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.
Highlights
cerebral microbleeds (CMBs) burden and distribution on MRI identify subgroups of intracerebral hemorrhage (ICH) survivors with higher ICH recurrence risk, which may help to predict ICH prognosis with relevance for clinical practice and treatment trials
The risk of bias assessment is summarized in table e-1 at Neurology.org
In the cerebral amyloid angiopathy (CAA)-unrelated ICH cohorts, among patients with CMBs, 30/656 (4.6%, 95% confidence intervals (CIs) 3.1%– 6.5%) experienced recurrent ICH, compared to 4/ 325 (1.2%, 95% CI 0.3%–3.1%) patients without CMBs
Summary
This was a meta-analysis of prospective cohorts following ICH, with blood-sensitive brain MRI soon after ICH. Two authors (A.C. and D.J.W.) searched PubMed between January 1, 1999, and October 1, 2015, using several combinations of medical subject heading terms and text words: (microbleed* or microhemorrhag* or microhaemorrhag*) and (intracerebral hemorrhage) or (intracerebral haemorrhage) or (brain hemorrhage) or (brain bleed*) and (MRI or MR imaging) and (recurren* or outcome or survival or predict*). Studies were eligible if they included adult patients with spontaneous symptomatic ICH confirmed by imaging and presumed due to sporadic cerebral small vessel disease; had a prospective design, with at least 3 months of follow-up; assessed the risk of recurrent symptomatic spontaneous ICH (main outcome) during follow-up; had data for the presence of CMBs on baseline T2*-GRE MRI; and were published in English. Two reviewers (A.C. and Y.Y.) determined study eligibility, resolving any disagreements or uncertainties with a third reviewer (D.J.W.) by consensus
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