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) 对低收入和中等收入国家的人民造成不成比例的影响，并且 与高发病率和死亡率相关。中风是 TBM 的常见并发症，可导致严重的并发症 不可逆的神经功能障碍。然而，与 TBM 相关的中风病理学研究主要集中在 主要针对未感染艾滋病毒的个体。该提案的总体目标是使用经颅多普勒和 脑成像以了解脑血管和脑血流量的变化，以确定 脑血管反应性的变化，描述中风的模式，并描述长期 HIV 相关 TBM 中的神经认知结果。中心假设是，在艾滋病毒感染者中， TBM 导致广泛的脑血管狭窄和脑血管反应性受损，降低 脑血流量减少，最终导致中风。中心假设将通过追求三个具体目标来检验： 1) 描述 HIV 相关 TBM 中脑血管反应性的变化； 2）表征模式 HIV 相关 TBM 中的卒中，并确定其是否与血管病变和/或损伤相关 脑血管反应性； 3）确定脑血管反应性受损是否预示着长期 HIV 相关 TBM 的长期神经学结果。在目标 1 下，将使用经颅多普勒仪 重复测量大脑中动脉血流速度和搏动指数。研究的一个子集 受试者还将针对刺激（吸入二氧化碳、血液变化）进行动态测量 压力和运动任务）。我们将确定 HIV 感染者的脑血管反应性是否受损 通过将测量值与没有神经系统感染的对照患者的测量值进行比较，将 TBM 相关联。在下面 目标 2，所有研究对象将在 TBM 治疗的前 2 周内进行脑部 MRI 检查，以确定 存在脑动脉中风和相关的脑动脉区域。我们将比较TCD 有或没有中风的参与者之间的读数。在目标 3 下，我们将研究 TCD 测量如何 研究入组与第 2 个月的神经认知测试结果和第 1 个月的功能评估结果相关 6. 最终，该提案的长期目标是描述脑血管反应性受损如何 HIV 相关的 TBM 会导致中风的发生并导致神经认知障碍和 残疾。本申请中提出的研究具有创新性，因为它结合了使用 床边经颅多普勒实时使用，用于 TBM 受试者的护理。拟议的 研究意义重大，因为它有望为开发提供强有力的科学依据 未来的临床试验将测试有针对性的干预措施，以改善脑血管反应性并预防 HIV 相关 TBM 中卒中的发生。最终，这些知识有可能防止 不可逆神经损伤的发展并改善短期和长期结果。