Responsiveness of gait analysis parameters in a cohort of 71 CMT subjects

摘要

Highlights ? Responsiveness of outcome measures is related to the degree of CMT disease severity. ? Kinematic parameters are more responsive at initial CMT disease stages. ? Kinetic parameters are more responsive at more advanced CMT disease stages. ? Gait parameters are suitable OMs for CMT natural history studies and clinical trials. ? Selection of endpoints according to disease severity is crucial in clinical trials. Abstract Detection of worsening in the slowly progressive Charcot–Marie–Tooth disease (CMT) is difficult. As previous clinical scales showed low responsiveness, novel outcome measures are under study, including innovative approaches such as quantitative muscle MRI and instrumented movement analysis. Since gait analysis proved able to reliably quantify CMT locomotor deficits, we aimed to explore whether it can be a sensitive-to-change outcome measure in CMT studies. Clinical and biomechanical evaluations were performed in 71 CMT subjects at baseline and after a mean (±sd) of 28.9?±?9.5 months. Locomotor tasks included natural walking, ascending and descending steps. Instrumented analysis of such tasks provided indexes related to muscle strength (kinetic parameters) and joint movement (kinematic parameters). Parameter responsiveness was expressed as Standardized Response Mean (SRM). Considering the whole CMT group, several parameters showed moderate responsiveness; subgrouping subjects according to disease severity allowed reaching high responsiveness (SRM >0.80). CMT Examination Score showed moderate responsiveness (SRM 0.53) in the minimally affected group; kinematic parameters were more responsive in this group, whereas kinetic parameters in the most severely affected one. Biomechanical parameters can represent suitable outcome measures for CMT by showing moderate-to-high responsiveness. These data suggest that appropriate selection of patient population and outcome measures is crucial for clinical trials' design.