Metabolic evidence for remote inhibition in epilepsies with continuous spike-waves during sleep

Epileptic syndromes with continuous spikes and waves during sleep (CSWS) are characterized by an acute phase with the emergence of psychomotor deficits and CSWS activity and by a recovery phase in which patients' clinical condition improves together with the remission of CSWS activity. The pathophysiological mechanisms of how CSWS activity induces psychomotor regression are still poorly understood. PET studies using [18F]-fluorodeoxyglucose (FDG) were performed in 9 children during acute and recovery phases of CSWS. PET data were analyzed at individual and group levels using statistical parametric mapping via subtractive, exclusive masking and variance analyses. Pathophysiological interaction analyses were conducted to determine the evolution of changes in effective connectivity between hypermetabolic and hypometabolic brain areas. At the individual level, CSWS recovery was characterized by a complete or almost complete regression of both hypermetabolic and hypometabolic abnormalities observed during the acute phase. Similar evolution was observed at the group level. Indeed, altered effective connectivity between focal hypermetabolism (centro-parietal regions and right fusiform gyrus) and widespread hypometabolism (prefrontal and orbitofrontal cortices, temporal lobes, left parietal cortex, precuneus and cerebellum) was found at the acute phase and markedly regressed at recovery. This study shows that the neurophysiological effects of CSWS activity are not restricted to the epileptic foci but spread via the inhibition of remote neurons within connected brain areas. The present study suggests that these reversible remote effects participate to the psychomotor repercussions of CSWS activity.