Potential Surrogate Marker of Epileptogenic Cortex

致癫痫皮层的潜在替代标志物

• 批准号: 7024579
• 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/7024579
• 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)：这项研究职业发展计划是一个多学科的指导计划，允许研究人员吴博士在儿童癫痫的定量脑电(EEC)和脑磁图(MEG)方面发展专业知识。吴博士将利用这一专业知识进一步了解EEC和MEG发现的临床意义，即阵发性快速活动(PFA)，并确定其作为癫痫产生皮质的定位和预测性替代标记物的潜力。吴医生是一名儿科神经学家和癫痫专家，在儿科癫痫和临床神经生理学方面拥有临床专长，并计划开发一项关于PFA的EEC和MEG联合研究计划，以加深对耐药癫痫的了解，并改善癫痫手术后的癫痫预后。她将接受神经外科医生和癫痫专家马森博士的指导，他在儿科癫痫外科和临床神经生理学方面具有独特的专业知识，并可获得在加州大学洛杉矶分校建立脑磁图实验室所需的支持和资源。共同导师Sutherling博士是一位拥有MEG专业知识的癫痫专家，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。利用加州大学洛杉矶分校的EEC和斯克里普斯研究所的MEG已有的评估癫痫和癫痫手术的基础设施，吴医生将前瞻性地研究PFA对癫痫产生脑区的共同定位价值，并研究PFA在术前预测接受癫痫手术的儿童术后复发风险的价值。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了致痫皮质，但其中很大一部分人仍将继续出现衰弱的癫痫发作。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。为了与NINDS的议程保持一致，以确定癫痫发生的标志物并“治愈癫痫”，这项提议寻求将PFA确立为一种潜在的替代标志物，首先通过确定其在所有接受长时间视频EEG和MEG的儿童中的癫痫产生区域的定位(假设1)，其次通过建立其在预测谁，尤其是大脑的哪个区域，将在所有接受癫痫手术的儿童术后癫痫发作的价值(假设2)。这项建议的结果将引出以下问题：这个潜在的替代标记物的潜在神经生理学机制是什么？PFA能否在高危人群(如中风、创伤、结节性硬化症)癫痫发作发生之前识别谁有癫痫发作的风险？完全切除PFA产生区域是否会导致更多手术后无癫痫发作的儿童？帮助回答这三个问题的研究是这位候选人的长期计划之一。