A Technique for Performing Electrical Impedance Myography in the Mouse Hind Limb: Data in Normal and ALS SOD1 G93A Animals

Objective: To test a method for performing electrical impedance myography (EIM) in the mouse hind limb for the assessment of disease status in neuromuscular disease models. Methods: An impedance measuring device consisting of a frame with electrodes embedded within an acrylic head was developed. The head was rotatable such that data longitudinal and transverse to the major muscle fiber direction could be obtained. EIM measurements were made with this device on 16 healthy mice and 14 amyotrophic lateral sclerosis (ALS) animals. Repeatability was assessed in both groups. Results: The technique was easy to perform and provided good repeatability in both healthy and ALS animals, with intra-session repeatability (mean ± SEM) of 5% ±1% and 12% ±2%, respectively. Significant differences between healthy and ALS animals were also identified (e.g., longitudinal mean 50 kHz phase was 18±0.6° for the healthy animals and 14±1.0° for the ALS animals, p = 0.0025). Conclusions: With this simple device, the EIM data obtained is highly repeatable and can differentiate healthy from ALS animals. Significance: EIM can now be applied to mouse models of neuromuscular disease to assess disease status and the effects of therapy

Electrical Characteristics of Rat Skeletal Muscle in Immaturity, Adulthood and After Sciatic Nerve Injury, and Their Relation to Muscle Fiber Size

Localized impedance methods can provide useful approaches for assessing neuromuscular disease. The mechanism of these impedance changes remains, however, uncertain. In order to begin to understand the relation of muscle pathology to surface impedance values, 8 immature rats, 12 mature rats, and 8 mature rats that had undergone sciatic crush were killed. Tissue from the gastrocnemius muscle from each animal was measured in an impedance cell, and the conductivity and relative permittivity of the tissue calculated in both the longitudinal and transverse directions for frequencies of 2 kHz to 1 MHz. In addition, quantitative histological analysis was performed on the tissue. Significant elevations in transverse conductivity and transverse relative permittivity were found with animal growth, but longitudinal values showed no difference. After sciatic crush, both transverse and longitudinal conductivity increased significantly, with no change in the relative permittivity in either direction. The frequency dependence of the values also changed after nerve injury. In the healthy animals, there was a strong linear relation between measured conductivity and relative permittivity with cell area, but not for the sciatic crush animals. These results provide a first step toward developing a comprehensive understanding of how the electrical properties of muscle alter in neuromuscular disease states

Utilizing a handheld electrode array for localized muscle impedance measurements

Introduction: Electrical impedance myography (EIM) is a non-invasive technique used for assessment of muscle health in which a high-frequency, low-amplitude electric current is applied to the skin overlying a muscle, and the resulting surface voltage is measured. We have previously used adhesive electrodes, application of which is inconvenient. We present data using a handheld electrode array (HEA) that we devised to expedite the EIM procedure in a clinical setting. Methods: Thirty-four healthy volunteers and 24 radiculopathy subjects underwent EIM testing using the HEA and adhesive electrodes. Results: The HEA was shown to have good test-retest reproducibility, with intraclass correlation coefficients as high as 0.99. HEA data correlated strongly with data from adhesive electrodes, ρ = 0.85 in healthy volunteers (p < 0.001) and ρ = 0.75 in radiculopathy subjects (p < 0.001). Discussion: These data support the potential use of a handheld array for performing rapid localized surface impedance measurements

Biomarkers of Sarcopenia in Clinical Trials—Recommendations from the International Working Group on Sarcopenia

Sarcopenia, the age-related skeletal muscle decline, is associated with relevant clinical and socioeconomic negative outcomes in older persons. The study of this phenomenon and the development of preventive/therapeutic strategies represent public health priorities. The present document reports the results of a recent meeting of the International Working Group on Sarcopenia (a task force consisting of geriatricians and scientists from academia and industry) held on June 7–8, 2011 in Toulouse (France). The meeting was specifically focused at gaining knowledge on the currently available biomarkers (functional, biological, or imaging-related) that could be utilized in clinical trials of sarcopenia and considered the most reliable and promising to evaluate age-related modifications of skeletal muscle. Specific recommendations about the assessment of aging skeletal muscle in older people and the optimal methodological design of studies on sarcopenia were also discussed and finalized. Although the study of skeletal muscle decline is still in a very preliminary phase, the potential great benefits derived from a better understanding and treatment of this condition should encourage research on sarcopenia. However, the reasonable uncertainties (derived from exploring a novel field and the exponential acceleration of scientific progress) require the adoption of a cautious and comprehensive approach to the subject

The effect of subcutaneous fat on electrical impedance myography when using a handheld electrode array: The case for measuring reactance

Objective Recent developments in electrical impedance myography (EIM) have led to the use of handheld electrode arrays (HEA) for data acquisition. Although preferable for several reasons, this approach tends to be more affected by subcutaneous fat (SF) than the original approach in which the impedance-measuring electrodes are widely spaced. In this study, we seek to identify the EIM parameter least impacted by subcutaneous fat (SF) when using an HEA. Methods 18 normal subjects underwent 50 kHz EIM and ultrasound of the medial gastrocnemius muscles on the dominant side. Coefficients of determination (R2 values) were calculated for each of the three major EIM variables (reactance, resistance, and phase) and SF thickness. Results For both resistance and phase, a strong relationship to SF thickness was observed (R2 = 0.64 and R2 = 0.70, respectively, p < 0.001 for both). In contrast, for reactance, the relationship was non-significant, with R2 = 0.07, p = 0.30. Conclusions Unlike resistance and phase, both of which are highly impacted by SF thickness, the reactance shows no significant relationship. Significance Future clinical studies employing HEA’s to perform EIM should evaluate alterations in reactance over those in resistance and phase

The effect of subacute denervation on the electrical anisotropy of skeletal muscle: Implications for clinical diagnostic testing

Objective Applied electrical current flows preferentially along rather than across muscle fibers, a characteristic called anisotropy. In this study, we investigate the alteration in muscle anisotropy after denervation. Methods Eight adult male rats underwent sciatic nerve crush and the gastrocnemius was harvested from 1 to 2.5 weeks later. Muscle from 12 additional healthy rats was also obtained. Multifrequency electrical impedance measurements were made on the tissue and its conductivity and relative permittivity (i.e., its polarizability) calculated. Anisotropy of the tissue was determined by calculating conductivity and permittivity differences, subtracting transverse from longitudinal values. Muscle fiber and blood vessel quantification were also performed. Results The mean conductivity difference for sciatic crush animals was higher (p <0.05) than for the healthy animals across the frequency spectrum, due to a greater increase in longitudinal conductivity than in transverse conductivity. For example, at 10 kHz, the conductivity difference was 0.15 S/m for healthy animals and 0.29 S/m for post-crush animals. Relative permittivity difference values, however, were similar between groups. There was a strong correlation of conductivity anisotropy to muscle fiber size but not to blood vessel area. Conclusions Anisotropy of muscle conductivity increases markedly after subacute denervation injury. Significance This alteration in anisotropy has direct relevance to the clinical application of electrical impedance myography. We also speculate that it may impact other forms of diagnostic testing, including needle electromyography and magnetic resonance imaging

Application of futility analysis to refine jitter recordings in myasthenia gravis

Introduction The current practice of single fiber electromyography (SFEMG) requires that 20 fiber pairs with normal jitter be collected to exclude myasthenia gravis (MG). We applied principles of futility analysis from clinical trials in an attempt to reduce that requirement. Methods We utilized conditional power futility analysis to assess the probability of an abnormal 20-pair SFEMG based on ongoing analysis of jitter as each pair is collected. Rules for early test termination in the presence of 0, 1 or 2 abnormal pairs were identified. These rules were then applied to previously collected SFEMG data. Results SFEMG could be stopped at just 12 pairs if all are normal and at 17 pairs if 1 is abnormal. The rules successfully determined when SFEMG could be stopped in 104/106 (98%) studies originally reported to be normal. Discussion If the first 12 SFEMG pairs have normal jitter, the study can be terminated and interpreted as normal

Critically Re-Evaluating a Common Technique: Accuracy, Reliability, and Confirmation Bias of EMG

Objectives: (1) To assess the diagnostic accuracy of EMG in radiculopathy. (2) To evaluate the intrarater reliability and interrater reliability of EMG in radiculopathy. (3) To assess the presence of confirmation bias in EMG. Methods: Three experienced academic electromyographers interpreted 3 compact discs with 20 EMG videos (10 normal, 10 radiculopathy) in a blinded, standardized fashion without information regarding the nature of the study. The EMGs were interpreted 3 times (discs A, B, C) 1 month apart. Clinical information was provided only with disc C. Intrarater reliability was calculated by comparing interpretations in discs A and B, interrater reliability by comparing interpretation between reviewers. Confirmation bias was estimated by the difference in correct interpretations when clinical information was provided. Results: Sensitivity was similar to previous reports (77%, confidence interval [CI] 63%–90%); specificity was 71%, CI 56%–85%. Intrarater reliability was good (κ 0.61, 95% CI 0.41–0.81); interrater reliability was lower (κ 0.53, CI 0.35–0.71). There was no substantial confirmation bias when clinical information was provided (absolute difference in correct responses 2.2%, CI −13.3% to 17.7%); the study lacked precision to exclude moderate confirmation bias. Conclusions: This study supports that (1) serial EMG studies should be performed by the same electromyographer since intrarater reliability is better than interrater reliability; (2) knowledge of clinical information does not bias EMG interpretation substantially; (3) EMG has moderate diagnostic accuracy for radiculopathy with modest specificity and electromyographers should exercise caution interpreting mild abnormalities. Classification of evidence: This study provides Class III evidence that EMG has moderate diagnostic accuracy and specificity for radiculopathy

Potential Utility of Electrical Impedance Myography in Evaluating Age-Related Skeletal Muscle Function Deficits

Skeletal muscle function deficits associated with advancing age are due to several physiological and morphological changes including loss of muscle size and quality (conceptualized as a reduction in the intrinsic force-generating capacity of a muscle when adjusted for muscle size). Several factors can contribute to loss of muscle quality, including denervation, excitation-contraction uncoupling, increased fibrosis, and myosteatosis (excessive levels of inter- and intramuscular adipose tissue and intramyocellular lipids). These factors also adversely affect metabolic function. There is a major unmet need for tools to rapidly and easily assess muscle mass and quality in clinical settings with minimal patient and provider burden. Herein, we discuss the potential for electrical impedance myography (EIM) as a tool to evaluate muscle mass and quality in older adults. EIM applies weak, non-detectible (e.g., 400 μA), mutifrequency (e.g., 1 kHz–1 MHz) electrical currents to a muscle (or muscle group) through two excitation electrodes, and resulting voltages are measured via two sense electrodes. Measurements are fast (~5 s/muscle), simple to perform, and unaffected by factors such as hydration that may affect other simple measures of muscle status. After nearly 2 decades of study, EIM has been shown to reflect muscle health status, including the presence of atrophy, fibrosis, and fatty infiltration, in a variety of conditions (e.g., developmental growth and maturation, conditioning/deconditioning, and obesity) and neuromuscular diseases states [e.g., amyotrophic lateral sclerosis (ALS) and muscular dystrophies]. In this article, we describe prior work and current evidence of EIM’s potential utility as a measure of muscle health in aging and geriatric medicine

Age- and Gender-Associated Differences in Electrical Impedance Values of Skeletal Muscle

Electrical impedance measurements of skeletal muscle may be sensitive to age-associated declines in muscle health. In an effort to evaluate this concept further, we performed electrical impedance myography (EIM) using a handheld array on 38 individuals aged 19–50 years and 41 individuals aged 60–85 years. Individuals either had 7 upper extremity or 7 lower extremity muscles measured. The 50 kHz reactance, resistance and phase were used as the major outcome variables. Although the phase values were similar in both groups, both reactance and resistance values were lower in the lower extremities of the older individuals as compared to the younger (−23 ± 6%, p = 0.001 for reactance and −27 ± 7%, p = 0.005 for resistance), whereas changes in upper extremity values were not significantly different (−9 ± 5%, p = 0.096 for reactance and +5 ± 9%, p = 0.55 for resistance). When analyzing the genders separately, it became clear that this reduction in lower extremity values was most pronounced in men and less consistently present in women. These findings suggest that age- and gender-associated differences in muscle condition are detectable using EIM. The relationship of these easily obtained parameters to standard functional, imaging, and pathological markers of sarcopenia deserves further study