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Whole-Body Pattern of Muscle Degeneration and Progression in Sarcoglycanopathies

Title: Whole-Body Pattern of Muscle Degeneration and Progression in Sarcoglycanopathies
Authors: 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
Source: Annals of Clinical and Translational Neurology, 2026
Publisher Information: John Wiley and Sons Inc
Publication Year: 2026
Collection: Newcastle University Library ePrints Service
Description: © 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 ...
Document Type: article in journal/newspaper
File Description: application/pdf
Language: unknown
Relation: https://eprints.ncl.ac.uk/309870; https://eprints.ncl.ac.uk/fulltext.aspx?url=309870/D177A1D0-3EF6-4D99-B349-D014CE1C3F61.pdf&pub_id=309870
Availability: https://eprints.ncl.ac.uk/309870
Rights: https://creativecommons.org/licenses/by/4.0/
Accession Number: edsbas.AE7CB535
Database: BASE