Dead in the Night: Sleep-Wake and Time-Of-Day Influences on Sudden Unexpected Death in Epilepsy
Open accessAbstract
Sudden unexpected death in epilepsy (SUDEP) is the leading cause of epilepsy-related death in patients with refractory epilepsy. Convergent lines of evidence suggest that SUDEP occurs due to seizure induced perturbation of respiratory, cardiac, and electrocerebral function as well as potential predisposing factors. It is consistently observed that SUDEP happens more during the night and the early hours of the morning. The aim of this review is to discuss evidence from patient cases, clinical studies, and animal research which is pertinent to the nocturnality of SUDEP. There are a number of factors which might contribute to the nighttime predilection of SUDEP. These factors fall into four categories: influences of (1) being unwitnessed, (2) lying prone in bed, (3) sleep-wake state, and (4) circadian rhythms. During the night, seizures are more likely to be unwitnessed; therefore, it is less likely that another person would be able to administer a lifesaving intervention. Patients are more likely to be prone on a bed following a nocturnal seizure. Being prone in the accouterments of a bed during the postictal period might impair breathing and increase SUDEP risk. Sleep typically happens at night and seizures which emerge from sleep might be more dangerous. Lastly, there are circadian changes to physiology during the night which might facilitate SUDEP. These possible explanations for the nocturnality of SUDEP are not mutually exclusive. The increased rate of SUDEP during the night is likely multifactorial involving both situational factors, such as being without a witness and prone, and physiological changes due to the influence of sleep and circadian rhythms. Understanding the causal elements in the nocturnality of SUDEP may be critical to the development of effective preventive countermeasures.
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The risk of sudden unexpected death in epilepsy patients is higher during the night.
“Furthermore, the risk of sudden unexpected death in epilepsy patients is higher during the night77.”
From Data quality evaluation in wearable monitoring (2022) · cites this paper as [77]
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Purnell, B. S., Murugan, M., Jani, R. N., & Boison, D. (2021) · Frontiers in Neuroscience · doi:10.3389/fnins.2021.708304 · Cited by 40 · see citing works
Self-citationPetrucci, A. N., Joyal, K. G., Chou, J. W., Li, R., Vencer, K. M., & Buchanan, G. F. (2020) · Neuroscience · doi:10.1016/j.neuroscience.2020.11.029 · Cited by 38 · see citing works
Self-citationScurrying to Understand Sudden Expected Death in Epilepsy: Insights From Animal Models
Li, R., & Buchanan, G. F. (2019) · Epiliepsy currents/Epilepsy currents · doi:10.1177/1535759719874787 · Cited by 33 · see citing works
Self-citationCircadian clock genes and respiratory neuroplasticity genes oscillate in the phrenic motor system
Kelly, M. N., Smith, D. N., Sunshine, M. D., Ross, A., Zhang, X., Gumz, M. L., Esser, K. A., & Mitchell, G. S. (2020) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00010.2020 · Cited by 30 · see citing works
Free-running circadian breathing rhythms are eliminated by suprachiasmatic nucleus lesion
Purnell, B. S., & Buchanan, G. F. (2020) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00211.2020 · Cited by 27 · see citing works
Self-citationSUDEP counseling: Where do we stand?
Whitney, R., Jones, K., Sharma, S., & RamachandranNair, R. (2023) · Epilepsia · doi:10.1111/epi.17617 · Cited by 26 · see citing works
Cyclical underreporting of seizures in patient‐based seizure documentation
Schulze‐Bonhage, A., Richardson, M. P., Brandt, A., Zabler, N., Dümpelmann, M., & Antonio‐Arce, V. S. (2023) · Annals of Clinical and Translational Neurology · doi:10.1002/acn3.51880 · Cited by 25 · see citing works
Purnell, B. S., Petrucci, A. N., Li, R., & Buchanan, G. F. (2021) · The Journal of Physiology · doi:10.1113/jp280856 · Cited by 24 · see citing works
Self-citationThe hidden rhythms of epilepsy: exploring biological clocks and epileptic seizure dynamics
Niu, R., Guo, X., Wang, J., & Yang, X. (2025) · Acta Epileptologica · doi:10.1186/s42494-024-00197-w · Cited by 22 · see citing works
Dong, C., Ye, T., Long, X., Aarts, R. M., van Dijk, J. P., Shang, C., Liao, X., Chen, W., Lai, W., Chen, L., et al. (2022) · IEEE Transactions on Instrumentation and Measurement · doi:10.1109/tim.2022.3173270 · Cited by 22 · see citing works
Sudden unexpected death in epilepsy
Buchanan, G. F., Maciel, A. T. N., & Summerfield, M. J. (2023) · Current Opinion in Neurology · doi:10.1097/wco.0000000000001135 · Cited by 19 · see citing works
Self-citationEpilepsy, gut microbiota, and circadian rhythm
Wang, Y., Zhuo, Z., & Wang, H. (2023) · Frontiers in Neurology · doi:10.3389/fneur.2023.1157358 · Cited by 18 · see citing works
Okanari, K., Otsubo, H., Pulcine, E., Rangrej, J., Baba, S., Ochi, A., Okanishi, T., Homma, Y., Nita, D. A., & Donner, E. J. (2017) · Pediatric Neurology · doi:10.1016/j.pediatrneurol.2017.06.018 · Cited by 18 · see citing works
Chronobiology of epilepsy and sudden unexpected death in epilepsy
Kreitlow, B. L., Li, W. H. C., & Buchanan, G. F. (2022) · Frontiers in Neuroscience · doi:10.3389/fnins.2022.936104 · Cited by 17 · see citing works
Self-citationKassinopoulos, M., Harper, R. M., Guye, M., Lemieux, L., & Diehl, B. (2021) · Frontiers in Neurology · doi:10.3389/fneur.2021.671890 · Cited by 16 · see citing works
Joyal, K. G., Kreitlow, B. L., & Buchanan, G. F. (2022) · Frontiers in Neural Circuits · doi:10.3389/fncir.2022.983211 · Cited by 17 · see citing works
Self-citationDiaphragmatic pacing for the prevention of sudden unexpected death in epilepsy
Purnell, B. S., Braun, A., Fedele, D., Murugan, M., & Boison, D. (2022) · Brain Communications · doi:10.1093/braincomms/fcac232 · Cited by 15 · see citing works
Self-citationProceedings of the Sleep and Epilepsy Workshop: Section 3 Mortality: Sleep, Night, and SUDEP
Buchanan, G. F., Gluckman, B. J., Kalume, F. K., Lhatoo, S. D., Maganti, R. K., Noebels, J. L., Simeone, K. A., Quigg, M., & Pavlova, M. K. (2021) · Epiliepsy currents/Epilepsy currents · doi:10.1177/15357597211004556 · Cited by 10 · see citing works
Self-citationCircadian (diurnal/nocturnal) pattern of cardiac arrhythmias
Manolis, A. S., Manolis, A. S., & Manolis, A. S. (2024) · Heart Rhythm · doi:10.1016/j.hrthm.2024.10.013 · Cited by 9 · see citing works
Impaired post-sleep apnea autonomic arousals in patients with drug-resistant epilepsy
Ricordeau, F., Chouchou, F., Pichot, V., Roche, F., Petitjean, T., Gormand, F., Bastuji, H., Charbonnier, E., Cam, P. L., Stauffer, É., et al. (2024) · Clinical Neurophysiology · doi:10.1016/j.clinph.2024.02.003 · Cited by 9 · see citing works
Gu, L., Qian, Y., Shen, Y. L., Wang, Y., Xu, Q. Y., & Zhang, H. (2022) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2022.112983 · Cited by 9 · see citing works
Soontornpun, A., Mouchati, C., Andrews, N. D., Bena, J., Grigg-Damberger, M. M., & Foldvary‐Schaefer, N. (2024) · Epilepsy & Behavior · doi:10.1016/j.yebeh.2024.110121 · Cited by 8 · see citing works
Joyal, K. G., Petrucci, A. N., Littlepage‐Saunders, M., Boodhoo, N. A., Wendt, L. H., & Buchanan, G. F. (2023) · Neuroscience · doi:10.1016/j.neuroscience.2023.01.016 · Cited by 8 · see citing works
Self-citationKreitlow, B. L., Maciel, A. T. N., Vázquez, A. M. H., & Buchanan, G. F. (2025) · The Journal of Physiology · doi:10.1113/jp288697 · Cited by 6 · see citing works
Self-citationNovel ML-Based Algorithm for Detecting Seizures from Single-Channel EEG
Dweiri, Y. M., & Omari, T. K. A. (2024) · NeuroSci · doi:10.3390/neurosci5010004 · Cited by 6 · see citing works
Kim, K. M., & Yang, K. I. (2023) · Sleep Medicine Research · doi:10.17241/smr.2023.01781 · Cited by 5 · see citing works
Eilbes, M., Gallo, A., Osmani, W. A., Bittencourt‐Silva, P. G., Manis, A. D., & Hodges, M. R. (2025) · Epilepsia · doi:10.1111/epi.18360 · Cited by 5 · see citing works
Mooney, S., Kollmar, R., Gurevich, R., Tromblee, J., Banerjee, A., Sundaram, K., Silverman, J. B., & Stewart, M. (2019) · Neurobiology of Disease · doi:10.1016/j.nbd.2019.104682 · Cited by 5 · see citing works
The epilepsy deaths register: Third-party reports of SUDEP in adults and older adolescents
Grundmann, A., Brolly, J., Craig, D. P., Osland, K., Hanna, J., Hughes, E., Kerr, M. P., Donovan, B., & Thomas, R. H. (2025) · Seizure · doi:10.1016/j.seizure.2025.08.031 · Cited by 4 · see citing works
Chronoepileptology: Mapping the Rhythms of Seizure Risk
Bernard, C., Buchanan, G. F., Koubeissi, M. Z., Loddenkemper, T., & Pennell, P. B. (2025) · Epiliepsy currents/Epilepsy currents · doi:10.1177/15357597251392099 · Cited by 4 · see citing works
Self-citationDüzkalır, H. G., Genç, B., Sağer, S. G., Türkyılmaz, A., & Günbey, H. P. (2023) · TURKISH JOURNAL OF MEDICAL SCIENCES · doi:10.55730/1300-0144.5754 · Cited by 4 · see citing works
Joyal, K. G., Boodhoo, N. A., & Buchanan, G. F. (2025) · Epilepsy & Behavior · doi:10.1016/j.yebeh.2025.110385 · Cited by 4 · see citing works
Self-citationHypothalamic-pituitary-adrenal axis dysfunction worsens epilepsy outcomes and increases SUDEP riskPreprint
Basu, T., Antonoudiou, P., Weiss, G. L., Friedman, D. J., Laze, J., Devinsky, O., & Maguire, J. L. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.03.15.484525 · Cited by 3 · see citing works
Kassinopoulos, M., Rolandi, N., Alphan, L., Harper, R. M., Oliveira, J. F. A., Scott, C. A., Kozák, L. R., Guye, M., Lemieux, L., & Diehl, B. (2025) · Imaging Neuroscience · doi:10.1162/imag.a.918 · Cited by 2 · see citing works
Sleep links hippocampal propensity for epileptiform activity to its viscerosensory inputs
Levichkina, E. V., Pigarev, I. N., Grayden, D. B., Petrou, S., & Vidyasagar, T. R. (2025) · Frontiers in Neuroscience · doi:10.3389/fnins.2025.1559529 · Cited by 1 · see citing works
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Elucidation of a proposed cardiorespiratory circadian rhythm impacting survival in SUDEP
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Time of day is an inaccurate surrogate marker for sleep-wake state in an epilepsy monitoring unit
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The heart of epilepsy: Cardiac comorbidity and sudden death
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Sleep-Related Epilepsy, Dysautonomia, and Sudden Nocturnal Death
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Bridging the Gaps: Complexities and Challenges in Studying SUDEP Using Animal Models
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Translational Research Symposium: Current State of SUDEP Research
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Effect of epileptogenesis on hypercapnic cardioventilatory response in kainic acid rats
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Sleep, Neural Circulatory Control, and Cardiovascular Disease: A Mechanistic Review
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The bed nucleus of the stria terminalis as a neuromodulatory target for refractory epilepsy
Murray, J., Hong, E., Mulloy, S., & Nobis, W. P. (2026) · Frontiers in Network Physiology · doi:10.3389/fnetp.2026.1800427
Lee, C.-H., Hong, J.-P., Lim, S.-N., Li, T.-E., Liao, T.-W., Chang, C.-W., Chen, B.-X., & Chen, H. (2026) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2026.102965
- Authors
- Purnell, B. S., Thijs, R. D., & Buchanan, G. F.
- Affiliations
- University of Iowa (US)
- Leiden University Medical Center (NL)
- Corresponding author
- Buchanan, Gordon F.
- Venue
- Frontiers in Neurology
- Publisher
- Frontiers Media SA
- Published
- 2018-12-11
- Volume
- 9
- Pages
- 1079-1079
- ISSN
- 1664-2295 (ISSN-L)
- PMC
- PMC6297781
- OpenAlex
- W2904372366
- Cited by
- 67
- References
- 183
- Citations by year
- 2026: 9 · 2025: 10 · 2024: 5 · 2023: 9 · 2022: 8 · 2021: 11 · 2020: 8 · 2019: 6 · 2017: 1
- FWCI
- 0.96
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Frontiers in Neurology (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Leiden Repository (Leiden University) (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- National Institutes of Health
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Epilepsy research and treatment
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and related disorders
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Neuroscience of respiration and sleep
- Keywords
- sudden unexpected death in epilepsy, sleep-wake states, circadian rhythm, time of day, prone position, postictal period, SUDEP prevention, drug-resistant epilepsy
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