P.176 Evaluation of thigh muscle fat fraction with quantitative MRI in 24 adult LGMDR12 patients over 2 years of follow-up.

Limb-Girdle Muscular Dystrophy autosomal recessive type 12 (LGMDR12) is a rare hereditary muscle disease for which outcome measures are lacking. We evaluated intramuscular fat fraction as an outcome measure to track disease progression, to determine if this could be useful in future clinical trials to evaluate potential therapies. We prospectively performed a 6-point Dixon MRI of the thighs in 24 genetically confirmed, adult LGMDR12 patients and 24 age- and sex-matched healthy controls at baseline and after 1 and 2 years. The most affected muscles were the semimembranosus, biceps femoris long head and adductor magnus, respectively, and there was generally an increase in proton density fat fraction (PDFF) with increasing age and disease duration. Patients with intermediate stage thigh muscle fat replacement at baseline (PDFF 20-70%) already showed a significant increase in PDFF in 8/14 evaluated thigh muscles after one year. The standardized response mean (SRM) demonstrated a high responsiveness to change in PDFF for 6 individual muscles over 2 years in this group. We also found that tracking PDFF changes in individual muscles over time was more sensitive than PDFF measurements in muscle groups as a whole. In patients with early (<20%) or end stage (>70%) muscle fat replacement, or in the control group, PDFF did not increase significantly over two years of follow-up. Finally, we observed a moderately strong correlation between total thigh PDFF and the following clinical outcome measures at baseline: six-minute walk distance (6MWD), 10-meter walk test (10MWT), Medical Research Council (MRC) sum scores and Biodex® isometric dynamometry. We conclude that thigh muscle PDFF imaging is a sensitive outcome measure to track progressive muscle fat replacement in selected LGMDR12 patients even after one year of follow-up and should be included as an outcome measure in future clinical trials. [ABSTRACT FROM AUTHOR]