Life Long Learning in Neurology - part 10 potx

169 Correct Answer: The correct answer is A. Following injury of the facial nerve, regenerating parasympathetic fibers destined to the salivary glands misdirect their growth and join the postganglionic sympathetic fibers in the auriculotemporal nerve that innervate the preauricular sweat glands. This results in pathologic preauricular sweating (Frey syndrome). 6. A 36-year-old man develops episodes of sharp, shooting pain involving his throat and left middle ear that are sometimes precipitated by chewing and swallowing large boluses of solid food such as steak but also occur without obvious provocation. Most of the time, they are also associated with lightheadedness or outright syncope due to a sudden drop in blood pressure. He is afraid to drive because of this problem and has had multiple sudden falls with injury due to syncope. Various evaluations have ruled out macroscopic lesions of the throat or thorax. Trials of medication have not been useful. Surgical transection of which of the following structures is most likely to stop his refractory syncopal spells? A. Cervical sympathetic chain B. Glossopharyngeal nerve C. Pharyngeal branches of vagus nerve D. Trigeminal ganglion E. Trigeminal nerve Correct Answer: The correct answer is B. Glossopharyngeal neuralgia is typically associated with pain or paresthesias referred to the throat or middle ear region, which is the region of glossopharyngeal nerve innervation. Occasionally, these attacks will be associated with a sudden drop in blood pressure due to bradycardia and/or loss of vasomotor tone. Antiepileptic medications may help, but in the case of refractory attacks of syncope, sectioning of the glossopharyngeal nerve may be beneficial. 7. A 38-year-old man is evaluated for episodes of paroxysmal hypertension. Neurologic examination reveals a left Horner syndrome, and magnetic resonance angiogram reveals a left internal carotid artery dissection. In this patient, hypertension can be explained by lack of baroreceptor input to which of the following areas? A. Dorsal vagal nucleus B. Nucleus ambiguus C. Nucleus of the solitary tract D. Posterior hypothalamus E. Rostral ventrolateral medulla Correct Answer: The correct answer is C. Paroxysmal hypertension in the setting of carotid artery disease is the manifestation of baroreflex failure. The baroreflex is a critical buffering mechanism for moment-to-moment maintenance of arterial pressure within narrow limits. Baroreceptors located in the carotid bulb and aortic arch send information via the glossopharyngeal and vagus nerves, respectively, to the nucleus of the solitary tract (NTS). Baroreceptive NTS sends excitatory signals to cardiovagal neurons of the nucleus ambiguus and, via the caudal ventrolateral medulla, inhibitory signals to sympathoexcitatory neurons of the rostral ventrolateral medulla. 8. A 60-year-old man is evaluated for a 5-month history of difficulty walking and lightheadedness. Examination reveals parkinsonism and orthostatic hypotension. Which of the following findings will support the diagnosis of Parkinson's disease over that of multiple system atrophy in this patient? A. Impaired cardiac uptake of fluorodopamine B. Impaired increase in plasma norepinephrine upon changing from supine to standing position C. REM sleep behavior disorder D. Uninhibited bladder detrusor contractions E. Upper gastrointestinal dysmotility Correct Answer: The correct answer is A. Impaired cardiac uptake of norepinephrine precursors, including fluorodopamine (by PET) is an indicator of postganglionic cardiac sympathetic denervation. This is typically reduced or absent in Lewy body disorders, including Parkinson's disease, dementia with Lewy bodies, and pure autonomic failure. In contrast, cardiac sympathetic innervation appears to be spared in most cases of multiple system atrophy (MSA). Both primarily preganglionic (MSA) or ganglionic (Lewy body) autonomic disorders causing orthostatic hypotension are characterized by impaired increase of plasma norepinephrine upon changing from supine to standing position. REM sleep behavior disorders, uninhibited bladder contractions, and upper gastrointestinal dysmotility commonly occur in both Parkinson's disease and MSA. 9. A 25-year-old woman has had multiple spells of fainting or near-syncope that only occur shortly after standing. She takes no medications and does not have diabetes mellitus. Her physician is puzzled to find that her tilt table study is normal. Which of the following options is the most likely cause of her orthostatic symptoms? A. Hypovolemia B. Initial orthostatic hypotension C. Neurally mediated syncope 170 D. Postural tachycardia syndrome E. Pure autonomic failure Correct Answer: The correct answer is B. Initial orthostatic hypotension is a commonly underrecognized cause of syncope and accounted for 4% of patients with syncope at one tertiary referral center. It is associated with a transient blood pressure decrease within 15 seconds after standing. It may be observed with continuous beat-to-beat blood pressure monitoring and occurs only during active standing. It is not typically detected on tilt table testing. The other listed causes of syncope would usually be detected by tilt table studies that included EKG monitoring. Correct Answer: Weiling W, Krediet CT, van Dijk N, et al. Initial orthostatic hypotension: review of a forgotten condition. Clin Sci (Lond) 2007 Feb;112(3):157-165. 10. A 72-year-old man with Parkinson's disease presents with episodes of choking and feeling as if food is caught in his throat. Upper endoscopy shows no structural obstructions. Modified barium swallow with video demonstrates repetitive spontaneous contractions of the esophagus suggestive of achalasia. Which of the following treatments is likely to help this problem? A. Bethanechol B. Botulinum toxin injections C. Increased doses of levodopa D. Jejunostomy E. Proton pump inhibitor Correct Answer: The correct answer is B. Achalasia can be treated with botulinum toxin injections into the gastric cardia. Bethanechol is not helpful as it increases the amplitude of gastric contractions in an uncoordinated manner. Levodopa does not affect peristalsis significantly. Feeding jejunostomy should only be considered as a last resort. A proton pump inhibitor agent will not benefit achalasia. 11. A 45-year-old man with a history of depression and insomnia starts treatment with trazodone. This drug has to be discontinued, however, because the patient develops orthostatic hypotension. Which of the following drug effects is the most likely cause of this complication? A. Blockade of 5-hydroxytryptamine receptors B. Blockade of [alpha]-1 receptors C. Blockade of muscarinic M 2 receptors D. Decreased norepinephrine uptake E. Decreased serotonin reuptake Correct Answer: The correct answer is B. Orthostatic hypotension results from impaired reflex vasoconstriction of skeletal and visceral blood vessels, which is mediated by a1-adrenergic receptors. 12. A 53-year-old man with a history of chronic intestinal pseudo-obstruction has recently developed bloating, diarrhea, and nausea. He has had diarrheal stools that float in water, and stool analysis shows an increased percentage of stool fat. He is anemic and has low serum vitamin B 12 levels. The gastroenterologist has found that several other vitamin deficiencies are present. Jejunal aspirate cultures grew out 10 6 colony-forming units. Which of the following treatments should be ordered? A. Fluoroquinolone B. Metoclopramide C. Nortriptyline D. Pyloromyotomy E. Tegaserod Correct Answer: The correct answer is A. This patient has a clinical syndrome and intestinal aspirates consistent with small intestine bacterial overgrowth. Treatment with antibiotics such as fluoroquinolone, amoxicillin- clavulanic acid, or rifaximin is often useful. The other treatments suggested will not benefit this condition. 13. A 71-year-old man presents with 2 months of dyspnea on exertion, orthopnea, and pedal edema. Review of systems with the patient is positive for orthostatic hypotension, gastroparesis, and urinary retention. General physical examination is positive for lateral displacement of the point of maximal impulse, edema, macroglossia, prominent cutaneous ecchymoses, and hepatomegaly. Neurologic examination is remarkable for distal reduction in light touch and pain sensation and diffuse hyporeflexia with absent reflexes at the ankles. Which of the following diagnostic tests should be ordered? A. Anti-ganglionic acetylcholine receptor antibody B. Anti-Hu antibody C. Chest CT scan D. Immunofixation electrophoresis of serum E. Supine plasma norepinephrine level 171 Correct Answer: The correct answer is D. This man presents with symptoms suggestive of congestive heart failure and cardiac enlargement as well as of autonomic dysfunction. Additional findings of macroglossia, hepatomegaly, and cutaneous ecchymoses suggest a constellation consistent with primary amyloidosis. Serum and urine should be sent for immunofixation electrophoresis, which detects immunoglobulins or light chains in 90% of patients with primary amyloidosis. Amyloidosis may also be diagnosed by detection of amyloid in a biopsy of subcutaneous fat, gingiva, or rectal mucosa. The other options are reasonable investigations for other syndromes of autonomic neuropathy that are not associated with the systemic features of amyloidosis reported in this patient. Anti-Hu antibody may be present in paraneoplastic syndromes associated with lung and other malignancies. Antibodies to the neuronal acetylcholine receptor in autonomic ganglia may be found in patients with autoimmune autonomic ganglionopathy. A chest CT might be helpful to detect lung carcinoma or thymoma, which may be associated with autonomic neuropathy. A supine plasma norepinephrine level may be helpful to diagnose some patients with pure autonomic failure. 14. A 52-year-old man with moderate orthostatic hypotension related to diabetic autonomic neuropathy often develops a diffuse neck pain that involves the suboccipital, posterior cervical, and shoulder regions when standing. Which of the following is the most likely underlying cause of neck pain in this man? A. Coronary artery disease B. Impaired myocardial perfusion C. Ischemia of neck musculature D. Parietal lobe ischemia E. Ventilation perfusion mismatch in lung apices Correct Answer: The correct answer is C. Patients with orthostatic hypotension may report neck pain in the suboccipital, posterior cervical, and shoulder regions (the "coat-hanger headache") that is most likely caused by neck muscle ischemia. Chest pain may occur due to hypoperfusion of coronary arteries even in the absence of atherosclerosis due to orthostasis. Ventilation perfusion mismatch in the lung apices may give rise to orthostatic dyspnea due to inadequate perfusion of lung apices. 15. Which of the following degenerative neurologic diseases is most likely to be associated with signs and symptoms of autonomic dysfunction? A. Alzheimer's disease B. Amyotrophic lateral sclerosis C. Corticobasal degeneration D. Dementia with Lewy bodies E. Progressive supranuclear palsy Correct Answer: The correct answer is D. Dementia with Lewy bodies (DLB) is often associated with prominent autonomic features. DLB is one type of [alpha]-synucleinopathy; autonomic dysfunction is common in the syncleinopathies, a class of disorders that also includes Parkinson's disease, pure autonomic failure, and multiple system atrophy. The other disorders listed are classified as tauopathies and are rarely associated with clinically significant autonomic failure. 16. A 39-year-old woman develops gradually worsening dysphagia for both solids and liquids. She also experiences intermittent heartburn, chest pain, and difficulty belching. A barium swallow study demonstrates a marked reduction in peristalsis of the smooth muscle of the esophagus and failure of the lower esophageal sphincter to relax. Which of the following is the most likely site of pathology associated with this gastroesophageal dysfunction? A. Auerbach's plexus B. Endothelial mechanoreceptors C. Interstitial cells of Cajal D. Meissner's plexus E. Postganglionic sympathetic neurons Correct Answer: The correct answer is A. This woman has symptoms and radiologic abnormalities consistent with achalasia. Tissue specimens from patients with achalasia have been shown to have a loss of ganglion cells in Auerbach's plexus, primarily involving nitric oxide-producing neurons that provide inhibitory innervation. Endothelial mechanoreceptors are not involved in achalasia. Interstitial cells of Cajal are believed to be the "pacemaker" cells of the gut that direct peristalsis. The Meissner's plexus primarily controls mucosal functions. Postganglionic sympathetic and parasympathetic neurons are involved in modulation of gut function. 17. A 69-year-old man presents with a 4-month history of weakness and fatigability. He denies diplopia or dysphagia. He has proximal lower extremity weakness on examination. Reflexes are diffusely diminished, and sensory examination is normal. Diagnostic evaluation is remarkable for an incrementing response of compound motor action potential with repetitive nerve stimulation testing, the presence of serum antibodies against P/Q 172 voltage-gated calcium channels, and mediastinal lymphadenopathy on chest x-ray. Which of the following autonomic complaints occurs most frequently in association with this man's illness? A. Constipation B. Dry mouth C. Postural hypotension D. Ptosis E. Urinary retention Correct Answer: The correct answer is B. Dry mouth and impotence (in men) are the most common manifestations of autonomic dysfunction in patients with Lambert-Eaton myasthenic syndrome. Autonomic complaints are present in the majority of patients but are often relatively mild. Cholinergic autonomic symptoms, including dry eye, reduced sweating, abnormal papillary function, and constipation, may be present. Adrenergic symptoms such as postural hypotension and ptosis are much less common. 18. A 45-year-old man with severe orthostatic hypotension secondary to diabetic autonomic neuropathy also has severe supine hypertension. He has developed left ventricular hypertrophy secondary to this problem. Which of the following agents might be useful to treat orthostatic hypotension with less exaggeration of supine hypertension? A. Ephedrine B. Methylphenidate C. Midodrine D. Phenylpropanolamine E. Pyridostigmine Correct Answer: The correct answer is E. The acetylcholinesterase inhibitor pyridostigmine, administered orally, increases blood pressure and reduced orthostatic hypotension in patients with neurogenic orthostatic hypotension with a modest increase in supine blood pressure. The rationale for the use of this agent is that inhibition of acetylcholinesterase may enhance sympathetic ganglionic neurotransmission less when supine than when upright. The other drugs-ephedrine, methylphenidate, and phenylpropanolamine- are sympathomimetic agents with a greater potential to worsen supine hypertension. Correct Answer: Singer W, Opfer-Gehrking TL, McPhee BR, et al. Acetylcholinesterase inhibition: a novel approach in the treatment of neurogenic orthostatic hypotension. J Neurol Neurosurg Psychiatry 2003;74(9):1294- 1298. 19. A 55-year-old woman is evaluated for episodes of severe hypothermia associated with profuse sweating. The episodes last from a few hours to 2 days and are associated with confusion and bradycardia. These episodes most likely reflect increased activity of neurons located in which of the following hypothalamic nuclei? A. Dorsomedial B. Preoptic C. Suprachiasmatic D. Supraoptic E. Ventromedial Correct Answer: The correct answer is B. Paroxysmal hyperhidrosis with hypothermia is a disorder that has been associated with agenesis of the corpus callosum (Shapiro syndrome), head trauma, subarachnoid hemorrhage, and HIV infections but commonly occurs with no identifiable cause. Hyperhidrosis, which is a primary cause of the hypothermia, is a manifestation of excessive sympathetic sudomotor activity triggered by warm-sensitive neurons located in the preoptic-anterior region of the hypothalamus. 20. A 34-year-old woman with myelopathy caused by multiple sclerosis is evaluated for urinary urgency and incontinence. Urodynamic testing shows detrusor overactivity and sphincter dyssynergia, reflecting interruption of sacral projections from neurons located at which of the following areas? A. Dorsal lateral pons B. Dorsomedial medulla C. Preoptic hypothalamus D. Ventrolateral medulla E. Ventromedial midbrain Correct Answer: The correct answer is A. Detrusor sphincter dyssynergia is the consequence of interruption of descending inputs from the pontine micturition center, located in the dorsal pontine tegmentum, to the sacral spinal cord. This descending pathway is critical for coordination of bladder detrusor contraction and relaxation of the external sphincter and is commonly affected in cervical or thoracic spinal cord lesions. 21. A 56-year-old woman develops orthostatic hypotension over several weeks accompanied by dry mouth, dry eyes, impaired pupillary light reflex, and bowel and bladder dysfunction. She has no sensory or motor deficits on examination. Her serum anti-ganglionic acetylcholine receptor antibody titer is high. She is treated with oral 173 corticosteroids and a course of IV immunoglobulin. Which of the following treatments might be particularly helpful for her orthostatic hypotension given the presumed underlying pathophysiology? A. Amlodipine besylate B. Fludrocortisone C. Metoprolol D. Pyridostigmine E. Ramipril Correct Answer: The correct answer is D. Acetylcholinesterase inhibitors have been used to treat orthostatic hypotension in patients with autoimmune autonomic gangliopathy. This treatment is supported by the rationale that the pathophysiology of autoimmune autonomic gangliopathy is presumed to be an impairment of ganglionic cholinergic synaptic transmission. Amlodipine besylate, metoprolol, and ramipril are antihypertensives of different mechanistic classes. Fludrocortisone might help with orthostatic hypotension but does not directly target the underlying pathophysiology. 22. A 59-year-old man presents with bradykinesia, swallowing difficulties, and disabling orthostatic and postprandial hypotension. While in the hospital for aspiration pneumonia, he is noted to have significant supine hypertension at night. Which of the following additional features should suggest the diagnosis of multiple system atrophy rather than Parkinson's disease? A. Festination B. Mild dementia C. Resting tremor D. Rigidity E. Stridor Correct Answer: The correct answer is E. Stridor is a characteristic feature of multiple system atrophy (MSA) that is rare in Parkinson's disease. Other characteristic features of MSA include dysarthria, early postural instability, rapid clinical deterioration, focal reflex myoclonus, Raynaud's phenomenon or acral cyanosis, severe dysphagia, snoring, pseudobulbar crying and laughing, and contractures. 23. A 45-year-old woman with agenesis of the corpus callosum is evaluated for episodes of severe hypothermia associated with profuse sweating. Which of the following drug effects is most likely to reduce the severity of these episodes? A. Activation of histamine receptors B. Blockade of [alpha]2 receptors C. Blockade of [beta]-adrenergic receptors D. Blockade of muscarinic receptors E. Inhibition of serotonin reuptake Correct Answer: The correct answer is D. In patients with paroxysmal hyperhidrosis with hypothermia, reduction of excessive sweating by muscarinic blockade with drugs such as oxybutynin or glycopyrrolate may help reduce severity of hypothermia. Other approaches include activation of central [alpha]2 receptors with clonidine or blockade of serotonergic receptors with cyproheptadine. 24. A 36-year-old woman is evaluated for recurrent episodes of severe right retro-orbital pain, associated with conjunctival injection, and nasal congestion. The episodes last 15 to 60 minutes, tend to wake her up every night for approximately 1 to 2 weeks, and then abate spontaneously for 1 to 2 months. Which of the following ganglia mediate conjunctival and nasal congestion during these events? A. Ciliary B. Geniculate C. Sphenopalatine D. Superior cervical E. Trigeminal Correct Answer: The correct answer is C. This patient has cluster headache. The autonomic manifestations (tearing, conjunctival injection, rhinorrhea) are mediated by parasympathetic neurons located in the sphenopalatine (pterygopalatine) ganglion. These neurons receive inputs from the superior salivatory nucleus via the facial nerve and utilize nitric oxide, vasoactive intestinal polypeptide, and acetylcholine as their neurotransmitters. 25. A 48-year-old man with a history of alcohol abuse and recent weight loss is brought to the emergency department because of progressive confusion over the past 6 hours. On examination, the patient is disoriented to time and space and has nystagmus and impaired ocular movements in all directions. His vital signs are unremarkable except for a rectal temperature of 34°C. Involvement of which of the following structures is most likely to contribute to hypothermia in this patient? A. Locus ceruleus 174 B. Mammillary bodies C. Nucleus ambiguus D. Nucleus of the solitary tract E. Periaqueductal gray Correct Answer: The correct answer is E. The history and findings are consistent with Wernicke encephalopathy. Hypothermia in this disorder likely results from involvement of areas that form part of cold-defense thermoregulatory pathways, including the periaqueductal gray and dorsomedial nucleus of the hypothalamus. 26. A 33-year-old woman is evaluated for abdominal discomfort and constipation. Clinical and neurologic examinations are normal. Autonomic function tests are unremarkable. She is diagnosed with constipation-subtype irritable bowel syndrome and is treated with tegaserod, with improvement of her symptoms. Which of the following mechanisms of action accounts for the beneficial effect of the drug? A. Blockade of M1 muscarinic receptors B. Blockade of serotonin 5-HT 3 receptors C. Stimulation of dopamine D 2 receptors D. Stimulation of M 2 muscarinic receptors E. Stimulation of serotonin 5-HT4 receptors Correct Answer: The correct answer is E. Tegaserod binds to 5-HT 4 receptors and increases motility of the gut, in part by facilitating the release of acetylcholine from myenteric neurons. It has been approved for treatment of constipation in irritable bowel syndrome (IBS). In contrast, drugs that block 5-HT 3 receptors, such as alosetron, may be helpful in diarrhea-subtype IBS, but their use has been associated with ischemic colitis. Stimulation of dopamine D2 receptors would worsen constipation by inhibiting acetylcholine release. 27. A 2-month-old infant is evaluated by his physician for failure to thrive. He has not kept up with growth curves because of problems with poor suck and feeding, vomiting, and dyscoordination of swallowing associated with apparent aspiration. Examination is remarkable for alacrima, absence of lingual fungiform papillae, diffuse hyporeflexia, and decreased response to painful stimuli. Which of the following is the most likely diagnosis? A. Botulism B. Fabry disease C. Familial dysautonomia D. Hereditary sensory and autonomic neuropathy type II (congenital sensory neuropathy) E. Tangier disease Correct Answer: The correct answer is C. Hereditary sensory and autonomic neuropathy (HSAN) type III is also known as Riley-Day syndrome or familial dysautonomia. It is an autosomal recessive disorder caused by gene mutation on chromosome 9 with an incidence of 1:3700 live births among Ashkenazi-Jewish individuals. HSAN- III presents in infancy with insensitivity to superficial pain and temperature, alacrima, hypoactive corneal and tendon reflexes, and the absence of lingual fungiform papillae. Feeding and swallowing problems as well as hypotonia and autonomic disturbances are common. Botulism is an acute neuromuscular disorder that begins with gastrointestinal manifestations followed by paralysis and autonomic features. Fabry disease is an X-linked disorder caused by deficiency of [alpha]-galactosidase A, which results in neuropathic pain, autonomic manifestations, and system involvement. HSAN-II is an autosomal recessive or sporadic disorder that presents in infancy with pan- modality sensory loss and autonomic features. Tangier disease is a rare inherited disorder of cholesterol transport associated with sensorimotor neuropathy and orange tonsils. 28. A 67-year-old man with a history of hypertension, diabetes, and cigarette smoking suffers a stroke. Following release from the hospital, he notices that he has a markedly reduced need to smoke. A lesion of which of the following cortical areas is most likely to account for the patient's reduced craving for cigarettes? A. Hippocampal formation B. Insular cortex C. Lateral prefrontal cortex D. Lateral temporal cortex E. Posterior cingulate cortex Correct Answer: The correct answer is B. The insular cortex is the area of representation of pain, thermal sensation, and visceral sensation and has been implicated in the sensation of internal body state and "feeling" a sense of well- being. This cortical area is activated by alcohol in alcohol-dependent individuals and by food in individuals with food cravings. Insular lesions have been reported to reduce the sensation of internal body state, including reduced craving for cigarettes in patients who smoked. 29. An 8-year-old boy with Lennox-Gastaut syndrome receives topiramate for management of his seizures. His parents should be counseled about which of the following potential side effects of the drug? A. Bradycardia 175 B. Constipation C. Hyperthermia D. Hypotension E. Urinary retention Correct Answer: The correct answer is C. Topiramate, like zonisamide, is a carbonic anhydrase inhibitor that reduces sweat production. This drug-induced anhidrosis may result in hyperthermia. 30. A 22-year-old nurse is evaluated for an 8-month history of painless urinary retention following a urinary tract infection. She has no sense of bladder fullness. Her neurologic examination is normal. MRI of the spine is unremarkable. Autonomic function tests are normal. Urodynamic study reveals a postvoid residual of 1000 cc. An EMG of the urethral sphincter shows myotonic-like discharges. Urethral pressure is 120 cm H 2 O. She has difficulty removing the catheter after performing intermittent self-catheterization and describes the sensation of something "gripping" the catheter. Which of the following treatments is most appropriate to attempt to restore voiding in this patient? A. Baclofen B. Oxybutynin C. Pudendal nerve stimulation D. Pyridostigmine E. Sacral neuromodulation Correct Answer: The correct answer is E. The history and urodynamic findings (including large postvoid residual and increased intraurethral pressure) together with the lack of evidence of an underlying neurologic disorder suggest the diagnosis of urinary retention in young women because of an overactive sphincter (Fowler's syndrome). Although intermittent self-catheterization is the mainstay of treatment, it is more difficult for this patient because of difficulty removing the catheter. The only intervention that has been shown to restore normal voiding in these patients is sacral neuromodulation. 31. A 45-year-old woman is evaluated for dysphagia to solids and liquids, heartburn, and weight loss. Esophagogram reveals loss of peristalsis in and inability of the lower esophageal sphincter to relax, most likely reflecting loss of enteric neurons producing which of the following chemical transmitters? A. Cholecystokinin B. Nitric oxide C. Norepinephrine D. Serotonin E. Substance P Correct Answer: The correct answer is B. The history and findings are typical of achalasia. This disorder has been associated with loss of nitric oxide-synthesizing neurons in the myenteric plexus, which mediates the relaxing effects of the vagus nerve on the lower esophageal sphincter. 32. A 15-year-old girl is evaluated for lifelong postural dizziness that has become more severe over the past 6 months. Neurologic examination is normal except for orthostatic hypotension. Autonomic reflex screen reveals normal postganglionic sudomotor function and heart rate responses to deep breathing and Valsalva maneuver. She has a marked fall of blood pressure during phase II, impaired blood pressure recovery in late phase II, and lack of overshoot in phase IV of the Valsalva maneuver. Plasma norepinephrine and dihydroxyphenylglycol (norepinephrine) levels are virtually undetectable whereas plasma dopamine and dihydroxyphenylalanine (DOPA) levels are elevated. Impaired function of which of the following proteins is most likely to account for the patient's condition? A. Dopamine-[beta]-hydroxylase B. L-Amino acid decarboxylase C. Monoamine oxidase D. Norepinephrine transporter E. Tyrosine hydroxylase Correct Answer: The correct answer is A. The combination of undetectable plasma levels of norepinephrine and its metabolite, dihydroxyphenylglycol (DHPG), and increased levels of dopamine and dihydroxyphenylalanine (DOPA) are the hallmarks of dopamine [beta]-hydroxylase deficiency. Amino acid decarboxylase deficiency would result in elevated levels of DOPA but low levels of dopamine. Deficiency of monoamine oxidase or the norepinephrine transporter results in low levels of DHPG. Tyrosine hydroxylase deficiency results in inability to synthesize all catecholamines. 33. A 44-year-old woman with chronic headache, back and leg pain, depression, and insomnia is evaluated for hyperhidrosis. Her medications include topiramate, gabapentin, bupropion, zolpidem, and a fentanyl patch. Which of these drugs is most likely to account for her hyperhidrosis? 176 A. Bupropion B. Fentanyl C. Gabapentin D. Topiramate E. Zolpidem Correct Answer: The correct answer is B. Fentanyl, like methadone, is an opioid agonist that can produce hyperhidrosis, presumably by increasing histamine release. Bupropion, unlike serotonin reuptake inhibitors, does not typically produce hyperhidrosis. Gabapentin may reduce hyperhidrosis in patients with spinal cord injury. Topiramate is a carbonic anhydrase inhibitor that can produce anhidrosis. Zolpidem, an imidazopyridine GABA A agonist, does not typically alter sweating, although hyperhidrosis may accompany acute withdrawal. 34. A 63-year-old woman has had chronic problems with nausea, vomiting, abdominal pain and bloating, and early satiety after meals. She has had type II diabetes mellitus for 35 years. Upper endoscopy is unremarkable. A gastric emptying study demonstrates delayed gastric emptying of moderate severity. Which of the following medications may be tried to help this woman's symptoms? A. Alprazolam B. Amitriptyline C. Meperidine D. Prochlorperazine E. Propanolol Correct Answer: The correct answer is D. This woman presents with symptoms and radiologic studies consistent with diabetic gastroparesis. Antiemetics such as prochlorperazine are beneficial for many patients with gastroparesis. The other agents may slow gastric emptying. 35. A 17-year-old girl reports dizziness, lightheadedness, palpitations, and weakness upon standing. Although these symptoms occur most of the time when she rises to a standing position, she has only experienced syncope twice, both times on hot days. Measurement of vitals during standing shows maintenance of blood pressure and a transient increase in heart rate to 130 beats/min. Which of the following findings would be most likely in this patient? A. Decreased sympathetic activation B. Increased norepinephrine spillover in the legs C. Increased plasma renin activity D. Increased red blood cell volume E. Sympathetic denervation of the lower extremities Correct Answer: The correct answer is E. This young woman has the postural tachycardia syndrome. It is thought that patients with this syndrome have sympathetic denervation of the lower extremities with preserved cardiac sympathetic innervation. Norepinephrine spillover in the legs is impaired. Patients with postural tachycardia syndrome also reduce red blood cell volume and increase sympathetic activation with normal plasma renin levels. 36. A 66-year-old man with a history of hypertension is evaluated for acute-onset vertigo and ataxia. Examination reveals right-sided upper limb dysmetria and gaze-evoked nystagmus. There is loss of taste sensation on the right side of the tongue. This latter finding indicates involvement of which of the following nuclei? A. Dorsal vagal nucleus B. Facial nucleus C. Nucleus of the solitary tract D. Nucleus prepositus hypoglossi E. Superior salivatory nucleus Correct Answer: The correct answer is C. The nucleus of the solitary tract (NTS) is the first relay station for taste afferents carried by the facial, glossopharyngeal, and vagus nerves. The NTS projects, both directly and via a relay in the parabrachial nucleus, the parvicellular portion of the ventromedial thalamic nucleus, which conveys taste information to the insular cortex. 37. A 56-year-old man is evaluated for progressive dysphagia and dysarthria. Neurologic examination reveals flaccid dysarthria, palatal weakness, and absent gag reflex bilaterally. An MRI of the head shows syringobulbia affecting the region of the nucleus ambiguus bilaterally but sparing the dorsomedial and dorsolateral medulla. Which of the following would be the most likely abnormality found in this patient? A. Abnormal fluctuations of blood pressure during stress B. Delayed gastric emptying C. Impaired taste sensation D. Loss of facial thermoregulatory sweating E. Loss of heart rate variability during deep breathing 177 Correct Answer: The correct answer is E. Experimental evidence indicates that neurons in the ventrolateral portion of the nucleus ambiguus provide most of the vagal innervation to the heart, particularly the sinus node. Involvement of these neurons likely explains the impaired heart rate response to deep breathing (respiratory sinus arrhythmia) that may occur in patients with syringobulbia. Involvement of the nucleus of the solitary tract, which is spared in this patient's lesion, may result in ipsilateral loss of taste sensation and baroreflex failure leading to wide fluctuations of blood pressure during stress or other conditions. Involvement of the dorsal vagal nucleus may produce delayed gastric emptying. Sweating depends on a sympathetic pathway that descends in the dorsolateral medulla. 38. A 67-year-old man presents with gait deterioration over the past 2 years. His examination is remarkable for moderate bradykinesia, cogwheel rigidity, and a resting tremor. He reports remarkable benefit from levodopa/carbidopa, and he has a family history of Parkinson's disease. He also reports constipation, urinary urgency, erectile dysfunction, and orthostatic lightheadedness. Which of the following signs is most likely to be associated with his orthostatic hypotension? A. Acute bradycardia during upright tilt B. Elevated plasma norepinephrine levels in the upright posture C. Hypotension in response to adrenoceptor agonists D. Increase in blood pressure during straining in Valsalva maneuver E. No increase in blood pressure after the release of straining during the Valsalva maneuver. Correct Answer: The correct answer is E. In normal subjects, after the release of straining during a Valsalva maneuver (ie, phase IV), blood pressure rises because sympathetic vasoconstrictor activity had increased during straining. This is referred to as "blood pressure overshoot." Because patients with Parkinson's disease (PD) and orthostatic hypotension (OH) have impaired sympathetic vasoconstrictor function, they have no increase in blood pressure during phase IV of the Valsalva maneuver. Acute bradycardia during tilt testing is seen in vasovagal syncope, not in patients with PD and OH. Patients with PD and OH show a blunted rise in plasma norepinephrine levels with standing. Increased vasoconstrictor responses to adrenoceptor agonists occur in PD suggesting denervation supersensitivity. During the straining phase of the Valsalva maneuver, blood pressure falls, both in normal subjects and in patients with PD and OH. 39. A 48-year-old man is evaluated for orthostatic dizziness and erectile failure over the past 8 months. A thermoregulatory sweat test reveals more than 70% body surface anhidrosis. Autonomic reflex screen reveals normal quantitative sudomotor axon reflex responses at all stimulation sites. Heart rate responses to deep breathing are markedly reduced. Beat-to-beat blood pressure responses during the Valsalva maneuver show absent late phase II and phase IV responses. He has a 30-mm Hg fall of systolic arterial pressure within 3 minutes of head-up tilt. Which of the following options is the most likely diagnosis? A. Amyloid neuropathy B. Diabetic neuropathy C. Multiple system atrophy D. Paraneoplastic ganglionopathy E. Pure autonomic failure Correct Answer: The correct answer is C. In patients with autonomic failure, the combination of impaired sweating responses during the thermoregulatory sweat test and preserved sudomotor axon reflex responses to local iontophoresis of acetylcholine typically indicates a central autonomic disorder, such as multiple system atrophy. In contrast, loss of sudomotor axon reflex responses indicates a peripheral lesion affecting the sympathetic ganglion or postganglionic axons, including pure autonomic failure, autoimmune ganglionopathies, and small fiber neuropathies such as those associated with diabetes or amyloidosis. 40. A 54-year-old woman presents with 6 months of gastrointestinal problems, including esophageal dysmotility, severe gastroparesis, and intestinal pseudo-obstruction. She has had a 40-lb weight loss despite attempts to maintain nutrition with high-protein, high-calorie supplements, prokinetic agents, and a trial of feeding via a nasogastric tube. Her gastroenterologist has recommended a short period of total parenteral nutrition to optimize her nutritional status for placement of a jejunostomy feeding tube. Abdominal and chest CT scans have not identified a malignancy. Which of the following tests should be performed? A. Antineuronal nuclear antibody type 1 (anti-Hu) antibody B. Muscarinic acetylcholine receptor antibody C. P/Q-type voltage-gated calcium channel antibody D. Sural nerve biopsy E. Voltage-gated potassium channel antibody Correct Answer: The correct answer is A. Enteric neuropathy is associated with the presence of either antineuronal nuclear antibody type 1 (ANNA-1) (anti-Hu) antibody or ganglionic acetylcholine receptor antibody. Voltage-gated 178 calcium channels are associated with Lambert-Eaton myasthenic syndrome. Voltage-gated potassium channels are associated with neuromyotonia. Antibodies to muscarinic (M 3 ) acetylcholine receptors have been associated with autonomic symptoms in Sjögren's syndrome. A sural nerve biopsy would fail to demonstrate the pathology of lymphocytic infiltration and destruction that is typically isolated to the myenteric ganglia of the gut. NEUROLOGIC MANIFESTATIONS OF SYSTEMIC DISEASE, February 2008 TYPE A QUESTIONS (ONE BEST ANSWER) 1. An 82-year-old man undergoes coronary artery bypass graft surgery. He develops postoperative delirium. Which of the following patient characteristics is the strongest risk factor for development of postoperative delirium? A. Advanced age B. Left ventricular ejection fraction of 28% C. Peripheral vascular disease D. Proximal aortic atherosclerosis E. Pulmonary disease Correct Answer: The correct answer is A. While all of the above patient characteristics are independent risk factors for the development of postoperative delirium, advanced age is one of the strongest. 2. A 68-year-old man with rheumatoid arthritis is treated with leflunomide. He reports numbness in his feet and a decrease in balance. Which of the following is a reported neurologic complication of leflunomide treatment and the most likely cause of his symptoms? A. Chronic inflammatory demyelinating polyneuropathy B. Demyelination of posterior columns C. Distal sensorimotor axonal polyneuropathy D. Sensory ataxic neuronopathy E. Vasculitic neuropathy Correct Answer: The correct answer is C. There have been multiple reports of an association between leflunomide treatment and the development of distal sensory or sensorimotor axonal polyneuropathy. Chronic inflammatory demyelinating polyneuropathy has been reported in patients treated with etanercept and infliximab. 3. A 74-year-old woman with known pancreatic cancer presents with aphasia. Which of the following brain MRI findings would be the most pathognomic pattern to support emboli due to nonbacterial thrombotic endocarditis as the underlying mechanism of her infarction? A. Hemorrhagic lobar infarct B. Lacunar infarct of the thalamus C. Remote ischemic infarct and fresh lobar hemorrhage D. Small and large multi-territorial infarction E. Subarachnoid hemorrhage Correct Answer: The correct answer is D. Small and large multi-territorial infarction is a radiographic pattern highly suggestive of nonbacterial thrombotic endocarditis. This may present as focal deficits or encephalopathy. Correct Answer: Singhal AB, Topcuoglu MA, Buonanno FS. Acute ischemic stroke patterns in infective and nonbacterial thrombotic endocarditis: a diffusion-weighted magnetic resonance imaging study. Stroke 2002;33(5):1267-1273. 4. An excess of which of the following amino acids is most likely to be important in the pathogenesis of hepatic encephalopathy? A. Aspartate B. Glutamine C. Methionine D. Phenylalanine E. Tryptophan Correct Answer: The correct answer is B. Extensive evidence indicates that a major factor in the pathogenesis of hepatic encephalopathy is increased serum concentration of ammonia, which is detoxified and metabolized to glutamine. Excess glutamine leads to astrocytic swelling, although the precise mechanism is not known. 5. A 63-year-old woman with diabetes, hyperlipidemia, and hypertension is admitted to the hospital medical intensive care unit for pneumonia and acute respiratory distress syndrome. She has no past history of epilepsy but does have a seizure on the fourth day of hospitalization. Her medications at that time include heparin, insulin, lisinopril, metformin, metoprolol, omeprazole, pregabalin, simvastatin, and levofloxacin. Which of her medications may contribute to lowering the seizure threshold? [...]... methylcobalamin inactive, producing clinical manifestations of cobalamin deficiency, especially in patients with preexisting subclinical cobalamin deficiency 10 A 54-year-old man presents with sudden onset of right hemiparesis He is noted to have a mitral regurgitant murmur on examination and is febrile to 39.9°C Blood cultures return positive for streptococcal species His head CT scan is remarkable for a 2.5-cm... weakness (including the forehead), diffuse hyperreflexia, and bilateral Babinski signs A brain MRI scan shows diffuse meningeal enhancement, particularly around the brainstem Spinal fluid examination is notable for elevated protein (72 mg/dL) and a mononuclear pleocytosis (64 cells/µL) This clinical presentation is most typical of which of the following conditions? A Celiac disease B Cobalamin (vitamin B12)... is E In one series of stroke in infective endocarditis, the most common mechanism was pyogenic endarteritis, especially in IV drug abusers with Staphylococcus aureus infection In several series, mycotic aneurysms are the cause of hemorrhagic stroke in a minority of patients with infective endocarditis Correct Answer: Hart RG, Kagan-Hallet K, Joerns SE Mechanisms of intracranial hemorrhage in infective... which of the following vitamins or minerals? A Calciferol (vitamin D) B Folate C Thiamine (vitamin B1) D [alpha]-Tocopherol (vitamin E) E Zinc Correct Answer: The correct answer is D Crohn disease and other causes of malabsorption can lead to deficiency of [alpha]-tocopherol (vitamin E), which typically causes a spinocerebellar syndrome, often with a superimposed polyneuropathy Thiamine deficiency can... yield, even in patients with no specific eye findings Lung or skin abnormalities are useful sites for targeted biopsies, but no evidence indicates that they are appropriate blind biopsy sites-and lung biopsies, like kidney and liver biopsies, are invasive 24 A 67-year-old man has had a large ischemic middle cerebral territory infarct due to infective endocarditis He has a prosthetic heart valve in the mitral... in the diagnosis of neurosarcoidosis 9 The likelihood of developing neurologic manifestations of nitrous oxide toxicity is greatest in patients with subclinical deficiency of which of the following? A Cobalamin (vitamin B12) B Copper C Thiamine (vitamin B1) D [alpha]-Tocopherol (vitamin E) E Zinc Correct Answer: The correct answer is A Nitrous oxide irreversibly oxidizes the cobalt core of cobalamin...179 A Levofloxacin B Lisinopril C Metformin D Omeprazole E Simvastatin Correct Answer: The correct answer is A Levofloxacin is a fluoroquinolone antibiotic The fluoroquinolones have been associated with seizures Other antibiotics that have been associated with seizures include penicillins, cephalosporins, carbapenems, isoniazid, and metronidazole 6 A 72-year-old woman with past medical... transplantation 18 A 45-year-old woman with rheumatoid arthritis presents with worsening pain, stiffness, and swelling despite treatment with nonsteroidal anti-inflammatory agents Hand films show evidence of significant joint erosion, and her rheumatologist recommends that an alternative therapy be tried Her medical history is positive for hypertension, hypothyroidism, and relapsing-remitting multiple sclerosis... Which of the following agents is contraindicated for treatment of this woman's rheumatoid arthritis? A Etanercept B Hydroxychloroquine C Methotrexate D Penicillamine E Sulfasalazine Correct Answer: The correct answer is A Etanercept and other tumor necrosis factor-[alpha] inhibitor drugs, such as infliximab and adalimumab, have been associated with CNS demyelinating events or worsening of known cases... develop in up to 13% of coronary artery bypass graft (CABG) patients postoperatively The majority are brachial radiculoplexopathy injuries that most often involve the C8-T1 roots Fortunately, most post-CABG peripheral nervous system deficits are transient 20 A 48-year-old man with a 1 0- year history of biopsy-proven Crohn disease has had progressive deterioration of his gait over the past year His examination . cobalamin and renders methylcobalamin inactive, producing clinical manifestations of cobalamin deficiency, especially in patients with preexisting subclinical cobalamin deficiency. 10. A 54-year-old. bradycardia during upright tilt B. Elevated plasma norepinephrine levels in the upright posture C. Hypotension in response to adrenoceptor agonists D. Increase in blood pressure during straining in Valsalva. the following proteins is most likely to account for the patient's condition? A. Dopamine-[beta]-hydroxylase B. L-Amino acid decarboxylase C. Monoamine oxidase D. Norepinephrine transporter