Effects of Topiramate in Two Models of Genetically Determined Generalized Epilepsy, the GAERS and the Audiogenic Wistar AS

Abstract

Summary:Purpose: The antiepileptic effects of topiramate (TPM) were assessed in two models of genetically determined generalized epilepsy. The model of nonconvulsive epilepsy used was a model of absence seizures, the GAERS (Genetic Absence Epilepsy Rat from Strasbourg); and the model of convulsive seizures was an audiogenic rat model, the Wistar Audiogenic Sensitive (AS) rat.Methods: GAERS were equipped with four cortical electrodes over the frontoparietal cortex, and the duration of spikeand-wave discharges (SWDs) on the EEG was recorded for periods of 20 to 120 or 300 min. In Wistar AS, the occurrence of, latency to, and duration of one or two wild running episodes and tonic seizures were recorded.Results: In the 16 GAERS studied, TPM (10, 30, and 60 mg/kg) dose-dependently reduced the expression of SWD that almost totally disappeared at the two highest doses between 40 and 120 min. SWD duration returned to control levels by 180 and 280 min after the injection of 30 and 60 mg/kg TPM, respectively. In Wistar AS, 10 mg/kg TPM induced the occurrence of a second running episode not present in control rats, indicative of a decrease in sensitivity of the rats to the stimulus and increased by 330% the latency to the tonic seizure that still occurred in the eight rats studied. At 30 and 60 mg/kg, the latency to wild running increased by 140%; the second running episode was suppressed in six and seven rats, respectively, whereas the tonic seizure occurred only in one of the eight rats studied at these two doses.Conclusions: These results support the broad spectrum of antiepileptic activity of TPM, confirming its efficacy in primary generalized seizures of both tonic-clonic and of the absence type.

The Acute and Chronic Effect of Vagus Nerve Stimulation in Genetic Absence Epilepsy Rats from Strasbourg (GAERS)

“…In the chronic VNS experiment, cumulative SWD duration was significantly reduced in the VNS group, but the effect was very similar in the control group, where it just did not reach significance. A previously reported spontaneous reduction of seizures in GAERS may be an interfering factor (17,18). This phenomenon is correlated with the decrease of vigilance resulting in more sleep episodes and less and shorter seizures (17,18).…”

“…A previously reported spontaneous reduction of seizures in GAERS may be an interfering factor (17,18). This phenomenon is correlated with the decrease of vigilance resulting in more sleep episodes and less and shorter seizures (17,18). It could also explain the fewer seizures and shorter mean SWD durations that we found in our chronic experiment (Table 1) compared to previously published experiments in GAERS, which were monitored only for a short period of time (2).…”

Topiramate in the treatment of partial and generalized epilepsy

“…Although it has no significant direct effects on blood sugar, it was found to be effective in several animal seizure models (Shank et al 2000). These include models predictive of efficacy against several human seizure types: tonic-clonic seizures – the rodent maximal electroshock model (Shank et al 1994), complex partial seizures – amygdalar kindling (Wauquier and Zhou 1996), and absence seizures – genetic absence epilepsy rats (Rigoulot et al 2003). …”

New drugs for the treatment of epilepsy: a practical approach

“…However, it has been observed that lamotrigine may cause an increase in myoclonic seizures in JME (Janz syndrome). 63 64 Although topiramate has been shown to have a broad spectrum of anticonvulsant activity in animal experiments, 65 there is insufficient experience with its clinical application in the treatment of primary generalised epilepsies at present, although it has been licensed for this indication in some countries. Smaller, open label studies, anecdotal reports, and one placebo controlled study suggest that topiramate has beneficial effects in generalised epilepsies.…”