Abstracts

Genetic Absence Epilepsy Rats from Strasbourg (GAERS) is an isomorphic and predictive model of absence epilepsy. The hallmark is the appearance of bilateral generalized [lsquo]spike and wave discharges[rsquo] (SWD) on the electroencephalogram (EEG) during clinical events that are characterized by behaviour arrest, sometimes accompanied by rhythmic twitching of the vibrissae. The first SWD appear around postnatal day 30 (PN30). At the age of 4 months, 100% of the GAERS have developed SWD on the EEG.
Administration of Levetiracetam (LEV) strongly suppresses the occurence of SWD in GAERS. In kindling models of epilepsy, LEV has shown to excert antiepileptogenic properties. In a previous pilot study of LEV in GAERS, an indication of a similar antiepileptogenic effect was found. In the present study, we want to further investigate the antiepileptogenic properties of LEV in this model of absence epilepsy.
From PN22 until PN60, LEV (54mg/kg) was administered intraperitoneally (i.p.) in GAERS (n=8), while the control Group (n=8) was treated with saline (0.9 % NaCl). All 16 animals were implanted with four epidural screw EEG electrodes at PN51. After a recuperation period of 1 week, EEG was recorded for 3 hours daily during the last 4 days of the treatment (PN57-PN60), while the animals were freely moving. In this period, LEV or saline was injected 1 hour after the start of EEG registration. Subsequently, treatment was halted and EEG was recorded during 4 additional days (PN60-PN64), 3 hours daily. Ictal activity was quantified by means of blinded visual inspection. For quantification purposes, the ictal discharges were classified into 3 types, because the morfology of SWD in young GAERS is very irregular when compared to SWD morphology in adult GAERS. According to their resemblance with SWD of adult GAERS, the following classification was made: [lsquo]Type 1[rsquo]: identical to adult SWD; [lsquo]Type 2[rsquo]: SWD-like but of lower amplitude and frequency; [lsquo]Type 3[rsquo]: irregular ictal discharges with spike and wave aspects. The different seizure types were assigned different statistical weights: scores from 1 to 3 were allocated respectively to [lsquo]Type 3[rsquo]-[lsquo]Type1[rsquo].
There was a highly significant (p[lt]0.01) difference in number of seizures between the treated and control animals on the first 4 days of EEG recording. During the following 4 days, when the administration of LEV was stopped, there still was a significant (p[lt]0.05) difference between the LEV treated and the control group.
In this study, LEV has shown to excert an antiepileptogenic effect on the development of SWD in young GAERS. To assess whether this effect is long-lasting, the animals will be reinvestigated at the age of 4 months.
[Supported by: The following grants: BOF 011D9601, FWO and the Ghent University Epilepsy Grant 1999-2003]