Investigation of Prognostic Factors in Childhood-Onset AIS: Role of Stroke Subtyp

描述（由申请人提供）：动脉缺血性卒中（AIS）是一种常见的和破坏性的儿童疾病。尽管如此，很少有证据表明病因或结果与通知治疗。该提案旨在支持学术儿科神经学家的早期职业发展，重点是儿童期发病AIS的预后因素的调查。具体来说，我们正在研究中风亚型和生物标志物对复发性中风风险的作用。初步结果表明，高凝状态的生物标志物急性升高可能与儿童期发病的AIS的特定亚型相关。此外，这些生物标志物可以是预后性或复发性AIS和/或不良神经学结果。某些中风亚型，如动脉病，也与复发性AIS有关。因此，我们试图探索亚型和高凝性生物标志物对脑卒中儿童复发性AIS的联合预后意义。为此，我们的初步目标是确认基于共识的分类系统在儿童期发病的AIS中的可靠性。该分析将作为已建立的NIH数据库的辅助研究进行，该数据库包含100多例连续入组的儿童期发作AIS患者。在一个单独的、前瞻性招募的儿童期发病AIS儿童的四中心队列中，我们将评估卒中亚型与高凝性生物标志物急性升高之间的关系。最后，我们将评估高凝状态、卒中亚型和全身炎症的生物标志物对儿童期发作的AIS患者复发性脑血管事件的预后意义。 公共卫生相关性：儿童中风是一种知之甚少的疾病。迄今为止确定的最普遍的危险因素包括中风亚型和凝血异常。系统收集所提出的生物标志物可以提供以下方面的见解：1）儿童卒中的病理生理学，2）复发性卒中的预测，以及3）需要更积极治疗的患者的识别。

DESCRIPTION (provided by applicant): Arterial ischemic stroke (AIS) is a common and devastating disorder of childhood. In spite of this, there is little evidence regarding etiology or outcomes with which to inform treatment. This proposal aims to support the early career development of an academic pediatric neurologist focusing upon the investigation of prognostic factors in childhood-onset AIS. Specifically, we are investigating the role of stroke subtype and biomarkers upon the risk of recurrent stroke. Preliminary results suggest that acutely elevated biomarkers of hypercoagulability are likely associated with specific subtypes in childhood-onset AIS. Further, these biomarkers may be prognostic or recurrent AIS and/or adverse neurological outcome. Certain stroke subtypes, such as arteriopathy, are also associated with recurrent AIS. Therefore, we seek to explore the combined prognostic significance of subtype and biomarkers of hypercoagulability upon recurrent AIS in children with stroke. To that end, our initial aim is to confirm the reliability of a consensus based classification system in childhood- onset AIS. This analysis will be performed as an ancillary study of an established NIH database of over 100 consecutively enrolled patients with childhood-onset AIS. In a separate, four-center cohort of prospectively enrolled children with childhood onset AIS, we will evaluate the relationship between stroke subtype and acutely elevated biomarkers of hypercoagulability. Finally, we will evaluate the prognostic significance of biomarkers of hypercoagulability, stroke subtype, and systemic inflammation for recurrent cerebrovascular events in childhood-onset AIS. PUBLIC HEALTH RELEVANCE: Childhood stroke is a poorly understood disease. The most prevalent risk factors identified to date include stroke subtype and coagulation abnormalities. The systematic collection of the proposed biomarkers may provide insight into 1) the pathophysiology of childhood stroke, 2) the prediction of recurrent stroke, and 3) the identification of patients who need more aggressive therapies.