Childhood Absence Epilepsy (CAE) is the most common childhood onset epilepsy syndrome, accounting for 10-17% of all childhood onset epilepsy. In its first 6 years, the 32 center CAE trial successfully completed a double blind randomized controlled comparative trial (NS045911 and NS045803) comparing short term outcomes for ethosuximide, lamotrigine and valproic acid as initial therapy for children with newly diagnosed CAE characterized by only absence seizures. The CAE trial established ethosuximide as the optimal initial short term therapy for children with newly diagnosed CAE. However, it is clear that long term outcomes remain the crucial outcomes that should be used to determine optimal therapy. We propose to use this well characterized, carefully monitored cohort treated through a randomized controlled trial to determine if ethosuximide maintains its superior effectiveness (freedom from failure) over the long term along with better seizure freedom, seizure remission, cognitive and safety outcomes than lamotrigine or valproic acid in this well defined idiopathic epilepsy syndrome. Serial assessment of seizure control (including occurrence of generalized tonic clonic seizures), seizure remission, behavioral/emotional status, quality of life and growth will occur over the entire 4 years of the study. All CAE subjects and a cohort of 150 comparable healthy unrelated control subjects will be assessed using a new neuropsychological testing battery to better understand the CAE subjects'neuropsychological function at 6 years after start of therapy. This study's results will identify the optimal initial monotherapy for best long term outcomes. These results will address knowledge gaps about the long term comparative effectiveness of initial monotherapy for CAE and allow clinicians to make more evidence based treatment decisions for initial therapy to optimize both seizure and cognitive long term outcomes.

Public Health Relevance

Epilepsy (CAE) is the most common childhood epilepsy syndrome. Although a recent clinical trial of 446 children with CAE found ethosuximide as optimal initial short term therapy, is it not clear how short term results relate to long term outcomes. Optimal long term therapy can be determined by following these children for four more years.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project--Cooperative Agreements (U01)
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Special Emphasis Panel (ZNS1-SRB-B (20))
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Fureman, Brandy E
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Cincinnati Children's Hospital Medical Center
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Nariai, Hiroki; Duberstein, Susan; Shinnar, Shlomo (2018) Treatment of Epileptic Encephalopathies: Current State of the Art. J Child Neurol 33:41-54
Arya, Ravindra; Peariso, Katrina; Gaínza-Lein, Marina et al. (2018) Efficacy and safety of ketogenic diet for treatment of pediatric convulsive refractory status epilepticus. Epilepsy Res 144:1-6
Knox, Andrew T; Glauser, Tracy; Tenney, Jeffrey et al. (2018) Modeling pathogenesis and treatment response in childhood absence epilepsy. Epilepsia 59:135-145
Galanopoulou, Aristea S; Mowrey, Wenzhu B; Liu, Wei et al. (2017) Preclinical Screening for Treatments for Infantile Spasms in the Multiple Hit Rat Model of Infantile Spasms: An Update. Neurochem Res 42:1949-1961
Shandra, Oleksii; Moshé, Solomon L; Galanopoulou, Aristea S (2017) Inflammation in Epileptic Encephalopathies. Adv Protein Chem Struct Biol 108:59-84
Uohara, Michael Y; Beslow, Lauren A; Billinghurst, Lori et al. (2017) Incidence of Recurrence in Posterior Circulation Childhood Arterial Ischemic Stroke. JAMA Neurol 74:316-323
Karrasch, Mira; Tiitta, Petri; Hermann, Bruce et al. (2017) Cognitive Outcome in Childhood-Onset Epilepsy: A Five-Decade Prospective Cohort Study. J Int Neuropsychol Soc 23:332-340
Glauser, Tracy A; Holland, Katherine; O'Brien, Valerie P et al. (2017) Pharmacogenetics of antiepileptic drug efficacy in childhood absence epilepsy. Ann Neurol 81:444-453
Garcia-Ramos, Camille; Bobholz, Sam; Dabbs, Kevin et al. (2017) Brain structure and organization five decades after childhood onset epilepsy. Hum Brain Mapp 38:3289-3299
Shinnar, Ruth C; Shinnar, Shlomo; Cnaan, Avital et al. (2017) Pretreatment behavior and subsequent medication effects in childhood absence epilepsy. Neurology 89:1698-1706

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