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01-01-2020 | Magnetic Resonance Imaging | Original Communication

European muscle MRI study in limb girdle muscular dystrophy type R1/2A (LGMDR1/LGMD2A)

Authors: Andrea Barp, Pascal Laforet, Luca Bello, Giorgio Tasca, John Vissing, Mauro Monforte, Enzo Ricci, Ariane Choumert, Tanya Stojkovic, Edoardo Malfatti, Elena Pegoraro, Claudio Semplicini, Roberto Stramare, Olivier Scheidegger, Jana Haberlova, Volker Straub, Chiara Marini-Bettolo, Nicoline Løkken, Jordi Diaz-Manera, Jon A. Urtizberea, Eugenio Mercuri, Martin Kynčl, Maggie C. Walter, Robert Y. Carlier

Published in: Journal of Neurology | Issue 1/2020

Abstract

Background

Limb girdle muscular dystrophy type R1/2A (LGMDR1/LGMD2A) is a progressive myopathy caused by deficiency of calpain 3, a calcium-dependent cysteine protease of skeletal muscle, and it represents the most frequent type of LGMD worldwide. In the last few years, muscle magnetic resonance imaging (MRI) has been proposed as a tool for identifying patterns of muscular involvement in genetic disorders and as a biomarker of disease progression in muscle diseases. In this study, 57 molecularly confirmed LGMDR1 patients from a European cohort (age range 7–78 years) underwent muscle MRI and a global evaluation of functional status (Gardner-Medwin and Walton score and ability to raise the arms).

Results

We confirmed a specific pattern of fatty substitution involving predominantly the hip adductors and hamstrings in lower limbs. Spine extensors were more severely affected than spine rotators, in agreement with higher incidence of lordosis than scoliosis in LGMDR1. Hierarchical clustering of lower limb MRI scores showed that involvement of anterior thigh muscles discriminates between classes of disease progression. Severity of muscle fatty substitution was significantly correlated with CAPN3 mutations: in particular, patients with no or one “null” alleles showed a milder involvement, compared to patients with two null alleles (i.e., predicting absence of calpain-3 protein). Expectedly, fat infiltration scores strongly correlated with functional measures. The “pseudocollagen” sign (central areas of sparing in some muscle) was associated with longer and more severe disease course.

Conclusions

We conclude that skeletal muscle MRI represents a useful tool in the diagnostic workup and clinical management of LGMDR1.

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Title: European muscle MRI study in limb girdle muscular dystrophy type R1/2A (LGMDR1/LGMD2A)
Authors: Andrea Barp
Pascal Laforet
Luca Bello
Giorgio Tasca
John Vissing
Mauro Monforte
Enzo Ricci
Ariane Choumert
Tanya Stojkovic
Edoardo Malfatti
Elena Pegoraro
Claudio Semplicini
Roberto Stramare
Olivier Scheidegger
Jana Haberlova
Volker Straub
Chiara Marini-Bettolo
Nicoline Løkken
Jordi Diaz-Manera
Jon A. Urtizberea
Eugenio Mercuri
Martin Kynčl
Maggie C. Walter
Robert Y. Carlier
Publication date: 01-01-2020
Publisher: Springer Berlin Heidelberg
Keywords: Magnetic Resonance Imaging
Magnetic Resonance Imaging
Muscular Dystrophy
Muscular Dystrophy
Published in: Journal of Neurology / Issue 1/2020
Print ISSN: 0340-5354
Electronic ISSN: 1432-1459
DOI: https://doi.org/10.1007/s00415-019-09539-y

At a glance: The STEP trials

Springer Medicine

European muscle MRI study in limb girdle muscular dystrophy type R1/2A (LGMDR1/LGMD2A)

Abstract

Background

Results

Conclusions

At a glance: The STEP trials

Springer Medicine

Abstract

Background

Results

Conclusions

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