Patient selection for seizure prophylaxis after traumatic brain injury (TBI) and duration of antiepileptic drug treatment for patients with early posttraumatic seizures (PTS) remain plagued with uncertainty. In early 2017, a collaborative group of neurosurgeons, neurologists, neurointensive care and rehabilitation medicine physicians was formed in the UK with the aim of assessing variability in current practice and gauging the degree of uncertainty to inform the design of future studies. The survey results demonstrated the variation in practice and uncertainty in both described aspects of management of patients who have suffered a TBI. The majority of respondents would want to participate in future research to help try and address this critical issue, and this shows the importance and relevance of these two clinical questions ¹⁾

Guidelines for the Management of Severe Traumatic Brain Injury, Fourth Edition:

Level I

• There was insufficient evidence to support a Level I recommendation for this topic.

Level II A

• Prophylactic use of phenytoin or valproate is not recommended for preventing late PTS.

• Phenytoin is recommended to decrease the incidence of early PTS (within 7 days of injury), when the overall benefit is felt to outweigh the complications associated with such treatment. However, early PTS have not been associated with worse outcomes. At the present time there is insufficient evidence to recommend levetiracetam over phenytoin regarding efficacy in preventing early post-traumatic seizures and toxicity.

Changes from Prior Edition

The recommendations have not changed for this update from the 3rd Edition. Two new Class 2 studies and four new Class 3 studies were added as evidence, but these and the Class 3 studies included from the 3rd Edition did not provide sufficient evidence to inform new recommendations.

see Posttraumatic seizures prevention.

Posttraumatic seizures treatment.

Wilson et al. assessed and compared the effectiveness of drugs on early and late PTS prevention.

A literature search revealed 120 articles. Data were included if the same factors were compared across studies with identical treatment arms. Random effects models were used for meta-analysis to combine data into an overriding odds ratio (OR) comparing PTS incidence. For early PTSs, PHT was compared with placebo and LEV with PHT. For late PTSs, each drug was compared with a placebo.

Sixteen studies were included. PHT was associated with decreased odds of early seizures relative to placebo (OR = 0.34, 95% confidence interval [CI] 0.19-0.62). There was no difference in early seizure incidence between LEV and PHT (OR = 0.83, 95% CI 0.33-2.1). Neither LEV (OR = 0.69, 95% CI 0.24-1.96) nor PHT (OR = 0.4, 95% CI 0.1-1.6) was associated with fewer late PTSs than placebo.

New literature is consistent with current guidelines supporting antiepileptic drug administration for prevention of early, but not late, PTSs. With regard to early PTS prevention, LEV and PHT are similarly efficacious, which is consistent with current guidelines. Side-effect profiles favor LEV administration over PHT ²⁾.