245. The answer is a. (Ropper, p 71.) Chorea gravidarum designates an involuntary movement disorder that occurs during pregnancy and involves relatively rapid and fluid, but not rhythmic, limb and trunk movements. This type of movement disorder may also appear with estrogen use, but the fundamental problem is a dramatic change in the hormonal environment of the brain. At the end of pregnancy or with the withdrawal of the offending estrogen, the movements abate. The movements that develop with chorea gravidarum may be quite asymmetric and forceful. Huntington chorea is a progressive, uniformly fatal hereditary disease that does not fit well with the given history. The other choices are not typically characterized by this type of movement disorder.
246. The answer is e. (Ropper, pp 736-737.) A variety of agents can induce signs and symptoms of parkinsonism on a temporary basis, but few will evoke a persistent parkinsonian syndrome. After the epidemic of encephalitis lethargica of 1918 to 1926, there were many cases of postencephalitic parkinsonism. The causative agent was believed to be an influenza virus, but it could not be isolated with the techniques available at the time of the epidemic. Postinfluenzal parkinsonism still develops, but the incidence is too rare to establish that this virus is the only virus capable of producing parkinsonism. Early in the infection, patients may exhibit a transient chorea. As the chorea abates, the parkinsonism appears and persists.
247. The answer is d. (Kandel, p 865.) Huntington disease is transmitted in an autosomal dominant fashion. The age at which the patient becomes symptomatic is variable and has no effect on the probability of transmitting the disease. The defect underlying this degenerative disease is an abnormal expansion of a region of chromosome 4 containing a triplicate repeat (CAG) sequence. Normal individuals have between 6 and 34 copies of this CAG section; patients with Huntington disease may have from 37 to more than 100 repeats. Once expanded beyond 40 copies, the repeats are unstable and may further increase as they are passed on from one generation to the next. An increased number of repeats in successive generations can lead to earlier disease onset, a phenomenon known as anticipation.
248. The answer is b. (Ropper, pp 1029-1030.) As the caudate atrophies, the frontal tip of the lateral ventricle becomes increasingly rhomboidal in shape. The head of the caudate is usually atrophic early in the course of Huntington disease, and this will usually be evident by the time the patient is symptomatic, if not sooner. On MRI or computed tomography (CT) scanning, the head of the caudate gives the frontal and parietal components of the lateral ventricle its typical comma, or boomerang, appearance.
249. The answer is e. (Ropper, pp 1027-1031.) Writhing and jerking movements of the limbs are part of the chorea that typically develops with Huntington disease. Dopaminergic drugs, such as L-dopa, bromocriptine, and lisuride, may unmask chorea. This is inadvisable as a diagnostic technique because it may contribute to the premature symptom of chorea. Dopamine antagonists, such as haloperidol, may be used to suppress chorea, but also carry the risk of provoking tardive dyskinesia. Huntington disease is characterized pathologically by loss of several neuronal types in the striatum (caudate and putamen). It has been hypothesized that the occurrence of dopaminergic-induced chorea in Huntington disease is related to increased sensitivity of the dopamine receptors in the remaining striatal neurons, although there are abnormalities in several other neurotransmitters as well. Choreiform movements develop in a variety of other conditions; the one most similar to Huntington disease is hereditary acanthocytosis.
250. The answer is d. (Ropper, pp 64, 67.) Young adults who have self-administered MPTP in an effort to achieve an opiate high have developed progressive damage to the substantia nigra. The neurological syndrome that results from this damage is indistinguishable from Parkinson disease, except that it evolves over weeks or months rather than years. Affected persons exhibit rigidity, tremor, and bradykinesia. That a toxin can produce a syndrome indistinguishable from Parkinson disease has increased speculation that some—perhaps many—persons with Parkinson disease have had environmental exposure to a toxin that produced degeneration of the substantia nigra.
251. The answer is d. (Ropper, pp 1033-1045.) The tremor is of a parkinsonian type. The patient also has the classic findings of Parkinson disease: asymmetric tremor, rigidity, and bradykinesia. Parkinson disease is primarily the result of loss of dopaminergic cells in the substantia nigra and other pigmented nuclei. Cerebral cortex is commonly involved in epilepsy, which is characterized by repeated unprovoked seizures. Guillain-Barré syndrome is a peripheral demyelinating disease that usually presents as an ascending motor deficit. Multiple sclerosis is a CNS demyelinating disease, involving cerebral white matter. It presents with individual episodes of CNS deficits, which usually recover to some extent. Cerebellar dysfunction may cause a tremor, but not rigidity and bradykinesia.
252. The answer is b. (Ropper, pp 64-65.) Current theory of Parkinson disease pathology is based on the premise that the substantia nigra pars compacta has decreased dopamine production, which eventually leads to overinhibition of thalamocortical pathways. The thalamus may be directly intervened on to decrease this overinhibition. Alternatively, the globus pallidus interna may be lesioned or stimulated, because it directly inhibits the thalamus. A third approach is to lesion or stimulate the subthalamic nucleus, which has an excitatory connection on the globus pallidus interna and substantia nigra pars reticulata. The medulla, hippocampus, temporal lobe, and occipital lobe are not involved in this pathway.
253. The answer is b. (Ropper, pp 1033-1045.) Parkinson disease symptoms are due in large part to dopamine depletion. Carbidopa-levodopa can replete dopamine and alleviate symptoms. Alteplase is used to dissolve blood clots during acute strokes or heart attacks. Glatiramer and interferon β-1A are used to treat multiple sclerosis and have been shown to decrease attacks. Both are thought to work through immunomodulation. Sertraline is a selective serotonin reuptake inhibitor. By increasing serotonin concentrations, it is effective for the treatment of depression.
254. The answer is c. (Ropper, pp 1033-1045.) The intracytoplasmic inclusion bodies commonly seen in patients with idiopathic Parkinson disease are called Lewy bodies. They are eosinophilic inclusions with poorly staining halos surrounding them. They may be round or oblong in shape and are most common in the substantia nigra, locus coeruleus, and substantia innominata. They appear to consist of aggregated neurofilaments. Degenerative changes may be remarkably asymmetric in patients with Parkinson disease.
255. The answer is a. (Ropper, p 106.) Trihexyphenidyl is an anticholinergic drug. It is presumed to decrease signs of parkinsonism caused by drugs that interfere with dopamine neurotransmission by creating a relative deficiency of acetylcholine neurotransmission. In a very simplistic view of the CNS, the cholinergic and dopaminergic systems have antagonistic actions. The offending psychiatric medication should also be slowly tapered off if feasible. Although useful for Parkinson disease, administering L-dopa in this case may worsen the psychiatric condition and would probably not help the parkinsonism.
256. The answer is a. (Ropper, p 465.) Language is not disturbed in Parkinson disease, as it is with aphasias. It is the clarity and volume of speech that deteriorate with the development of hypophonia. Handwriting is similarly disturbed. The patient has increasingly smaller and less legible penmanship as he or she continues to write. This is referred to as micrographia.
257. The answer is d. (Ropper, pp 1033-1045.)L-Dopa crosses the blood–brain barrier easily and is subsequently converted to dopamine in the CNS. Conversion of L-dopa to dopamine occurs outside the CNS in a wide variety of tissues, but once converted to dopamine in the periphery, the drug becomes inaccessible to the brain. Peripheral conversion of L-dopa to dopamine is routinely inhibited by adding a dopa decarboxylase inhibitor to the therapeutic regimen. Carbidopa, the inhibitor most widely used, does not penetrate the blood–brain barrier substantially. Because it is largely excluded from the CNS, carbidopa cannot inhibit the conversion of L-dopa to dopamine in the brain.
258. The answer is e. (Ropper, pp 107-108.) The scenario described is that associated with Tourette syndrome. The affected person is usually more than 21 years of age and cannot control the obscene and scatological remarks. With Tourette syndrome there appears to be an autosomal dominant pattern of inheritance with variable penetrance. Most affected persons are men. A variety of drugs may help suppress the tics that are characteristic of this syndrome. These include haloperidol, pimozide, trifluoperazine, and fluphenazine. Antiepileptics, such as carbamazepine and phenytoin, are not useful. Trihexyphenidyl and benztropine are useful in suppressing the parkinsonism that may develop with haloperidol administration, but are not useful in the management of Tourette syndrome.
259. The answer is e. (Ropper, pp 1040-1041.) Dopa decarboxylase converts L-dopa to dopamine. Carbidopa crosses the blood–brain barrier poorly, and so its inhibition of this enzyme is restricted to activity outside the CNS. Conversion of L-dopa to dopamine continues to occur in the CNS when the patient takes Sinemet, a combination of L-dopa and carbidopa.
260. The answer is c. (Ropper, pp 1039-1045.) The on-off effect is commonly seen in persons who have had Parkinson disease for several years. Maintaining more stable levels of antiparkinsonian medication in the blood does not eliminate this phenomenon of abruptly worsening and remitting symptoms. Variability in the responsiveness of the CNS to the medication, rather than in the medication levels, underlies the phenomenon.
261. The answer is a. (Ropper, pp 103-105.) Meige syndrome is a form of focal dystonia characterized by blepharospasm, forceful jaw opening, lip retraction, neck contractions, and tongue thrusting. Sometimes these features are produced by phenothiazine or butyrophenone use, but they may also occur idiopathically, more often in women than men, with onset in the sixth decade. Botulinum toxin injection has been more effective in treatment than any oral medication.
262. The answer is f. (Ropper, pp 102-104.) Spasmodic torticollis is another very common form of focal dystonia. It usually begins in early adult life. The contractions of the neck muscles may be painful and also produce hypertrophy. Standing and walking worsen the contractions, and typically a trick, or geste, such as touching the chin or resting the head against a pillow, may reduce the spasms. Spontaneous remissions may occur. Trihexyphenidyl and a number of other medications may be used, generally without much success; effective improvement generally does not occur until botulinum toxin injections are given.
263. The answer is i. (Ropper, pp 90-91.) Essential tremor comes on during action and remits when the limb is relaxed, unlike the tremor of Parkinson disease. It often affects the head as well as the arms, also unlike Parkinson disease. Patients are often very disturbed by the tremor, particularly as it leads to a great deal of social embarrassment. There is no associated slowness of activity (bradykinesia), rigidity, or cognitive disturbance. Patients frequently report improvement with alcohol, to the extent that some patients may resort to use of alcohol on a chronic basis to reduce their symptoms. Although it is often referred to as familial tremor, there is some disagreement on this point because it may simply be the case that patients with the condition are more likely to refer relatives for evaluation. Beta-blockers and primidone may be used to treat this condition.
264. The answer is c. (Ropper, pp 1033-1045.) Idiopathic Parkinson disease is characterized by the classic combination of tremor, rigidity, bradykinesia, and postural instability. The typical tremor is a 4-Hz pill-rolling tremor, affecting one side more than the other. Action tremor may also occur. The classic pathological hallmarks of the disease are a loss of pigmented cells in the substantia nigra and other nuclei, and the finding of the Lewy body, which is an eosinophilic cytoplasmic inclusion in the remaining cells of the substantia nigra.
265. The answer is a. (Ropper, pp 940-942.) Hepatolenticular degeneration (Wilson disease) often becomes symptomatic in the second or third decade of life, but its initial presentation may be delayed until the fourth or fifth decade. Renal tubular acidosis develops along with hepatic fibrosis. Systemic problems include heart and lung damage, but most patients become most symptomatic from their brain and liver disease. Dementia is progressive if the patient is not treated. Hepatic disease will progress to hepatic failure if the patient is left untreated. Appropriate treatment includes the chelating agent penicillamine, which depletes the body of copper.
266. The answer is h. (Ropper, pp 1154-1155.) Butyrophenones, the most commonly prescribed of which is haloperidol, routinely produce some signs of parkinsonism if they are used at high doses for more than a few days. This psychotic young woman proved to be less sensitive to the parkinsonian effects of the phenothiazine thioridazine than she was to haloperidol. Adding the anticholinergic trihexyphenidyl may also have helped to reduce the patient’s parkinsonism. Another commonly used medication that can cause parkinsonism, in addition to tardive dyskinesia, is metoclopramide hydrochloride.
267. The answer is f. (Ropper, p 344.) Consciousness is preserved in the locked-in syndrome, but the patient is paralyzed from the eyes down. Survival is usually limited to days or weeks in patients with this clinical syndrome. In most cases, the locked-in syndrome develops because of ischemic or hemorrhagic damage to the pons, such as that occurring with basilar artery occlusion.
268. The answer is j. (Ropper, pp 342-343.) The vegetative state is a clinical condition in which autonomic activity is sustained with little evidence of cognitive function. With protracted asystole, the patient may sustain extensive damage to the cerebral cortex, with little damage to the brainstem. The ischemic damage to the cerebrum should be evident on MRI soon after the injury. This type of damage is usually responsible for the appearance of the vegetative state. It also may develop with drowning or other causes of protracted hypoxia.
269. The answer is b. (Ropper, p 1393.) Primary hyperparathyroidism develops in the elderly and may be overlooked or misdiagnosed. The elevated calcium (more than 11.5 mg/dL) that is characteristic of the disturbance is dismissed as an immobilization phenomenon or misconstrued as evidence of an occult neoplasm. The appearance of pseudogout should raise the probability of hyperparathyroidism substantially. The calcium level may in fact be normal when it is checked, but the parathyroid hormone levels will be elevated.