Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Japan.
Institute for Biomedical Sciences, Iwate Medical University, Yahaba, Japan.
Int J Stroke. 2022 Jul;17(6):628-636. doi: 10.1177/17474930211035023. Epub 2021 Aug 3.
We determined to investigate the incidence and clinical impact of new cerebral microbleeds after intravenous thrombolysis in patients with acute stroke.
The THAWS was a multicenter, randomized trial to study the efficacy and safety of intravenous thrombolysis with alteplase in patients with wake-up stroke or unknown onset stroke. Prescheduled T2*-weighted imaging assessed cerebral microbleeds at three time points: baseline, 22-36 h, and 7-14 days. Outcomes included new cerebral microbleeds development, modified Rankin Scale (mRS) ≥3 at 90 days, and change in the National Institutes of Health Stroke Scale (NIHSS) score from 24 h to 7 days.
Of all 131 patients randomized in the THAWS trial, 113 patients (mean 74.3 ± 12.6 years, 50 female, 62 allocated to intravenous thrombolysis) were available for analysis. Overall, 46 (41%) had baseline cerebral microbleeds (15 strictly lobar cerebral microbleeds, 14 mixed cerebral microbleeds, and 17 deep cerebral microbleeds). New cerebral microbleeds only emerged in the intravenous thrombolysis group (seven patients, 11%) within a median of 28.3 h, and did not additionally increase within a median of 7.35 days. In adjusted models, number of cerebral microbleeds (relative risk (RR) 1.30, 95% confidence interval (CI): 1.17-1.44), mixed distribution (RR 19.2, 95% CI: 3.94-93.7), and cerebral microbleeds burden ≥5 (RR 44.9, 95% CI: 5.78-349.8) were associated with new cerebral microbleeds. New cerebral microbleeds were associated with an increase in NIHSS score ( = 0.023). Treatment with alteplase in patients with baseline ≥5 cerebral microbleeds resulted in a numerical shift toward worse outcomes on ordinal mRS (median [IQR]; 4 [3-4] vs. 0 [0-3]), compared with those with <5 cerebral microbleeds (common odds ratio 17.1, 95% CI: 0.76-382.8). The association of baseline ≥5 cerebral microbleeds with ordinal mRS score differed according to the treatment group ( interaction = 0.042).
New cerebral microbleeds developed within 36 h in 11% of the patients after intravenous thrombolysis, and they were significantly associated with mixed-distribution and ≥5 cerebral microbleeds. New cerebral microbleeds development might impede neurological improvement. Furthermore, cerebral microbleeds burden might affect the effect of alteplase.
我们旨在研究急性卒中患者静脉溶栓后新出现的脑微出血的发生率和临床影响。
THAWS 是一项多中心、随机试验，旨在研究阿替普酶静脉溶栓治疗觉醒性卒中或不明原因起病卒中患者的疗效和安全性。预设的 T2*-加权成像在三个时间点评估脑微出血：基线、22-36 小时和 7-14 天。结局包括新出现的脑微出血、90 天改良 Rankin 量表（mRS）评分≥3 分，以及 24 小时至 7 天内 NIHSS 评分的变化。
在 THAWS 试验中，所有 131 例随机分组的患者中，113 例（平均年龄 74.3±12.6 岁，50 例女性，62 例接受静脉溶栓治疗）可进行分析。总体而言，46 例（41%）患者基线存在脑微出血（15 例严格的脑叶微出血，14 例混合性脑微出血，17 例深部脑微出血）。静脉溶栓组仅在中位时间 28.3 小时后出现新的脑微出血（7 例，11%），且在中位时间 7.35 天内没有进一步增加。在调整模型中，脑微出血数量（相对风险（RR）1.30，95%置信区间（CI）：1.17-1.44）、混合分布（RR 19.2，95%CI：3.94-93.7）和脑微出血负荷≥5（RR 44.9，95%CI：5.78-349.8）与新出现的脑微出血相关。新出现的脑微出血与 NIHSS 评分的增加相关（ = 0.023）。基线存在≥5 个脑微出血的患者接受阿替普酶治疗后，其 ordinal mRS 评分的变化趋势更差（中位数[IQR]；4 [3-4] vs. 0 [0-3]），与基线脑微出血<5 个的患者相比（常见比值比 17.1，95%CI：0.76-382.8）。基线存在≥5 个脑微出血与 ordinal mRS 评分之间的相关性因治疗组而异（交互 = 0.042）。
静脉溶栓后 11%的患者在 36 小时内出现新的脑微出血，且其与混合分布和≥5 个脑微出血显著相关。新出现的脑微出血可能会阻碍神经功能的改善。此外，脑微出血负荷可能会影响阿替普酶的疗效。
