article published yes Yvette S. Crijnen author Verena Endmayr author Suzanne C. Franken author Nadine A.M.E. Van Der Beek author Maartje Louter author Thomas Ströbel author Ellen Gelpi author Inga Koneczny author Ryuichi Shigemoto author 499F3ABC-F248-11E8-B48F-1D18A9856A870000-0001-8761-9444 Jan Lewerenz author Birgit Högl author Julia V. Wanschitz author Ulrich He Hofstadt-Van Oy author Robin W. Van Steenhoven author Mariska M.P. Nagtzaam author Jeroen Kerstens author Juliette Brenner author Anna E.M. Bastiaansen author Robert M. Verdijk author Thierry P.P. Van Den Bosch author Marco Schreurs author Sharon Veenbergen author Marcel M. Verbeek author Dave L. Roelen author Mar Guasp author Peter A.E. Sillevis Smitt author Lidia Sabater author Juna M. De Vries author Romana Höftberger author Maarten J. Titulaer author RySh department LGI1 antibody-induced pathophysiology in synapses project Background and Objectives: Anti-immunoglobulin-like cell adhesion molecule 5 (IgLON5) disease is a novel and poten- tially treatable entity. Therefore, it is important to recognize all clinical symptoms and di- agnostic clues. We specifically investigated neuromuscular signs and symptoms and muscle biopsy pathology, providing a link between IgLON5 and clinical features of myopathy. Methods: All patients diagnosed with anti-IgLON5 disease in the Netherlands between 2016 and 2023 were included. Serum and CSF samples were tested with immunohistochemistry on rat brain and in-house cell-based assay using live cells. Biopsies of the vastus lateralis muscle were performed in patients with neuromuscular signs and symptoms and analyzed in Vienna to- gether with 3 biopsies of non-Dutch patients sent to Vienna for second opinion. Results: Twenty patients with anti-IgLON5 disease were included (10 male, 50%). The median age at onset was 61.5 years (range 45–85), and the median time from onset to diagnosis was 30 months (range 3–280). Neuromuscular symptoms were present in over half of the patients (11/20), including proximal limb weakness (n = 11), axial weakness (n = 1), muscle atrophy (n = 6), and fasciculations (n = 5). All 12 muscle biopsies (9 from the Dutch cohort, 3 external) showed mild myopathic alterations, 2 additionally presented target fibers and fiber type grouping (compatible with neu- rogenic myopathy), and 3 patients showed immune cell infiltration. We found a strong upregulation of IgLON5 expression in muscle fibers in all patients and also in different muscle disease controls, while immunoreactivity in healthy control muscle was faint/absent. Discussion: Our data support that IgLON5 might play a role in muscle regeneration, which might result in proximal myopathy as a prominent clinical feature in anti-IgLON5 disease. This finding broadens the clinical phenotype of anti-IgLON5 disease and can be an important clue for earlier diagnosis and start of immunotherapy. https://research-explorer.ista.ac.at/download/22615/22631/2026_Neurology_Crijnen.pdf application/pdfno Wolters Kluwer2026 eng 2332-7812 4244193010.1212/NXI.0000000000200525 135e200525 Crijnen YS, Endmayr V, Franken SC, et al. Muscle regeneration failure may lead to clinical features of myopathy in anti-IgLON5 disease. <i>Neurology, Neuroimmunology &#38; Neuroinflammation</i>. 2026;13(5):e200525. doi:<a href="https://doi.org/10.1212/NXI.0000000000200525">10.1212/NXI.0000000000200525</a> Y. S. Crijnen <i>et al.</i>, “Muscle regeneration failure may lead to clinical features of myopathy in anti-IgLON5 disease,” <i>Neurology, Neuroimmunology &#38; Neuroinflammation</i>, vol. 13, no. 5. Wolters Kluwer, p. e200525, 2026. Crijnen, Yvette S., et al. “Muscle Regeneration Failure May Lead to Clinical Features of Myopathy in Anti-IgLON5 Disease.” <i>Neurology, Neuroimmunology &#38; Neuroinflammation</i>, vol. 13, no. 5, Wolters Kluwer, 2026, p. e200525, doi:<a href="https://doi.org/10.1212/NXI.0000000000200525">10.1212/NXI.0000000000200525</a>. Crijnen YS, Endmayr V, Franken SC, Van Der Beek NAME, Louter M, Ströbel T, Gelpi E, Koneczny I, Shigemoto R, Lewerenz J, Högl B, Wanschitz JV, Hofstadt-Van Oy UH, Van Steenhoven RW, Nagtzaam MMP, Kerstens J, Brenner J, Bastiaansen AEM, Verdijk RM, Van Den Bosch TPP, Schreurs M, Veenbergen S, Verbeek MM, Roelen DL, Guasp M, Sillevis Smitt PAE, Sabater L, De Vries JM, Höftberger R, Titulaer MJ. 2026. Muscle regeneration failure may lead to clinical features of myopathy in anti-IgLON5 disease. Neurology, Neuroimmunology &#38; Neuroinflammation. 13(5), e200525. Y.S. Crijnen, V. Endmayr, S.C. Franken, N.A.M.E. Van Der Beek, M. Louter, T. Ströbel, E. Gelpi, I. Koneczny, R. Shigemoto, J. Lewerenz, B. Högl, J.V. Wanschitz, U.H. Hofstadt-Van Oy, R.W. Van Steenhoven, M.M.P. Nagtzaam, J. Kerstens, J. Brenner, A.E.M. Bastiaansen, R.M. Verdijk, T.P.P. Van Den Bosch, M. Schreurs, S. Veenbergen, M.M. Verbeek, D.L. Roelen, M. Guasp, P.A.E. Sillevis Smitt, L. Sabater, J.M. De Vries, R. Höftberger, M.J. Titulaer, Neurology, Neuroimmunology &#38; Neuroinflammation 13 (2026) e200525. Crijnen, Y. S., Endmayr, V., Franken, S. C., Van Der Beek, N. A. M. E., Louter, M., Ströbel, T., … Titulaer, M. J. (2026). Muscle regeneration failure may lead to clinical features of myopathy in anti-IgLON5 disease. <i>Neurology, Neuroimmunology &#38; Neuroinflammation</i>. Wolters Kluwer. <a href="https://doi.org/10.1212/NXI.0000000000200525">https://doi.org/10.1212/NXI.0000000000200525</a> Crijnen, Yvette S., Verena Endmayr, Suzanne C. Franken, Nadine A.M.E. Van Der Beek, Maartje Louter, Thomas Ströbel, Ellen Gelpi, et al. “Muscle Regeneration Failure May Lead to Clinical Features of Myopathy in Anti-IgLON5 Disease.” <i>Neurology, Neuroimmunology &#38; Neuroinflammation</i>. Wolters Kluwer, 2026. <a href="https://doi.org/10.1212/NXI.0000000000200525">https://doi.org/10.1212/NXI.0000000000200525</a>. 226152026-08-02T22:01:52Z2026-08-03T08:16:04Z