Generalized epilepsy with bilateral synchronous spike and wave discharge. New findings concerning its physiological mechanisms.

A hypothesis for the mechanism of generalized spike and wave discharge in human generalized epilepsy is proposed in the light of findings obtained in feline generalized penicillin epilepsy. It is postulated that generalized bilaterally synchronous spike and wave discharge depends upon a diffuse and relatively mild state of cortical hyperexcitability which increases the responsiveness of cortical neurons. Afferent thalamo-cortical volleys normally involved in the genesis of spindles and recruiting responses are most likely to precipitate spike and wave discharges under these conditions. The spike and wave pattern probably results from the activation of a recurrent intracortical inhibitory pathway which becomes activated when cortical neurons discharge in greater number and more repetitively than is normally the case. During spike and wave discharges a large number of neurons oscillate between short periods of excitation, corresponding to the spike, and longer periods of inhibition, corresponding to the slow wave component of the spike and wave complex. This disrupts the normal transactional processes of cortical neurons which are presumably responsible for mental activity, particularly for the close integration of perception, cognition and voluntary motor responsiveness. The degree of this interference varies greatly and in mild absence seizure it is not justified to speak of "loss of consciousness". The fundamental disturbance in absence seizures brought about by the generalized cortical spike and wave discharges is therefore better regarded as a "clouding of the mind". Loss of consciousness can be said to occur only when the interference with mental activity becomes particularly intense. Loss of consciousness in absence seizures can therefore not be used as an argument in favor of primary involvement of higher brain-stem mechanisms.