Real-Time Prediction of Delayed Cerebral Ischemia after Subarachnoid Hemorrhage

蛛网膜下腔出血后迟发性脑缺血的实时预测

• 批准号: 9895870
• 负责人: Eric S. Rosenthal
• 金额: $ 20.09万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-04-01 至 2023-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9895870
• 关键词: Admission activity; Age; American; Biological Markers; Biometry; Blinded; Blood Pressure; Blood Vessels; Brain; Brain Injuries; Brain region; Caring; Cerebral Ischemia; Cerebrum; Characteristics; Clinical; Clinical Data; Clinical Trials; Clinical Trials Design; Clinical assessments; Clinical/Radiologic; Common Data Element; Complex; Complication; Data; Deterioration; Development; Development Plans; Diagnosis; Early treatment; Educational Curriculum; Electroencephalography; Endothelin; Enrollment; Environment; Epilepsy; Evaluation; Event; Frequencies; Future; General Hospitals; Goals; Hypertension; Impaired cognition; Impairment; Individual; Infarction; Investigation; Investigational Therapies; Ischemia; Knowledge; Massachusetts; Measures; Mentors; Mentorship; Metabolic; Metabolism; Methods; Modeling; Monitor; Morbidity - disease rate; Nervous System Trauma; Neurologic Symptoms; Neuronal Dysfunction; Neuronal Injury; Neurons; Outcome; Patient Selection; Patients; Perioperative; Physiological; Population; Postoperative Period; Prevention; Preventive therapy; Principal Investigator; Probability; Protocols documentation; Radiology Specialty; Reporting; Research; Research Project Grants; Resources; Risk; Risk Factors; Ruptured Aneurysm; Science; Scientist; Secure; Societies; Specific qualifier value; Stroke; Structure; Subarachnoid Hemorrhage; Survival Analysis; Survivors; Testing; Time; United States National Institutes of Health; Vasospasm; Work; base; career; career development; clinical application; clinical center; clinical investigation; clinical risk; cohort; cost effective; critical period; exhaustion; experience; functional independence; functional outcomes; high risk; improved; medical schools; multimodality; neurophysiology; novel; patient oriented research; placebo group; predict clinical outcome; predicting response; prevent; prognostic tool; programs; prospective; real time model; recruit; signal processing; skills; success; tertiary care; tool; treatment response

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.

在每年发生SAH的30，000名美国人中，20 - 40%的人随后发生迟发性脑血管病。 缺血（DCI），这三倍的风险差的功能结果，产生损害在相对年轻的年龄 与其他中风亚型相比。因为SAH后的DCI通常仅在其被诊断为脑出血后才被检测到。 不可逆的，需要一种准确的工具来识别即将发生的DCI，以便在DCI恢复正常之前开始治疗。 因此，预防DCI的新临床疗法有最好的成功机会。理想情况下， 监测工具应提供实时评估神经功能的影响，由不同的血管和 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的准确性， 连续EEG通过评估早期、症状前脑恶化预测即将发生的DCI 活动主要研究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，延长至术后的时间临床数据可改善DCI的预测 （2）确定临床神经生理学家是否实时报告预先指定的EEG特征 改善DCI预测; 3）检查血压对神经元EEG测量的影响 DCI前后的功能障碍。拟议的研究基于申请人使用收集的试点数据 入院后的实时临床数据，根据NIH通用数据对DCI进行设盲评估 元素，并将血压和EEG α功率的研究扩展到一个大型队列， 多模态监测在初级导师乔纳森·罗桑博士和共同导师乔纳森·罗桑博士的指导下， 悉尼现金，李恒，和纳泽姆Atassi，PI提出了一个职业发展计划，利用 马萨诸塞州总医院和哈佛医学院的世界级环境资源， 熟练掌握生物统计学，多状态生存分析和信号处理，执行该项目， 过渡到一个独立的临床医生，科学家研究SAH相关的发病率和预防。 该项目的总体目标是制定检测即将发生DCI的早期迹象的策略， 预防性治疗：1）及时提供; 2）提供给适当的患者。这将提供 一个有效的，成功的未来DCI预防临床试验的框架。汇集了尖端的临床 神经生理学，MGH的分析资源，以及具有相关专业知识的导师团队，该项目将 定义DCI风险最高的SAH患者人群，同时了解 血压对脑功能的影响，导致DCI。以病人为中心的研究 项目，与指导和结构化课程的方法，包括生物统计学，多国 生存分析，信号处理和临床试验设计，将提供罗森塔尔博士的技能，发展 一个独立的职业生涯在蛛网膜下腔出血研究的前沿科学。