Muscle magnetic resonance imaging in myotonic dystrophy type 1 (DM1) : Refining muscle involvement and implications for clinical trials
Garibaldi, Matteo (Sant'Andrea Hospital)
Nicoletti, Tommaso (Università Cattolica del Sacro Cuore)
Bucci, Elisabetta (Sant'Andrea Hospital)
Fionda, Laura (Sant'Andrea Hospital. Sapienza University of Rome)
Leonardi, Luca (Sant'Andrea Hospital)
Morino, Stefania (Sant'Andrea Hospital)
Tufano, Laura (Sant'Andrea Hospital)
Alfieri, Girolamo (Sant'Andrea Hospital)
Lauletta, Antonio (Sant'Andrea Hospital)
Merlonghi, Gioia (Sant'Andrea Hospital)
Perna, Alessia (Università Cattolica del Sacro Cuore)
Rossi, Salvatore (Università Cattolica del Sacro Cuore)
Ricci, Enzo (Università Cattolica del Sacro Cuore)
Alonso-Pérez, Jorge (Institut d'Investigació Biomèdica Sant Pau)
Tartaglione, Tommaso (Istituto Dermopatico dell'Immacolata)
Petrucci, Antonio (San Camillo Forlanini Hospital)
Pennisi, Elena Maria (San Filippo Neri Hospital)
Salvetti, Marco (IRCCS Istituto Neurologico Mediterraneo (INM) Neuromed)
Cutter, Gary (University of Alabama at Birmingham)
Diaz-Manera, Jordi (Institut d'Investigació Biomèdica Sant Pau)
Silvestri, Gabriella (Università Cattolica del Sacro Cuore)
Antonini, Giovanni (Sant'Andrea Hospital)

Data:	2021
Resum:	Only a few studies have reported muscle imaging data on small cohorts of patients with myotonic dystrophy type 1 (DM1). We aimed to investigate the muscle involvement in a large cohort of patients in order to refine the pattern of muscle involvement, to better understand the pathophysiological mechanisms of muscle weakness, and to identify potential imaging biomarkers for disease activity and severity. One hundred and thirty-four DM1 patients underwent a cross-sectional muscle magnetic resonance imaging (MRI) study. Short tau inversion recovery (STIR) and T1 sequences in the lower and upper body were analyzed. Fat replacement, muscle atrophy and STIR positivity were evaluated using three different scales. Correlations between MRI scores, clinical features and genetic background were investigated. The most frequent pattern of muscle involvement in T1 consisted of fat replacement of the tongue, sternocleidomastoideus, paraspinalis, gluteus minimus, distal quadriceps and gastrocnemius medialis. Degree of fat replacement at MRI correlated with clinical severity and disease duration, but not with CTG expansion. Fat replacement was also detected in milder/asymptomatic patients. More than 80% of patients had STIR-positive signals in muscles. Most DM1 patients also showed a variable degree of muscle atrophy regardless of MRI signs of fat replacement. A subset of patients (20%) showed a 'marbled' muscle appearance. Muscle MRI is a sensitive biomarker of disease severity alsofor the milder spectrum of disease. STIR hyperintensity seems to precede fat replacement in T1. Beyond fat replacement, STIR positivity, muscle atrophy and a 'marbled' appearance suggest further mechanisms of muscle wasting and weakness in DM1, representing additional outcome measures and therapeutic targets for forthcoming clinical trials. We refined the pattern of muscle involvement in DM1 by upper and lower body muscle magnetic resonance imaging (MRI), identifying the most frequent pattern of fat replacement and confirming that muscle MRI is a sensitive biomarker of disease burden in DM1. We also observed: STIR-positive muscles in 80% of patients preceding fat replacement, muscle atrophy in muscles unreplaced by fat, and progeroid muscle appearance supporting a premature muscle senescence. Our findings provide novel insights into the pathophysiological mechanisms of muscle wasting and weakness in DM1, and could represent additional outcome measures and therapeutic targets for forthcoming clinical trials.
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Clinical trials ; CTG ; Muscle atrophy and inflammation ; Muscle MRI ; Myotonic dystrophy type 1
Publicat a:	European Journal of Neurology, Vol. 29 (december 2021) , p. 843-854, ISSN 1468-1331

DOI: 10.1111/ene.15174
PMID: 34753219

12 p, 2.9 MB

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