High Frequency Oscillation as a Biomarker in Childhood Epilepsy

描述(由申请人提供)：本提案的目标是双管齐下地建立发作间期高频振荡(HFO)作为发作期高频振荡的空间定位生物标志物 作为儿童癫痫发病过程的时间预测生物标志物。癫痫是一组常见的儿童疾病，尽管有新的抗癫痫药物和手术切除了致痫皮质，但其中很大一部分人仍将每周或每天发作一次，使人虚弱。尽管目前最好的内科和手术治疗，但癫痫发作仍有增无减的原因尚不清楚。利用加州大学洛杉矶分校现有的评估儿童癫痫和癫痫手术的基础设施，这项提议试图将HFO确立为致痫区域的空间定位生物标记物(假设1)。同样，通过三个专科诊所跟踪三组高风险的癫痫前期儿童，该提案还旨在建立HFO作为癫痫发生过程的时间预测标记(假设2)，并使用预期的连续视频脑电图。这项提案的结果自然会引出下一组问题 研究目标：1)在临床试验中将HFO定位数据纳入手术决策；2)在切除的皮质标本中进一步研究HFO背后的细胞和分子机制，以更好地了解癫痫的发生和可能的抗癫痫药物机制；3)在癫痫发作之前，对高危儿童进行潜在的治疗干预。帮助回答这些问题的研究是一些长期计划。

DESCRIPTION (provided by applicant): The goal of this proposal is a two-pronged approach to establish interictal high frequency oscillation (HFO) as a spatially localizing biomarker of the epileptogenic zone and as a temporally predictive biomarker of the epileptogenic process in childhood epilepsy. Epilepsy is a common group of disorders in children, a significant portion of whom will continue to have debilitating weekly or daily seizures despite new anticonvulsants and despite surgical resection of epileptogenic cortex. Why seizures continue unabated despite the best current medical and surgical therapy is unclear. Taking advantage of the already existing infrastructure that evaluates children for epilepsy and epilepsy surgery at UCLA, this proposal seeks to establish HFO as a spatially localizing biomarker of the epileptogenic zone (Hypothesis 1). Similarly, with three specialty clinics that follow 3 groups of high-risk pre- epileptic children, the proposal also aims to establish HFO as a temporally predictive marker of the epileptogenic process (Hypothesis 2) of who may go on to have epilepsy, with prospective serial video-EEGs. The results from this proposal will naturally lead to the next set of questions and research aims: 1) to incorporate HFO localization data in surgical decision-making in a clinical trial; 2) to further study the cellular and molecular mechanisms underlying HFO in resected cortical specimens to better understand epileptogenesis and possible antiepileptic drug mechanisms; 3) to enable potential therapeutic intervention in high-risk children, before seizure onset. Studies to help answer these questions are some of the long-term plans.