Life Long Learning in Neurology - part 9 docx

150 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 151 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 B 1 . 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? 152 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. 153 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, 154 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 155 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 156 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. 157 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 infections, chronic cough, hypertension, depression, and insomnia. She is now receiving 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 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 158 E. Serum vitamin B 12 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 159 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 [...]... of life? A Botulinum toxin A injection into detrusor muscle B Botulinum toxin A injection into urinary sphincter C Change to equivalent doses of extended-duration anticholinergic medication D Desmopressin nightly E Oral alpha blocker medication Correct Answer: The correct answer is A Injection of botulinum toxin A into the smooth detrusor muscle has been shown to result in a significant improvement in. .. multiple sclerosis: a meta-analysis Gadolinium MRI Meta-analysis Group Lancet 199 9:353(20) ;96 4 -9 69 Correct Answer: Rudick RA, Lee JC, Simon J, Fisher E Significance of T2 lesions in multiple sclerosis: a 13-year longitudinal study Ann Neurol 2006;60(2):23 6-2 42 22 A 30-year-old woman presents to her primary care physician for vertigo that began 3 days ago She describes a spinning sensation and is mildly... dysfunction Injection of botulinum toxin into the urinary sphincter will lead to increased incontinence and will not improve quality of life A change in anticholinergic medication preparations for a longer half -life may lead to an easier regimen and better compliance but does not help significantly more with urinary symptoms at equivalent doses Desmopressin may help with nocturia but not with daytime urinary... Río J, et al Baseline MRI predicts future attacks and disability in clinically isolated syndromes Neurology 2006;67(6) :96 8-7 2 16 Which of the following drugs is most likely to produce clinical worsening in a patient with MS? A Celecoxib B Daclizumab C Estriol D Infliximab E Phenytoin Correct Answer: The correct answer is D Tumor necrosis factor (TNF )-[ alpha] inhibitors including infliximab, adalimumab,... Simon J, et al Defining interferon beta response status in multiple sclerosis patients Ann Neurol 2004;56(4):54 8-5 55 Correct Answer: Tomassini V, Paolillo A, Russo P, et al Predictors of long- term clinical response to interferon beta therapy in relapsing multiple sclerosis J Neurol 2006;253(3):28 7-2 93 28 Which of the following statements best characterizes cortical demyelination in MS? A The extent... has been confirmed Interestingly, patients with MS reported a later age of infection for measles, mumps, and rubella, although no direct association with MS has been made 19 In a patient receiving interferon beta-1a for treatment of relapsing-remitting MS, which of the following statements is most accurate concerning the development and/or importance of developing interferon neutralizing antibodies (Nabs)?... al Imaging brain damage in first-degree relatives of sporadic and familial multiple sclerosis Ann Neurol 2006, 59( 4);63 4-6 39 10 Which of the following descriptions best characterizes the pattern II-type of demyelination in an active MS plaque? A Active lesions associated with T-cell and macrophage infiltration B Apoptosis of oligodendrocytes and preferential loss of myelin-associated glycoprotein C Deposition... shown to reduce gadolinium-enhancing activity on MRIs, and presence of gadolinium-enhancing lesions in treated patients may portend a poor response to medication (Rudick et al, 2004, Tomassini et al, 2006), lack of enhancing lesions may correlate poorly with progressive (usually ambulation-related) decline Choice A is insufficient to explain a decline in gait and is probably not true in general Correct... 2005;11(4): 39 0-3 94 13 A 30-year-old teacher with a diagnosis of relapsing-remitting MS comes for routine follow-up with her physician She was initially diagnosed at age 28 after presenting with optic neuritis from which she recovered well One year later, she suffered a relapse with a cervical cord lesion; she was left with residual dysesthesias in the arms, for which she takes gabapentin, and urinary frequency,... in which patients with clinically isolated syndrome received monthly MRI scans Findings concluded that the chance of demonstrating new lesions after an initial clinical event and with either one enhancing lesion or three nonenhancing lesions on the first scan was 80% to 90 % Correct Answer: Pestozza IF, Pozzilli C, Di Legge S, et al Monthly brain magnetic resonance imaging scans in patients with clinically . 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. 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. neurocardiogenic syncope. Heart 199 8; 79( 1):4 5-4 9. 3. A 45-year-old woman with multiple sclerosis is very inconvenienced by urinary urgency, frequency, and incontinence. Oral anticholinergic medications