Results From a Three-Year Pilot Study of Clinical Outcome Measures in Congenital Muscular Dystrophy

SIGNIFICANCE: Congenital muscular dystrophies (CMDs) comprise a clinically diverse and genetically heterogeneous group of early onset muscle disorders. Most are chronically progressive and lead to increasing muscle weakness, respiratory insufficiency, and contractures early in life. Due to a broad phenotypic spectrum, a battery of outcome measures are often used but have not been validated in CMD. As potential therapeutic interventions are being developed for CMD and other neuromuscular disorders, the validation of clinical outcome measures becomes a priority.

INNOVATION: We implemented a novel prospective cohort study design to validate outcome measures in CMD. Approximately 17 outcome measures were administered over a 2-day period for 3 consecutive yr. The International Classification of Functioning, Disability and Health (ICF) was used to both understand and identify outcome measures and to examine changes over time.

APPROACH: Our main goal was to validate clinical measurements in CMD. We hypothesized that significant changes in motor performance, function, and quality of life (QoL) can be captured through a battery of validated outcome measures over a minimum of 3 yr.

Potential therapies are currently under development for many forms of CMD. However, appropriate clinical outcome measures for clinical trials have not been validated.

METHOD: Using a prospective cohort design, we explored outcomes in CMD over 3 yr. Participants were from various geographic locations; the National Institutes of Health (NIH) paid for all travel and lodging. Clinical outcome measures were given over a 2-day period. Breaks, refreshments, and meals were provided.

Participants were seen at the NIH Clinical Center over a 2-day period for 3 consecutive yr. All measures were assessed by licensed occupational and physical therapists, nurse practitioners, and neuromuscular pediatricians.

A cohort of 33 participants with confirmed CMD (aged 4 to 21 yr) and their parent(s) participated. Participants were recruited by clinical staff at the NIH, the Children’s National Medical Center, and advocacy groups, such as Cure CMD.

Outcome measures included the Motor Function Measure—32 (MFM–32), North Star Ambulatory Assessment, Hammersmith Functional Motor Scales, 6-min walk test, supine to stand, myometry and goniometry, 10-m walk, Egen Klassifikation—2 (EK–2), Quality of Upper Extremity Skills Test (QUEST), ACTIVLIM (activity limitations for patients with upper and/or lower limb impairments), pulmonary function tests, Pediatric Evaluation of Disability Inventory (PEDI), and QoL.

Descriptive statistics were completed for all measures. Intraclass correlation coefficients were used to explore interrater reliability. Spearman rank order correlations examined concurrent validity between scales. Correlations were designed as weak (.39), moderate (.40 to .59), strong (.60 to .79), and very strong (.80 to 1.00).

RESULTS: Interrater reliability was good to high; internal consistency was more than .86 for all scales. With few exceptions, correlations were statistically significant and showed moderate to strong associations.

CONCLUSION: Most scales were feasible and reliable for use in individuals with CMD. All but a few domains showed both very high interrater reliability and internal consistency. Limitations include large standard deviations in goniometry as well as a ceiling and floor effect with the MFM-32. Outcome measures provided novel insight into progression of the disease as well as measures best suited for clinical trials.