NEUROPSYCHOLOGICAL PROGRESSION IN NEW ONSET EPILEPSY

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。我们之前对成人慢性定位相关（颞叶）癫痫和健康对照的调查显示，儿童期癫痫与脑结构和认知功能的广泛不良神经发育影响有关（NS-37738）。本研究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。采用横断面和纵向联合设计，将75名新发定位相关癫痫的儿童（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、弥散张量成像和磁化转移成像）的横断面和两年纵向评估将与有关神经发展史、临床癫痫特征和精神疾病的信息相结合，以阐明大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)与对照组相比，新发定位相关性癫痫患儿将表现为全面性认知障碍、脑组织总体积（尤其是脑白质体积）的全面性减少以及脑白质微结构异常。(2)与对照组相比，新发癫痫儿童先前存在的神经发育异常的频率将显著增加，并将与癫痫发作时的神经影像学和认知异常有关；(3)与对照组相比，持续的儿童癫痫发作将与正常认知和大脑发育滞后（尤其是脑白质）和精神疾病发病率增加有关。(4)癫痫发作年龄较早将是大脑发育和认知发育滞后的最强预测因子，而癫痫发作严重程度将与精神疾病发病率的增加密切相关。

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. (from CRISP website) 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 study 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.