196. The answer is a. (Swaiman, pp 667-668.) Children with Tay-Sachs disease die prematurely and exhibit mental retardation, seizures, and blindness. This is a ganglioside storage disease that occurs more commonly in Ashkenazi Jews than in the general population. The early-onset form will produce macrocephaly and a cherry red spot in the fundus.
197. The answer is a. (Swaiman, pp 670-671.) The disease responsible for the accumulation of glucosylceramide is Gaucher disease. Gaucher disease is inherited as an autosomal recessive trait and may be diagnosed by demonstrating deficient glucocerebrosidase in fibroblasts or leukocytes. The severity of disease varies from nonneuronopathic types to acute infantile neuronopathic disease. Gaucher disease produces hepatosplenomegaly and may cause lethal CNS disease. It is one of a collection of storage diseases called sphingolipidoses, which include Niemann-Pick disease, Krabbe disease, and Fabry disease. Fabry disease involves the accumulation of another ceramide, trihexosylceramide. All the sphingolipids are nothing more than lipids that contain a sphingosine moiety. Sphingosine is a class of long-chain compounds with hydroxyl groups on carbons 1 and 3 and an amino group on carbon 2. They form ceramides by joining with fatty acids across the subterminal amino group. GM2 ganglioside accumulates in Tay-Sachs disease, and galactosyl sulfatides accumulate in metachromatic leukodystrophy.
198. The answer is b. (Ropper, pp 1090-1093.) The clinical picture presented suggests hepatic failure. Copper poisoning may lead to hepatic failure, but the altered consciousness would be a consequence of the liver disease rather than the heavy metal poison itself. Similarly, vitamin B12 deficiency may lead to dementia, but it would not produce the signs of hepatic insufficiency exhibited by this patient. Encephalopathy that develops with chronic hepatic disease and portal hypertension is often called portal-systemic encephalopathy because of the importance of toxin-laden blood bypassing the liver as portal hypertension develops. Precisely what toxins produce the encephalopathy is still debatable, but ammonia is probably the most important one. This type of encephalopathy will develop if flow through the liver is obstructed and the liver is otherwise normal. This is distinct from the terminal coma that may develop with acute hepatic necrosis.
199. The answer is d. (Ropper, pp 1090-1093.) Long-standing hepatic disease may produce a profound encephalopathy, but changes in the brain are notably sparse with portal-systemic encephalopathy. The most obvious change is an increase in Alzheimer type II astrocytes. These astrocytes are relatively large cells. Rarely patients show more dramatic changes, which include neuronal loss and focal necrosis. With chronic alcoholism and hepatic insufficiency, patients exhibit a loss of Purkinje cells in the cerebellum, but this is a consequence of alcohol toxicity or thiamine deficiency rather than of toxic injury from the hepatic dysfunction.
200. The answer is c. (Ropper, pp 822-824.) The elevation with hypertensive encephalopathy is variable because intracranial hemorrhage may occur with the hypertensive crisis, but most patients will have moderate increases in CSF protein. Lowering of the blood pressure may reduce the protein elevation.
201. The answer is a. (Fauci, p 269.) The type of peripheral neuropathy most commonly developing with chronic renal failure is a symmetric, distal, mixed sensorimotor neuropathy. The legs are generally affected first and most severely. Men are more commonly affected than women. Most of the peripheral neuropathies in patients with chronic renal failure involve axonal degeneration. The neuropathy usually improves with dialysis.
202. The answer is b. (Ropper, pp 382-383.) The restless legs syndrome is characterized by a feeling of discomfort in the legs that is relieved by movement. The sensation is felt deep within the limb, and is variably described as a pulling, stretching, or cramping. Restless legs syndrome occurs primarily at night, shortly after the patient lies down. It differs from akathisia, which is a restlessness that occurs during the daytime. It may be associated with peripheral neuropathy and anemia and is seen in patients with chronic renal disease, diabetes mellitus, and many other medical conditions. Exercise before going to bed may alleviate much of the discomfort. Agents that may be effective in alleviating symptoms include clonazepam, gabapentin, L-dopa, dopamine agonists (eg, pramipexole or ropinirole), and opiates. Neuroleptics, calcium channel blockers, and caffeine may worsen symptoms.
203. The answer is e. (Fauci, pp 1779-1781.) B vitamins are generally replaced when patients receive dialysis. Thiamine is water-soluble and so is easily lost during dialysis, but even replacing thiamine is not nearly as effective in retarding or reversing the neuropathy of chronic renal failure as is renal transplantation. There are presumed to be neurotoxins in the blood of patients with uremia that are not removed by routine dialysis.
204. The answer is b. (Fauci, p 2540.) Intrinsic factor is a glycoprotein that is secreted by the gastric parietal cells. In most people with vitamin B12 deficiency, the problem is inadequate production of intrinsic factor rather than inadequate vitamin B12 in the diet. Persons with pernicious anemia usually have an atrophic gastritis with inadequate intrinsic factor production as a consequence. This is presumed to be mediated by an autoimmune disorder.
205. The answer is b. (Fauci, p 2540.) Vitamin B12 (cobalamin) is an essential cofactor in the conversion of L-methylmalonyl-CoA to succinyl-CoA and of homocysteine to methionine. Without sufficient vitamin B12, the conversion of propionic acid to succinic acid is blocked, and the intermediate compound, methylmalonic acid, accumulates in the blood. It is readily excreted and may help in the diagnosis of cobalamin deficiency when it is found in excess in the urine. Serum homocysteine levels, but not cysteine levels, may also be elevated because the conversion of homocysteine to methionine is disrupted if vitamin B12 is not available to expedite the methylation of homocysteine. Without this conversion of homocysteine to methionine, folate metabolism is disturbed, which probably interferes with DNA synthesis in red blood cell precursor cells.
206. The answer is e. (Fauci, p 1499.) Both the lateral and posterior columns of the spinal cord are damaged with cobalamin deficiency, but a positive Romberg sign develops with impaired position sense, a sensory modality carried in the posterior columns of the cord. Because both sensory and motor functions are disturbed with cobalamin deficiency, the resulting condition is called combined systems disease. The microscopic changes in the posterior and lateral columns of the spinal cord in the patient with combined systems disease include demyelination, gliosis, and vacuolar degeneration. The regions of the spinal cord most severely damaged are the lower cervical and upper thoracic. The vacuolar changes observed arise in the myelin sheaths of very large nerve fibers. Although this starts as a predominantly demyelinating lesion, it evolves into axonal loss. Patients develop spasticity and weakness, as well as disturbed vibration and position sense. The clinical picture becomes more confused because a peripheral neuropathy may also develop with cobalamin deficiency. The peripheral neuropathy of the sort occurring with vitamin B12 deficiency would ordinarily produce hyporeflexia. The lateral column damage, which involves the corticospinal tracts, would ordinarily cause hyperreflexia. Because both peripheral nerves and corticospinal tracts are damaged with vitamin B12deficiency, the effect on reflexes is difficult to predict and often changes over time. The patient will usually start with hyperreflexia and then develop either clonus or hyporeflexia.
207. The answer is a. (Ropper, pp 1117-1121.) The blind spot that normally occurs in each eye enlarges and extends temporally to involve central vision in patients with chronic vitamin B12 deficiency. This is similar to the blind spot that is associated with alcohol and tobacco excess, a problem called tobacco-alcohol amblyopia. Tobacco-alcohol amblyopia also seems to develop because of a vitamin B deficiency, but the deficiency is presumed to be of thiamine rather than of cobalamin.
208. The answer is e. (Ropper, pp 1172-1173.) Methotrexate inhibits dihydrofolate reductase, thereby interfering with the metabolism of folate. As is the case with cobalamin deficiency, this results in a megaloblastic anemia. Defective DNA synthesis underlies the marrow disturbance that is seen with both folate and cobalamin deficiencies.
209. The answer is e. (Ropper, pp 1109-1114.) This woman was at risk for Wernicke encephalopathy. She should have received supplemental thiamine for at least 3 days, even though this would not have prevented the cognitive deterioration that she exhibited. There was no indication for using a neuroleptic (eg, haloperidol, chlorpromazine, or prochlorperazine), even though her alcohol and benzodiazepine use placed her at risk for developing a withdrawal psychosis. The anticholinergic trihexyphenidyl would not be appropriate as either a neuroleptic or an antiepileptic.
210. The answer is c. (Ropper, pp 1135-1139.) Chlordiazepoxide at relatively high doses of 25-to-100 mg, four to six times daily, will usually block the more malignant features of both alcohol and benzodiazepine withdrawal. This drug is itself a benzodiazepine, but once the patient has passed through the withdrawal period for the drugs he or she has been taking, the chlordiazepoxide can be systematically and uneventfully reduced. There are no apparent advantages to using an antiepileptic such as phenytoin.
211. The answer is c. (Ropper, p 909.) Any patient treated with isoniazid must receive supplemental pyridoxine. Isoniazid does not interfere with pyridoxine absorption, but it does interfere with its participation in metabolic pathways. Persistently low pyridoxine activity leads to the development of a peripheral neuropathy. This is most likely to be seen as an isolated deficiency in patients on antituberculous therapy.
212. The answer is f. (Ropper, pp 1109-1114.) An apparently acute deterioration in cognitive function in an alcoholic may stem from any one of several causes. Bleeding from esophageal varices may have produced a profound anemia. Inapparent head trauma may have produced a subarachnoid hemorrhage or subdural hematomas. If the patient’s problem is caused by a nutritional deficiency, it is most likely thiamine deficiency associated with alcoholism. That this patient has no alcohol in her blood at the time of the deterioration is irrelevant. The triad of dementia, gait difficulty, and oculomotor paresis is characteristic of Wernicke encephalopathy, the rapidly progressive and potentially lethal form of thiamine deficiency. Peripheral neuropathy commonly develops with thiamine deficiency, but it is not a component of the encephalopathy caused by thiamine deficiency.
213. The answer is a. (Ropper, pp 1122-1123.) The vitamin deficiency specifically responsible for injury to the optic nerve in persons who chronically smoke tobacco and drink ethanol is still uncertain. It probably arises from combined deficits of vitamins B1, B12, and riboflavin. This condition is also known as nutritional optic neuropathy and as tobacco-alcohol amblyopia. There has been considerable speculation about its arising as a consequence of chronic cyanide poisoning from tobacco smoking combined with vitamin B12 deficiency associated with alcoholism, but this theory has little support.
214. The answer is g. (Ropper, p 1109.) Persons with limited diet devoid of animal fats and rich in corn are at risk for pellagra, a nutritional deficiency of nicotinic acid or its precursor, tryptophan. This disease typically affects the skin, digestive tract, CNS, and hematopoietic system. People with diets limited to corn (maize) are especially vulnerable because of the low levels of tryptophan and niacin in this grain.
215. The answer is b. (Ropper, pp 1117-1121.) The slow evolution of gait difficulty, bladder dysfunction, paresthesias, hyporeflexia, impaired position and vibration sense, and anemia suggests combined systems disease, the neurological equivalent of pernicious anemia. Persons with this disease may have a diet rich in vitamin B12, but they will develop deficiency if they lack intrinsic factor in the stomach. Patients usually acquire a megaloblastic anemia associated with the spastic paraparesis. Finding hyper-segmented polymorphonuclear cells on the peripheral blood smear helps establish the diagnosis.
216. The answer is d. (Ropper, p 1109.) Vitamin E deficiency that causes neurological disease is rare, but when it does develop it is usually during early childhood. The most common syndrome involves spinocerebellar degeneration, polyneuropathy, and pigmentary retinopathy. Clarke’s columns, the spinocerebellar tracts, the posterior columns, the nuclei of Goll and Burdach, and sensory roots are especially likely to exhibit degeneration in persons with vitamin E deficiency. The most obvious symptom of the deficiency is likely to be ataxia.
217. The answer is h. (Ropper, p 1108.) Protein deficiency states, such as those occurring with kwashiorkor, produce a wide range of neurological signs and symptoms. Although the CNS is somewhat sheltered from the ravages of malnutrition, severe protein-calorie deficiencies during childhood development may leave the child neurologically impaired for life. Even when dietary supplements have been introduced to correct the chronic deficiency, the children are likely to exhibit little improvement in mobility or alertness for weeks or months.
218. The answer is n. (Ropper, p 717.) This woman is at relatively high risk for AIDS encephalopathy because she has required transfusion of clotting factors that have until recently been available only from pooled samples of blood products. The neurological deficits that she exhibits are not specific for HIV-1–associated subacute encephalomyelitis (AIDS encephalitis) and are quite compatible with multiple sclerosis (MS). That her MRI does not reveal plaques of demyelination scattered throughout the brain makes the diagnosis of MS improbable. To establish the diagnosis of AIDS encephalopathy, HIV-1 antibodies should be sought and the helper/suppressor (CD4/CD8) T-lymphocyte ratio should be checked. Patients with symptomatic AIDS usually have a CD4/CD8 T-lymphocyte ratio of less than 0.5.
219. The answer is o. (Ropper, p 390.) Obesity associated with hypersomnia qualifies as pickwickian syndrome if the patient exhibits other characteristic features, such as sleep apnea. The patient with this syndrome is likely to have hypoxemia and pulmonary hypertension. Smoking increases the risk of developing the syndrome. Sleep attacks usually abate with cessation of smoking and weight loss.
220. The answer is e. (Ropper, pp 719-721.) With herpes encephalitis in the person who is not immunodeficient, the first clinical signs of disease are likely to be psychiatric. Depression, irritability, and labile affect are especially common. The organic basis for the encephalopathy usually becomes self-evident when the affected person has a seizure. Because the temporal lobe is especially involved by herpes encephalitis, the initial seizure is likely to be complex partial, but seizures often become more generalized. EEG will usually reveal the focal character of the cerebral damage. Intracranial pressure is usually increased with a fulminant infection. Temporal lobe swelling may be severe enough to produce lethal herniation.
221. The answer is i. (Ropper, pp 874-896.) Optic neuritis is often the first symptom that motivates the patient with multiple sclerosis to consult a physician. Clumsiness, stumbling, and other symptoms of ataxia are usually dismissed as inconsequential by the patient. Even those with profoundly slow and slurred speech are often unaware of their dysarthria. When the patient finally does consult a physician, multiple neurological abnormalities are usually evident. This patient would be expected to have a positive swinging flashlight test (Marcus Gunn pupil) and evidence of widespread demyelination on MRI of the head.
222. The answer is l. (Ropper, p 673.) With acute bacterial meningitis, the time between the first symptoms and death may be only days. A petechial rash developing over the lower parts of the body in the setting of fever, headache, nuchal rigidity, photophobia, and stupor must be considered presumptive evidence of a meningococcal meningitis. Rapid diagnosis and treatment are essential if the patient is to survive. The spinal fluid typically reveals a low glucose content, high protein content, and leukocytosis with a large number of polymorphonuclear cells. Treatment with intravenous penicillin G, 12 million-to-15 million U daily (divided into four to six doses), early in the course of illness may decide whether the patient survives more than a few hours or days.
223. The answer is a. (Ropper, pp 304-335.) After significant head trauma, the victim is at considerable risk for a seizure. A patient’s seizure threshold is lowest when he or she is asleep or sleep-deprived. If the posttraumatic seizure occurs during sleep, it may go unnoticed. The patient’s improving cognition suggests a postictal state. His hemiparesis is probably a Todd paralysis, but any patient with posttraumatic seizures and focal weakness must be investigated for an acute or chronic subdural hematoma.
224. The answer is j. (Ropper, pp 1090-1093.) Carbon tetrachloride is a potent hepatic toxin. This woman may have attempted to commit suicide by drinking cleaning fluid. As hepatic damage progressed, she developed fetor hepaticus, a distinctive smell to her breath that reflects a profound metabolic disturbance. The serum ammonia level rose as liver function declined. The triphasic waves typically seen in hepatic encephalopathy may occur with uremia and other causes of metabolic encephalopathy.