Title

Three-year quantitative magnetic resonance imaging and phosphorus magnetic resonance spectroscopy study in lower limb muscle in dysferlinopathy

Authors

Harmen Reyngoudt, NMR Laboratory, Neuromuscular Investigation Center, Institute of Myology, Paris, France.
Fiona E. Smith, Magnetic Resonance Centre, Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.
Ericky Caldas de Almeida Araújo, NMR Laboratory, Neuromuscular Investigation Center, Institute of Myology, Paris, France.
Ian Wilson, Magnetic Resonance Centre, Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.
Roberto Fernández-Torrón, The John Walton Muscular Dystrophy Research Centre, Translational and Clinical Research Institute, Newcastle University and Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.
Meredith K. James, The John Walton Muscular Dystrophy Research Centre, Translational and Clinical Research Institute, Newcastle University and Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.
Ursula R. Moore, The John Walton Muscular Dystrophy Research Centre, Translational and Clinical Research Institute, Newcastle University and Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.
Jordi Díaz-Manera, The John Walton Muscular Dystrophy Research Centre, Translational and Clinical Research Institute, Newcastle University and Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.
Benjamin Marty, NMR Laboratory, Neuromuscular Investigation Center, Institute of Myology, Paris, France.
Noura Azzabou, NMR Laboratory, Neuromuscular Investigation Center, Institute of Myology, Paris, France.
Heather Gordish, Center for Translational Science, Division of Biostatistics and Study Methodology, Children's National Health System, Washington, DC, USA.
Laura Rufibach, The JAIN Foundation, Seattle, WA, USA.
Tim Hodgson, Magnetic Resonance Centre, Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.
Dorothy Wallace, Magnetic Resonance Centre, Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.
Louise Ward, Magnetic Resonance Centre, Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.
Jean-Marc Boisserie, NMR Laboratory, Neuromuscular Investigation Center, Institute of Myology, Paris, France.
Julien Le Louër, NMR Laboratory, Neuromuscular Investigation Center, Institute of Myology, Paris, France.
Heather Hilsden, The John Walton Muscular Dystrophy Research Centre, Translational and Clinical Research Institute, Newcastle University and Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.
Helen Sutherland, The John Walton Muscular Dystrophy Research Centre, Translational and Clinical Research Institute, Newcastle University and Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.
Aurélie Canal, Neuromuscular Physiology and Evaluation Laboratory, Neuromuscular Investigation Center, Institute of Myology, Paris, France.
Jean-Yves Hogrel, Neuromuscular Physiology and Evaluation Laboratory, Neuromuscular Investigation Center, Institute of Myology, Paris, France.
Marni Jacobs, Center for Translational Science, Division of Biostatistics and Study Methodology, Children's National Health System, Washington, DC, USA.
Tanya Stojkovic, Neuromuscular Reference Center, Institute of Myology, Pitié-Salpêtrière Hospital (AP-HP), Paris, France.
Kate Bushby, The John Walton Muscular Dystrophy Research Centre, Translational and Clinical Research Institute, Newcastle University and Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.
Anna Mayhew, The John Walton Muscular Dystrophy Research Centre, Translational and Clinical Research Institute, Newcastle University and Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.

Document Type

Journal Article

Publication Date

6-1-2022

Journal

Journal of cachexia, sarcopenia and muscle

Volume

13

Issue

3

DOI

10.1002/jcsm.12987

Keywords

31P MRS; Dysferlinopathy; Longitudinal; Outcome measures; Quantitative MRI

Abstract

BACKGROUND: Natural history studies in neuromuscular disorders are vital to understand the disease evolution and to find sensitive outcome measures. We performed a longitudinal assessment of quantitative magnetic resonance imaging (MRI) and phosphorus magnetic resonance spectroscopy ( P MRS) outcome measures and evaluated their relationship with function in lower limb skeletal muscle of dysferlinopathy patients. METHODS: Quantitative MRI/ P MRS data were obtained at 3 T in two different sites in 54 patients and 12 controls, at baseline, and three annual follow-up visits. Fat fraction (FF), contractile cross-sectional area (cCSA), and muscle water T in both global leg and thigh segments and individual muscles and P MRS indices in the anterior leg compartment were assessed. Analysis included comparisons between patients and controls, assessments of annual changes using a linear mixed model, standardized response means (SRM), and correlations between MRI and P MRS markers and functional markers. RESULTS: Posterior muscles in thigh and leg showed the highest FF values. FF at baseline was highly heterogeneous across patients. In ambulant patients, median annual increases in global thigh and leg segment FF values were 4.1% and 3.0%, respectively (P < 0.001). After 3 years, global thigh and leg FF increases were 9.6% and 8.4%, respectively (P < 0.001). SRM values for global thigh FF were over 0.8 for all years. Vastus lateralis muscle showed the highest SRM values across all time points. cCSA decreased significantly after 3 years with median values of 11.0% and 12.8% in global thigh and global leg, respectively (P < 0.001). Water T values in ambulant patients were significantly increased, as compared with control values (P < 0.001). The highest water T values were found in the anterior part of thigh and leg. Almost all P MRS indices were significantly different in patients as compared with controls (P < 0.006), except for pH , and remained, similar as to water T , abnormal for the whole study duration. Global thigh water T at baseline was significantly correlated to the change in FF after 3 years (ρ = 0.52, P < 0.001). There was also a significant relationship between the change in functional score and change in FF after 3 years in ambulant patients (ρ = -0.55, P = 0.010). CONCLUSIONS: This multi-centre study has shown that quantitative MRI/ P MRS measurements in a heterogeneous group of dysferlinopathy patients can measure significant changes over the course of 3 years. These data can be used as reference values in view of future clinical trials in dysferlinopathy or comparisons with quantitative MRI/S data obtained in other limb-girdle muscular dystrophy subtypes.

Department

Genomics and Precision Medicine

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