A Systematic Review and Meta-Analysis of Antiepileptic Prophylaxis in Spontaneous Intracerebral Hemorrhage

Background: Frequency of clinical seizures may be as high as 16% in patients with spontaneous intracerebral hemorrhage (ICH). Current guidelines recommend against antiepileptic drug (AED) prophylaxis, but this recommendation is based on older trials, and the effect of newer AEDs is uncertain. The aim of this review was to study effects of AEDs on seizure occurrence and outcome in patients with spontaneous ICH.

Methods: We searched key databases using combinations of the following terms: "levetiracetam," "prophylaxis," "ICH," "intracerebral hemorrhage," "intraparenchymal hemorrhage." Selected studies were reviewed for level of evidence and overall quality of data using Grading of Recommendations, Assessment, Development and Evaluations criteria. A meta-analysis was performed to evaluate seizure prevention, functional outcome, and mortality in patients with seizure prophylaxis compared with no prophylaxis following spontaneous ICH.

Results: Seven articles met inclusion criteria and were graded level III studies. Administration of AEDs was not associated with reduced seizure risk (odds ratio 1.14, 95% confidence interval 0.47-2.77, P = 0.77). There was an association between AED prophylaxis and poor functional outcome (odds ratio 1.65, 95% confidence interval 1.17-2.31, P = 0.004) but not mortality (odds ratio 1.04, 95% confidence interval 0.62-1.72, P = 0.89). The overall quality of evidence using Grading of Recommendations, Assessment, Development and Evaluations criteria was low.

Conclusions: This systematic review and meta-analysis including recent studies focusing on newer AEDs supports the 2015 guidelines regarding AED use in spontaneous ICH. There are some important caveats, including a possible confounding association between AED use and higher ICH score and the overall poor quality of the available data. A randomized clinical trial may be helpful.