1.
A 37-year-old man who is HIV-1-positive has had increasing memory problems for the past year. He is depressed.
During the past 3 months, he has had increasing problems with motor function and is now unable to stand or walk. For the
past 3 days, he has had fever, cough, and dyspnea. A bronchoalveolar lavage shows cysts of Pneumocystis jiroveci. MRI
of the brain shows diffuse cerebral atrophy; no focal lesions are identified. On microscopic examination of the brain, which
of the following findings is most likely to be present?
A. 
Plaques of demyelination in periventricular white matter
B. 
Neocortical senile plaques and neurofibrillary tangles
C. 
Multiple lacunar infarcts in basal ganglia
D. 
Spongiform change involving cerebellum and neocortex
E. 
White matter microglial nodules with multinucleate cells
2.
A term infant is born to a 32-year-old woman whose pregnancy was uncomplicated. A newborn physical examination
shows a small lower lumbar skin dimple with a protruding tuft of hair. A radiograph shows that the underlying L4 vertebra
has lack of closure of the posterior arches. What is the most likely diagnosis?
A. 
Dandy-Walker malformation
B. 
C. 
D. 
Arnold-Chiari malformation
E. 
3.
A 5-year-old boy has been irritable for the past 2 days and has complained of an earache for the past 5 days. On
physical examination, he has a temperature of 39.1°C. Laboratory examination of the CSF from a lumbar puncture shows
numerous neutrophils, slightly increased protein level, and decreased glucose concentration. On Gram staining of the
CSF, which of the following is most likely to be seen microscopically?
A. 
B. 
C. 
D. 
E. 
4.
A 55-year-old man who had been healthy all his life now has progressive, symmetric muscular weakness. Two years
ago, he noted weakness in the area of the head and neck, which caused difficulty with speech, eye movements, and
swallowing. In the past year, the weakness in the upper and lower extremities has increased, and he can no longer stand,
walk, or feed himself. His mental function remains intact. What is the most likely diagnosis?
A. 
Amyotrophic lateral sclerosis
B. 
C. 
D. 
E. 
5.
A neonate is born prematurely at 28 weeks gestation to a 22-year-old primigravida. The infant is initially stable, and a
newborn physical examination shows no abnormalities. The infant becomes severely hypoxemic 24 hours later, and
seizure activity is observed. There is poor neurologic development during infancy. CT scan of the head shows
symmetrically enlarged cerebral ventricles at 8 months of age. Which of the following perinatal complications most likely
produced these findings?
A. 
Germinal matrix hemorrhage
B. 
C. 
D. 
Congenital cytomegalovirus infection
E. 
6.
A 79-year-old woman was driving her automobile when she had a sudden, severe headache. She drove to a service
station, stopped the vehicle, and slumped over the wheel. She was taken to the emergency department, where she
remained comatose and died 6 hours later. The gross appearance of the brain at autopsy is shown in the figure. What is
the most likely diagnosis?
A. 
Hemorrhage in a glioblastoma multiforme
B. 
Thromboembolization with cerebral infarction
C. 
Tearing of the bridging veins
D. 
Rupture of a berry aneurysm
E. 
Hyaline arteriolosclerosis with hemorrhage
7.
A study is conducted to identify causes of neuronal loss in patients 18 to 90 years old who died in the hospital from a
natural manner of death and who had autopsies performed. Histologic sections are taken from multiple areas of the brain
in each patient. The sections are analyzed for the appearance of red, shrunken neurons, decreased numbers of neurons,
or absent neurons. A subset of patients is identified in which the hippocampal pyramidal cells, the cerebellar Purkinje cells,
and the superior parasagittal neocortical pyramidal cells are affected. The medical records of these patients are reviewed
to determine what risk factors for neuronal loss were present before death. What condition is most likely to be the major
cause of neuronal loss in this subset of patients?
A. 
B. 
C. 
D. 
E. 
F. 
G. 
8.
An 83-year-old woman slips in the bathtub in her home and falls backward, striking her head. She is taken to the
emergency department, where examination shows a 3-cm, reddish, slightly swollen area over the occiput. She is
arousable but somnolent. There are no motor or sensory deficits. There is no papilledema. CT scan of the head is
performed. Acute hemorrhage in which of the following locations is most likely to be seen?
A. 
B. 
C. 
D. 
E. 
F. 
9.
A 36-year-old woman is involved in a motor vehicle accident. She is not wearing a safety belt and is ejected from the
vehicle. When paramedics arrive, her vital signs are stable with pulse 80/min, respirations 17/min, and blood pressure
125/80 mm Hg. On examination in the emergency department, she has multiple contusions and abrasions over the skin of
her head, torso, and extremities. There is no papilledema, there is no decerebrate posturing, and she has no spontaneous
movements. She is not conscious. CT scan of the head shows no intracranial hemorrhage or edema and no skull
fractures. She remains in a persistent vegetative state. What lesion is most likely to be present in this patient?
A. 
B. 
Cerebellar tonsillar herniation
C. 
D. 
E. 
Multiple cortical contusions
F. 
10.
A 4-year-old girl developed clumsiness and difficulty ambulating over 6 months. On physical examination, she showed
difficulty with balance while walking, dysarthria, poor hand coordination, absent deep tendon reflexes, and a bilateral
Babinski sign. Light touch and vibratory sensation were greatly diminished. There was no muscular weakness. Over the
next 5 years, she developed congestive heart failure from hypertrophic cardiomyopathy. She also had hyperglycemia. At
autopsy, there was increased perinuclear iron deposition within cardiac myocytes. Which of the following genetic
abnormalities with trinucleotide repeat expansions was most likely present in this patient?
A. 
CAG repeats in the huntingtin gene
B. 
CAG repeats in the spinocerebellar ataxia 7 gene
C. 
CGG repeats in the FMR1 gene
D. 
CTG repeats in the dystrophila myotonia-protein kinase gene
E. 
GAA repeats in the frataxin gene
11.
A 63-year-old man had increasing irritability over 3 years. He spent a lot of time wandering about his neighborhood,
complaining to the neighbors about everything. He had no memory loss and was always able to find his way home. The
neighbors were pleased when he developed aphasia. On physical examination, there were no motor or sensory deficits
and no gait disturbances or tremor. MRI of the brain showed bilateral marked temporal and frontal lobe gyral atrophy. He
died of pneumonia 1 year later. At autopsy, the frontal cortex microscopically shows extensive neuronal loss, and some
remaining neurons show intracytoplasmic, faintly eosinophilic, rounded inclusions that stain immunohistochemically for tau
protein. What is the most likely diagnosis?
A. 
B. 
C. 
D. 
E. 
F. 
G. 
12.
A 20-year-old, mentally retarded woman saw the physician because she had flank pain for 1 week. Physical
examination showed right costovertebral angle tenderness. Patches of leathery-appearing (shagreen patches) and
hypopigmented (ash-leaf patches) skin were scattered over her body. There was a subungual nodule on her right index
finger. Abdominal CT scan showed bilateral renal cysts and tumor masses. MRI of the brain showed subependymal
nodules and 1- to 4-cm cortical foci with loss of the gray-white distinction. CT scan of the chest showed a 3-cm mass
involving the interventricular septum. Two years later, she has sudden, severe headache. MRI now shows a nodule
obstructing the cerebral aqueduct. Neurosurgery is performed, and a subependymal giant-cell astrocytoma is removed.
What is the most likely diagnosis?
A. 
B. 
C. 
D. 
E. 
F. 
Von Hippel–Lindau disease
13.
A 40-year-old man, who rarely had headaches, now has been experiencing headaches for the past 6 months. He
comes to the physician because of a seizure that occurred 1 day ago. On physical examination, there are no remarkable
findings. MRI of the brain shows a solitary, circumscribed 3-cm mass in the right parietal centrum semiovale. The mass
has small cysts and areas of calcification and hemorrhage. Neurosurgery is performed, and the mass is removed.
Microscopically, the mass consists of sheets of cells with round nuclei that have granular chromatin. The cells have a
moderate amount of clear cytoplasm. These cells mark with GFAP by immunohistochemical staining. The patient receives
adjuvant radiation and chemotherapy, and there is no recurrence. Which of the following neoplasms was most likely
present in this patient?
A. 
B. 
Diffuse large B-cell lymphoma
C. 
D. 
E. 
F. 
Metastatic renal cell carcinoma
G. 
14.
A 46-year-old woman has had increasing weakness and loss of sensation in the lower extremities for the past 5
months. She comes to the physician because she has been unable to walk without assistance for the past week. On
physical examination, there is 4/5 motor strength in the right lower extremity and 3/5 motor strength in the left lower
extremity. There is bilateral loss of sensation to light touch from the lateral midthigh distally. MRI of the spine shows a 1 ×
4 cm lesion in the filum terminale. The mass is removed. Microscopically, the mass is composed of cuboidal cells around
papillary cores in a myxoid background. Which of the following was most likely present in this patient?
A. 
B. 
C. 
D. 
Metastatic transitional cell carcinoma
E. 
F. 
G. 
15.
A 52-year-old woman has had malaise for the past 6 months. On physical examination, there are no remarkable
findings. Laboratory studies show hemoglobin, 9.3 g/dL; hematocrit, 27.9%; platelet count, 549,000/mm3; and WBC count,
282,000/mm3 with 64% segmented neutrophils, 10% bands, 3% metamyelocytes, 2% myelocytes, 2% lymphocytes, 1%
monocytes, 9% eosinophils, and 9% basophils. She undergoes chemotherapy. Two months later, she develops neurologic
deficits with ataxia, motor weakness in the right arm, difficulty swallowing, and sensory changes in the left leg. MRI of the
brain shows irregular areas of increased attenuation in white matter of the cerebral hemispheres and the cerebellum. A
stereotaxic biopsy specimen shows perivascular chronic inflammation, marked gliosis, large reactive astrocytes with
bizarre nuclei, and intranuclear inclusions within oligodendroglia. What infection most likely caused these findings?
A. 
B. 
C. 
D. 
E. 
F. 
16.
A 39-year-old man who has been HIV-positive for at least 8 years has received no antiretroviral therapy. He has had
left-sided weakness for the past month. He sees the physician 1 day after experiencing a generalized seizure. On physical
examination, he is afebrile. There is 4/5 motor strength in the left upper extremity. CT scan of the head shows no
intracranial hemorrhage, but there is a midline shift. MRI of the brain shows a 4-cm mass in the region of the putamen near
the right internal capsule, a 3-cm mass in the right centrum semiovale, and a 1-cm mass near the splenium of the corpus
callosum. These masses are circumscribed and solid. CSF from a lumbar puncture shows an elevated protein
concentration and a normal glucose level. Cytologic examination shows large cells with large nuclei and scant cytoplasm
that mark with CD19, but not with GFAP or cytokeratin. What is the most likely diagnosis?
A. 
Cytomegalovirus encephalitis
B. 
C. 
D. 
E. 
Progressive multifocal leukoencephalopathy
F. 
17.
A 60-year-old woman had problems related to movement for 5 years. Physical examination showed cogwheel rigidity of
limbs and a festinating gait, which she had difficulty initiating. Her face was expressionless. She was given levodopa, and
her condition improved. Two years later, she had difficulty performing activities of daily living and showed marked
cognitive decline. She died of aspiration pneumonia. Autopsy findings include mild cerebral atrophy and loss of substantia
nigra pigmentation. Microscopically, there is loss of pigmented neurons, and the remaining substantia nigra neurons and
cortical neurons show spheroidal, intraneuronal, cytoplasmic, and eosinophilic inclusions. Immunohistochemical staining
for which of the following proteins is most likely to be positive in these inclusions?
A. 
B. 
Amyloid precursor protein
C. 
D. 
E. 
F. 
18.
A 70-year-old woman comes to the physician because of an episode 2 days earlier during which she lost
consciousness for several minutes. Afterward, she had difficulty speaking clearly and had paresthesias in the lower right
arm that persisted for several minutes. On physical examination, there is 4/5 motor strength in the right upper extremity
and decreased sensation to pinprick on the ulnar aspect of the lower right arm and hand. There are bilateral carotid bruits.
A lumbar puncture is performed with normal opening pressure. Laboratory studies on 10 mL of clear, colorless CSF show
two mononuclear WBCs/mm3, no RBCs, protein concentration of 40 mg/dL, and glucose concentration of 70 mg/dL. The
serum glucose concentration is 95 mg/dL. CT scan of the head shows no intracranial hemorrhage, but there is a slight
midline shift; MRI of the brain shows an ill-defined area of edema near the left internal capsule. Which of the following
laboratory findings is most suggestive of the risk factor for this patient's disease?
A. 
Positive antiphospholipid antibody test result
B. 
Blood culture positive for Streptococcus pneumoniae
C. 
Elevated serum concentration of very long chain fatty acids
D. 
E. 
F. 
Oligoclonal bands on CSF electrophoresis
G. 
H. 
Positive serologic test result for syphilis
19.
A 15-year-old girl is brought to the physician because she has had progressive difficulty speaking during the past 6
months. She becomes dizzy and falls frequently. She complains of headache and facial and neck pain. During the past
month, she has had decreasing bladder and bowel control. On physical examination, there is loss of pain and temperature
sensation over the nape of the neck, shoulders, and upper arms, but vibration and position sensation are preserved. She
has muscle wasting in the lower neck and shoulders. MRI of the spinal cord shows cervical and thoracic enlargement with
a CSF collection dilating the central canal. MRI of the brain shows gross findings similar to those shown in the figure.
Which of the following is the most likely diagnosis?
A. 
Arnold-Chiari II malformation
B. 
C. 
Dandy-Walker malformation
D. 
E. 
F. 
20.
An infant was born at 36 weeks' gestation to a 22-year-old primigravida. A fetal screening ultrasound study at 18 weeks
showed a single large cerebral ventricle and fused thalami. On physical examination at birth, the infant was small for
gestational age and had multiple anomalies, including postaxial polydactyly of hands and feet, cyclopia, microcephaly, cleft
lip and palate, and rocker-bottom feet. The infant died 1 hour after birth. Which of the following CNS abnormalities best
explains these findings?
A. 
B. 
Arnold-Chiari II malformation
C. 
Dandy-Walker malformation
D. 
E. 
Periventricular leukomalacia
F. 
21.
An 86-year-old man has become progressively unable to live independently for the past 10 years, and he now requires
assistance with bathing, dressing, toileting, feeding, and transfers in and out of chairs and bed. On physical examination,
he has no motor or sensory deficits. He cannot give the current date or state where he is. Six months later, he suddenly
becomes comatose and dies. At autopsy, there is a large superficial left parietal lobe hemorrhage. Histologic examination
of the brain shows numerous neocortical neuritic plaques and neurofibrillary tangles. The peripheral cerebral arteries and
the core of each plaque stain positively with Congo red. Which of the following mechanisms is most likely responsible for
his disease?
A. 
Aggregation of Aβ peptide
B. 
Conformational change in the prion protein (PrP)
C. 
Mutations in the tau gene
D. 
Mutations in the frataxin gene
E. 
F. 
Expansion of polyglutamine repeats
22.
A 55-year-old man has experienced headaches for the first time in his life beginning 2 months ago. He comes to the
emergency department following a generalized tonic-clonic seizure. MR imaging of his brain shows an ill-defined 2 cm
mass in the right posterior parietal cortex. A stereotaxic biopsy of the mass microscopically shows pleomorphic cells
positive for glial fibrillary acidic protein (GFAP). Molecular analysis shows abnormalities of p53 and platelet-derived growth
factor-alpha (PDGF-α). He receives treatment for this lesion. Which of the following neoplasms is he most likely to develop
in the future?
A. 
Diffuse large B cell lymphoma
B. 
C. 
D. 
E.