Antiepileptogenesis in humans: disappointing clinical evidence and ways to move forward.

PURPOSE OF REVIEW: Preclinical research in epileptology has been very successful in developing antiseizure drugs (ASDs). Several preclinical proof-of-concept studies have also provided evidence for positive treatment effects of some antiepileptogenic drugs to prevent the development of epilepsy. Disappointingly, all human antiepileptogenesis trials to prevent epilepsy after brain insults have failed, because of several reasons.

RECENT FINDINGS: None of the currently available ASDs have been shown to prevent epilepsy after stroke, traumatic brain injury, or in brain tumours. Retrospective series and post-hoc analyses of randomized controlled trials of patients undergoing combined radiochemotherapy for malignant glioblastoma found an increased survival of patients with valproate, thus suggesting a possible role against the symptoms related to the comorbidity of epilepsy in these patients. Target-oriented treatments such as rapamycin and everolimus are currently under clinical investigation to prevent epilepsy in patients with tuberous sclerosis.

SUMMARY: An orchestrated effort among basic and clinical scientists is needed to develop proper antiepileptogenic drugs, powerful biomarkers, and valid clinical trial designs to bring new treatments on the market that can successfully prevent epilepsy.