Generalized tonic-clonic seizures

Abstract

Generalized tonic-clonic seizures (GTCs) have long been assumed to produce their dramatic clinical effects through a widely distributed and uniform dysfunction of the human cerebral cortex. However, evidence from a diversity of sources is mounting that GTCs actually exert their influence through discrete cortical and subcortical brain areas, while leaving the intervening structures unaffected. This dysfunction may be produced directly through spatially circumscribed seizure activity or remotely through propagated network dysfunction. Specialized imaging and analysis methods have identified the distinct brain areas affected by GTCs as those also implicated in maintaining both the level of consciousness and its content. The subcortical areas identified in these imaging studies likely play a critical role in the characteristic motor manifestations of GTCs, as well as the complete disruption of alertness. A notable strong cerebellar activation of the late-ictal and postictal period may be the source of dramatic postictal confusion with GTCs, mediated by its strong inhibitory connections to the thalamus. By propagating this inhibitory influence through its divergent thalamocortical connections, the thalamus may effectively deactivate broad areas of the cortex. These deactivated cortical areas correspond conspicuously with those implicated in the so-called default mode network, the widely distributed network of functional units thought to be responsible for personal awareness and conscious processing of environmental inputs.