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September 15, 2015; 85 (11) Article

Cerebral microbleeds and postthrombolysis intracerebral hemorrhage risk

Updated meta-analysis

Andreas Charidimou, Ashkan Shoamanesh, Duncan Wilson, Qiang Gang, Zoe Fox, H. Rolf Jäger, Oscar R. Benavente, David J. Werring
First published August 21, 2015, DOI: https://doi.org/10.1212/WNL.0000000000001923
Andreas Charidimou
From the UCL Stroke Research Centre (A.C., D.W., Q.G., D.J.W.) and Neuroradiological Academic Unit (H.R.J.), Department of Brain Repair and Rehabilitation, UCL Institute of Neurology and the National Hospital for Neurology and Neurosurgery, London, UK; Department of Medicine (Neurology) (A.S.), McMaster University and Population Health Research Institute, Hamilton, Canada; Biomedical Research Centre (Z.F.), UCL and the Education Unit, UCL Institute of Neurology, London, UK; and Division of Neurology (O.R.B.), Department of Medicine, Stroke and Cerebrovascular Health Program, University of British Columbia, UBC Hospital, Vancouver, Canada.
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Ashkan Shoamanesh
From the UCL Stroke Research Centre (A.C., D.W., Q.G., D.J.W.) and Neuroradiological Academic Unit (H.R.J.), Department of Brain Repair and Rehabilitation, UCL Institute of Neurology and the National Hospital for Neurology and Neurosurgery, London, UK; Department of Medicine (Neurology) (A.S.), McMaster University and Population Health Research Institute, Hamilton, Canada; Biomedical Research Centre (Z.F.), UCL and the Education Unit, UCL Institute of Neurology, London, UK; and Division of Neurology (O.R.B.), Department of Medicine, Stroke and Cerebrovascular Health Program, University of British Columbia, UBC Hospital, Vancouver, Canada.
MD
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Duncan Wilson
From the UCL Stroke Research Centre (A.C., D.W., Q.G., D.J.W.) and Neuroradiological Academic Unit (H.R.J.), Department of Brain Repair and Rehabilitation, UCL Institute of Neurology and the National Hospital for Neurology and Neurosurgery, London, UK; Department of Medicine (Neurology) (A.S.), McMaster University and Population Health Research Institute, Hamilton, Canada; Biomedical Research Centre (Z.F.), UCL and the Education Unit, UCL Institute of Neurology, London, UK; and Division of Neurology (O.R.B.), Department of Medicine, Stroke and Cerebrovascular Health Program, University of British Columbia, UBC Hospital, Vancouver, Canada.
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Qiang Gang
From the UCL Stroke Research Centre (A.C., D.W., Q.G., D.J.W.) and Neuroradiological Academic Unit (H.R.J.), Department of Brain Repair and Rehabilitation, UCL Institute of Neurology and the National Hospital for Neurology and Neurosurgery, London, UK; Department of Medicine (Neurology) (A.S.), McMaster University and Population Health Research Institute, Hamilton, Canada; Biomedical Research Centre (Z.F.), UCL and the Education Unit, UCL Institute of Neurology, London, UK; and Division of Neurology (O.R.B.), Department of Medicine, Stroke and Cerebrovascular Health Program, University of British Columbia, UBC Hospital, Vancouver, Canada.
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Zoe Fox
From the UCL Stroke Research Centre (A.C., D.W., Q.G., D.J.W.) and Neuroradiological Academic Unit (H.R.J.), Department of Brain Repair and Rehabilitation, UCL Institute of Neurology and the National Hospital for Neurology and Neurosurgery, London, UK; Department of Medicine (Neurology) (A.S.), McMaster University and Population Health Research Institute, Hamilton, Canada; Biomedical Research Centre (Z.F.), UCL and the Education Unit, UCL Institute of Neurology, London, UK; and Division of Neurology (O.R.B.), Department of Medicine, Stroke and Cerebrovascular Health Program, University of British Columbia, UBC Hospital, Vancouver, Canada.
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H. Rolf Jäger
From the UCL Stroke Research Centre (A.C., D.W., Q.G., D.J.W.) and Neuroradiological Academic Unit (H.R.J.), Department of Brain Repair and Rehabilitation, UCL Institute of Neurology and the National Hospital for Neurology and Neurosurgery, London, UK; Department of Medicine (Neurology) (A.S.), McMaster University and Population Health Research Institute, Hamilton, Canada; Biomedical Research Centre (Z.F.), UCL and the Education Unit, UCL Institute of Neurology, London, UK; and Division of Neurology (O.R.B.), Department of Medicine, Stroke and Cerebrovascular Health Program, University of British Columbia, UBC Hospital, Vancouver, Canada.
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Oscar R. Benavente
From the UCL Stroke Research Centre (A.C., D.W., Q.G., D.J.W.) and Neuroradiological Academic Unit (H.R.J.), Department of Brain Repair and Rehabilitation, UCL Institute of Neurology and the National Hospital for Neurology and Neurosurgery, London, UK; Department of Medicine (Neurology) (A.S.), McMaster University and Population Health Research Institute, Hamilton, Canada; Biomedical Research Centre (Z.F.), UCL and the Education Unit, UCL Institute of Neurology, London, UK; and Division of Neurology (O.R.B.), Department of Medicine, Stroke and Cerebrovascular Health Program, University of British Columbia, UBC Hospital, Vancouver, Canada.
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David J. Werring
From the UCL Stroke Research Centre (A.C., D.W., Q.G., D.J.W.) and Neuroradiological Academic Unit (H.R.J.), Department of Brain Repair and Rehabilitation, UCL Institute of Neurology and the National Hospital for Neurology and Neurosurgery, London, UK; Department of Medicine (Neurology) (A.S.), McMaster University and Population Health Research Institute, Hamilton, Canada; Biomedical Research Centre (Z.F.), UCL and the Education Unit, UCL Institute of Neurology, London, UK; and Division of Neurology (O.R.B.), Department of Medicine, Stroke and Cerebrovascular Health Program, University of British Columbia, UBC Hospital, Vancouver, Canada.
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Citation
Cerebral microbleeds and postthrombolysis intracerebral hemorrhage risk
Updated meta-analysis
Andreas Charidimou, Ashkan Shoamanesh, Duncan Wilson, Qiang Gang, Zoe Fox, H. Rolf Jäger, Oscar R. Benavente, David J. Werring
Neurology Sep 2015, 85 (11) 927-934; DOI: 10.1212/WNL.0000000000001923

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Abstract

Objective: We performed a systematic review and meta-analysis to assess whether the presence of cerebral microbleeds (CMBs) on pretreatment MRI scans of patients with acute ischemic stroke treated with thrombolysis is associated with an increased risk of symptomatic intracerebral hemorrhage (ICH).

Methods: We searched PubMed for relevant studies and calculated pooled odds ratios (ORs) for symptomatic ICH, using the Mantel–Haenszel fixed-effects method, among individuals with vs without CMBs on pretreatment MRI scans. To minimize potential bias, sensitivity analysis was performed including studies providing data on patients treated only with IV thrombolysis.

Results: Ten eligible studies including 2,028 patients were pooled in meta-analysis. The overall prevalence of CMBs was 23.3%. Among patients with CMBs, 40 of 472 (8.5%; 95% confidence interval [CI]: 6.1%–11.4%) experienced a symptomatic ICH after thrombolysis compared with 61 of 1,556 patients (3.9%; 95% CI: 3%–5%) without CMBs. The pooled OR of ICH across all studies was 2.26 (95% CI: 1.46–3.49; p < 0.0001). Eight studies, including 1,704 patients (n = 401 with CMBs), provided data on patients treated with IV thrombolysis only; OR for the presence of CMBs and the development of symptomatic ICH was 2.87 (95% CI: 1.76–4.69; p < 0.0001).

Conclusions: Our meta-analysis of the available published data demonstrates an increased risk of symptomatic ICH after thrombolysis for acute ischemic stroke in patients with CMBs. However, we cannot fully exclude bias or confounding, so our results should be considered hypothesis-generating. Detecting CMBs should not prevent thrombolytic treatment based on present evidence. Further analyses, taking into account CMB number and location, as well as measures of functional outcome, are needed.

GLOSSARY

CI=
confidence interval;
CMB=
cerebral microbleed;
ICH=
intracerebral hemorrhage;
OR=
odds ratio;
rtPA=
recombinant tissue plasminogen activator;
SWI=
susceptibility-weighted imaging

Footnotes

  • Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Supplemental data at Neurology.org

  • Editorial, page 925

  • Received December 1, 2014.
  • Accepted in final form April 23, 2015.
  • © 2015 American Academy of Neurology
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Letters: Rapid online correspondence

  • Author Response: Cerebral microbleeds and postthrombolysis intracerebral hemorrhage risk: Updated meta-analysis
    • Andreas Charidimou, Post-doctoral research fellow, UCL Institute of Neurology and The National Hospital for Neurology and Neurosurgery, Queen Square, L[email protected]
    • David Werring, UCL Institute of Neurology and The National Hospital for Neurology and Neurosurgery, Queen Square, London WC1N 3BG, UK
    Submitted December 08, 2015
  • Cerebral microbleeds and postthrombolysis intracerebral hemorrhage risk: Updated meta-analysis
    • Manuel Cappellari, Stroke Consultant, Stroke Unit, Department of Neuroscience, Azienda Ospedaliera Universitaria Integrata Verona[email protected]
    • Paolo Bovi, Verona, Italy
    Submitted September 25, 2015
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