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: 9487038
• 负责人: Catherine J Chu
• 金额: $ 20.09万
• 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/9487038
• 关键词: Accounting; Address; Adverse effects; Age; Aggressive behavior; Anatomy; 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; Drug Prescriptions; Electroencephalogram; Electroencephalography; Electrophysiology (science); Environment; Epilepsy; Evaluation; Evolution; Functional Magnetic Resonance Imaging; Funding; General Hospitals; Goals; High Frequency Oscillation; Hostility; Hour; Image; Imaging Techniques; Imaging technology; Injury; Joints; Knowledge; Magnetic Resonance Imaging; Massachusetts; Measures; Mentorship; Methods; Modeling; Monitor; Multimodal Imaging; Nervousness; Pharmaceutical Preparations; Pharmacotherapy; Physiological; Population; Positioning Attribute; Predictive Value; Predisposition; Process; Program Development; Property; Recurrence; Research; Resolution; Risk; School-Age Population; Seizures; Single Seizures; Source; Study Subject; Syndrome; Techniques; Technology; Testing; Training; base; candidate identification; candidate marker; career; career development; clinical practice; clinically relevant; cohort; density; experience; human imaging; improved; magnetic resonance imaging biomarker; multimodality; nervous system disorder; neuroimaging; neurophysiology; novel; patient oriented research; predictive modeling; premature; prevent; programs; prospective; psychosocial; public health relevance; signal processing; tool; tractography; translational scientist; 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.

 凯瑟琳·朱（Catherine Chu）博士是马萨诸塞州ERAL医院（MGH）的儿科癫痫病和临床神经生理学家（MGH），其目标是开发一个独立的研究计划，非侵入性人类成像和神经物质学，以改善我们对机制，疾病过程以及疾病过程以及指标的理解，以及指标，疾病过程以及指标，疾病过程，以及指标发育中的大脑癫痫发作。 ）何时进行癫痫发作，而三分之二的人可能会癫痫发作。在大量儿童的认知，心理社会和行为的关键时期，过度或不及格的人会使用可用的非侵入性技术来假设这些特性会确定这些特性领先的转化研究人员Drs，MGH的Sydney Cash和Steven Steven，在一项横断面的研究中，DHU向第一个评估患有癫痫病的儿童，以识别使用高级EEG和MRI技术的候选皮质生物标志物在初始评估后，将评估预测模型的实用性，这些研究的知识将导致：1）量化生理和解剖学过程在其他癫痫发作的癫痫发作中，R01资助的清晰测试在儿童期癫痫病中的癫痫发作风险。 将在小儿癫痫中发展将在面向患者的地址和临床相关问题中发展积极的独立职业。