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

Barp, Andrea; Laforet, Pascal; Bello, Luca; Tasca, Giorgio; Vissing, John; Monforte, Mauro; Ricci, Enzo; Choumert, Ariane; Stojkovic, Tanya; Malfatti, Edoardo; Pegoraro, Elena; Semplicini, Claudio; Stramare, Roberto; Scheidegger, Oliver; Haberlova, Jana; Straub, Volker; Marini-Bettolo, Chiara; Løkken, Nicoline; Diaz-Manera, Jordi; Urtizberea, Jon A; ... (2020). European muscle MRI study in limb girdle muscular dystrophy type R1/2A (LGMDR1/LGMD2A). Journal of neurology, 267(1), pp. 45-56. Springer-Medizin-Verlag 10.1007/s00415-019-09539-y

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Head Organs and Neurology (DKNS) > Clinic of Neurology
04 Faculty of Medicine > Department of Radiology, Neuroradiology and Nuclear Medicine (DRNN) > Institute of Diagnostic and Interventional Neuroradiology

UniBE Contributor:

Scheidegger, Oliver

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0340-5354

Publisher:

Springer-Medizin-Verlag

Language:

English

Submitter:

Martin Zbinden

Date Deposited:

08 Oct 2019 08:44

Last Modified:

14 Jan 2020 01:31

Publisher DOI:

10.1007/s00415-019-09539-y

PubMed ID:

31555977

Uncontrolled Keywords:

CAPN3 mutations LGMDR1/LGMD2A Mercuri score Muscle MRI

BORIS DOI:

10.7892/boris.133712

URI:

https://boris.unibe.ch/id/eprint/133712

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