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Published on: January 12, 2019
Motor Function in Limb-Girdle Muscular Dystrophy R1/2A: Validation of Clinical Outcome Assessments for Clinical Care
Meredith K James1, Megan A Iammarino2, Natalie F Reash2
1John Walton Muscular Dystrophy Research Centre, Translational and Clinical Research Institute, The Newcastle upon Tyne Hospitals NHS Trust and Newcastle University, United Kingdom.
Background And Objectives:
Limb-girdle muscular dystrophy (LGMD) type R1/2A, calpain-3-related, is a rare, autosomal recessive disorder caused by pathogenic variants in the CAPN3 gene. LGMDR1/2A causes progressive weakness of upper and lower limbs, leading to difficulty walking and use of arms for overhead activities. The rate of progression of LGMDR1/2A is unknown because of the limited number of published cohorts and the lack of validated outcome measures. Quantifying the natural history of LGMDR1/2A using standardized outcome measures is critical for understanding the rate of disease progression and improving clinical care and clinical trial readiness. The aim of this cross-sectional study was to evaluate the suitability of the North Star Assessment for limb-girdle type muscular dystrophies (NSAD), 100-meter timed test (100MTT), and Performance of Upper Limb 2.0 (PUL) as outcome measures for quantifying disease presentation and progression in individuals with LGMDR1/2A.
Methods:
Ninety-two individuals were evaluated by physiotherapy teams at Nationwide Children's Hospital and the John Walton Muscular Dystrophy Research Centre. Psychometric analysis of NSAD and PUL was completed using Rasch measurement methods. Descriptive statistics and correlation coefficients explored the relationship among all outcomes.
Results:
Psychometric analyses demonstrated that NSAD and PUL were valid and appropriate functional outcome measures for ambulant and nonambulant individuals with LGMDR1/2A. The NSAD and 100MTT velocity were highly correlated (Spearman rho Rs(88) = 0.89) The 100MTT was particularly useful for the strongest and asymptomatic cohort.
Discussion:
In this largest reported cohort of individuals with LGMDR1/2A, NSAD, PUL, and 100MTT were suitable to quantify functional impact of the disease. International harmonization of outcome measures creates meaningful clinical data to inform clinical management and trial design.
Insights
Limb-girdle muscular dystrophy (LGMD) type R1/2A is a rare genetic disorder. This study found the NSAD, 100MTT, and PUL are suitable measures to track disease progression in LGMD R1/2A patients.
Area of Science:
- Neurology
- Genetics
- Clinical Trials
Background:
- Limb-girdle muscular dystrophy (LGMD) type R1/2A, caused by CAPN3 gene variants, leads to progressive muscle weakness.
- The natural history and progression rate of LGMD R1/2A are poorly understood due to limited data and lack of validated outcome measures.
- Standardized outcome measures are crucial for understanding disease progression and advancing clinical trial readiness for LGMD R1/2A.
Purpose of the Study:
- To evaluate the suitability of the North Star Assessment for limb-girdle type muscular dystrophies (NSAD), 100-meter timed test (100MTT), and Performance of Upper Limb 2.0 (PUL) as outcome measures.
- To quantify disease presentation and progression in individuals with LGMD R1/2A.
Main Methods:
- A cross-sectional study involving 92 individuals with LGMD R1/2A.
- Psychometric analysis of NSAD and PUL using Rasch measurement methods.
- Descriptive statistics and correlation coefficients to analyze relationships among outcome measures.
Main Results:
- NSAD and PUL were validated as appropriate functional outcome measures for both ambulant and nonambulant individuals with LGMD R1/2A.
- A strong correlation was found between NSAD and 100MTT velocity (Spearman rho = 0.89).
- The 100MTT proved particularly useful for assessing the strongest and asymptomatic individuals.
Conclusions:
- NSAD, PUL, and 100MTT are suitable for quantifying the functional impact of LGMD R1/2A in the largest reported cohort.
- International harmonization of these outcome measures will facilitate meaningful clinical data collection.
- Standardized outcome measures are essential for improving clinical management and informing future clinical trial design for LGMD R1/2A.
