Treatment of late lithium-pilocarpine-induced status epilepticus with diazepam

It is well known that status epilepticus (SE) becomes increasingly difficult to control over time. Previous studies have indicated that the electroencephalographic pattern at the time of intervention is predictive of the probability of successful treatment. However, these findings are based on studies limited to the first 2h of SE onset. Little data is available on the efficacy of treating SE at later time points.

The aim of the present study was to investigate the efficacy of diazepam (DZP) treatment given at two different phases of SE in a lithium-pilocarpine rat model: during continuous ictal discharges (CIDs, phase 3), and during late periodic epileptiform discharges (late PEDs, phase 5). Changes in cortical and hippocampal electroencephalographs (EEGs) were observed continuously during the phases of SE, as well as at 24, 36, 48, and 72h after SE onset. The effects of DZP treatment during CIDs or during late PEDs were compared to control DZP-untreated rats.

In all three groups, hippocampal and cortical EEGs displayed five distinct phases of SE. There were no statistical differences in the duration of phases 1 and 2 among the three groups. Although DZP administration during CIDs did not terminate CIDs in most rats, it did significantly shorten the duration of phases 3 and 4 of SE. Importantly, DZP given during phase 5 successfully ended behavioral and electrographic seizures in most rats.

Hippocampal and cortical EEGs displayed five distinct phases of SE that were similarly responsive to DZP treatment. Termination of electrographic seizures with DZP treatment was more effective in the last phase of SE (late PEDs) than in phase 3 (CIDs). These findings suggest that previous reports of DZPs decrease in efficacy over time may not be applicable to DZP treatment at 4h-post onset.