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.

APHP Department of Radiology Garches Neuromuscular Center Garches France

APHP G H Pitié Salpêtrière Institut de Myologie Centre de Référence des Maladies Neuromusculaires Paris Est Paris France

Centre de Compétence Neuromusculaire Filnemus APHP Hôpital Marin Hendaye France

Centre de Référence des Maladies Neuromusculaires PACA Réunion Rhônes Alpes CHU La Réunion France

Copenhagen Neuromuscular Center Rigshospitalet University of Copenhagen Copenhaghen Denmark

Department of Medicine Institute of Radiology University of Padova Padua Italy

Department of Neurology Institute for Diagnostic and Interventional Neuroradiology Inselspital Bern University Hospital University of Bern Bern Switzerland

Department of Neurosciences DNS Neuromuscular Centre University of Padova Padua Italy

Department of Neurosciences DNS Neuromuscular Centre University of Padova Padua Italy APHP G H Pitié Salpêtrière Institut de Myologie Centre de Référence des Maladies Neuromusculaires Paris Est Paris France

Department of Paediatric Neurology Charles University Prague Prague Czech Republic

Friedrich Baur Institut Ludwig Maximilians University Munich Munich Germany

John Walton Muscular Dystrophy Research Centre MRC Centre for Neuromuscular Diseases Institute of Genetic Medicine Newcastle Upon Tyne UK

Neurology Department Raymond Poincaré Teaching Hospital Centre de Référence Des Maladies Neuromusculaires Nord Est Ile de France AP HP Garches France

Pediatric Neurology and Nemo Clinical Centre Università Cattolica Sacro Cuore Fondazione Policlinico Universitario A Gemelli Rome Italy

Radiology Department Faculty Hospital Motol Prague Czech Republic

Unità Operativa Complessa Di Neurologia Dipartimento Di Scienze Dell'Invecchiamento Neurologiche Ortopediche E Della Testa Colo Fondazione Policlinico Universitario A Gemelli IRCCS Rome Italy

Unitat de Malalties Neuromusculars Servei de Neurologia Hospital de La Santa Creu 1 Sant Pau Barcelona Spain

000      

00000naa a2200000 a 4500

001      

bmc20028645

003      

CZ-PrNML

005      

20210114154547.0

007      

ta

008      

210105s2020 gw f 000 0|eng||

009      

AR

024    7_

$a 10.1007/s00415-019-09539-y $2 doi

035    __

$a (PubMed)31555977

040    __

$a ABA008 $b cze $d ABA008 $e AACR2

041    0_

$a eng

044    __

$a gw

100    1_

$a Barp, Andrea $u Department of Neurosciences DNS, Neuromuscular Centre, University of Padova, Padua, Italy. andrea.barp1985@libero.it. APHP, G-H Pitié-Salpêtrière, Institut de Myologie, Centre de Référence des Maladies Neuromusculaires Paris Est, Paris, France. andrea.barp1985@libero.it.

245    10

$a European muscle MRI study in limb girdle muscular dystrophy type R1/2A (LGMDR1/LGMD2A) / $c A. Barp, P. Laforet, L. Bello, G. Tasca, J. Vissing, M. Monforte, E. Ricci, A. Choumert, T. Stojkovic, E. Malfatti, E. Pegoraro, C. Semplicini, R. Stramare, O. Scheidegger, J. Haberlova, V. Straub, C. Marini-Bettolo, N. Løkken, J. Diaz-Manera, JA. Urtizberea, E. Mercuri, M. Kynčl, MC. Walter, RY. Carlier,

520    9_

$a 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.

650    _2

$a mladiství $7 D000293

650    _2

$a dospělí $7 D000328

650    _2

$a senioři $7 D000368

650    _2

$a dítě $7 D002648

650    _2

$a ženské pohlaví $7 D005260

650    _2

$a lidé $7 D006801

650    12

$a magnetická rezonanční tomografie $7 D008279

650    _2

$a mužské pohlaví $7 D008297

650    _2

$a lidé středního věku $7 D008875

650    _2

$a kosterní svaly $x diagnostické zobrazování $x patologie $x patofyziologie $7 D018482

650    _2

$a pletencové svalové dystrofie $x diagnostické zobrazování $x genetika $x patologie $x patofyziologie $7 D049288

650    _2

$a mladý dospělý $7 D055815

651    _2

$a Evropa $7 D005060

655    _2

$a časopisecké články $7 D016428

700    1_

$a Laforet, Pascal $u Neurology Department, Raymond-Poincaré Teaching Hospital, Centre de Référence Des Maladies Neuromusculaires Nord/Est/Ile-de-France, AP-HP, Garches, France.

700    1_

$a Bello, Luca $u Department of Neurosciences DNS, Neuromuscular Centre, University of Padova, Padua, Italy.

700    1_

$a Tasca, Giorgio $u Unità Operativa Complessa Di Neurologia, Dipartimento Di Scienze Dell'Invecchiamento, Neurologiche, Ortopediche E Della Testa-Colo, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.

700    1_

$a Vissing, John $u Copenhagen Neuromuscular Center, Rigshospitalet, University of Copenhagen, Copenhaghen, Denmark.

700    1_

$a Monforte, Mauro $u Unità Operativa Complessa Di Neurologia, Dipartimento Di Scienze Dell'Invecchiamento, Neurologiche, Ortopediche E Della Testa-Colo, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.

700    1_

$a Ricci, Enzo $u Unità Operativa Complessa Di Neurologia, Dipartimento Di Scienze Dell'Invecchiamento, Neurologiche, Ortopediche E Della Testa-Colo, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.

700    1_

$a Choumert, Ariane $u Centre de Référence des Maladies Neuromusculaires PACA-Réunion-Rhônes-Alpes CHU, La Réunion, France.

700    1_

$a Stojkovic, Tanya $u APHP, G-H Pitié-Salpêtrière, Institut de Myologie, Centre de Référence des Maladies Neuromusculaires Paris Est, Paris, France.

700    1_

$a Malfatti, Edoardo $u Neurology Department, Raymond-Poincaré Teaching Hospital, Centre de Référence Des Maladies Neuromusculaires Nord/Est/Ile-de-France, AP-HP, Garches, France.

700    1_

$a Pegoraro, Elena $u Department of Neurosciences DNS, Neuromuscular Centre, University of Padova, Padua, Italy.

700    1_

$a Semplicini, Claudio $u Department of Neurosciences DNS, Neuromuscular Centre, University of Padova, Padua, Italy.

700    1_

$a Stramare, Roberto $u Department of Medicine (DIMED), Institute of Radiology, University of Padova, Padua, Italy.

700    1_

$a Scheidegger, Olivier $u Department of Neurology, Institute for Diagnostic and Interventional Neuroradiology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.

700    1_

$a Haberlova, Jana $u Department of Paediatric Neurology, Charles University in Prague, Prague, Czech Republic.

700    1_

$a Straub, Volker $u John Walton Muscular Dystrophy Research Centre, MRC Centre for Neuromuscular Diseases, Institute of Genetic Medicine, Newcastle Upon Tyne, UK.

700    1_

$a Marini-Bettolo, Chiara $u John Walton Muscular Dystrophy Research Centre, MRC Centre for Neuromuscular Diseases, Institute of Genetic Medicine, Newcastle Upon Tyne, UK.

700    1_

$a Løkken, Nicoline $u Copenhagen Neuromuscular Center, Rigshospitalet, University of Copenhagen, Copenhaghen, Denmark.

700    1_

$a Diaz-Manera, Jordi $u Unitat de Malalties Neuromusculars, Servei de Neurologia, Hospital de La Santa Creu I Sant Pau, Barcelona, Spain.

700    1_

$a Urtizberea, Jon A $u Centre de Compétence Neuromusculaire Filnemus/APHP, Hôpital Marin, Hendaye, France.

700    1_

$a Mercuri, Eugenio $u Pediatric Neurology and Nemo Clinical Centre, Università Cattolica Sacro Cuore, Fondazione Policlinico Universitario, A. Gemelli, Rome, Italy.

700    1_

$a Kynčl, Martin $u Radiology Department, Faculty Hospital Motol, Prague, Czech Republic.

700    1_

$a Walter, Maggie C $u Friedrich-Baur Institut, Ludwig-Maximilians University Munich, Munich, Germany.

700    1_

$a Carlier, Robert Y $u APHP, Department of Radiology, Garches Neuromuscular Center (GNMH), Raymond Poincaré University Hospital (UVSQ, U 1179), Garches, France.

773    0_

$w MED00002835 $t Journal of neurology $x 1432-1459 $g Roč. 267, č. 1 (2020), s. 45-56

856    41

$u https://pubmed.ncbi.nlm.nih.gov/31555977 $y Pubmed

910    __

$a ABA008 $b sig $c sign $y a $z 0

990    __

$a 20210105 $b ABA008

991    __

$a 20210114154543 $b ABA008

999    __

$a ok $b bmc $g 1608980 $s 1119825

BAS    __

$a 3

BAS    __

$a PreBMC

BMC    __

$a 2020 $b 267 $c 1 $d 45-56 $e 20190925 $i 1432-1459 $m Journal of neurology $n J Neurol $x MED00002835

LZP    __

$a Pubmed-20210105