Potential Surrogate Marker of Epileptogenic Cortex

致癫痫皮层的潜在替代标志物

• 批准号: 6910519
• 负责人: JOYCE Y WU
• 金额: $ 16.14万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-04-01 至 2010-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6910519
• 关键词: biomarker; cerebral cortex; children; clinical research; electroencephalography; epilepsy; human subject; longitudinal human study; magnetic resonance imaging; magnetoencephalography; neurophysiology; patient oriented research; positron emission tomography

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.

描述（由申请人提供）：本研究职业发展计划是一项多学科指导计划，允许研究者Dr. Wu发展儿科癫痫定量脑电图（EEC）和脑磁图（MEG）方面的专业知识。吴博士将运用这一专业知识，进一步了解EEC和MEG发现的临床意义，阵发性快速活动（PFA），并确定其作为脑皮层的定位和预测替代标记物的潜力。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，并计划开发一项关于PFA的EEC和MEG联合研究计划，以提高对耐药性癫痫的理解并改善癫痫手术后的癫痫发作结果。她将由神经外科医生和癫痫病学家Mauritus博士指导，Mauritus博士在儿科癫痫手术和临床神经生理学方面拥有独特的专业知识，并获得在UCLA开发MEG实验室所需的支持和资源。共同导师Sutherling博士是具有MEG专业知识的癫痫病学家，他将监督定制的MEG奖学金，并将成为加州大学洛杉矶分校MEG实验室发展的关键资源。利用已经存在的基础设施，评估儿童癫痫和癫痫手术与EEC在加州大学洛杉矶分校和斯克里普斯研究所的MEG，吴博士将前瞻性地检查PFA的共同定位价值的大脑区域，以及检查PFA的价值，在术前预测，哪些儿童接受癫痫手术是在术后复发性癫痫发作的高风险。癫痫是儿童常见的一组疾病，尽管使用了新的抗惊厥药物和手术切除了致癫痫皮质，但其中很大一部分儿童仍会继续出现使人衰弱的癫痫发作。尽管目前最好的药物和手术治疗，癫痫发作仍有增无减的原因尚不清楚。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，该提案寻求将PFA确定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EEG和MEG的儿童中定位癫痫发生区域的价值（假设1），第二，通过确定它在预测谁，特别是哪个大脑区域，在所有接受癫痫手术的儿童中，术后都会出现癫痫发作（假设2）。这一提议的结果将导致以下问题：这种潜在的替代标记物的潜在神经生理机制是什么？PFA是否能够在癫痫发作发生前识别高危人群（如中风、创伤、脑硬化症）中哪些人有癫痫发作的风险？完全切除PFA生成区域是否会导致术后更多的儿童无复发？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。