Water T2 could predict functional decline in patients with dysferlinopathy.

Autor:	Moore U; The John Walton Muscular Dystrophy Research Centre, Translational and Clinical Research Institute, Newcastle University and Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK., Caldas de Almeida Araújo E; NMR Laboratory, Neuromuscular Investigation Center, Institute of Myology, Paris, France.; NMR Laboratory, CEA/DRF/IBFJ/MIRCen, Paris, France., Reyngoudt H; NMR Laboratory, Neuromuscular Investigation Center, Institute of Myology, Paris, France.; NMR Laboratory, CEA/DRF/IBFJ/MIRCen, Paris, France., Gordish-Dressman H; Center for Translational Science, Division of Biostatistics and Study Methodology, Children's National Health System, Washington, DC, USA.; Pediatrics, Epidemiology and Biostatistics, George Washington University, Washington, DC, USA., Smith FE; Magnetic Resonance Centre, Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK., Wilson I; Magnetic Resonance Centre, Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK., James M; The John Walton Muscular Dystrophy Research Centre, Translational and Clinical Research Institute, Newcastle University and Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK., Mayhew A; The John Walton Muscular Dystrophy Research Centre, Translational and Clinical Research Institute, Newcastle University and Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK., Rufibach L; Jain Foundation, Seattle, WA, USA., Day JW; Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA., Jones KJ; The Children's Hospital at Westmead and The University of Sydney, Sydney, NSW, Australia., Bharucha-Goebel DX; Department of Neurology, Children's National Health System, Washington, DC, USA.; National Institutes of Health (NINDS), Bethesda, MD, USA., Salort-Campana E; Service des maladies neuromusculaire et de la SLA, Hôpital de La Timone, Marseille, France., Pestronk A; Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA., Walter MC; Friedrich-Baur-Institute, Department of Neurology, Ludwig-Maximilians-University of Munich, Munich, Germany., Paradas C; Neuromuscular Unit, Department of Neurology, Hospital U. Virgen del Rocío/Instituto de Biomedicina de Sevilla, Sevilla, Spain., Stojkovic T; Centre de référence des maladies neuromusculaires, Institut de Myologie, AP-HP, Sorbonne Université, Hôpital Pitié-Salpêtrière, Paris, France., Mori-Yoshimura M; Department of Neurology, National Center Hospital, National Center of Neurology and Psychiatry, Tokyo, Japan., Bravver E; Neuroscience Institute, Carolinas Neuromuscular/ALS-MDA Center, Carolinas HealthCare System, Charlotte, NC, USA., Pegoraro E; Department of Neuroscience, University of Padova, Padua, Italy., Mendell JR; The Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH, USA., Bushby K; The John Walton Muscular Dystrophy Research Centre, Translational and Clinical Research Institute, Newcastle University and Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK., Blamire AM; Magnetic Resonance Centre, Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK., Straub V; The John Walton Muscular Dystrophy Research Centre, Translational and Clinical Research Institute, Newcastle University and Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK., Carlier PG; Université Paris-Saclay, CEA, DRF, Service Hospitalier Frederic Joliot, Orsay, France., Diaz-Manera J; The John Walton Muscular Dystrophy Research Centre, Translational and Clinical Research Institute, Newcastle University and Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.; Neuromuscular Disorders Unit, Neurology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.; Centro de Investigación Biomédica en Red en Enfermedades Raras (CIBERER), Madrid, Spain.
Jazyk:	angličtina
Zdroj:	Journal of cachexia, sarcopenia and muscle [J Cachexia Sarcopenia Muscle] 2022 Dec; Vol. 13 (6), pp. 2888-2897. Date of Electronic Publication: 2022 Sep 04.
DOI:	10.1002/jcsm.13063
Abstrakt:	Background: Water T2 (T2 H2O ) mapping is increasingly being used in muscular dystrophies to assess active muscle damage. It has been suggested as a surrogate outcome measure for clinical trials. Here, we investigated the prognostic utility of T2 H2O to identify changes in muscle function over time in limb girdle muscular dystrophies. Methods: Patients with genetically confirmed dysferlinopathy were assessed as part of the Jain Foundation Clinical Outcomes Study in dysferlinopathy. The cohort included 18 patients from two sites, both equipped with 3-tesla magnetic resonance imaging (MRI) systems from the same vendor. T2 H2O value was defined as higher or lower than the median in each muscle bilaterally. The degree of deterioration on four functional tests over 3 years was assessed in a linear model against covariates of high or low T2 H2O at baseline, age, disease duration, and baseline function. Results: A higher T2 H2O at baseline significantly correlated with a greater decline on functional tests in 21 out of 35 muscles and was never associated with slower decline. Higher baseline T2 H2O in adductor magnus, vastus intermedius, vastus lateralis, and vastus medialis were the most sensitive, being associated bilaterally with greater decline in multiple timed tests. Patients with a higher than median baseline T2 H2O (>40.6 ms) in the right vastus medialis deteriorated 11 points more on the North Star Ambulatory Assessment for Dysferlinopathy and lost an additional 86 m on the 6-min walk than those with a lower T2 H2O (<40.6 ms). Optimum sensitivity and specificity thresholds for predicting decline were 39.0 ms in adductor magnus and vastus intermedius, 40.0 ms in vastus medialis, and 40.5 ms in vastus lateralis from different sites equipped with different MRI systems. Conclusions: In dysferlinopathy, T2 H2O did not correlate with current functional ability. However, T2 H2O at baseline was higher in patients who worsened more rapidly on functional tests. This suggests that inter-patient differences in functional decline over time may be, in part, explained by different severities of the active muscle damage, assessed by T2 H2O measure at baseline. Significant challenges remain in standardizing T2 H2O values across sites to allow determining globally applicable thresholds. The results from the present work are encouraging and suggest that T2 H2O could be used to improve prognostication, patient selection, and disease modelling for clinical trials. (© 2022 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu Plný text