Validation of the North Star Assessment for Limb-Girdle Type Muscular Dystrophies

Abstract

Objective: The North Star Assessment for limb-girdle type muscular dystrophies (NSAD), a clinician-reported outcome measure (ClinRO) of motor performance, was initially developed and validated for use in dysferlinopathy, an autosomal recessive form of limb-girdle muscular dystrophy (LGMD R2/2B). Recent developments in treatments for limb-girdle muscular dystrophies (LGMD) have highlighted the urgent need for disease-specific ClinROs. The purpose of this study was to understand the ability of the NSAD to quantify motor function across the broad spectrum of LGMD phenotypes.

Methods: Assessments of 130 individuals with LGMD evaluated by the physical therapy teams at Nationwide Children's Hospital and the John Walton Muscular Dystrophy Research Centre were included in the analysis. NSAD, 100-m timed test (100MTT), and Performance of Upper Limb 2.0 assessment data were collected. Psychometric analysis with Rasch measurement methods was used to examine the NSAD for suitability and robustness by determining the extent to which the observed data "fit" with predictions of those ratings from the Rasch model. The NSAD score was correlated with the 100MTT and Performance of Upper Limb 2.0 assessment scores for external construct validity.

Results: The NSAD demonstrated a good spread of items covering a continuum of abilities across both individuals who had LGMD and were ambulatory and individuals who had LGMD and were weaker and nonambulatory. Items fit well with the construct measured, validating a summed total score. The NSAD had excellent interrater reliability [intraclass correlation coefficient (ICC) = 0.986, 95% CI = 0.981-0.991] and was highly correlated with the 100MTT walk/run velocity (Spearman rho correlation coefficient of rs(134) = .92).

Conclusion: Although LGMD subtypes may differ in age of onset, rate of progression, and patterns of muscle weakness, the overall impact of progressive muscle weakness on motor function is similar. The NSAD is a reliable and valid ClinRO of motor performance for individuals with LGMD and is suitable for use in clinical practice and research settings.

Impact: Recent developments in potential pharmacological treatments for LGMD have highlighted the urgent need for disease-specific outcome measures. Validated and meaningful outcome measures are necessary to capture disease presentation, to inform expected rates of progression, and as endpoints for measuring the response to interventions in clinical trials. The NSAD, a scale of motor performance for both individuals who have LGMD and are ambulatory and those who are nonambulatory, is suitable for use in clinical and research settings.

Keywords: Clinician-Reported Outcome Measure; Limb-Girdle Muscular Dystrophy; Motor Performance; Neuromuscular Diseases; Rasch Methods.

© The Author(s) 2022. Published by Oxford University Press on behalf of the American Physical Therapy Association.

Figures

Figure 1

North Star Assessment for limb-girdle type muscular dystrophies (NSAD) person-item threshold distribution plot demonstrating good coverage of items for the population. The top histogram illustrates the abilities of the population, from the weakest on the left to the strongest on the right. The bottom histogram demonstrates a well-distributed range of items that test the ability of the population, with a ceiling for the individuals who were the very strongest and asymptomatic.

Figure 2

Item thresholds with 27/29 ordered scoring thresholds demonstrating that as an individual’s ability increases, so does the probability of obtaining a higher score.

Figure 3

Test correlations. (A) North Star Assessment for limb-girdle type muscular dystrophies (NSAD) total score and 100-m timed test velocity (m/s) scatterplot. There was a strong correlation between motor performance, as measured with the NSAD total score, and run/walk velocity. The line at 4 m/s indicates normal 100-m velocity for children 8 to 14 years old. (B) NSAD total score and Performance of Upper Limb 2.0 assessment score scatterplot. Despite excellent gross motor performance, as indicated by high NSAD scores, some individuals who were ambulatory experienced significant upper limb dysfunction.