The Epidemiology of Posttraumatic Epilepsy

Treatment and Prevention of Epilepsy Following Traumatic Brain Injury

As with other epilepsies with focal onset, posttraumatic epilepsy can be notoriously difficult to treat, and seizure freedom may be hard to obtain.^[25] However, epilepsy after TBI is potentially preventable because posttraumatic seizures may follow the injury only after several years (Fig. 4).^{[8,14,15,26,27]} This provides an "open treatment window," and there have been several clinical trials of antiepileptic drugs to try to prevent posttraumatic epilepsy. In addition, development of posttraumatic epilepsy has been suggested, in part, to rely on activation of the N-methyl-D-aspartate- (NMDA-) glutamate receptors, an effect that is blocked by extracellular Mg²⁺ ions. Magnesium has therefore also been studied in patients with TBI in an effort to prevent epileptogenesis; the neuroprotective properties of magnesium are believed to be mediated by their effect on NMDA receptors^{[9,26,28–30]}

Three major trials stand out as conclusive for the effects of antiepileptic drugs in the prevention of posttraumatic epilepsy.^[9,28–30] In these trials, sodium valproate, carbamazepine, and phenytoin did not prevent the development of late seizures (epilepsy) after moderate-to-severe TBI. However, phenytoin treatment prevented early seizures in the first week after TBI (Fig. 7). There were similar results of a protective effect with carbamazepine against early posttraumatic seizures, but carbamazepine also failed to protect against late seizures (epilepsy).^[30] Magnesium did not provide protection against posttraumatic epilepsy in a human clinical trial.^[31]