Life Long Learning in Neurology - part 10 potx

Both primarily preganglionic MSA or ganglionic Lewy body autonomic disorders causing orthostatic hypotension are characterized by impaired increase of plasma norepinephrine upon changing

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

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 M2 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 B12 levels The gastroenterologist has found that several other vitamin deficiencies are present Jejunal aspirate cultures grew out 106 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

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

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

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

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-HT3 receptors

C Stimulation of dopamine D2 receptors

D Stimulation of M2 muscarinic receptors

E Stimulation of serotonin 5-HT4 receptors

Correct Answer: The correct answer is E Tegaserod binds to 5-HT4 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-HT3 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

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 H2O 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?

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 GABAA 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

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

calcium channels are associated with Lambert-Eaton myasthenic syndrome Voltage-gated potassium channels are associated with neuromyotonia Antibodies to muscarinic (M3) 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?