The 100 meter timed test (100m) is a fixed distance ambulatory assessment used to quantify maximal ambulatory ability in persons with neuromuscular disorders. It has been validated in a cross-sectional cohort of boys with Duchenne muscular dystrophy (DMD) with comparison to typically-developing peers. The purpose of our study was to understand change in 100m performance over time to better interpret expected change as a result of natural history or treatment efficacy, as well as predict loss of ambulation (LOA). Additionally, we explored whether a data-driven phenotype matched traditional clinical diagnosis. We enrolled 231 patients with a dystrophinopathy (age range: 3–16 years), and 148 completed at least 1 follow up (range: 1-11 visits, 3-42 months). The 100m (time and % predicted) and 10 meter walk (10m) were completed at each study visit. The 100m and 10m were significantly better at baseline in boys exposed to steroids compared to steroid-naïve (P<0.01 and P<0.05 respectively) and boys initiating steroids at <4.5 years of age during our study demonstrated the largest improvement within the first 6 months post-initiation. Test-retest reliability was 0.95 and minimal detectable change using the standard error of measure was 4.5 seconds. In our cohort, a threshold of 39% predicted was optimal for predicting LOA. Predicting prognosis in new patients based on genetic results alone can be problematic. Exploratory analysis of our 100m data revealed 2 distinct phenotypic severity clusters (based on 100m time, age, height, and weight). The clusters suggest that 100m time greater than 73.6 seconds at any age defines a more severe phenotype. Clustering based on 100m speed has the potential to more stringently characterize disease severity leading to more accurate clinical counseling, as well as refined enrollment and interpretation of change in clinical trials. The 100m is reliable, responsive to change, and useful in predicting functional loss in dystrophinopathy.
Read full abstract