The Role of Infection in Childhood Stroke

描述（由申请人提供）：中风是一种越来越被认可的儿童残疾原因，每年每10万名儿童中就有13人中风。尽管对该病的认识有所提高，但我们对该病病理生理学的了解仍然有限。更好的理解可以改善我们对这些儿童的护理，也可以揭示适用于儿童和成人的非动脉粥样硬化性中风机制。感染可能是儿童中风的一个重要危险因素，要么是由于炎症介质的全身性作用导致相对的促血栓状态，要么是通过各种机制直接或间接地影响血管。该项目的总体目标是探索感染在儿童中风中的作用，从而提高我们对这种疾病的潜在机制的理解。该研究的具体目的是：1)确定感染（近期发热性感染、严重急性感染如脑膜炎和远处水痘）是否是儿童首次中风的危险因素；2)确定首次中风前的感染史是否预测中风复发，3)确定针对水痘带状疱疹病毒、流感病毒和脑膜炎细菌病因的疫苗接种是否对儿童中风有保护作用。我们建议在Kaiser Permanente医疗保健计划（KPMCP）注册的大约100万儿童中进行病例对照研究，KPMCP是一个健康维护组织，包括北加州的16家医院和36家门诊机构。我们将纳入17年期间（1993年至2009年）所有中风儿童的病例；对照将从KPMCP人群中随机选择，并根据年龄进行匹配。将通过审查电子和传统医疗记录以及对受试者或其代理人的电话访谈来测量暴露史。公共卫生相关性：这项研究将提高我们对儿童中风原因的理解，中风是导致终身身心残疾的重要原因，往往发生在年龄最小的儿童身上，即出生后第一年的儿童。了解儿童中风发生的原因是设计有效预防中风方法的第一步。

DESCRIPTION (provided by applicant): Stroke is an increasingly recognized cause of childhood disability, occurring in as many as 13 per 100,000 children per year. Despite improved recognition, our understanding of the pathophysiology of this disease remains limited. A better understanding could improve our care of these children, and also shed light on non-atherosclerotic mechanisms of stroke applicable to both children and adults. Infection may be an important risk factor for childhood stroke, either due to systemic effects of inflammatory mediators causing a relatively pro-thrombotic state, or by direct or indirect effects on blood vessels through a variety of mechanisms. The overall goal of this project is explore the role of infection in childhood stroke, and thereby improve our understanding of the mechanisms underlying this disease. The Specific Aims of the study are: 1) to determine whether infections (recent febrile infection, severe acute infections such as meningitis and remote chicken pox) are risk factors for first childhood stroke; 2) to determine whether a history of infection prior to a first stroke predicts stroke recurrence, and 3) to determine whether vaccinations against varicella-zoster virus, influenza virus and bacterial etiologies of meningitis are protective against childhood stroke. We propose a case-control study within the well-defined population of approximately 1 million children enrolled in Kaiser Permanente Medical Care Program (KPMCP), a health maintenance organization including 16 hospitals and 36 out-patient facilities in Northern California. We will include as cases all children with stroke over a 17 year time period (1993 to 2009); controls will be randomly selected from the KPMCP population and matched for age. Exposure history will be measured through review of electronic and traditional medical records, and by telephone interview of subjects or their surrogates. Public Health Relevance: This study will improve our understanding of why children have strokes, an important cause of life-long physical and mental disability that tends to occur in the very youngest of children, those in the first year of life. Understanding why strokes occur in children is the first step towards designing effective methods of preventing stroke.