40751 - Epilepsy Prognosis and Treatment William H Theodore...

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Epilepsy: Prognosis and Treatment William H Theodore MD Chief, Clinical Epilepsy Section National Institute of Neurological Disorders and Stroke National Institutes of Health Bethesda, Maryland, USA
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Prevalence and Incidence Third most common neurologic disorder First seizure incidence: 20-70 / 100,000 Epilepsy incidence: 30-50 / 100, 000 Prevalence: 5-10 / 1000 Reported higher in some developing countries Cumulative adjusted lifetime risk: 1.3%–3.3% Hauser WA, Hesdorffer DC.  Epilepsy: Frequency, Causes, and Consequences . New York, NY:  Demos; 1991:1.
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Annegers 1993 Etiology of Symptomatic Epilepsy USA 0 10 20 30 40 50 60 70 80 <15 15-24 25-44 45-64 >65 devel infection trauma CVD tumor degen
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Epidemiology by Seizure Types Reproduced with permission from Hauser WA.   Epilepsia .  1992;33(suppl 4):S10. Complex Partial  (36%) Unclassified (3%) Myoclonic (3%) Absence (6%) Partial Unknown  (7%) Other Generalized  (8%) Simple Partial  (14%) Generalized TC   (23%)
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Prognosis After a Single Seizure Reported 30-70% recurrence over 3 years sampling, etiology, seizure types Increased if underlying lesion Decreased if avoidable acute precipitant CBZ reduced recurrence in children (Camfield 1989) 1/3 stopped drug due to side effects 18% Rx vs 38% no RX in 2 years PHT, CBZ, VPA, PB (First Seizure Trial Group 1989)
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AED Peak Plasma concentration Protein binding clearance T ½ Drug interactions Therapeutic level (μmol/L) lamotrigine 1-3h 55% hepatic 15-60 AEDs 10-60 gabapentin 2-3h ≈ ≈ dose 0 renal 6-7h # minimal 40-120 tiagabine 1-2h 96 CYP3A 5-8h AEDs # vigabatrin 1-2h 0 5-7h # # Topiramate 2-4h 15 mixed 18-23h Lithium, OCs, some AEDs 10-60 Oxcarbazepine (MHD metabolite) 1-2h 40 Non-CYP mediated 10-12 hr (MHD metabolite) AEDs oral contraceptives 50-140 (MHD) Felbamate 2-6h 22-25 hepatic 15-23hr AEDs 200-400 Phenobarbital 1-4 h 40-55 hepatic 80-130 extensive 50-130 Phenytoin 2-6 hr 90 Hepatic*** extensive 40-80 Carbamazepine Slow, variable 70-75 hepatic 18-55 hr* 12 hr** extensive 15-45 Levetiracetam 1-2 h 0 Renal 6-10 hr minimal # Zonisamide 3-4 h 40-60 CYP3A 50-60 hr extensive 35-200 Valproic acid 1-2 h 90 Hepatic 10-15 hr AEDs 300-600 Ethosuximide 3-5 h 0 hepatic 30-60 hr AEDs 300-600
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Drug Sodium channels Calcium channels GABA system Glutamate receptors Clinical Efficacy LRE PGE SGE Phenytoin ++ Y N N Carbamazepine ++ Y N N Oxcarbazepine ++ Y N N Lamotrigine ++ + Y Y Y Zonisamide ++ + Y Valproate + + + Y Y Y Felbamate + + + + Y Y Topiramate + + + + Y Y Ethosuximide ++ + N Y N Gabapentin ++ + Y Levetiracetam + + Y Phenobarbital + + + Y
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Epilepsy Therapy in 525 Patients Kwan and Brodie 2000
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Veterans Administration Cooperative Study Reproduced with permission from Mattson RH, et al.  N   Engl J Med . 1985;313:145-151. Percent Continuing
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40751 - Epilepsy Prognosis and Treatment William H Theodore...

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