TY - JOUR

T1 - European muscle MRI study in limb girdle muscular dystrophy type R1/2A (LGMDR1/LGMD2A)

AU - Barp, Andrea

AU - Laforet, Pascal

AU - Bello, Luca

AU - Tasca, Giorgio

AU - Vissing, John

AU - Monforte, Mauro

AU - Ricci, Enzo

AU - Choumert, Ariane

AU - Stojkovic, Tanya

AU - Malfatti, Edoardo

AU - Pegoraro, Elena

AU - Semplicini, Claudio

AU - Stramare, Roberto

AU - Scheidegger, Olivier

AU - Haberlova, Jana

AU - Straub, Volker

AU - Marini-Bettolo, Chiara

AU - Løkken, Nicoline

AU - Diaz-Manera, Jordi

AU - Urtizberea, Jon A

AU - Mercuri, Eugenio

AU - Kynčl, Martin

AU - Walter, Maggie C

AU - Carlier, Robert Y

PY - 2020/1

Y1 - 2020/1

N2 - 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.

AB - 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.

U2 - 10.1007/s00415-019-09539-y

DO - 10.1007/s00415-019-09539-y

M3 - Journal article

C2 - 31555977

VL - 267

SP - 45

EP - 56

JO - Deutsche Zeitschrift fur Nervenheilkunde

JF - Deutsche Zeitschrift fur Nervenheilkunde

SN - 0939-1517

IS - 1

ER -