{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T06:36:06Z","timestamp":1772692566273,"version":"3.50.1"},"reference-count":84,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["NINDS NS072179"],"award-info":[{"award-number":["NINDS NS072179"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01NS126418"],"award-info":[{"award-number":["R01NS126418"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["NINDS R21NS111389"],"award-info":[{"award-number":["NINDS R21NS111389"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100007254","name":"Creighton University","doi-asserted-by":"crossref","award":["LB692"],"award-info":[{"award-number":["LB692"]}],"id":[{"id":"10.13039\/100007254","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Nebraska State Biomedical Research Resources","award":["G20RR024001"],"award-info":[{"award-number":["G20RR024001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background: Sudden unexpected death in epilepsy (SUDEP) causes significant mortality, affecting approximately 1 in 1000 people with epilepsy. Clinical and preclinical studies have identified severe seizures, bradycardia, apnea, severe postictal hypoxia, and sleep deficiency that emerge prior to SUDEP and thus may represent temporal biomarkers. The metabolic ketogenic diet (KD) therapy increases longevity in preclinical SUDEP models. Here, the hypothesis that KD therapy would determine whether the emergent sleep deficiency, bradycardia, apnea and\/or hypoxemia persist as temporal biomarkers in preclinical SUDEP was tested. Methods: Kv1.1 knockout (KO) mice, a preclinical SUDEP model, and wild-type littermates were weaned onto a standard diet (SD) or treated with KD. In separate cohorts, approximately every 10 days, seizures and sleep architecture were recorded with electroencephalography\u2013electromyography (EEG-EMG), heart rate was measured with noninvasive ECGenie, apnea was assessed with noninvasive airway mechanics, and blood O2 saturation was measured with pulse oximetry. Data were aligned from the day of sudden death and analyzed retrospectively. Results: KD treatment significantly increased longevity and reduced seizures, reproducing previous studies. Using retrospective analyses from the day of death, KD treatment attenuated the emergence of (i) interictal intermittent bradycardia in the last 20 days of life, (ii) apnea, and (iii) intermittent hypoxemia in the last 10 days of life. In contrast, (iv) KD treatment did not rescue REM and NREM sleep deficiencies during the last 10 days of life. Conclusions: Our findings provide novel preclinical support for KD as a candidate therapy to attenuate seizure frequency and burden, bradycardia, apnea, and hypoxemia in SUDEP. In addition, sleep deficiency persisted as a potential temporal biomarker of preclinical SUDEP; however, causality will need to be tested in future studies.<\/jats:p>","DOI":"10.3390\/nu18050809","type":"journal-article","created":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T16:18:45Z","timestamp":1772554725000},"page":"809","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Longitudinal Study of the Effects of Ketogenic Diet on Seizures, Cardiorespiration, Sleep Architecture and Mortality in the Kv1.1 Knockout Mouse Model of Sudden Unexpected Death in Epilepsy (SUDEP)"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7164-2495","authenticated-orcid":false,"given":"Shruthi H.","family":"Iyer","sequence":"first","affiliation":[{"name":"Department of Pharmacology & Neuroscience, Creighton University School of Medicine, Omaha, NE 68178, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephanie A.","family":"Matthews","sequence":"additional","affiliation":[{"name":"Department of Pharmacology & Neuroscience, Creighton University School of Medicine, Omaha, NE 68178, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3892-8213","authenticated-orcid":false,"given":"Jodi","family":"Hallgren","sequence":"additional","affiliation":[{"name":"Department of Pharmacology & Neuroscience, Creighton University School of Medicine, Omaha, NE 68178, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lauren","family":"Netzel","sequence":"additional","affiliation":[{"name":"Department of Pharmacology & Neuroscience, Creighton University School of Medicine, Omaha, NE 68178, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8716-7211","authenticated-orcid":false,"given":"Timothy A.","family":"Simeone","sequence":"additional","affiliation":[{"name":"Department of Pharmacology & Neuroscience, Creighton University School of Medicine, Omaha, NE 68178, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5072-3694","authenticated-orcid":false,"given":"Kristina A.","family":"Simeone","sequence":"additional","affiliation":[{"name":"Department of Pharmacology & Neuroscience, Creighton University School of Medicine, Omaha, NE 68178, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/j.yebeh.2018.06.037","article-title":"Incidence Rate of Sudden Death in Epilepsy: A Systematic Review and Meta-Analysis","volume":"86","author":"Saetre","year":"2018","journal-title":"Epilepsy Behav."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1479","DOI":"10.1111\/epi.12666","article-title":"Sudden Unexpected Death in Epilepsy: Assessing the Public Health Burden","volume":"55","author":"Thurman","year":"2014","journal-title":"Epilepsia"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1150","DOI":"10.1111\/j.1528-1167.2010.02952.x","article-title":"Combined Analysis of Risk Factors for SUDEP","volume":"52","author":"Hesdorffer","year":"2011","journal-title":"Epilepsia"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1111\/epi.16434","article-title":"Progressive Cardiorespiratory Dysfunction in Kv1.1 Knockout Mice May Provide Temporal Biomarkers of Pending Sudden Unexpected Death in Epilepsy (SUDEP): The Contribution of Orexin","volume":"61","author":"Iyer","year":"2020","journal-title":"Epilepsia"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"107259","DOI":"10.1016\/j.eplepsyres.2023.107259","article-title":"Personalization of SUDEP Risk: A Survey of Transient Subclinical Comorbid Changes","volume":"199","author":"Simeone","year":"2024","journal-title":"Epilepsy Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e419","DOI":"10.1212\/WNL.0000000000008741","article-title":"Clinical Risk Factors in SUDEP: A Nationwide Population-Based Case-Control Study","volume":"94","author":"Sveinsson","year":"2020","journal-title":"Neurology"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1497","DOI":"10.1016\/S0140-6736(25)01636-8","article-title":"Risk Markers for Sudden Unexpected Death in Epilepsy: An Observational, Prospective, Multicentre Cohort Study","volume":"406","author":"Luo","year":"2025","journal-title":"Lancet"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"966","DOI":"10.1016\/S1474-4422(13)70214-X","article-title":"Incidence and Mechanisms of Cardiorespiratory Arrests in Epilepsy Monitoring Units (MORTEMUS): A Retrospective Study","volume":"12","author":"Ryvlin","year":"2013","journal-title":"Lancet Neurol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.seizure.2018.10.011","article-title":"Ictal Hypoxemia: A Systematic Review and Meta-Analysis","volume":"63","author":"Bruno","year":"2018","journal-title":"Seizure"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e227","DOI":"10.1212\/WNL.0000000000007778","article-title":"SUDEP in the North American SUDEP Registry","volume":"93","author":"Verducci","year":"2019","journal-title":"Neurology"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e171","DOI":"10.1212\/WNL.0000000000006785","article-title":"Postconvulsive Central Apnea as a Biomarker for Sudden Unexpected Death in Epilepsy (SUDEP)","volume":"92","author":"Vilella","year":"2019","journal-title":"Neurology"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e6","DOI":"10.1111\/epi.12489","article-title":"High-resolution molecular genomic autopsy reveals complex sudden unexpected death in epilepsy risk profile","volume":"55","author":"Klassen","year":"2014","journal-title":"Epilepsia"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Bagnall, R.D., Crompton, D.E., and Semsarian, C. (2017). Genetic basis of sudden unexpected death in epilepsy. Front. Neurol., 8.","DOI":"10.3389\/fneur.2017.00348"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"D\u2019Adamo, M.C., Liantonio, A., Rolland, J.F., Pessia, M., and Imbrici, P. (2020). Kv1.1 Channelopathies: Pathophysiological Mechanisms and Therapeutic Approaches. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms21082935"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Paulhus, K., Ammerman, L., and Glasscock, E. (2020). Clinical Spectrum of KCNA1 Mutations: New Insights into Episodic Ataxia and Epilepsy Comorbidity. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21082802"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1808","DOI":"10.1111\/epi.12793","article-title":"The Kv1.1 Null Mouse, a Model of Sudden Unexpected Death in Epilepsy (SUDEP)","volume":"55","author":"Moore","year":"2014","journal-title":"Epilepsia"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1016\/S0896-6273(00)81018-1","article-title":"Deletion of the Kv1.1 Potassium Channel Causes Epilepsy in Mice","volume":"20","author":"Smart","year":"1998","journal-title":"Neuron"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"E178","DOI":"10.1111\/epi.13444","article-title":"Ketogenic Diet Treatment Increases Longevity in Kcna1 -Null Mice, a Model of Sudden Unexpected Death in Epilepsy","volume":"57","author":"Simeone","year":"2016","journal-title":"Epilepsia"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1111\/epi.13971","article-title":"Respiratory Dysfunction Progresses with Age in Kcna1-Null Mice, a Model of Sudden Unexpected Death in Epilepsy","volume":"59","author":"Simeone","year":"2018","journal-title":"Epilepsia"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1016\/j.nbd.2019.04.006","article-title":"Cardiorespiratory Profiling Reveals Primary Breathing Dysfunction in Kcna1-Null Mice: Implications for Sudden Unexpected Death in Epilepsy","volume":"127","author":"Dhaibar","year":"2019","journal-title":"Neurobiol. Dis."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"5167","DOI":"10.1523\/JNEUROSCI.5591-09.2010","article-title":"Kv1.1 Potassium Channel Deficiency Reveals Brain-Driven Cardiac Dysfunction as a Candidate Mechanism for Sudden Unexplained Death in Epilepsy","volume":"30","author":"Glasscock","year":"2010","journal-title":"J. Neurosci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"357","DOI":"10.5665\/sleep.5444","article-title":"Orexin Receptor Antagonism Improves Sleep and Reduces Seizures in Kcna1-Null Mice","volume":"39","author":"Roundtree","year":"2016","journal-title":"Sleep"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"840","DOI":"10.1016\/S1474-4422(25)00273-X","article-title":"Sleep EEG and respiratory biomarkers of sudden unexpected death in epilepsy (SUDEP): A case-control study","volume":"24","author":"Maganti","year":"2025","journal-title":"Lancet Neurol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1111\/epi.13953","article-title":"Accumulation of Rest Deficiency Precedes Sudden Death of Epileptic Kv1.1 Knockout Mice, a Model of Sudden Unexpected Death in Epilepsy","volume":"59","author":"Iyer","year":"2018","journal-title":"Epilepsia"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e67","DOI":"10.1111\/epi.12614","article-title":"Heart Rate Variability Analysis Indicates Preictal Parasympathetic Overdrive Preceding Seizure-Induced Cardiac Dysrhythmias Leading to Sudden Unexpected Death in a Patient with Epilepsy","volume":"55","author":"Jeppesen","year":"2014","journal-title":"Epilepsia"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"D\u2019Andrea Meira, I., Rom\u00e3o, T.T., Pires do Prado, H.J., Kr\u00fcger, L.T., Pires, M.E.P., and da Concei\u00e7\u00e3o, P.O. (2019). Ketogenic Diet and Epilepsy: What We Know So Far. Front. Neurosci., 13.","DOI":"10.3389\/fnins.2019.00005"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.eplepsyres.2007.09.008","article-title":"Effects of Ketogenic Diet on Epileptiform Activity in Children with Therapy Resistant Epilepsy","volume":"77","author":"Lundgren","year":"2007","journal-title":"Epilepsy Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"944","DOI":"10.1001\/jamapediatrics.2020.2282","article-title":"Efficacy of Ketogenic Diet, Modified Atkins Diet, and Low Glycemic Index Therapy Diet Among Children With Drug-Resistant Epilepsy: A Randomized Clinical Trial","volume":"174","author":"Sondhi","year":"2020","journal-title":"JAMA Pediatr."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1111\/j.1528-1167.2006.00834.x","article-title":"Ketogenic Diet Improves Sleep Quality in Children with Therapy-Resistant Epilepsy","volume":"48","author":"Lundgren","year":"2007","journal-title":"Epilepsia"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2027","DOI":"10.1111\/j.1528-1167.2009.02163.x","article-title":"Ketogenic Diet Treatment Abolishes Seizure Periodicity and Improves Diurnal Rhythmicity in Epileptic Kcna1-Null Mice","volume":"50","author":"Wilke","year":"2009","journal-title":"Epilepsia"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"784","DOI":"10.1111\/resp.14526","article-title":"Ketogenic Diet Acutely Improves Gas Exchange and Sleep Apnoea in Obesity Hypoventilation Syndrome: A Non-Randomized Crossover Study","volume":"28","author":"Osman","year":"2023","journal-title":"Respirology"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1007\/s00408-015-9806-7","article-title":"Effects of Twenty Days of the Ketogenic Diet on Metabolic and Respiratory Parameters in Healthy Subjects","volume":"193","author":"Rubini","year":"2015","journal-title":"Lung"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1426","DOI":"10.1002\/epi4.70105","article-title":"CURE Epilepsy SUDEP Data Standardization Project Steering Committee; CURE Epilepsy SUDEP Data Standardization Project Working Group Members. Enhancing sudden unexpected death in epilepsy (SUDEP) research through development of common data elements","volume":"10","author":"Iyengar","year":"2025","journal-title":"Epilepsia Open"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1439","DOI":"10.1002\/epi4.70103","article-title":"CURE Epilepsy SUDEP Data Standardization Project Steering Committee; Working Group Members. A companion to the development of common data elements for Sudden Unexpected Death in Epilepsy (SUDEP)","volume":"10","author":"Iyengar","year":"2025","journal-title":"Epilepsia Open"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"174656","DOI":"10.1016\/j.ejphar.2021.174656","article-title":"Pharmacoresponsiveness of Spontaneous Recurrent Seizures and the Comorbid Sleep Disorder of Epileptic Kcna1-Null Mice","volume":"913","author":"Deodhar","year":"2021","journal-title":"Eur. J. Pharmacol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1016\/j.seizure.2025.08.005","article-title":"Short and long-term side effects of the Classic Ketogenic Diet in pediatric epilepsy treatment: A systematic review of clinical trials","volume":"131","author":"Sepehrar","year":"2025","journal-title":"Seizure"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"108334","DOI":"10.1016\/j.yebeh.2021.108334","article-title":"A Ketogenic Diet Protects DBA\/1 and Scn1aR1407X\/+ Mice against Seizure-Induced Respiratory Arrest Independent of Ketosis","volume":"124","author":"Crotts","year":"2021","journal-title":"Epilepsy Behav."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Teran, F.A., Kim, Y., Crotts, M.S., Bravo, E., Emaus, K.J., and Richerson, G.B. (2019). Time of Day and a Ketogenic Diet Influence Susceptibility to SUDEP in Scn1aR1407X\/+ Mice. Front. Neurol., 10.","DOI":"10.3389\/fneur.2019.00278"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Auerbach, D.S., Jones, J., Clawson, B.C., Offord, J., Lenk, G.M., Ogiwara, I., Yamakawa, K., Meisler, M.H., Parent, J.M., and Isom, L.L. (2013). Altered Cardiac Electrophysiology and SUDEP in a Model of Dravet Syndrome. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0077843"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1186\/s12967-025-06382-w","article-title":"Knock-in Kcnh2 rabbit model of long QT syndrome type-2, epilepsy, and sudden death","volume":"23","author":"Singh","year":"2025","journal-title":"J. Transl. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1016\/j.braindev.2016.03.009","article-title":"Does ketogenic diet have any negative effect on cardiac systolic and diastolic functions in children with intractable epilepsy?: One-year follow-up results","volume":"38","author":"Ozdemir","year":"2016","journal-title":"Brain Dev."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"hcae175.799","DOI":"10.1093\/qjmed\/hcae175.799","article-title":"Study of the Cardiovascular Effects of Ketogenic Diet Regimen in Epileptic Children","volume":"117","author":"Mohammed","year":"2024","journal-title":"QJM Int. J. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1055\/s-0036-1582139","article-title":"The Impact of 3:1 Ketogenic Diet on Cardiac Repolarization Changes in Children with Refractory Seizures: A Prospective Follow-Up Study","volume":"47","author":"Karadeniz","year":"2016","journal-title":"Neuropediatrics"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1016\/j.pediatrneurol.2008.08.013","article-title":"Sudden Cardiac Death in Association With the Ketogenic Diet","volume":"39","author":"Bank","year":"2008","journal-title":"Pediatr. Neurol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.nutres.2025.03.008","article-title":"Ketone Therapy Improves Cardiac Function and Structure in Rodents with Heart Failure: A Systematic Review and Meta-Analysis","volume":"137","author":"Lv","year":"2025","journal-title":"Nutr. Res."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Polito, R., Valenzano, A., Monda, V., Cibelli, G., Monda, M., Messina, G., Villano, I., and Messina, A. (2022). Heart Rate Variability and Sympathetic Activity Is Modulated by Very Low-Calorie Ketogenic Diet. Int. J. Environ. Res. Public Health, 19.","DOI":"10.3390\/ijerph19042253"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"e209","DOI":"10.5114\/amsad.2021.112475","article-title":"Ketone Bodies and the Heart","volume":"6","author":"Papazafiropoulou","year":"2021","journal-title":"Arch. Med. Sci. Atheroscler. Dis."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Zhang, W., Guo, X., Chen, L., Chen, T., Yu, J., Wu, C., and Zheng, J. (2021). Ketogenic Diets and Cardio-Metabolic Diseases. Front. Endocrinol., 12.","DOI":"10.3389\/fendo.2021.753039"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"109513","DOI":"10.1016\/j.neuropharm.2023.109513","article-title":"Sudden Unexpected Death in Epilepsy Is Prevented by Blocking Postictal Hypoxia","volume":"231","author":"George","year":"2023","journal-title":"Neuropharmacology"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"3239","DOI":"10.1093\/brain\/awn277","article-title":"Ictal hypoxemia in localization-related epilepsy: Analysis of incidence, severity and risk factors","volume":"131","author":"Bateman","year":"2008","journal-title":"Brain"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1359","DOI":"10.1111\/j.1528-1167.2009.02518.x","article-title":"Respiratory changes with seizures in localization-related epilepsy: Analysis of periictal hypercapnia and airflow patterns","volume":"51","author":"Seyal","year":"2010","journal-title":"Epilepsia"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"e19352","DOI":"10.7554\/eLife.19352","article-title":"Postictal behavioural impairments are due to a severe prolonged hypoperfusion\/hypoxia event that is COX-2 dependent","volume":"5","author":"Farrell","year":"2016","journal-title":"eLife"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/j.sleep.2024.08.020","article-title":"Impact of a ketogenic diet on sleep quality in people with relapsing multiple sclerosis","volume":"122","author":"Perlman","year":"2024","journal-title":"Sleep. Med."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"105335","DOI":"10.1016\/j.nbd.2021.105335","article-title":"The ketogenic diet raises brain oxygen levels, attenuates postictal hypoxia, and protects against learning impairments","volume":"154","author":"Gom","year":"2021","journal-title":"Neurobiol. Dis."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Gangitano, E., Tozzi, R., Mariani, S., Lenzi, A., Gnessi, L., and Lubrano, C. (2021). Ketogenic Diet for Obese COVID-19 Patients: Is Respiratory Disease a Contraindication? A Narrative Review of the Literature on Ketogenic Diet and Respiratory Function. Front. Nutr., 8.","DOI":"10.3389\/fnut.2021.771047"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1016\/0002-9343(84)90177-3","article-title":"Effect of Low Calorie Intake on Abnormal Pulmonary Physiology in Patients with Chronic Hypercapneic Respiratory Failure","volume":"77","author":"Tirlapur","year":"1984","journal-title":"Am. J. Med."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Hampson, J.P., Lacuey, N., Rani, M.S., Hampson, J.S., Simeone, K.A., Simeone, T.A., Narayana, P.A., Lemieux, L., and Lhatoo, S.D. (2022). Functional MRI Correlates of Carbon Dioxide Chemosensing in Persons With Epilepsy. Front. Neurol., 13.","DOI":"10.3389\/fneur.2022.896204"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Dereli, A.S., Apaire, A., and El Tahry, R. (2025). Sudden Unexpected Death in Epilepsy: Central Respiratory Chemoreception. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26041598"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"16354","DOI":"10.1073\/pnas.1004587107","article-title":"Central Serotonin Neurons Are Required for Arousal to CO2","volume":"107","author":"Buchanan","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"C1493","DOI":"10.1152\/ajpcell.00282.2004","article-title":"Cellular mechanisms involved in CO(2) and acid signaling in chemosensitive neurons","volume":"287","author":"Putnam","year":"2004","journal-title":"Am. J. Physiol.-Cell Physiol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2711","DOI":"10.1523\/JNEUROSCI.4331-15.2016","article-title":"Impaired Serotonergic Brainstem Function during and after Seizures","volume":"36","author":"Zhan","year":"2016","journal-title":"J. Neurosci."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"e184231","DOI":"10.1172\/jci.insight.184231","article-title":"Developmental progression of respiratory dysfunction in a mouse model of Dravet syndrome","volume":"10","author":"Milla","year":"2025","journal-title":"JCI Insight"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"e256","DOI":"10.1111\/epi.18623","article-title":"Development and Characterization of an Autoresuscitation Test for Preclinical SUDEP Models","volume":"66","author":"Iyer","year":"2025","journal-title":"Epilepsia"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1007\/978-94-007-4584-1_16","article-title":"The Retrotrapezoid Nucleus and Breathing","volume":"758","author":"Guyenet","year":"2012","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Gonye, E.C., and Bayliss, D.A. (2023). Criteria for Central Respiratory Chemoreceptors: Experimental Evidence Supporting Current Candidate Cell Groups. Front. Physiol., 14.","DOI":"10.3389\/fphys.2023.1241662"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"106592","DOI":"10.1016\/j.nbd.2024.106592","article-title":"Altered Ventilatory Responses to Hypercapnia-Hypoxia Challenges in a Preclinical SUDEP Model Involve Orexin Neurons","volume":"199","author":"Iyer","year":"2024","journal-title":"Neurobiol. Dis."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"e14073","DOI":"10.1111\/jsr.14073","article-title":"The Effects of Ketogenic Dietary Therapies on Sleep: A Scoping Review","volume":"33","author":"Pasca","year":"2024","journal-title":"J. Sleep Res."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"hcae175.809","DOI":"10.1093\/qjmed\/hcae175.809","article-title":"Effect of Ketogenic Diet on Sleep Quality of Children with Drug Resistant Epilepsy and Their Mothers","volume":"117","author":"Nassar","year":"2024","journal-title":"QJM Int. J. Med."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"108327","DOI":"10.1016\/j.yebeh.2021.108327","article-title":"Evaluation of the Effects of Ketogenic Diet Therapy on Sleep Quality in Children with Drug-Resistant Epilepsy and Their Mothers","volume":"124","author":"Baysal","year":"2021","journal-title":"Epilepsy Behav."},{"key":"ref_70","unstructured":"Detlev, B., and Susan, A.M. (2016). Sleep. Homeostatic Control of Brain Function, Oxford Academic."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Zhao, B., Jin, X., Yang, J., Ma, Q., Yang, Z., Wang, W., Bai, L., Ma, X., and Yan, B. (2022). Increased Rapid Eye Movement Sleep Is Associated With a Reduced Risk of Heart Failure in Middle-Aged and Older Adults. Front. Cardiovasc. Med., 9.","DOI":"10.3389\/fcvm.2022.771280"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1241","DOI":"10.1001\/jamaneurol.2020.2108","article-title":"Association of Rapid Eye Movement Sleep With Mortality in Middle-Aged and Older Adults","volume":"77","author":"Leary","year":"2020","journal-title":"JAMA Neurol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1580","DOI":"10.18632\/aging.101858","article-title":"Influence of Rapid Eye Movement Sleep on All-Cause Mortality: A Community-Based Cohort Study","volume":"11","author":"Zhang","year":"2019","journal-title":"Aging"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.psyneuen.2005.06.009","article-title":"Effects of Sleep Deprivation on Cardiac Autonomic and Pituitary-Adrenocortical Stress Reactivity in Rats","volume":"31","author":"Sgoifo","year":"2006","journal-title":"Psychoneuroendocrinology"},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Liu, L., Wang, Y., Sun, J., Wang, Y., Tan, X., and Wang, W. (2024). Sleep Deprivation Reduces the Baroreflex Sensitivity through Elevated Angiotensin (Ang) II Subtype 1 Receptor Expression in the Nucleus Tractus Solitarii. Front. Neurosci., 18.","DOI":"10.3389\/fnins.2024.1401530"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/S0893-133X(97)00025-0","article-title":"Effects of Sleep Deprivation on Serotonergic Neuronal Activity in the Dorsal Raphe Nucleus of the Freely Moving Cat","volume":"17","author":"Gardner","year":"1997","journal-title":"Neuropsychopharmacology"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1259","DOI":"10.1007\/s12264-020-00524-4","article-title":"Sleep Deprivation Selectively Down-Regulates Astrocytic 5-HT2B Receptors and Triggers Depressive-Like Behaviors via Stimulating P2 \u00d7 7 Receptors in Mice","volume":"36","author":"Xia","year":"2020","journal-title":"Neurosci. Bull."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"245","DOI":"10.5935\/1984-0063.20220046","article-title":"Sleep Deprivation: A Risk for Epileptic Seizures","volume":"15","author":"Soti","year":"2022","journal-title":"Sleep Sci."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1111\/j.1535-7597.2004.04509.x","article-title":"Sleep Deprivation and Epilepsy","volume":"4","author":"Malow","year":"2004","journal-title":"Epilepsy Curr."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"107114","DOI":"10.1016\/j.psyneuen.2024.107114","article-title":"The Effect of Total Sleep Deprivation on Autonomic Nervous System and Cortisol Responses to Acute Stressors in Healthy Individuals: A Systematic Review","volume":"168","author":"Messa","year":"2024","journal-title":"Psychoneuroendocrinology"},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Zhang, S., Niu, X., Ma, J., Wei, X., Zhang, J., and Du, W. (2025). Effects of Sleep Deprivation on Heart Rate Variability: A Systematic Review and Meta-Analysis. Front. Neurol., 16.","DOI":"10.3389\/fneur.2025.1556784"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"886","DOI":"10.1164\/ajrccm.156.3.9610060","article-title":"Ventilatory and Arousal Responses to Hypoxia and Hypercapnia in a Canine Model of Obstructive Sleep Apnea","volume":"156","author":"Kimoff","year":"1997","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_83","first-page":"e33005","article-title":"Sleep Deprivation Is Associated With Increased Risk for Hypertensive Heart Disease: A Nationwide Population-Based Cohort Study","volume":"14","author":"Evbayekha","year":"2022","journal-title":"Cureus"},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Allen, L.A., Harper, R.M., Kumar, R., Guye, M., Ogren, J.A., Lhatoo, S.D., Lemieux, L., Scott, C.A., Vos, S.B., and Rani, S. (2017). Dysfunctional Brain Networking among Autonomic Regulatory Structures in Temporal Lobe Epilepsy Patients at High Risk of Sudden Unexpected Death in Epilepsy. Front. Neurol., 8.","DOI":"10.3389\/fneur.2017.00544"}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/18\/5\/809\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T05:16:24Z","timestamp":1772687784000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/18\/5\/809"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,1]]},"references-count":84,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,3]]}},"alternative-id":["nu18050809"],"URL":"https:\/\/doi.org\/10.3390\/nu18050809","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,1]]}}}