P.299Disease progression using quantitative MRI outcome measures in limb girdle muscular dystrophy 2L

Abstract

Traditionally outcome measures for clinical trials in neuromuscular diseases are based on physical assessments which are dependent on patient effort, and may not be sensitive to progression over short trial periods in slow-progressing diseases. Limb girdle muscular dystrophy type 2L (LGMD2L) is a slowly progressive disease with weakness and atrophy of proximal muscles; elevated creatine kinase levels; and dystrophic findings on muscle biopsy. There is no effective treatment available for LGMD2L, but clinical trials have been conducted over the past years, which call for quantitative and reliable outcome measures to be developed. In this study, we investigated disease progression over 12 months in 16 patients with genetically confirmed LGMD2L, using quantitative outcome measures, including Dixon magnetic resonance imaging (MRI). We used MRI to assess changes in muscle fat content and stationary dynamometry to assess changes in muscle strength. Disease progression was also investigated with handheld dynamometry, handgrip strength and manual muscle testing (MMT). Preliminary results show a tendency of increased muscle fat fraction in the muscles analyzed using the quantitative MRI technique from baseline to 12 months follow up. The muscle fat fraction increased with 2% on average and the intrinsic back muscles showed the largest increase. Stationary dynamometry and handgrip strength decreased slightly, whereas handheld dynamometry and manual muscle testing did not change. The present study demonstrates a slow disease progression in LGMD2L. Dixon MRI detected increases in muscle fat content and is therefore a suitable candidate for an outcome measure in natural history or treatment studies in LGMD2L. The stationary dynamometry also seems to be reliable outcome measures for LMGMD2L.