European muscle MRI study in limb girdle muscular dystrophy type R1/2A (LGMDR1/LGMD2A)
Por:
Barp, A, Laforet, P, Bello, L, Tasca, G, Vissing, J, Monforte, M, Ricci, E, Choumert, A, Stojkovic, T, Malfatti, E, Pegoraro, E, Semplicini, C, Stramare, R, Scheidegger, O, Haberlova, J, Straub, V, Marini-Bettolo, C, Lokken, N, Diaz-Manera, J, Urtizberea, JA, Mercuri, E, Kyncl, M, Walter, MC, Carlier, RY
Publicada:
1 ene 2020
Resumen:
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.
Filiaciones:
Barp, A:
Univ Padua, Neuromuscular Ctr, Dept Neurosci DNS, Padua, Italy
Laforet, P:
Raymond Poincare Teaching Hosp, AP HP, Ctr Reference Malad Neuromusculaires Nord Est Ile, Dept Neurol, Garches, France
Bello, L:
Univ Padua, Neuromuscular Ctr, Dept Neurosci DNS, Padua, Italy
Tasca, G:
Fdn Policlin Univ A Gemelli IRCCS, Dipartimento Sci Invecchiamento Neurol Ortoped &, Unita Operat Complessa Neurol, Rome, Italy
Vissing, J:
Univ Copenhagen, Rigshosp, Copenhagen Neuromuscular Ctr, Copenhaghen, Denmark
Monforte, M:
Fdn Policlin Univ A Gemelli IRCCS, Dipartimento Sci Invecchiamento Neurol Ortoped &, Unita Operat Complessa Neurol, Rome, Italy
Ricci, E:
Fdn Policlin Univ A Gemelli IRCCS, Dipartimento Sci Invecchiamento Neurol Ortoped &, Unita Operat Complessa Neurol, Rome, Italy
Choumert, A:
CHU, Ctr Reference Malad Neuromusculaires PACA Reunion, St Pierre, Reunion, France
Stojkovic, T:
G H Pitie Salpetriere, APHP, Inst Myol, Ctr Reference Malad Neuromusculaires Paris Est, Paris, France
Malfatti, E:
Raymond Poincare Teaching Hosp, AP HP, Ctr Reference Malad Neuromusculaires Nord Est Ile, Dept Neurol, Garches, France
Pegoraro, E:
Univ Padua, Neuromuscular Ctr, Dept Neurosci DNS, Padua, Italy
Semplicini, C:
Univ Padua, Neuromuscular Ctr, Dept Neurosci DNS, Padua, Italy
Stramare, R:
Univ Padua, Inst Radiol, Dept Med DIMED, Padua, Italy
Scheidegger, O:
Univ Bern, Inst Diagnost & Intervent Neuroradiol, Dept Neurol, Inselspital,Bern Univ Hosp, Bern, Switzerland
Haberlova, J:
Charles Univ Prague, Dept Paediat Neurol, Prague, Czech Republic
Straub, V:
John Walton Muscular Dystrophy Res Ctr, MRC Ctr Neuromuscular Dis, Inst Med Genet, Newcastle Upon Tyne, Tyne & Wear, England
Marini-Bettolo, C:
John Walton Muscular Dystrophy Res Ctr, MRC Ctr Neuromuscular Dis, Inst Med Genet, Newcastle Upon Tyne, Tyne & Wear, England
Lokken, N:
Univ Copenhagen, Rigshosp, Copenhagen Neuromuscular Ctr, Copenhaghen, Denmark
Diaz-Manera, J:
Hosp Santa Creu & Sant Pau, Serv Neurol, Unitat Malalties Neuromusculars, Barcelona, Spain
Urtizberea, JA:
Hop Marin, APHP, Ctr Competence Neuromusculaire Filnemus, Hendaye, France
Mercuri, E:
Univ Cattolica Sacro Cuore, Fdn Policlin Univ Gemelli, Pediat Neurol & Nemo Clin Ctr, Rome, Italy
Kyncl, M:
Fac Hosp Motol, Dept Radiol, Prague, Czech Republic
Walter, MC:
Ludwig Maximilians Univ Munchen, Friedrich Baur Inst, Munich, Germany
Carlier, RY:
UVSQ, Raymond Poincare Univ Hosp, APHP, Dept Radiol,Garches Neuromuscular Ctr GNMH,U1179, Garches, France
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