Abstracts

Status epilepticus (SE) and complicated febrile seizures are thought to increase the risk of subsequent epilepsy. Early treatment intervention may prevent the development of epilepsy during the period of epileptogenesis. Based upon lamotrigine[rsquo]s (LTG) mechanisms of action and demonstrated neuroprotective properties in stroke models, we hypothesized that LTG would prevent/delay epilepsy in a rodent model of SE. The objective of this study was to determine if early treatment with lamotrigine prevents epileptogenesis after self-sustained status epilepticus (SSSE) in rats.
21 adult male Sprague Dawley rats were randomized to treatment with either LTG (25 mg/kg/dose i.p., n=7), carbamazepine (CBZ; 30 mg/kg/dose; i.p; n=7) or vehicle (VE; i.p.; n=7). Animals did not differ in average weight at time of surgery (VE: 360 g, CBZ: 344 g, LTG: 315 g). One week after hippocampal depth electrode implantation (5.3 mm posterior from the bregma, 4.9 mm lateral from the midline, 5 mm deep from the surface of the brain, incisor bar set at -3.3 mm), unilateral stimulation of the hippocampus was delivered to induce SE (parameters: biphasic square wave stimulus of 800 uA peak to peak at 50 Hz; 10s trains were delivered every 11s (10 s on, 1 s off) for 90 minutes). Treatment was performed 1 and 24 hours after the end of stimulation. Following stimulation, EEG recordings from depth and surface electrodes were monitored continuously for the presence of spontaneous seizures following SE. Efficacy was determined by the percentage of rats developing epilepsy ([ge]2 spontaneous seizures) in each group, the time to the first spontaneous seizure, and the total number of seizures in the first 2 weeks after stimulation.
Baseline monitoring for 24 hours prior to stimulation did not reveal spontaneous seizures after surgery. All animals developed SE following stimulation. The median duration of SE did not differ among the groups (LTG 26.1 hrs, CBZ 29.9 hrs, VE 32.8 hrs). All animals, regardless of treatment developed spontaneous seizures following hippocampal stimulation. Median time to first epileptic seizure was 10 days (range 4-22) in the LTG group, 11 days (4-20) in the CBZ group, and 12 days (6-15) in the VE group (not significant). The median number of seizures during the first 14 days following stimulation was 2 in all groups (range 0-34 for LTG; 0-13 for CBZ; 0-12 for VE).
Brief high dose treatment with CBZ or LTG during SSSE does not shorten the duration of SSSE, prevent epilepsy or affect seizure frequency in this animal model of temporal lobe epilepsy. Further studies are needed to determine if a longer treatment course may prevent secondary epileptogenesis following prolonged SE.
[Supported by: GlaxoSmithKline]