Runs of rapid spikes in sleep: a characteristic EEG expression of generalized malignant epileptic encephalopathies. A conceptual review with new pharmacological data.

The generalized repetitive fast discharge (GRFD) is an ictal pattern representing the EEG counterpart of tonic seizures occurring mainly in Lennox-Gastaut syndrome (LGS) during slow-wave sleep. The history of terminology, electromorphology, correlations with sleep, ictal clinical correlations and associations with different epileptic syndromes as well as the clinical significance of the pattern is described reviewing the pertinent literature and our own experiences. The physiopathogenesis from both the electrophysiological and pharmacological aspects is discussed in the framework of a concept according to which GRFD is considered as a malignant derivative of an existing slow spike-wave mechanism, due to the permanent or momentary breakdown of the GABA-ergic inhibitory process. In observations performed on some patients we found a paradoxical GRFD-eliciting effect of BDZ drugs and hexobarbiturate after chronic treatment with BDZ agents and/or barbiturate, and a GRFD-blocking effect of Anexate (Flumazenil), a BDZ antagonist on the pattern, appearing either spontaneously in slow-wave sleep or elicited by diazepam or barbiturate. Our findings support the assumption that BDZ (Barbiturate) GABA-Chloride Ionophore Complex plays an important role, both in the development of and possibly in the therapeutic approach to, the GRFD phenomena. Some hypotheses about the role played by the complex based on these observations are put forward.