Electroencephalographic signatures of dysfunctional cerebrovascular autoregulation as biomarkers of brain injury in aneurysmal subarachnoid hemorrhage (SAH)

脑血管自动调节功能障碍的脑电图特征作为动脉瘤性蛛网膜下腔出血（SAH）脑损伤的生物标志物

• 批准号: 10667162
• 负责人: Jennifer A Kim
• 金额: $ 25.13万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-04-15 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10667162
• 关键词: Acute; Adult; Affect; Aneurysmal Subarachnoid Hemorrhages; Benchmarking; Biological Markers; Blood Pressure; Blood Vessels; Brain; Brain Injuries; Brain hemorrhage; Caring; Cerebral Ischemia; Cerebral hemisphere hemorrhage; Cerebral perfusion pressure; Cerebrovascular Circulation; Cerebrovascular Disorders; Cerebrovascular Spasm; Cerebrum; Clinical; Clinical Trials; Cohort Studies; Compensation; Complication; Coupled; Critical Illness; Data; Detection; Deterioration; Development; Disabled Persons; Disease; Distress; Early Diagnosis; Early Intervention; Electroencephalography; Exogenous Factors; Failure; Fright; Functional disorder; Future; Goals; Hemorrhage; Homeostasis; Individual; Informatics; Infrastructure; Intervention; Intracranial Pressure; Ischemia; Ischemic Stroke; Knowledge; Link; Metabolic; Metabolism; Mission; Modeling; Monitor; Morbidity - disease rate; Nature; Near-Infrared Spectroscopy; Nervous System Trauma; Neurologic; Neurologic Deficit; Neurology; Neurons; Operative Surgical Procedures; Outcome; Patients; Pattern; Perfusion; Phase; Phenotype; Physiological; Physiology; Play; Principal Investigator; Protocols documentation; Quality of life; Recovery; Research; Research Proposals; Resources; Rest; Risk; Risk Assessment; Ruptured Aneurysm; Sedation procedure; Signal Transduction; Stroke; Subarachnoid Hemorrhage; Subarachnoid Space; Survivors; Technology; Testing; Therapeutic; Time; Transcranial Doppler Ultrasonography; United States; United States National Institutes of Health; Vasospasm; biomarker driven; blood pressure control; cerebral hemodynamics; cerebral hypoperfusion; cerebrovascular; clinical center; clinical investigation; clinical practice; cohort; data repository; diagnostic strategy; disability; epileptiform; exhaust; functional improvement; functional outcomes; high risk; hypoperfusion; improved; individual patient; innovation; insight; nervous system disorder; neurophysiology; neuroprotection; neurovascular; novel; personalized approach; personalized medicine; pharmacologic; population based; precision medicine; pressure; prevent; prospective; risk mitigation; signal processing; tissue oxygenation; tool; treatment strategy

Abstract Aneurysmal subarachnoid hemorrhage (aSAH) remains a devastating disease affecting approximately 30,000 adults in the United States per year. Forty percent of aSAH patients die within 30 days, and over one-third of survivors sustain major neurologic deficits, in part due to feared secondary complications like vasospasm and delayed cerebral ischemia (DCI). Despite advances in care, few interventions can mitigate the risk of neurologic worsening after the initial bleed, and current monitoring strategies to identify impending DCI have limited accuracy. Abnormalities in cerebrovascular autoregulation and flow-metabolism uncoupling in the acute phase after aSAH have been shown to increase the risk of secondary brain injury and likely represent key players in the development of DCI. In this proposal, we plan to develop and refine an innovative, personalized approach to blood pressure management to identify patients most likely to benefit from therapeutic BP manipulation. To carry out this overarching aim, we will track continuous recordings of intracranial pressure, near-infrared spectroscopy, and EEG to determine patient-specific blood pressure targets that yield optimal brain blood flow and metabolism. This research proposal will evaluate if cerebral hemodynamic dysregulation drives EEG deterioration (Aim 1) and if a deviation from optimized blood pressure targets is associated with DCI and poor outcomes (Aim 2). We will then prospectively validate our results in a pilot cohort study. This proposal’s feasibility rests on (1) several years of research conducted by the principal investigators on signal processing, autoregulatory physiology, and continuous EEG in disease states like SAH and ischemic stroke, and (2) promising preliminary analyses evaluating the hypotheses being explored in this proposal. In total, this autoregulation-oriented neuroprotective therapy aims to optimize cerebral perfusion and ultimately improve clinical and functional outcomes. This research proposal is thus directly aligned with the NIH mission to reduce the burden of neurological disorders and enhance the quality of life of people with disabilities. The study will leverage Yale’s cutting-edge neuro- monitoring technologies along with extensive informatics and research resources of the Yale Center for Clinical Investigation to generate new insights into cerebral hemodynamics after aSAH and identify treatment opportunities. This line of research is readily translatable to the bedside and also applies to other cerebrovascular diseases like intracerebral hemorrhage and ischemic stroke, both of which likely encompass dysautoregulation as a critical physiologic variable. Knowledge gained in this study is anticipated to lead to a significant shift in the treatment approach for aSAH patients. It may ultimately lead to a clinical trial testing autoregulation-based treatment strategies, including tailored pharmacologic BP modulation based on patients’ real-time autoregulatory status. Our long-term goal is to use neuro-monitoring to develop physiology-based, personalized, early interventions to reduce the disability and morbidity associated with neurologic injury.

抽象的 动脉瘤性蛛网膜下腔出血（ASAH）仍然是一种毁灭性疾病，影响约30,000 每年在美国的成年人。 40％的屁股患者在30天内死亡，超过三分之一 幸存者维持主要的神经系统防御，部分是由于血管痉挛（血管痉挛）和 延迟的脑缺血（DCI）。尽管有护理的进步，但很少有干预措施可以减轻神经系统的风险 最初出血后担心，当前的监测策略以识别即将来临的DCI已有限制 准确性。急性期脑血管自动调节和流量 - 代谢解偶联的异常 显示ASAH后已显示出增加次要脑损伤的风险，并可能代表主要参与者 DCI的发展。在此提案中，我们计划开发和完善一种创新的个性化方法 血压管理以确定最有可能受益于治疗性BP操纵的患者。携带 除了这个总体目的，我们将跟踪颅内压的连续记录，近红外光谱， 和脑电图确定患者特异性的血压靶标，可产生最佳的脑血流和代谢。 该研究建议将评估脑血液动力学失调是否驱动脑电图定义（AIM 1） 如果与优化的血压目标偏离与DCI和差的结果有关（AIM 2）。我们 然后将在一项试点队列研究中前瞻性地验证我们的结果。该提议的可行性取决于（1）几个 首席研究人员对信号处理，自动调节生理学和 SAH和缺血性中风等疾病状态的连续脑电图，以及（2）有希望的初步分析 评估本提案中探讨的假设。总体而言，这种面向自动调节的神经保护 治疗旨在优化脑灌注并最终改善临床和功能结果。这 因此，研究建议与NIH的任务直接保持一致，以减少神经系统疾病的燃烧 并提高残疾人的生活质量。该研究将利用耶鲁大学的尖端神经 - 监测技术以及耶鲁临床中心的广泛信息和研究资源 调查以产生对ASAH后脑血流动力学的新见解并确定治疗 机会。这一研究很容易翻译成床边，也适用于其他脑血管 脑部出血和缺血性中风等疾病，两者都可能涵盖dydysoaregulation 作为关键的生理变量。预计在这项研究中获得的知识将导致重大转变 屁股患者的治疗方法。它最终可能导致基于自动调节的临床试验测试 治疗策略，包括基于患者的实时自动调节的量身定制的化色BP调制 地位。我们的长期目标是使用神经监控来开发基于生理的个性化，早期 减少与神经系统损伤相关的残疾和发病率的干预措施。