{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T15:10:17Z","timestamp":1783091417228,"version":"3.54.6"},"reference-count":40,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2020,7,19]],"date-time":"2020-07-19T00:00:00Z","timestamp":1595116800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["G0802012"],"award-info":[{"award-number":["G0802012"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/M00841X\/1"],"award-info":[{"award-number":["MR\/M00841X\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["U01\u2010NS090407"],"award-info":[{"award-number":["U01\u2010NS090407"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2020,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objectives<\/jats:title><jats:p>Hypoxia, or abnormally low blood\u2010oxygen levels, often accompanies seizures and may elicit brain structural changes in people with epilepsy which contribute to central processes underlying sudden unexpected death in epilepsy (SUDEP). The extent to which hypoxia may be related to brain structural alterations in this patient group remains unexplored.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We analyzed high\u2010resolution T1\u2010weighted magnetic resonance imaging (MRI) to determine brain morphometric and volumetric alterations in people with generalized tonic\u2010clonic seizures (GTCS) recorded during long\u2010term video\u2010electroencephalography (VEEG), recruited from two sites (n\u00a0=\u00a022), together with data from age\u2010 and sex\u2010matched healthy controls (n\u00a0=\u00a043). Subjects were sub\u2010divided into those with mild\/moderate (GTCS\u2010hypox\u2010mild\/moderate, n\u00a0=\u00a012) and severe (GTCS\u2010hypox\u2010severe, n\u00a0=\u00a010) hypoxia, measured by peripheral oxygen saturation (SpO<jats:sub>2<\/jats:sub>) during VEEG. Whole\u2010brain voxel\u2010based morphometry (VBM) and regional volumetry were used to assess group comparisons and correlations between brain structural measurements as well as the duration and extent of hypoxia during GTCS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Morphometric and volumetric alterations appeared in association with peri\u2010GTCS hypoxia, including volume loss in the periaqueductal gray (PAG), thalamus, hypothalamus, vermis, cerebellum, parabrachial pons, and medulla. Thalamic and PAG volume was significantly reduced in GTCS patients with severe hypoxia compared with GTCS patients with mild\/moderate hypoxia. Brainstem volume loss appeared in both hypoxia groups, although it was more extensive in those with severe hypoxia. Significant negative partial correlations emerged between thalamic and hippocampal volume and extent of hypoxia, whereas vermis and accumbens volumes declined with increasing hypoxia duration.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>Brain structural alterations in patients with GTCS are related to the extent of hypoxia in brain sites that serve vital functions. Although the changes are associative only, they provide evidence of injury to regulatory brain sites related to respiratory manifestations of seizures.<\/jats:p><\/jats:sec>","DOI":"10.1111\/epi.16615","type":"journal-article","created":{"date-parts":[[2020,7,19]],"date-time":"2020-07-19T12:58:45Z","timestamp":1595163525000},"page":"1570-1580","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["Peri\u2010ictal hypoxia is related to extent of regional brain volume loss accompanying generalized tonic\u2010clonic seizures"],"prefix":"10.1111","volume":"61","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4988-1457","authenticated-orcid":false,"given":"Luke A.","family":"Allen","sequence":"first","affiliation":[{"name":"Department of Clinical and Experimental Epilepsy UCL Institute of Neurology University College London London UK"},{"name":"Epilepsy Society MRI Unit Chalfont St Peter UK"},{"name":"The Center for SUDEP Research National Institute of Neurological Disorders and Stroke Bethesda MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald M.","family":"Harper","sequence":"additional","affiliation":[{"name":"The Center for SUDEP Research National Institute of Neurological Disorders and Stroke Bethesda MD USA"},{"name":"UCLA Brain Research Institute Los Angeles CA USA"},{"name":"Department of Neurobiology David Geffen School of Medicine at UCLA Los Angeles CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8502-4487","authenticated-orcid":false,"given":"Sjoerd B.","family":"Vos","sequence":"additional","affiliation":[{"name":"The Center for SUDEP Research National Institute of Neurological Disorders and Stroke Bethesda MD USA"},{"name":"Centre for Medical Image Computing University College London London UK"},{"name":"Neuroradiological Academic Unit UCL Institute of Neurology University College London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine A.","family":"Scott","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Epilepsy UCL Institute of Neurology University College London London UK"},{"name":"The Center for SUDEP Research National Institute of Neurological Disorders and Stroke Bethesda MD USA"},{"name":"Department of Clinical Neurophysiology National Hospital for Neurology and Neurosurgery UCLH London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nuria","family":"Lacuey","sequence":"additional","affiliation":[{"name":"The Center for SUDEP Research National Institute of Neurological Disorders and Stroke Bethesda MD USA"},{"name":"Department of Neurology University of Texas Health Sciences Center at Houston Houston TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Vilella","sequence":"additional","affiliation":[{"name":"The Center for SUDEP Research National Institute of Neurological Disorders and Stroke Bethesda MD USA"},{"name":"Department of Neurology University of Texas Health Sciences Center at Houston Houston TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel S.","family":"Winston","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Epilepsy UCL Institute of Neurology University College London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8824-367X","authenticated-orcid":false,"given":"Benjamin P.","family":"Whatley","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Epilepsy UCL Institute of Neurology University College London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajesh","family":"Kumar","sequence":"additional","affiliation":[{"name":"The Center for SUDEP Research National Institute of Neurological Disorders and Stroke Bethesda MD USA"},{"name":"Department of Neurobiology David Geffen School of Medicine at UCLA Los Angeles CA USA"},{"name":"Department of Anaesthesiology David Geffen School of Medicine at UCLA Los Angeles CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Ogren","sequence":"additional","affiliation":[{"name":"The Center for SUDEP Research National Institute of Neurological Disorders and Stroke Bethesda MD USA"},{"name":"UCLA Brain Research Institute Los Angeles CA USA"},{"name":"Department of Neurobiology David Geffen School of Medicine at UCLA Los Angeles CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaison S.","family":"Hampson","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Texas Health Sciences Center at Houston Houston TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandhya","family":"Rani","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Texas Health Sciences Center at Houston Houston TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9395-1478","authenticated-orcid":false,"given":"Gavin P.","family":"Winston","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Epilepsy UCL Institute of Neurology University College London London UK"},{"name":"Epilepsy Society MRI Unit Chalfont St Peter UK"},{"name":"Division of Neurology Department of Medicine Queen's University Kingston Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louis","family":"Lemieux","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Epilepsy UCL Institute of Neurology University College London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0260-3855","authenticated-orcid":false,"given":"Samden D.","family":"Lhatoo","sequence":"additional","affiliation":[{"name":"The Center for SUDEP Research National Institute of Neurological Disorders and Stroke Bethesda MD USA"},{"name":"Department of Neurology University of Texas Health Sciences Center at Houston Houston TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6896-854X","authenticated-orcid":false,"given":"Beate","family":"Diehl","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Epilepsy UCL Institute of Neurology University College London London UK"},{"name":"The Center for SUDEP Research National Institute of Neurological Disorders and Stroke Bethesda MD USA"},{"name":"Department of Clinical Neurophysiology National Hospital for Neurology and Neurosurgery UCLH London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,7,19]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.14689"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awv233"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(13)70214-X"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000006785"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awn277"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2004.10.091"},{"issue":"98","key":"e_1_2_9_8_1","first-page":"958","article-title":"Hypoxia reveals posterior thalamic, cerebellar, midbrain, and limbic deficits in congenital central hypoventilation syndrome","volume":"2005","author":"Macey PM","year":"1985","journal-title":"J Appl Physiol"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.1998.79.5.2383"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00412.2015"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00863.2004"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.17-22-08828.1997"},{"key":"e_1_2_9_13_1","first-page":"331","article-title":"Why do Purkinje cells die so easily after global brain ischemia? Aldolase C, EAAT4 and the cerebellar contribution to posthypoxic myoclonus","volume":"89","author":"Welsh JP","year":"2002","journal-title":"Adv Neurol"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410070106"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.14006"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1109\/TMI.2015.2418298"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nicl.2019.102060"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/hbm.24325"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1993.sp019503"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0149-7634(97)00010-9"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2015.00240"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1983.sp014549"},{"issue":"96","key":"e_1_2_9_23_1","first-page":"367","article-title":"Oxygen\u2010sensing neurons in the central nervous system","volume":"2004","author":"Neubauer JA","year":"1985","journal-title":"J Appl Physiol"},{"key":"e_1_2_9_24_1","volume-title":"Principles of anatomy and physiology","author":"Tortora GJ","year":"2018"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/cphy.c100015"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/0034-5687(88)90112-0"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eplepsyres.2018.08.005"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1086\/317521"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.108.2807.413"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2006.08.002"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0006436"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrdd.1032"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1203\/00006450-200106000-00003"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/0741-8329(92)90004-T"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2009.09.013"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0079-6123(04)48029-7"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1378\/chest.14-0500"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1177\/194589240101500505"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep43276"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2013.08.046"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2007.09.066"}],"container-title":["Epilepsia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fepi.16615","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/epi.16615","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/epi.16615","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/epi.16615","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,5]],"date-time":"2023-09-05T10:55:55Z","timestamp":1693911355000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/epi.16615"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,7,19]]},"references-count":40,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2020,8]]}},"alternative-id":["10.1111\/epi.16615"],"URL":"https:\/\/doi.org\/10.1111\/epi.16615","archive":["Portico"],"relation":{},"ISSN":["0013-9580","1528-1167"],"issn-type":[{"value":"0013-9580","type":"print"},{"value":"1528-1167","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,7,19]]},"assertion":[{"value":"2020-02-28","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-06-24","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-07-19","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}