Seizure likelihood varies with day-to-day variations in sleep duration in patients with refractory focal epilepsy: A longitudinal EEG investigation

Background While the effects of prolonged sleep deprivation (≥24 hours) on seizure occurrence has been thoroughly explored, little is known about the effects of day-to-day variations in the duration and quality of sleep on seizure probability. A better understanding of the interaction between sleep and seizures may help to improve seizure management. Methods To explore how sleep and epileptic seizures are associated, we analysed continuous intracranial EEG recordings collected from 10 patients with refractory focal epilepsy undergoing ordinary life activities. A total of 4340 days of sleep-wake data were analysed (average 434 days per patient). EEG data were sleep scored using a semi-automated machine learning approach into wake, stages one, two, and three non-rapid eye movement sleep, and rapid eye movement sleep categories. Findings Seizure probability changes with day-to-day variations in sleep duration. Logistic regression models revealed that an increase in sleep duration, by 1·66 ± 0·52 hours, lowered the odds of seizure by 27% in the following 48 hours. Following a seizure, patients slept for longer durations and if a seizure occurred during sleep, then sleep quality was also reduced with increased time spent aroused from sleep and reduced REM sleep. Interpretation Our results demonstrate that day-to-day deviations from regular sleep duration correlates with changes in seizure probability. Sleeping longer, by 1·66 ± 0·52 hours, may offer protective effects for patients with refractory focal epilepsy, reducing seizure risk. Furthermore, the occurrence of a seizure may disrupt sleep patterns by elongating sleep and, if the seizure occurs during sleep, reducing its quality. Funding Australian National Health and Medical Research Council, US National Institutes of Health and Czech Technical University in Prague and Epilepsy Foundation of America Innovation Institute ### Competing Interest Statement KD, LK and DG report grant support from the Australian National Health and Medical Research Council. VK, BB and GW reports grant support from the USA National Institutes of Health. VK reports institutional support from Czech Technical University in Prague. BB reports grant support from the Epilepsy Foundation of America, equity in Cadence Neuroscience Inc. GW and BB report patents issued and pending in the field of epilepsy and device supplementation for research purposes by Medtronic Inc. WD reports grant support from Eisai Australia and UCB Pharma Global, travel support from UCB Australia, speaker honoraria from Eisai Australia and UCB Pharma Australia, scientific advisory board honoraria from UCB Pharma Australia, Elsai Australia, Liva Nova, and Tilray as well as equity interest in EpiMinder and KeyLead Health. MC reports the position of chair of the SEER Medical board and equity in EpiMinder and SEER Medical. GW reports royalties and equity in NeuroOne Inc., speaker honoraria from Medtronic Inc. and has licenced intellectual property to NeuroOne Inc. and Cadence Neuroscience Inc. All other authors have no conflicts to report. ### Funding Statement This research was supported by Australian National Health and Medical Research Council Project Grant 1130468, US National Institutes of Health Grant R01 NS09288203, Czech Technical University in Prague Grant OHK4-026/21 and Epilepsy Foundation of America Innovation Institute, My Seizure Gauge. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Approved by the Human Research Ethics Committees of the three participating clinical centres: Austin Health, The Royal Melbourne Hospital, and St Vincent's Hospital of the Melbourne University Epilepsy Group (LRR145/13). All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes Deidentified recordings of the seizures and some segments of the data used in this study are publicly available on epilepsyecosystem.org. Other relevant data may be made available upon reasonable request by contacting the authors.