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J Neurol Neurosurg Psychiatry. 2018 Oct;89(10):1071-1081. doi: 10.1136/jnnp-2017-317488. Epub 2018 May 7.

Muscle MRI in patients with dysferlinopathy: pattern recognition and implications for clinical trials.

Author information

1
Centro de Investigación Biomédica en Red en Enfermedades Raras (CIBERER), Barcelona, Spain.
2
Neuromuscular Disorders Unit, Neurology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
3
Neuromuscular Area, Biodonostia Health Research Institute, Neurology Service, Donostia University Hospital, Donostia-San Sebastian, Spain.
4
The John Walton Muscular Dystrophy Research Centre, MRC Centre for Neuromuscular Diseases, Newcastle upon Tyne, UK.
5
Radiology Department, Universitat Autònoma de Barcelona, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
6
Magnetic Resonance Centre, Institute for Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.
7
AIM & CEA NMR Laboratory, Institute of Myology, Pitié-Salpêtrière University Hospital, Paris, France.
8
The Jain Foundation, Seattle, Washington, USA.
9
Center for Translational Science, Division of Biostatistics and Study Methodology, Children's National Health System, Washington, District of Columbia, USA.
10
Department of Pediatrics, Epidemiology and Biostatistics, George Washington University, Washington, District of Columbia, USA.
11
Department of Radiology, Nationwide Children's Hospital, Columbus, Ohio, USA.
12
Radiology Unit, Department of Medicine, University of Padova, Padova, Italy.
13
Department of Radiology, National Center Hospital, National Center of Neurology and Psychiatry, Tokyo, Japan.
14
Department of Radiology, CMC Mercy Charlotte, Carolinas Healthcare System Neurosciences Institute, Charlotte, North Carolina, USA.
15
Department of Radiology, Hospital U. Virgen de Valme, Sevilla, Spain.
16
Department of Clinical Radiology, Ludwig-Maximilians-University, Munich, Germany.
17
Center for Clinical Imaging Research CCIR, Washington University, St. Louis, Missouri, USA.
18
Centre de Résonance, Magnétique Biologique et Médicale, Marseille, France.
19
Aix-Marseille Université, Marseille, France.
20
Department of Diagnostic Imaging and Radiology, Children's National Health System, Washington, District of Columbia, USA.
21
Department of Radiology, Westmead Hospital, Westmead, New South Wales, Australia.
22
Faculty of Health Sciences, University of Sydney, Sydney, Australia.
23
Lucas Center for Imaging, Stanford University School of Medicine, Stanford, California, USA.
24
Charite Muscle Research Unit, Experimental and Clinical Research Center, A Joint Co-operation of the Charité Medical Faculty and the Max Delbrück Center for Molecular Medicine, Berlin, Germany.
25
Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California, USA.
26
Institute for Neuroscience and Muscle Research, Children's Hospital at Westmead, University of Sydney, Sydney, New South Wales, Australia.
27
Department of Neurology, Children's National Health System, Washington, District of Columbia, USA.
28
National Institutes of Health (NINDS), Bethesda, Maryland, USA.
29
Neuromuscular and ALS Center, La Timone Hospital, Aix-Marseille Université, Marseille, France.
30
Department of Neurology, Washington University School of Medicine, St. Louis, Missouri, USA.
31
Friedrich-Baur-Institute, Department of Neurology, Ludwig-Maximilians-University of Munich, Munich, Germany.
32
Neuromuscular Unit, Department of Neurology, Hospital U. Virgen del Rocío/Instituto de Biomedicina de Sevilla, Sevilla, Spain.
33
Institut de Myologie, AP-HP, G.H. Pitié-Salpêtrière, Paris, Île-de-France, France.
34
Department of Neurology, National Center Hospital, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan.
35
Neurosciences Institute, Carolinas Healthcare System, Charlotte, North Carolina, USA.
36
Department of Neurosciences, University of Padova, Padova, Italy.
37
Nationwide Children's Hospital, Columbus, Ohio, USA.

Abstract

BACKGROUND AND OBJECTIVE:

Dysferlinopathies are a group of muscle disorders caused by mutations in the DYSF gene. Previous muscle imaging studies describe a selective pattern of muscle involvement in smaller patient cohorts, but a large imaging study across the entire spectrum of the dysferlinopathies had not been performed and previous imaging findings were not correlated with functional tests.

METHODS:

We present cross-sectional T1-weighted muscle MRI data from 182 patients with genetically confirmed dysferlinopathies. We have analysed the pattern of muscles involved in the disease using hierarchical analysis and presented it as heatmaps. Results of the MRI scans have been correlated with relevant functional tests for each region of the body analysed.

RESULTS:

In 181 of the 182 patients scanned, we observed muscle pathology on T1-weighted images, with the gastrocnemius medialis and the soleus being the most commonly affected muscles. A similar pattern of involvement was identified in most patients regardless of their clinical presentation. Increased muscle pathology on MRI correlated positively with disease duration and functional impairment.

CONCLUSIONS:

The information generated by this study is of high diagnostic value and important for clinical trial development. We have been able to describe a pattern that can be considered as characteristic of dysferlinopathy. We have defined the natural history of the disease from a radiological point of view. These results enabled the identification of the most relevant regions of interest for quantitative MRI in longitudinal studies, such as clinical trials.

CLINICAL TRIAL REGISTRATION:

NCT01676077.

KEYWORDS:

dysferlinopathy; muscle MRI; muscular dystrophy; outcome measures

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