Electrical Impedance Myography and Quantitative Ultrasound Detect Steroid Related Improvements in Duchenne Muscular Dystrophy (I4.003)

OBJECTIVE: To determine whether electrical impedance myography (EIM) and quantitative ultrasound (QUS) can detect the beneficial effect of corticosteroids in boys with Duchenne muscular dystrophy (DMD). BACKGROUND: We recently completed a 2-year natural history study of EIM and QUS in boys with DMD; a small subset of boys was initiated corticosteroids during the study. Given the beneficial impact of corticosteroids in DMD, these boys’ data were analyzed separately to determine if EIM and QUS could detect a steroid effect. DESIGN/METHODS: Of the boys with DMD who were enrolled, 4 who had at least one visit before starting steroids and at least 2 visits after were identified. For each, the EIM and QUS data for multiple muscles was analyzed. In addition, the Northstar Ambulatory Assessment (NSAA) was performed. Data for both EIM and QUS were collected on 6 different muscles unilaterally including, deltoid, biceps, forearm flexors, quadriceps, tibialis anterior, and medial gastrocnemius). Given the small number of subjects, formal statistical analysis was not performed. The data are presented as mean (range). RESULTS: Both EIM and QUS showed improvement in the months following initiation of corticosteroids. Specifically, the 6-muscle average EIM reactance ratio increased by 20.5[percnt] (11[percnt]-31.5[percnt]) and the 6-muscle QUS grays scale level decreased by 12.2[percnt] (6.9[percnt]-15[percnt]). These improvements were consistent with those observed in NSAA, which improved by 17.5[percnt] (3.2[percnt]-40[percnt]) for three patients on whom it was performed. CONCLUSIONS: These data suggest that EIM and QUS appear to be sensitive to corticosteroid effects in boys with DMD, mirroring the functional improvements that are typically observed in the months following corticosteroid initiation. More importantly, it suggests that both of these approaches to muscle assessment could play useful roles as pharmacodynamic biomarkers in future early phase clinical therapeutic trials. Study Supported by: Grant R01AR060850 from the National Institutes of Health.