A functional scale for spinal and bulbar muscular atrophy: Cross-sectional and longitudinal study

Abstract

We aimed to develop, validate, and evaluate a disease-specific outcome measure for SBMA: the Spinal and Bulbar Muscular Atrophy Functional Rating Scale (SBMAFRS). We examined the Japanese version (SBMAFRS-J) in 80 Japanese SBMA subjects to evaluate its validity and reliability. We then assessed this scale longitudinally in 41 additional SBMA subjects. The English version (SBMAFRS-E) was also tested in 15 US subjects. The total score of the SBMAFRS-J was distributed normally without an extreme ceiling or floor effect. For SBMAFRS-J, the high intra- and inter-rater agreement was confirmed (intra-class correlation coefficients [ICCs] 0.910 and 0.797, respectively), and internal consistency was satisfactory (Cronbach's alpha 0.700-0.822). In addition, SBMAFRS-J demonstrated concurrent, convergent, and discriminant validity, except for the respiratory subscale. The inter-rater reliability and internal consistency of SBMAFRS-E were also satisfactory. Longitudinally, SBMAFRS-J showed a higher sensitivity to disease progression than the existing clinical measures. In conclusion, we developed and validated a disease-specific functional rating scale for SBMA in both Japanese and English versions, although it needs to be re-assessed in interventional studies with a larger sample size including English speaking subjects.

Keywords: Functional rating scale; Motor neuron disease; Spinal and bulbar muscular atrophy; Validation.

Fig. 1

Score distribution of the SBMAFRS and the ALSFRS-R. The SBMAFRS-J was distributed in a normal manner (A). The total score distribution of the SBMAFRS varied from low to high without ceiling or floor effects (A), although that of the ALSFRS-R skewed to the right with a ceiling effect (B).

Fig. 2

Individual change of the functional scores. The change of the total score of SBMAFRS (A) and that of ALSFRS-R (B) in individual subjects.

Fig. 3

Sample size estimation. Estimated sample size per arm for a 2-arm interventional clinical trial based on the observed variability of the chronological progression rate found in the present study (power 0.80, α0.05). SBMAFRS = Spinal and Bulbar Muscular Atrophy Functional Rating Scale; ALSFRS-R = Revised Amyotrophic Lateral Sclerosis Functional Rating Scale.