Real-Time Prediction of Delayed Cerebral Ischemia after Subarachnoid Hemorrhage

在每年发生SAH的30,000名美国人中，有20%-40%的人随后会出现迟发性脑出血 缺血(DCI)，这会使功能预后不良的风险增加两倍，在相对较小的年龄就会产生损害 与其他卒中亚型比较。因为SAH之后的DCI通常只有在 不可逆转的是，需要一种准确的工具来识别即将到来的DCI，以便在DCI好转之前开始治疗 因此，预防DCI的新临床疗法具有最好的成功机会。理想情况下， 监测工具应实时评估不同血管和血管对神经元功能的影响 导致DCI的代谢机制。 拟议的科学计划旨在检查实时临床评估和 连续脑电通过评估早期、症状前脑损害来预测即将发生的DCI 活动。首席调查者有三个具体的研究目标：(1)确定是否纳入真实的- 与入院时相比，延长术后时间的临床资料可改善DCI的预测 数据本身；(2)确定临床神经生理学家是否实时报告预先指定的脑电特征 改进DCI预测；以及3)检查血压对神经元脑电测量的影响 DCI治疗前后的功能障碍。拟议的研究以申请人通过使用以下方式收集的试点数据为基础 入院后实时临床数据，基于NIH公共数据对DCI进行盲法评估 元素，并将血压和脑电阿尔法功率的研究扩展到同步的大队列 多模式监测。在主要导师乔纳森·罗桑德博士和共同导师博士的指导下。 悉尼·卡什、Hang Lee和Nazem Atassi，PI提出了一项职业发展计划，利用 马萨诸塞州综合医院和哈佛医学院的世界级环境资源 精通生物统计学、多状态生存分析和信号处理，开展项目和 转变为研究SAH相关发病率及其预防的独立临床医生兼科学家。 这个项目的总体目标是制定策略，以检测即将到来的DCI的早期迹象，以实现 预防性治疗：1)及时提供；2)提供给适当的患者。这将提供 为未来预防DCI的有效、成功的临床试验提供一个框架。汇聚尖端临床 MGH的神经生理学和分析资源，以及具有相关专业知识的导师团队，该项目将 确定SAH患者中DCI风险最高的人群，同时了解 血压对脑功能的影响在不同阶段导致DCI。建议的以患者为中心的研究 项目，与导师指导和包括生物统计、多国方法在内的结构化课程相结合 生存分析、信号处理和临床试验设计将为罗森塔尔博士提供发展的技能 在科学前沿从事蛛网膜下腔出血研究的独立职业。

Of the 30,000 Americans who develop SAH each year, 20-40% have a subsequent event of delayed cerebral ischemia (DCI), which triples the risk of poor functional outcome, producing impairment at a relatively young age compared with other stroke subtypes. Because DCI following SAH is commonly detected only after it is irreversible, an accurate tool is needed to identify impending DCI so that therapies can begin before DCI is well established and so that new clinical therapies for DCI prevention have the best opportunity for success. Ideally, monitoring tools should afford real-time assessment of neuronal function impacted by the diverse vascular and metabolic mechanisms leading to DCI. The proposed scientific program aims to examine the accuracy of real-time clinical assessments and continuous EEG for predicting impending DCI by evaluating for early, pre-symptomatic deterioration in brain activity. The principal investigator has three specific research aims: (1) to determine whether incorporating real- time clinical data extending through the postoperative period improves prediction of DCI compared to admission data alone; (2) to determine whether real-time clinical neurophysiologist reporting of pre-specified EEG features improves DCI prediction; and 3) to examine the influence of blood pressure on EEG measures of neuronal dysfunction before and after DCI. The proposed studies build on pilot data collected by the applicant by using real-time clinical data beyond admission, performing blinded assessments for DCI based on NIH Common Data Elements, and extending the study of blood pressure and EEG alpha power to a large cohort with synchronized multimodality monitoring. Under the mentorship of primary mentor Dr. Jonathan Rosand, and co-mentors Drs. Sydney Cash, Hang Lee, and Nazem Atassi, the PI proposes a career development plan leveraging the resources of a world-class environment at Massachusetts General Hospital and Harvard Medical School to develop proficiency in biostatistics, multi-state survival analysis, and signal processing, carry out the project and transition to an independent clinician-scientist studying SAH-related morbidity and its prevention. The overall goal of this project is to develop strategies for detecting early signs of impending DCI to enable preventative therapies to be delivered 1) in a timely manner and 2) to the appropriate patients. This will provide a framework for efficient, successful future clinical trials of DCI prevention. Bringing together cutting-edge clinical neurophysiology, analytic resources at MGH, and a team of mentors with relevant expertise, this project will define the population of SAH patients at greatest risk for DCI, while drawing understanding about the impact of blood pressure on brain function at various stages leading to DCI. The proposed patient-oriented research project, in concert with mentorship and a structured curriculum in methods including biostatistics, multi-state survival analysis, signal processing, and clinical trial design, will provide Dr. Rosenthal with the skills to develop an independent career in subarachnoid hemorrhage research at the cutting edge of science.