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

Andreas Charidimou; Toshio Imaizumi; Solene Moulin; Alexandro Biffi; Neshika Samarasekera; Yusuke Yakushiji; Andre Peeters; Yves Vandermeeren; Patrice Laloux; Jean-Claude Baron; Mar Hernandez-Guillamon; Joan Montaner; Barbara Casolla; Simone M Gregoire; Dong-Wha Kang; Jong S Kim; H Naka; Eric E Smith; Anand Viswanathan; Hans R Jäger; Rustam Al-Shahi Salman; Steven M Greenberg; Charlotte Cordonnier; David J Werring

doi:10.1212/WNL.0000000000004259

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

Neurology. 2017 Aug 22;89(8):820-829. doi: 10.1212/WNL.0000000000004259. Epub 2017 Jul 26.

Authors

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. [email protected].

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.

Publication types

Meta-Analysis
Review

MeSH terms

Brain / diagnostic imaging
Cerebral Hemorrhage / diagnostic imaging*
Cerebral Hemorrhage / epidemiology*
Humans
Magnetic Resonance Imaging
Recurrence
Risk

Abstract

Publication types

MeSH terms

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