Sources of error in the spike-triggered averaging method of motor unit number estimation (MUNE)

Motor unit number estimation (MUNE) is an electrophysical technique to estimate the number of motor units innervating a muscle or muscle group. MUNE may be useful as a measure of progression of lower motor neuron loss in amyotrophic lateral sclerosis (ALS). Several methods of MUNE have been developed. The spike-triggered averaging method can be readily performed on EMG machines with signal averaging capabilities and is suitable for estimating the number of motor neurons innervating proximal muscles. We have used MUNE as a measure of disease state in a drug efficacy trial for ALS. From our experience with this method we have identified sources of error which can affect MUNE accuracy. We have investigated these sources and report their effect on MUNE.© 1995 John Wiley & Sons, Inc.     

Motor unit estimation: Reproducibility of the spike-triggered averaging technique in normal and ALS subjects

Reproducibility of the spike-triggered averaging technique of motor unit estimation (MUE) was assessed in biceps-brachialis muscle in 10 normal subjects and 15 subjects with amyotrophic lateral sclerosis (ALS). MUE was calculated by dividing the compound muscle action potential by the mean amplitude of 15 surface motor unit potentials (S-MUPs) of low recruitment threshold. Averaged MUE values in normal subjects were higher than in ALS subjects, with few values overlapping. Differences between test and retest MUE values were not significant for either subject group. The relative differences between test-retest values were 45.3% for normal subjects and 32.6% for ALS subjects. Correlation coefficients between test and retest values were low (r = 0.07) for normal subjects when influential outlying points were removed, and higher (r = 0.65) for ALS subjects when individuals with MUE values within the normal range were removed. The higher correlation of testretest MUE values in ALS subjects compared to normal subjects may be due to a greater probability of resampling among the smaller number of motor units in ALS subjects. In summary, the reproducibility and technical aspects of the spike-triggered averaging technique are similar to those reported for other MUE techniques. © 1993 John Wiley & Soncs, Inc.     

Motor unit number estimation: A technology and literature review

Introduction: Numerous methods for motor unit number estimation (MUNE) have been developed. The objective of this article is to summarize and compare the major methods and the available data regarding their reproducibility, validity, application, refinement, and utility. Methods: Using specified search criteria, a systematic review of the literature was performed. Reproducibility, normative data, application to specific diseases and conditions, technical refinements, and practicality were compiled into a comprehensive database and analyzed. Results: The most commonly reported MUNE methods are the incremental, multiple‐point stimulation, spike‐triggered averaging, and statistical methods. All have established normative data sets and high reproducibility. MUNE provides quantitative assessments of motor neuron loss and has been applied successfully to the study of many clinical conditions, including amyotrophic lateral sclerosis and normal aging. Conclusions: MUNE is an important research technique in human subjects, providing important data regarding motor unit populations and motor unit loss over time. Muscle Nerve 50 : 884–893, 2014     

Motor unit number estimation,isometric strength,and electromyographic measures in amyotrophic lateral sclerosis

Pathologic progression in amyotrophic lateral sclerosis (ALS) results from motor neuron death, while the clinical expression also reflects the compensatory effects of collateral reinnervation consequent to lower motor neuron loss. In a cross-sectional study of ALS subjects, we made comparisons between motor unit number estimation (MUNE) values and several measures reflecting collateral reinnervation, including isometric strength, compound muscle action potential (CMAP) amplitude, surface motor unit action potential (S-MUAP) amplitude, fiber density (FD), macro-EMG potential amplitude, turns-to-amplitude (T/A) ratio, and amplitude and recruitment pattern of low threshold voluntary motor units in elbow flexor muscles. Before comparisons were made, testretest reproducibility of these measures was assessed in ALS subjects, and is highest for isometric strength, and lower but similar for EMG measures. When the effects of multiple comparisons are considered, borderline significant correlations are found between MUNE values and isometric strength. Neither MUNE values nor isometric strength are significantly correlated with macro-EMG amplitude, FD, T/A ratio, or amplitude and recruitment rate of low threshold voluntary motor units. There are significant correlations of CMAP and S-MUAP with MUNE values, but these are statistical artifacts with no independent interpretation. We conclude that collateral reinnervation prevents isometric strength and EMG measures from accurately reflecting lower motor neuron death in ALS. MUNE measurements are better suited to provide insight into the true natural history of the disease process and may be clinically useful to follow progression and response in drug trials. © 1993 John Wiley & Sons, Inc.     

Decomposition-enhanced spike-triggered averaging: Contraction level effects

Decomposition-enhanced spike-triggered averaging (DE-STA) was applied to the vastus medialis muscle to examine size distributions of surface-detected motor unit action potentials (S-MUAPs) at various force levels. Using DE-STA, 15–20 S-MUAPs were identified during 5%, 10%, 20%, and 30% of maximum voluntary contraction. Average S-MUAPs showed increase in peak to peak (and negative peak) amplitude with force (in μV): 5% = 37.9 ± 6.1 (16.6 ± 2.5), 10% = 44.0 ± 4.0 (20.4 ± 1.8), 20% = 80.7 ± 9.3 (41.3 ± 4.5), and 30% = 102.5 ± 10.3 (53.6 ± 5.0). Test-retest variability of peak to peak (and negative peak amplitude) between repeated trials was 0.10 (0.14), 0.14 (0.14), 0.17 (0.15), and 0.21 (0.20) at 5%, 10%, 20%, and 30% respectively. A relationship was found between the S-MUAP amplitude and force (r² = 0.78, df = 90, F = 160, P < 0.001). Increase in average S-MUAP amplitude with force suggests that STA performed only at low levels of contraction may result in a biased sampling and small average S-MUAP amplitudes. © 1997 John Wiley & Sons, Inc. Muscle Nerve 20: 976–982, 1997     

Motor unit number estimation: Sample size considerations

A computer model of the motor unit number estimation procedure was developed to evaluate the sampling error associated with estimates of the number of motor units in muscles. Two different distributions were used to model the motor unit amplitude distribution and were chosen in such a manner that they qualitatively matched the distributions observed under both normal and neurogenic conditions. As expected, the results indicated that estimation error decreases as a function of sample size. However, the relationship between these two variables was nonlinear in the sense that successive increases in sample size lead to progressively smaller decreases in estimation error. The results also indicated that the shape of the motor unit amplitude distribution plays an important role. Specifically, estimates obtained using the distribution modeling normal muscle were generally higher than the actual number of motor units in the muscle, which was not the case for the distribution modeling neurogenic muscle. In addition, the neurogenic distribution was associated with much smaller estimation error, suggesting that motor unit number estimation is well suited to the analysis of neurogenic disease processes. © 1997 John Wiley & Sons, Inc.     

Motor unit number estimation by spatial-temporal summation of single motor unit potentials

Current techniques for motor unit number estimation (MUNE) rely on the amplitude of the compound muscle action potential (CMAP) evoked by supramaximal stimulation and mean amplitude of single motor unit potentials (SMUPs). The phase cancellation during summation is not considered. We developed a technique to address this issue. Slow and fast types of motor unit potentials were collected from 5 normal subjects from their abductor pollicis brevis muscles by low-level voluntary contractions, and near-threshold nerve stimulation, respectively. Two of each type of SMUPs were used as templates for reconstructing the best fitted CMAP using a feed-forward neural network. The total number of SMUPs simulated from the four templates during the reconstruction served as MUNE. The mean MUNE was 222 ± 98. The technique is simple and noninvasive, and may be applied in the future for MUNE in patients. © 1997 John Wiley & Sons, Inc. Muscle Nerve, 20, 461–468, 1997     

Motor unit number estimates and quantitative motor unit analysis in healthy subjects and patients with amyotrophic lateral sclerosis

Limitations associated with global measures of function in patients with amyotrophic lateral sclerosis (ALS) and the qualitative nature of needle electromyography have stimulated the development of alternate means of monitoring disease severity and progression in ALS. Thus, the objective of this study was to examine the ability of one these techniques, decomposition-based quantitative electromyography (DQEMG), to obtain electrophysiological data, including motor unit number estimates (MUNEs), from a group of patients with ALS. The first dorsal interosseous and biceps brachii muscles were studied in 10 healthy subjects and 9 patients with ALS. Following the acquisition of a maximum M wave, needle- and surface-detected EMGs were collected simultaneously during 30-second contractions performed at 10% of the maximum voluntary contraction force to obtain motor unit potential (MUP) trains. DQEMG was then used to extract the surface-detected MUP associated with each MUP train, the mean size of which was divided into the maximum M wave to obtain a MUNE. The results suggest that quantitative electrophysiological data obtained using DQEMG are representative of the pathophysiological changes in the lower motor system in ALS patients, supporting its use in studies documenting the natural history and progression of the disease.     

Intra- and inter-rater reliability of motor unit number estimation and quantitative motor unit analysis in the upper trapezius

Objective

To collect normative data and assess the intra- and inter-rater reliability of decomposition-enhanced spike-triggered averaging (DE-STA) motor unit number estimation (MUNE) and quantitative MU analysis obtained using decomposition-based quantitative electromyography (DQEMG) in the upper trapezius (UT).

Methods

In 10 control subjects, the experimental protocol was performed twice by the same examiner, and once by a second examiner.

Results

Mean MUNE values were 339 ± 121 (rater 1a), 320 ± 131 (rater 1b), and 262 ± 115 (rater 2) MUs. Intra- and inter-rater reliability was good for maximum CMAP (ICC = 0.77 and 0.79, respectively) and moderate for MUNE (ICC = 0.69 and 0.73, respectively), with poor inter-rater reliability for mean S-MUP (ICC = 0.42). Significant differences between rater 1a and 2 were found for mean S-MUP (p = 0.014) and MUNE (p = 0.002), and moderate to good levels of reliability found for quantitative needle-detected MUP parameters.

Conclusions

Various components of the protocol may have contributed to mean S-MUP variability, and may require particular attention in a large, proximal muscle like the UT.

Significance

This study has established preliminary data using DQEMG in a novel muscle which may be relevant to study in patients with ALS.     

Motor unit action potential topography and its use in motor unit number estimation

High-density multichannel electromyography (EMG) recordings add spatial information to the temporal information content of the surface EMG (sEMG) signal. This study explores the potential value of such multichannel information at a single motor unit level, in particular for the improvement of motor unit number estimation (MUNE) techniques. It is shown that multichannel recordings make it easier to distinguish motor unit action potentials (MUAPs) and that MUAP combinations can be better resolved. Furthermore, the spatiotemporal information allows a quantitative assessment of the representativity of the mean of the recorded MUAPs in relation to the maximum CMAP, i.e., for the muscle as a whole. In general, this is practically impossible on the basis of temporal information alone. For these reasons, we expect that high-density sEMG has the potential to address several methodological limitations of single channel surface EMG recordings. This is specifically illustrated in this study for one of the MUNE techniques in use, the F-response method.     

A new approach to motor unit estimation with surface EMG triggered averaging technique

A new method for estimating the number of motor units using a surface EMG triggered averaging technique is described. This method provides an estimation of mean motor unit potential (MUP) amplitude at different leveles of contraction, which can be utilized to estimate the number of motor units in a given muscle. Motor unit count estimated in abductor pollicis brevis (APB) muscle of 11 normal healthy subjects ranged from 131 to 371 with a mean of 246 ± 68. In our preliminary study of patients with lower motor neuron lesions, there was a significant reduction in the number of motor units. We believe our new noninvasive method of motor unit counting is a relatively simple and reproducible physiological technique.© 1995 John Wiley &Sons, Inc.     

Motor unit number estimates in the tibialis anterior muscle of young, old, and very old men

The rate of motor unit (MU) loss and its influence on the progression of sarcopenia is not well understood. Therefore, the main purpose of this study was to estimate and compare numbers of MUs in the tibialis anterior (TA) of young men ( approximately 25 years) and two groups of older men ( approximately 65 years and >/=80 years). Decomposition-enhanced spike-triggered averaging was used to collect surface and intramuscular electromyographic signals during isometric dorsiflexions at 25% of maximum voluntary contraction. The mean surface-MU potential size was divided into the maximum M wave to calculate the motor unit number estimate (MUNE). The MUNE was significantly reduced in the old (91) compared to young (150) men, and further reduced in the very old men (59). Despite the smaller MUNE at age 65, strength was not reduced until beyond 80 years. This suggests that age-related MU loss in the TA does not limit function until a critical threshold is reached.     

Motor unit number index (MUNIX): principle, method, and findings in healthy subjects and in patients with motor neuron disease

The motor unit number index (MUNIX) is a method for assessment of number and size (MUSIX) of motor units (MUs) using the compound muscle action potential (CMAP) and surface electromyographic interference pattern (SIP). This method was used to study the hypothenar muscle in 34 healthy subjects to define normal range, and to study reproducibility. Four healthy subjects and 13 patients with amyotrophic lateral sclerosis (ALS) were studied serially over a 1-year period. In healthy subjects, MUNIX showed good reproducibility. In serial studies, healthy subjects showed no change in the CMAP amplitude and MUNIX. ALS patients with minimal change in CMAP amplitude had a significant drop in MUNIX and increase in MUSIX, indicating MU loss compensated by reinnervation. When the CMAP changed significantly (>30%) in 1 year, the CMAP and MUNIX decreased in parallel. MUNIX would be useful to study MU loss in degenerative diseases of motor neurons. Muscle Nerve 42: 798-807, 2010.     

Motor unit number estimation in facial paralysis

The value of motor unit number estimation (MUNE) in determining the prognosis of acute peripheral facial paralysis (PFP) was evaluated in 89 patients with PFP on days 6, 8, 11, 14, 20, and 30 of PFP and repeated once per month until complete recovery or the end of the first year. The symptomatic/asymptomatic side ratios of the compound muscle action potential (CMAP) amplitudes recorded from nasalis muscles and MUNEs studied using the incremental method by recording from the same muscle were assessed with regard to three outcome groups (Group I, complete recovery; Group II, mild dysfunction; Group III, moderate-moderately severe dysfunction). CMAP and MUNE ratios were parallel to each other in all patient groups throughout the observation period with lower values in the more severe groups. However, CMAP amplitude loss was significantly greater than the MUNE loss in the first 3 weeks of PFP. The MUNE method is not superior to CMAP size in determining prognosis in PFP. However, the significant disparity between the CMAP and MUNE ratios in the early period may have some physiological relevance with regard to the pathophysiology of the Wallerian degeneration process and deserves further research into its potential sources.     

Intra-rater reliability of motor unit number estimation and quantitative motor unit analysis in subjects with amyotrophic lateral sclerosis

ObjectivesTo assess the intra-rater reliability of decomposition-enhanced spike-triggered averaging (DE-STA) motor unit number estimation (MUNE) and quantitative motor unit potential analysis in the upper trapezius (UT) and biceps brachii (BB) of subjects with amyotrophic lateral sclerosis (ALS) and to compare the results from the UT to control data.MethodsPatients diagnosed with clinically probable or definite ALS completed the experimental protocol twice with the same evaluator for the UT (n = 10) and BB (n = 9).ResultsIntra-rater reliability for the UT was good for the maximum compound muscle action potential (CMAP) (ICC = 0.88), mean surface-detected motor unit potential (S-MUP) (ICC = 0.87) and MUNE (ICC = 0.88), and for the BB was moderate for maximum CMAP (ICC = 0.61), and excellent for mean S-MUP (ICC = 0.94) and MUNE (ICC = 0.93). A significant difference between tests was found for UT MUNE. Comparing subjects with ALS to control subjects, UT maximum CMAP (p < 0.01) and MUNE (p < 0.001) values were significantly lower, and mean S-MUP values significantly greater (p < 0.05) in subjects with ALS.ConclusionsThis study has demonstrated the ability of the DE-STA MUNE technique to collect highly reliable data from two separate muscle groups and to detect the underlying pathophysiology of the disease.SignificanceThis was the first study to examine the reliability of this technique in subjects with ALS, and demonstrates its potential for future use as an outcome measure in ALS clinical trials and studies of ALS disease severity and natural history.     

Motor unit number estimation in infants and children with spinal muscular atrophy

Spinal muscular atrophy (SMA) is a disease of lower motor neurons. Motor unit number estimation (MUNE) is an electrophysiologic method to estimate the number of motor neurons innervating a muscle group. We applied the multiple point stimulation technique to the ulnar nerve--hypothenar muscle group to study lower motor neuron loss in 14 SMA subjects, including those presymptomatic, and varying from newborn through 45 years of age. Preliminary data support the value of MUNE to help understand the time course of motor neuron loss in SMA.     

Motor unit number estimation in the evaluation of focal conduction block

Temporal dispersion and phase cancellation limit the utility of amplitude reduction in compound muscle action potential (CMAP) as a measure of focal conduction block but may not affect motor unit number estimation (MUNE). Hence, MUNE offers the potential of a specific measure of conduction block. We investigated the role of MUNE in 11 patients with ulnar neuropathy and conduction block at the elbow and also in 8 normal subjects. MUNE failed to detect motor unit dropout in the patient group because reduced values for surface-recorded motor unit potentials (SMUPs) were obtained at proximal locations, suggesting that focal compression selectively damages larger motor axons, an hypothesis that has support from animal studies. We conclude that, because MUNE is affected by the physiological characteristics of functional axons surviving the underlying pathological process, the utility of MUNE is limited to diseases in which the expected pathology affects motor axons uniformly.     

Motor unit number estimation predicts disease onset and survival in a transgenic mouse model of amyotrophic lateral sclerosis

Motor unit number estimation (MUNE) has proved useful in predicting rate of progression and survival in patients with amyotrophic lateral sclerosis (ALS). In animal models, it has demonstrated physiological effects of experimental medications that were not evident behaviorally. We sought to determine more specifically what aspects of function and survival that MUNE could predict in the G93A transgenic mouse model of ALS. Transgenic mice were examined in two distinct treatment studies, neither of which showed an effect of drug on survival, behavioral measures, or MUNE. MUNE was performed using a modification of the incremental stimulation method by stimulating the sciatic nerve at the sciatic notch, and recording with a circumferential surface electrode around the ipsilateral distal hindlimb. Both limbs were studied and the results averaged. MUNE was performed longitudinally on all animals from near onset to premorbid state. Each study was evaluated separately. For both studies, MUNE at initial study correlated significantly with behavioral determination of disease onset, and MUNE slope from initial to final study correlated significantly with disease duration, as measured from onset to time of death. However, the final MUNE value did not correlate with survival. Thus, in two studies involving animals with quite different disease courses, initial MUNE effectively predicted symptom onset and MUNE slope predicted survival. This suggests that MUNE has potential efficacy as a useful functional outcome measure in both animal and human studies of ALS.     

Motor unit number estimation and neuromuscular fidelity in 3 stages of sarcopenia

Introduction: Loss of motor units (MUs) and alterations in MU properties are major factors in development of sarcopenia. The purpose of this study was to compare MU properties among 3 groups categorized as either pre‐sarcopenic (n = 7), sarcopenic (n = 7), or severely sarcopenic (n = 5), all with similarly aged subjects (75–82 years). Methods: Using decomposition‐enhanced quantitative electromyography, MU number estimates and neuromuscular stability measures of near‐fiber (NF) jitter and jiggle were derived in addition to contractile properties of ankle dorsiflexors. Results: MU number estimates were similar across groups; however, maximal voluntary strength in the severe sarcopenia group was 27% and 37% less than the sarcopenic and pre‐sarcopenic groups, respectively. Moreover, NF jiggle was 31% greater in the severe group compared with pre‐sarcopenia, NF jitter was 43% greater in the severe group compared with the pre‐sarcopenic group. Conclusion: Unlike MU number estimates, strength and MU stability differed across groups and related to degree of sarcopenia. Muscle Nerve 55: 676–684, 2017