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It is characterized by autoantibodies against IgLON5, 85% association with HLA-DQB1*05:\u223c and a brainstem-dominant tauopathy. Cellular and murine models report pathogenic effects of the autoantibodies, and neurodegenerative factors suggest progressive atrophy as a common sequela. However, evidence from in vivo patient data and long-term follow-up is limited, and the degree of progression remains elusive.<\/jats:p>\n                  <jats:p>In this multicentre study, clinical and brain MRI data were collected from 127 patients across 12 countries to investigate the relationships between clinical presentations and the development of distinct brain atrophy patterns. Our data show that most patients develop a complex multisystem phenotype as the disease progresses; however, neuromuscular manifestations rarely emerge at later disease stages. By comparison to healthy controls, this disease presents with severe substructure-specific atrophy, especially affecting the hypothalamus, brainstem, accumbens and basal ganglia, which, in age-independent analyses, show significant ventricular enlargement and also suggest progression of brainstem atrophy over the disease course. Moreover, the focality of atrophy was functionally linked to specific symptoms, with more severe involvement of the basal ganglia in patients with movement disorders, and greater atrophy in the hippocampus and thalamus in patients with cognitive impairment.<\/jats:p>\n                  <jats:p>Taken together, our results provide evidence of distinct atrophy patterns in anti-IgLON5 disease, which closely mirror sites of pathophysiologic processes, including autoantibody binding and tau deposition. Our data emphasize the brainstem as the pathophysiological hub of the disease and provide normative data for the incorporation of atrophy measurements into routine clinical assessments and future treatment studies to monitor disease trajectory and evaluate future treatment strategies.<\/jats:p>","DOI":"10.1093\/brain\/awaf256","type":"journal-article","created":{"date-parts":[[2025,7,12]],"date-time":"2025-07-12T16:01:48Z","timestamp":1752336108000},"page":"884-896","source":"Crossref","is-referenced-by-count":7,"title":["Brain atrophy patterns in anti-IgLON5 disease"],"prefix":"10.1093","volume":"149","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-4221-7131","authenticated-orcid":false,"given":"Selina M","family":"Yogeshwar","sequence":"first","affiliation":[{"name":"Department of Neurology and Experimental Neurology, Charit\u00e9-Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t Berlin , Berlin 10117 ,","place":["Germany"]},{"name":"Einstein Center for Neurosciences Berlin, Charit\u00e9- Universit\u00e4tsmedizin Berlin , Berlin 10117 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3523-4520","authenticated-orcid":false,"given":"Frederik","family":"Bartels","sequence":"additional","affiliation":[{"name":"Department of Neurology and Experimental Neurology, Charit\u00e9-Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t Berlin , Berlin 10117 ,","place":["Germany"]},{"name":"Institute for Immunity, Transplantation, and Infection, Stanford University School of Medicine , Stanford, CA 94305 ,","place":["USA"]},{"name":"Berlin Institute of Health at Charit\u00e9, Universit\u00e4tsmedizin Berlin , Berlin 10178 ,","place":["Germany"]},{"name":"Berlin School of Mind and Brain, Humboldt-Universit\u00e4t zu Berlin , Berlin 10117 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8927-9818","authenticated-orcid":false,"given":"Thomas","family":"Gr\u00fcter","sequence":"additional","affiliation":[{"name":"Department of Neurology, St. Josef Hospital, Ruhr University Bochum , Bochum 44791 ,","place":["Germany"]},{"name":"Department of Neurology, Evangelic Hospital Lippstadt , Lippstadt 59555 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5958-3288","authenticated-orcid":false,"given":"Sergio","family":"Mu\u00f1iz-Castrillo","sequence":"additional","affiliation":[{"name":"French Reference Centre on Paraneoplastic Neurological Syndromes and Autoimmune Encephalitis, Hospices Civils de Lyon , Lyon 69677 ,","place":["France"]},{"name":"Department of Neurology, Hospital Universitario 12 de Octubre , Madrid 28041 ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G\u00e9raldine","family":"Picard","sequence":"additional","affiliation":[{"name":"French Reference Centre on Paraneoplastic Neurological Syndromes and Autoimmune Encephalitis, Hospices Civils de Lyon , Lyon 69677 ,","place":["France"]},{"name":"Institut MeLiS INSERM U1314\/CNRS UMR 5284, Universit\u00e9 Claude Bernard Lyon 1, 69372 Lyon ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yvette S","family":"Crijnen","sequence":"additional","affiliation":[{"name":"Department of Neurology, Erasmus University Medical Center , Rotterdam 3015GD ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilien","family":"Bernard","sequence":"additional","affiliation":[{"name":"Lyon ALS Reference Center, H\u00f4pital Neurologique Pierre Wertheimer, Hospices Civils de Lyon, Universit\u00e9 de Lyon , Bron 69677 ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Heidbreder","sequence":"additional","affiliation":[{"name":"Department of Neurology, Johannes Kepler University Linz , Linz 4020 ,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anastasia","family":"Zekeridou","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, Mayo Clinic , Rochester, MN 55905 ,","place":["USA"]},{"name":"Department of Neurology, Mayo Clinic , Rochester, MN 55905 ,","place":["USA"]},{"name":"Center for Multiple Sclerosis and Autoimmune Neurology, Mayo Clinic , Rochester, MN 55905 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marius","family":"Ringelstein","sequence":"additional","affiliation":[{"name":"Department of Neurology, Medical Faculty and University Hospital, Heinrich-Heine-University D\u00fcsseldorf , D\u00fcsseldorf 40225 ,","place":["Germany"]},{"name":"Department of Neurology, Center for Neurology and Neuropsychiatry, LVR-Klinikum, Heinrich-Heine-University D\u00fcsseldorf , D\u00fcsseldorf 40629 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Kraft","sequence":"additional","affiliation":[{"name":"Department of Neurology, Martha-Maria Hospital Halle , Halle 06120 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stjepana","family":"Kovac","sequence":"additional","affiliation":[{"name":"Department of Neurology with Institute of Translational Neurology, University of M\u00fcnster , M\u00fcnster 48149 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus-Peter","family":"Wandinger","sequence":"additional","affiliation":[{"name":"Institute of Clinical Chemistry, University Hospital Schleswig-Holstein , Kiel 24105 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juna M","family":"de Vries","sequence":"additional","affiliation":[{"name":"Department of Neurology, Erasmus University Medical Center , Rotterdam 3015GD ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnita J W","family":"Boon","sequence":"additional","affiliation":[{"name":"Department of Neurology, Erasmus University Medical Center , Rotterdam 3015GD ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon","family":"Veenbergen","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Immunology, Department of Immunology, Erasmus University Medical Center, University Medical Center , Rotterdam 3015GD ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Geis","sequence":"additional","affiliation":[{"name":"Section Translational 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