Skeletal Muscle Magnetic Resonance Biomarkers in GNE Myopathy

Objective To characterize muscle involvement and evaluate disease severity in patients with GNE myopathy using skeletal muscle MRI and proton magnetic resonance spectroscopy (H-1-MRS). Methods Skeletal muscle imaging of the lower extremities was performed in 31 patients with genetically confirmed GNE myopathy, including T1-weighted and short tau inversion recovery (STIR) images, T1 and T2 mapping, and H-1-MRS. Measures evaluated included longitudinal relaxation time (T1), transverse relaxation time (T2), and H-1-MRS fat fraction (FF). Thigh muscle volume was correlated with relevant measures of strength, function, and patient-reported outcomes. Results The cohort was representative of a wide range of disease progression. Contractile thigh muscle volume ranged from 5.51% to 62.95% and correlated with thigh strength (r = 0.91), the 6-minute walk test (r = 0.82), the adult myopathy assessment tool (r = 0.83), the activities-specific balance confidence scale (r = 0.65), and the inclusion body myositis functional rating scale (r = 0.62). Four stages of muscle involvement were distinguished by qualitative (T1W and STIR images) and quantitative methods: stage I: unaffected muscle (T1 = 1,033 +/- 74.2 ms, T2 = 40.0 +/- 1.9 ms, FF = 7.4 +/- 3.5%); stage II: STIR hyperintense muscle with minimal or no fat infiltration (T1 = 1,305 +/- 147 ms, T2 = 50.2 +/- 3.5 ms, FF = 27.6 +/- 12.7%); stage III: fat infiltration and STIR hyperintensity (T1 = 1,209 +/- 348 ms, T2 = 73.3 +/- 12.6 ms, FF = 57.5 +/- 10.6%); and stage IV: complete fat replacement (T1 = 318 +/- 39.9 ms, T2 = 114 +/- 21.2 ms, FF = 85.6 +/- 4.2%). 1H-MRS showed a significant decrease in intramyocellular lipid and trimethylamines between stage I and II, suggesting altered muscle metabolism at early stages. Conclusion MRI biomarkers can monitor muscle involvement and determine disease severity noninvasively in patients with GNE myopathy.

Automated summary

This study characterized muscle involvement and disease severity in patients with GNE myopathy using skeletal muscle MRI and proton magnetic resonance spectroscopy. The findings showed that muscle volume correlated with strength, function, and patient-reported outcomes, indicating the potential of MRI biomarkers to monitor disease progression noninvasively.