Abstracts

Levetiracetam (LEV) and valproate (VPA) are antiepileptic drugs (AED[rsquo]s) currently available for patients with partial and generalised epilepsy. Besides their anticonvulsive effects, both have displayed powerful antiepileptogenic properties in the amygdala kindling model.
Rapid Kindling with Recurrent Hippocampal Seizures (RKRHS) provides a fast and reliable rat kindling model for temporal lobe epilepsy. The aim of the present study is to demonstrate in the RKRHS model the anticonvulsive effect of LEV and antiepileptogenic effects of LEV as mono therapy and add-on therapy with VPA.
Male wistar rats (n= 19, 300g) were implanted with four epidural EEG electrodes and with both a bipolar stimulation electrode and a monopolar recording electrode in the right hippocampus. The rats were stimulated according to the RKRHS protocol (10s trains of 1ms biphasic square wave pulses at 20Hz and 400 [mu]A every 30 min, 12 times a day).
properties were tested by injecting fully kindled rats (n=6) with LEV (54 mg/kg, i.p.). Three control animals were injected with saline (2 ml/kg, i.p.). One hour after injection, effects of LEV were assessed by giving all animals 4 kindling stimulations.
properties of LEV and VPA were examined by daily administration of LEV (54 mg/kg, i.p.) and/or VPA (200 mg/kg, i.p.) to non-kindled animals (n=8) for 24 consecutive days. Again, three rats served as controls and were injected with saline (2 ml/kg, i.p.). One week after the last injection, kindling procedures were applied.
In both tests, afterdischarge duration (ADD) and behavioral manifestations were used as parameters for measuring the effects of the AED[rsquo]s.
In the anticonvulsive test, a highly significant reduction in ADD was seen after injection of LEV (p[lt]0,01). Average ADD was reduced from 50,58s (SD=19,15s) to 28,75s (SD=21,07s) (p[lt]0,01). This also became evident in behavioural manifestations; mean behavioural seizure score (scale of Racine) was reduced from 4,60 (SD=0,75) to 2,75 (SD=1,30) (p[lt]0,01), meaning a seizure reduction from rearing, falling and tonic-clonic convulsions (stage 4 and 5) to myoclonic jerks, jaw movement and wet dog shakes (stages 1,2 and 3). The antiepileptogenic test failed to produce evidence for an antiepileptogenic effect of LEV and/or VPA.
LEV displayed strong anticonvulsive properties in the RKRHS model. Mean ADD duration was shorter in treated animals, and mean behavioural seizures were severely reduced. No clear antiepileptogenic effects of LEV or VPA were detected. The antiepileptogenic test however, should be expanded using more animals both in the treated as in the control group.
[Supported by: The following grants; BOF O11D9601, FWO and the Ghent University Epilepsy Grant 1999-2003]