Identification of Cortical Biomarkers for Seizure Risk in Childhood Epilepsy

儿童癫痫发作风险的皮质生物标志物的鉴定

• 批准号: 9133481
• 负责人: Catherine J Chu
• 金额: $ 19.35万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-01 至 2020-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9133481
• 关键词: Accounting; Address; Adverse effects; Age; Aggressive behavior; Antiepileptic Agents; Attentional deficit; Behavioral; Benign; Biological Markers; Biometry; Brain; Cessation of life; Child; Childhood; Chronic; Clinical; Clinical Research; Clinical Trials; Cognitive; Complement; Cross-Sectional Studies; Data; Data Set; Development; Diagnostic tests; Disease; Disease remission; Drowsiness; Drug Exposure; Electroencephalogram; Electrophysiology (science); Environment; Epilepsy; Evaluation; Evolution; Functional Magnetic Resonance Imaging; Funding; General Hospitals; Goals; Health; High Frequency Oscillation; Hostility; Hour; Human; Image; Imaging Techniques; Imaging technology; Injury; Joints; Knowledge; Lead; Magnetic Resonance Imaging; Massachusetts; Measures; Mentorship; Methods; Modeling; Monitor; Multimodal Imaging; Nervousness; Pharmaceutical Preparations; Pharmacotherapy; Physiological; Population; Positioning Attribute; Predictive Value; Predisposition; Process; Property; Recurrence; Research; Research Personnel; Resolution; Risk; School-Age Population; Seizures; Single Seizures; Source; Study Subject; Syndrome; Techniques; Technology; Testing; Training; base; candidate marker; career; career development; clinical practice; clinically relevant; cohort; density; experience; improved; nervous system disorder; neuroimaging; neurophysiology; novel; patient oriented research; predictive modeling; premature; prevent; programs; prospective; psychosocial; signal processing; tool; treatment strategy; white matter

 DESCRIPTION (provided by applicant): Dr. Catherine Chu is a practicing pediatric epileptologist and clinical neurophysiologist at Massachusetts General Hospital (MGH), whose goal is to develop an independent research program utilizing non-invasive human imaging and neurophysiological recordings to improve our understanding of the mechanisms, disease process, and indicators of seizure risk in the developing brain. Dr. Chu proposes to study the most common pediatric epilepsy syndrome, benign epilepsy with Centro temporal spikes (BECTS) using novel methods to integrate advanced neuroimaging, electrophysiology, and signal processing techniques to identify key cortical biomarkers of seizure risk. Despite extensive clinical experience with this disease, it remains a challenge to determine who will benefit from antiepileptic drug (AED) treatment and when it is safe to discontinue. One- third of these children will have only a single seizure, while two-thirds may have recurrent seizures over several years. Although non-treatment or premature taper may result in seizures, chronic AED exposure introduces cognitive side effects in 30-70% of exposed children. A biomarker to isolate which children are at risk for ongoing seizures is needed to prevent the unnecessary consequences of over- or under-medication during critical years of cognitive, psychosocial and behavioral maturation in this large cohort of children. As seizures are thought to result from abnormal cortical excitability and connectivity, Dr. Chu hypothesizes those principled measures of these properties using available non-invasive techniques will identify clinically relevant biomarkers of seizure risk. Dr. Chu has developed preliminary results supporting the feasibility of her proposed approach. Under the joint mentorship of leading translational researchers Drs. Kevin Staley, Sydney Cash and Steven Stufflebeam at MGH, Dr. Chu proposes to first evaluate children with BECTS with active epilepsy and in remission in a cross-sectional study to identify candidate cortical biomarkers for seizure risk using advanced EEG and MRI techniques. She will then assess the utility of adding longitudinal data to the predictive models by re-studying th subjects in the cross sectional dataset one year after initial evaluation. The knowledge gained by these studies will lead to: 1) quantification of the physiological and anatomical processes associated with increased seizure risk in childhood epilepsy; 2) identification of candidate biomarkers of seizure risk which may have broader relevance to other epilepsies; 3) the development of novel tools and advanced expertise to identify and quantify these processes; and 4) preliminary data for an R01-funded clinical trial to test non- invasive biomarkers of seizure risk in childhood epilepsy. The career development program outlined in this proposal provides the candidate with advanced training in multimodal imaging techniques, prospective clinical research, and biostatistics in an outstanding training environment. The expertise that she will develop will position her for a productive independent career in patient-oriented research in which she can focus advanced imaging technologies to address pressing and clinically relevant questions in pediatric epilepsy.

 描述（由申请人提供）：Catherine Chu 博士是马萨诸塞州总医院 (MGH) 的一名执业儿科癫痫病学家和临床神经生理学家，她的目标是利用非侵入性人体成像和神经生理学记录开发一个独立的研究项目，以提高我们对以下疾病的理解： Chu 博士建议使用新型药物来研究最常见的儿童癫痫综合征，即伴有颞部棘波的良性癫痫 (BECTS)。整合先进的神经影像学、电生理学和信号处理技术来识别癫痫风险的关键皮质生物标志物的方法尽管在这种疾病方面拥有丰富的临床经验，但确定谁将从抗癫痫药物（AED）治疗中受益以及何时安全仍然是一个挑战。其中三分之一的儿童只会出现一次癫痫发作，而三分之二的儿童可能会在几年内反复癫痫发作。 30-70% 的暴露儿童需要一种生物标志物来隔离哪些儿童有持续癫痫发作的风险，以防止在这一大群儿童的认知、心理社会和行为成熟的关键时期因用药过量或不足而产生不必要的后果。由于癫痫被认为是由异常的皮质兴奋性和连接性引起的，朱博士已得出初步结果支持她提出的可行性在 MGH 的领先转化研究人员 Kevin Staley、Sydney Cash 和 Steven Stufflebeam 博士的联合指导下，Chu 博士建议首先在一项横断面研究中评估患有活动性癫痫和缓解期的 BECTS 儿童，以确定候选皮质生物标志物。然后，她将使用先进的脑电图和核磁共振技术来评估将纵向数据添加到预测模型中的效用，方法是在初次评估一年后重新研究横截面数据集中的受试者所获得的知识。这些研究将导致：1）量化与儿童癫痫发作风险增加相关的生理和解剖过程；2）识别可能与其他癫痫有更广泛相关性的癫痫风险候选生物标志物；以及识别和量化这些过程的先进专业知识；4) R01 资助的临床试验的初步数据，用于测试儿童癫痫发作风险的非侵入性生物标志物。候选人在出色的培训环境中接受过多模态成像技术、前瞻性临床研究和生物统计学方面的高级培训。 将发展将使她在以患者为导向的研究中获得富有成效的独立职业生涯，其中她可以专注于先进的成像技术来解决小儿癫痫中紧迫的和临床相关的问题。