Sleep slow wave homeostasis and cognitive functioning in children with electrical status epilepticus in sleep

Abstract

Study Objectives: Encephalopathy with electrical status epilepticus in sleep (ESES) is characterized by non-rapid eye movement (non-REM)-sleep-induced epileptiform activity and acquired cognitive deficits. The synaptic homeostasis hypothesis describes the process of daytime synaptic potentiation balanced by synaptic downscaling in non-REM-sleep and is considered crucial to retain an efficient cortical network. We aimed to study the overnight decline of slow waves, an indirect marker of synaptic downscaling, in patients with ESES and explore whether altered downscaling relates to neurodevelopmental and behavioral problems. Methods: Retrospective study of patients with ESES with at least one whole-night electroencephalogram (EEG) and neuropsychological assessment (NPA) within 4 months. Slow waves in the first and last hour of non-REM-sleep were analyzed. Differences in slow-wave slope (SWS) and overnight slope course between the epileptic focus and non-focus electrodes and relations to neurodevelopment and behavior were analyzed. Results: A total of 29 patients with 44 EEG ~ NPA combinations were included. Mean SWS decreased from 357 to 327 µV/s (−8%, p < 0.001) across the night and the overnight decrease was less pronounced in epileptic focus than in non-focus electrodes (−5.6% vs. −8.7%, p = 0.003). We found no relation between SWS and neurodevelopmental test results in cross-sectional and longitudinal analyses. Patients with behavioral problems showed less SWS decline than patients without and the difference was most striking in the epileptic focus (−0.9% vs. −8.8%, p = 0.006). Conclusions: Slow-wave homeostasis-a marker of synaptic homeostasis-is disturbed by epileptiform activity in ESES. Behavioral problems, but not neurodevelopmental test results, were related to severity of this disturbance. Statement of Significance The hallmark of encephalopathy with electrical status epilepticus in sleep (ESES) is near-continuous epileptiform activity in slow-wave sleep, accompanied by neuropsychological disturbances. Slow-wave sleep is of known importance for cognitive functioning. The synaptic homeostasis hypothesis proposes a framework for the role of slow-wave sleep in cognitive functioning. With this study, we analyzed whether slow waves are related to neurodevelopmental and behavioral functioning in children with ESES. We found that an impaired overnight decline in slow-wave slope is related to behavioral problems. Disrupted slow-wave homeostasis might link epileptiform activity in non-REM sleep to neuropsychological problems. Unraveling the mechanisms behind neuropsychological deficits, may lead to a better understanding of this epileptic encephalopathy and how disturbances of sleep physiology impact cognition.