Background and aim: We determined to investigate the incidence and clinical impact of new cerebral microbleeds (CMBs) after intravenous thrombolysis (IVT) in patients with acute stroke.

Methods: The THAWS was a multicenter, randomized trial to study the efficacy and safety of IVT with alteplase in patients with wake-up stroke or unknown onset stroke. Prescheduled T2*-weighted imaging assessed CMBs at 3-time points: baseline, 22–36 hours, and 7–14 days. Outcomes included new CMBs 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.

Results: Of all 131 patients randomized in the THAWS trial, 113 patients (mean 74.3±12.6 years, 50 female, 62 allocated to IVT) were available for analysis. Overall, 46 (41%) had baseline CMBs (15 strictly lobar CMBs, 14 mixed CMBs, and 17 deep CMBs). New CMBs only emerged in the IVT group (7 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 CMBs (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 CMBs burden ≥5 (RR 44.9, 95%CI: 5.78–349.8) were associated with new CMBs. New CMBs was associated with an increase in NIHSS score (p=0.023). Treatment with alteplase in patients with baseline ≥5 CMBs 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 CMBs (common odds ratio 17.1, 95% CI: 0.76 –382.8). The association of baseline ≥5 CMBs with ordinal mRS score differed according to the treatment group (P interaction=0.042).

Conclusion: New CMBs developed within 36 h in 11% of the patients after IVT, and they were significantly associated with mixed-distribution and ≥5 CMBs. New CMBs development might impede neurological improvement. Furthermore, CMBs burden might affect the effect of alteplase.

背景和目的：我们决定调查急性卒中患者静脉溶栓 (IVT) 后新发脑微出血 (CMB) 的发生率和临床影响。

方法：THAWS 是一项多中心、随机试验，旨在研究 IVT 联合阿替普酶治疗清醒卒中或未知发病卒中患者的疗效和安全性。预定的 T2* 加权成像在 3 个时间点评估 CMB：基线、22-36 小时和 7-14 天。结果包括新的 CMBs 开发、90 天时改良的 Rankin 量表 [mRS] ≥ 3，以及美国国立卫生研究院中风量表 [NIHSS] 评分从 24 小时到 7 天的变化。

结果：在 THAWS 试验中随机分配的所有 131 名患者中，113 名患者（平均 74.3±12.6 岁，50 名女性，62 名分配到 IVT）可用于分析。总体而言，46 个（41%）有基线 CMB（15 个严格的叶状 CMB，14 个混合 CMB，17 个深部 CMB）。新的 CMB 仅在 IVT 组（7 名患者，11%）中出现，中位数为 28.3 小时，并且在中位数 7.35 天内没有额外增加。在调整后的模型中，CMB 的数量（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 CMB 负担≥ 5 (RR 44.9, 95%CI: 5.78-349.8) 与新的 CMB 相关联。新的 CMB 与 NIHSS 评分的增加相关（p=0.023）。基线≥5 CMB 的患者使用阿替普酶治疗导致序数 mRS 的结果向更差的数值转变（中位数 [IQR]；4 [3-4] vs. 0 [0 - 3]），与 <5 个 CMB 的患者相比（共同优势比 17.1，95% CI：0.76 - 382.8）。基线≥ 5 CMB 与序数mRS 评分的关联因治疗组而异（P 交互= 0.042）。

结论： 11% 的 IVT 患者在 36 小时内出现新的 CMB，并且它们与混合分布和≥5 CMB 显着相关。新的 CMB 的发展可能会阻碍神经系统的改善。此外，CMBs 负担可能会影响阿替普酶的作用。