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Volume changes in brain areas mediating recovery from extreme cardiorespiratory challenges may indicate failure mechanisms and allow prospective identification of <jats:styled-content style=\"fixed-case\">SUDEP<\/jats:styled-content> risk.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We retrospectively imaged <jats:styled-content style=\"fixed-case\">SUDEP<\/jats:styled-content> cases (n\u00a0=\u00a025), patients comparable for age, sex, epilepsy syndrome, localization, and disease duration who were high\u2010risk (n\u00a0=\u00a025) or low\u2010risk (n\u00a0=\u00a023), and age\u2010 and sex\u2010matched healthy controls (n\u00a0=\u00a025) with identical high\u2010resolution T1\u2010weighted scans. Regional gray matter volume, determined by voxel\u2010based morphometry, and segmentation\u2010derived structure sizes were compared across groups, controlling for total intracranial volume, age, and sex.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Substantial bilateral gray matter loss appeared in <jats:styled-content style=\"fixed-case\">SUDEP<\/jats:styled-content> cases in the medial and lateral cerebellum. This was less prominent in high\u2010risk subjects and absent in low\u2010risk subjects. The periaqueductal gray, left posterior and medial thalamus, left hippocampus, and bilateral posterior cingulate also showed volume loss in <jats:styled-content style=\"fixed-case\">SUDEP<\/jats:styled-content>. High\u2010risk subjects showed left thalamic volume reductions to a lesser extent. Bilateral amygdala, entorhinal, and parahippocampal volumes increased in <jats:styled-content style=\"fixed-case\">SUDEP<\/jats:styled-content> and high\u2010risk patients, with the subcallosal cortex enlarged in <jats:styled-content style=\"fixed-case\">SUDEP<\/jats:styled-content> only. Disease duration correlated negatively with parahippocampal volume. Volumes of the bilateral anterior insula and midbrain in <jats:styled-content style=\"fixed-case\">SUDEP<\/jats:styled-content> cases were larger the closer to <jats:styled-content style=\"fixed-case\">SUDEP<\/jats:styled-content> from magnetic resonance imaging.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">SUDEP<\/jats:styled-content> victims show significant tissue loss in areas essential for cardiorespiratory recovery and enhanced volumes in areas that trigger hypotension or impede respiratory patterning. Those changes may shed light on <jats:styled-content style=\"fixed-case\">SUDEP<\/jats:styled-content> pathogenesis and prospectively detect patterns identifying those at risk.<\/jats:p><\/jats:sec>","DOI":"10.1111\/epi.14689","type":"journal-article","created":{"date-parts":[[2019,3,14]],"date-time":"2019-03-14T07:10:53Z","timestamp":1552547453000},"page":"718-729","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":83,"title":["Cerebellar, limbic, and midbrain volume alterations in sudden unexpected death in epilepsy"],"prefix":"10.1111","volume":"60","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 University College London Institute of Neurology  London UK"},{"name":"Magnetic Resonance Imaging Unit, Epilepsy Society  London UK"},{"name":"Center for Sudden 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