Muscle strength and motor function in adolescents and adults with spinal muscular atrophy

OBJECTIVE: To assess longitudinal patterns of muscle strength, motor function, and maximal compound muscle action potential amplitudes (CMAPMAX) in older patients with spinal muscular atrophy (SMA), hypothesizing a continued decline of motor function parameters throughout life. METHODS: We measured muscle strength (Medical Research Council), motor function (Hammersmith Functional Motor Scale Expanded [HFMSE] and Motor Function Measure), and CMAPMAX in treatment-naive patients. We used both longitudinal and cross-sectional data in mixed models to analyze natural history patterns. RESULTS: We included 250 patients with SMA types 1c through 4. Median patient age at assessment was 26.8 years, the number of assessments per patient ranged from 1 to 6. Baseline muscle strength and motor function scores differed significantly between SMA types, but annual rates of decline were largely similar and mostly linear. HFMSE floor effects were present for all patients with SMA type 1c, and adolescents and adults with types 2 and 3a. CMAPMAX differed significantly between SMA types but did not decline significantly with increasing age. Muscle strength correlated very strongly with motor function (τ ≥ 0.8) but only moderately with CMAPMAX (τ ≈ 0.5-0.6). CONCLUSION: Muscle strength and motor function decline in older patients with SMA are constant without periods of slower progression or a plateau phase. The floor effects of the HFMSE preclude its use for long-term follow-up of adult patients with SMA types 1c through 3a. Muscle strength sum scores represent an alternative, feasible outcome measure for adolescent and adult patients with SMA.