Seizures and Children's Outcomes after Stroke (SCOUTS)

癫痫发作和中风后儿童的结局 (SCOUTS)

基本信息

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
项目类别：
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

项目摘要

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.

项目概要/摘要癫痫是儿童缺血性中风后可能导致的常见问题之一。中风癫痫的认知结果较差，生活质量较差，健康指标也较差。需要了解中风后癫痫的决定因素（患有急性癫痫发作的儿童）。中风后一周内发生的情况）更有可能在童年后期患上癫痫， 10 年癫痫累积发病率达到 58% 炎症和梗塞部位是两个潜在的联系。基于动物研究，急性癫痫发作与小儿中风后癫痫的发展之间的关系。和之前的工作一样，急性癫痫发作反过来会加剧中风后发生的炎症，炎症可能是另一种可能性是急性癫痫发作是癫痫损伤的标志。这项辅助研究提案将检查诱发癫痫的大脑解剖区域或网络。中风儿童（出生后 28 天至 19 岁中风时）的癫痫发作和中风后癫痫入组的两个独立队列将被用作一项发现。一组来自已完成的儿童中风 VIPS I 研究，第二组来自已完成的儿童中风研究。正在进行的儿童中风 VIPS II 研究的目标 1：炎症信号通路被激活。将使用从中风后收集的儿童血液库来确定急性癫痫发作，验证 VIPS I 队列的初步工作在目标 2 中，炎症信号通路的变化将是。在后来发生癫痫的儿童中发现的癫痫结果将在两个队列中确定。在中风后的几个时间点收集的储存血液将用于确定差异表达目标 3 中，癫痫患者与未患癫痫患者的分析物分布情况。和病变区域网络映射将识别与中风后相关的大脑和功能网络机器学习技术将用于整合这三个目标的结果，创建模型。包括相关的实验室数据、临床数据和影像数据。中风后（SCOUTS）”研究很重要，因为它将提高对小儿卒中后癫痫的了解结果将为与癫痫发作和中风相关的分子和解剖学途径提供证据。癫痫发生，并将用于未来抗炎治疗药物的研究，以降低癫痫发生的风险 SCOUTS 研究将确定癫痫的预测因素，以改善预后。家庭并为未来试验的纳入标准提供丰富的纵向卒中结果数据集。这项研究的长期目标是找到一种可以在治疗后给予的治疗方法。有效促进孩子中风康复并预防癫痫。