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Updated: Feb 26, 2026
A Fibrin-Enriched and tPA-Sensitive Photothrombotic Stroke Model
Published on: June 4, 2021
Microbleeds, Cerebral Hemorrhage, and Functional Outcome After Stroke Thrombolysis
Andreas Charidimou1, Guillaume Turc1, Catherine Oppenheim1
1From the Stroke Research Centre, UCL Institute of Neurology, London, United Kingdom (A.C., D.W., D.J.W.); Hemorrhagic Stroke Research Group, Massachusetts General Hospital, Boston (A.C.); Departments of Neurology and Radiology, Hôpital Sainte-Anne, Université Paris Descartes, France (G.T., C.O., M.E.-G., J.-C.B.); Department of Neurology, the 2nd Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou, China (S.Y., M.L.); Department of Neurology and Center for Stroke Research, Charite Universitätsmedizin, Berlin, Germany (J.F.S., H.E., C.H.N.); Department of Diagnostic and Interventional Neuroradiology, and Neurology, Inselspital, University Hospital Bern, Switzerland (P.P.K.-G., M.E.-K., H.P.M., S.J.); Department of Neurology, Tokai University School of Medicine, Japan (W.T., Y.M., S.T.); Department of Neurology, University of Arizona, Tucson (C.S.K.); UCLA Comprehensive Stroke Center, Geffen School of Medicine, Los Angeles (J.L.S.); Univ. Lille, Inserm, CHU Lille, U1171, Degenerative and Vascular Cognitive Disorders, France (A.S., S.M., C.C.); Department of Neurology, Austin Health and Florey Institute, Heidelberg, Victoria, Australia (V.T.); Department of Statistical Science, University College London, United Kingdom (Z.F., G.A.); Department of Medicine (Neurology), McMaster University and Population Health Research Institute, Hamilton, Ontario, Canada (A.S.); Stanford Stroke Center, Palo Alto, CA (G.W.A.); Division of Neurology, Stroke and Cerebrovascular Health Program, University of British Columbia Hospital, Vancouver, Canada (O.R.B.); Lysholm Department of Neuroradiology, National Hospital, London, United Kingdom (H.R.J.); Department of Neurological Science, Nippon Medical School Graduate School of Medicine, Tokyo, Japan (J.A., K.K.); and Department of Rehabilitation Medicine, the Jikei University School of Medicine, Tokyo, Japan (W.K.).
Abstract:
Background and Purpose- We assessed whether the presence, number, and distribution of cerebral microbleeds (CMBs) on pre-intravenous thrombolysis MRI scans of acute ischemic stroke patients are associated with an increased risk of intracerebral hemorrhage (ICH) or poor functional outcome. Methods- We performed an individual patient data meta-analysis, including prospective and retrospective studies of acute ischemic stroke treated with intravenous tissue-type plasminogen activator. Using multilevel mixed-effects logistic regression, we investigated associations of pre-treatment CMB presence, burden (1, 2-4, ≥5, and >10), and presumed pathogenesis (cerebral amyloid angiopathy defined as strictly lobar CMBs and noncerebral amyloid angiopathy) with symptomatic ICH, parenchymal hematoma (within [parenchymal hemorrhage, PH] and remote from the ischemic area [remote parenchymal hemorrhage, PHr]), and poor 3- to 6-month functional outcome (modified Rankin score >2). Results- In 1973 patients from 8 centers, the crude prevalence of CMBs was 526 of 1973 (26.7%). A total of 77 of 1973 (3.9%) patients experienced symptomatic ICH, 210 of 1806 (11.6%) experienced PH, and 56 of 1720 (3.3%) experienced PHr. In adjusted analyses, patients with CMBs (compared with those without CMBs) had increased risk of PH (odds ratio: 1.50; 95% confidence interval: 1.09-2.07; P=0.013) and PHr (odds ratio: 3.04; 95% confidence interval: 1.73-5.35; P<0.001) but not symptomatic ICH. Both cerebral amyloid angiopathy and noncerebral amyloid angiopathy patterns of CMBs were associated with PH and PHr. Increasing CMB burden category was associated with the risk of symptomatic ICH ( P=0.014), PH ( P=0.013), and PHr ( P<0.00001). Five or more and >10 CMBs independently predicted poor 3- to 6-month outcome (odds ratio: 1.85; 95% confidence interval: 1.10-3.12; P=0.020; and odds ratio: 3.99; 95% confidence interval: 1.55-10.22; P=0.004, respectively). Conclusions- Increasing CMB burden is associated with increased risk of ICH (including PHr) and poor 3- to 6-month functional outcome after intravenous thrombolysis for acute ischemic stroke.
Insights
The number of cerebral microbleeds (CMBs) in acute ischemic stroke patients before IV thrombolysis predicts hemorrhage risk and poor outcomes. Higher CMB burden increases the likelihood of parenchymal hemorrhage and worse functional status post-treatment.
Area of Science:
- Neurology
- Radiology
- Stroke Medicine
Background:
- Cerebral microbleeds (CMBs) are common in acute ischemic stroke patients.
- The association between CMBs and outcomes after intravenous thrombolysis requires further investigation.
Purpose of the Study:
- To assess if CMBs on pre-treatment MRI predict intracerebral hemorrhage (ICH) or poor functional outcomes in acute ischemic stroke patients receiving intravenous thrombolysis.
- To determine the impact of CMB number, distribution, and presumed pathogenesis on these risks.
Main Methods:
- Individual patient data meta-analysis of prospective and retrospective studies.
- Inclusion of acute ischemic stroke patients treated with intravenous tissue-type plasminogen activator.
- Multilevel mixed-effects logistic regression to analyze CMB presence, burden, and patterns against symptomatic ICH, parenchymal hemorrhage (PH), remote parenchymal hemorrhage (PHr), and poor functional outcome (modified Rankin score >2).
Main Results:
- CMBs were present in 26.7% of 1973 patients.
- CMB presence was associated with increased risk of PH (OR 1.50) and PHr (OR 3.04), but not symptomatic ICH.
- Increasing CMB burden (≥5 or >10) independently predicted poor 3- to 6-month functional outcomes (ORs 1.85 and 3.99, respectively).
Conclusions:
- Higher cerebral microbleed burden is linked to a greater risk of intracerebral hemorrhage, including remote parenchymal hemorrhage.
- Increased CMB burden is an independent predictor of poor functional outcomes 3-6 months after intravenous thrombolysis for acute ischemic stroke.
