Microbleeds, Cerebral Hemorrhage, and Functional Outcome After Stroke Thrombolysis
Individual Patient Data Meta-Analysis
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Abstract
Background and Purpose—We
assessed whether the presence, number, and distribution of cerebral
microbleeds (CMBs) on pre-intravenous thrombolysis MRI scans of acute
ischemic stroke patients are associated with an increased risk of
intracerebral hemorrhage (ICH) or poor functional outcome.
Methods—We
performed an individual patient data meta-analysis, including
prospective and retrospective studies of acute ischemic stroke treated
with intravenous tissue-type plasminogen activator. Using multilevel
mixed-effects logistic regression, we investigated associations of
pre-treatment CMB presence, burden (1, 2–4, ≥5, and >10), and
presumed pathogenesis (cerebral amyloid angiopathy defined as strictly
lobar CMBs and noncerebral amyloid angiopathy) with symptomatic ICH,
parenchymal hematoma (within [parenchymal hemorrhage, PH] and remote
from the ischemic area [remote parenchymal hemorrhage, PHr]), and poor
3- to 6-month functional outcome (modified Rankin score >2).
Results—In
1973 patients from 8 centers, the crude prevalence of CMBs was 526 of
1973 (26.7%). A total of 77 of 1973 (3.9%) patients experienced
symptomatic ICH, 210 of 1806 (11.6%) experienced PH, and 56 of 1720
(3.3%) experienced PHr. In adjusted analyses, patients with CMBs
(compared with those without CMBs) had increased risk of PH (odds ratio:
1.50; 95% confidence interval: 1.09–2.07; P=0.013) and PHr (odds ratio: 3.04; 95% confidence interval: 1.73–5.35; P<0.001)
but not symptomatic ICH. Both cerebral amyloid angiopathy and
noncerebral amyloid angiopathy patterns of CMBs were associated with PH
and PHr. Increasing CMB burden category was associated with the risk of
symptomatic ICH (P=0.014), PH (P=0.013), and PHr (P<0.00001).
Five or more and >10 CMBs independently predicted poor 3- to 6-month
outcome (odds ratio: 1.85; 95% confidence interval: 1.10–3.12; P=0.020; and odds ratio: 3.99; 95% confidence interval: 1.55–10.22; P=0.004, respectively).
Conclusions—Increasing
CMB burden is associated with increased risk of ICH (including PHr) and
poor 3- to 6-month functional outcome after intravenous thrombolysis
for acute ischemic stroke.
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