Each year about 140,000 Americans and 280,000 Europeans are diagnosed with epilepsy. Epidemiological studies suggest that symptomatic and presumed symptomatic etiologies comprise about 60% of the cases. These data suggest that about 250,000 individuals undergo epileptogenesis each year in the two continents. Even though the elevated risk of epileptogenesis after epileptogenic insult like head trauma, stroke, or status epilepticus (SE) is readily identifiable, there is no evidence-based treatment that can be offered to patients at risk of epileptogenesis.
Aim of the present study is to investigate whether administration of 3 standard antiepileptic drugs (carbamazepine, valproate, levetiracetam) as monotherapy during epileptogenic phase (1) prevents the development of epilepsy, and if not, (2) has a disease modifying effect. The compounds were chosen based on their different mechanism of action and variable effects on the development of kindling, a model considered to predict the antiepileptogenic effects in humans. To mimic clinical situation, administration of compounds (carbamazepine 120 mg/kg/d, valproate 600 mg/kg/d, levetiracetam 150 mg/kg/d, or vehicle) will be started 24 h after the beginning of SE (SE is stopped at 4 h with diazepam) induced by electrical stimulation of the amygdala in adult male Sprague-Dawley rats (n=10-20 per group). Treatment will be continued for 1 wk that corresponds to 20-25% of the latency period. The first 2-wk continuous video-EEG monitoring will be started 10 wk after SE. To confirm antiepileptogenesis or disease modification, the second 2-wk continuous video-EEG will be started 14 wk after SE. Thereafter, animals will undergo behavioral testing (Morris water-maze and fear-conditioning). Finally, animals will be perfused for histology. As outcome measures we use (1) development of epilepsy (yes/no), (2) severity of epilepsy (frequency, duration, behavioral severity of seizures), (3) spatial and emotional learning and memory, and (4) pathology (cell death, mossy fiber sprouting).
|Pitkänen, Asla; Nehlig, Astrid; Brooks-Kayal, Amy R et al. (2013) Issues related to development of antiepileptogenic therapies. Epilepsia 54 Suppl 4:35-43|
|Pitkänen, Asla (2010) Therapeutic approaches to epileptogenesis--hope on the horizon. Epilepsia 51 Suppl 3:2-17|