Comparison of the antiepileptogenic effects of an early long‐term treatment with ethosuximide or levetiracetam in a genetic animal model of absence epilepsy

Abstract

Epilepsy is a heterogeneous syndrome characterized by recurrent, spontaneous seizures; continuous medication is, therefore, necessary, even after the seizures have long been suppressed with antiepileptic drug (AED) treatments. The most disturbing issue is the inability of AEDs to provide a persistent cure, because these compounds generally suppress the occurrence of epileptic seizures without necessarily having antiepileptogenic properties. The aim of our experiments was to determine, in the WAG/Rij model of absence epilepsy, if early long-term treatment with some established antiabsence drugs might prevent the development of seizures, and whether such an effect could be sustained. WAG/Rij rats were treated for ∼3.5 months (starting at 1.5 months of age, before seizure onset) with either ethosuximide (ETH; drug of choice for absence epilepsy) or levetiracetam (LEV; a broad-spectrum AED with antiabsence and antiepileptogenic properties). We have demonstrated that both drugs are able to reduce the development of absence seizures, exhibiting antiepileptogenic effects in this specific animal model. These findings suggest that absence epilepsy in this strain of rats very likely follows an epileptogenic process during life and that early therapeutic intervention is possible, thereby opening a new area of research for absence epilepsy and AED treatment strategies.