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

描述(申请人提供)：动脉缺血性中风(AIS)是一种常见的和破坏性的儿童疾病。尽管如此，几乎没有关于病因或结果的证据来指导治疗。这项建议旨在支持儿科神经科学术专家的早期职业发展，重点是调查儿童期发病的AIS的预后因素。具体地说，我们正在研究卒中亚型和生物标记物在卒中复发风险中的作用。初步结果表明，高凝状态的生物标志物的急剧升高可能与儿童期发病的AIS的特定亚型有关。此外，这些生物标志物可能是预后或复发的AIS和/或不良的神经学结果。某些中风亚型，如动脉病变，也与复发的AIS有关。因此，我们试图探索高凝状态的亚型和生物标记物对中风儿童复发的AIS的联合预后意义。为此，我们最初的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。这项分析将作为对美国国立卫生研究院建立的数据库的辅助研究，该数据库包括100多名连续登记的儿童期AIS患者。在一个独立的四中心队列中，我们将评估卒中亚型与高凝状态生物标记物显著升高之间的关系。最后，我们将评估高凝状态、卒中亚型和全身炎症等生物标志物对儿童期AIS复发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卒中亚型和凝血功能异常。对所提出的生物标志物的系统收集可以为1)儿童中风的病理生理学，2)中风复发的预测，以及3)识别需要更积极治疗的患者提供洞察。

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.