Long-term natural history of dynamometer measured muscle power in untreated spinal muscular atrophy types 2 and 3



Poster Number: 108


Thomas Crawford MD


1. The Johns Hopkins University School of Medicine

Background: Natural history studies of spinal muscular atrophy (SMA) have traditionally relied upon ordinal functional scales or non-linear (MRC) strength measures, which provide limited insight into the underlying motor neuron degeneration. The natural history of SMA motor function is the product of multiple factors, including power, development, weight, size, and complications of disease. By contrast, direct measurement of muscle power focuses upon a proximate marker of cumulative motor unit function.

Objectives: We present dynamometer measurements of muscle power from a single investigator cohort of later-onset SMA patients at ~1,100 routine clinic visits over a 31 year period (1989-2020). The 104 participants (60 type 2, 44 type 3) were ages 1-53 years at entry (mean 8.0). Blinded dynamometer measurements of bilateral elbow and knee flexion and extension were obtained over a mean (SD) of 13.5 (8.1) years. The association between age and square root muscle power was modeled using linear mixed effects regression, separately by SMA type and muscle group (elbow or knee extension/flexion). Each model included fixed effects for a 4-DF restricted cubic spline function of age and random intercepts.

Results: Muscle power increased during childhood to a peak, followed by persistent decline. The age of peak power for elbow flexion in SMA type 2 was at 10.0 years, and for type 3 at 10.5 years, notwithstanding substantial difference in mean peak muscle power (3.7 [95% CI: 3.2-4.2] lbs vs 15.6 [95% CI: 11.9-19.9] lbs). This general pattern was common to all muscle groups.

Conclusions: The natural histories of dynamometer measured muscle power of SMA types 2 and 3 were remarkably similar in time course, despite substantial differences in magnitude. This differs from natural histories of function that scale SMA type 2 and 3 by functional ability or MRC grading. Muscle power increases throughout middle childhood. After the peak of muscle power, when normal development is no longer a confounding effect, muscle power declines continuously, counter to the commonly held idea that the course of SMA eventually settles into a “plateau” phase. This dynamometer study used, across the spectrum of later-onset SMA, a continuous measure of the disease manifestation most closely linked to the neuropathology of SMA. Commonality of the course of muscle power degeneration was observed across the wide range of individuals with later-onset SMA.

Analytic Support: Biogen