Abstract
BACKGROUND: Perihematomal edema (PHE) after intracerebral hemorrhage (ICH) is a biomarker of secondary brain injury. We aimed to determine the direction, strength, and temporality of the association between PHE and functional outcome after ICH onset. METHODS: We did a systematic review to identify cohort studies or trials that used brain computed tomography (CT) imaging to diagnose ICH, and measured functional outcome. We sought individual participant data if they had a diagnostic CT within 72 hours, a repeat CT within 14 days of the diagnostic scan, and were not treated with surgery or therapy that could affect PHE. We did a 2-stage individual participant data meta-analysis. The primary analysis was the association between the change in absolute PHE volume between the diagnostic CT and repeat CT and the primary outcome of death or dependence (modified Rankin Scale score, 3-6) at 90±14 days after ICH onset. We quantified the association between change in absolute PHE volume at 2 repeat CT time points (24±12 and 72±12 hours) and outcome, both unadjusted and adjusted for age, sex, ICH volume on the diagnostic CT, and intraventricular extension using multivariable logistic regression. RESULTS: From 12 969 studies, 38 were eligible, of which 12 studies (with 1 unpublished cohort and the VISTA [Virtual International Stroke Trials Archive]-ICH databank) provided data. We included 1523 participants, of whom 1347 participants (516 [38%] participants female; median age, 66 [interquartile range, 55-75] years) had repeat CT at 24±12 hours, and 495 (195 [39%] participants female; median age, 66 [interquartile range, 55-74] years) had repeat CT at 72±12 hours. 319 participants contributed to both analyses. Death or dependence was associated with absolute PHE growth both in the first 24±12 hours (unadjusted odds ratio, 1.04 per mL increase [95% CI, 1.01-1.06]; P<0.01; adjusted odds ratio, 1.04 per mL increase [95% CI, 1.01-1.06]; P<0.01) and in the first 72±12 hours (unadjusted odds ratio, 1.03 per mL [95% CI, 1.01-1.04]; P<0.01; adjusted odds ratio, 1.02 [95% CI, 1.01-1.04] per 1 mL increase; P<0.01). CONCLUSIONS: PHE growth within 24 and 72 hours of ICH onset is independently associated with death or dependence after ICH.