Seizures and Children's Outcomes after Stroke (SCOUTS)

癫痫发作和中风后儿童的结局 (SCOUTS)

• 批准号: 10367580
• 负责人: Christine K. Fox
• 金额: $ 74.27万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-01-01 至 2026-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10367580
• 关键词: 19 year old; Acute; Anatomy; Ancillary Study; Animal Model; Animals; Anti-Inflammatory Agents; Area; Biological; Biological Assay; Blood Banks; Blood Vessels; Brain; Brain Injuries; Brain region; Child; Child Support; Childhood; Childhood stroke; Chronic; Clinical Data; Clinical Trials; Cognitive; Data; Data Set; Development; Enrollment; Epilepsy; Epileptogenesis; Family; Funding; Future; Health; Human; Incidence; Infarction; Infection; Inflammation; Inflammatory; Information Networks; Infrastructure; Injury; Interferon Type II; Intervention; Ischemic Stroke; Knowledge; Laboratories; Lesion; Libraries; Life; Link; Location; Machine Learning; Measures; Mediator of activation protein; Modeling; Molecular; Motor; Outcome; Pathway interactions; Plasma; Prevention; Preventive therapy; Prognosis; Quality of life; Recovery; Reproducibility; Research; Risk; Role; Sampling; Seizures; Serum; Signal Pathway; Signal Transduction; Stroke; Study models; Symptoms; Techniques; Testing; Therapeutic Agents; Time; United States National Institutes of Health; Validation; Work; acute stroke; base; clinical imaging; cognitive development; cohort; connectome data; data repository; design; differential expression; healing; high risk; improved; inclusion criteria; inflammatory marker; longitudinal dataset; machine learning method; neuroimaging; novel; novel strategies; post stroke; prevent; prognostication; stroke outcome; stroke survivor; systemic inflammatory response

PROJECT SUMMARY/ABSTRACT Epilepsy is one of the common problems that can result after ischemic stroke in a child. Children with post- stroke epilepsy have poorer cognitive outcomes, poorer quality of life and worse health measures. A better understanding of the determinants of post-stroke epilepsy is needed. Children who have acute seizures (those that occur within one week of the stroke) are more likely to develop epilepsy later in childhood, with a cumulative epilepsy incidence of 58% by 10 years. Inflammation and infarct location are two potential links between acute seizures and later development of epilepsy after pediatric stroke. Based on studies in animals and prior work, acute seizures worsen the inflammation that occurs after a stroke; in turn, inflammation may be an important mediator of epilepsy. Another possibility is that acute seizures are a marker of an injury to the anatomic brain regions or networks that are epileptogenic. This ancillary study proposal will examine acute seizures and post-stroke epilepsy in children who had a stroke (28 days of life up to 19 years of age at stroke onset) who were enrolled in two separate cohorts. The two independent cohorts will be utilized as a discovery and validation set. One cohort is from the completed VIPS I study of childhood stroke, and the second is from the ongoing VIPS II study of childhood stroke. In Aim 1, the inflammatory signaling pathways activated by acute seizures will be determined using banked blood collected from children after stroke, validating preliminary work from the VIPS I cohort. In Aim 2, changes in inflammatory signaling pathways will be identified in children who later develop epilepsy. Epilepsy outcomes will be ascertained in both cohorts. Banked blood collected at several timepoints after the stroke will be utilized to determine differential expression of analytes in those who develop epilepsy compared to those who do not. In Aim 3, lesion-symptom mapping and lesion-network mapping will identify the brain regions and functional networks associated with post-stroke epilepsy. Machine learning techniques will be used to integrate results from these three aims, creating models that include relevant laboratory data, clinical data and imaging data. The “Seizures and Children's Outcomes after Stroke (SCOUTS)” study is important because it will improve understanding of epilepsy after pediatric stroke. The results will provide evidence for molecular and anatomic pathways associated with seizures and epileptogenesis and will be used in future research of anti-inflammatory therapeutic agents to reduce the risk of post-stroke epilepsy. The SCOUTS study will identify predictors of epilepsy to improve prognostication for families and inform inclusion criteria in future trials. A rich dataset of longitudinal stroke outcomes will also be a legacy of the study. The long-term objectives of this research are to find a treatment that can be given after a child has a stroke to effectively improve recovery and prevent epilepsy.

项目摘要/摘要 癫痫是儿童缺血性中风后常见的问题之一。有后遗症的儿童 中风癫痫患者的认知结果较差，生活质量较差，健康措施也较差。更好的 需要了解卒中后癫痫的决定因素。有急性癫痫发作的儿童(那些 发生在中风后一周内)更有可能在童年后期患上癫痫， 到10年累计癫痫发病率为58%。炎症和梗塞部位是两个潜在的联系 儿童中风后急性癫痫发作和后来的癫痫发展之间的关系。基于对动物的研究 先前的研究表明，急性癫痫发作会加重中风后的炎症；反过来，炎症可能是 癫痫的重要中介人。另一种可能性是急性癫痫发作是脑部损伤的标志。 致痫的大脑解剖区域或网络。这项辅助研究建议将研究急性 中风儿童的癫痫发作和中风后癫痫(中风时28天至19岁) 开始)，他们被登记在两个不同的队列中。这两个独立的队列将被用作一项发现 和验证集。一组来自我对儿童中风的研究完成的VIP，另一组来自 正在进行的VIPS II儿童中风研究。在目标1中，炎症信号通路被激活 急性癫痫发作将使用从中风后儿童身上收集的库存血液来确定，验证 我的贵宾队列的初步工作。在目标2中，炎症信号通路的变化将是 在后来患上癫痫的儿童中发现。癫痫的结果将在两个队列中得到确定。 在中风后的几个时间点收集的库存血液将被用来确定差异表达 患有癫痫的人与未患癫痫的人相比，分析物的含量。在目标3中，病变-症状图 病变网络图将确定与中风后相关的大脑区域和功能网络 癫痫。将使用机器学习技术来整合这三个目标的结果，创建模型 这些数据包括相关实验室数据、临床数据和成像数据。《癫痫发作与儿童结局》 中风后(童子军)“研究很重要，因为它将提高对儿童中风后癫痫的认识 卒中。这些结果将为与癫痫和癫痫相关的分子和解剖途径提供证据。 并将用于未来的抗炎治疗药物的研究，以降低患癫痫的风险 中风后癫痫。童子军研究将确定癫痫的预测因素，以改善对 并在未来的试验中告知纳入标准。一个丰富的纵向中风结果数据集也将是 这项研究的遗产。这项研究的长期目标是找到一种治疗方法，可以在 对有中风的儿童有效提高康复和预防癫痫。