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.

项目总结/摘要 癫痫是儿童缺血性中风后常见的问题之一。有产后抑郁症的儿童 中风癫痫的认知结果较差，生活质量较差，健康状况较差。更好的 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（ 在中风后一周内发生的）更有可能在童年后期发展为癫痫， 10年累积癫痫发病率为58%。炎症和梗死部位是两个潜在的联系 急性癫痫发作和儿童中风后癫痫的发展之间的关系。基于动物研究 和以前的工作，急性癫痫发作恶化炎症发生后，中风;反过来，炎症可能是 癫痫的重要介质。另一种可能性是，急性癫痫发作是脑损伤的标志。 癫痫的解剖学大脑区域或网络。这项辅助研究提案将审查急性 中风儿童（中风时28天至19岁）的癫痫发作和中风后癫痫 两人分别被分到两个不同的队列中。这两个独立的队列将被用作发现 和验证集。一个队列来自已完成的VIPS I儿童卒中研究，第二个队列来自 正在进行的儿童中风VIPS II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中收集的库存血液来确定， VIPS I队列的初步工作。在目标2中，炎症信号传导通路的变化将是 在后来患上癫痫的儿童中发现。将确定两个队列的癫痫结局。 在中风后的几个时间点收集的库存血液将用于确定差异表达 癫痫患者与未患癫痫患者的分析物的差异。在目标3中，病变-症状映射 损伤网络映射将识别与中风后相关的大脑区域和功能网络， 癫痫机器学习技术将用于整合这三个目标的结果，创建模型 包括相关实验室数据、临床数据和成像数据。癫痫发作和儿童结局 “脑卒中后癫痫（SCOUTS）”研究很重要，因为它将提高对儿童脑卒中后癫痫的理解。 中风这些结果将为癫痫发作相关的分子和解剖学途径提供证据， 癫痫发生，并将用于未来的抗炎治疗剂的研究，以减少风险， 中风后癫痫SCOUTS研究将确定癫痫的预测因素，以改善癫痫的诊断。 并在未来的试验中告知入选标准。还将提供纵向卒中结局的丰富数据集， 研究的遗产。这项研究的长期目标是找到一种治疗方法， 孩子中风后能有效促进恢复，预防癫痫。