Neurophychological Progression in New Onset Epilepsy

描述（由申请人提供）：我们之前对慢性局部相关（颞叶）癫痫成人和健康对照的研究表明，儿童期发作的癫痫与对大脑结构和认知功能的一般性不良神经发育影响相关（NS-37738）。本提案的目的是直接描述这种不良神经发育影响的时间、原因和后果。采用横断面和纵向相结合的设计，将75名新发定位相关癫痫儿童（年龄8-18岁）与75名年龄和性别匹配的对照组进行比较。神经心理状态和神经影像学（定量MRI、扩散张量成像和磁化传递成像）的横断面和2年纵向评估将与有关神经发育史、临床癫痫特征和精神病发病率的信息相结合，以阐明脑结构和认知明显异常的时间、病因和后果。 我们假设如下：（1）新发定位相关癫痫的儿童将表现出全身性认知障碍，全身性脑组织体积减少，（尤其是脑白色物质体积）和与对照相比脑白色物质的微结构异常，（二）与对照组相比，新发癫痫儿童中既存神经发育异常的频率将显著增加，癫痫发作时的神经影像学和认知异常，（3）持续的儿童癫痫发作将与正常认知和大脑发育的滞后相关（特别是大脑白色物质）和精神病发病率增加，以及（4）癫痫发作的早期年龄将是大脑生长和认知发育滞后的最强预测因素，而癫痫发作的严重程度将与精神病发病率增加。

DESCRIPTION (provided by applicant): Our prior investigation of adults with chronic localization-related (temporal lobe) epilepsy and healthy controls has shown childhood onset epilepsy to be associated with a generalized adverse neurodevelopmental impact on brain structure and cognitive function (NS-37738). The purpose of this proposal is to directly characterize the timing, cause and consequences of this adverse neurodevelopmental impact. Using a combined cross-sectional and longitudinal design, 75 children (age 8-18) with new onset localization-related epilepsy will be compared to 75 age and gender matched controls. Cross-sectional and two-year longitudinal assessment of neuropsychological status and neuroimaging (quantitative MRI, diffusion tensor imaging, and magnetization transfer imaging) will be integrated with information regarding neurodevelopmental history, clinical epilepsy characteristics and psychiatric morbidity in order to clarify the timing, etiology and consequences of evident abnormalities in brain structure and cognition. We hypothesize the following: (1) children with new onset localization-related epilepsy will exhibit generalized cognitive impairment, generalized reduction in total brain tissue volumes (especially cerebral white matter volumes), and microstructural abnormalities in cerebral white matter compared to controls, (2) frequency of preexisting neurodevelopmental abnormalities will be significantly increased in children with new onset epilepsy compared to controls and will be associated with neuroimaging and cognitive abnormalities at epilepsy onset, (3) ongoing childhood onset epilepsy will be associated with lags in normal cognitive and brain development (especially cerebral white matter) and increased psychiatric morbidity compared to controls, and (4) earlier age of epilepsy onset will be the strongest predictor of lags in brain growth and cognitive development while seizure severity will be most strongly associated with increased psychiatric morbidity.