Reducing sample size requirements for future ALS clinical trials with a dedicated electrical impedance myography system.

OBJECTIVE: In this longitudinal multicenter cohort study, we evaluated the potential of a dedicated electrical impedance myography (EIM) device to assess ALS progression and the system's basic reproducibility and diagnostic accuracy. METHODS: Forty-six ALS patients underwent up to five sequential measurements of multiple muscles over a period of 8 months at 2-month intervals using the mView EIM device (Myolex, Inc., San Francisco, CA). Standard measures of disease status were also obtained. A group of 30 healthy volunteers and 30 ALS-mimics were evaluated once to determine if the technique could assist with initial diagnosis. Several electrode arrays and EIM outcomes were assessed. RESULTS: EIM tracked ALS progression; power analyses suggested a 5.2-fold reduction in sample size requirements compared to ALSFRS-R by utilizing 50 kHz phase value from the muscle with the greatest EIM decline in each subject. This progression rate correlated to total ALSFRS-R progression, with R = 0.371, p = 0.021. Reproducibility was high, with both intra- and inter-rater intraclass correlation coefficients for individual muscles mostly greater than 0.90. The mean 50 kHz phase distinguished between ALS patients and healthy controls (area-under-curve 0.78, 95% confidence intervals (CIs) 0.68, 0.89), but not between mimics and ALS patients (area-under-curve 0.60, 95% CIs 0.47, 0.73). CONCLUSIONS: While limited in its specificity to identify ALS versus disease mimics, these results support the hypothesis that single-muscle EIM can serve as a convenient, repeatable, and powerful outcome measure in ALS clinical trials.

Electrical impedance myography in Duchenne muscular dystrophy and healthy controls: A multicenter study of reliability and validity.

INTRODUCTION: Electrical impedance myography (EIM) is a non-invasive, painless, objective technique to quantify muscle pathology. METHODS: We measured EIM in 8 arm and leg muscles in 61 boys with Duchenne muscular dystrophy (DMD) and 31 healthy boys, ages 3-12 years, at 5 centers. We determined the reliability of EIM and compared results in boys with DMD to controls and to 6-minute walk distance (6MWD), North Star Ambulatory Assessment (NSAA), timed functional tests (TFTs), and strength (hand-held dynamometry). RESULTS: EIM was well tolerated and had good inter- and intrarater reliability (intraclass correlation coefficient 0.81-0.96). The averaged EIM phase value from all muscles was higher (P < 0.001) in controls (10.45 ± 2.29) than boys with DMD (7.31 ± 2.23), and correlated (P ≤ 0.001) with 6MWD (r = 0.55), NSAA (r = 0.66), TFTs (r = -0.56), and strength (r = 0.44). CONCLUSION: EIM is a reliable and valid measure of disease severity in DMD. Longitudinal studies comparing EIM with other assessments over time in DMD are warranted.