Potential Surrogate Marker of Epileptogenic Cortex

描述（由申请人提供）：该研究职业发展计划是一个多学科指导计划，允许研究者吴博士在儿童癫痫的定量脑电图（EEC）和脑磁图（MEG）方面发展专业知识。吴博士将运用这一专业知识进一步了解脑电图和脑磁图发现的临床意义，即阵发性快速活动（PFA），并确定其作为癫痫发生皮层定位和预测替代标记的潜力。吴博士是一名儿科神经学家和癫痫学家，在儿科癫痫和临床神经生理学方面具有临床专业知识，并计划开发一个联合脑电图和脑磁图研究PFA的项目，以提高对耐药癫痫的认识，改善癫痫手术后的发作结果。她将由神经外科医生和癫痫学家Mathern博士指导，他在儿童癫痫手术和临床神经生理学方面都有独特的专业知识，并且可以获得加州大学洛杉矶分校MEG实验室发展所需的支持和资源。共同导师Sutherling博士是具有脑磁图专业知识的癫痫学家，他将监督一个定制的脑磁图奖学金，并将成为加州大学洛杉矶分校脑磁图实验室发展的关键资源。利用加州大学洛杉矶分校的脑电图和斯克里普斯研究所的脑电图评估儿童癫痫和癫痫手术的现有基础设施，吴博士将前瞻性地研究PFA在癫痫发作的大脑区域的共定位价值，并研究PFA在术前预测哪些接受癫痫手术的儿童术后复发癫痫的高风险方面的价值。癫痫是儿童中常见的一组疾病，尽管有新的抗惊厥药物和手术切除致癫痫皮质，但很大一部分儿童仍会出现使人虚弱的癫痫发作。为什么尽管目前最好的医学和外科治疗，癫痫发作仍有增无减，目前尚不清楚。为了与NINDS确定癫痫发生标志物和“治愈癫痫”的议程保持一致，本提案寻求将PFA作为潜在的替代标志物，首先通过确定其在所有接受长时间视频脑电图和MEG的儿童中定位癫痫发生区域的价值（假设1），其次通过确定其在所有接受癫痫手术的儿童中预测谁，特别是哪个脑区域将在术后发生癫痫发作的价值（假设2）。这项提议的结果将导致以下问题：这种潜在的替代标志物的潜在神经生理机制是什么？PFA是否能够在高风险人群（如中风、创伤、结节性硬化症）癫痫发作前识别出谁有癫痫发作的风险？完全切除pfa产生区是否会导致更多的儿童术后无癫痫发作？帮助回答这三个问题的研究是这位候选人的一些长期计划。

DESCRIPTION (provided by applicant): This research career development proposal is a multidisciplinary mentored program allowing the investigator, Dr. Wu, to develop expertise in quantitative electroencephalography (EEC) and magnetoencephalography (MEG) in pediatric epilepsy. Dr. Wu will apply this expertise to further the understanding of the clinical significance of an EEC and MEG finding, paroxysmal fast activity (PFA), and determine its potential as a localizing and predictive surrogate marker of the seizure-generating cortex. Dr. Wu is a pediatric neurologist and epileptologist with clinical expertise in pediatric epilepsy and clinical neurophysiology, and plans to develop a program of combined EEC and MEG research on PFA for improved understanding of drug-resistant epilepsy and improved seizure outcome after epilepsy surgery. She will be mentored by neurosurgeon and epileptologist Dr. Mathern, who brings a unique expertise in both pediatric epilepsy surgery and clinical neurophysiology as well as access to the support and resources necessary for development of a MEG laboratory at UCLA. Co-mentor Dr. Sutherling, epileptologist with MEG expertise, will supervise a customized MEG fellowship and will be a critical resource for the development of a MEG laboratory at UCLA. Taking advantage of the already existing infrastructure that evaluates children for epilepsy and epilepsy surgery with EEC at UCLA and MEG at Scripps Institute, Dr. Wu will prospectively examine the co-localizing value of PFA to the seizure-generating brain region, as well as examine the value of PFA in predicting, preoperatively, which children undergoing epilepsy surgery are at high risk for having recurrent seizures postoperatively. Epilepsy is a common group of disorders in children, a significant portion of whom will continue to have debilitating 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. In keeping with the NINDS agenda to identify markers of epileptogenesis and to "cure epilepsy", this proposal seeks to establish PFA as a potential surrogate marker, first by establishing its value in localizing the seizure-generating region in all children receiving prolonged video EEG and MEG (Hypothesis 1), and second by establishing its value in predicting who, and particularly which brain region, will have seizures postoperatively in all children undergoing epilepsy surgery (Hypothesis 2). The results from this proposal will lead to the questions of: what is the underlying neurophysiologic mechanism of this potential surrogate marker?; is PFA able to identify who is at risk for seizures in high-risk populations (such as stroke, trauma, Tuberous Sclerosis), before their seizures occur?; would complete resection of the PFA-generating region lead to more seizure-free children after surgery? Studies to help answer all three questions are some of the long-term plans of this candidate.