---
DOAJ_listed: '1'
OA_place: publisher
OA_type: gold
PlanS_conform: '1'
_id: '22615'
abstract:
- lang: eng
  text: "Background and Objectives: \r\nAnti-immunoglobulin-like cell adhesion molecule
    5 (IgLON5) disease is a novel and poten-\r\ntially treatable entity. Therefore,
    it is important to recognize all clinical symptoms and di-\r\nagnostic clues.
    We specifically investigated neuromuscular signs and symptoms and muscle biopsy
    pathology, providing a link between IgLON5 and clinical features of myopathy.\r\nMethods:
    \r\nAll 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-\r\ngether with 3 biopsies of non-Dutch patients sent
    to Vienna for second opinion.\r\nResults: \r\nTwenty 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-\r\nrogenic 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.\r\nDiscussion:
    \r\nOur 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."
acknowledgement: "One author (Manuela Paunovic) was removed from the paper due to
  personal circumstances. Her contributions were removed from the manuscript before
  final review. The authors thank all patients for their participation and all referring
  physicians. The authors thank Professor Joachim Weis at the Medical Faculty RWTH
  Aachen University for his contribution to the manuscript. The authors would like
  to thank Andrea Polt and Irene Erber at the Medical University of Vienna, and Jacqueline
  Montanaro at IST Austria, for their assistance in the laboratory. N.A.M.E. van der
  Beek participates in EURO-NMD. M.W.J. Schreurs, P.A.E. Sillevis Smitt, J.M. de Vries,
  and M.J. Titulaer are members of the European Reference Network for Rare Immunodeficiency,
  Autoinflammatory and Autoimmune Diseases–Project ID No 739543 (ERN-RITA; HCP Erasmus
  MC). IK was funded by the Austrian Science Fund (FWF, T996-B30). RS was funded by
  the Austrian Science Fund (FWF, SYNABS, I6565-B). JL was funded by German Federal
  Ministry of Education and Research (BMBF, Forschungsverbund CONNECT-GEN-\r\nERATE,
  01 GM2208B). RvS was funded by AEA Seed Grant 2023 and InterAct Grant of Alzheimer
  Nederland 2023. LS was funded by Instituto de Salud Carlos III (ISCIII, PI21/ 00165)
  and the Networking Support Scheme funded from the European Union’s Horizon 2020
  research and innovation program (EJP RD COFUND-EJP N° 825575). JdV was funded by
  AEA Seed Grant 2021. RH was funded by grants from the Austrian Science Fund (FWF,
  SYNABS, I4685-B, I6565-B), Forschungsf¨orderungsgesellschaft (FFG, IGNITE-\r\nMIND,
  FO999920011), and the Austrian Society of\r\nNeurology (\r\n¨\r\nOsterreichische
  Gesellschaft f¨ur Neurologie).\r\nMT was funded by the Dutch EpilepsieNL Foundation
  (NEF 19-08), an Interlaken Leadership award, Dioraphte (2001 0403) the Dutch Research
  Council (ZonMW, PARADE-\r\nVIMP) and E-RARE JTC 2018 (UltraAIE, 90030376505)."
article_processing_charge: Yes
article_type: original
author:
- first_name: Yvette S.
  full_name: Crijnen, Yvette S.
  last_name: Crijnen
- first_name: Verena
  full_name: Endmayr, Verena
  last_name: Endmayr
- first_name: Suzanne C.
  full_name: Franken, Suzanne C.
  last_name: Franken
- first_name: Nadine A.M.E.
  full_name: Van Der Beek, Nadine A.M.E.
  last_name: Van Der Beek
- first_name: Maartje
  full_name: Louter, Maartje
  last_name: Louter
- first_name: Thomas
  full_name: Ströbel, Thomas
  last_name: Ströbel
- first_name: Ellen
  full_name: Gelpi, Ellen
  last_name: Gelpi
- first_name: Inga
  full_name: Koneczny, Inga
  last_name: Koneczny
- first_name: Ryuichi
  full_name: Shigemoto, Ryuichi
  id: 499F3ABC-F248-11E8-B48F-1D18A9856A87
  last_name: Shigemoto
  orcid: 0000-0001-8761-9444
- first_name: Jan
  full_name: Lewerenz, Jan
  last_name: Lewerenz
- first_name: Birgit
  full_name: Högl, Birgit
  last_name: Högl
- first_name: Julia V.
  full_name: Wanschitz, Julia V.
  last_name: Wanschitz
- first_name: Ulrich He
  full_name: Hofstadt-Van Oy, Ulrich He
  last_name: Hofstadt-Van Oy
- first_name: Robin W.
  full_name: Van Steenhoven, Robin W.
  last_name: Van Steenhoven
- first_name: Mariska M.P.
  full_name: Nagtzaam, Mariska M.P.
  last_name: Nagtzaam
- first_name: Jeroen
  full_name: Kerstens, Jeroen
  last_name: Kerstens
- first_name: Juliette
  full_name: Brenner, Juliette
  last_name: Brenner
- first_name: Anna E.M.
  full_name: Bastiaansen, Anna E.M.
  last_name: Bastiaansen
- first_name: Robert M.
  full_name: Verdijk, Robert M.
  last_name: Verdijk
- first_name: Thierry P.P.
  full_name: Van Den Bosch, Thierry P.P.
  last_name: Van Den Bosch
- first_name: Marco
  full_name: Schreurs, Marco
  last_name: Schreurs
- first_name: Sharon
  full_name: Veenbergen, Sharon
  last_name: Veenbergen
- first_name: Marcel M.
  full_name: Verbeek, Marcel M.
  last_name: Verbeek
- first_name: Dave L.
  full_name: Roelen, Dave L.
  last_name: Roelen
- first_name: Mar
  full_name: Guasp, Mar
  last_name: Guasp
- first_name: Peter A.E.
  full_name: Sillevis Smitt, Peter A.E.
  last_name: Sillevis Smitt
- first_name: Lidia
  full_name: Sabater, Lidia
  last_name: Sabater
- first_name: Juna M.
  full_name: De Vries, Juna M.
  last_name: De Vries
- first_name: Romana
  full_name: Höftberger, Romana
  last_name: Höftberger
- first_name: Maarten J.
  full_name: Titulaer, Maarten J.
  last_name: Titulaer
citation:
  ama: 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>
  apa: 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>
  chicago: 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>.
  ieee: 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.
  ista: 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.
  mla: 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>.
  short: 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.
das_tickbox: '1'
dataavailabilitystatement: Any data not published within this article are available
  at Erasmus MC, Rotterdam, and Medical University of Vienna. Data will be shared
  on reasonable request from any qualified investigator, ascertaining anonymization
  of the individual patients, in line with European privacy regulations.
date_created: 2026-08-02T22:01:52Z
date_published: 2026-09-01T00:00:00Z
date_updated: 2026-08-03T08:16:04Z
day: '01'
ddc:
- '570'
department:
- _id: RySh
doi: 10.1212/NXI.0000000000200525
external_id:
  pmid:
  - '42441930'
file:
- access_level: open_access
  checksum: 7cc4c4c180a2cf65603a02bef7b75784
  content_type: application/pdf
  creator: dernst
  date_created: 2026-08-03T08:06:16Z
  date_updated: 2026-08-03T08:06:16Z
  file_id: '22631'
  file_name: 2026_Neurology_Crijnen.pdf
  file_size: 1122644
  relation: main_file
  success: 1
file_date_updated: 2026-08-03T08:06:16Z
has_accepted_license: '1'
intvolume: '        13'
issue: '5'
language:
- iso: eng
month: '09'
oa: 1
oa_version: Published Version
page: e200525
pmid: 1
project:
- _id: 05970B30-7A3F-11EA-A408-12923DDC885E
  grant_number: I04638
  name: LGI1 antibody-induced pathophysiology in synapses
publication: Neurology, Neuroimmunology & Neuroinflammation
publication_identifier:
  eissn:
  - 2332-7812
publication_status: published
publisher: Wolters Kluwer
quality_controlled: '1'
researchdata_availability: upon request
scopus_import: '1'
status: public
supplementarymaterial: no
title: Muscle regeneration failure may lead to clinical features of myopathy in anti-IgLON5
  disease
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 13
year: '2026'
...