Water T2 could predict functional decline in patients with dysferlinopathy
Moore, Ursula. (The John Walton Muscular Dystrophy Research Centre. Translational and Clinical Research Institute. Newcastle University and Newcastle Hospitals NHS Foundation Trust)
Caldas de A. Araújo, Ericky (NMR Laboratory. CEA/DRF/IBFJ/MIRCen)
Reyngoudt, Harmen (NMR Laboratory. CEA/DRF/IBFJ/MIRCen)
Gordish-Dressman, Heather (Pediatrics. Epidemiology and Biostatistics. George Washington University)
Smith, Fiona E. (Magnetic Resonance Centre. Translational and Clinical Research Institute. Newcastle University)
Wilson, Ian (Magnetic Resonance Centre. Translational and Clinical Research Institute. Newcastle University)
James, Meredith (The John Walton Muscular Dystrophy Research Centre. Translational and Clinical Research Institute. Newcastle University and Newcastle Hospitals NHS Foundation Trust)
Mayhew, Anna (The John Walton Muscular Dystrophy Research Centre. Translational and Clinical Research Institute. Newcastle University and Newcastle Hospitals NHS Foundation Trust)
Rufibach, Laura (Jain Foundation)
Day, John W. (Department of Neurology and Neurological Sciences. Stanford University School of Medicine)
Jones, Kristi J. (The Children's Hospital at Westmead and The University of Sydney)
Bharucha-Goebel, Diana (National Institutes of Health (Bethesda, Estats Units d'Amèrica))
Salort-Campana, Emmanuelle (Service des maladies neuromusculaire et de la SLA. Hôpital de La Timone)
Pestronk, Alan (Washington University School of Medicine)
Walter, Maggie C. (Friedrich-Baur-Institute. Department of Neurology. Ludwig-Maximilians-University of Munich)
Paradas, Carmen (Instituto de Biomedicina de Sevilla)
Stojkovic, Tanya (Centre de référence des maladies neuromusculaires. Institut de Myologie. AP-HP. Sorbonne Université. Hôpital Pitié-Salpêtrière)
Mori-Yoshimura, Madoka (Department of Neurology. National Center Hospital. National Center of Neurology and Psychiatry)
Bravver, Elena (Neuroscience Institute. Carolinas Neuromuscular/ALS-MDA Center. Carolinas HealthCare System)
Pegoraro, Elena (Department of Neuroscience. University of Padova)
Mendell, Jerry R. (The Abigail Wexner Research Institute at Nationwide Children's Hospital)
Bushby, Kate (The John Walton Muscular Dystrophy Research Centre. Translational and Clinical Research Institute. Newcastle University and Newcastle Hospitals NHS Foundation Trust)
Blamire, Andrew (Magnetic Resonance Centre. Translational and Clinical Research Institute. Newcastle University)
Straub, Volker (Newcastle University)
Carlier, Pierre G. (Université Paris-Saclay. CEA. DRF. Service Hospitalier Frederic Joliot)
Diaz-Manera, Jordi (Institut d'Investigació Biomèdica Sant Pau)

Date:	2022
Abstract:	Background: Water T2 (T2) 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 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 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 at baseline, age, disease duration, and baseline function. Results: A higher T2 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 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 (>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 (<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 did not correlate with current functional ability. However, T2 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 measure at baseline. Significant challenges remain in standardizing T2 values across sites to allow determining globally applicable thresholds. The results from the present work are encouraging and suggest that T2 could be used to improve prognostication, patient selection, and disease modelling for clinical trials.
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Magnetic resonance imaging ; Water T2 ; Limb girdle muscular dystrophy ; Limb girdle muscular dystrophy R2 ; Limb girdle muscular dystrophy 2B
Published in:	Journal of Cachexia, Sarcopenia and Muscle, Vol. 13 Núm. 6 (december 2022) , p. 2888-2897, ISSN 2190-6009

DOI: 10.1002/jcsm.13063
PMID: 36058852

10 p, 585.1 KB

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