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1、Management of Seizure Disorders Mark Kotlarewsky, MD FACP Department of Medicine Medstar Washington Hospital Center,Learning objectives,Understand the definition of seizure, epilepsy Understand the types of treatment, both medical and surgical Understand notable side effects of common antiepileptic
2、drugs Understand treatment and management of epilepsy-related comorbidities Management of antiepileptic drugs in women Management of status epilepticus,Conflicts of interest,None,Definitions,seizure: abnormal, excessive, or synchronous neuronal activity in the cerebral cortex 1-2 min, altered consci
3、ousness is common, confusion/fatigue after an episode, increased HR, tonic-clonic movement, paresthesias, aphasia epilepsy: two or more unprovoked seizures,Seizure types,Partial simple - does not impair awareness (eg. epileptic auras, jacksonian march) complex - impairs awareness by typically spread
4、ing to one or both temporal lobes secondarily generalized - when simple type spreads to involve both hemispheres diffusely Generalized primary - tonic-clonic absence - impairment of consciousness myoclonic - muscle contractions in rapid succession without consciousness impairment,Epilepsy types,part
5、ial temporal lobe - mesial temporal sclerosis generalized juvenile myoclonic - morning myoclonus, absence,Mesial temporal sclerosis,Epilepsy-related comorbidities,psychiatric disorders - depression, suicide, anxiety cognitive problems - visual/verbal memory, attention osteoporosis, heart disease, hy
6、pertension, stroke, obesity, obstructive sleep apnea sudden death,Choosing an antiepileptic drug (AED),effectiveness for seizure type side effects drug-drug interactions comorbid conditions age gender lifestyle, patient preferences cost,Choosing an AED by epilepsy type,partial - nearly all, particul
7、arly lamotrigine, carbamazepine, oxcarbazepine, levetiracetam generalized - lamotrigine, levetiracetam, topiramate, zonisamide, NOT carbamazepine, gabapentin, pregabalin as they can sometimes exacerbate this type absence - ethosuximide, valproate atypical absence, myoclonic, atonic - valproate, lamo
8、trigine, levetiracetam,Initiating/adding treatment,usually one drug, rather than two or more 2nd drug should have different mechanism, different side effect profile published therapeutic serum ranges should not be used if patient is doing well clinically (?) unclear whether generic substitutions lea
9、d to poorer control,Mechanisms,inhibitory transmission (benzodiazepines, clobazam, phenobarbital, tiagabine, vigabatrin) sodium channels (carbamazepine, lacosamide, lamotrigine, oxcarbazepine, phenytoin, rufinamide) calcium channels (ethosuximide) potassium channels (ezogabine) excitatory transmissi
10、on (perampanel) multiple mechanisms (felbamate, valproate, gabapentin, levetiracetam, topiramate),AED side effects,sedation, ataxia folate deficiency renal metabolism - gabapentin, levetiracetam, pregabalin, topiramate, zonisamide hepatic metabolism - carbamazepine, phenytoin, valproate elderly: YES
11、 - gabapentin, lamotrigine, levetiracetam NO - oxcarbazepine, phenytoin, carbamazepine,AED side effects,suicide - levetiracetam, topiramate, vigabatrin Stevens Johnson Synrome, toxic epidermal necrolysis, drug rash - phenytoin, carbamazepine (allele screening hlab1502 in asians), oxacarbazepine, pri
12、midone, phenobarbital, zonisamide, lamotrigine osteoporosis - especially with: phenytoin, carbamazepine, phenobarbital, primidone and valproate; consider checking bone mineral density after five years use with caution in patients with cardiac conduction pathology: lacosamide, phenytoin, ezogabine,AE
13、D side effects,weight loss - zonisamide, felbamate, topiramate weight gain - pregabalin, gabapentin, valproate insomnia - felbamate, lamotrigine nephrolithiasis - topiramate, zonisamide valproic acid - exacerbates sx of polcystic ovarian disease carbamazepine - induces own metabolism,Oral contracept
14、ives,carbamazepine, phenytoin, phenobarbital, primidone tend to decrease contraceptive serum levels (also felbamate, topiramate, oxcarbazepine, rufinamide, clobazam, perampanel) no interaction with levetiracetam, valproate reduced lamotrigine concentrations, which then go up during the week of inact
15、ive tablets,Pregnancy,4-6% rate of teratogenicity, 2-3x general population seizure control more important than teratogenicity aim: monotherapy at lowest dose for control avoid older AEDs: phenytoin, phenobarbital, valproate; latter two associated with oral cleft, cardiac, urinary tract, and neural t
16、ube defects, lower IQ topiramate: oral cleft, hypospadias better: lamotrigine, carbamazepine, levetiracetam, oxcarbazepine, gabapentin, but monitor levels closely,Pregnancy,induces AED metabolism, esp. lamotrigine phenytoin, carbamazepine, primidone, phenobarbital: hemorrhage in newborn due to vitam
17、in K deficiency folate: give 4mg starting 1-3 months prior to conception if on carbamazepine, valproic acid; standard dose for others,Drug-drug interactions,phenytoin, carbamazepine, primidone, phenobarb, (oxcarbazepine, topiramate) warfarin, OCPs, anti-infectives, anti-cancer between AEDs (eg. carbamazepine reduces lamotrigine levels, valproate increases them) alcohol: 1-2 drinks in well-controlled patient OK, highest risk of seizure 7-48hrs after cessation of alcohol,
