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Practice parameter: Antiepileptic drug prophylaxis in severe traumatic brain injury

Report of the Quality Standards Subcommittee of the American Academy of Neurology

From the Comprehensive Epilepsy Center, Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA.

Address correspondence and reprint requests to the American Academy of Neurology, 1080 Montreal Avenue, St. Paul, MN 55116.

Objective: To review the evidence regarding antiepileptic drug (AED) prophylaxis in patients with severe traumatic brain injury (TBI) in order to make practice recommendations.

Methods: The authors identified relevant studies by searching multiple databases and reviewing reference lists of other sources. They included studies that prospectively compared post-traumatic seizure rates in patients given AED prophylaxis vs controls. Each study was graded (class I to IV) according to a standard classification-of-evidence scheme and results were analyzed and pooled.

Results: Pooled class I studies demonstrated a significantly lower risk of early post-traumatic seizures (those occurring within 7 days after injury) in patients given phenytoin prophylaxis compared to controls (relative risk 0.37, 95% CI 0.18 to 0.74). Pooled class I and class II studies demonstrated no significant difference in the risk of late post-traumatic seizures (those occurring beyond 7 days after injury) in patients given AED prophylaxis compared to controls (relative risk 1.05, 95% CI 0.82 to 1.35). Serum AED levels were suboptimal in these studies and adverse effects were mild but frequent.

Conclusions: For adult patients with severe TBI, prophylaxis with phenytoin is effective in decreasing the risk of early post-traumatic seizures. AED prophylaxis is probably not effective in decreasing the risk of late post-traumatic seizures. Further studies addressing milder forms of TBI, the use of newer AEDs, the utility of EEG, and the applicability of these findings to children are recommended.

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