Cerebral microbleeds development after stroke thrombolysis: A secondary analysis of the THAWS randomized clinical trial. Issue 6 (July 2022)

• Record Type: Journal Article
• Authors: Miwa, Kaori; Koga, Masatoshi; Inoue, Manabu; Yoshimura, Sohei; Sasaki, Makoto; Yakushiji, Yusuke; Fukuda-Doi, Mayumi; Okada, Yasushi; Nakase, Taizen; Ihara, Masafumi; Nagakane, Yoshinari; Takizawa, Shunya; Asakura, Koko; Aoki, Junya; Kimura, Kazumi; Yamamoto, Haruko; Toyoda, Kazunori
• Is Part Of: International journal of stroke. Volume 17:Issue 6(2022)
• Page Start: 628
• Page End: 636
• Publication Date: 2022-07
• Subjects: Ischemic stroke -- cerebral microbleeds -- thrombolysis -- cerebral small vessel disease; 616.8005
• DOI: 10.1177/17474930211035023
• Languages: English
• ISSNs: 1747-4930

Abstract

Background and aim: We determined to investigate the incidence and clinical impact of new cerebral microbleeds after intravenous thrombolysis in patients with acute stroke. Methods: 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. Results: 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 ( p = 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 ( p interaction = 0.042). Conclusion: 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.