Apolipoprotein E Modifies Neurological Outcome by Affecting Cerebral Edema but not Hematoma Size after Intracerebral Hemorrhage in Humans

IntroductionTo address the mechanisms by which apoE polymorphism affects functional outcome after intracerebral hemorrhage in humans, we tested the hypothesis that the presence of the APOE4 allele results in amplified inflammatory responses and increased cerebral edema.MethodsWe prospectively enrolled and collected data on 21 adult patients consecutively admitted to Duke University Hospital with supratentorial intracerebral hematoma including hemorrhage volume, midline shift, modified Rankin Score, Glasgow Outcome Score, and APOE genotype. Hemorrhage size (cm3) and midline shift (mm), at the level of the thalamus, were measured by computed tomography within 36 hours of admission. Rankin and Glasgow Scores were determined at discharge. Student's t-test was used to analyze hemorrhage size, midline shift, and Glasgow Outcome Score and logistical regression were used to measure allele affect on modified Rankin Score. When analyzing modified Rankin Score, patients were grouped by favorable outcome (0-2) or unfavorable (3-6).ResultsOut of 21 patients, 11 possessed at least 1 APOE4 allele (APOE4+). There was no difference in hemorrhage volume (25.8 v 38.3 mm for APOE4- v APOE4+, respectively) between the groups, but there was a significant difference in midline shift (P = .04, 0.7 v 4 mm). Functional outcomes were worse for the patients possessing at least 1 APOE4 allele (P = .04)ConclusionThe presence of APOE4 is associated with poor functional outcomes in humans after intracerebral hemorrhage. Our data suggest that the mechanism for this may be increased cerebral edema and not larger hematoma volume.