Asymmetry of sleep electrophysiological markers in patients with focal epilepsy

Laurent Sheybani; Pierre Mégevand; Nicolas Roehri; Laurent Spinelli; Andreas Kleinschmidt; Pieter van Mierlo; Margitta Seeck; Serge Vulliémoz

doi:10.1093/braincomms/fcad161

Asymmetry of sleep electrophysiological markers in patients with focal epilepsy

Brain Commun. 2023 May 24;5(3):fcad161. doi: 10.1093/braincomms/fcad161. eCollection 2023.

Authors

Laurent Sheybani^{1

2}, Pierre Mégevand^{1

3}, Nicolas Roehri^{1

2}, Laurent Spinelli¹, Andreas Kleinschmidt⁴, Pieter van Mierlo⁵, Margitta Seeck¹, Serge Vulliémoz^{1

2}

Affiliations

¹ EEG and Epileptology Unit, Neurology Service, Department of Clinical Neuroscience, Geneva University Hospitals, 1205 Geneva and Faculty of Medicine of Geneva, University of Geneva, 1206 Geneva, Switzerland.
² Epilepsy and Brain Networks Lab, Department of Clinical Neuroscience, Faculty of Medicine of Geneva, University of Geneva, 1206 Geneva, Switzerland.
³ Human Neuron Lab, Department of Fundamental Neuroscience, Faculty of Medicine of Geneva, University of Geneva, 1206 Geneva, Switzerland.
⁴ Neurology Service, Department of Clinical neuroscience, Geneva University Hospitals, 1205 Geneva, Switzerland.
⁵ Medical Image and Signal Processing (MEDISIP), Department of Electronics and Information Systems (ELIS), Ghent University, 9052 Ghent, Belgium.

Abstract

Sleep can modulate epileptic activities, but our knowledge of sleep perturbation by epilepsy remains sparse. Interestingly, epilepsy and sleep both present with defining electrophysiological features in the form of specific graphoelements on EEG. This raises the possibility to identify, within ongoing EEG activity, how epilepsy impacts and disrupts sleep. Here, we asked whether the presence of a lateralized epileptic focus interferes with the expression of the dominant electrophysiological hallmarks of sleep: slow oscillations, slow waves and spindles. To this aim, we conducted a cross-sectional study and analysed sleep recordings with surface EEG from 69 patients with focal epilepsy (age range at EEG: 17-61 years, 29 females, 34 left focal epilepsy). Comparing patients with left and right focal epilepsy, we assessed inter-hemispheric asymmetry of sleep slow oscillations power (delta range, 0.5-4 Hz); sleep slow wave density; amplitude, duration and slope; and spindle density, amplitude, duration as well as locking to slow oscillations. We found significantly different asymmetries in slow oscillation power (P < 0.01); slow wave amplitude (P < 0.05) and slope (P < 0.01); and spindle density (P < 0.0001) and amplitude (P < 0.05). To confirm that these population-based differences reflect actual patient-by-patient differences, we then tested whether asymmetry of sleep features can classify laterality of the epileptic focus using a decision tree and a 5-fold cross-validation. We show that classification accuracy is above chance level (accuracy of 65%, standard deviation: 5%) and significantly outperforms a classification based on a randomization of epileptic lateralization (randomization data accuracy: 50%, standard deviation 7%, unpaired t-test, P < 0.0001). Importantly, we show that classification of epileptic lateralization by the canonical epileptic biomarker, i.e. interictal epileptiform discharges, improves slightly but significantly when combined with electrophysiological hallmarks of physiological sleep (from 75% to 77%, P < 0.0001, one-way ANOVA + Sidak's multiple comparisons test). Together, we establish that epilepsy is associated with inter-hemispheric perturbation of sleep-related activities and provide an in-depth multi-dimensional profile of the main sleep electrophysiological signatures in a large cohort of patients with focal epilepsy. We provide converging evidence that the underlying epileptic process interacts with the expression of sleep markers, in addition to triggering well-known pathological activities, such as interictal epileptiform discharges.

Keywords: electrophysiology; epilepsy; sleep.