Whole-Body Pattern of Muscle Degeneration and Progression in Sarcoglycanopathies.
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Costa-Comellas Laura, Monforte Mauro, Sanchez-Montañez Angel, Romero-Duque Penélope, Pegoraro Elena, Díaz-Manera Jordi, Vlodavets Dmitry, Maggi Lorenzo, Moscatelli Marco, D'Amico Adele, Olivé Montse, Alonso-Pérez Jorge, Comi Giacomo, Escudero-Fernández José Miguel, Urcuyo Gabriela S, Pichiecchio Anna, Berardinelli Angela, Claeys Kristl G, Bruno Claudio, Panicucci Chiara, Bortolani Sara, Torchia Eleonora, Ricci Enzo, Monges Soledad, Bevilacqua Jorge A, Diaz-Jara Jorge, Walter Maggie C, Thiele Simone, Løkken Nicoline, Vissing John, Quijano-Roy Susana, Carlier Robert Y, Voermans Nicol C, Marini-Bettolo Chiara, Guglieri Michela, Straub Volker, Leonardis Lea, Munell Francina, Gómez-Andrés David, Tasca Giorgio
Аннотация
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.