Kaori Miwa1, Masatoshi Koga1, Manabu Inoue1, Sohei Yoshimura1, Makoto Sasaki2, Yusuke Yakushiji3,4, Mayumi Fukuda-Doi1,5, Yasushi Okada6, Taizen Nakase7, Masafumi Ihara8, Yoshinari Nagakane9, Shunya Takizawa10, Koko Asakura5, Junya Aoki11, Kazumi Kimura12, Haruko Yamamoto5, Kazunori Toyoda1. 1. Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Japan. 2. Institute for Biomedical Sciences, Iwate Medical University, Yahaba, Japan. 3. Division of Neurology, Department of Internal Medicine, Saga University Faculty of Medicine, Saga, Japan. 4. Department of Neurology, Kansai Medical University, Hirakata, Japan. 5. Center for Advancing Clinical and Translational Sciences, National Cerebral and Cardiovascular Center, Suita, Japan. 6. Department of Cerebrovascular Medicine and Neurology, Cerebrovascular Center, National Hospital Organization Kyushu Medical Center, Fukuoka, Japan. 7. Department of Stroke Science, Research Institute for Brain and Blood Vessels, Akita, Japan. 8. Department of Neurology, National Cerebral and Cardiovascular Center, Suita, Japan. 9. Department of Neurology, Kyoto Second Red Cross Hospital, Kyoto, Japan. 10. 0Division of Neurology, Department of Internal Medicine, Tokai University School of Medicine, Isehara, Japan. 11. 1Department of Neurology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan. 12. Department of Neurology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan.
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.
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.
Entities:
Keywords:
Ischemic stroke; cerebral microbleeds; cerebral small vessel disease; thrombolysis
Authors: Tim Bastian Braemswig; Jan Vynckier; Märit Jensen; Florent Boutitie; Ivana Galinovic; Claus Z Simonsen; Bastian Cheng; Tae-Hee Cho; Jan F Scheitz; Jens Fiehler; Josep Puig; Vincent Thijs; Jochen B Fiebach; Keith W Muir; Norbert Nighoghossian; Martin Ebinger; Salvador Pedraza; Götz Thomalla; Christian Gerloff; Matthias Endres; Robin Lemmens; Ludwig Schlemm; Christian H Nolte Journal: J Neurol Date: 2022-05-19 Impact factor: 6.682