Abstracts

Rationale: Status epilepticus (SE) is a neurologic emergency associated with significant morbidity and mortality. The duration of SE appears to be a significant independent factor associated with increased mortality. Although data from clinical trials support the use of lorazepam as the initial treatment of choice in SE, clinical observations and data from models suggest that the efficacy of benzodiazepines decreases as a function of SE duration. Therefore, a need exists for more effective treatments for prolonged SE. Our earlier observations suggest that topiramate has neuroprotective properties when administered after limbic SE. The goal of this experiment was to study the anticonvulsant properties of topiramate and lorazepam, alone and in combination, in prolonged limbic SE. Methods: Limbic SE was induced in 36 adult male Wistar rats via unilateral dorsal hippocampal electrical stimulation using a protocol permitting direct control over SE duration. After 60 minutes of SE, rats received two intraperitoneal injections of either vehicle (n=9), vehicle+lorazepam (1 mg/kg, n=9), vehicle+topiramate (80 mg/kg, n=9) or topiramate (80 mg/kg)+lorazepam (1 mg/kg, n=9). Injections were separated by 5 minutes. Hippocampal electrical stimulation was maintained for an additional 80 minutes. The amount of ictal EEG activity was measured for the 60 minutes prior to treatment and the 80 minutes following treatment. Results: The amount of ictal EEG activity between groups did not differ significantly prior to treatment. After treatment the amount of ictal activity was 69.4 b9 min for rats treated with vehicle, 62.13 b9.5 min for rats treated with topiramate, 36.5 b11.2 min for rats treated with lorazepam and 8.4 b1.6 min for rats treated with lorazepam+topiramate. An Analysis of Variance indicated a significant reduction in ictal EEG activity when lorazepam treatment was compared to vehicle treatment, as well as when lorazepam+topiramate treatment was compared to lorazepam treatment. Topiramate alone had no significant effect on ictal activity. Discussion: These data suggest that topiramate may enhance the anticonvulsant effect of lorazepam in SE.