Question #1
A 12-year-old girl is brought to the physician because of stumbling and falls. She has a broad-based, slow, clumsy gait with a tendency to lurch from side to side. Several years later, she develops clumsiness of fine movements and a coarse intention tremor of the upper limbs. Her illness progresses slowly to kyphoscoliosis and foot deformities. She eventually becomes bedridden and dies in the fourth decade of life from congestive heart failure.
Which of the following neurologic findings is most likely on autopsy?
Answer:
The correct answer is B.
The disease is Friedreich ataxia, which is an autosomal recessive degenerative disorder and is the most common hereditary ataxia. This disease is caused by a mutation in the frataxin (FXN) gene on chromosome 9, which codes for the mitochondrial protein, frataxin. The majority of these patients have an expanded trinucleotide (GAA) repeat in this gene, which leads to decreased expression of frataxin, an iron-binding protein. One theory is that decreased frataxin levels produce mitochondrial iron overload, leading to oxidative stress. Degeneration of large myelinated axons in peripheral nerves, posterior (dorsal) columns, spinocerebellar tracts, and corticospinal tracts occurs, causing the spinal cord and dorsal root ganglia to atrophy. The cerebellum also degenerates to a lesser extent.
Symptoms typically appear between age 5 and 15, and begin with a gait ataxia and eventually spread to the arms and trunk. Eventually, patients become wheelchair-bound, and finally, bedridden. As the disease progresses, dysarthria and dysphagia occur. Speech becomes incomprehensible and because of incoordination of breathing, speaking, and swallowing, patients can nearly choke while speaking. Scoliosis and foot deformities are frequent findings and hypertrophic cardiomyopathy occurs in over 50% of patients. No treatment is known that can alter the course of this devastating disease. Most patients die from cardiac causes (e.g., CHF, arrhythmias) between the ages of 30 to 40.
Atrophy of the caudate (choice A) is seen in Huntington disease, which is characterized by choreoathetosis, dementia, and eventual death. This autosomal dominant disorder is caused by a CAG repeat, and typically does not present until midlife.
Depigmentation of the substantia nigra (choice C) is seen in Parkinson disease, a hypokinetic movement disorder characterized by rigidity, bradykinesia, and a slow resting tremor.
Diffuse cortical atrophy (choice D) is seen in Alzheimer disease, a cause of dementia in the aged population.
Selective frontal and temporal lobe atrophy (choice E) is seen in Pick disease, a severe dementing disease presenting in older populations.
Question #2
A 65-year-old man with a history of hypertension, hyperlipidemia, and myocardial infarction is brought to the emergency department after tripping down the stairs this morning. He reports some disturbances in his vision after waking up this morning that were not present previously. Visual field testing reveals a right lower quadrantanopia.
A CT scan of the head is most likely to show a lesion of which of the following?
Answer:
The correct answer is D.
A right lower quadrantanopia is produced by a left parietal lobe lesion. See lesion # 6 below.
Note that like a camera, the lens inverts the image of the visual field, so
the nasal retina receives information from the temporal visual field, and
the temporal retina receives information from the nasal visual field
At the optic chiasm, optic nerve fibers from the nasal half of each retina cross and project to the contralateral optic tract.
Similarly
the upper retina receives information from the lower visual field, and will subsequently travel in the parietal lobe. Note that information from the upper retina information remains more superior—parietal lobe and cuneus gyrus (above the calcarine sulcus) of the occipital lobe.
the lower retina receives information from the upper visual field, and will subsequently travel in the temporal lobe (Meyer's loop). Note that information from the lower retina information remains more inferior—temporal lobe and lingual gyrus (below the calcarine sulcus) of the occipital lobe.
In this case, light from the right lower quadrant of the visual field strikes the upper nasal retina of the right eye and upper temporal region of the retina in the left eye. Nasal impulses from the right eye decussate at the optic chiasm to join impulses from the temporal left eye that do not decussate. Together, these impulses are carried via the left optic tract to the left lateral geniculate nucleus. From the lateral geniculate nucleus, these impulses from the superior retina radiate through the left parietal lobe to the left occipital cortex.
A lesion in the optic nerve (choice A) can produce a complete visual field defect in the affected eye . See lesion #1.
A lesion in the optic tract (choice B) can produce a contralateral homonymous hemianopia. See lesion #4.
A lesion in the left lateral geniculate nucleus (choice C) can produce a right homonymous hemianopia. This would produce the same effect as lesion #4 of the left optic tract.
A lesion in the left temporal lobe (choice E) can produce a right upper quadrantanopia. This part of the visual radiations is also called Meyer's loop. See lesion #5 (sometimes referred to as "pie in the sky").
Question #3
A 35-year-old man is brought to the emergency department after developing alterations in consciousness and extreme irritability. He returned to the United States 6 weeks ago after a trip to Central America. He initially had some low-grade fevers and myalgia for about a week, which were then followed by his neurologic symptoms. He is currently taking antiretroviral therapy for HIV, and his most recent CD4 count is 600 cells/mm3 with an undetectable viral load. Physical examination shows significant facial muscle spasticity, sweating, hypersalivation, and pupillary dilation. Drinking water and drafts of air trigger painful pharyngeal spasms. All diagnostic investigations and supportive therapy are unsuccessful, and the patient becomes comatose and dies. Autopsy reveals elongated eosinophilic intracytoplasmic inclusions within the pyramidal neurons of the hippocampus and Purkinje neurons of cerebellum.
Which of the following is the most likely diagnosis?
Answer:
The correct answer is E.
This patient presents with the classic symptoms of rabies, which is still endemic in many areas of the world, including regions of Central and South America. The etiologic agent is a negative-sense single-stranded RNA virus transmitted to humans by animal bite (classically a rabid dogor vampire bats). The virus replicates near the site of the bite and enters local motor or sensory neurons, after which it migrates along peripheral nerves to reach the central nervous system.
CMV encephalitis (choice A) affects fetuses (in utero TORCH infection) and immunocompromised patients (HIV patients with CD4 < 50 cells/mm3). The most distinctive microscopic feature is the presence of cytomegalic cells, i.e., abnormally large cells with a large eosinophilic intranuclear inclusion and granular basophilic cytoplasmic inclusions. Given our patient's higher CD4 count, presence of Negri bodies, and atypical findings of hydrophobia and aerophobia, CMV encephalitis is unlikely.
Herpes encephalitis (choice B) could be confused with rabies within the clinical context provided here, but it is not associated with Negri bodies. Histologically, nuclear and cytoplasmic inclusions and microglial nodules are present. It is caused by herpes simplex virus type 1 and frequently leads to hemorrhagic necrosis of the temporal lobes. Patients usually present with focal neurological findings including hemiparesis, cranial nerve defects, and focal seizures.
HIV encephalitis (choice C) is frequently seen in AIDS patients and is due to direct involvement of the CNS by HIV. Dementia, incontinence, and seizures are frequent manifestations. Distinguishing pathologic features in the brain include microglial nodules, with multinucleated giant cells, not seen in our patient. Additionally, this is classically seen in late stage HIV, when CD4 counts fall below 200 cells/mm3.
Lewy body disease (choice D) is a dementia disorder characterized clinically by progressive loss of memory, parkinsonism, and visual/auditory hallucinations, and pathologically by Lewy bodies (round intracytoplasmic neuronal inclusions that contain alpha-synuclein) in the substantia nigra and neocortex. The clinical features are also markedly different from rabies and occur much more gradually. Lewy bodies are also characteristic of Parkinson disease.
Question #4
A 39-year-old woman comes to the physician because of a 2-month history of headaches. She has no history of major medical illness. Vital signs are within normal limits. A head CT shows a mass above the left petrous bone. A biopsy specimen shows a malignant schwannoma on the left trigeminal nerve. The patient undergoes surgery for resection of the mass.
Which of the following is most likely to be found on examination if there is damage to the nerve during the surgery?
Answer:
The correct answer is B.
The trigeminal nerve (CN V) is a mixed (sensory and motor) nerve. It provides sensory innervation to the face, cornea, mucous membranes of the nasal and oral cavities, frontal sinus, anterior two-thirds of the tongue, teeth, and hard palate. It also provides motor innervation for the muscles of mastication (i.e., temporalis, masseter, lateral and medial pterygoids), anterior belly of the digastric, tensor tympani, tensor palati, and the mylohyoid muscles.
If this patient's left CN V was lesioned during surgery, she could lose the corneal (blink) reflex on the left. The corneal reflex is elicited by stimulation of the cornea (such as with cotton) and results in both a direct (ipsilateral) and consensual (contralateral) blink response. The afferent (sensory) limb is transmitted by CN V (unilateral) and the efferent (motor) limb (bilateral) is transmitted by the facial nerve, CN VII.
Additional symptoms that patient could also have include left facial anesthesia, ipsilateral flaccid paralysis of muscles of mastication, deviation of the jaw to the left, paralysis of the tensor tympani muscle (causing hypoacusis), and trigeminal neuralgia.
Accommodation (choice A) involves many structures, such as CN III, the superior colliculus, and the pretectal nucleus. CN V is not involved in accommodation.
The gag reflex (choice C) is a reflex contraction of the back of the throat that is elicited by touching the back of the mouth and throat. This reflex involves only CN IX (afferent, unilateral) and CN X (efferent, bilateral). CN V does not provide sensory function in this area and is not involved in this reflex.
Taste from the anterior two-thirds of the tongue (choice D) is transmitted by the chorda tympani of the facial nerve, CN VII. CN V carries general somatic information from the anterior-two thirds of the tongue, but not taste.
Adduction of the left eye (choice E) is controlled by the oculomotor nerve (CN III) via the action of the medial rectus.
Question #5
A 34-year-old man is brought to the emergency department because of a tonic-clonic seizure. He tested positive for HIV three years ago. In the emergency department, he is conscious but confused. His temperature is 37.2°C (99°F), pulse is 76/min, and respirations are 18/min. Physical examination shows cachexia, oral thrush, and isolated weakness of lateral gaze on the right. Laboratory studies show a CD4 count of 35 cells/µL. An MRI of the brain shows multicentric ring-enhancing lesions in the brain and meninges. The patient undergoes a brain biopsy for diagnostic histologic confirmation.
From which of the following cell types did the lesions most likely arise?
Answer:
The correct answer is B.
Approximately one-third of AIDS patients will experience significant morbidity from neurologic disease. Primary central nervous system (CNS) lymphoma is rare in the general population but is a relatively common type of lymphoma in AIDS patients. Presenting symptoms include seizures, headache, and cranial nerve deficits (e.g., the abducens nerve palsy in this patient). The lesions are often multicentric, and may involve the leptomeninges in a significant number of cases. The lesions present classically as a ring-enhancing lesion on imaging. Other examples of ring-enhancing lesions in the CNS include toxoplasmosis, bacterial abscess, glioblastoma multiforme, and metastases from extracranial primary tumors (e.g., melanoma, breast cancer).
Presenting symptoms include seizures, headache, and cranial nerve deficits (e.g., the abducens nerve palsy in this patient). The lesions are often multicentric, and may involve the leptomeninges in a significant number of cases. The lesions present classically as a ring-enhancing lesion on imaging. Other examples of ring-enhancing lesions in the CNS include toxoplasmosis, bacterial abscess, glioblastoma multiforme, and metastases from extracranial primary tumors (e.g., melanoma, breast cancer).
Primary CNS lymphoma is typically a late manifestation of AIDS (median CD4 count: 40 cells/µL). This lymphoma is usually an intermediate to high-grade B-cell lymphoma; evidence of Epstein-Barr virus reactivation is commonly present (PCR to identify EBV DNA). The peripheral blood leukocyte differential may or may not reveal elevated lymphocyte count. A lumbar puncture with CSF and cytologic analysis are better methods to confirm the diagnosis of CNS lymphoma.
Astrocytoma is a neoplasm derived from cells in the astrocyte (choice A) lineage. This is not particularly associated with AIDS. There are several grades of astrocytoma; however, the most severe manifestation (grade IV) is known as glioblastoma multiforme, which is the most common primary brain tumor in adults. CT scan can show large ring-enhancing or heterogeneously enhancing unicentric lesions located in the cerebral hemispheres, which can also cross to the contralateral side. Pathologic examination usually reveals malignant cells that form pseudopalisading arrangement around a central area of necrosis.
Ependymal cells (choice C) line the ventricles and produce CSF. Microscopically, tumors derived from ependymal cells (called ependymomas) characteristically produce rosettes or perivascular pseudorosettes. Ependydomas classically occur in pediatric patients (median age of 5) in the fourth ventricle and produce hydrocephalus due to CSF outflow obstruction. They are not particularly associated with HIV.
Melanoma is a neoplasm arising from transformation of melanocytic cells (choice D). Although the brain is a favorite site for metastatic melanoma, the incidence of melanoma is not particularly increased in AIDS patients. Metastases to the brain are the most common tumors of the adult brain. Lesions classically present along the gray matter-white matter junction due to arteriolar narrowing in these regions, which trap tumor emboli; a similar mechanism is seen with localization of brain abscesses from bacterial endocarditis.
Oligodendrocytes (choice E) are responsible for producing myelin in the CNS. Neoplasms arising from cells in the oligodendrocyte lineage are called oligodendrogliomas, and can present with new-onset seizures. Calcification is frequently present, and may be visible on CT scan. These tumors are slow-growing, occur in the white matter (site of myelination), and are comprised of cells with clear cytoplasm around central nuclei, surrounded by thin capillary network ("fried egg" and "chicken wire" appearance, respectively) on histology. This neoplasm is not common in AIDS patients. However, another condition, progressive multifocal leukoencephalopathy (PML), a JC virus infection of oligodendrocytes, can occur in AIDS patients and CT scans show hypodense lesions in the white matter.
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