000285470 001__ 285470 000285470 005__ 20260309093634.0 000285470 0247_ $$2doi$$a10.1093/brain/awaf256 000285470 0247_ $$2pmid$$apmid:40650880 000285470 0247_ $$2ISSN$$a0006-8950 000285470 0247_ $$2ISSN$$a1460-2156 000285470 037__ $$aDZNE-2026-00247 000285470 041__ $$aEnglish 000285470 082__ $$a610 000285470 1001_ $$00009-0001-4221-7131$$aYogeshwar, Selina M$$b0 000285470 245__ $$aBrain atrophy patterns in anti-IgLON5 disease. 000285470 260__ $$aOxford$$bOxford Univ. Press$$c2026 000285470 3367_ $$2DRIVER$$aarticle 000285470 3367_ $$2DataCite$$aOutput Types/Journal article 000285470 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1773045266_14562 000285470 3367_ $$2BibTeX$$aARTICLE 000285470 3367_ $$2ORCID$$aJOURNAL_ARTICLE 000285470 3367_ $$00$$2EndNote$$aJournal Article 000285470 520__ $$aAnti-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. 000285470 536__ $$0G:(DE-HGF)POF4-353$$a353 - Clinical and Health Care Research (POF4-353)$$cPOF4-353$$fPOF IV$$x0 000285470 588__ $$aDataset connected to CrossRef, PubMed, , Journals: pub.dzne.de 000285470 650_7 $$2Other$$aIgLON5 000285470 650_7 $$2Other$$aMRI 000285470 650_7 $$2Other$$aatrophy 000285470 650_7 $$2Other$$aautoimmune encephalitis 000285470 650_7 $$2NLM Chemicals$$aIgLON5 protein, human 000285470 650_7 $$2NLM Chemicals$$aAutoantibodies 000285470 650_7 $$2NLM Chemicals$$aCell Adhesion Molecules, Neuronal 000285470 650_2 $$2MeSH$$aHumans 000285470 650_2 $$2MeSH$$aMale 000285470 650_2 $$2MeSH$$aAtrophy: pathology 000285470 650_2 $$2MeSH$$aFemale 000285470 650_2 $$2MeSH$$aMiddle Aged 000285470 650_2 $$2MeSH$$aBrain: pathology 000285470 650_2 $$2MeSH$$aBrain: diagnostic imaging 000285470 650_2 $$2MeSH$$aAged 000285470 650_2 $$2MeSH$$aMagnetic Resonance Imaging 000285470 650_2 $$2MeSH$$aAdult 000285470 650_2 $$2MeSH$$aAutoantibodies: immunology 000285470 650_2 $$2MeSH$$aCell Adhesion Molecules, Neuronal: immunology 000285470 650_2 $$2MeSH$$aDisease Progression 000285470 650_2 $$2MeSH$$aAutoimmune Diseases of the Nervous System: pathology 000285470 650_2 $$2MeSH$$aAutoimmune Diseases of the Nervous System: diagnostic imaging 000285470 650_2 $$2MeSH$$aAutoimmune Diseases of the Nervous System: immunology 000285470 650_2 $$2MeSH$$aEncephalitis: pathology 000285470 650_2 $$2MeSH$$aEncephalitis: immunology 000285470 650_2 $$2MeSH$$aEncephalitis: diagnostic imaging 000285470 7001_ $$00000-0003-3523-4520$$aBartels, Frederik$$b1 000285470 7001_ $$00000-0001-8927-9818$$aGrüter, Thomas$$b2 000285470 7001_ $$00000-0001-5958-3288$$aMuñiz-Castrillo, Sergio$$b3 000285470 7001_ $$aPicard, Géraldine$$b4 000285470 7001_ $$aCrijnen, Yvette S$$b5 000285470 7001_ $$aBernard, Emilien$$b6 000285470 7001_ $$aHeidbreder, Anna$$b7 000285470 7001_ $$aZekeridou, Anastasia$$b8 000285470 7001_ $$aRingelstein, Marius$$b9 000285470 7001_ $$aKraft, Andrea$$b10 000285470 7001_ $$aKovac, Stjepana$$b11 000285470 7001_ $$aWandinger, Klaus-Peter$$b12 000285470 7001_ $$ade Vries, Juna M$$b13 000285470 7001_ $$aBoon, Agnita J W$$b14 000285470 7001_ $$aVeenbergen, Sharon$$b15 000285470 7001_ $$aGeis, Christian$$b16 000285470 7001_ $$aPenner, Loana$$b17 000285470 7001_ $$00000-0002-2420-701X$$aMelzer, Nico$$b18 000285470 7001_ $$00000-0002-8972-515X$$aLeypoldt, Frank$$b19 000285470 7001_ $$aBlaabjerg, Morten$$b20 000285470 7001_ $$00000-0002-6140-5584$$aPittock, Sean J$$b21 000285470 7001_ $$aGaig, Carles$$b22 000285470 7001_ $$aSabater, Lidia$$b23 000285470 7001_ $$aSantamaria, Joan$$b24 000285470 7001_ $$aGraus, Francesc$$b25 000285470 7001_ $$aDalmau, Josep$$b26 000285470 7001_ 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