Prevalence and Impact of Cerebral Microbleeds on Clinical and Safety Outcomes in Acute Ischaemic Stroke Patients Receiving Reperfusion Therapy: A Systematic Review and Meta-Analysis

Abstract

Background: Cerebral microbleeds (CMBs), a notable neuroimaging finding often associated with cerebral microangiopathy, demonstrate a heightened prevalence in patients diagnosed with acute ischemic stroke (AIS), which is in turn linked to less favourable clinical prognoses. Nevertheless, the exact prevalence of CMBs and their influence on post-reperfusion therapy outcomes remain inadequately elucidated.

Materials and methods: Through systematic searches of PubMed, Embase and Cochrane databases, studies were identified adhering to specific inclusion criteria: (a) AIS patients, (b) age ≥ 18 years, (c) CMBs at baseline, (d) availability of comparative data between CMB-positive and CMB-negative groups, along with relevant post-reperfusion therapy outcomes. The data extracted were analysed using forest plots of odds ratios, and random-effects modelling was applied to investigate the association between CMBs and symptomatic intracerebral haemorrhage (sICH), haemorrhagic transformation (HT), 90-day functional outcomes, and 90-day mortality post-reperfusion therapy.

Results: In a total cohort of 9776 AIS patients who underwent reperfusion therapy, 1709 had CMBs, with a pooled prevalence of 19% (ES 0.19; 95% CI: 0.16, 0.23, p < 0.001). CMBs significantly increased the odds of sICH (OR 2.57; 95% CI: 1.72; 3.83; p < 0.0001), HT (OR 1.53; 95% CI: 1.25; 1.88; p < 0.0001), as well as poor functional outcomes at 90 days (OR 1.59; 95% CI: 1.34; 1.89; p < 0.0001) and 90-day mortality (OR 1.65; 95% CI: 1.27; 2.16; p < 0.0001), relative to those without CMBs, in AIS patients undergoing reperfusion therapy (encompassing intravenous thrombolysis [IVT], endovascular thrombectomy [EVT], either IVT or EVT, and bridging therapy). Variations in the level of association can be observed among different subgroups of reperfusion therapy.

Conclusions: This meta-analysis underscores a significant association between CMBs and adverse postprocedural safety outcomes encompassing sICH, HT, poor functional outcome, and increased mortality in AIS patients undergoing reperfusion therapy. The notable prevalence of CMBs in both the overall AIS population and those undergoing reperfusion therapy emphasizes their importance in post-stroke prognostication.

Keywords: cerebral microbleeds; haemorrhage; meta-analysis; prevalence; reperfusion therapy; stroke.

Figure 1

The Preferred Reporting System for Systematic Reviews and Meta-Analyses (PRISMA) flowchart showing the studies included in this meta-analysis. Abbreviations: n = number of studies, n = total number of patients, CMBs = cerebral microbleeds, IVT = intravenous thrombolysis EVT = endovascular thrombectomy, BT = bridging therapy, sICH = symptomatic intracerebral haemorrhage, HT = haemorrhagic transformation.

Figure 2

Prevalence of cerebral microbleeds in acute ischemic stroke patients undergoing reperfusion therapy [11,15,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40]. Note: a, b and c correspond to cohorts receiving IVT, EVT and bridging, respectively, in the said study. Choi et al. [21] and Choi et al. (2) [22] refer to studies from 2019 and 2020, respectively. Abbreviations: CMB = cerebral microbleeds, AIS = acute ischaemic stroke, n = number of patients with CMBs, C = total cohort number, p = prevalence, IVT = intravenous thrombolysis, EVT = endovascular thrombectomy, ES = effect size, I² = heterogeneity value, p = p-value.

Figure 3

Forest plots of association of cerebral microbleeds with clinical outcomes: (A) symptomatic intracerebral haemorrhage (sICH) [11,15,18,19,21,23,25,26,27,28,29,36,40] and (B) haemorrhagic transformation (HT) [19,20,21,24,26,27,28,29,31,38,39] in acute ischemic stroke patients undergoing reperfusion therapy. Note: Capuana et al. a, b, c corresponds to cohorts assessed for sICH using the SITS-MOST, ECASS-II and NINDS criteria, respectively, in the said study. Schlemm et al. a, b, c, d correspond to cohorts assessed for sICH using the SITS-MOST, ECASS-II, ECASS-III, and NINDS, respectively. Gratz et al. [11] a, b, c and overall represent cohorts receiving IVT, EVT, Bridging and IVT and/or EVT, respectively, within this study. Abbreviations: CMBs = cerebral microbleeds, sICH = symptomatic intracerebral haemorrhage, HT = haemorrhagic transformation, IVT = intravenous thrombolysis, EVT = endovascular thrombectomy, OR = odds ratio, CI = confidence interval, p = p-value, DL = DerSimmonian and Laird, I² = heterogeneity, ECASS = European Cooperative Acute Stroke Study, ECASS-II = second European Cooperative Acute Stroke Study, ECASS-III = third European Cooperative Acute Stroke Study, NINDS = National Institute of Neurological Disorders and Stroke, SITS-MOST = Safe Implementation of Thrombolysis in Stroke-Monitoring Study, PROACT-II = Prolyse in Acute Cerebral Thromboembolism trial 2.

Figure 4

Forest plots of association of cerebral microbleeds with adverse outcomes: (A) poor functional outcome at 90 days [11,15,18,19,21,25,38] and (B) mortality at 90 days [11,15,18,21,25] in acute ischemic stroke patients undergoing reperfusion therapy. Note: Gratz et al. a, b and c correspond to cohorts receiving IVT, EVT and bridging therapy, respectively, in the said study. Abbreviations: IVT = intravenous thrombolysis, EVT = endovascular thrombectomy, OR = odds ratio, CI = confidence interval, p = p-value, DL = DerSimmonian and Laird, I² = heterogeneity.