Mechanisms of Stroke in Intracranial Stenosis and Stenting(MoSISS)

描述（由申请人提供）：脑卒中在颅内狭窄和支架置入中的机制（MoSISS）该提案是SAMMPRIS的一项前瞻性多中心辅助研究，SAMMPRIS是一项正在进行的NIH资助的试验，评估颅内支架置入加强化药物治疗与单独强化药物治疗对近期出现症状的高度颅内狭窄的疗效。该应用程序的目的是了解支架和非支架患者缺血性卒中的机制，因为机制方面和相关成像分析未纳入SAMMPRIS。这项建议的结果将有助于确定预测中风风险的适当参数，并可能导致新的治疗方法来解决中风的特定机制。我们的主要假设是颅内动脉粥样硬化中缺血性梗死的几种机制。该提案将评估SAMMPRIS队列样本中中风的6种特定机制：顺行血流减少、狭窄进展、近侧支血流减少、远侧支血流减少、脑血管储备受损和动脉-动脉栓塞。主要结果将是有症状的动脉区域发生缺血性卒中，这是SAMMPRIS研究的一个主要终点。在SAMMPRIS研究中，共有100名接受医学治疗的患者和50名接受支架治疗的患者将采用3种成像方式进行研究，包括：A)在SAMMPRIS随机分组之前进行常规血管造影；b)基线QMRA评估容量流速，作为顺行血流和近侧支血流的标志；c)连续TCD测量基线、4、8、12、24个月以及缺血性脑卒中发生时的血流速度；d)基线TCD检测颅内颈动脉或大脑中动脉狭窄患者的栓塞信号；e)基线TCD伴屏气评估颅内颈动脉或大脑中动脉狭窄患者的血管舒缩反应性。

DESCRIPTION (provided by applicant): Mechanisms of Stroke in Intracranial Stenosis and Stenting (MoSISS) This proposal is a prospective multi-center ancillary study to SAMMPRIS, an ongoing NIH- funded trial that evaluates intracranial stenting plus intensive medical therapy versus intensive medical therapy alone for recently symptomatic high-grade intracranial stenosis. The objective of this application is to understand the mechanisms that underlie ischemic stroke in stented and non-stented patients, as mechanistic aspects and related imaging analyses are not incorporated in SAMMPRIS. The results of this proposal will help define the appropriate parameters that predict stroke risk and may lead to novel therapeutics to address specific mechanisms of stroke. Our primary hypothesis is that several mechanisms underlie ischemic infarction in intracranial atherosclerosis. This proposal will evaluate 6 specific mechanisms of stroke in a sample of the SAMMPRIS cohort: decreased antegrade flow, progression of stenosis, decreased proximal collateral flow, decreased distal collateral flow, impaired cerebrovascular reserve, and artery-artery embolism. The main outcome will be ischemic stroke occurrence in the territory of the symptomatic artery, a principal endpoint in the SAMMPRIS study. A total of 100 medically-treated and 50 stented patients enrolled in the SAMMPRIS study will be studied with 3 imaging modalities, including: a) conventional angiography performed prior to randomization in SAMMPRIS; b) baseline QMRA to assess volumetric flow rate as a marker of antegrade flow and proximal collateral flow; c) serial TCD to measure flow velocities at baseline, 4, 8, 12 and 24 months, and at the time of ischemic stroke occurrence; d) baseline TCD to detect embolic signals in patients with intracranial carotid or middle cerebral artery stenosis; and e) baseline TCD with breath-holding to assess vasomotor reactivity in patients with intracranial carotid or middle cerebral artery stenosis. PUBLIC HEALTH RELEVANCE: Lay Summary: Mechanisms of Stroke in Intracranial Stenosis and Stenting (MoSISS) MoSISS is an ancillary study to the ongoing Stenting and Aggressive Medical Management for Preventing Recurrent stroke in Intracranial Stenosis (SAMMPRIS) study. Narrowing of the brain arteries due to plaque formation (intracranial atherosclerotic disease) is a common cause of stroke. The risk of stroke recurrence is significant, particularly in those with greater than 70% narrowing, even with medical therapy. Because of this, SAMMPRIS is evaluating stenting plus intensive medical therapy vs. intensive medical therapy alone. The objective of this proposal is to understand the causes of stroke in those with narrowed brain arteries and stented brain arteries through the use of non-invasive imaging tests such as ultrasound and MRI.