Life Long Learning in Neurology - part 9 docx

Which of the following antiepileptic agents has the potential to exacerbate myoclonic seizures in this patient.. This patient's symptoms are most consistent with a seizure involving whic

listed options, in this case no evidence exists for addition of a second drug that could have competed for protein binding (which can lead to an increase in free, rather than total, phenytoin levels); induction of hepatic metabolism would lead to reduced, rather than increased, levels of a drug; and there is no evidence to suggest impaired renal clearance as the cause of the increase in level in this patient

13 A 28-year-old woman comes to the office for evaluation of intermittent episodes of a choking sensation associated with profuse salivation and repetitive swallowing Her episodes last approximately 2 minutes, occur several times per month, and are often preceded by an unusual taste There is no definite loss of consciousness This patient's symptoms are most consistent with epilepsy arising from which of the following cortical regions?

A Cingulate

B Insula

C Lateral temporal

D Mesial temporal

E Orbitofrontal

Correct Answer: The correct answer is B Insular seizures have prominent oral symptoms including chewing, salivation, repetitive swallowing, speech arrest, and laryngeal symptoms such as choking or stridor Autonomic, epigastric, emotional, or gustatory (as in this patient) auras can occur

14 An 8-year-old girl is brought to the office because of a 6-month history of episodes of brief head jerks No associated loss of consciousness occurs, and the episodes seem to worsen under periods of stress She has no other significant past medical or family history On examination, the patient has occasional brief episodic jerking of the head to the left She is able to briefly repress the movements after being asked to do so, but this is followed by an increase in the frequency of the jerking movements Neurologic examination is otherwise normal Which of the following is the most appropriate next step in diagnosis?

A Brain MRI

B EEG-video monitoring

C No further diagnostic testing is indicated

D Psychiatric evaluation

E Routine EEG

Correct Answer: The correct answer is C This patient's symptoms are most consistent with simple motor tics Features typical of tics include an urge to manifest the behavior, the stereotyped nature of the movements, and their repressibility; as seen in this patient, repression of the tics is often followed by a flurry of the tic manifestation Because her symptoms are classic for a tic disorder, further diagnostic testing for an epileptic (or other) cause of her symptoms is not indicated at this time If a doubt remains, video-EEG could be helpful

15 A 25-year-old man with complex partial seizures continues to have daily spells despite treatment with carbamazepine Valproate is added to his regime Which of the following is the most likely consequence of adding this drug to the previous regime?

A Decreased intestinal absorption of carbamazepine

B Decreased plasma levels of carbamazepine

C Increased levels of carbamazepine epoxide

D Increased risk of bone marrow toxicity

E Increased risk of hyponatremia

Correct Answer: The correct answer is C Valproate inhibits epoxide hydrolase, leading to accumulation of carbamazepine-10,11-epoxide, with risk of carbamazepine toxicity without a concomitant increase in serum carbamazepine concentration Hyponatremia is not due to the epoxide, as this can also occur with oxcarbazepine, which is not metabolized to an epoxide Bone marrow toxicity is an idiosyncratic reaction

16 A 10-year-old right-handed boy with a history of febrile seizures is evaluated for spells during which he stares ahead, is unresponsive to the environment, and exhibits automatic lip-smacking movements The spells occur up to

6 times per week despite treatment with maximally tolerated doses of carbamazepine and valproate At least once a week he experiences a generalized tonic-clonic activity His neurologic examination is normal His interictal EEG shows a left temporal spike during sleep recording The MRI of the head reveals atrophy of the left hippocampus His parents seek advice regarding the possibility of epilepsy surgery Which of the following is the most appropriate advice about surgery in this patient?

A It has a 60% to 80% chance, in the long run, to render the patient seizure free

B It is not indicated, as the lesion is nonprogressive

C It should be avoided, as the risk of speech disorder following surgery outweighs its benefits

D It should be considered if seizures persist despite vagus nerve stimulation

E It should be postponed until after the late teens to allow for full brain development

Correct Answer: The correct answer is A Medically refractory focal seizures, at any age, are not benign and carry

the risk of cognitive decline, social disability, and sudden unexplained death These patients should be evaluated

for candidacy for epilepsy surgery sooner rather than later Patients with mesial temporal sclerosis in whom there is

concordance of the MRI and EEG findings have an 60% to 80% chance to be rendered seizure free by anterior

temporal lobectomy

17 A 46-year-old woman comes to the office for follow-up after being admitted to the hospital 1 week ago for an

episode of left hand tingling followed by a generalized tonic-clonic seizure Phenytoin was started in the

emergency department; workup in the hospital included a normal MRI and an EEG that showed occasional left

hemispheric spikes There has been no recurrence since discharge The patient is concerned about the risk of

osteomalacia from her anticonvulsant A switch to which of the following antiepileptic drugs would be most

appropriate?

A Carbamazepine

B Levetiracetam

C Mysoline

D Phenobarbital

E Valproate

Correct Answer: The correct answer is B Hepatic enzyme inhibitors (such as phenytoin, carbamazepine,

phenobarbital, and primidone) and inhibitors (such as valproate) alter the clearance of compounds metabolized

through the liver, including vitamins Vitamin D metabolism may be affected, leading to an increased risk of

osteomalacia; vitamin D and calcium supplementation, therefore, are particularly important when these drugs are

prescribed Although valproate does not interfere with vitamin D, some evidence suggests that it may increase bone

turnover due to other mechanisms, although this has not been definitively established Noninducing agents, such as

the newer antiepileptic drugs, may be preferable in patients in whom the risk of osteoporosis is a concern

18 For the past 6 months, a 75-year-old man has had arousals during sleep in which he exhibits violent behaviors,

including kicking and slapping his wife He appears to be asleep or confused during these episodes, and on

awakening he has no memory of them However, he does report having vivid and sometimes violent dreams during

the nights he has these episodes Which of the following disorders is most likely to develop in this patient?

A Carbamazepine may increase the need for zinc supplementation

B Carbamazepine may interfere with the potential beneficial effect of vitamins

C Grapefruit juice may trigger carbamazepine toxicity

D High-carbohydrate diet may reduce the efficacy of carbamazepine

E High-protein meals may reduce absorption of carbamazepine

Correct Answer: The correct answer is C Ingestion of grapefruit juice leads to inhibition of CYP3A4, predisposing

to increased plasma level and toxicity of carbamazepine Carbamazepine, like other cytochrome P450 inducers,

reduces the levels of vitamin D but does not affect metabolism of vitamin B1 There is no evidence of interactions

between dietary proteins or carbohydrates with carbamazepine or of effect of carbamazepine on iron metabolism

19 A 19-year-old woman comes to the office because of a 2-year-history of episodes of sudden loss of postural

tone and falls without loss of consciousness She has had one to two episodes every few months, and these are

usually triggered by an intense emotion She has been sleepy during the day and frequently falls asleep during her

college classes, even after she feels she has slept well at night Neurologic examination is normal Which of the

following is the most likely diagnosis?

A Atonic seizures

B Cataplexy

C Panic attacks

D Psychogenic nonepileptic seizures

E Syncope

Correct Answer: The correct answer is B Although this patient's symptoms can be mistaken for atonic seizures, the

triggering of her events with emotion and the presence of her daytime sleepiness and sleep attacks are much more

characteristic of cataplexy seen in patients with narcolepsy She has no loss of consciousness to suggest syncope,

and her symptoms are not characteristic of panic attacks

20 A 5-year-old girl is evaluated for reports of spells of headache and feeling sick followed by pallor and vomiting

while remaining aware of her environment According to her parents, later during the spells her face becomes

flushed, she salivates excessively, and she becomes incontinent of urine On several occasions she has lost

consciousness An individual episode may last from 30 minutes to 2 hours Neurologic examination and MRI of the

head are normal Her interictal EEG reveals a normal background with multifocal spike-and-wave discharges that

are maximal at the parieto-occipital regions and occipital spikes Which of the following is the most likely

diagnosis?

A Basilar artery migraine

B Convulsive syncope

C Idiopathic childhood occipital epilepsy (Gastaut type)

D Landau-Kleffner syndrome

E Panayiotopoulos syndrome

Correct Answer: The correct answer is E The clinical picture is highly suggestive of Panayiotopoulos syndrome, a seizure type characterized by autonomic seizures and autonomic status epilepticus Gastaut-type occipital epilepsy

is characterized by visual simple partial seizures that are often brief, lasting seconds to minutes, and occur several times daily and mainly while awake Landau-Kleffner syndrome is acquired aphasia with epilepsy of childhood

21 An 18-year-old woman is admitted to the hospital because of a generalized tonic-clonic seizure that occurred upon awakening this morning Upon questioning, she describes a 2-year history of occasional morning myoclonic jerks Neurologic examination is normal EEG shows intermittent bursts of 6-Hz bilateral spike-wave complexes Which of the following antiepileptic agents has the potential to exacerbate myoclonic seizures in this patient?

A Clonazepam

B Lamotrigine

C Levetiracetam

D Topiramate

E Valproate

Correct Answer: The correct answer is B This patient has juvenile myoclonic epilepsy Lamotrigine may exacerbate myoclonic epilepsy Valproate and topiramate are the first-line drugs for treatment of this disorder Levetiracetam has not been reported to exacerbate this type of seizure

22 A 77-year-old man with history of coronary artery disease, atrial fibrillation, hypertension, and a stroke 2 years ago is evaluated for recent-onset seizures Current medications include warfarin (Coumadin), verapamil, lisinopril, and hydrochlorothiazide His neurologic examination reveals mild residual left hemiparesis and a moderate postural tremor A CT scan of the head reveals an old left frontal lobe stroke but no new lesions Which of the following would be the most appropriate antiepileptic drug in this patient?

A Carbamazepine

B Phenobarbital

C Phenytoin

D Topiramate

E Valproate

Correct Answer: The correct answer is D In a patient receiving multiple drugs known to undergo liver metabolism topiramate is an appropriate choice as this drug is predominantly eliminated by the kidneys and does not interact significantly with hepatic drug-metabolizing enzymes Carbamazepine, phenytoin, and phenobarbital induce cytochrome P450 activity and thus reduce the efficacy of warfarin and verapamil In addition, verapamil inhibits carbamazepine metabolism, increasing the risk of carbamazepine toxicity Valproate is often a poor choice in older patients because of the risk of causing delirium

23 A 28-year-old man comes to the office for evaluation of a 1-year history of episodes of posturing of both arms, described by his wife as flexion of one arm and extension of the other arm, head turn, and facial grimacing He does not seem to lose consciousness during the episodes, which occur up to once a week and usually last less than 1 minute This patient's symptoms are most consistent with a seizure involving which of the following frontal lobe regions?

A Cingulate

B Dorsolateral frontal

C Motor strip

D Orbitofrontal

E Supplementary motor area

Correct Answer: The correct answer is E Supplementary motor area seizures are brief and show explosive onset with sustained asymmetric tonic posturing of the limbs Patients often assume complex limb positions (eg, fencer posture with abduction of the contralateral arm, flexion of the ipsilateral arm, and contraversive head turn) and have facial grimacing, vocalization, and contralateral version of the head and eyes Consciousness may be preserved, and there is little or no postictal confusion Dorsolateral or anterior frontopolar seizures typically involve contralateral or bilateral tonic or clonic movements, contralateral head and eye version, and speech arrest Cingulate seizures are characterized by complex motor automatisms, autonomic symptoms, and changes in mood

or affect Seizures arising from the motor strip are typically clonic seizures involving contralateral face or limbs Orbitofrontal seizures have symptoms similar to mesial temporal lobe seizures because they typically spread quickly to limbic structures

24 A 9-year-old boy is evaluated for poor performance at school According to his teacher, he is inattentive and

appears to "space out" and "daydream" several times during class Neurologic examination is normal After 1

minute of hyperventilation, he stares and becomes unresponsive for approximately 10 seconds, after which he

immediately returns to his normal baseline Which of the following is a correct step in the assessment and

management of this child's condition?

A Advise that the patient will likely need antiepileptic treatment for life

B Ask his parents if they or other family members have had similar spells

C Conduct prolonged video-EEG monitoring to exclude a psychogenic seizure

D Obtain a blood sample to check for hypocalcemia

E Start treatment with carbamazepine

Correct Answer: The correct answer is B The patient probably has typical childhood absence epilepsy It is

probable the other members of his family may have a similar condition that remained undiagnosed and resolved

spontaneously in adolescence or early adulthood The ictal EEG shows a typical 2.5-Hz to 4.0-Hz generalized

spike-and-wave discharge, and thus prolonged video-EEG monitoring is not indicated unless the spells fail to

respond to medication, which includes ethosuximide, valproate, or lamotrigine Carbamazepine is contraindicated

in this condition as it can trigger spike-and wave stupor

25 A 16-year-old girl comes to the office for evaluation of a 6-month history of early nighttime episodes

characterized by sudden arousal from sleep, lifting her head, and dystonic posturing of her extremities, sometimes

followed by getting out of bed and ambulating around the room for 1 to 2 minutes There is a history of similar

symptoms in her brother, father, and paternal grandmother Mutation of which of the following genes is most likely

to be present in this patient?

A Cystatin B

B [gamma]-Aminobutyric acid (GABA) subunit

C Leucine-rich glioma inactivated

D Neuronal nicotinic acetylcholine receptor

E Sodium channel

Correct Answer: The correct answer is D This patient's symptoms are most compatible with the syndrome of

autosomal dominant nocturnal frontal lobe epilepsy, which is associated in some families with mutations in the

neuronal nicotinic acetylcholine receptor gene Cystatin B mutations are associated with Unverricht-Lundborg

disease, a progressive myoclonic epilepsy Mutations in a [gamma]-aminobutyric acid subunit gene or in sodium

channel genes have been seen in the syndrome generalized epilepsy with febrile seizures plus Mutations in the

leucine-rich glioma inactivated gene are associated with autosomal dominant partial epilepsy with auditory

features

26 A 9-month-old infant is brought to the office because of four episodes in the last 2 weeks of limb posturing,

body stiffening, and upward eye deviation The episodes have only occurred during sleep or soon after feeding

Episodes of vomiting have also recently occurred Neurologic examination is normal Which of the following is the

most likely diagnosis?

A Absence seizure

B Cyanotic breath-holding spell

C Gastroesophageal reflux

D Myoclonic seizure

E Shuddering attack

Correct Answer: The correct answer is C This patient's symptoms are most consistent with Sandifer syndrome,

which is a condition in children consisting of gastroesophageal reflux and laryngospasm associated with abnormal

movements, including limb posturing, eye deviation, and even opisthotonus Clues to the diagnosis include that the

events tend to occur during sleep and in the postprandial period and are typically associated with recurrent

vomiting The disorder typically resolves by treatment of the reflux

27 A 5-year-old boy with fever and a single generalized convulsion continues to be unresponsive and shows

persistent electrographic seizure activity despite having received 0.1 mg/kg of lorazepam followed by fosphenytoin

20 mg/kg What would be a potentially serious side effect of using high-dose propofol in this patient?

A Hemoglobinuria

B Hyperammonemia

C Hyperthermia

D Hypoglycemia

E Metabolic acidosis

Correct Answer: The correct answer is E High-dose or prolonged use of propofol, particularly in children, may

result in a potentially fatal metabolic syndrome characterized by metabolic acidosis, hyperlipidemia,

rhabdomyolysis, tachyarrhythmia, and cardiac failure It is therefore necessary to closely follow acid-base status, creatine kinase, triglycerides, and cardiovascular status if using propofol at high doses (greater than 5 mg/kg/h) or for a prolonged time

28 An 18-year-old woman with a 6-year history of medically refractory complex partial seizures is being evaluated for seizure surgery Ictal EEG shows spikes emanating from the left frontal region No abnormality is seen on MRI Which of the following findings on SPECT would most likely be seen to support a left frontal lobe seizure focus in this patient?

A Ictal hyperperfusion in the left frontal lobe

B Ictal hypoperfusion in the left frontal lobe

C Interictal hyperperfusion in the left frontal lobe

D Interictal hyperperfusion in the right frontal lobe

E Interictal hypoperfusion in the left frontal lobe

Correct Answer: The correct answer is A Ictal SPECT scanning, produced by injecting the patient with the radioisotope within seconds of the first ictal clinical signs and symptoms, can show hyperperfusion due to hypermetabolism in the region of the seizure focus, giving complementary information to support seizure localization in cases in which no structural lesion is seen Unlike ictal SPECT, the sensitivity of interictal SPECT in showing interictal hypoperfusion (due to interictal hypometabolism) of an epileptic focus is low

29 A 2-year-old girl is brought to the office because her parents have witnessed three episodes over the past 3 months of the patient "shivering" for about 10 seconds, associated with sudden flexion of her neck and trunk and body stiffening Her parents do not think she lost consciousness with the episodes The episodes occurred while the patient was awake and playing On examination the patient appears bright and attentive, and her neurologic examination is normal Which of the following is the most likely diagnosis?

A Absence seizure

B Cyanotic breath-holding spell

C Myoclonic seizure

D Shuddering attack

E Tonic seizure

Correct Answer: The correct answer is D This patient's symptoms are most consistent with shuddering attacks Shuddering attacks are benign paroxysmal spells of older infants and young children, which can mimic several seizure types, including tonic, absence (typical and atypical), and myoclonic This condition is seen in older infants and young children and does not seem to involve loss of consciousness The episode usually lasts 5 to 15 seconds Unlike epileptic seizures, shuddering attacks do not occur during sleep Unlike shuddering attacks, cyanotic breath-holding spells are associated with loss of consciousness

30 A 32-year-old woman with primary generalized tonic-clonic seizures continues to have episodes despite use of lamotrigine A decision is made to add valproate to the regime Which of the following should be considered as a consequence of potential drug interactions?

A Follow free lamotrigine levels

B Follow free valproate levels

C Increase the dose of lamotrigine

D Increase the dose of valproate

E Reduce the dose of lamotrigine

Correct Answer: The correct answer is E Valproate inhibits uridine glucosyl transferase, the enzyme that metabolizes lamotrigine Initiation of valproate therapy (>=500 mg/d) typically requires an immediate 50% reduction of the dose of lamotrigine

31 A 7-year-old right-handed boy is admitted to the hospital for evaluation of a 2-year history of loss of expressive and receptive speech, and occasional episodes of brief impairment of consciousness with eyelid fluttering He had normal speech development prior to the regression at the age of 5 years MRI of the brain is normal, and multiple EEGs have shown nocturnally predominant bursts of spike and slow-wave activity that begin focally over the primary speech cortex and then quickly become bisynchronous His symptoms have persisted despite multiple trials

of antiepileptic drugs and a trial of steroids Neurologic examination is normal except for his severe impairment of receptive and expressive language, and he appears otherwise bright and cooperative Which of the following surgical treatments would be most appropriate to consider for this patient?

A Corpus callosotomy

B Cortical resection

C Hemispherectomy

D Multiple subpial transactions

E Radiosurgery

Correct Answer: The correct answer is D This patient's history and findings are most compatible with

Landau-Kleffner syndrome (acquired epileptic aphasia) Because patients with this syndrome have epileptic involvement of

primary speech cortex, resection of cortex is risky; the surgical procedure of multiple subpial transactions disrupts

lateral cortical connections responsible for seizure spread but leaves intact the columnar cortical architecture

necessary for cortical functioning Fifty percent to 75% of patients with Landau-Kleffner syndrome show

improvement after this procedure

32 A 23-year-old man has myoclonic seizures well controlled on valproate He develops an upper respiratory tract

infection leading to an exacerbation of his long-standing asthma He is started on acetaminophen, erythromycin,

terbutaline, prednisone, and cimetidine Two days later, the patient develops drowsiness, nausea, vomiting, and

tremor Interactions with which of the following drugs is most likely to be responsible for this complication?

A Acetaminophen

B Cimetidine

C Erythromycin

D Prednisone

E Terbutaline

Correct Answer: The correct answer is B Valproate levels may be increased to potentially toxic levels by

cimetidine, as well as isoniazid

33 A 22-year-old woman is evaluated for spells during which she appears alert but stares ahead and is

unresponsive to her environment The spells occur up to 6 times per week despite treatment with maximally

tolerated doses of carbamazepine and valproate, and they have prevented her from driving On two occasions she

had a spell of loss of consciousness with generalized tonic-clonic activity Her neurologic examination is normal

Her interictal EEG is normal The MRI of the head reveals atrophy of the left hippocampus Which of the following

is the most appropriate approach?

A Add gabapentin or levetiracetam

B Recommend psychiatric evaluation for nonepileptic psychogenic seizures

C Refer to an epilepsy center for consultation and video-EEG monitoring

D Substitute phenytoin for carbamazepine

E Substitute topiramate for valproate

Correct Answer: The correct answer is C The patient appears to have complex partial seizures, presumably arising

from the left medial temporal lobe However, the diagnosis of seizures requires documentation during an ictal EEG

Patients with focal seizures who fail to respond to two medications of different mechanisms of action and at

maximally tolerated doses are very unlikely to respond to drug substitution or addition of a third drug Such

patients should undergo video-EEG monitoring as they are potential candidates for epilepsy surgery

34 A 36-year-old woman comes to the office because of recurrent episodes of a sensation of room tilting Her

episodes occur 3 to 4 times per month and last less than a minute She had a similar sensation of room tilting

preceding a generalized convulsion 1 year ago, for which she was started on oxcarbazepine Neurologic

examination is normal Seizures originating from which of the following brain regions are the most likely source of

this patient's symptoms?

A Frontal

B Lateral temporal

C Mesial temporal

D Occipital

E Parietal

Correct Answer: The correct answer is B This patient's symptoms are most consistent with focal vertiginous

seizures, which secondarily generalized 1 year ago Vertiginous seizures typically arise from the lateral temporal

region (superior temporal gyrus) or less often the frontal region Symptoms of vertiginous seizures include

dizziness, disequilibrium, unsteadiness, spinning, or room tilting as in this patient

35 A 9-year-old boy with partial-onset epilepsy is brought to the emergency department after he was found

confused by his mother after he walked home from school with a friend on a very hot humid day He has no other

medical problems, and his only medication is topiramate On examination, temperature is 42°C, blood pressure is

96/60 mm Hg, and pulse is 120/min He is lethargic, and his neck is supple; the remainder of his general physical

and neurologic examination is normal Routine laboratory tests are normal Cooling of the patient produces

resolution of the fever and level of alertness within an hour of presentation No infection is found Which of the

following is the most likely pathophysiologic mechanism of hyperthermia in this patient?

A Blockade of striatal dopamine receptors

B Catecholamine excess

C Hypohidrosis

D Thyrotoxicosis

E Volume depletion

Correct Answer: The correct answer is C Although all of the listed options are potential causes, this patient's hyperthermia most likely occurred due to topiramate-induced hypohidrosis Hypohidrosis is an infrequent side effect that has been reported in patients, particularly children, taking either topiramate or zonisamide Hypohidrosis induced by either topiramate or zonisamide can lead to the complication of heat stroke due to impaired heat-dissipation mechanisms

36 A 16-year-old boy comes to the office at the request of his pediatrician for evaluation of possible seizures He has had three episodes of loss of consciousness over the past 2 years Each episode is preceded by lightheadedness and pallor, followed by several seconds of loss of consciousness and loss of postural tone His mother witnessed two of the events and described brief myoclonic jerks of his arms with both events There has been no tongue biting

or incontinence He recalls that one of the episodes occurred while he was watching a "gory" movie, another episode occurred while standing in church, and another occurred during a very stressful event Which of the following is the most likely diagnosis?

A Atonic seizures

B Hypoglycemia

C Myoclonic seizure

D Psychogenic nonepileptic seizures

E Syncope

Correct Answer: The correct answer is E The typical precipitants (eg, emotion, the sight of blood) and the brief duration of the attacks are much more suggestive of syncope (most likely vasovagal, although other causes of syncope should also be considered) than an epileptic event The brief myoclonic jerks associated with this patient's episodes are commonly seen during syncope and should not be misinterpreted as evidence of a seizure disorder Unlike the jerking activity commonly seen during syncope, myoclonic seizures typically involve no detectable loss

of consciousness Atonic seizures may cause abrupt falls but not prolonged loss of consciousness Hypoglycemia is unlikely because of the absence of risk factors for hypoglycemia (eg, diabetes), the brief duration of the event, and the absence of prodromal symptoms that would be typical of hypoglycemia; in addition, hypoglycemia rarely causes complete loss of consciousness This patient's episodes are classic for syncopal events and do not suggest psychogenic nonepileptic seizures

37 A 33-year-old man with complex partial seizures is started on phenytoin Since the seizures are incompletely controlled with maximally tolerated doses of this drug, valproate is added to the regime Which of the following is

a likely consequence of interactions between these two drugs?

A Decreased absorption of phenytoin

B Decreased clearance of valproate

C Increased clearance of phenytoin

D Increased free plasma levels of phenytoin

E Increased total plasma levels of valproate

Correct Answer: The correct answer is D Several interactions occur between valproate and phenytoin Valproate displaces phenytoin from its protein-binding sites, leading to increased levels of free phenytoin (free fraction) Valproate also inhibits CYP2C9, and thus phenytoin clearance Phenytoin induces metabolism of valproate There

is no evidence that valproate reduces intestinal absorption of phenytoin

38 A 15-year-old girl is evaluated for spells of jerking of the arms and legs that occur particularly in the morning Her spells are more common when she is sleep deprived, fatigued, or under stress, and during menses She is moderately overweight Her neurologic examination is normal The interictal EEG shows diffuse bilateral polyspike-and-wave discharges at 4 Hz to 6 Hz with frontocentral predominance Which of the following would be the most appropriate drug therapy for this patient?

A Carbamazepine

B Clonazepam

C Gabapentin

D Lamotrigine

E Topiramate

Correct Answer: The correct answer is E The patient likely has juvenile myoclonic epilepsy Drug treatment includes valproate, topiramate, or levetiracetam In this patient topiramate would be a better choice than valproate,

as the patient is overweight and the treatment is long lasting, posing a risk of valproate for the fetus if she becomes pregnant Carbamazepine exacerbates idiopathic generalized epilepsies Clonazepam may control myoclonus but is not a first-line drug for myoclonic epilepsy Gabapentin is of benefit for partial seizures Lamotrigine may exacerbate the myoclonic seizures

39 A 33-year-old woman with a history of febrile seizures during childhood is evaluated for a recent episode of

generalized tonic-clonic seizure Approximately 2 months ago she was evaluated for recurrent urinary tract

trimethoprim/sulfamethoxazole, enalapril, codeine, bupropion, and zolpidem Which of the following drugs is most

likely to have predisposed the patient to a recurrent seizure?

A Bupropion

B Codeine

C Enalapril

D Trimethoprim/sulfamethoxazole

E Zolpidem

Correct Answer: The correct answer is A Bupropion is relatively contraindicated in patients with a history of

seizure disorder as it can lower the seizure threshold, particularly at higher doses (The bupropion in smoking

cessation products is low dose and not likely to cause seizures.) Whereas some antibiotics such as penicillins and

cephalosporins may have similar effect, this is not the case with trimethoprim or sulfamethoxazole Codeine, at

doses used for cough suppression, is not likely to have any effect on seizures, although other opioids such as

meperidine, fentanyl, and propoxyphene, have been associated with increased susceptibility to seizures Zolpidem,

a benzodiazepine receptor agonist, and enalapril, an angiotensin-converting enzyme inhibitor, are not expected to

reduce seizure threshold

40 A 12-year-old boy with an 8-year history of medically intractable temporal lobe epilepsy is being evaluated for

a left temporal lobectomy Which of the following clinical features would be most predictive of a good outcome for

seizure control following temporal lobectomy in this patient?

A Absence of ictal SPECT abnormalities

B Absence of interictal EEG abnormalities

C Absence of mesial temporal sclerosis on MRI

D No history of febrile seizures

E Unilateral ictal EEG abnormalities

Correct Answer: The correct answer is E Good prognostic features for seizure control following temporal

lobectomy include the presence of mesial temporal sclerosis on MRI scan, a history of febrile seizures, and

predominantly unilateral ictal and interictal EEG abnormalities

Multiple sclerosis Oct 2007

1 Which of the following genes is most strongly linked to the risk of developing MS?

A APOE

B CACNA1A

C HLA-DR2

D Myelin protein zero

E NOTCH3

Correct Answer: The correct answer is C Genetic susceptibility to MS is associated with the HLA antigen region

located on the short arm of chromosome 6 (6p) HLA class I and II-encoded molecules play a fundamental role in

self-immune/non-self-immune recognition The association of MS with HLA class II genes, specifically the

HLA-DR2 or DRB1*15 haplotype, is well established Carriage of one or two copies of HLA-DR2 confers a threefold to

sixfold risk of developing MS as compared with genotypes lacking the haplotype Patients who are HLA-DR2

positive are more likely to harbor oligoclonal bands in the CSF The other genes listed are not associated with MS

Mutations or certain haplotypes in the genes myelin protein zero, CACNA1A, APOE, and NOTCH3 are linked to

Charcot-Marie-Tooth disease, hemiplegic migraine, Alzheimer's disease, and cerebral autosomal dominant

arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), respectively

2 A 45-year-old woman is seen 24 hours after developing acute loss of vision in the left eye Her past medical

history is negative Family history is significant for a sister with rheumatoid arthritis On examination, she has light

perception only in the left eye and an afferent pupillary defect MRI of the brain is performed and is normal Six

months later, she develops numbness and weakness in both legs, which progresses to quadriplegia with bowel and

bladder involvement over the next 3 days At this juncture, MRI of the cervical and thoracic spines reveals an

elongated T2 hyperintense lesion extending from C3 to C8 Which of the following studies is most likely to be

abnormal in this patient?

A Brain stem auditory evoked response

B CSF oligoclonal banding

C Neuromyelitis optica-immunoglobulin (Ig) G

D Repeat brain MRI

E Serum vitamin B12 level

Correct Answer: The correct answer is C The patient described presents a picture of optic nerve and extensive spinal cord involvement with a demyelinating process Clinically, this is suggestive of neuromyelitis optica (NMO) NMO-IgG is an autoantibody that has been demonstrated in cases of NMO This disease is now felt to be pathologically distinct from MS Brain stem auditory evoked responses should be normal in this case where no brain pathology was demonstrated clinically or radiologically In NMO, CSF tends to be devoid of oligoclonal bands, and brain MRI is also likely to be normal Vitamin B12 deficiency, which tends to involve peripheral nerve

as well as spinal cord, would not typically present in such a fulminant manner and would not account for the highly abnormal spine MRI described here

3 A 40-year-old man with relapsing-remitting MS has been receiving interferon beta-1a 33 µg IM weekly for the past 12 months He has had no major adverse effects and no MS relapses since starting the medication He is found

to have interferon-neutralizing antibodies (Nabs) in his serum Which of the following is the most appropriate next step?

A Continue the current formulation of interferon beta-1a, and add monthly natalizumab

B Make no change in therapy as Nabs have no effect on drug efficacy

C Recheck Nab titers in 3 months and if still elevated switch to glatiramer acetate

D Switch to subcutaneous interferon beta-1b

E Switch to the subcutaneous preparation of interferon beta-1a

Correct Answer: The correct answer is C There appears to be an association between high titers off Nabs and reduction on efficacy of interferon beta as well as disease progression There is evidence that Nabs affect interferon beta and have an effect on disease progression Changing interferon preparations or route of administration may have no effect as there is cross-reactivity of the antibodies Moreover, subcutaneous administration is more likely to

be associated with Nab production Natalizumab carries the risk of opportunistic infection with JC virus and is usually reserved for patients who have failed other safer disease-modifying agents At this stage, the most prudent step might be to repeat antibody testing in 3 months If the Nab titer remains elevated, then switching to a noninterferon alternate agent (glatiramer acetate) may be considered

Correct Answer: Goodin DS, Frohman EM, Hurwitz B, et al Neutralizing antibodies to interferon beta: Assessment of their clinical and radiographic impact: an evidence report Report of the therapeutics and technology assessment subcommittee of the American Academy of Neurology Neurology 2007;68:977-984

4 In attempting to define incidence of MS in a particular population, epidemiologists often have to rely on the time

of disease diagnosis as the point of onset of a new case Because current diagnostic criteria still call for evidence of dissemination in space and time, data associating incidence of MS with which of the following factors are most affected?

A Environmental exposures

B Ethnic background

C Gender

D Genes

E Nutritional status

Correct Answer: The correct answer is A The authors of the chapter "Genetics and Epidemiology of Multiple Sclerosis" note that defining incidence of MS in a particular population still requires evidence of disseminated CNS disease Therefore, if one has to wait for a second demyelinating event to confirm the diagnosis, as is still the case,

it is possible that an environmental exposure or influence on the development of MS will lose its temporal association for the epidemiologist by the time a new case is confirmed The other factors listed are either not temporally sensitive (choices B, C, D) or would not be expected to change rapidly (choice E) in most cases

5 Several long-term studies have looked at rates of conversion to clinically definite MS (CDMS) in patients with one clinical demyelinating event who are followed by MRI A 20-year-old college student is seen by an ophthalmologist 2 days after developing a fogginess to her vision in the left eye associated with pain on moving that eye On examination, her visual acuity is 20/400 and papillitis is noted MRI of the brain is performed, and two nonenhancing hyperintense T2 lesions are seen on the scan According to data from the Optic Neuritis Treatment Trial, how much more likely is this patient to develop CDMS than someone with optic neuritis and a normal baseline scan?

A Equal chance of developing CDMS

B Slightly greater chance of developing CDMS

C Over 2 times as likely to develop CDMS

D Five times as likely to develop CDMS

E Ten times as likely to develop CDMS

Correct Answer: The correct answer is C In the Optic Neuritis Treatment Trial performed in the United States,

patients were followed for 10 years by MRI after a first presentation with optic neuritis Those with normal MRI

brain scans at baseline had an approximately 22% conversion rate to CDMS while those with at least one T2

hyperintense lesion at baseline converted at a rate of 56%, making choice C the best choice

Correct Answer: Beck RW, Trobe JD, Moke PS, et al; Optic Neuritis Study Group High- and low-risk profiles for

the development of multiple sclerosis within 10 years after optic neuritis: experience of the optic neuritis treatment

trial Arch Ophthalmol 2003;121(7):944-949

6 A 40-year-old man with relapsing-remitting MS is seen by his physician 2 months after a relapse involving a

large lesion in the upper cervical cord He has remained ambulatory but has urinary issues and pain in the arms He

is concerned because he notices that when he looks down suddenly, he gets an "electric jolt" down the middle of

his back Physical examination shows mild proximal weakness of the right arm, increased reflexes throughout, and

hyperesthesia in both arms With neck flexion, he grimaces and states that his "jolt" feels exactly like that Which

of the following types of medications is most likely to benefit this patient for his Lhermitte phenomenon?

A Anticholinergics

B Anticonvulsants

C Antispasticity agents

D Benzodiazepines

E Selective serotonin reuptake inhibitors (SSRIs)

Correct Answer: The correct answer is B The authors of the chapter "Symptomatic Management of Multiple

Sclerosis" note that patients who experience paroxysmal sensory symptoms may derive benefit from anticonvulsant

medications The other choices given have other potential uses in MS: antispasticity agents for spasms and cramps,

anticholinergics for disinhibited bladder, SSRIs for depression and anxiety, and benzodiazepines occasionally in

spasticity

7 A 37-year-old woman had a single episode of optic neuritis 3 weeks ago MRI shows a few small areas of

T2-signal abnormality without contrast enhancement or mass effect in the periventricular white matter, none of which

enhance Spinal fluid examination reveals normal protein, glucose, and nucleated cell count with three oligoclonal

bands No previous episodes of neurologic dysfunction have occurred Which of the following agents has Level A

evidence supporting its use for this patient's disease at this time?

A Glatiramer acetate

B Interferon beta-1a

C IV immunoglobulin

D Methylprednisolone

E Mitoxantrone

Correct Answer: The correct answer is B This patient has a clinically isolated syndrome (CIS) CIS is defined as a

single episode of demyelination affecting the optic nerve, spinal cord, or brain stem in isolation Without

disease-modifying therapy (DMT), 50% of patients will go on to develop clinically definite MS within 5 years, particularly

if multiple white matter lesions are present on MRI at the time of diagnosis The interferons have been shown to

reduce the probability or prolong the time to development of clinically definite MS and have been given a Level A

recommendation (Appendix A) A Level A recommendation has been given to glatiramer acetate for the treatment

of relapsing-remitting MS (RRMS) The other medications have been used either for the treatment of acute

relapses, refractory RRMS, or secondary progressive MS The United States Food and Drug Administration

(USFDA) has approved interferon beta-1a and interferon beta-1b for the treatment of CIS based on the CHAMPS

and BENEFIT trials Glatiramer acetate does not have specific USFDA approval for the CIS, although a clinical

trial is currently underway

8 Which of the following environmental factors has been implicated in having an influence on the incidence and

progression of MS?

A Agent Orange

B Alcohol consumption

C Ionizing radiation

D Smokeless tobacco

E Vitamin D deficiency

Correct Answer: The correct answer is E Besides pathogen exposure, environmental factors implicated in the

incidence and progression of MS include insufficient levels of vitamin D and smoking The other environmental

factors listed have not been linked to the development of MS

9 A 25-year-old woman experiences an episode of eye pain and visual loss She is diagnosed with optic neuritis

Two years later, she has an episode of ataxia and vertigo and is diagnosed with MS Family history is significant

for MS in her father The patient's 30-year-old sister makes an appointment with a neurologist because she has had