CHILDHOOD ABSENCE EPILEPSY RX, PK-PD-PHARMACOGENETICS

这个子项目是许多利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 儿童失神癫痫（CAE）的特征是在其他正常儿童中非常频繁的失神发作。 失神性癫痫发作通常在4至8岁之间，发病高峰在6至7岁。 20%的CAE年轻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%。 三种抗癫痫药物（AED），乙琥胺（ETX），拉莫三嗪（LTG）和丙戊酸（VPA），是唯一的AED已被证明有效的初始单一治疗CAE。 然而，迄今为止还没有研究在前瞻性随机对照临床试验中比较这些AED的长期疗效和耐受性。 没有一种AED是普遍接受的CAE首选药物。 本研究将（1）确定用于CAE儿童初始治疗的最佳抗惊厥药，（2）确定抗惊厥药疗效和毒性个体间差异的药物遗传学和其他非遗传因素，（3）确定和对比乙琥胺、拉莫三嗪和丙戊酸单药治疗对认知的影响（注意力）、行为和生活质量。

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.