CHILDHOOD ABSENCE EPILEPSY RX, PK-PD-PHARMACOGENETICS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 儿童失神癫痫(CAE)的特征是在其他方面正常的儿童中非常频繁地出现失神发作。失神癫痫的发病年龄一般在4-8岁之间，6-7岁发病率最高。在患有CAE的年轻人中，20%的人在失神发作期间受伤。据估计，失神发作造成意外伤害的风险为每人每年3%。 乙琥胺(ETX)、拉莫三嗪(LTG)和丙戊酸(VPA)三种抗癫痫药物(AED)是唯一被证明有效的CAE初始单一治疗药物。然而，到目前为止，还没有研究在前瞻性随机对照临床试验中比较这些AEDs的长期疗效和耐受性。没有一种AED是公认的CAE的首选药物。 这项研究将(1)确定用于CAE儿童初始治疗的最佳抗惊厥药物，(2)确定导致抗惊厥药物疗效和毒性个体间差异的药物遗传和其他非遗传因素，以及(3)确定和比较乙琥胺、拉莫曲金和丙戊酸单一疗法对CAE儿童认知(注意力)、行为和生活质量的影响。

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. Absence epilepsy onset is typically between the ages of 4 to 8 years with a peak incidence of 6 to 7 years of age. 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 the only AEDs with proven efficacy as initial monotherapy for CAE. No study to date, however, has compared the long-term efficacy and tolerability of these AEDs in a prospective randomized controlled clinical trial. No one AED is the universally accepted drug of first choice for CAE. This study will (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.