Antiepileptic drugs to prevent neural degeneration associated with epilepsy: assessing the prospects for neuroprotection

With increasing evidence for cumulative adverse effects of seizures in experimental models, human imaging observations and neuropsychological studies, the concept of neuroprotective treatment in epilepsy is beginning to receive attention. This section of the Workshop on "New Horizons in the Development of Antiepileptic Drugs" (November 28-29, Philadelphia, PA) addressed the rationale for development of neuroprotective treatment in epilepsy. In this review and commentary on the discussion in this section of the Workshop, some of the experimental observations that provide a conceptual basis for neuroprotective therapy in epilepsy are presented. Potentially important factors influencing the assessment of neuroprotective effects, which include genetic background, duration of seizures, effects of previous seizures, timing of intervention relative to seizure occurrence, the necessity of specific, sensitive, long-term outcome measures, and neuroprotection for epileptogenesis vs. consequences of seizures are considered. While there are major challenges in detecting and assessing neuroprotective action in experimental models and at the bedside, efforts to understand how and when injury or seizures produce adverse effects are likely to provide opportunities for new therapeutic approaches that modify epileptogenesis and the consequences of seizures. (C) 2002 Elsevier Science B.V. All rights reserved.