Prospects of epileptogenesis prevention

Abstract

Epilepsy is a common neurologic disease, affecting about 1-2% of the population. In around 30% of patients with epilepsy, their seizures are not satisfactorily controlled and drug-resistant epilepsy constitutes a real therapeutic challenge. Consequently, there are efforts aimed at the inhibition of epileptogenesis, a process of converting a normal into an epileptic brain. Data on this problem have been mainly obtained in post-status epilepticus rodent models in which spontaneous seizure activity and behavioral disturbances develop over time. Among antiepileptic drugs, diazepam at high dose of 20mg/kg given during status epilepticus, significantly inhibited the development of spontaneous seizures and also, a strong neuroprotective effect was evident. Also gabapentin and valproate (over a period of 40 days) proved effective in the inhibition of spontaneous seizure activity and reduction of behavioral deficit. However, there are also data that valproate (over 28 days) significantly improved the behavioral performance without affecting the occurrence of spontaneous seizures. A number of antiepileptic drugs, carbamazepine, lamotrigine, levetiracetam, phenobarbital, and topiramate were completely ineffective. Among non-antiepileptic drugs, some promise show rapamycin, losartan and combinations of anti-inflammatory drugs, targeting different inflammatory pathways. Inhibition of epileptogenesis may become a valuable therapeutic approach provided that there are reliable markers of this process. Actually, such markers begin to emerge.

Keywords: Antiepileptic drugs; Epilepsy; Epileptogenesis; Neurodegeneration; Spontaneous seizures.