Strategies for antiepileptogenesis: Antiepileptic drugs versus novel approaches evaluated in post-status epilepticus models of temporal lobe epilepsy

Epileptogenesis, i.e., the process leading to epilepsy, is a common sequel of brain insults such as head trauma, stroke, infections, tumors, status epilepticus (SE), and complex febrile seizures. Following such brain insults, there is a cascade of morphological and functional changes in the injured area over months to years before the occurrence of spontaneous recurrent seizures, i.e., the hallmark of epilepsy. This latent (“silent”) period may offer a therapeutic window for the prevention of epileptogenesis. For identifying pharmacological interventions that prevent, interrupt or reverse the epileptogenic process, two groups of animal models, kindling and SE-induced recurrent seizures, have been recommended as potentially useful tools. Furthermore, genetic rodent models of epileptogenesis are increasingly used in assessing antiepileptogenic treatments. Two approaches have been used in these different model categories: testing clinically established antiepileptic drugs (AEDs) for antiepileptogenic or disease-modifying effects, and specific targeting the key causative changes during epileptogenesis. Based on experimental findings with AEDs, two ongoing clinical trials will adress the antiepileptogenic potential of topiramate and levetiracetam in patients with traumatic brain injury, hopefully translating laboratory discoveries into successful therapies. The second approach has highlighted neurodegeneration, inflammation, and neuronal hyperexcitability as interesting targets for antiepileptogenesis or disease modification.