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Leveraging a large multicenter cross\u2010sectional cohort, we investigated whether regional morphometric changes occur in a sequential manner, and whether these changes in people with mesial temporal lobe epilepsy and hippocampal sclerosis (MTLE\u2010HS) correlate with clinical features.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We extracted regional measures of cortical thickness, surface area, and subcortical brain volumes from T1\u2010weighted (T1W) magnetic resonance imaging (MRI) scans collected by the ENIGMA\u2010Epilepsy consortium, comprising 804 people with MTLE\u2010HS and 1625 healthy controls from 25 centers. Features with a moderate case\u2013control effect size (Cohen <jats:italic>d<\/jats:italic>\u2009\u2265\u2009.5) were used to train an event\u2010based model (EBM), which estimates a sequence of disease\u2010specific biomarker changes from cross\u2010sectional data and assigns a biomarker\u2010based fine\u2010grained disease stage to individual patients. We tested for associations between EBM disease stage and duration of epilepsy, age at onset, and antiseizure medicine (ASM) resistance.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In MTLE\u2010HS, decrease in ipsilateral hippocampal volume along with increased asymmetry in hippocampal volume was followed by reduced thickness in neocortical regions, reduction in ipsilateral thalamus volume, and finally, increase in ipsilateral lateral ventricle volume. EBM stage was correlated with duration of illness (Spearman <jats:italic>\u03c1\u2009=<\/jats:italic>\u00a0.293, <jats:italic>p<\/jats:italic>\u00a0=\u00a07.03\u2009\u00d7\u200910<jats:sup>\u221216<\/jats:sup>), age at onset (<jats:italic>\u03c1\u2009=<\/jats:italic>\u2009\u2212.18, <jats:italic>p\u2009=<\/jats:italic>\u00a09.82\u2009\u00d7\u200910<jats:sup>\u22127<\/jats:sup>), and ASM resistance (area under the curve\u00a0=\u00a0.59, <jats:italic>p<\/jats:italic>\u00a0=\u00a0.043, Mann\u2013Whitney <jats:italic>U<\/jats:italic> test). However, associations were driven by cases assigned to EBM Stage 0, which represents MTLE\u2010HS with mild or nondetectable abnormality on T1W MRI.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>From cross\u2010sectional MRI, we reconstructed a disease progression model that highlights a sequence of MRI changes that aligns with previous longitudinal studies. This model could be used to stage MTLE\u2010HS subjects in other cohorts and help establish connections between imaging\u2010based progression staging and clinical features.<\/jats:p><\/jats:sec>","DOI":"10.1111\/epi.17316","type":"journal-article","created":{"date-parts":[[2022,6,3]],"date-time":"2022-06-03T06:34:32Z","timestamp":1654238072000},"page":"2081-2095","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Event\u2010based modeling in temporal lobe epilepsy demonstrates progressive atrophy from cross\u2010sectional data"],"prefix":"10.1111","volume":"63","author":[{"given":"Seymour M.","family":"Lopez","sequence":"first","affiliation":[{"name":"Centre for Medical Image Computing, Department of Medical Physics and Biomedical Engineering University College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leon M.","family":"Aksman","sequence":"additional","affiliation":[{"name":"Centre for Medical Image Computing, Department of Medical Physics and Biomedical Engineering University College London  London UK"},{"name":"Stevens Neuroimaging and Informatics Institute, Keck School of Medicine University of Southern California  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil P.","family":"Oxtoby","sequence":"additional","affiliation":[{"name":"Centre for Medical Image Computing, Department of Computer Science University College London  London UK"}],"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":"Centre for Medical Image Computing, Department of Medical Physics and Biomedical Engineering University College London  London UK"},{"name":"Neuroradiological Academic Unit, UCL Queen Square Institute of Neurology University College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Rao","sequence":"additional","affiliation":[{"name":"Department of Psychiatry University of California, San Diego  La Jolla California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3252-5365","authenticated-orcid":false,"given":"Erik","family":"Kaestner","sequence":"additional","affiliation":[{"name":"Department of Psychiatry University of California, San Diego  La Jolla California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saud","family":"Alhusaini","sequence":"additional","affiliation":[{"name":"Department of Neurology Alpert Medical School of Brown University  Providence Rhode Island USA"},{"name":"Department of Molecular and Cellular Therapeutics Royal College of Surgeons in Ireland  Dublin 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Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8947-9518","authenticated-orcid":false,"given":"Neda","family":"Bernasconi","sequence":"additional","affiliation":[{"name":"Neuroimaging of Epilepsy Laboratory Montreal Neurological Institute, McGill University  Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9256-6041","authenticated-orcid":false,"given":"Boris","family":"Bernhardt","sequence":"additional","affiliation":[{"name":"Multimodal Imaging and Connectome Analysis Laboratory, McConnell Brain Imaging Centre, Montreal Neurological Institute and Hospital McGill University  Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonardo","family":"Bonilha","sequence":"additional","affiliation":[{"name":"Department of Neurology Emory University  Atlanta 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Research Center, Department of Medical and Surgical Sciences Magna Gr\u00e6cia University of Catanzaro  Catanzaro Italy"},{"name":"Institute of Neurology, Department of Medical and Surgical Sciences Magna Gr\u00e6cia University of Catanzaro  Catanzaro Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4212-4146","authenticated-orcid":false,"given":"Ezequiel","family":"Gleichgerrcht","sequence":"additional","affiliation":[{"name":"Department of Neurology Medical University of South Carolina  Charleston South Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7272-7079","authenticated-orcid":false,"given":"Renzo","family":"Guerrini","sequence":"additional","affiliation":[{"name":"Neuroscience Department University of Florence  Florence 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K.","family":"Kreilkamp","sequence":"additional","affiliation":[{"name":"Institute of Systems, Molecular and Integrative Biology University of Liverpool  Liverpool UK"},{"name":"Clinical Neurophysiology University Medical Center G\u00f6ttingen  G\u00f6ttingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8827-7324","authenticated-orcid":false,"given":"Angelo","family":"Labate","sequence":"additional","affiliation":[{"name":"Neuroscience Research Center, Department of Medical and Surgical Sciences Magna Gr\u00e6cia University of Catanzaro  Catanzaro Italy"},{"name":"Institute of Neurology, Department of Medical and Surgical Sciences Magna Gr\u00e6cia University of Catanzaro  Catanzaro Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5701-1307","authenticated-orcid":false,"given":"Sara","family":"Larivi\u00e8re","sequence":"additional","affiliation":[{"name":"Multimodal Imaging and Connectome Analysis Laboratory, McConnell Brain Imaging Centre, Montreal Neurological Institute and Hospital McGill University  Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo","family":"Lenge","sequence":"additional","affiliation":[{"name":"Pediatric Neurology, Neurogenetics and Neurobiology Unit and Laboratories A. 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