Abstracts

Prevention of epileptogenesis in patients with acute brain damaging insults like status epilepticus (SE) is a major challenge. We investigated whether carbamazepine (CBZ), levetiracetam (LEV), and valproic acid (VPA) as monotherapy are antiepileptogenic or disease modifying. To mimic clinical study design, treatment was started 24 h after the beginning of electrically induced SE., SE was induced by stimulating the lateral nucleus of the amygdala of adult Sprague-Dawley rats (n=98) electrically for 20-40 min. One group of vehicle treated non-stimulated animals served as controls for histology and behavioral analysis (SHAM, n=37). SE was stopped with diazepam (20 mg/kg, intraperitoneally, i.p.) at 4 h after SE induction (additional injection of DZP 10 mg/kg was given at 3h after the first injection). Administration of compounds (CBZ 120 mg/kg/d, n=17; LEV 300 mg/kg/d, n=18; VPA 600 mg/kg/d, n=16; vehicle VEH, n=47) was started 24 h after the beginning of SE. On the first day, AEDs were administered intraperitoneally, and thereafter i.g. All compounds were administered at 8 h intervals for 7 d. SE and the development of spontaneous seizures were monitored with video-EEG. The occurrence of epilepsy and seizure frequency were assessed at 10 weeks after SE induction with a continuous video-EEG monitoring (24h/day) for 2 weeks. To confirm antiepileptogenesis or disease modification, the second 2-weeks continuous video-EEG was started 14 weeks after SE. Thereafter, animals underwent behavioural testing (Morris water-maze and fear conditioning) and were perfused for histology., Altogether, 62% of VEH, 89% of LEV, 53% of CBZ, and 88% of VPA treated animals developed epilepsy. The mean seizure frequency in the VEH group was 6.3 [plusmn] 12.8 sz/d (range 0.04-50, median 0.39), in the LEV group 4.8 [plusmn] 7.6 sz/d (range 0.04-24.2, median 0.88), and in the VPA group 7.6 [plusmn] 18.5 sz/d (range 0.07-70). In CBZ group the mean seizure frequency was 0.6 [plusmn] 0.6 sz/day (range 0.04-1.63, median 0.46). However it did not differ from that in the VEH group. Mean behavioural seizure severity did not differ between groups. The mean seizure duration was longer in the CBZ group compared to that in the VEH group (77 [plusmn] 16 sec [italic]vs[/italic]. 68 [plusmn] 19 sec, p[lt]0.05)., The three AEDs with different mechanisms of action, LEV, CBZ, and VPA were not antiepileptogenic when started at 24 h after SE induction and continued for 7 days., (Supported by NIH/NINDS R21 NS 049525.)