Natural history of facioscapulohumeral muscular dystrophy evaluated by multiparametric quantitative MRI: a prospective cohort study.

Background: Facioscapulohumeral muscular dystrophy (FSHD) is a genetic disorder characterized by progressive skeletal muscle wasting. Longitudinal muscle magnetic resonance imaging (MRI) studies demonstrated that the risk of developing irreversible fatty replacement is higher in muscles showing edematous lesions. The quantification of this phenomenon is an understudied topic in FSHD and intramuscular water content can also represent a potential biomarker sensitive to the effect of investigational drugs. We applied a multiparametric quantitative muscle MRI protocol to assess disease progression quantifying fatty replacement and muscle edema over 2 years, using fat fraction (FF) and water-T2 (wT2) metrics.

Methods: Thirty FSHD patients with at least one muscle showing signs of edema on conventional MRI were enrolled. FF and wT2 maps were assessed in 12 thigh and 6 leg muscles for each side, and a linear mixed model was employed to explore their variations over time. The measurements were acquired at baseline, 12, and 24 months. Quantitative MRI parameters were also correlated with clinical scales and functional assessments collected at baseline.

Results: The average yearly increase in FF was 2 ± 0.6% at thigh level and 1.9 ± 0.7% at leg level. No significant longitudinal changes in wT2 were observed. Muscles with intermediate FF (15-30%) at baseline and those with baseline wT2 values above 41 ms showed the highest increase in fat replacement. Both FF and wT2 showed significant correlations with clinical scales and functional assessments.

Conclusions: Our longitudinal study identified muscles and compartments more likely to show FF increase in FSHD subjects. Multiparametric quantitative MRI metrics should be incorporated into clinical trial frameworks to explore their potential in detecting early therapeutic effects.