Background: Intracerebral hemorrhage (ICH) is associated with a risk of early seizure and guidelines recommend consideration of prophylactic antiepileptic drugs (AEDs) for some patients although the utility is uncertain. We investigated the association between AED use and outcome from acute ICH. Methods: We performed an analysis of data from the placebo arm of the Cerebral Hemorrhage And NXY-059 Trial (CHANT), which enrolled patients up to 6 hours from onset of symptoms. Multivariable regression analyses were performed to determine whether early AED use was associated with poor outcome at day 90, defined as a modified Rankin Scale of 5 or 6 (severely disabled or dead). Results: Excluding patients previously taking AEDs, the primary analysis included 295 patients. The median ICH volume at admission was 14.9 (IQR 7.9-32.7) mL and the mean was 23.3 ((plus or minus) SD 22.8) mL Seizures occurred in 5 patients (1.7%) after enrollment and 82 patients (28%) had a poor outcome at day 90. 23 patients (8%) were initiated on AEDs without documented seizure during the first 10 days of the trial. Initiation of AEDs was robustly associated with poor outcome (OR 7.2; 95%CI: 2.3-22.6, p=0.001) after adjustment for other known predictors of outcome after ICH (age, initial hematoma volume, presence of intraventricular blood, initial Glasgow Coma Score, infratentorial location, and prior warfarin use). AED use remained a significant predictor when the analysis was limited to those patients with AEDs initiated after the first day, to account for patients who may have had seizure prior to enrollment (OR=5.5, 95%CI: 1.2-24.3, p=0.03). The following figure displays the calculated distribution of modified Rankin scores at day 90, comparing patients who did and did not receive AEDs, adjusted for the predictors of outcome from ICH. Ordered logistic regression incorporating the same variables confirmed that AED use was associated with a significantly increased likelihood of a higher modified Rankin score across the entire spectrum of outcomes (OR=2.9, 95% CI: 1.2-7.0, p=0.02). Discussion: In this trial cohort, seizures after the first few hours following ICH were uncommon. In addition, AED use was associated with a substantially increased risk of death and severe disability independent of other established predictors of poor outcome from ICH.
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