Pathophysiology of generalized penicillin epilepsy in the cat: the role of cortical and subcortical structures. II. Topical application of penicillin to the cerebral cortex and to subcortical structures.

Abstract In the cat, topical applications of a weak penicillin solution to large areas of cortex of both hemispheres (50–250 I.U./hemisphere) induces bilaterally synchronous epileptiform discharges, often of a characteristic spike and wave type, which in all respects are similar to those obtained with intramuscular injection of high doses of penicillin. The only difference is that with diffuse cortical application no synchronous paroxysmal high voltage discharges are seen in subcortical structures. This cortically induced generalized epileptiform condition responds in the same manner to single shock and low frequency stimulation of a variety of brain structures as that induced by intramuscular injection of penicillin: bilaterally synchronous epileptiform discharges are precipitated with a high probability by stimulations in those subcortical structures which in the normal cat easily induce spindle waves or recruiting responses (intralaminar and midline nuclei of the thalamus and some association nuclei); in contrast, stimulation of other cortical and subcortical structures which are much less effective in inducing spindles and recruiting responses, are also less effective in precipitating bilaterally synchronous epileptiform discharges. Topical application of penicillin to subcortical sites, particularly to the thalamus, including the intralaminar and midline nuclei, fails to elicit any form of epileptic discharge (except for penicillin application to the amygdala). It is concluded that the epileptogenic alteration of neuronal behavior in generalized penicillin epilepsy of the cat resides in the cortex, but that subcortical structures involved in spindle generation and recruiting responses are the most potent triggers for precipitating bilaterally synchronous epileptic discharges. A functional alteration of thalamic structures is clearly insufficient for precipitating bilaterally synchronous epileptic discharges. The findings of this and of the preceding paper (Quesney et al. 1977) indicate that the basic pathophysiological mechanism of feline generalized penicillin epilepsy, and by extraplation, perhaps that of human generalized corticoreticular (“centrecephalic”) epilepsy, is based on a mild, diffuse cortical epileptogenic state, with subcortical structures involved in spindle generation and recruiting responses, (particularly the “thalamic reticular system”) acting as the most potent triggers of generalized bilaterally synchronous spike and wave discharge. Thus both cortical and subcortical mechanisms are important for the elaboration of generalized bilaterally synchronous spike and wave discharge.