Review

. 2017 Aug 22;89(8):820-829.

doi: 10.1212/WNL.0000000000004259. Epub 2017 Jul 26.

Brain hemorrhage recurrence, small vessel disease type, and cerebral microbleeds: A meta-analysis

Andreas Charidimou¹, Toshio Imaizumi¹, Solene Moulin¹, Alexandro Biffi¹, Neshika Samarasekera¹, Yusuke Yakushiji¹, Andre Peeters¹, Yves Vandermeeren¹, Patrice Laloux¹, Jean-Claude Baron¹, Mar Hernandez-Guillamon¹, Joan Montaner¹, Barbara Casolla¹, Simone M Gregoire¹, Dong-Wha Kang¹, Jong S Kim¹, H Naka¹, Eric E Smith¹, Anand Viswanathan¹, Hans R Jäger¹, Rustam Al-Shahi Salman¹, Steven M Greenberg¹, Charlotte Cordonnier¹, David J Werring²

Affiliations

¹ From the Stroke Research Centre (A.C., Y.Y., S.M.G., H.R.J., D.J.W.), Department of Brain Repair and Rehabilitation, UCL Institute of Neurology and The National Hospital for Neurology and Neurosurgery, Queen Square, London, UK; Hemorrhagic Stroke Research Program, Department of Neurology (A.C., A.B., E.E.S., A.V., S.M.G.), Massachusetts General Hospital Stroke Research Center, Harvard Medical School, Boston; Department of Neurosurgery (T.I.), Kushiro City General Hospital, Hokkaido, Japan; Degenerative & Vascular Cognitive Disorders (S.M., B.C., C.C.), Univ Lille, Inserm, CHU Lille, France; Centre for Clinical Brain Sciences (N.S., R.A.-S.S.), University of Edinburgh, UK; Department of Neurology (A.P.), Cliniques Universitaires UCL Saint Luc; Department of Neurology (Y.V., P.L.), CHU Dinant Godinne, Université Catholique de Louvain; Institute of Neuroscience (Y.V., P.L.), Université Catholique de Louvain, Brussels, Belgium; Department of Clinical Neurosciences (J.-C.B.), University of Cambridge, Addenbrooke's Hospital, UK; UMR 894 INSERM-Université Paris 5 (J.-C.B.), Sorbonne Paris Cité, Paris, France; Department of Neurology (M.H.-G., J.M.), Hospital Vall d'Hebron, Vall d'Hebron Research Institute, Universitat Autònoma de Barcelona, Spain; Department of Neurology (D.-W.K., J.S.K.), Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea; Department of Neurology (H.N.), Hiroshima Prefectural Hospital, Japan; and Hotchkiss Brain Institute (E.E.S.), University of Calgary, Canada.
² From the Stroke Research Centre (A.C., Y.Y., S.M.G., H.R.J., D.J.W.), Department of Brain Repair and Rehabilitation, UCL Institute of Neurology and The National Hospital for Neurology and Neurosurgery, Queen Square, London, UK; Hemorrhagic Stroke Research Program, Department of Neurology (A.C., A.B., E.E.S., A.V., S.M.G.), Massachusetts General Hospital Stroke Research Center, Harvard Medical School, Boston; Department of Neurosurgery (T.I.), Kushiro City General Hospital, Hokkaido, Japan; Degenerative & Vascular Cognitive Disorders (S.M., B.C., C.C.), Univ Lille, Inserm, CHU Lille, France; Centre for Clinical Brain Sciences (N.S., R.A.-S.S.), University of Edinburgh, UK; Department of Neurology (A.P.), Cliniques Universitaires UCL Saint Luc; Department of Neurology (Y.V., P.L.), CHU Dinant Godinne, Université Catholique de Louvain; Institute of Neuroscience (Y.V., P.L.), Université Catholique de Louvain, Brussels, Belgium; Department of Clinical Neurosciences (J.-C.B.), University of Cambridge, Addenbrooke's Hospital, UK; UMR 894 INSERM-Université Paris 5 (J.-C.B.), Sorbonne Paris Cité, Paris, France; Department of Neurology (M.H.-G., J.M.), Hospital Vall d'Hebron, Vall d'Hebron Research Institute, Universitat Autònoma de Barcelona, Spain; Department of Neurology (D.-W.K., J.S.K.), Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea; Department of Neurology (H.N.), Hiroshima Prefectural Hospital, Japan; and Hotchkiss Brain Institute (E.E.S.), University of Calgary, Canada. d.werring@ucl.ac.uk.

PMID: 28747441
PMCID: PMC5580863
DOI: 10.1212/WNL.0000000000004259

Review

Brain hemorrhage recurrence, small vessel disease type, and cerebral microbleeds: A meta-analysis

Andreas Charidimou et al. Neurology. 2017.

. 2017 Aug 22;89(8):820-829.

doi: 10.1212/WNL.0000000000004259. Epub 2017 Jul 26.

Authors

Affiliations

¹ From the Stroke Research Centre (A.C., Y.Y., S.M.G., H.R.J., D.J.W.), Department of Brain Repair and Rehabilitation, UCL Institute of Neurology and The National Hospital for Neurology and Neurosurgery, Queen Square, London, UK; Hemorrhagic Stroke Research Program, Department of Neurology (A.C., A.B., E.E.S., A.V., S.M.G.), Massachusetts General Hospital Stroke Research Center, Harvard Medical School, Boston; Department of Neurosurgery (T.I.), Kushiro City General Hospital, Hokkaido, Japan; Degenerative & Vascular Cognitive Disorders (S.M., B.C., C.C.), Univ Lille, Inserm, CHU Lille, France; Centre for Clinical Brain Sciences (N.S., R.A.-S.S.), University of Edinburgh, UK; Department of Neurology (A.P.), Cliniques Universitaires UCL Saint Luc; Department of Neurology (Y.V., P.L.), CHU Dinant Godinne, Université Catholique de Louvain; Institute of Neuroscience (Y.V., P.L.), Université Catholique de Louvain, Brussels, Belgium; Department of Clinical Neurosciences (J.-C.B.), University of Cambridge, Addenbrooke's Hospital, UK; UMR 894 INSERM-Université Paris 5 (J.-C.B.), Sorbonne Paris Cité, Paris, France; Department of Neurology (M.H.-G., J.M.), Hospital Vall d'Hebron, Vall d'Hebron Research Institute, Universitat Autònoma de Barcelona, Spain; Department of Neurology (D.-W.K., J.S.K.), Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea; Department of Neurology (H.N.), Hiroshima Prefectural Hospital, Japan; and Hotchkiss Brain Institute (E.E.S.), University of Calgary, Canada.
² From the Stroke Research Centre (A.C., Y.Y., S.M.G., H.R.J., D.J.W.), Department of Brain Repair and Rehabilitation, UCL Institute of Neurology and The National Hospital for Neurology and Neurosurgery, Queen Square, London, UK; Hemorrhagic Stroke Research Program, Department of Neurology (A.C., A.B., E.E.S., A.V., S.M.G.), Massachusetts General Hospital Stroke Research Center, Harvard Medical School, Boston; Department of Neurosurgery (T.I.), Kushiro City General Hospital, Hokkaido, Japan; Degenerative & Vascular Cognitive Disorders (S.M., B.C., C.C.), Univ Lille, Inserm, CHU Lille, France; Centre for Clinical Brain Sciences (N.S., R.A.-S.S.), University of Edinburgh, UK; Department of Neurology (A.P.), Cliniques Universitaires UCL Saint Luc; Department of Neurology (Y.V., P.L.), CHU Dinant Godinne, Université Catholique de Louvain; Institute of Neuroscience (Y.V., P.L.), Université Catholique de Louvain, Brussels, Belgium; Department of Clinical Neurosciences (J.-C.B.), University of Cambridge, Addenbrooke's Hospital, UK; UMR 894 INSERM-Université Paris 5 (J.-C.B.), Sorbonne Paris Cité, Paris, France; Department of Neurology (M.H.-G., J.M.), Hospital Vall d'Hebron, Vall d'Hebron Research Institute, Universitat Autònoma de Barcelona, Spain; Department of Neurology (D.-W.K., J.S.K.), Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea; Department of Neurology (H.N.), Hiroshima Prefectural Hospital, Japan; and Hotchkiss Brain Institute (E.E.S.), University of Calgary, Canada. d.werring@ucl.ac.uk.

PMID: 28747441
PMCID: PMC5580863
DOI: 10.1212/WNL.0000000000004259

Abstract

Objective: We evaluated recurrent intracerebral hemorrhage (ICH) risk in ICH survivors, stratified by the presence, distribution, and number of cerebral microbleeds (CMBs) on MRI (i.e., the presumed causal underlying small vessel disease and its severity).

Methods: This was a meta-analysis of prospective cohorts following ICH, with blood-sensitive brain MRI soon after ICH. We estimated annualized recurrent symptomatic ICH rates for each study and compared pooled odds ratios (ORs) of recurrent ICH by CMB presence/absence and presumed etiology based on CMB distribution (strictly lobar CMBs related to probable or possible cerebral amyloid angiopathy [CAA] vs non-CAA) and burden (1, 2-4, 5-10, and >10 CMBs), using random effects models.

Results: We pooled data from 10 studies including 1,306 patients: 325 with CAA-related and 981 CAA-unrelated ICH. The annual recurrent ICH risk was higher in CAA-related ICH vs CAA-unrelated ICH (7.4%, 95% confidence interval [CI] 3.2-12.6 vs 1.1%, 95% CI 0.5-1.7 per year, respectively; p = 0.01). In CAA-related ICH, multiple baseline CMBs (versus none) were associated with ICH recurrence during follow-up (range 1-3 years): OR 3.1 (95% CI 1.4-6.8; p = 0.006), 4.3 (95% CI 1.8-10.3; p = 0.001), and 3.4 (95% CI 1.4-8.3; p = 0.007) for 2-4, 5-10, and >10 CMBs, respectively. In CAA-unrelated ICH, only >10 CMBs (versus none) were associated with recurrent ICH (OR 5.6, 95% CI 2.1-15; p = 0.001). The presence of 1 CMB (versus none) was not associated with recurrent ICH in CAA-related or CAA-unrelated cohorts.

Conclusions: CMB burden and distribution on MRI identify subgroups of ICH survivors with higher ICH recurrence risk, which may help to predict ICH prognosis with relevance for clinical practice and treatment trials.

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Figures

**Figure 1. Flow chart of study selection**

**Figure 2. Pooled risks of recurrent symptomatic intracerebral hemorrhage (ICH) during follow-up in included studies**
Weights are shown by the point estimate area. CAA = cerebral amyloid angiopathy; CI = confidence interval; rICH = recurrent ICH.

Figure 3. Meta-analysis of the associations between cerebral microbleeds (CMBs) presence or burden and the risk of recurrent symptomatic spontaneous intracerebral hemorrhage (ICH) in cerebral amyloid angiopathy (CAA)–unrelated ICH cohorts
Weights are shown by the point estimate area. I² is used to test statistical heterogeneity between the subgroup pooled estimates across the different studies. CI = confidence interval; OR = odds ratio.

Figure 4. Meta-analysis of the associations between cerebral microbleeds (CMBs) presence or burden and the risk of recurrent spontaneous intracerebral hemorrhage (ICH) in cerebral amyloid angiopathy (CAA)–related ICH cohorts
Weights are shown by the point estimate area. I² is used to test statistical heterogeneity between the subgroup pooled estimates across the different studies. CI = confidence interval; OR = odds ratio.

See this image and copyright information in PMC

References

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Brain hemorrhage recurrence, small vessel disease type, and cerebral microbleeds: A meta-analysis

Affiliations

Brain hemorrhage recurrence, small vessel disease type, and cerebral microbleeds: A meta-analysis

Authors

Affiliations

Abstract

Figures

References

Publication types

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources

Medical