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J Neurol. 2019 Sep 25. doi: 10.1007/s00415-019-09539-y. [Epub ahead of print]

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

Author information

1
Department of Neurosciences DNS, Neuromuscular Centre, University of Padova, Padua, Italy. andrea.barp1985@libero.it.
2
APHP, G-H Pitié-Salpêtrière, Institut de Myologie, Centre de Référence des Maladies Neuromusculaires Paris Est, Paris, France. andrea.barp1985@libero.it.
3
Neurology Department, Raymond-Poincaré Teaching Hospital, Centre de Référence Des Maladies Neuromusculaires Nord/Est/Ile-de-France, AP-HP, Garches, France.
4
Department of Neurosciences DNS, Neuromuscular Centre, University of Padova, Padua, Italy.
5
Unità Operativa Complessa Di Neurologia, Dipartimento Di Scienze Dell'Invecchiamento, Neurologiche, Ortopediche E Della Testa-Colo, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.
6
Copenhagen Neuromuscular Center, Rigshospitalet, University of Copenhagen, Copenhaghen, Denmark.
7
Centre de Référence des Maladies Neuromusculaires PACA-Réunion-Rhônes-Alpes CHU, La Réunion, France.
8
APHP, G-H Pitié-Salpêtrière, Institut de Myologie, Centre de Référence des Maladies Neuromusculaires Paris Est, Paris, France.
9
Department of Medicine (DIMED), Institute of Radiology, University of Padova, Padua, Italy.
10
Department of Neurology, Institute for Diagnostic and Interventional Neuroradiology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
11
Department of Paediatric Neurology, Charles University in Prague, Prague, Czech Republic.
12
John Walton Muscular Dystrophy Research Centre, MRC Centre for Neuromuscular Diseases, Institute of Genetic Medicine, Newcastle Upon Tyne, UK.
13
Unitat de Malalties Neuromusculars, Servei de Neurologia, Hospital de La Santa Creu I Sant Pau, Barcelona, Spain.
14
Centre de Compétence Neuromusculaire Filnemus/APHP, Hôpital Marin, Hendaye, France.
15
Pediatric Neurology and Nemo Clinical Centre, Università Cattolica Sacro Cuore, Fondazione Policlinico Universitario, A. Gemelli, Rome, Italy.
16
Radiology Department, Faculty Hospital Motol, Prague, Czech Republic.
17
Friedrich-Baur Institut, Ludwig-Maximilians University Munich, Munich, Germany.
18
APHP, Department of Radiology, Garches Neuromuscular Center (GNMH), Raymond Poincaré University Hospital (UVSQ, U 1179), Garches, France.

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.

KEYWORDS:

CAPN3 mutations; LGMDR1/LGMD2A; Mercuri score; Muscle MRI

PMID:
31555977
DOI:
10.1007/s00415-019-09539-y

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