Disease progression and outcome measures in spinobulbar muscular atrophy

Objective Methods Spinal and bulbar muscular atrophy (SBMA) is a slowly progressive disease with weakness of bulbar and extremity muscles. There is no curative treatment for the disease, but several clinical trials have been conducted over the past years. The results from these trials have uncovered a great need to develop quantitative, reliable outcome measures. In this study, we prospectively investigated disease progression over 18 months in 29 patients with genetically confirmed SBMA, 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 the SBMA functional rating scale, bulbar rating scale, 6-minute walk test, and blood samples, among others. Results Interpretation Mean muscle fat content, muscle strength in knee extensors, handgrip strength, walking distance, and creatinine levels changed significantly. Mean muscle fat content increased by 2 +/- 1.25%, and knee extension strength decreased from 83 +/- 60 to 76 +/- 56Nm, handgrip strength from 31 +/- 13 to 29 +/- 13kg, walking distance from 362 +/- 216 to 336 +/- 219m, and creatinine level from 58 +/- 21 to 54 +/- 20 mu mol/l. Functional rating scores did not change. The present study demonstrates a slow and steady disease progression in SBMA. Dixon MRI detected increases in muscle fat content in all investigated muscles and is therefore a suitable candidate for an outcome measure in natural history or treatment studies in SBMA. The 6-minute walk test and handgrip strength also seem to be reliable outcome measures for SBMA. Ann Neurol 2018;84:762-773