Search

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 nonblinded 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 old, 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 2 years, this difference was -0.048/month, p < 0.0001, 95% CI = -0.028, -0.068. In boys ≤ 7.0 years old, differences appeared at 6 months in gastrocnemius (EIM phase slope = -0.83 °/kHz/mo, 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/mo, p = 0.00019, 95% CI = 0.028, 0.086) and EIM phase slope (0.14 °/kHz/mo, 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. Because 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. Ann Neurol 2017;81:622-632., (© 2017 American Neurological Association.)

Objective: We assessed changes in quantitative muscle ultrasound data in boys with Duchenne muscular dystrophy (DMD) and healthy controls to determine whether ultrasound can serve as a biomarker of disease progression. Two approaches were used: gray scale level (GSL), measured from the ultrasound image, and quantitative backscatter analysis (QBA), measured directly from the received echoes., Methods: GSL and QBA were obtained from 6 unilateral arm/leg muscles in 36 boys with DMD and 28 healthy boys (age = 2-14 years) for up to 2 years. We used a linear mixed effects model with random intercept and slope terms to compare trajectories of GSL, QBA, and functional assessments. We analyzed separately a subset of boys who initiated corticosteroids., Results: Compared to healthy boys, increasing GSL in DMD boys >7.0 years old was first identified at 6 months (eg, anterior forearm slope difference of 1.16 arbitrary units/mo, p = 0.004, 95% confidence interval [CI] = 0.38-1.94); in boys ≤ 7 years old, differences in GSL first appeared at 12 months (0.82 arbitrary units/mo, p = 0.04, 95% CI = 0.075-1.565, in rectus femoris). QBA performed similarly to GSL (eg, DMD boys > 7 years old: 0.41dB/mo, p = 0.01, 95% CI = 0.096-0.72, in anterior forearm at 6 months). Ultrasound identified differences earlier than functional measures including 6-minute walk and supine-to-stand tests. However, neither QBA nor GSL showed an effect of corticosteroid initiation., Interpretation: QBA performs similarly to GSL, and both appear more sensitive than functional assessments for detecting muscle deterioration in DMD. Additional studies will be required to determine whether quantitative muscle ultrasound can detect therapeutic efficacy. Ann Neurol 2017;81:633-640., (© 2017 American Neurological Association.)

Objective: We sought to understand the alteration in the anisotropic, or direction dependent, character of muscle as measured by electrical impedance myography (EIM) in subjects with Duchenne muscular dystrophy (DMD) and its potential to serve as a biomarker of disease status., Methods: Thirty-six boys with DMD and 27 healthy controls were measured with EIM, with electrical current applied both parallel and perpendicular to the major muscle fiber direction. In addition, muscle extracted from 10 mdx and 10 wild-type mice were measured analogously., Results: Normalized reactance anisotropy, a direction-dependent measure of membrane charge storage capability, was significantly lower in the four muscles of DMD subjects as compared to controls (p<0.01). Normalized reactance anisotropy also decreased with increasing age in DMD subjects (r=-0.36, p=0.031), but not in healthy boys. Analogous changes were observed in mdx mouse gastrocnemius as compared to wild type (p=0.019)., Conclusion: These results support that loss of electrical anisotropy is a previously unrecognized feature of dystrophic muscle., Significance: Anisotropic alterations may offer novel indices to assist in neuromuscular disease diagnosis and to serve as easy-to-obtain biomarkers in clinical therapeutic trials., (Copyright © 2016 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.)