Cerebral small vessel disease and prognosis in intracerebral haemorrhage: A systematic review and meta-analysis of cohort studies

Background and purpose The aim was to investigate whether cerebral small vessel disease (CSVD) markers and the total CSVD burden are associated with functional outcome, mortality, stroke recurrence and haematoma expansion in patients with spontaneous intracerebral haemorrhage (ICH). Methods Following a previously registered protocol (PROSPERO protocol: CRD42021287743), PubMed, Web of Science and Embase were systematically searched to identify relevant literature up to November 2021. Cohort studies that examined the association between CSVD markers (white matter hyperintensity [WMH], lacune, enlarged perivascular space [EPVS], cerebral microbleed [CMB] and brain atrophy) or CSVD burden and prognosis in patients with ICH were included. The pooled estimates were calculated using random effects models. Results Forty-one studies with 19,752 ICH patients were pooled in the meta-analysis. WMH (odds ratio [OR] 1.50, 95% confidence interval [CI] 1.32-1.70), lacune (OR = 1.32, 95% CI 1.18-1.49), CMB (OR = 2.60, 95% CI 1.13-5.97) and brain atrophy (OR = 2.22, 95% CI 1.48-3.31) were associated with worse functional outcome. CSVD markers concerning increased risk of mortality were WMH (OR = 1.57, 95% CI 1.38-1.79) and brain atrophy (OR = 1.84, 95% CI 1.11-3.04), and markers concerning increased risk of stroke recurrence were WMH (OR = 1.62, 95% CI 1.28-2.04) and lacune (OR = 3.00, 95% CI 1.68-5.37). Enlarged perivascular space was not related to prognosis. There was a lack of association between CSVD markers and haematoma expansion. CSVD burden increased the risk of worse functional outcome, mortality and stroke recurrence by 57%, 150% and 44%, respectively. Conclusions In patients with spontaneous ICH, WMH, lacune, CMB, brain atrophy and the total CSVD burden are associated with substantially increased risk of worse functional outcome, mortality or stroke recurrence.