Abnormal local markers of sleep homeostasis in patients with focal epilepsy

Abstract Given the importance of sleep for the regulation of cortical excitability, altered sleep homeostasis may contribute to the development and persistence of focal epilepsy. The goal of the present study was to quantify high-density EEG markers of sleep homeostasis in patients with focal epilepsy compared to healthy age- and gender-matched controls. In particular, we investigated the ability of sleep homeostasis markers to differentiate focal epilepsy vs healthy controls and quantified the deleterious effects of nocturnal epileptiform discharges on sleep homeostasis. Thirty-nine patients with focal epilepsy and forty-eight healthy controls underwent overnight 256-Electrode high-density EEG recordings. Statistical analysis tested for differences in overnight slow-wave activity (i.e. delta power, 1-4 Hz, and theta power, 4-8 Hz) and average slope of slow waves between patients and healthy controls. We assessed the predictive value of sleep homeostasis parameters to identify focal epilepsy at the individual level. Finally, we investigated the relationship between the frequency of epileptiform discharges and abnormal overnight declines in sleep slow-wave activity and slow waves slope. Patients with focal epilepsy displayed higher slow-wave activity and a steeper average slope of slow wave compared to healthy controls, exhibiting slow-wave activity values at the end of the night similar to those observed in healthy controls at the beginning of the night. Among sleep homeostasis markers, the presence of high local extremes in the topographical distribution of theta values proved to be discriminative at the single-subject level for distinguishing patients from healthy controls (Area under the Curve = 0.84). A significant negative association was observed between left-lateralized nocturnal epileptiform discharges and the overnight decline in slow-wave activity and slow wave slope, with the most pronounced effects over the left fronto-temporal leads. Local abnormalities in sleep homeostasis may constitute a reliable biomarker for focal epilepsy. Further studies are needed to determine whether it could also be used to identify focal epilepsy early in the disease course. Furthermore, frequent epileptiform discharges during sleep may contribute to abnormalities in sleep homeostasis, and thus to the persistence of cortical hyperexcitability in focal epilepsy.