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Home , Ethosuximide, Tiagabine

Multiple Choice Questions for Part IV

1. Which of the following antiepileptic drugs C. The audiogenic model in mice would be the best initial choice in an adoles- predicts efficacy against focal cent girl with juvenile myoclonic ? D. was effective in both MES and PTZ models A. E. The 6 Hz model is predictive of efficacy B. against absence seizures C. D. Valproic acid 4. The cooperative VA studies showed: E. Levetiracetam A. Carbamazepine and were 2. A 26-year-old female had frequent episodes overall more efficacious than phenobar- of focal left hand shaking followed by gen- bital and eralized tonic–clonic seizure activity. On B. and primidone were less two occasions, she broke her jaw and her well tolerated than carbamazepine and right shoulder. Routine EEG is normal, and phenytoin brain imaging is unremarkable. Which C. Phenobarbital was more efficacious than would be most appropriate antiepileptic drug primidone for this patient? D. Primidone was better tolerated than A. phenobarbital B. E. Primidone was more efficacious than C. phenobarbital D. Phenobarbital E. 5. Which of the following is not a 1,4 ? 3. Which is true about animal models of epilepsy? A. B. fi A. The PTZ model helps predict ef cacy C. against absence seizures D. B. The kindling model typically has spon- E. taneously recurring seizures 254 Multiple Choice Questions for Part IV

6. Which of the following has 11. Urinary retention is most likely to occur with important active metabolites? A. A. Clonazepam B. Levetiracetam B. Clobazam C. Ezogabine C. Diazepam D. D. B and C E. Pregabalin E. All the above 12. Which is not likely to happen with the 7. Dupuytren’s contractures and plantar fibro- addition of felbamate? matosis are chronic adverse effects of A. Increased phenobarbital level A. B. Increased phenytoin level B. Phenobarbital C. Increased carbamazepine level C. D. Increased valproate level D. Clobazam E. Toxicity related to carbamazepine epoxide E. Clorazepate 13. A 4-month-old infant is diagnosed with 8. Simvastatin efficacy is reduced with: infantile spasms. He did not respond to 2-week course of ACTH at 150 units/m2. A. Lamotrigine Which of the following antiepileptic medi- B. Carbamazepine cations would you use next? C. Levetiracetam D. Pregabalin A. Vigabatrin E. Ezogabine B. Levetiracetam C. Topiramate 9. An adolescent boy with epilepsy presents D. Clobazam with overheating and fever following exer- E. Tiagabine cise. The likely cause is as follows: 14. Irritability is most common with the fol- A. Levetiracetam lowing AEDs: B. Lamotrigine C. A. Lamotrigine and oxcarbazepine D. Valproate B. Perampanel and levetiracetam E. Phenobarbital C. Felbamate and zonisamide D. Phenobarbital and primidone 10. The following antiepileptic drug is FDA E. Valproate and approved for once-daily dosing: 15. is most likely with which of the A. Perampanel following? B. Zonisamide C. Ethosuximide A. D. Clobazam B. Pregabalin E. Topiramate C. Ezogabine D. Perampanel Multiple Choice Questions for Part IV 255

E. Felbamate 21. The optimal dosage of folic acid in high-risk pregnant patients with the history of major 16. The mechanism of action of levetiracetam is congenital malformations is as follows: as follows: A. 0.4 mg/day A. Binding to the synaptic vesicle protein B. 1 mg/day B. Binding to the GABA A receptor C. 2 mg/day C. Antagonism of NMDA receptors D. 5 mg/day D. Blocking of sodium channels E. No need for folic acid E. Opening of potassium channels 22. Following are all risk factors for the devel- 17. Which AED is an NMDA receptor opment of epilepsy in elderly patients except: antagonist? A. REM behavior disorder A. Perampanel B. B. Topiramate C. C. Phenobarbital D. Cardiovascular disease D. Zonisamide E. Obstructive sleep apnea E. Felbamate 23. A 19-year-old neurologically challenged 18. Q-T interval prolongation is a potential male had ongoing complex partial seizures adverse effect of: in spite of a therapeutic dose of depakote. The addition of topiramate reduced his sei- A. Levetiracetam zures significantly. However, his caregiver B. Ezogabine reports progressive and C. Lacosamide decreased responsiveness. The next most D. Vigabatrin appropriate step is as follows: E. Tiagabine A. Urgent EEG to rule out subclinical status 19. All is true about perampanel except: B. Lumbar puncture C. Urgent brain imaging A. Weight gain D. Ammonia level B. Short half-life E. Topiramate blood level C. Selective AMPA antagonist D. Black box warning on behavioral 24. All of these AEDs are highly protein-bound abnormalities except E. High protein bounding A. Carbamazepine 20. In general, antiepileptic drug levels in B. Valproate : C. Tiagabine D. Phenytoin A. Increase E. Lamotrigine B. Decrease C. No changes 25. Which antiepileptic drug has an FDA indi- D. Antiepileptic drugs should not be used cation for myoclonic seizures? during pregnancy E. None of the above A. Pregabalin B. Valproate 256 Multiple Choice Questions for Part IV

C. Ethosuximide 30. Which of the following is not true about D. Levetiracetam ? E. Lamotrigine A. Analog of levetiracetam 26. Physiologic changes with advanced age B. Less potent than levetiracetam include all of the following except: C. Binds to SV2A D. Blocks sodium channels A. Decreased renal clearance E. All of the above is true about B. Decreased hepatic clearance brivaracetam C. Decreased and erratic drug absorption D. Increased protein binding 31. A 77-year-old man with newly diagnosed E. Increased blood levels epilepsy started having suspicious for Parkinson’s disease. The likely cause: 27. Progesterone therapy was effective in the following patient subgroup: A. Carbamazepine B. Valproate A. Patients with catamenial epilepsy with C. Phenytoin seizure exacerbation at ovulation D. Clonazepam B. Postmenopausal women E. Ethosuximide C. Women with catamenial epilepsy and seizure exacerbation around 32. All of the following are animal models of menstruation partial epilepsy except? D. Women with anovulatory cycles E. All women with catamenial epilepsy A. Pentylenetetrazole B. Kindling 28. Which of the following is an animal model C. Pilocarpine of drug-resistant epilepsy? D. 6-Hz psychomotor seizures E. Poststatus epilepticus model in rats A. 6-Hz psychomotor seizures B. PTZ (pentylenetetrazole) 33. The visual field changes with vigabatrin: C. Maximal electroshock (MES) D. Penicillin A. Are reversible E. All of the above B. Represent an optic neuropathy C. Are related to dose and duration of 29. Which of the following is true about cata- treatment menial epilepsy? D. Typically occur within 2 months of treatment A. Seizure cluster around ovulation in C1 E. Are less likely when vigabatrin is com- pattern bined with a blocking B. Seizure cluster before and during menses drug in C2 pattern C. Seizure cluster in anovulatory cycles in 34. Which of the following is true about C3 pattern tiagabine? D. Estrogen is E. Progesterone is proconvulsant A. Can be given once daily at bedtime B. Is effective against absence seizures Multiple Choice Questions for Part IV 257

C. Is approved as initial monotherapy 39. Incidence of epilepsy in institutionalized D. Increases GABA levels at the synapse patients with intellectual developmental E. Is associated with retinal toxicity disability is as follows:

35. Which is not true of felbamate idiosyncratic A. 5% toxicity? B. 9% C. 21% A. Aplastic anemia has not been reported D. 32% below age 13 E. 80% B. Aplastic anemia and hepatic failure are most likely within one month of initiat- 40. Which antiepileptic requires monitoring of ing therapy visual fields during treatment? C. Underlying autoimmune disease increa- ses the risk of aplastic anemia A. Clobazam D. Aplastic anemia is highly unlikely to B. Vigabatrin occur after one year of therapy C. Tiagabine E. The risk of aplastic anemia is estimated D. Primidone at one in 5000 exposures E. Clorazepate

36. Which of the following is unlikely to exac- 41. Screening for potential psychosocial barriers erbate absence seizures? to the safety and success of the ketogenic diet should take place before initiation of A. Carbamazepine therapy. Which of the following features B. Oxcarbazepine makes the ketogenic diet a better/easier C. Valproate treatment option? D. Tiagabine E. Vigabatrin A. Presence of a gastrostomy tube B. Severe failure to thrive/inability to 37. Which of the following antiepileptic drug is maintain adequate nutrition not known to modulate GABA? C. Potential surgically resectable seizure focus A. Phenobarbital D. Multiple siblings in an unstructured B. Tiagabine home environment C. Clonazepam E. Available premanufactured formulas D. Pregabalin E. Topiramate 42. Prolonged episodes of altered responsive- ness are most likely with: 38. For which of the following conditions is the ketogenic diet indicated? A. Tiagabine B. Perampanel A. Primary carnitine deficiency C. Vigabatrin B. Pyruvate carboxylase deficiency D. Clobazam C. Pyruvate dehydrogenase deficiency E. Pregabalin D. E. None of the above 258 Multiple Choice Questions for Part IV

43. Screening for disorders of meta- D. Deficiency of calcium and vitamin D, bolism should be performed prior to initia- leading to bone mineralization loss tion of the ketogenic diet. Specifically, this E. Encephalopathy due to hypoglycemia, testing could include which of the dehydration, and excessive acidosis following? 46. Epilepsy is most commonly associated with: A. Complete blood count and complete metabolic panel including function A. Dementia tests and BUN and creatinine B. Stroke B. Acylcarnitine profile, urine organic acids, C. Birth defect and carnitine D. Bipolar disorder C. CSF glucose, lactate, folate metabolites, E. amino acids, and D. ultrasound and nephrology 47. There is a need for more research and data consult regarding the incidence and prevention of long-term complications in patients who 44. A 23-year-old man with idiopathic general- have been on the ketogenic diet for long ized epilepsy was initially maintained on durations, for instance greater than 5 years. lamotrigine. Valproate was added as adjunct Which of the following tests would be rea- therapy. Which of the following effects sonable to perform in such a patient, who is may result from interaction between these otherwise asymptomatic? drugs? A. Blood draw for amylase, lipase A. Lamotrigine toxicity because of glu- B. Renal ultrasound looking for renal stone curonidation inhibition C. Abdominal X-ray for stool B. Decreased lamotrigine efficacy due to D. Blood draw for 25-hydroxy-vitamin D inhibition of cytochrome 2C9 and 2C19 and consideration of bone density scan C. Decreased valproate efficacy due to E. CRP induction of CYP2C9 D. Increased risk of liver disease 48. The literature supports the probable benefit E. Valproate toxicity due to inhibition of its of the ketogenic diet in which of the fol- b-oxidation lowing conditions?

45. With rare exceptions, the ketogenic diet is A. Benign myoclonus of infancy initiated during an inpatient hospitalization. B. Juvenile myoclonic epilepsy Complications during the initiation period C. Glucose transporter protein 1 deficiency could include all of the below, except: D. Pyruvate carboxylase deficiency

A. due to hypoglycemia, dehy- 49. A 36-year-old male from Nepal is evaluated dration, excessive acidosis, , for a generalized tonic seizure. Few weeks or exacerbation of gastroesophageal ago, he started taking rifampin and reflux for a positive tuberculin test. His neurolog- B. Precipitation of deterioration in a patient ical examination, EEG, and brain MRI are with an undiagnosed disorder of fat all normal. What is the likely mechanism responsible for his seizure? C. Excessive metabolic acidosis in a patient also treated with a carbonic anhydrase A. Reversible inhibition of GABA B. Impaired pyridoxine synthesis Multiple Choice Questions for Part IV 259

C. Activation of glutamate B. Valproate exposure during gestation is D. Hypermagnesemia associated with autism E. Prolactin surge C. Valproate teratogenicity is dose-dependent 50. A trial comparing valproate, ethosuximide, D. Folate supplementation reduces and lamotrigine for absence demonstrated valproate-associated teratogenicity rate to control value A. All three AEDs were equally effective E. Malformation rate with valproate expo- B. Valproate and ethosuximide were more sure is elevated with both monotherapy effective than lamotrigine and polytherapy C. Valproate was better tolerated than lamotrigine 54. A 58-year-old man was started on phenytoin D. Valproate had less neuropsychological for weekly partial seizures. His seizure fre- adverse effects than ethosuximide quency dramatically decreased but has not E. Ethosuximide was more effective than reached seizure freedom. He developed valproate postherpetic neuralgia in the left abdominal dermatome 6 months ago with persistent 51. Which of the following statements accu- pain. He also had a history of diabetes and a rately conveys the typical recommendations history of a previous lacunar infarct. (by consensus) for discontinuation of the Attempts to increase the dose of phenytoin ketogenic diet? resulted in intolerable drowsiness. Which of the following would be the most appropriate A. Discontinue the ketogenic diet if it seems adjunct therapy in this patient? ineffective by 1 month following initiation A. Carbamazepine B. Wait for 3 months following initiation B. Lamotrigine before deciding to discontinue the diet C. Pregabalin C. Abrupt discontinuation is preferred over D. Levetiracetam gradual weaning over 2–3 months E. Lacosamide D. Wean after 1 year of seizure freedom 55. Which is incorrect of valproate and pheny- 52. A 23-year-old male from El Salvador is seen toin protein binding? for new onset–partial seizures. His brain MRI shows multiple ring-enhancing lesions. A. Both phenytoin and valproate are highly The best treatment is as follows: protein-bound B. When used together, phenytoin free A. Ceftriaxone fraction is increased B. Acyclovir C. Valproate protein binding is increased at C. Albendazole and steroids higher concentration D. Natalizumab D. Phenytoin free fraction is increased in E. Aspirin low protein states E. Intravenous valproate may displace war- 53. Which is not true of valproate farin from protein binding teratogenicity? 56. The potential benefit of the ketogenic diet A. Valproate exposure during gestation is has been suggested for and is being inves- associated with decreased verbal IQ tigated in all of the following except: 260 Multiple Choice Questions for Part IV

A. Amyotrophic lateral sclerosis B. Ceftriaxone B. Traumatic brain injury C. Grapefruit juice C. Alzheimer’s disease D. D. Brain tumors E. Propoxyphene E. Epileptologists studying for the epilepsy boards 62. Estrogen affects seizure control by:

57. Which of the following antiepileptic drugs A. Enhancing inhibition at GABA A does not affect bone health in women with receptor epilepsy? B. Increasing GABA synthesis C. Accentuating the action of glutamate A. Topiramate D. Inhibiting synthesis of GABA B. Lamotrigine E. Estrogen in protective against seizures C. Phenytoin D. Phenobarbital 63. In patients with epilepsy, the yield of first E. All of the above routine EEG is as follows:

58. All of the following AEDs are appropriate to A. 25% use in elderly with epilepsy except: B. 50% C. 75% A. Lamotrigine D. 100% B. Gabapentin E. EEG is not needed for diagnosis C. Levetiracetam D. Topiramate 64. Autism has been associated with the E. Pregabalin intrauterine exposure to:

59. Faciobrachial dystonic seizures are an early A. Phenobarbital manifestation of: B. Lamotrigine C. Phenytoin A. Anti-NMDA antibody limbic encephalitis D. Carbamazepine B. Anti-LGI1 antibody limbic encephalitis E. Valproate C. Anti-GAD antibody limbic encephalitis D. Hashimoto’s encephalitis 65. Which has the shortest half-life for parent E. Landau–Kleffner syndrome drug and active metabolite?

60. Which of the following does not cause A. Diazepam phenytoin accumulation? B. Lorazepam C. Clorazepate A. D. Clonazepam B. Carbamazepine E. Clobazam C. Cimetidine D. Fluconazole 66. The half-life of the following AED is pro- E. Felbamate longed when the serum concentration is above the recommended therapeutic range: 61. Which of the following does not cause car- bamazepine accumulation? A. Phenobarbital B. Carbamazepine A. Erythromycin C. Phenytoin Multiple Choice Questions for Part IV 261

D. Valproate 71. All of the following features are associated E. Oxcarbazepine with higher seizure recurrence except:

67. The half-life of the following AED becomes A. Focal onset shorter after two weeks of treatment: B. Cluster seizures C. A. Phenobarbital D. Intermittent temporal slow activity B. Carbamazepine E. Abnormal brain imaging C. Phenytoin D. Valproate 72. Oral contraceptive can be E. Oxcarbazepine affected by all except:

68. A 42-year-old man is brought to the ED A. Oxcarbazepine because of a generalized tonic–clonic sei- B. Phenytoin zures. He has no previous history of sei- C. Primidone zures, and his MRI is normal. His EEG D. Topiramate reveals left temporal sharp waves. His sei- E. Levetiracetam zure recurrence rate is as follows: 73. Ophthalmological adverse effects can be A. 10% seen with: B. 20% C. 50% A. Rufinamide, ezogabine, and vigabatrin D. 80% B. Ezogabine, vigabatrin, and topiramate E. 100% C. Zonisamide, topiramate, and felbamate D. Vigabatrin, perampanel, and zonisamide 69. Which of the following is incorrect about E. Clobazam, rufinamide, and pregabalin primidone? 74. An adolescent boy treated for seizures suf- A. Same acute adverse effects as fers from a heatstroke during a soccer game. phenobarbital The boy is most likely taking: B. Similar chronic adverse effects as phenobarbital A. Ezogabine C. The primidone dose needed to produce a B. Pregabalin certain phenobarbital level is about 5 C. Zonisamide times that of phenobarbital D. Valproate D. Similar interactions to phenobarbital E. Carbamazepine E. Produces two active metabolites 75. Risk of seizure recurrence after first symp- 70. Which of the following antiepileptic drugs tomatic seizure is highest in: requires dose adjustment in a patient with newly diagnosed creatinine of 4 mg/dl? A. Acute Stroke B. Remote stroke A. Phenytoin C. Acute head trauma B. Carbamazepine D. Remote head trauma C. Phenobarbital E. All of the above carry the same seizure D. Gabapentin recurrence rate E. Perampanel 262 Multiple Choice Questions for Part IV

76. Which is not true about vigabatrin’s visual 81. Which antiepileptic drug blocks T-type cal- defect? cium channel:

A. Most visual field defects are irreversible A. Ethosuximide and valproate B. Central vision is most affected B. Carbamazepine and valproate C. Risk of visual defect increases with the C. Felbamate and pregabalin treatment duration D. Valproate and felbamate D. Periodic eye examination may detect E. Lamotrigine and valproate early damage E. May occur in up to one-third of patients 82. Before starting a Taiwanese man on carba- mazepine for trigeminal neuralgia, which 77. All of the following antiepileptic drugs are genetic testing is recommended: considered to be broad spectrum except: A. HLA-B 23 A. Valproate B. HLA-A 322 B. Zonisamide C. HLA-B 1502 C. Pregabalin D. HLA-A 150 D. Lamotrigine E. No need for genetic testing E. Felbamate 83. Which of the following is known to be an 78. Clinical trials have been completed or are inducer of the (CYP): underway for all but one of the following treatments for acute repetitive seizures: A. Aspartame B. White chocolate A. Intramuscular diazepam by autoinjector C. Aloe Vera B. Intranasal diazepam D. Yohimbine C. Intranasal lorazepam E. St John’s wort D. Intranasal E. Buccal midazolam 84. In seizure-free patients, seizure recurrence after antiepileptic drug withdrawal is lower 79. All but one of the following has an extended in: release preparation: A. Children A. Topiramate B. Adults B. Zonisamide C. Men C. Levetiracetam D. Women D. Oxcarbazepine E. Same in all of the above E. Lamotrigine 85. In December 2006, at the American Epilepsy 80. As compared to older AEDs, newer AEDs Society meeting, the Charlie Foundation tend to have: commissioned a panel of 26 pediatric epileptologists and dietitians from 9 coun- A. Similar safety tries with expertise in the ketogenic diet, in B. Better efficacy order to create a consensus statement C. Lower drug–drug interaction regarding the clinical management of the D. Lower cost ketogenic diet. Which of the following E. Higher protein binding statements accurately conveys the Multiple Choice Questions for Part IV 263

International Ketogenic Diet Study Group’s epilepsy syndromes showed that only recommendation? 20% had a greater than 75% decrease in seizures A. The ketogenic diet should be considered D. There are currently no randomized con- in a patient whose epilepsy is controlled trolled trials published on the efficacy of by a single , but whose family dietary therapies in epilepsy treatment prefers “natural” therapies B. The ketogenic diet should be considered 88. Which antiepileptic drug should be avoided only as a last resort, since it is hard to in a patient with known sulfa drug allergy? administer, is unpalatable, and there is no data from randomized controlled trials to A. Pregabalin support it B. Zonisamide C. The ketogenic diet should be considered C. Carbamazepine in a child who has failed 2–3 anticon- D. Vigabatrin vulsant therapies, as long as he/she is E. Lamotrigine older than 1 year and younger than 12 years of age 89. The following statement is false: D. The ketogenic diet should be considered in a child who has failed 2–3 anticon- A. A common ratio of the ketogenic diet is vulsant therapies, regardless of age or 4 g of fat to 1 g of protein plus carbo- gender hydrate (4:1) B. In a 4:1 ratio ketogenic diet, approxi- 86. Brivaracetam has the following mechanism mately 90% of energy comes from fat of action: C. A fasting period during initiation of the ketogenic diet is necessary to achieve A. opening ketosis B. Blocking of sodium channels D. The modified Atkins diet is approxi- C. Binding to the synaptic vesicle protein mately a 1:1 ratio D. Binding to the GABAA receptor E. In the low glycemic index treatment, E. Binding to the synaptic vesicle protein foods are chosen which produce and blocking of sodium channels slower/steadier changes in blood glucose

87. There has been growing interest and confi- 90. A 72-year-old man is seen in clinic for a new dence in the use of the ketogenic diet and diagnosis of epilepsy, with recurrent partial subsequently a growing body of literature. seizures secondary to a right MCA ischemic Which of the following statements is true? infarct. His medical history includes chronic afib (for which he takes warfarin), osteo- A. Four randomized controlled trials porosis, and a history of kidney stones. showed that at least 38% of patients had Which of the following is the most appro- a 50% reduction in seizures compared to priate antiepileptic medication for this controls at 3 months, with this response patient? maintained for up to a year B. A meta-analysis has shown that a third of A. Carbamazepine all patients on the ketogenic diet may B. Levetiracetam become seizure-free C. Primidone C. A recent retrospective, multicenter study D. Ethosuximide assessing the ketogenic diet for various E. Zonisamide 264 Multiple Choice Questions for Part IV

91. In addition to the traditional ketogenic diet, does not typically have spontaneous sei- alternative dietary therapies have been zures. The audiogenic seizure model is pre- developed for epilepsy treatment. Which of dictive of efficacy against generalized tonic– the following is an alternative dietary ther- clonic seizures. Levetiracetam efficacy was apy for epilepsy treatment? missed by the maximal electroshock model (MES) and PTZ models. The 6 Hz model is A. The low glycemic index treatment a model of pharmacoresistant epilepsy. B. The Atkins diet 4. (B). In the first VA cooperate, all four C. The Paleo diet antiepileptic drugs compared had equal effi- D. The short-chain triglyceride diet cacy, but phenobarbital and primidone were less well tolerated. 92. The blood levels of which antiepileptic will 5. (D). In contrast to the listed benzodi- not be altered after the addition of azepines, Clobazam is a 1,5 benzodiazepine; phenytoin? the brand name “On-fi” is derived from “One-five.” A. Felbamate 6. (D). Diazepam and clobazam have important B. Topiramate active metabolites (desmethyldiazepam and C. Zonisamide desmethylclobazam). Clonazepam is con- D. Tiagabine verted to an inactive metabolite. E. Pregabalin 7. (B). Connective tissue diseases in particular Dupuytren’s contractures and plantar fibro- matosis may be seen with long-term phe- Answers nobarbital use. 8. (B). -inducing antiepileptic medica- 1. (E). In this case, levetiracetam is the most tions can induce the metabolism of other appropriate choice for treating juvenile concomitant medications such as carba- myoclonic epilepsy in a woman of child- mazepine and phenytoin and can lower the bearing age. Pregabalin and carbamazepine serum concentration of simvastatin by about are typically efficacious against partial–onset 50%. seizures and may potentially exacerbate 9. (C). Both zonisamide and topiramate are generalized seizures, notably absence and mild carbonic anhydrase inhibitors. The myoclonic seizures. Lacosamide lacks evi- resulting decreased sweat may lead to over- dence to support its use in this condition, heating and possible heatstrokes especially while valproate should be avoided in women in children. of childbearing age due to significant risk of 10. (A). While some of the other antiepileptic teratogenicity. drugs have a long half-life (such as zon- 2. (A). The clinical scenario describes partial isamide, clobazam, and ethosuximide), they seizures with secondarily generalization. do not have FDA approval for once-daily Oxcarbazepine is an appropriate drug for dosing. The main reasons are the potential treating this condition. Lamotrigine and sedation and cognitive or gastrointestinal topiramate would not be a good choice due side effects that may incur from high doses to the slow titration schedule. Phenobarbital given once daily. and valproate must be avoided in women of 11. (C). Ezogabine may be associated with uri- childbearing age. nary retention in about 2% of patients. It is 3. (A). The pentylenetetrazole (PTZ) model is generally reported within the first six months predictive of efficacy against absence sei- of treatment, but can also be observed later. zures, although some effective drugs may be 12. (C). Felbamate reduces carbamazepine level missed by this model. The kindling model through induction of CYP3A4, but may Multiple Choice Questions for Part IV 265

cause accumulation of carbamazepine start folic acid 3–6 months before epoxide leading to carbamazepine toxicity. conception. 13. (A). Treatment of infantile spasms should be 22. (A). REM behavior disorder is a risk factor started as soon as the diagnosis is confirmed. for degenerative neurologic disease but not The first-line recommended therapy includes for epilepsy while all the other choices are high-dose ACTH or vigabatrin. If the cause established risk factors for developing epi- is tuberous sclerosis, vigabatrin tends to be lepsy in the elderly. more effective than ACTH. 23. (D). The addition of topiramate to valproate 14. (B). Among the listed antiepileptic drugs, may cause accumulation of ammonia, which both levetiracetam and perampanel are more could explain the increased responsiveness associated with irritability, which may limit and somnolence. their use. 24. (E). Lamotrigine protein binding is low 15. (E). In contrast to most antiepileptic drugs (55%) compared to the other choices that which are sedating, felbamate and lamot- have higher protein binding (>70%) causing rigine are stimulating drugs and may be high potential for drug–drug interactions. associated with insomnia. 25. (D). Levetiracetam is indicated as adjunctive 16. (A). Levetiracetam was first approved in treatment for myoclonic seizures. USA in 1999. Its mechanism of action is 26. (D). With advancing age, several physio- binding to the synaptic vesicle protein logical changes have a direct effect on drug SV2A. This seems to result in nonspecific . These include decreased decrease in release. There is renal and hepatic clearance, reduced and a functional correlation between SV2A erratic absorption, and decreased protein binding affinity and anticonvulsant potency binding. All these changes can result in of levetiracetam analogues. higher antiepileptic blood levels with higher 17. (E). Felbamate is anti-NMDA receptor risks of adverse effects and toxicity. antagonist. Topiramate and perampanel are 27. (C). Progesterone can be effective in the AMPA antagonists. subgroup of women with catamenial epi- 18. (B). Q-T prolongation may occur with the lepsy who have the C1 pattern, with seizure use of ezogabine, while P-R prolongation exacerbations around menstrual periods. may occur with the use of lacosamide. 28. (A). The 6-Hz psychomotor seizure model in 19. (B). All of the listed properties are true about mice and the methylazoxymethanol acetate perampanel except for a short half-life. Per- (MAM) rat model of cortical dysplasia serve ampanel’s half-life is long, about 105 h on as a model of pharmacoresistant epilepsy. average. 29. (C). In catamenial epilepsy, seizures tend to 20. (B). Changes in AED pharmacokinetics are follow a cyclical pattern related to the common during pregnancy due to increased menstrual cycle. There are three cyclical clearance most prominent for lamotrigine, patterns of catamenial epilepsy: C1 pattern but other AEDs show substantially more where seizures increase in frequency just modest increases in clearance. Seizures before and during menses, C2 pattern where worsen when AED levels fall >35% from seizures increase around the time of ovula- preconception levels. Regular monthly tion, and C3 pattern where seizures occur monitoring of AED levels during pregnancy with anovulatory cycles. Catamenial epi- is recommended to adjust the dose to prevent lepsy is thought to be related to progesterone seizure recurrence. and estrogen fluctuations. Estrogen appears 21. (D). For high-risk pregnant patients with to be proconvulsant, and progesterone previous history of major teratogenicity, appears to be anticonvulsant. higher folic acid dose of 4–5 mg/day is 30. (B). Brivaracetam is an analog drug of recommended. It is also recommended to levetiracetam which has a sodium blocking 266 Multiple Choice Questions for Part IV

mechanism in addition to its SV2A binding. tricarboxylic acid cycle, to be used for In general, it exhibits a similar profile to energy production or ketone body produc- levetiracetam general but with a higher tion. A shift to use of fats as the primary potency (about 10 times higher). energy source in disorders of fat metabolism 31. (B). Valproate can produce tremors and would precipitate deterioration. Lack of Parkinsonism that is usually dose-dependent carbohydrates would exacerbate acute inter- and more common in the elderly. It is usu- mittent porphyria. ally reversible with reduction or elimination 39. (D). Incidence of epilepsy increases with the of the drug. severity of mental retardation (MR), but it 32. (A). Pentylenetetrazole (PTZ) is an animal varies depending on epidemiological model of absence seizures, while the other methodologies as well. In population-based listed animal models are specific for partial studies, 21% of those with mild MR had seizures. epilepsy. Another study reported epilepsy in 33. (C). Vigabatrin visual toxicity is a slowly 11% of subjects with mild MR and in 23% progressive, usually irreversible retinopathy in those with severe MR. On the other hand, that is related to dose and duration of in institution-based studies including treatment. patients with severe MR, the prevalence of 34. (D). Tiagabine has a short half-life; it is a epilepsy varies from 32 to 34%. narrow-spectrum agent for partial (focal) 40. (B). Vigabatrin use is associated with visual seizures, approved only as adjunctive ther- field constriction in about one-third of apy; it increases GABA levels by inhibiting patients. Periodic visual field monitoring is its reuptake in the synapse. required for the prescription of vigabatrin. 35. (A). Aplastic anemia and hepatic failure are 41. (E). Premanufactured ketogenic formulas are unlikely within one month of initiating fel- available, ensuring more accuracy of mea- bamate therapy. Known risk factors include surements and minimizing barriers such as prior cytopenia, allergy to or significant food refusal or aversions. toxicity with other antiepileptic drugs, and 42. (A). Prolonged encephalopathy or noncon- underlying autoimmune disease. vulsive status epilepticus may be seen as a 36. (C). Valproate is a wide-spectrum dose-related adverse effect of tiagabine. antiepileptic drug effective against absence 43. (B). This should adequately screen for dis- seizures; the other listed AEDs may exac- orders of fatty acid metabolism including erbate absence seizures. carnitine deficiency, CPT I or II deficiency, 37. (D). Unlike other listed antiepileptic drugs, carnitine translocase deficiency, and the pregabalin does not interact with GABA beta-oxidation defects. The other choices are receptors. also reasonable considerations for preinitia- 38. (C). In pyruvate dehydrogenase deficiency, tion screening, but for other conditions. pyruvate cannot be metabolized into 44. (A). Valproate inhibits uridine glucosyl acetyl-coA. The ketogenic diet bypasses this transferase, the enzyme that metabolizes step and provides ketones as an alternative lamotrigine. Initiation of valproate therapy fuel for the brain. All of the other choices are will result in lamotrigine toxicity. This contraindications to the ketogenic diet. addition usually requires immediate reduc- Long-chain fatty acids are transported across tion of the dose of lamotrigine by about the mitochondrial membrane by carnitine 50%. (helped by CPT I and II and carnitine 45. (D). This would be a longer-term compli- translocase); once in the mitochondrion, cation. Osteoporosis in the ketogenic diet is fatty acids are beta-oxidized to 2 carbon contributed to by calcium/vitamin D defi- units of acetyl-CoA that can then enter the ciency as well as acidosis. Multiple Choice Questions for Part IV 267

46. (B). Most common known etiology for epi- of choice for pure generalized absence lepsy is cerebrovascular disease at 11%, seizures. followed by neurologic deficits from birth, 51. (B). Although the benefit on seizure control mental retardation, or cerebral palsy at 8%. can be seen within 2 weeks after initiation 47. (D). Long-term complications in children on (in 75% of children in one study), it is rec- the ketogenic diet for >2 years have not ommended that the ketogenic diet be con- been systematically reviewed. There may be tinued for 3 months before deciding to increased fractures and kidney stones. continue or discontinue. Gradual weaning Symptoms, however, would be expected in rather than abrupt discontinuation is pre- the setting of pancreatitis, renal calculi, or ferred and may assist with determining severe constipation. Specific guidelines for whether there has been benefit of the keto- monitoring of bone health, however, still genic diet on seizure control. The recom- need to be delineated. mendation is to discontinue after 2 years of 48. (C). In GLUT1 deficiency syndrome, glu- seizure freedom, similar to the time period cose transport across the blood-brain barrier used for anticonvulsant medications. is impaired. Since the ketogenic diet pro- 52. (C). The likely diagnosis of this patient is vides ketones that bypass the metabolic neurocysticercosis. Epilepsy is the most defect, serving as an alternative fuel to the common presentation (70% of patients) fol- brain, the ketogenic diet is the treatment of lowed by , stroke, and psychiatric choice for this syndrome. Such epilepsy manifestations. It is more common in treatment is not necessary for benign myo- Southern America due to ingestion of clonus of infancy. Although the ketogenic uncooked egg-infected pork meat. Brain diet may be particularly helpful for gener- imaging often reveals several ring-enhancing alized , there has not been data lesions. Treatment consists of anthelminthic supporting its use in JME as of yet. The medication (such as albendazole) and ster- ketogenic diet is contraindicated for pyru- oids (e.g., dexamethasone) to suppress the vate carboxylase deficiency, which would inflammatory response induced by destruc- impair tricarboxylic acid cycle function and tion of live cysticerci. energy production in the ketogenic diet. 53. (D). Valproate exposure during pregnancy is 49. (B). Isoniazid is an antibiotic commonly associated with decreased verbal IQ and used in treating tuberculosis. It may trigger autism in offsprings. The teratogenic effect is de novo seizures by competing with the dose-dependent and is irrespective of mechanism of pyridoxine and its metabo- monotherapy or polytherapy use. Supple- lites. Pyridoxine is an essential cofactor for mentation with folic acid is not sufficient to many enzymatic reactions, including GABA reverse the teratogenic effect. an inhibitory neurotransmitter. 54. (C). This patient is suffering from partial– 50. (B). A large, multicenter, double-blind, ran- onset seizures and postherpetic neuralgia for domized, controlled trial to compare the which pregabalin is FDA indicated for. efficacy, tolerability, and neuropsychological Topiramate, lamotrigine, and levetiracetam effects of ethosuximide, valproic acid, and have not yet been proven effective in this lamotrigine favored ethosuximide. After setting. Carbamazepine could be helpful but 16 weeks of therapy, the has the risk of drug interactions at the level freedom-from-failure rates for ethosuximide of hepatic metabolism. and valproic acid were similar and higher 55. (C). Both valproate and phenytoin are highly than the rate for lamotrigine. However, protein-bound antiepileptic drugs. When attentional dysfunction was more common used together or added to a highly with valproic acid than with ethosuximide. protein-bound medication (such as war- As a result, ethosuximide became the drug farin), they can compete on protein binding, 268 Multiple Choice Questions for Part IV

increasing the free fraction of either drugs. abnormal initial routine EEG. An additional Valproate free fraction decreases at higher 35% were identified to have abnormalities concentrations due to protein saturation. on the second sleep-deprived EEG. An 56. (E). The use of the KD is being investigated in abnormal EEG predicts a higher recurrence several neurologic conditions beyond epi- rate, and a normal EEG predicts a lower lepsy and in traumatic brain injury, Alzhei- recurrence rate but does not rule out mer’s disease, amyotrophic lateral sclerosis, epilepsy. autism, glial tumors, diabetic nephropathy, 64. (E). Maternal use of valproate during preg- and Parkinson’s disease. In addition, in nancy was associated with a significantly development is 2-deoxy-(D)-glucose (2-DG), increased risk of autism spectrum disorder an agent which is a nonmetabolizable glucose and childhood autism in the offspring. analog that inhibits glycolysis. 65. (B). Lorazepam and clonazepam do not have 57. (B). Lamotrigine does not affect bone health active metabolites; lorazepam has the short- while phenytoin, phenobarbital, and topira- est half-life. mate can, because of their enzyme induction 66. (C). Phenytoin has nonlinear (saturable) properties. kinetics; its half-life becomes longer after 58. (D). Topiramate should be avoided in elderly the saturation point which is usually within because it has significant cognitive effects. the recommended therapeutic range. These can significantly limit or compromise 67. (B). Carbamazepine induces its own meta- their intellectual reserves. bolism so that its half-life becomes shorter 59. (B). Faciobrachial dystonic seizures are fre- with continued use. The process of autoin- quent brief dystonic seizures, typically duction is completed over 2–4 weeks. affecting the ipsilateral arm and face found 68. (C). Recurrence rate after the first seizure in association with LGI1 antibodies. Facio- averages around 30–40% by two years. The brachial dystonic seizures often precede risk is higher (approaching 50–60%) when LGI1-antibody encephalitis. Recognition the EEG or brain MRI is positive. may lead to early diagnosis and early insti- 69. (A). Primidone is converted into phenobar- tution of immunotherapy, with improved bital and phenylethylmalonamide (PEMA), outcome. which is also an active metabolite. Primi- 60. (A). Excluding carbamazepine, all the other done has acute toxic reactions that are dif- four medications (amiodarone, cimetidine, ferent from phenobarbital. It can produce fluconazole, and felbamate) may inhibit transient drowsiness, , , nau- phenytoin metabolism and may cause sea, and vomiting that can be debilitating. phenytoin accumulation. These reactions are present even before 61. (B). Excluding ceftriaxone, all the other phenobarbital has appeared as a metabolite. three medications (erythromycin, fluoxetine, 70. (D). Among the listed antiepileptic drugs, and propoxyphene) and grapefruit juice may gabapentin is mostly excreted in urine; inhibit carbamazepine metabolism and may hence, its dose should be reduced according cause carbamazepine accumulation. to the renal function. 62. (D). Estrogen may be proconvulsant as it 71. (D). Overall, risk factors that carry higher may reduce inhibition at the GABAA seizure recurrence rate include focal-onset receptor and also inhibits the synthesis of seizures, status epilepticus or cluster seizures GABA. On the other hand, progesterone at first seizure, abnormal EEG with epilep- may be anticonvulsant as it enhances inhi- tiform activity (sharp waves or spikes), and bition at the GABAA receptor and increases abnormal brain MRI or neurological GABA synthesis. examination. 63. (B). In one pooled analysis of 1766 subjects, 72. (E). Levetiracetam does not interact with 51% of patients (pooled analysis) had an oral contraceptive medications, while all the Multiple Choice Questions for Part IV 269

other choices can lower oral contraceptive tend to offer pharmacological advantages in medication levels. regard to lower protein binding, minimal 73. (B). Antiepileptic drugs with potential oph- drug–drug interaction, and absence or mini- thalmological adverse effects include topi- mal liver inhibition/induction. They are, ramate (acute open-angle glaucoma), however, more expensive than older AEDs. vigabatrin (peripheral visual constriction), 81. (A). Ethosuximide and valproate are both and ezogabine (photoreceptor damage). known to block T-type calcium channels, 74. (C). Zonisamide and topiramate are mild which conveys efficacy against absence carbonic anhydrase inhibitors and are known seizures. to decrease sweat production (causing 82. (C). HLA allele B*1502 is a marker for anhydrosis or hypohydrosis). This may par- carbamazepine-induced Stevens–Johnson ticularly be dangerous in patients with high syndrome and toxic epidermal necrolysis, physical activity, without compensatory particularly in Han Chinese. The FDA rec- hydration. ommends genotyping all Asians for the 75. (B). Risk of seizure recurrence after first allele before treatment initiation. symptomatic seizure is about 33% in an 83. (E). St John’s wort (or Hypericum perfora- acute (less than 7 days) stroke setting and tum) is a popular medicinal herb used for the 70% in a remote setting (more than 7 days). treatment of depression. It is known to Risk of seizure recurrence after first symp- induce cytochrome P450 affecting the phar- tomatic seizure is about 13% in the setting of macokinetics of several AEDs such as phe- acute TBI and 45% in the setting of remote nobarbital, carbamazepine, and phenytoin, TBI. resulting in adverse events. 76. (B). Vigabatrin’s visual field defect may 84. (A). Overall, 11–41% of patients will relapse affect about one-third of patients with vari- after antiepileptic drug discontinuation. The able severity. It primarily consists of relapse rate tends to be lower in children peripheral visual field constriction. Risk (*20%) and higher in adults (*40). factors include longer duration of treatment 85. (D). This is the consensus statement made and higher dosage. by the International Ketogenic Diet Study 77. (C). All of the listed antiepileptic drugs are Group. considered to be broad-spectrum except 86. (E). Brivaracetam binds to the synaptic pregabalin which targets focal-onset seizures vesicle protein as well as blocks sodium and may alternatively worsen generalized channels. seizures especially myoclonic seizures. 87. (A). Compared to the Cochrane Review 78. (C). Several clinical trials were concluded or performed in 2003, in which no RCTs were underway for (up to the current writing) the available, the Cochrane Review in 2012 treatment of acute repetitive seizures. This reviewed 4 RCTs, which showed that at least includes intranasal diazepam and midazo- 38% of patients had a 50% decrease in sei- lam, intramuscular diazepam (by autoinjec- zures at 3 months, with this positive tor), and buccal midazolam. response maintained for a year. Hender- 79. (B). Zonisamide does not have an extended son CB et al’s meta-analysis in 2006 showed release preparation, but has a prolonged 1/3 of patients having a >90% decrease in half-life, obviating the need for such a seizures. Caraballo R et al’s multicenter preparation. retrospective study in 2011 showed 22% 80. (C). Overall, when compared to older AEDs, with seizure freedom and 56% with greater newer AEDs tend to have better safety profile than 75% decrease. and tolerability (except for felbamate, viga- 88. (B). Zonisamide’s chemical structure batrin) but comparable efficacy. They also includes a sulfa moiety and thus should be 270 Multiple Choice Questions for Part IV

avoided in patients with known history of exclusively against absence seizures. Car- sulfa allergy. bamazepine and primidone are liver enzyme 89. (C). Traditionally, the patient would fast for inducers that can decrease warfarin efficacy 24–48 h. Once urine ketones appeared, the and worsen osteoporosis. Zonisamide can ketogenic diet would then be initiated grad- precipitate kidney stones. ually. Data support the fact that ketosis 91. (A). The Modified Atkins diet, the medium- occurs without this initial fasting period and chain triglyceride diet, and the low glycemic that tolerance of the diet may be higher index treatment are alternative dietary ther- without this fasting period. apies developed for epilepsy treatment. 90. (B). In this case, levetiracetam is the most 92. (E). Pregabalin is not metabolized and is not appropriate choice for treating partial sei- affected by phenytoin and other enzyme zures. Ethosuximide is efficacious inducers.