Journal Article

DZNE-2026-00247

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Brain atrophy patterns in anti-IgLON5 disease.

Yogeshwar, S. M. ; Bartels, F. ; Grüter, T. ; Muñiz-Castrillo, S. ; Picard, G. ; Crijnen, Y. S. ; Bernard, E. ; Heidbreder, A. ; Zekeridou, A. ; Ringelstein, M. ; Kraft, A. ; Kovac, S. ; Wandinger, K.-P. ; de Vries, J. M. ; Boon, A. J. W. ; Veenbergen, S. ; Geis, C. ; Penner, L. ; Melzer, N. ; Leypoldt, F. ; Blaabjerg, M. ; Pittock, S. J. ; Gaig, C. ; Sabater, L. ; Santamaria, J. ; Graus, F. ; Dalmau, J. ; Prüss, H.DZNE* ; Höftberger, R. ; Schreiner, B. ; McKeon, A. ; Lewerenz, J. ; Irani, S. ; Mignot, E. ; Titulaer, M. J. ; Ayzenberg, I. ; Honnorat, J. ; Finke, C. ; Consortium, I. I. (Collaboration Author) ; Francillard, A. M. I. (Contributor) ; Renard, D. (Contributor) ; Desestret, V. (Contributor) ; Capet, N. (Contributor) ; Davion, J. (Contributor) ; Boucher, J. (Contributor) ; Zephir, H. (Contributor) ; Damier, P. (Contributor) ; Combres, H. (Contributor) ; Rafiq, M. (Contributor) ; Bonneville, F. (Contributor) ; Cumin, M. (Contributor) ; Soulages, A. (Contributor) ; Compoint, M. (Contributor) ; Moulin, M. (Contributor) ; Berling, E. (Contributor) ; Garrigues, E. (Contributor) ; Chanson, M. (Contributor) ; Bourg, V. (Contributor) ; Giordana, C. (Contributor) ; Benoit, J. (Contributor) ; Flabeau, O. (Contributor) ; Derivoyre, E. (Contributor) ; Ryckewaert, G. (Contributor) ; Alberto, T. (Contributor) ; Carriere, N. (Contributor) ; Mostoufizadehs, S. (Contributor) ; Barbay, M. (Contributor) ; Benaiteau, M. (Contributor) ; Vogrig, A. (Contributor) ; Sellal, F. (Contributor) ; Casez, O. (Contributor) ; Bruel, C. (Contributor) ; Kalifa, L. (Contributor) ; Rusu, E. C. (Contributor) ; Demortiere, S. (Contributor) ; Maarouf, A. (Contributor) ; Wang, A. (Contributor) ; Brasset, A. (Contributor) ; Dalliere, C. C. (Contributor) ; Attal, A. (Contributor) ; Demourant, C. (Contributor) ; Cluse, F. (Contributor) ; Houeto, J.-L. (Contributor) ; Brueggemann, N. (Contributor) ; Dargvainiene, J. (Contributor) ; Seifert, T. (Contributor) ; Oy, U. H. (Contributor) ; Nagel, M. (Contributor) ; Urbanek, C. (Contributor) ; Schroeder, I. (Contributor) ; Schramm, P. (Contributor) ; Tonner, S. (Contributor) ; Seitz, C. (Contributor) ; Tschernatsch, M. (Contributor) ; Chung, H.-Y. (Contributor) ; Wickel, J. (Contributor) ; Schoeberl, F. (Contributor) ; Macher, S. (Contributor) ; Simabukuro, M. M. (Contributor) ; Zittel-Dirks, S. (Contributor) ; Wildemann, B. (Contributor) ; Kothaj, J. (Contributor) ; Ordas, C. (Contributor) ; Álvarez, J. V. (Contributor) ; Angstwurm, K. (Contributor) ; Macher, S. (Contributor) ; Berger-Sieczkowski, E. (Contributor) ; Tomás, Á. M. (Contributor) ; Bastida, A. M. (Contributor) ; Quintas, S. (Contributor) ; Tambasco, N. (Contributor) ; Nigro, P. (Contributor) ; Iorio, R. (Contributor) ; Ono, Y. (Contributor) ; Shimohata, T. (Contributor) ; Akio, K. (Contributor) ; Akira, T. (Contributor) ; Scheller-Nissen, M. (Contributor) ; Hartmann, C. (Contributor) ; Bastiaansen, D. (Contributor) ; van Steenhoven, R. (Contributor) ; Schwichtenberg, K. (Contributor)

2026
Oxford Univ. Press Oxford

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Please use a persistent id in citations: doi:10.1093/brain/awaf256

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.

Keyword(s): Humans (MeSH) ; Male (MeSH) ; Atrophy: pathology (MeSH) ; Female (MeSH) ; Middle Aged (MeSH) ; Brain: pathology (MeSH) ; Brain: diagnostic imaging (MeSH) ; Aged (MeSH) ; Magnetic Resonance Imaging (MeSH) ; Adult (MeSH) ; Autoantibodies: immunology (MeSH) ; Cell Adhesion Molecules, Neuronal: immunology (MeSH) ; Disease Progression (MeSH) ; Autoimmune Diseases of the Nervous System: pathology (MeSH) ; Autoimmune Diseases of the Nervous System: diagnostic imaging (MeSH) ; Autoimmune Diseases of the Nervous System: immunology (MeSH) ; Encephalitis: pathology (MeSH) ; Encephalitis: immunology (MeSH) ; Encephalitis: diagnostic imaging (MeSH) ; IgLON5 ; MRI ; atrophy ; autoimmune encephalitis ; IgLON5 protein, human ; Autoantibodies ; Cell Adhesion Molecules, Neuronal

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Contributing Institute(s):

1. Autoimmune Encephalopathies (AG Prüß)

Research Program(s):

1. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 10 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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