This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Childhood Absence Epilepsy (CAE) is characterized by very frequent absence seizures in an otherwise normal child with an EEG usually demonstrating 3 per second bilateral, synchronous, symmetrical spike-wave pattern with normal background activity. CAE occurs in 5% to 10% of all children with epilepsy with an annual incidence of 6.3 to 8 per 100,000 in children less than 15 years of age. Epilepsy onset is typically between the ages of 4 to 8 years with a peak incidence of 6 to 7 years of age. The long-term remission rates for absence epilepsy range from 21% to 89%. This wide reported range likely resulted from inconsistent and variable study inclusion criteria, methods, follow-up length, and outcome definitions. Twenty percent of young adults with CAE had an injury during an absence seizure. The risk of accidental injury resulting from an absence seizure has been estimated to be 3% per person year. Three anti-epileptic drugs (AED), ethosuximide (ETX), lamotrogine (LTG), and valproic acid (VPA), are commonly used as initial monotherapy for CAE. These three AEDs have advantages and disadvantages. Ethosuximide, lamotrogine, and valproic acid are the only AEDs with controlled clinical trial evidence of efficacy in absence seizures. No study to date, however, has examined the long-term efficacy and tolerability of these AEDs in a prospective randomized controlled clinical trial. The efficacy for these three AEDs are in the 50% to 70% range. No one AED is the universally accepted drug of first choice for CAE. Current medication treatment for CAE remains largely empiric: (1) one of three commonly used AEDs is selected as first line therapy based on clinician preference, (2) the AED dosage is empirically escalated in variable increments to a primarily subjective clinical endpoint, and (3) an alternative first line AED is selected when seizures fail to be adequately controlled or toxicity supervenes for the initial therapy. This study proposes to: (1) identify the optimal anticonvulsant used for the initial treatment of children with CAE, (2) determine the pharmacogenetic and other non-heritable factors underlying the inter-individual variation in anticonvulsants response efficacy and toxicity, and (3) define and contrast the effects of ethosuximide, lamotrogine, and valproic acid monotherapy on cognition (attention), behavior and quality of life in children with CAE.
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