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Lookup NU author(s): Professor Michela GuglieriORCiD, Professor Volker StraubORCiD, Professor Giorgio TascaORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2025 The Author(s). Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.Objective: To characterize whole-body intramuscular fat distribution pattern in patients with sarcoglycanopathies and explore correlations with disease severity, duration and age at onset. Methods: Retrospective, cross-sectional, multicentric study enrolling patients with variants in one of the four sarcoglycan genes who underwent whole-body muscle MRI. Intramuscular fatty replacement was evaluated on T1-weighted images and represented by heatmaps. Dimensionality reduction and linear spline models examined relationships between patterns of intramuscular fat replacement and clinical findings. Results: MRI scans from 64 patients (age range 4–67 years) covering 4160 muscles were analyzed. Disease severity ranged from asymptomatic (9%) to non-ambulant (39%) patients. Sarcoglycanopathies showed consistent, selective patterns of muscle involvement across genotypes. Latissimus dorsi and subscapularis were the earliest affected muscles in the upper body, whereas head, neck and forearm muscles remained largely preserved. Distinct gradients characterized the topography of degeneration both within individual muscles and along body and limb axes. Disease severity correlated with MRI changes in both upper and lower body muscles, and with one of the dimensions identified by the multi-correspondence analysis. Patients with onset in the first decade showed a steeper cross-sectional association between disease duration and MRI abnormalities, while later-onset patients displayed a more gradual, linear relationship. Interpretation: Sarcoglycanopathies display selective muscle vulnerability with characteristic gradients of fat replacement. Scapular girdle muscles are affected early in the disease course. Intramuscular fat correlates with functional impairment and disease duration, supporting its use as a surrogate endpoint in clinical trials. Age at onset emerges as a critical prognostic factor.
Author(s): Costa-Comellas L, Monforte M, Sanchez-Montanez A, Romero-Duque P, Pegoraro E, Diaz-Manera J, Vlodavets D, Maggi L, Moscatelli M, D'Amico A, Olive M, Alonso-Perez J, Comi G, Escudero-Fernandez JM, Urcuyo GS, Pichiecchio A, Berardinelli A, Claeys KG, Bruno C, Panicucci C, Bortolani S, Torchia E, Ricci E, Monges S, Bevilacqua JA, Diaz-Jara J, Walter MC, Thiele S, Lokken N, Vissing J, Quijano-Roy S, Carlier RY, Voermans NC, Marini-Bettolo C, Guglieri M, Straub V, Leonardis L, Munell F, Gomez-Andres D, Tasca G
Publication type: Article
Publication status: Published
Journal: Annals of Clinical and Translational Neurology
Year: 2026
Pages: epub ahead of print
Online publication date: 31/12/2025
Acceptance date: 17/12/2025
Date deposited: 12/01/2026
ISSN (electronic): 2328-9503
Publisher: John Wiley and Sons Inc
URL: https://doi.org/10.1002/acn3.70303
DOI: 10.1002/acn3.70303
Data Access Statement: MRI scores are openly available in Figshare at doi: 10.6084/m9.figshare.25481632. Raw imaging data supporting the findings of this study are available on request to the corresponding author.
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