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, 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

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.

Copyright © 2017 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

Figures

Figure 1. Flow chart of study selection
Figure 1. Flow chart of study selection
Figure 2. Pooled risks of recurrent symptomatic…
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…
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…
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.

References

    1. Wardlaw JM, Smith EE, Biessels GJ, et al. . Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration. Lancet Neurol 2013;12:822–838.
    1. Poon MT, Fonville AF, Al-Shahi Salman R. Long-term prognosis after intracerebral haemorrhage: systematic review and meta-analysis. J Neurol Neurosurg Psychiatry 2014;85:660–667.
    1. Pantoni L. Cerebral small vessel disease: from pathogenesis and clinical characteristics to therapeutic challenges. Lancet Neurol 2010;9:689–701.
    1. Charidimou A, Gang Q, Werring DJ. Sporadic cerebral amyloid angiopathy revisited: recent insights into pathophysiology and clinical spectrum. J Neurol Neurosurg Psychiatry 2012;83:124–137.
    1. Viswanathan A, Greenberg SM. Cerebral amyloid angiopathy in the elderly. Ann Neurol 2011;70:871–880.
    1. Samarasekera N, Smith C, Al-Shahi Salman R. The association between cerebral amyloid angiopathy and intracerebral haemorrhage: systematic review and meta-analysis. J Neurol Neurosurg Psychiatry 2012;83:275–281.
    1. Bailey RD, Hart RG, Benavente O, Pearce LA. Recurrent brain hemorrhage is more frequent than ischemic stroke after intracranial hemorrhage. Neurology 2001;56:773–777.
    1. Viswanathan A, Rakich SM, Engel C, et al. . Antiplatelet use after intracerebral hemorrhage. Neurology 2006;66:206–209.
    1. Weimar C, Benemann J, Terborg C, Walter U, Weber R, Diener HC. Recurrent stroke after lobar and deep intracerebral hemorrhage: a hospital-based cohort study. Cerebrovasc Dis 2011;32:283–288.
    1. Hill MD, Silver FL, Austin PC, Tu JV. Rate of stroke recurrence in patients with primary intracerebral hemorrhage. Stroke 2000;31:123–127.
    1. Greenberg SM, Vernooij MW, Cordonnier C, et al. . Cerebral microbleeds: a guide to detection and interpretation. Lancet Neurol 2009;8:165–174.
    1. Lee SH, Ryu WS, Roh JK. Cerebral microbleeds are a risk factor for warfarin-related intracerebral hemorrhage. Neurology 2009;72:171–176.
    1. Cordonnier C, Al-Shahi Salman R, Wardlaw J. Spontaneous brain microbleeds: systematic review, subgroup analyses and standards for study design and reporting. Brain 2007;130:1988–2003.
    1. Charidimou A, Werring DJ. Cerebral microbleeds as a predictor of macrobleeds: what is the evidence? Int J Stroke 2014;9:457–459.
    1. Lee SH, Bae HJ, Kwon SJ, et al. . Cerebral microbleeds are regionally associated with intracerebral hemorrhage. Neurology 2004;62:72–76.
    1. Linn J, Halpin A, Demaerel P, et al. . Prevalence of superficial siderosis in patients with cerebral amyloid angiopathy. Neurology 2010;74:1346–1350.
    1. Knudsen KA, Rosand J, Karluk D, Greenberg SM. Clinical diagnosis of cerebral amyloid angiopathy: validation of the Boston criteria. Neurology 2001;56:537–539.
    1. DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials 1986;7:177–188.
    1. Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ 2009;339:b2535.
    1. Charidimou A, Peeters AP, Jager R, et al. . Cortical superficial siderosis and intracerebral hemorrhage risk in cerebral amyloid angiopathy. Neurology 2013;81:1666–1673.
    1. Kang DW, Han MK, Kim HJ, et al. . New ischemic lesions coexisting with acute intracerebral hemorrhage. Neurology 2012;79:848–855.
    1. Imaizumi T, Inamura S, Kohama I, et al. . Antithrombotic drug uses and deep intracerebral hemorrhages in stroke patients with deep cerebral microbleeds. J Stroke Cerebrovasc Dis 2013;22:869–875.
    1. Domingues-Montanari S, Hernandez-Guillamon M, Fernandez-Cadenas I, et al. . ACE variants and risk of intracerebral hemorrhage recurrence in amyloid angiopathy. Neurobiol Aging 2011;32:551 e13–551.e22.
    1. Biffi A, Halpin A, Towfighi A, et al. . Aspirin and recurrent intracerebral hemorrhage in cerebral amyloid angiopathy. Neurology 2010;75:693–698.
    1. Jeon SB, Kang DW, Cho AH, et al. . Initial microbleeds at MR imaging can predict recurrent intracerebral hemorrhage. J Neurol 2007;254:508–512.
    1. Naka H, Nomura E, Takahashi T, et al. . Combinations of the presence or absence of cerebral microbleeds and advanced white matter hyperintensity as predictors of subsequent stroke types. AJNR Am J Neuroradiol 2006;27:830–835.
    1. Imaizumi T, Horita Y, Hashimoto Y, Niwa J. Dotlike hemosiderin spots on T2*-weighted magnetic resonance imaging as a predictor of stroke recurrence: a prospective study. J Neurosurg 2004;101:915–920.
    1. Samarasekera N, Fonville A, Lerpiniere C, et al. . Influence of intracerebral hemorrhage location on incidence, characteristics, and outcome: population-based study. Stroke 2015;46:361–368.
    1. Pasquini M, Benedictus MR, Boulouis G, Rossi C, Dequatre-Ponchelle N, Cordonnier C. Incident cerebral microbleeds in a cohort of intracerebral hemorrhage. Stroke 2016;47:689–694.
    1. Passero S, Burgalassi L, D'Andrea P, Battistini N. Recurrence of bleeding in patients with primary intracerebral hemorrhage. Stroke 1995;26:1189–1192.
    1. Yen CC, Lo YK, Li JY, Lin YT, Lin CH, Gau YY. Recurrent primary intracerebral hemorrhage: a hospital based study. Acta Neurol Taiwan 2007;16:74–80.
    1. Hanger HC, Wilkinson TJ, Fayez-Iskander N, Sainsbury R. The risk of recurrent stroke after intracerebral haemorrhage. J Neurol Neurosurg Psychiatry 2007;78:836–840.
    1. Charidimou A, Werring DJ. The dilemma of atrial fibrillation in intracerebral haemorrhage: how to balance the risks of ischaemia and bleeding. Eur J Neurol 2014;21:549–551.
    1. Horstmann S, Rizos T, Jenetzky E, Gumbinger C, Hacke W, Veltkamp R. Prevalence of atrial fibrillation in intracerebral hemorrhage. Eur J Neurol 2014;21:570–576.
    1. Eckman MH, Rosand J, Knudsen KA, Singer DE, Greenberg SM. Can patients be anticoagulated after intracerebral hemorrhage? A decision analysis. Stroke 2003;34:1710–1716.
    1. Charidimou A, Krishnan A, Werring DJ, Rolf Jager H. Cerebral microbleeds: a guide to detection and clinical relevance in different disease settings. Neuroradiology 2013;55:655–674.
    1. Greenberg SM, Eng JA, Ning M, Smith EE, Rosand J. Hemorrhage burden predicts recurrent intracerebral hemorrhage after lobar hemorrhage. Stroke 2004;35:1415–1420.
    1. Chen YW, Lee MJ, Smith EE. Cerebral amyloid angiopathy in East and West. Int J Stroke 2010;5:403–411.
    1. Charidimou A, Linn J, Vernooij MW, et al. . Cortical superficial siderosis: detection and clinical significance in cerebral amyloid angiopathy and related conditions. Brain 2015;138:2126–2139.
    1. Biffi A, Anderson CD, Battey TW, et al. . Association between blood pressure control and risk of recurrent intracerebral hemorrhage. JAMA 2015;314:904–912.

Source: PubMed

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