TY - JOUR
T1 - Water T2 could predict functional decline in patients with dysferlinopathy
AU - The Jain COS Consortium
AU - Moore, Ursula
AU - Caldas de Almeida Araújo, Ericky
AU - Reyngoudt, Harmen
AU - Gordish-Dressman, Heather
AU - Smith, Fiona E.
AU - Wilson, Ian
AU - James, Meredith
AU - Mayhew, Anna
AU - Rufibach, Laura
AU - Day, John W.
AU - Jones, Kristi J.
AU - Bharucha-Goebel, Diana X.
AU - Salort-Campana, Emmanuelle
AU - Pestronk, Alan
AU - Walter, Maggie C.
AU - Paradas, Carmen
AU - Stojkovic, Tanya
AU - Mori-Yoshimura, Madoka
AU - Bravver, Elena
AU - Pegoraro, Elena
AU - Mendell, Jerry R.
AU - Bushby, Kate
AU - Blamire, Andrew M.
AU - Straub, Volker
AU - Carlier, Pierre G.
AU - Diaz-Manera, Jordi
N1 - Publisher Copyright:
© 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.
PY - 2022/12
Y1 - 2022/12
N2 - Background: Water T2 (T2H2O) 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 T2H2O 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. T2H2O 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 T2H2O at baseline, age, disease duration, and baseline function. Results: A higher T2H2O 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 T2H2O 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 T2H2O (>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 T2H2O (<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, T2H2O did not correlate with current functional ability. However, T2H2O 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 T2H2O measure at baseline. Significant challenges remain in standardizing T2H2O values across sites to allow determining globally applicable thresholds. The results from the present work are encouraging and suggest that T2H2O could be used to improve prognostication, patient selection, and disease modelling for clinical trials.
AB - Background: Water T2 (T2H2O) 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 T2H2O 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. T2H2O 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 T2H2O at baseline, age, disease duration, and baseline function. Results: A higher T2H2O 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 T2H2O 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 T2H2O (>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 T2H2O (<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, T2H2O did not correlate with current functional ability. However, T2H2O 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 T2H2O measure at baseline. Significant challenges remain in standardizing T2H2O values across sites to allow determining globally applicable thresholds. The results from the present work are encouraging and suggest that T2H2O could be used to improve prognostication, patient selection, and disease modelling for clinical trials.
KW - Limb girdle muscular dystrophy
KW - Limb girdle muscular dystrophy 2B
KW - Limb girdle muscular dystrophy R2
KW - Magnetic resonance imaging
KW - Water T2
UR - http://www.scopus.com/inward/record.url?scp=85137325319&partnerID=8YFLogxK
U2 - 10.1002/jcsm.13063
DO - 10.1002/jcsm.13063
M3 - Article
C2 - 36058852
AN - SCOPUS:85137325319
SN - 2190-5991
VL - 13
SP - 2888
EP - 2897
JO - Journal of Cachexia, Sarcopenia and Muscle
JF - Journal of Cachexia, Sarcopenia and Muscle
IS - 6
ER -