Quantitative Muscle MRI as Outcome Measure in Patients With Becker Muscular Dystrophy—A 1-Year Follow-Up Study

Abstract

Introduction: With the advent of emerging molecular therapies for muscular dystrophies, the need for knowledge about natural history course of such diseases is of utmost importance in the preparation for future trials. However, for Becker muscular dystrophy such knowledge is scarce.Objective: In this 1-year follow-up study, we examined disease progression in Becker muscular dystrophy by monitoring changes in MRI-assessed muscle fat fraction (FF) in axial and lower limb muscles and quantitative muscle strength of axial muscles.Methods and Materials: Sixteen patients with Becker muscular dystrophy were investigated by (1) muscle strength of the trunk using a Biodex dynamometer and (2) Dixon muscle MRI of paraspinal and lower limb muscles. Quantitative MRI data was analyzed in two parts: The first part consisted of all participants (N = 16). The second analysis assessed two separate groups comprising lesser affected participants (N = 5) and more severely affected patients (n = 11).Results: Trunk extension and flexion strength remained stable from baseline to follow-up. MRI did not show any significant increase in muscle FF % from baseline to follow-up in all patients, except for multifidus at the spinal level T12 (p = 0.01). However, when we analyzed the two subgroups, according to disease severity, FF% increased in the lesser severely affected group at L4/L5 erector spinae (p = 0.047), sartorius (p = 0.028), gracilis (p = 0.009), tibialis anterior (p = 0.047), peroneals (p = 0.028), and gastrocnemius medialis (p = 0.009), while the severely affected group only increased significantly at T12 multifidus (p = 0.028) and T12 erector spinae (p = 0.011). No difference in muscle strength was observed in the two subgroups.Conclusion: Our results add to the existing knowledge about the natural rate of disease progression in BMD. As quantitative MRI was able to identify changes where strength assessment was not, MRI could be a strong biomarker for change in BMD. However, our findings show that it is important to stratify patients with BMD according to phenotype for future clinical trials.

Givinostat for Becker muscular dystrophy: A randomized, placebo-controlled, double-blind study

“…For a patient with BMD, the fat fraction increase over time can be described by a sigmoidal curve, similar to that which has been shown in DMD ( 32 – 34 ), and the baseline value can therefore predict future fat fractions ( 23 , 35 ). Given these various findings, it may be useful not only to stratify patients into future studies by their functional status (the 6MWT may not be the best instrument for this), but, if MRI is to be used as an endpoint, according to their MRI fat fraction ( 22 ).…”

Baseline fat fraction is a strong predictor of disease progression in Becker muscular dystrophy

“…In BMD, the average increase in fat fraction over 2 years is around 0.7%–1.9% for the lower and upper leg, 18 respectively, which is much lower compared with the 3%–7% over 1 year in DMD patients 15 . In addition, BMD shows considerable variability between patients with fat fraction increases after 2 years ranging from −1.0% to 6.4% 18,19 . With these limited changes and large variability, it is very important to be able to identify key muscles or patients that are likely to show a large increase in fat fraction within the duration of a clinical trial.…”

“… 15 In addition, BMD shows considerable variability between patients with fat fraction increases after 2 years ranging from −1.0% to 6.4%. 18 , 19 With these limited changes and large variability, it is very important to be able to identify key muscles or patients that are likely to show a large increase in fat fraction within the duration of a clinical trial.…”

Selection Approach to Identify the Optimal Biomarker Using Quantitative Muscle MRI and Functional Assessments in Becker Muscular Dystrophy

“…In BMD, longitudinal MRI data are limited. In a recent one year follow-up study in 16 patients no significant increase in FF was found (14). Although FF correlated to functional outcomes in cross-sectional studies (15)(16)(17)(18), there is a large variability in FF between muscles.…”