Default mode network hypometabolism in epileptic encephalopathies with CSWS

Abstract

Previous studies investigating cerebral metabolic changes associated with continuous spike-waves during sleep (CSWS) compared the metabolism of children with CSWS with that of healthy adults, precluding any assessment in brain areas showing physiologic age-related metabolic changes. Here, we investigated the metabolic and connectivity changes characterizing the acute phase of CSWS activity by comparing awake brain metabolism of children with CSWS with that of pediatric pseudo-controls. Positron emission tomography using [18F]-fluorodeoxyglucose (FDG-PET) was performed in 17 awake children with cryptogenic CSWS (5 girls, age: 5-11 years). Voxel-based analyses identified significant metabolic changes in CSWS patients compared with 18 pediatric pseudo-controls (12 girls, age: 6-11 years, non-CSWS focal cryptogenic epilepsy with normal FDG-PET). CSWS-induced changes in the contribution of brain areas displaying metabolic changes to the level of metabolic activity in other brain areas were investigated using pathophysiological interaction. Hypermetabolism in perisylvian regions bilaterally and hypometabolism in lateral and mesial prefrontal cortex, precuneus, posterior cingulate cortex and parahippocampal gyri characterized the acute phase of CSWS (p<0.05 FWE). No change in thalamic metabolism was disclosed. Altered functional connectivity was found between hyper- and hypometabolic regions in CSWS patients compared with pediatric pseudo-controls. This study demonstrates hypometabolism in key nodes of the default mode network (DMN) in awake patients with CSWS, in relation with a possible phenomenon of sustained remote inhibition from the epileptic foci. This hypometabolism might account for some of the acquired cognitive or behavioral features of CSWS epileptic encephalopathies. This study failed to find any evidence of thalamic metabolic changes, which supports the primary involvement of the cortex in CSWS genesis.