-ataxic gait, Romberg sign, moderate upper motor
distribution weakness in lower limbs with bilateral Babinski signs, and impaired vibration and joint position sense
in the toes. Electromyography shows decreased sensory and motor nerve conduction velocities. Vitamin B
12
level is
normal, and HIV serology is negative. Plasma prolactin is normal, cortisol and testosterone are low, and
corticotropin is elevated. Which of the following substances is most likely to be also found elevated in this patient's
plasma?
A. [beta]-Lipoproteins
B. Very long chain fatty acids
C. Ceruloplasmin

D. [alpha]-Tocopherol
E. Hexosaminidase A
Correct Answer: The correct answer is B. The patient has a myeloneuropathy. The elevated corticotropin and low
cortisol levels suggest adrenal insufficiency, which can occur in up to 60% of males with adrenomyeloneuropathy.
Elevated plasma levels of very long chain fatty acids characterize this peroxisomal disorder.
13. A 23-year-old woman is evaluated for onset of progressive leg numbness and gait instability over the past 2
days. Three years ago, she had an episode of loss of vision in the right eye, which recovered over 2 weeks.
Neurological examination reveals minimal weakness in the iliopsoas, hamstring, and anterior tibialis muscles
bilaterally, mild hyperreflexia, and loss of vibration sense in the toes. Which of the following findings is most
likely to indicate that the patient has multiple sclerosis rather than neuromyelitis optica?
A. Asymmetrically abnormal visual evoked response latencies
B. Absence of elevated IgG index or oligoclonal bands in the CSF
C. MRI lesion extending less than two spinal cord segments
D. CSF leukocytosis with neutrophils
E. Abnormal tibial somatosensory evoked potential
Correct Answer: The correct answer is C. Neuromyelitis optica (Devic's disease) manifests with a severe
myelopathy that commonly affects more than three contiguous segments of the spinal cord and most of the
transverse extent of the cord. Other typical features of the disease are the presence of neutrophils and absence of
oligoclonal bands in the CSF and the presence of a circulating neuromyelitis optica antibody in serum.
14. A 22-year-old man with history of intravenous drug use presents with a 6-week history of progressive
difficulties with gait and urinary urgency. Examination reveals weakness and spasticity in the lower limbs.
Urodynamic study reveals overactive detrusor contractions with detrusor-sphincter dyssynergy. MRI reveals
atrophy of the thoracic cord. Which of the following tests is most appropriate at this time?
A. Spinal angiography
B. Serum antiphospholipid antibodies
C. PCR for human T-cell lymphotropic virus type I in CSF
D. Syphilis serology
E. Serum angiotensin-converting enzyme
Correct Answer: The correct answer is C. Intravenous drug users are at high risk of neurological complications,
including human T-cell lymphotropic virus type I myelopathy.

15. Which of the following is the best dietary source of vitamin B
12
?
A. Beef
B. Carrots
C. Lettuce
D. Limes
E. Soybeans


30
Correct Answer: The correct answer is A. Vitamin B
12
is present in animal proteins and virtually absent in fruits
and vegetables. The typical dietary sources are meat and eggs. Strict vegetarians and vegans must take care to
ensure that they supplement their diets with adequate amounts of vitamin B
12
.
16. A 45-year-old man with a history of diabetes developed fever, back pain, leg weakness, and urinary hesitancy.
Examination reveals paraparesis, absent knee jerks, exaggerated ankle jerks, and bilateral Babinski signs. An MRI
of the lumbar spine reveals a contrast-enhancing epidural lesion at T11 with associated swelling of the spinal cord.
Which of the following is the most likely organism involved?
A. Streptococcus pneumoniae
B. Staphylococcus epidermidis
C. Staphylococcus aureus
D. Enterococcus
E. Anaerobic bacteria
Correct Answer: The correct answer is C. The patient has a spinal epidural abscess, which is a surgical emergency.
The most common causative agent is S. aureus.
17. A 35-year-old Vietnamese woman is evaluated for a 2-week history of fever, progressive back pain, and leg

weakness. Examination reveals spastic paraparesis with a sensory level at T8. MRI of the spine shows anterior
wedging of the T6 and T7 vertebrae with loss of disk space and involvement of the adjacent spinal cord. Which of
the following is the most likely causative agent?
A. Aspergillus fumigatus
B. Treponema pallidum
C.E Mycobacterium tuberculosis
D. Taenia solium
E. Schistosoma mansoni
Correct Answer: The correct answer is C. Neurological complications of M. tuberculosis remain common in
developing countries. Myelopathy may occur in the setting of tuberculous spondylitis (Pott's disease), which
typically affects the anterior portions of the vertebral bodies. Although the other agents listed as alternative options
can produce myelopathy by several mechanisms, bone involvement is not a typical feature.
18. A 3-year-old boy is evaluated for mental retardation and delayed motor milestones. Examination reveals lower
extremity spasticity and adducted thumbs. He has a similarly affected brother and two unaffected sisters. Which of
the following findings is expected on MRI?
A. Band heterotopy
B. Polymicrogyria
C. Corpus callosum hypoplasia
D. Dandy-Walker malformation
E. Syringobulbia
Correct Answer: The correct answer is C. The clinical picture suggests a complicated X-linked syndromic HSP
referred to with the acronym CRASH (corpus callosum hypoplasia, retardation, adducted thumbs, spasticity, and
hydrocephalus). The CRASH syndrome is linked to mutations affecting a gene encoding L1 cell adhesion
molecule.
19. A 38-year-old man with a 15-year history of slowly progressive spastic paraparesis is found to have a mutation
in the spastin gene. He reports that two of his five sisters, both of his brothers, three paternal aunts, and his paternal
grandfather all have similar symptoms, but neither of his parents does. What is the most likely explanation for the
absence of clinical symptoms in both of his parents?
A. Autosomal recessive mode of inheritance
B. Environmental protective factors

C. Inaccurate attribution of paternity
D. Inaccurate genetic test results
E. Incomplete penetrance
Correct Answer: The correct answer is E. About 25% of subjects carrying the mutations for HSP remain totally
asymptomatic due to reduced penetrance. With respect to mutations in the spastin gene, variable penetrance may be
explained in part by varying degrees of protein expression, especially in splice site mutations that may lead to leaky
splicing and variable levels of message and protein. Intragenic polymorphisms have also been shown to contribute
to clinical heterogeneity. There is no reason to question the accuracy of the genetic test or of paternity in this case,
given the strong family history (in a pattern much more consistent with dominant inheritance than recessive) and
the fact that four paternal relatives are symptomatic.
20. Which of the following findings is most likely to occur in patients suffering an infarct in the most vulnerable
territory of the anterior spinal artery circulation in the setting of severe hypotension?


31
A. Horner syndrome
B. Orthostatic hypotension
C. Impaired tibial somatosensory evoked potential
D. Increased thermal sensory threshold in the lateral shoulder
E. Fibrillation potentials in the gastrocnemius muscles
Correct Answer: The correct answer is B. The T4 through T8 level is considered particularly vulnerable to ischemia
during global hypoperfusion due to the paucity of feeder vessels in this region. Lesions above the T9 level interrupt
sympathoexcitatory pathways, leading to orthostatic hypotension. The dorsal columns, and thus the somatosensory
evoked potentials, are spared in anterior spinal artery territory infarcts.
21. A 28-year-old woman has experienced two episodes of aseptic meningitis over the past year that resolved
spontaneously. She now presents with a 3-day history of progressive lower extremity weakness, paresthesia, and
urinary difficulties. Examination reveals mild paraparesis with hyperactive knee and ankle reflexes, Babinski sign,
and decreased vibratory sensation in the toes bilaterally. MRI examination reveals mild enlargement of the lower
thoracic cord with a focal area of increased T2 signal and contrast enhancement at this level. Which of the
following tests in CSF is most likely to be diagnostic in this case?

A. Syphilis serology
B. PCR for herpes simplex virus type 2 DNA
C. PCR for cytomegalovirus DNA
D. Borrelia burgdorferi IgG
E. PCR for JC virus DNA
Correct Answer: The correct answer is B. Herpes simplex virus type 2 is a well-recognized cause of recurrent
aseptic meningitis and may cause an ascending myelitis, which can also be recurrent. Spontaneous resolution of
aseptic meningitis would not be expected with neurosyphilis or fungal meningitis.
22. A 34-year-old woman developed numbness and weakness in her legs that progressed over 1 week to the point
where she was unable to move her legs at all. She was also unable to urinate. There had been no antecedent illness,
and her past medical history was unremarkable. Examination reveals flaccid paraplegia and a sensory level to all
modalities at T6. A spine MRI shows an area of increased T2 signal at T3 through T6 involving the left and right
sides equally, covering most of the transverse extent of the cord. It enhances with gadolinium. A brain MRI is
normal. Spinal fluid shows 10 white blood cells, all mononuclear, with normal glucose and protein and absence of
oligoclonal bands. What is the likelihood that this patient will subsequently develop neurological manifestations
that meet clinical criteria for multiple sclerosis?
A. Less than 20%
B. 20% to 40%
C. 40% to 60%
D. 60% to 80%
E. Greater than 80%
Correct Answer: The correct answer is A. The clinical scenario and test results are consistent with transverse
myelitis. A patient with monofocal central nervous system demyelination (transverse myelitis or optic neuritis)
whose brain MRI is normal has an 11% chance of meeting clinical criteria for multiple sclerosis over the
subsequent decade (compared with 83% of such patients whose brain MRI shows lesions consistent with
demyelination). The symmetrical clinical findings, absence of oligoclonal bands, and spinal cord lesion that
occupies more than half the cord diameter and more than two rostrocaudal segments are all findings associated with
a lower likelihood of developing multiple sclerosis.
23. A 55-year-old woman with a 10-month history of progressive lower extremity weakness, punctuated by several
episodes of more abrupt deterioration, was found to have a dural arteriovenous fistula of the spinal cord. Which of

the following would be the most appropriate management plan?
A. Aggressive blood pressure control
B. Anticoagulation with warfarin
C. Endovascular embolization
D. Lumbar drain
E. Observation and symptomatic treatment
Correct Answer: The correct answer is C. Patients with dural arteriovenous fistulas of the spinal cord have a high
likelihood of disability if not treated. Treatment can be either surgical or endovascular.
24. A 45-year-old woman with a 20-year history of slowly progressive spastic paraparesis has been thoroughly
evaluated for structural lesions affecting the brain or spinal cord, inflammatory and demyelinating diseases,
leukodystrophies, motor neuron disease, and nonfamilial metabolic causes of myelopathy (such as vitamin B
12

deficiency and copper deficiency). All of the test results have been normal. She has no affected family members.


32
What is the likelihood that a screening battery of genetic tests for mutations known to cause HSP will reveal a de
novo mutation?
A. Less than 10%
B. 20% to 30%
C. 40% to 50%
D. 60% to 70%
E. 80% to 90%
Correct Answer: The correct answer is A. Testing for genes associated with autosomal dominant HSP is unlikely to
yield a diagnosis in true sporadic cases. The reported frequency of new mutations varies between 7% and less than
1%.
25. A 64-year-old man presents with a 2-day history of back pain and rapidly progressive weakness and numbness
in the lower limbs associated with inability to void. Neurological examination reveals flaccid weakness in the
iliopsoas, hamstring, and foot muscles bilaterally, a pinprick level at T4, and loss of vibration and position sense in

the toes. MRI of the spine shows segmental enlargement, increased T2 signal, and an area of gadolinium
enhancement in the upper thoracic cord. MRI of the head is normal. Which of the following CSF findings may
most likely correlate with long-term disability in this patient?
A. Markedly elevated IgG index and oligoclonal bands
B. Marked lymphocytic pleocytosis
C. Elevated angiotensin-converting enzyme
D. Increased complement C3 and C5 fractions
E. Elevated interleukin-6 and 14-3-3 proteins
Correct Answer: The correct answer is E. Increased levels of interleukin-6 or 14-3-3 proteins in CSF may predict
the severity of long-term disability in patients with transverse myelitis.
26. A 46-year-old man with systemic lupus erythematosus and nonbacterial thrombotic endocarditis suddenly
developed bilateral leg weakness. Examination reveals flaccid paraplegia with a sensory level to pinprick at T10.
Position and vibration sense are intact. Which of the following tests will be most helpful?
A. Blood cultures
B. CSF oligoclonal bands
C. MRI of thoracic cord
D. Somatosensory evoked potentials
E. Spinal angiogram
Correct Answer: The correct answer is C. This patient has a clinical syndrome typical of spinal cord infarction
(especially given the sparing of posterior column sensory modalities), and an obvious risk factor (nonbacterial
thrombotic endocarditis). Nonetheless, he must be evaluated for spinal cord compression, especially if he is
immunosuppressed for his lupus (which would put him at risk for epidural abscess) or anticoagulated because of
the nonbacterial thrombotic endocarditis (putting him at risk for epidural hematoma). Thus, he needs an MRI of the
spinal cord (or a myelogram/computed tomography if MRI is impossible). Blood cultures were presumably
obtained before making the diagnosis of nonbacterial thrombotic endocarditis. Since a likely cause of spinal cord
infarction is already known, there is no reason to look for evidence of inflammation or a vascular abnormality, and
somatosensory evoked potentials would not add anything to the examination findings already available.
27. A previously healthy 18-year-old man had sudden onset of back pain, leg weakness, and inability to void within
36 hours after lifting exercises in a squat position. Examination reveals severe flaccid paraparesis, a sensory level at
T8, and urinary retention. A magnetic resonance reveals a swollen spinal cord with a central area of T2

hyperintensity and contrast enhancement involving the T8 through T10 levels. CSF examination is normal. Which
of the following is the most likely cause?
A. Diskogenic epidural cord compression at T6
B. Posterior spinal artery infarction
C. Fibrocartilaginous embolism
D. Syringomyelia
E. Devic's disease
Correct Answer: The correct answer is C. Fibrocartilaginous embolism is a rare but well-recognized cause of spinal
cord infarction following trauma or heavy lifting. This is a diagnosis of exclusion that should be considered when
other more common causes, such as vertebral artery dissection, have been excluded. Epidural cord compression is
unlikely to produce contrast enhancement from T8 through T10. Syringomyelia should not produce contrast
enhancement. Devic's disease would be unlikely in the presence of normal CSF. Posterior spinal artery infarction is
rare and should spare spinothalamic and corticospinal tract functions, which are affected in this case.


33
28. A 20-year-old woman with a history of celiac disease and malabsorption is evaluated for an 8-month history of
progressive gait difficulties and incoordination. Examination reveals a pigmentary retinopathy, ataxic gait with
Romberg sign, mild weakness and areflexia in the lower limbs, and severe loss of joint position and vibration sense
up to the knees bilaterally. Which of the following is the most likely diagnosis?
A. Gliadin-induced immune myelopathy
B. [alpha]-Tocopherol deficiency
C. Inflammatory demyelinating neuropathy with celiac disease
D. [alpha]-Lipoprotein deficiency
E. Adrenomyeloneuropathy
Correct Answer: The correct answer is B. The combination of sensory loss and ataxia resembling a spinocerebellar
syndrome and pigmentary retinal degeneration should suggest vitamin E ([alpha]-tocopherol) deficiency. This may
be due to an autosomal recessive mutation of the gene encoding the [alpha]-tocopherol transport protein or as an
acquired disorder as seen with celiac disease and malabsorption.
29. The pathological features classically associated with pure forms of HSP are characterized by:

A. Apoptosis of anterior horn cells and dorsal root ganglia cells
B. Axonal degeneration affecting predominantly distal portions of the corticospinal tracts and dorsal columns
C. Axonal degeneration affecting predominantly proximal portions of the corticospinal tracts and dorsal columns
D. Diffuse demyelination affecting corticospinal tracts and dorsal columns
E. Segmental demyelination affecting corticospinal tracts and dorsal columns
Correct Answer: The correct answer is B. Although not many descriptions of the histopathology of pure HSP are
available, probably because of its benign course, the cases that have been described are characterized by a length-
dependent axonal degeneration affecting distal portions of the long corticospinal tracts and dorsal columns in the
cord. The dorsal root ganglia and posterior roots are spared, and anterior horn cell pathology is variable.
30. A 44-year-old man developed gait disturbance that progressed over several months, and he also experienced
electric shock sensations down his back when he flexed his neck. His past history is notable for diabetes,
hypertension, hyperlipidemia, and bariatric surgery for obesity. Examination reveals lower extremity spasticity,
hyperreflexia, and markedly impaired proprioception. Serum vitamin B12 level is at the low end of the normal
range. Serum levels of which of the following should be checked to pursue the possibility of vitamin B12
deficiency further?
A. Ceruloplasmin
B. Folate
C. Methylmalonic acid
D. Parietal cell antibodies
E. Zinc
Correct Answer: The correct answer is C. Many patients with neurological symptoms from vitamin B
12
deficiency
have normal or borderline serum B
12
levels. All patients with suspected subacute combined degeneration should
have serum methylmalonic acid and homocysteine checked unless the diagnosis has already been established on the
basis of a low serum B
12
level.

31. A 58-year-old woman developed numbness and weakness in her legs that progressed over 2 days and then
stabilized. She has noted dry eyes and dry mouth over the past 6 months and intermittent joint pains, but she has
been healthy otherwise. Examination reveals mild weakness (4/5) of both lower extremities, especially the right.
She has hyperreflexia in both lower extremities and bilateral Babinski signs. Proprioception is impaired at the toes
and ankles bilaterally, and she has reduced sensation on the left at the T4 level and below. Spine MRI demonstrates
an area of increased T2 signal in the cord from C2 through C5 and another from T2 through T6, primarily on the
right. The thoracic lesion enhances with contrast. Brain MRI shows multiple periventricular areas of increased
signal with no enhancement. Spinal fluid contains 120 white blood cells, 80% mononuclear, a protein of 90, normal
glucose, and absence of oligoclonal bands. She has an elevated sedimentation rate and positive rheumatoid factor,
but normal antinuclear antibody and anti-double-stranded DNA. Which of the following tests is most likely to
establish the diagnosis?
A. Antiphospholipid antibodies
B. Chest computed tomography
C. Complement levels
D. Salivary gland biopsy
E. Visual evoked responses
Correct Answer: The correct answer is D. The combination of transverse myelitis, dry eyes, dry mouth, arthralgia,
elevated sedimentation rate, and positive rheumatoid factor is very suggestive of Sjögren syndrome. Salivary gland
biopsy is the most specific test.


34
32. Which of the following features is associated with a good outcome after transverse myelitis?
A. Back pain as an initial symptom
B. Progression to maximal symptoms within hours of onset
C. Residual voluntary movement and reflexes even at peak of illness
D. Sensory disturbance up to the cervical level
E. Urinary retention
Correct Answer: The correct answer is C. Back pain as an initial complaint, rapid progression to maximal
symptoms within hours of onset, and sensory disturbance up to the cervical level are all associated with a poor

outcome from acute transverse myelitis. So is spinal shock; thus, patients with residual voluntary movement and
reflexes even at the peak of the illness have a higher likelihood of a good outcome.
33. A 68-year-old man is evaluated for a 4-month history of progressive gait difficulties. He has not experienced
low back pain or leg numbness but has noticed progressively more difficulty initiating voiding. His neurological
examination reveals mild weakness in the proximal and moderately severe weakness in the distal lower extremity
muscles, decreased knee and absent ankle jerks, and bilateral Babinski signs. Electromyogram reveals fibrillation
potentials in the lumbar paraspinal muscles. Vibration sense is decreased at the toes. What is the most likely
diagnosis?
A. Primary progressive multiple sclerosis
B. Lumbar spinal stenosis with neurogenic claudication
C. Vitamin B
12
deficiency
D. Dural arteriovenous fistula
E. Motor neuron disease
Correct Answer: The correct answer is D. Dural arteriovenous fistulas cause a progressive ischemic myelopathy
due to venous congestion. The combination of upper and lower motor neuron signs and involvement of the bladder
are consistent with this diagnosis.
34. A 42-year-old woman who had undergone bariatric surgery and is currently receiving vitamin and mineral
supplementation is evaluated for a 6-month history of progressive gait difficulties and leg numbness. Neurological
examination reveals a spastic-ataxic gait, Romberg sign, moderate upper motor distribution weakness in lower
limbs with bilateral Babinski signs, and impaired vibration and joint position sense in the toes. Electromyography
shows decreased sensory and motor nerve conduction velocities. Plasma zinc levels are elevated, probably as a
result of excessive dietary intake. Which of the following abnormalities is most likely to be found in this patient's
plasma?
A. Increased [alpha]-lipoprotein
B. Increased transferrin
C. Increased cobalamin
D. Decreased ceruloplasmin
E. Decreased transthyretin

Correct Answer: The correct answer is D. The patient has a progressive myeloneuropathy resembling that occurring
with vitamin B
12
deficiency. Both bariatric surgery and increased intake of zinc reduce absorption of copper.
Copper deficiency associated with reduced levels of ceruloplasmin has been recently recognized as a potentially
treatable cause of myeloneuropathy.
35. A 19-year-old woman with a very slowly progressive gait disturbance is found on examination to have
pigmentary retinopathy, truncal and appendicular ataxia, hyporeflexia, and markedly impaired vibration and
position sensation. Which of the following is most likely?
A. Abetalipoproteinemia
B. Adrenomyeloneuropathy
C. Copper deficiency
D. Hyperglycinemia
E. Vacuolar myelopathy
Correct Answer: The correct answer is A. Patients with abetalipoproteinemia have impaired absorption of vitamin
E, resulting in sensory deficits, ataxia, hyporeflexia, and a pigmentary retinopathy (Bassen-Kornzweig syndrome).
36. A 24-year-old man presents with a 2-day history of rapidly progressive weakness and paresthesia in the lower
limbs. He has a history of joint pain, recurrent visual symptoms attributed in the past to uveitis, and recurrent
genital ulcers. Physical examination shows aphthous ulcers in the mouth. Neurological examination reveals
weakness in the iliopsoas, hamstring, and foot muscles bilaterally, hyperreflexia in the lower limbs, and severe loss
of vibration and loss of position sense in the toes. MRI of the spine reveals swelling and an area of increased T2
signal and contrast enhancement at the midthoracic level. What is the most likely diagnosis?
A. Systemic lupus erythematous


35
B. Sjögren disease
C. Sarcoidosis
D. Wegener's disease
E. Behçet's disease

Correct Answer: The correct answer is E. The presence of oral ulcers and the history of recurrent uveitis and genital
ulcers are strongly suggestive of Behçet's disease.
37. A 72-year-old man with a history of diabetes mellitus and hypertension suffers a cardiorespiratory arrest. Upon
successful resuscitation he is fully alert but unable to move his legs. Neurological examination reveals flaccid
paraparesis, a pinprick sensory level up to the nipples, and preserved joint position sense in the toes. This is
consistent with a lesion in the area irrigated by branches of which of the following arteries?
A. Anterior cerebral
B. Basilar
C. Vertebral
D. External carotid
E. Internal carotid
Correct Answer: The correct answer is C. The patient suffered an infarction in the territory of the anterior spinal
artery due to global hypoperfusion as a consequence of a cardiac arrest. The anterior spinal artery is formed
rostrally by branches of the vertebral artery.
38. Which of the following is most likely to occur as a result of a vertebral artery dissection?
A. Brachial plexopathy
B. Brown-Sequard syndrome
C. Central cord syndrome
D. Cervical radiculopathy
E. Posterior spinal artery syndrome
Correct Answer: The correct answer is D. In one review, cervical radiculopathy was reported nearly as commonly
as cervical myelopathy in patients with spinal cord symptoms due to vertebral artery dissection. The posterior
spinal arteries are derived from segmental arteries, not the vertebral arteries, and the vertebral arteries do not supply
the brachial plexus. Central cord and Brown-Sequard syndromes involve lesions that do not conform to any arterial
distribution.
39. A 24-year-old woman is evaluated for rapidly progressive weakness and sensory loss in the lower limbs over
the past 24 hours. She has a history of polyarthritis, anemia, thrombocytopenia, and mild renal failure. Neurological
examination reveals flaccid weakness in the iliopsoas, hamstring, and foot muscles bilaterally, a pinprick level at
T5, and loss of vibration and position sense in the toes. MRI of the spine shows segmental enlargement, increased
T2 signal, and an area of gadolinium enhancement in the midthoracic cord. MRI of the head is normal. Which of

the following abnormalities is most likely to provide the diagnosis in this patient?
A. Serology for Lyme disease
B. Double-strand DNA antibodies
C. Angiotensin-converting enzyme level
D. PCR for human T-cell lymphotropic virus type I DNA
E. Serology for Campylobacter jejuni
Correct Answer: The correct answer is B. Acute transverse myelitis is a well-recognized manifestation of systemic
lupus erythematous. The history of polyarthritis, anemia, thrombocytopenia, and renal failure should raise this
possibility in a young patient.
40. A 50-year-old woman with a 6-month history of gradually deteriorating gait and sphincter function is found to
have spastic paraparesis. The patient was born and raised in Mexico and moved to the United States 20 years ago.
MRI reveals a large cystic lesion compressing the cord at the T10 level with several smaller cysts in the cervical
cord. An MRI scan of the brain reveals scattered calcified cysts. This infection was most likely acquired as a result
of which of the following?
A. A mosquito bite
B. A tick bite
C. Ingestion of food contaminated by fecal matter
D. Ingestion of inadequately cooked pork
E. Swimming in snail-infested water
Correct Answer: The correct answer is C. The presence of multifocal cysts in the brain and spinal cord, some of
them calcified, is very suggestive of neurocysticercosis, especially in a patient from an area where the infection is
endemic. This condition is an infection caused by Taenia solium, a tapeworm for which humans are the definitive
hosts. Pigs are the usual intermediate hosts, ingesting eggs excreted in human feces by the adult worm.