Electrical impedance myography for assessment of Duchenne muscular dystrophy

Abstract

Objective Sensitive, objective and easily applied methods for evaluating disease progression and response to therapy are needed for clinical trials in Duchenne muscular dystrophy (DMD). In this study, we evaluated whether electrical impedance myography (EIM) could serve this purpose. Methods In this non-blinded study, 36 boys with DMD and 29 age-similar healthy boys underwent multifrequency EIM measurements for up to 2 years on 6 muscles unilaterally along with functional assessments. A linear mixed-effects model with random intercept and slope terms was used for the analysis of multifrequency EIM values and functional measures. Seven DMD boys were initiated on corticosteroids; these data were analyzed using a piecewise linear mixed-effects model. Results In boys >7.0 years, a significant difference in the slope of EIM phase-ratio trajectories in the upper extremity was observed by 6 months of -0.074/month, p=0.023, 95% confidence interval (CI)[−0.013,−0.14]); at two years, this difference was −0.048/month, p<0.0001 95%CI[−0.028,−0.068]. In boys ≤7.0 years, differences appeared at 6 months in gastrocnemius (EIM phase-slope −0.83°/kHz-month, p=0.007 95%CI[−0.26,−1.40]). EIM outcomes showed significant differences earlier than functional tests. Initiation of corticosteroids significantly improved the slope of EIM phase-ratio (0.057/month, p=0.00019 95%CI[0.028,0.086]) and EIM phase-slope (0.14°/kHz-month, p=0.013 95%CI[0.028,0.25]), consistent with corticosteroids’ known clinical benefit. Interpretation EIM detects deterioration in muscles of both younger and older boys by 6 months; it also identifies the therapeutic effect of corticosteroid initiation. Since EIM is rapid to apply, painless, and requires minimal operator training, the technique deserves to be further evaluated as a biomarker in DMD clinical therapeutic trials.

Quantitative muscle ultrasound detects disease progression in Duchenne muscular dystrophy

“…As anticipated, the application of a false discovery rate analysis reduced the significance of these results to some extent, yet many remained significant. This parallels the clinical course of boys with DMD, who may not show functional decline until approximately age 7 years, and this is similar to prior longitudinal studies of GSL ultrasound and MRI in DMD, as well as to EIM as described in the companion article . The muscles in our study that were most sensitive to disease progression in DMD compared to healthy boys included the anterior forearm and upper extremity average in older boys and the rectus femoris and proximal muscle average in younger boys.…”

“…A total of 37 DMD boys and a total of 31 healthy controls were initially screened and enrolled. Of these, a number were excluded from the analysis or otherwise did not have sufficient data as shown in the Consort Diagram in Figure 3 of the companion article; in addition, 1 healthy control, who only had 1 visit, had no adequate ultrasound data obtained and was excluded entirely from the analysis. Thus, a total 36 boys with DMD, mean age = 7.3 years (range = 2.2–13.3), and a total of 28 healthy controls, mean age = 7.1 years (range = 3.3–14.6 years), had data that were included in the analysis; these ages were comparable ( p = 0.86).…”

“…Sixteen boys with DMD were taking steroids throughout the study, 7 started steroids during the study, and 13 were not on steroids. There was a total of 246 healthy subjects and 211 DMD QUS assessments over the 2‐year period; functional assessment data are provided in the companion article …”

“…We calculated effect sizes and sample sizes for hypothetical clinical trials based on rates of progression, as described in our companion article . Sample sizes necessary for clinical trials were generally smaller using QBA and GSL than with functional measurements, based on the observed effects in our study (Table ).…”

“…There was a total of 246 healthy subjects and 211 DMD QUS assessments over the 2-year period; functional assessment data are provided in the companion article. 11…”