Extending Window of IV TPA for Brainstein and Cerebeller Stroke

临床和病理研究表明，后脑，特别是脑干，有更大的 对缺血的耐受性强于前脑结构。在基底动脉血栓形成的患者中，就是这样 这一假说为目前的血运重建实践提供了理论基础，最长可达24小时 症状出现。如果对这些患者有好处，无论机制是什么(相对缺血耐受性， 侧支循环)，基底动脉分支有血栓的患者极有可能 也能从中受益。目前，tPA延迟再灌流的益处在任何一种人群中都未得到证实。 这一群体代表了大量的患者：10%到20%的缺血性中风位于 脑干或小脑。这项研究是一项试验性、单中心、随机、前瞻性、盲法安全性和 脑干发病后1小时内静脉注射0.9 mg/kg t-PA的可行性试验 和/或小脑缺血性中风。在计算机断层扫描排除出血后， 将进行磁共振(MR)检查以确认脑干和/或小脑中风。六十 患者将被随机平均分配到治疗组或对照组。主要安全端点将是 输液后36小时内出现症状性颅内出血。如果有神经性疾病，将进行CT扫描 衰落就会发生。本研究的次要目标是获得有关疗效的初步数据(目标2)。 记录输液后24小时、7-10天和90天的功能结果。这一速度 NIH卒中评分在24小时内提高8分，90天后功能恢复 治疗组间比较。将进行24小时重复磁共振扫描(血管再通， 所有患者在注射tPA后90天(最终梗死灶体积)和90天(最终梗死灶体积)的弥散加权成像(DWI)病变增长。经济增长的速度 24小时磁共振弥散加权成像病变体积，24小时MRA血管再通，最终病变体积和 90天后MR检查的病变生长情况将在不同组间进行比较。其他次要目标是调查 临床和影像预后预测指标(目标3)，并评估牛津郡标准的准确性 (目的4)用于脑干和小脑卒中患者的识别。这些数据将用于 设计并计划在这一患者群体中进行进一步的调查。

Clinical and pathological studies indicate that the hindbrain, particularly the brainstem, has a greater tolerance to ischemia than the forebrain structures. In patients with basilar artery thrombosis, it is this hypothesis that provides the rationale for the current practice of revascularization up to 24 hours after symptom onset. If there is a benefit for these patients, whatever the mechanism (relative ischemic tolerance, collateral circulation), it is very likely that patients with thrombus in the branches of the basilar artery would benefit as well. Currently, the benefit of such delayed reperfusion with tPA is unproven in either population. This group represents a large number of patients: 10 to 20% of all ischemic strokes are located in the brainstem or cerebellum. The study is a pilot, single-center, randomized, prospective, blinded safety and feasibility trial of 0.9 mg/kg iv t-PA given over one hour between 3 to 24 hours after onset of brainstem and/or cerebellar ischemic stroke. After a computed tomographic (CT) scan to exclude hemorrhage, a magnetic resonance (MR) study will be obtained to confirm brainstem and/or cerebellar stroke. Sixty patients will be randomized evenly to treatment or control arms. The primary safety endpoint will be symptomatic intracranial hemorrhage within 36 hours after infusion. CT scans will be obtained if neurological decline occurs. Secondary aims of the present study are to obtain preliminary data on efficacy (Aim 2). Twenty-four hour post infusion, 7-10 day, and 90-day functional outcome will be recorded. The rate of improvement by > 8 points on the NIH Stroke Scale at 24 hours and functional outcome at 90 days will be compared between treatment groups. Repeat MR scans will be obtained 24 hours (vessel recanalization, DWI lesion growth) and 90 days (final infarct volume) after tPA infusion in all patients. The rate growth of the DWI lesion volume on 24 hour MR, vessel recanalization by MRA at 24 hours, the final lesion volume and lesion growth at 90 day MR will be compared between groups. Other secondary aims are to investigate clinical and imaging predictors of outcome (Aim 3), and to assess the accuracy of the Oxfordshire criteria (Aim 4) for the identification of patients with brainstem and cerebellar stroke. These data will be used to design and plan further investigation in this patient population.