{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T22:00:49Z","timestamp":1792879249948,"version":"4.5.0"},"reference-count":19,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2025,8,19]],"date-time":"2025-08-19T00:00:00Z","timestamp":1755561600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,8,19]],"date-time":"2025-08-19T00:00:00Z","timestamp":1755561600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Dravet syndrome (DS) is a developmental and epileptic encephalopathy associated with pathogenic variants in the\n                    <jats:italic>SCN1A<\/jats:italic>\n                    gene. The neuropathological features of adult DS remain poorly understood. We report the postmortem findings of a 55\u2010year\u2010old woman with DS due to a confirmed\n                    <jats:italic>SCN1A<\/jats:italic>\n                    pathogenic variant leading to Nav1.1 loss of function. Clinically, she developed pharmacoresistant seizures, intellectual disability, progressive ataxia, parkinsonism, and cognitive decline. Neuropathological examination revealed a striking excess and several layers of corpora amylacea (wasteosomes) covering the whole convexity of the brain. In addition, abundant p62\u2010positive gray matter neuritic profiles were found mostly in limbic regions and in the white matter in neocortical regions. Pericellular TMEM106B\u2010positive deposits and prominent immunoreactivity for aquaporin 4 were also observed. There was severe Purkinje cell loss in some lobes of the cerebellum together with variable neuronal loss in the substantia nigra, neocortex, and hippocampus. No \u03b1\u2010synuclein, amyloid\u2010\u03b2, or phospho\u2010TDP\u201043 pathology was present. Immunostaining for phosphorylated tau revealed neurofibrillary pathology consistent with Braak stage I (left) \u2013II (right). In summary, our study reveals pathological alterations suggestive of chronic glymphatic insufficiency, impaired autophagy, and some degree of neuronal loss without currently known misfolded protein deposits. These findings are suggestive of an accelerated aging and neurodegenerative process in this adult with DS.\n                  <\/jats:p>","DOI":"10.1111\/epi.18613","type":"journal-article","created":{"date-parts":[[2025,8,19]],"date-time":"2025-08-19T08:50:36Z","timestamp":1755593436000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Novel neuropathological observations in an adult with Dravet syndrome"],"prefix":"10.1111","volume":"66","author":[{"given":"Danielle M.","family":"Andrade","sequence":"first","affiliation":[{"name":"Adult Genetic Epilepsy (AGE) Program, Division of Neurology University of Toronto  Toronto Ontario Canada"},{"name":"Comprehensive Epilepsy Program, Toronto Western Hospital University Health Network, University of Toronto  Toronto Ontario Canada"},{"name":"Division of Neurology, Department of Medicine, Temerty Faculty of Medicine University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne S.","family":"Bassett","sequence":"additional","affiliation":[{"name":"The Dalglish Family 22q Clinic, Department of Mental Health and Division of Cardiology, and Toronto General Hospital Research Institute University Health Network, University of Toronto  Toronto Ontario Canada"},{"name":"Clinical Genetics Research Program and Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, and Department of Psychiatry University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3984-5276","authenticated-orcid":false,"given":"Quratulain","family":"ZulfiqarAli","sequence":"additional","affiliation":[{"name":"Adult Genetic Epilepsy (AGE) Program, Division of Neurology University of Toronto  Toronto Ontario Canada"},{"name":"Department of Molecular Genetics University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor S. T.","family":"Lira","sequence":"additional","affiliation":[{"name":"Adult Genetic Epilepsy (AGE) Program, Division of Neurology University of Toronto  Toronto Ontario Canada"},{"name":"Comprehensive Epilepsy Program, Toronto Western Hospital University Health Network, University of Toronto  Toronto Ontario Canada"},{"name":"Division of Neurology, Department of Medicine, Temerty Faculty of Medicine University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolai Gil","family":"Reyes","sequence":"additional","affiliation":[{"name":"Division of Neurology, Department of Medicine, Temerty Faculty of Medicine University of Toronto  Toronto Ontario Canada"},{"name":"Edmond J. Safra Program in Parkinson's Disease and Morton and Gloria Shulman Movement Disorders Centre Krembil Research Institute, Toronto Western Hospital, University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Carmela","family":"Tartaglia","sequence":"additional","affiliation":[{"name":"Division of Neurology, Department of Medicine, Temerty Faculty of Medicine University of Toronto  Toronto Ontario Canada"},{"name":"Tanz Centre for Research in Neurodegenerative Disease University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5346-0180","authenticated-orcid":false,"given":"Alfonso","family":"Fasano","sequence":"additional","affiliation":[{"name":"Division of Neurology, Department of Medicine, Temerty Faculty of Medicine University of Toronto  Toronto Ontario Canada"},{"name":"Edmond J. Safra Program in Parkinson's Disease and Morton and Gloria Shulman Movement Disorders Centre Krembil Research Institute, Toronto Western Hospital, University of Toronto  Toronto Ontario Canada"},{"name":"Department of Biomedical Sciences Humanitas University, IRCCS Humanitas Research Hospital  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabor G.","family":"Kovacs","sequence":"additional","affiliation":[{"name":"Division of Neurology, Department of Medicine, Temerty Faculty of Medicine University of Toronto  Toronto Ontario Canada"},{"name":"Tanz Centre for Research in Neurodegenerative Disease University of Toronto  Toronto Ontario Canada"},{"name":"Laboratory Medicine Program &amp; Krembil Brain Institute University Health Network, University of Toronto  Toronto Ontario Canada"},{"name":"Department of Laboratory Medicine and Pathobiology University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,8,19]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2017.01.025"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/mgg3.217"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000200028"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2024.109624"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awr129"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2211326119"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eplepsyres.2007.01.003"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-18115-2"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2990.2007.00884.x"},{"issue":"1","key":"e_1_2_10_11_1","first-page":"87","article-title":"Ubiquitin immunoreactive structures in normal human brains. 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