Brain atrophy patterns in anti-IgLON5 disease

Anti-IgLON5 disease is an autoimmune encephalitis that presents with a heterogenous clinical phenotype, including sleep disorders, movement abnormalities and bulbar involvement. It is characterized by autoantibodies against IgLON5, 85% association with HLA-DQB1*05:∼ 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. 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. 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.

Authors

Institutions

Publication Details

Journal
Brain
Published
2025-07-12
DOI
https://doi.org/10.1093/brain/awaf256
Citations
2
Primary Topic
Autoimmune Neurological Disorders and Treatments
Type
article
Field-Weighted Citation Impact
2.78

Funders

Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

Brain atrophy patterns in anti-IgLON5 disease

Morten Blaabjerg, Anna E.M. Bastiaansen, Nicolas Carrière, Jan Lewerenz et al.
2 citations
Brain
Autoimmune Neurological Disorders and Treatments
2.78
article

Brain atrophy patterns in anti-IgLON5 disease

Morten Blaabjerg, Anna E.M. Bastiaansen, Nicolas Carrière, Jan Lewerenz, Veronique Bourg, Jeanne Benoit, Dimitri Renard, Brigitte Wildemann, Caroline Giordana, Jean‐Baptiste Davion, E Bernard, Francesc Graus, Michael Nagel, Caspar Seitz, Agnita J.W. Boon, Marie Bénaiteau, Selina Yogeshwar, Frank Leypoldt, Lídia Sabater, Sonia Quintas, Christian Urbanek, Silke Tonner, Géraldine Picard, Αναστασία Ζεκερίδου, Frederik Bartels, Anna Heidbreder, Ha‐Yeun Chung, Antoine Soulages, Klaus‐Peter Wandinger, Harald Prüß, Ulrich Hofstadt‐van Oy, Peter Schramm, Yvette S. Crijnen, Marius Ringelstein, Joan Santamaría, Akio Kimura, Alberto Vogrig, Yoya Ono, Olivier Flabeau, Sarah Demortière, Marie Rafiq, Bettina Schreiner, Thomas Grüter, Sarosh R. Irani, Florent Cluse, Raffaele Iorio, Pasquale Nigro, Ángela Milán Tomás, Katia Schwichtenberg, Julie Boucher, Fabrice Bonneville, Simone Zittel-Dirks, Takayoshi Shimohata, Maarten J. Titulaer, Clarisse Carra‐Dallière, Juna M. de Vries, Evelyn Berger–Sieczkowski, L G Kalifa, Josep Dalmau, Jérôme Honnorat, Ina Schroeder, Hélène Zéphir, Marc Chanson, Nico Melzer, Sergio Muñiz‐Castrillo, Klemens Angstwurm, Justina Dargvainiene, Javier Villacieros‐Álvarez, Emmanuel Mignot, Loana Penner, François Sellal, Romana Höftberger, Norbert Brüggemann, Carsten Finke, Nicolas Capet, Ján Kothaj, Carlos Ordás, Stefan Macher, Cédric Bruel, Gilles Ryckewaert, Philippe Damier, Mateus Mistieri Simabukuro, Marlene Tschernatsch, Édouard Berling, Maximilien Moulin, Nicola Tambasco, Jonathan Wickel, Sean Joseph Pittock, Carles Gaig, Christian Geis, Tifanie Alberto, Antonio Martin Bastida, Ilya Ayzenberg, Thomas Seifert‐Held, Stjepana Kovac, Olivier Casez, Mélanie Barbay, Jean‐Luc Houéto, Christian Hartmann, Sharon Veenbergen, Adrien Wang, Andrea Kraft, Elena Rusu, Adil Maarouf, Florian Schoeberl, Virginie Desestret, Robin van Steenhoven, Takekoshi Akira, Mette Scheller-Nissen, Aurélie Méneret Isabelle Francillard, Helene Combres, Marina Cumin, Mathilde Compoint, Eve Garrigues, Emmanuelle Derivoyre, Sohrab Mostoufizadehs, Adelaide Brasset, Arthur Attal, Céline Demourant
article en
2 citations

Abstract

Anti-IgLON5 disease is an autoimmune encephalitis that presents with a heterogenous clinical phenotype, including sleep disorders, movement abnormalities and bulbar involvement. It is characterized by autoantibodies against IgLON5, 85% association with HLA-DQB1*05:∼ 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. 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. 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.

BrainVol. 149(3)
Université Claude Bernard Lyon 1 (FR), Johannes Kepler University of Linz (AT), Centre National de la Recherche Scientifique (FR), Mayo Clinic (US), Inserm (FR), University of Southern Denmark (DK), University of Zurich (CH), University of Münster (DE), Odense University Hospital (DK), German Center for Neurodegenerative Diseases (DE), Jacksonville College (US), Erasmus MC (NL), Oxford Research Group (GB), WinnMed (US), Humboldt-Universität zu Berlin (DE), University of Oxford (GB), Hamm-Lippstadt University of Applied Sciences (DE), Düsseldorf University Hospital (DE), Comprehensive Cancer Center Vienna (AT), University Hospital of Zurich (CH), Hospices Civils de Lyon (FR), Hospital Universitario 12 De Octubre (ES), University Hospital Münster (DE), Hôpital Pierre Wertheimer (FR), University Hospital Schleswig-Holstein (DE), Centro de Investigación Biomédica en Red (ES), Hospital Clínic de Barcelona (ES), Mayo Clinic in Arizona (US), Institut NeuroMyoGène (FR), Klinikum Lippe (DE), Jena University Hospital (DE), Stanford Medicine (US), St. Josef-Hospital (DE), Berlin Institute of Health at Charité - Universitätsmedizin Berlin (DE), Martha-Maria Hospital (DE), Mayo Clinic in Florida (US), University Hospital Ulm (DE), Fundació Clínic per a la Recerca Biomèdica (ES), Consorci Institut D'Investigacions Biomediques August Pi I Sunyer (ES), Einstein Center for Neurosciences Berlin (DE), Institute of Infection and Immunity (CA), Heinrich Heine University Düsseldorf (DE), Universitat de Barcelona (ES), Medical University of Vienna (AT), University of Pennsylvania (US), University of Lübeck (DE), Stanford University (US)
Foundation for the National Institutes of Health, National Multiple Sclerosis Society, Amgen, Alexion Pharmaceuticals, Alzheimer's Disease Neuroimaging Initiative, CSL Behring, Northern California Institute for Research and Education, Wellcome Trust, E-Rare, Argenx, Horizon Therapeutics, National Institute for Health and Care Research, Epilepsy Research UK, British Medical Association, Multiple Sclerosis Society, US-UK Fulbright Commission, Guarantors of Brain, University of Oxford, Deutscher Akademischer Austauschdienst, Deutsche Forschungsgemeinschaft, Agence Nationale de la Recherche, ZonMw, Bundesministerium für Bildung und Forschung, Austrian Science Fund, Generalitat de Catalunya, Nederlandse Organisatie voor Wetenschappelijk Onderzoek, Vereniging Trustfonds Erasmus Universiteit Rotterdam, Einstein Stiftung Berlin, Stiftung für Pathobiochemie und Molekulare Diagnostik, Stichting Dioraphte, Berlin Institute of Health, National Institutes of Health, HORIZON EUROPE Framework Programme, Canadian Institutes of Health Research, Medical Research Council, Instituto de Salud Carlos III, NIHR Oxford Biomedical Research Centre, H2020 Marie Skłodowska-Curie Actions
Partnerships for the goals
Openalex Percentile: Top 9%
Autoimmune Neurological Disorders and Treatments
2.78
DOIOpen Access PDFOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.