GABAergic Disinhibition and Reversible Secondary Epileptogenesis in Man

Hughlings Jackson rightly proposed that seizures result from “excessive neuronal discharge”. A growing body of evidence suggests that disinhibition may be necessary but not sufficient for initiating excessive neuronal discharge (2). From a study of penicillin-induced generalized epilepsy in the cat, Gloor (14) has argued that: “... bilaterally synchronous spike-and-wave discharge represents an abnormal response pattern of cortical neurons to afferent thalamocortical volleys normally involved in the elicitation of spindles. Such a response occurs under conditions of diffuse mild cortical hyperexcitability that causes cortical neurons to generate an increased number of action potentials per afferent volley. This secondarily leads to powerful activation of the intracortical recurrent inhibitory pathway. The result is an alternation of short periods of increased cortical excitation corresponding to the EEG spike with longer-lasting periods of intense cortical inhibition corresponding to the wave component of the spike-and-wave complex. This pattern of wide-spread synchronous oscillation between increased excitation and increased inhibition profoundly disrupts the normal pattern of cortical neuronal activity necessary for sustaining higher nervous functions....