Supplementary Material for: Magnetic Resonance Imaging-Based versus Computed Tomography-Based Thrombolysis in Acute Ischemic Stroke: Comparison of Safety and Efficacy within a Cohort Study

Background: In acute ischemic stroke, brain imaging is mandatory in the decision whether to perform intravenous thrombolysis with recombinant tissue plasminogen activator. The most widespread used imaging modality to exclude intracranial hemorrhage is plain computed tomography (CT). However, there is an ongoing debate whether the information provided by magnetic resonance imaging (MRI) could improve the selection of patients for thrombolysis. We investigated whether the choice of imaging modality (MRI vs. CT) affects therapy safety and the patients' outcome. Methods: Analyses are based on data from a prospective, single-center observational study that included all patients with acute ischemic stroke who received intravenous thrombolysis within 4.5 h. Stroke severity was assessed by the National Institutes of Health Stroke Scale. Safety was assessed by rates of symptomatic intracranial hemorrhage (SICH), brain edema with mass effect and 7-day mortality. Outcome was assessed at 3 months as mortality and proportion of independent patients (modified Rankin Scale score between 0 and 2). Results: We analyzed 345 patients of whom 141 received multimodal MRI and 204 received plain CT prior to treatment. Groups did not differ significantly in terms of age, neurological deficit, rate of elevated glucose level or rate of very high blood pressure. However, patients with CT-based thrombolysis had significantly higher rates of cardiac comorbidities (coronary artery disease, heart failure). In the MRI group, we observed a lower rate of 7-day mortality (1 vs. 10%; p = 0.001), a lower rate of SICH (1 vs. 6%; p = 0.010) and a nonsignificantly lower rate of brain edema with mass effect (2 vs. 6%; n.s.). In multivariable analysis, 7-day mortality was independently associated with MRI-based thrombolysis, even if cardiac comorbidities were taken into account. For mortality at 3 months, there was a nonsignificant difference in favor of the MRI group (16 vs. 23%; n.s.). In multivariable analyses, mortality at 3 months was independently associated with older age, higher stroke severity, brain edema with mass effect, SICH, pneumonia and coronary artery disease. Neither mortality nor independent outcome was influenced by initial imaging modality. Conclusions: Thrombolysis based on multimodal MRI is associated with reduced rates of SICH and early death. Our results suggest that these complications affect survival principally in the acute phase after thrombolysis. However, nonneurological and especially cardiac comorbidities also influence survival after stroke and are underrepresented in stroke patients undergoing MRI. Selection bias has to be considered.研究背景：在急性缺血性脑卒中（acute ischemic stroke）的诊疗决策中，脑成像是判断是否采用重组组织型纤溶酶原激活剂（recombinant tissue plasminogen activator）行静脉溶栓的强制性检查项目。目前临床最常用于排除颅内出血（intracranial hemorrhage）的成像方式为平扫计算机断层扫描（computed tomography，CT）。然而，关于磁共振成像（magnetic resonance imaging，MRI）所提供的影像信息能否优化溶栓患者的筛选流程，目前仍存在广泛争议。本研究旨在探讨成像方式（MRI与CT）的选择是否会影响治疗安全性及患者预后。 研究方法：本项分析的数据来源于一项前瞻性单中心观察性研究，该研究纳入了发病4.5小时内接受静脉溶栓的所有急性缺血性脑卒中患者。采用美国国立卫生研究院卒中量表（National Institutes of Health Stroke Scale，NIHSS）评估卒中严重程度。安全性终点包括症状性颅内出血（symptomatic intracranial hemorrhage，SICH）发生率、伴占位效应的脑水肿发生率及7天死亡率；预后终点于发病3个月时评估，包括死亡率及功能独立患者占比（改良Rankin量表（modified Rankin Scale）评分0~2分）。 研究结果：本研究共纳入345例患者，其中141例于治疗前接受多模态MRI检查，204例接受平扫CT检查。两组患者在年龄、神经功能缺损程度、血糖升高发生率及重度高血压发生率方面均无显著差异。但接受CT引导溶栓的患者合并心脏疾病（冠状动脉粥样硬化性心脏病（coronary artery disease）、心力衰竭（heart failure））的比例显著更高。 MRI组的7天死亡率显著更低（1% vs. 10%；p=0.001），症状性颅内出血发生率显著更低（1% vs. 6%；p=0.010），伴占位效应的脑水肿发生率呈降低趋势但无统计学意义（2% vs. 6%）。多因素分析显示，即使校正心脏合并症因素，7天死亡率仍与MRI引导溶栓独立相关。 关于3个月死亡率，MRI组虽呈获益趋势但无统计学意义（16% vs. 23%）。多因素分析显示，3个月死亡率与年龄更大、卒中严重程度更高、伴占位效应的脑水肿、症状性颅内出血、肺炎及冠状动脉粥样硬化性心脏病独立相关。初始成像方式并未对死亡率或功能独立预后产生显著影响。 研究结论：基于多模态MRI的溶栓治疗与症状性颅内出血及早期死亡风险降低相关。本研究结果提示，上述并发症主要对溶栓后急性期的生存产生影响。但非神经系统合并症（尤其是心脏合并症）同样会影响卒中后生存，且在接受MRI检查的卒中患者中占比偏低。本研究需考虑选择偏倚的潜在影响。