Overview of Studies to Prevent Posttraumatic Epilepsy

Abstract

Purpose: Prevention of posttraumatic epilepsy (PTE) is of primary importance to reduce the degree of functional morbidity following traumatic brain injury (TBI). However, the effects of antiepileptic drugs (AEDs) in patients with TBI must be assessed separately in terms of prevention and control of provoked seizures (which include immediate and early post-traumatic seizures) and prevention of subsequent unprovoked seizures (late posttraumatic seizures or PTE). Methods: Potential mechanisms for prevention of epileptogenesis as well as reports and systematic reviews were evaluated to determine strategies and results of attempts to reduce or prevent the development of epilepsy following TBI. Results: In observational studies, after a period ranging from 6 months to 13 years, the proportion of cases developing seizures was 0-10% in patients receiving treatment compared to 2-50% in those who were left untreated. In randomized clinical trials, the difference between active treatment [phenytoin (PHT), phenobarbital, or carbamazepine (CBZ)} and placebo was less remarkable after a follow-up ranging from 3 to 60 months and was virtually lacking for the prevention of PTE. In a Cochrane systematic review of 890 patients from 10 RCTs assessing PHT or CBZ, the pooled relative risk (RR) for prevention of early seizures was 0.33 (95% CI 0.21-0.52). By contrast, the RR for prevention of late seizures was 1.28 (95% CI 0.90-1.81). Mortality and neurological disability were similar in the two treatment groups. The use of PHT was followed by an increased (nonsignificant) risk of skin rashes. In addition, cognitive performance was significantly affected by PHT in severely injured patients at 1 month and treatment withdrawal was followed by improvement in cognitive function. Conclusions: The failure to influence the risk of PTE in studies of patients with TBI are similar to findings of meta-analysis of randomized clinical trials on seizure prevention in other conditions, such as febrile seizures, cerebral malaria, craniotomy, and excessive alcohol intake. For these reasons, the prophylactic use of AEDs should be short-lasting and limited to the prevention of immediate and early seizures. Chronic treatment should be considered only after a diagnosis of PTE.