Impact of Initial Therapy and Response on Long Term Outcome in Children with CAE

描述（由申请人提供）：儿童失神癫痫（CAE）是最常见的儿童发作性癫痫综合征，占所有儿童发作性癫痫的10-17%。在最初的6年中，32个中心的CAE试验成功完成了一项双盲随机对照比较试验（NS 045911和NS 045803），比较了乙琥胺、拉莫三嗪和丙戊酸作为新诊断的CAE儿童（仅表现为失神发作）的初始治疗的短期结局。CAE试验确定乙琥胺是新诊断CAE儿童的最佳初始短期治疗。然而，很明显，长期结果仍然是确定最佳治疗的关键结果。我们建议使用这一通过随机对照试验治疗的特征良好、监测仔细的队列，以确定乙琥胺在这种定义明确的特发性癫痫综合征中是否在长期沿着比拉莫三嗪或丙戊酸更好的无癫痫发作、癫痫缓解、认知和安全性结局方面保持其上级有效性（无失败）。在整个4年研究期间，将对癫痫控制（包括全身强直阵挛性癫痫发作的发生）、癫痫缓解、行为/情绪状态、生活质量和生长进行系列评估。所有CAE受试者和150名相当的健康无关对照受试者的队列将使用新的神经心理测试组合进行评估，以更好地了解CAE受试者在治疗开始后6年的神经心理功能。本研究的结果将确定最佳的初始单药治疗，以获得最佳的长期结局。这些结果将解决有关CAE初始单药治疗的长期比较有效性的知识差距，并允许临床医生为初始治疗做出更多基于证据的治疗决策，以优化癫痫发作和认知长期结局。 癫痫（CAE）是最常见的儿童癫痫综合征。尽管最近一项对446名CAE儿童进行的临床试验发现乙琥胺是最佳的初始短期治疗，但目前尚不清楚短期结果与长期结果之间的关系。最佳的长期治疗可以通过对这些儿童进行四年以上的随访来确定。

DESCRIPTION (provided by applicant): 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. 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.