Abstracts

Rationale: The process of seizure generalization from a focus is not well understood. Recent studies suggest that the convulsions secondarily generalized seizures may involve limited cortical regions instead of whole brain. Several of the rat genetic absence models are resistant to secondary generalization during kindling, and we studied their kindling to examine how secondary generalization may occur. Methods: WAG/Rij rats with spike wave seizures were compared to non epileptic Sprague Dawley (SD) rats during hippocampal kindling. Following the implantation of a unilateral hippocampal electrode, as well as frontal and parietal cortical electrodes, rats were kindled while under continuous video EEG monitoring. We evaluated the evolution of the after discharge duration (ADD) , behavioral seizure severity (BSS), cortical involvement and the frequency of the seizure discharge until rats were fully kindled or they were experienced 50 stimulations. BSS was documented according to the Racine Scale. Generalization was defined as BSS of 4 or higher. Animals were considered kindled if they experienced consecutive stage 4 or 5 seizures. Results: SD (n =5) rats were fully kindled after 21.6±4.15 (Mean ±S.E.M) stimulations. Four WAG/Rij rats were kindled after 31±8.54 stimulations and 4 WAG/Rij rats were not kindled after 50 stimulations. Key differences between rats that kindled and those that didn’t are the spread of the AD to the frontal cortex and a higher discharge frequency of the AD in kindled animals. Conclusions: These data suggest that secondary generalization may result from two key steps: First is the spread of seizure activity to the frontal cortex and the second is a shift to higher discharge frequencies. The observed difference between rat strains raises the possibility that there are intrinsic differences in the seizure circuitry that allows or prevents secondary generalization.