Cerebral Hemodynamics and Stroke in HIV-associated TB Meningitis.

HIV 相关结核性脑膜炎的脑血流动力学和中风。

• 批准号: 10762713
• 负责人: Mahsa Abassi
• 金额: $ 22.75万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-01 至 2025-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10762713
• 关键词: Affect; Age; Basal Ganglia; Blood Flow Velocity; Blood Pressure; Blood Vessels; Blood flow; Brain imaging; Carbon Dioxide; Caring; Categories; Central Nervous System Infections; Cephalic; Cerebral Infarction; Cerebrovascular Circulation; Cerebrovascular Physiology; Cerebrovascular system; Cerebrum; Clinical; Clinical Trials; Collaborations; Communicable Diseases; Complication; Development; Disease; Enrollment; Functional disorder; Future; Goals; HIV; HIV Infections; Image; Immune response; Impairment; Individual; Infection; Inhalation; Intervention; Knowledge; Magnetic Resonance Imaging; Measurement; Measures; Meningeal Tuberculosis; Meningitis; Minnesota; Mission; Morbidity - disease rate; Motor; National Institute of Neurological Disorders and Stroke; Necrosis; Nervous System Trauma; Neurocognitive; Neurocognitive Deficit; Neurologic; Neurological outcome; Outcome; Outcome Assessment; Participant; Pathogenesis; Pathology; Patients; Pattern; Perforating Artery; Performance; Persons; Phase; Productivity; Prospective, cohort study; Public Health; Research; Stimulus; Stroke; Study Subject; Survivors; Testing; Time; Transcranial Doppler Ultrasonography; Uganda; Universities; Vascular Diseases; brain magnetic resonance imaging; cerebral artery; cerebral hemodynamics; cerebrovascular; disability; experience; follow-up; functional outcomes; improved; indexing; innovation; low and middle-income countries; middle cerebral artery; mortality; nervous system disorder; neurocognitive test; novel; predict responsiveness; prevent; randomized, clinical trials; response; stroke incidence; theories

Abstract Tuberculous meningitis (TBM) disproportionally affects people in low- and middle-income countries and is associated with high morbidity and mortality. Stroke is a common complication in TBM and can lead to severe irreversible neurological disability. Studies on TBM-associated stroke pathology, however, have focused primarily on HIV-uninfected individuals. The overall objective of this proposal is to use transcranial doppler and brain imaging to understand changes in cerebral blood vessels and cerebral blood flow in order to determine changes in cerebrovascular responsiveness, characterize patterns of stroke, and describe long-term neurocognitive outcomes in HIV-associated TBM. The central hypothesis is that in HIV-infected individuals, TBM causes extensive cerebral vascular narrowing and impaired cerebrovascular responsiveness, decreased cerebral blood flow, and ultimately stroke. The central hypothesis will be tested by pursuing three specific aims: 1) describe changes in cerebrovascular responsiveness in HIV-associated TBM; 2) characterize the patterns of stroke in HIV-associated TBM and determine whether it is associated with vasculopathy and/or impairments in cerebrovascular responsiveness; and 3) determine if impaired cerebrovascular responsiveness predicts long- term neurological outcome in HIV-associated TBM. Under Aim 1, transcranial doppler will be used to take repeated measurements of the middle cerebral artery flow velocity and pulsatility index. A subset of study subjects will also have dynamic measurements made in response to stimuli (inhaled CO2, changes in blood pressure, and motor tasks). We will determine whether cerebrovascular responsiveness is impaired in HIV- associated TBM by comparing measurements to those of control patients with no neurological infection. Under Aim 2, all study subjects will have a brain MRI performed within the first 2-weeks of TBM treatment to identify the presence of a cerebral artery stroke and the associated cerebral artery territory. We will compare TCD readings between participants with or without stroke. Under Aim 3, we will examine how TCD measurements at study enrolment relate to the results of neurocognitive testing at month 2 and functional assessment at month 6. Ultimately, the long-term goal of the proposal is to describe how impaired cerebrovascular responsiveness in HIV-associated TBM contributes to the development of strokes and resulting neurocognitive impairment and disability. The research proposed in this application is innovative because it incorporates the use of transcranial doppler at the bedside, to be used in real time, in the care of subjects with TBM. The proposed research is significant because it is expected to provide strong scientific justification for the development of future clinical trials testing targeted interventions to improve cerebrovascular responsiveness and prevent the development of strokes in HIV-associated TBM. Ultimately, such knowledge has the potential of preventing the development of irreversible neurological injury and improving both short and long-term outcomes.

抽象的 结核性脑膜炎（TBM）不成比例地影响低收入国家和中等收入国家的人 与高发病和死亡率有关。中风是TBM的常见并发症，可能导致严重 不可逆的神经疾病。但是，关于与TBM相关的中风病理学的研究已集中 主要是关于艾滋病毒未感染的个体。该提案的总体目的是使用经颅多普勒和 脑成像以了解大脑血管和脑血流的变化，以确定 脑血管反应性的变化，表征中风模式并描述长期 与HIV相关的TBM中的神经认知结果。中心假设是在感染HIV的个体中 TBM导致广泛的脑血管狭窄和脑血管反应受损，降低 脑血流，最终中风。中心假设将通过追求三个具体目标来检验： 1）描述与HIV相关的TBM中脑血管反应的变化； 2）表征 与HIV相关的TBM中风，并确定它是否与血管病和/或损害相关 脑血管反应； 3）确定受损的脑血管反应能力是否可以预测长期 与HIV相关的TBM中的术语神经系统结果。在AIM 1下，将使用经颅多普勒来服用 重复测量中大脑中动脉流速度和脉动指数。研究子集 受试者还将对刺激进行动态测量（吸入CO2，血液的变化 压力和运动任务）。我们将确定HIV中的脑血管反应能力是否受损 通过将测量结果与没有神经系统感染的对照患者进行比较，相关的TBM。在下面 AIM 2，所有研究对象将在TBM治疗的前2周内进行大脑MRI 脑动脉中风和相关的脑动脉领土的存在。我们将比较TCD 有或没有中风的参与者之间的读数。在AIM 3下，我们将研究TCD测量 研究入学率与第2个月的神经认知测试的结果和每月的功能评估有关 6。最终，该提案的长期目标是描述脑血管反应受损 与HIV相关的TBM有助于中风的发展和导致的神经认知障碍和 残疾。本应用程序中提出的研究具有创新性，因为它结合了 床边的经颅多普勒，可实时使用TBM受试者。提议 研究之所以重要，是因为预计将为发展提供强有力的科学理由 未来的临床试验测试目标干预措施，以提高脑血管反应性并防止 艾滋病毒相关的TBM中风的发展。最终，这种知识有潜力 发展不可逆的神经损伤并改善短期和长期结局。