Localized bioimpedance analysis is a novel, noninvasive technique with potential application to neuromuscular disease. In this procedure, high-frequency alternating current is passed through muscle, and parameters related to the consequent voltage pattern are evaluated. Currents flowing perpendicular to muscle fibers encounter many more cell membranes than do currents flowing parallel to them, producing surface voltage patterns that are altered by disease. Using this technique, 45 normal subjects and 25 patients with various neuromuscular diseases were studied, including 4 with amyotrophic lateral sclerosis, 4 with inflammatory myopathy, and 11 with inclusion-body myositis. Two parameters, the spatially averaged phase and the effective longitudinal resistivity, were altered in patients with neuromuscular disease. Reductions in phase correlated to disease progression, whereas normalization of phase correlated with disease remission. In patients with inclusion-body myositis, a unique pattern of reduced phase and elevated resistivity was identified. These findings suggest that localized bioimpedance analysis has the potential of playing a substantial role in the diagnostic and therapeutic evaluation of neuromuscular disease.

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Electrical impedance myography (EIM) is a noninvasive technique for neuromuscular assessment in which low-intensity alternating current is applied to a muscle and the consequent surface voltage patterns are evaluated. Previous work using a single frequency of 50 kHZ has demonstrated quantitative correlation of EIM parameters with disease status. In this investigation we examined the use of multifrequency EIM, studying a prototypical neurogenic disease (amyotrophic lateral sclerosis, ALS) and myopathic disorder (inflammatory myopathy, IM). Eleven ALS patients, 7 IM patients, and 46 normal subjects participated in the study. Although disease-specific patterns were not identified such that IM could be differentiated from ALS, impedance vs. frequency patterns for diseased subjects differed substantially from those of the age-matched normal subjects, with the greatest alterations occurring in the most severe cases. Multifrequency EIM may be well-suited to serve as an easily applied technique to assess disease severity in a variety of neuromuscular conditions.

Objective-Standard outcome measures used for amyotrophic lateral sclerosis (ALS) clinical trials, including the ALS Functional Rating Scale-revised (ALSFRS-R), maximal voluntary isometric contraction testing (MVICT), and manual muscle testing (MMT) are limited in their ability to detect subtle disease progression. Electrical impedance myography (EIM) is a new non-invasive technique that provides quantitative data on muscle health by measuring localized tissue impedance. This study investigates whether EIM could provide a new outcome measure for use in ALS clinical trials work.Methods-Fifteen ALS patients underwent repeated EIM measurements of one or more muscles over a period of up to 18 months and the primary outcome variable, θ z-max , measured. The θ z-max megascore was then calculated using the same approach as has been applied in the past for MVICT. This and the MMT data were then used to assess each measure's statistical power to detect a given effect on disease progression in a hypothetical planned clinical therapeutic trial.Results-θ z-max showed a mean decline of about 21% for the test period, averaged across all patients and all tested muscles. The θ z-max megascore had a power of 73% to detect a 10% treatment effect in our planned hypothetical trial, as compared to a 28% power for MMT. These results also compared favorably to historical data for ALSFRS-R and MVICT arm megascore from the trial of celecoxib in ALS, where both measures had only a 23% power to detect the same 10% treatment effect.Conclusions-The θ z-max megascore may provide a powerful new outcome measure for ALS clinical trials.Significance-The application of EIM to future ALS trials may allow for smaller, faster studies with an improved ability to detect subtle treatment effects.