Proximal-distal motor unit number estimation-dynamic changes in patients with amyotrophic lateral sclerosis A one-year follow-up

BACKGROUND:Amyotrophic lateral sclerosis (ALS) is the most common of all the motor neuron diseases and the absence of a biologic marker has made both diagnosis and tracking evolution of the disease difficult, Electrodiagnostic tests play a fundamental role in quantifying pathological changes in the motor unit pool.OBJECTIVE:We assessed distal-proximal Motor Unit (MU) loss and changes using the method of motor unit number estimation (MUNE).DESIGN, TIME AND SETTING:A case-control study was performed at the Department of Neuroscience, Pisa University Medical School, Italy from December 1999 to November 2009. PARTICIPANTS:A total of 50 ALS patients were recruited, 30 males:mean age (59.6 ± 13.3) years; 20 females:mean age (63.9 ± 11.7) years; range (30-82) years; all patients had probable or definite ALS. Thirty healthy volunteers were recruited from department staffs, including 20 males and 10 females; mean age (57.7 ± 13.8) years served as controls.METHODS:MUNE was performed for both the biceps brachii and abductor digiti minimi muscles of the same side. The technique used relayed substantially on manual incremental stimulation of the motor nerve, known as the McComas technique (50 ms sweep duration, a gain of 2 mV/Div for M wave, 0.5 mV/Div for each step; filters 10-20 kHz).MAIN OUTCOME MEASURES:MUNE results were measured.RESULTS:Functioning MU numbers, measured by MUNE, decreased in the biceps brachii and abductor digiti minimi muscles over the entire one-year follow-up period (one assessment every three months) compared with baseline determination, the rate of MU decrease was similar in both muscles, but steeper distally.CONCLUSION:MUNE is a feasible method for ALS patients both proximally and distally to track changes over time in muscle MUs during the disease's evolution.     

Motor unit properties of biceps brachii during dynamic contractions in chronic stroke patients

The aim of this study was to investigate motor unit (MU) characteristics of the biceps brachii during sinusoidal contractions in chronic stroke patients using high-density surface electromyography. Ten sinusoidal elbow flexion and extension movements were performed both passively and actively by 18 stroke patients and 20 healthy subjects. Motor unit action potentials (MUAPs) were extracted, and their root-mean-square value (RMS(MUAP)) was calculated. RMS(MUAP) was significantly larger in stroke than in healthy subjects. In both groups RMS(MUAP) was smaller during the stretch phase of passive movement than during active movement. The larger MUAPs indicate enlarged MUs, possibly as a result of reinnervation. The lower RMS(MUAP) values during passive stretch than during active movement indicates that the stretch reflex mainly activates smaller MUs, while a larger part of the MU pool can be recruited voluntarily. RMS(MUAP) may have added value for monitoring changes in peripheral MU properties after stroke.     

Decomposition-based quantitative electromyography: methods and initial normative data in five muscles

Quantitative electromyographic (EMG) techniques provide clinically useful information to aid in the diagnosis and follow the course or response to treatment of diseases affecting the motor system. The purpose of this study was to describe a decomposition-based quantitative electromyography method (DQEMG) designed to obtain clinically applicable information relating to motor unit potential (MUP) size and configuration, and motor unit (MU) firing characteristics. Additionally, preliminary normative data were obtained from the deltoid, biceps brachii, first dorsal interosseous, vastus medialis, and tibialis anterior muscles of 13 control subjects. DQEMG was capable of efficiently and accurately extracting MUP data from complex interference patterns during mild to moderate contractions. MUP amplitude, surface-detected MUP (S-MUP) amplitude, MUP duration, number of phases, and MU firing frequencies varied significantly across muscles. The mean parameter values for the individual muscles studied were similar to previous reports based on other quantitative methods. The main advantages of this method are the speed of data acquisition and processing, the ability to obtain MUPs from MUs with low and higher recruitment thresholds, and the ability to obtain both S-MUP or macro-MUP data as well as MU firing rate information.     

Motor unit size estimation of enlarged motor units with surface electromyography

Surface EMG is hardly used to estimate motor unit (MU) characteristics, while its non-invasiveness is less stressful for patients and allows multi-electrode recordings to investigate different sites of the muscle and MU. The present study compares motor unit potentials (MUPs) obtained with surface EMG and macro EMG during voluntary contraction of the biceps brachii muscle of patients with enlarged MUs caused by prior poliomyelitis. Averaged surface MUPs were obtained by means of needle EMG (SMUP1) and surface EMG (SMUP2) triggering. The MUPs area and peak amplitudes correlated well when comparing the macro MUP and SMUP1 of the same MUs. When MU populations of different patients were compared, the SMUP1s and SMUP2s were equally sensitive to pathology as macro MUPs. In this, the late non-propagating positive wave (only present in unipolar recordings) is more robust than the triphasic propagating wave. Therefore, surface EMG can be used for detecting enlarged MUs. © 1998 John Wiley & Sons, Inc. Muscle Nerve 21:878–886, 1998.     

Motor unit properties of biceps brachii in chronic stroke patients assessed with high‐density surface EMG

The aim of this study was to investigate motor unit (MU) characteristics of the biceps brachii in poststroke patients using high‐density surface electromyography (sEMG). Eighteen chronic hemiparetic stroke patients took part. The Fugl‐Meyer score for the upper extremity was assessed. Subjects performed an isometric step contraction consisting of force levels from 5%–50% maximal voluntary contraction while sEMG of the biceps brachii was recorded with a two‐dimensional 16‐channel electrode array. This was repeated for both sides. Motor unit action potentials (MUAPs) were extracted from the EMG signals, and their root‐mean‐square value (RMS_MUAP, reflecting MU size) and mean frequency of the power spectrum (FMEAN_MUAP, reflecting recruitment threshold) were calculated. FMEAN_MUAP was smaller on the affected than on the unaffected side, indicating an increased contribution of low‐threshold MUs, possibly related to degeneration of high‐threshold MUs. The ratio of RMS_MUAP on the affected side divided by that on the unaffected side correlated significantly with the Fugl‐Meyer score. This ratio may reflect the extent to which reinnervation has occurred on the affected side. © 2008 Wiley Periodicals, Inc. Muscle Nerve 2008     

Experimental muscle pain increases trapezius muscle activity during sustained isometric contractions of arm muscles.

OBJECTIVE: In the present study, the influence of experimental muscle pain on muscle co-ordination and fatigue development during sustained isometric elbow flexion was investigated. METHODS: Conventional surface electromyography (EMG) was recorded from the biceps brachii, brachioradialis, deltoideus and trapezius muscle during isometric elbow flexion at 40% maximum force. Single motor unit (MU) conduction velocity in the biceps brachii was assessed using a high spatial resolution surface EMG technique. Measurements were performed on 15 healthy subjects before, during and after (1) injection of hypertonic (pain condition) and (2) isotonic saline (control) into the biceps brachii. The pain intensity was assessed on a 10 cm visual analogue scale. RESULTS: The experimental results showed in both experimental sessions a fatigue-related increase of the root mean square value of EMG (222+/-164% of the baseline), and a decrease of the median frequency (118+/-16% of the baseline) in all investigated muscles. A maximum pain level of in average 3.2 cm on the visual analogue scale was reached after injection of hypertonic saline during contraction. Differences between painful and control condition were seen in an increased trapezius activity (230+/-141%) during pain. The global EMG activity of the brachioradialis and biceps brachii was unaffected by experimental muscle pain in line with unaffected single MU conduction velocity in the biceps brachii. Differences in endurance time (mean 89.3 and 102.3 s, pain and control, respectively) were not significant. CONCLUSIONS/SIGNIFICANCE: The findings suggest that upper extremity pain could be a possible source for overloading the trapezius muscle and as such is an important factor in occupational settings.     

Motor unit size estimation: confrontation of surface EMG with macro EMG

Surface EMG (SEMG) is little used for diagnostic purposes in clinical neurophysiology, mainly because it provides little direct information on individual motor units (MUs). One of the techniques to estimate the MU size is intra-muscular Macro EMG. The present study compares SEMG with Macro EMG. Fifty-eight channel SEMG was recorded simultaneously with Macro EMG. Individual MUPs were obtained by single fiber triggered averaging. All recordings were made from the biceps brachii of healthy subjects during voluntary contraction at low force. High positive correlations were found between all Macro and Surface motor unit potential (MUP) parameters: area, peak-to-peak amplitude, negative peak amplitude and positive peak amplitude. The MUPs recorded with SEMG were dependent on the distance between the MU and the skin surface. Normalizing the SEMG parameters for MU location did not improve the correlation coefficient between the parameters of both techniques. The two measurement techniques had almost the same relative range in MUP parameters in any individual subject compared to the others, especially after normalizing the surface MUP parameters for MU location. MUPs recorded with this type of SEMG provide useful information about the MU size.     

Within-subject reliability of motor unit number estimates and quantitative motor unit analysis in a distal and proximal upper limb muscle.

OBJECTIVE: To establish within-subject reliability of motor unit number estimates (MUNEs) and quantitative MU analysis using decomposition-based quantitative electromyography (DQEMG). METHODS: Following the acquisition of a maximum M-wave, needle and surface-detected EMG signals were collected during contractions of the first dorsal interrosseous (FDI) and biceps brachii (BB). DQEMG was used to extract motor unit potential (MUP) trains and surface-detected MUPs associated with each train, the mean size of which was divided into the maximum M-wave to obtain a MUNE. Retests were performed following the initial test to evaluate reliability. RESULTS: Subjects test-retest MUNEs were highly correlated (r=0.72 FDI; 0.97 BB) with no significant differences between test and retest MUNE values (P>0.10). Ninety-five percent confidence intervals were calculated to establish the range of expected retest MUNE variability and were +/-41 MUs for the FDI and BB. Quantitative information pertaining to MU size, complexity and firing rate were similar for both tests. CONCLUSION: MUNEs and quantitative MU data can be obtained reliably from the BB and FDI using DQEMG in individual subjects. SIGNIFICANCE: Establishing within-subject reliability of MUNEs and quantitative MU analysis allow clinicians to longitudinally follow changes in the MU pool of individuals with disorders of the central or peripheral nervous system in addition to assessing their response to treatments.     

Motor unit recruitment pattern during low-level static and dynamic contractions

Motor unit (MU) recruitment patterns were studied during dynamic and static contractions at workloads corresponding to 10% of maximal voluntary contraction force. The dynamic contraction consisted of a 20% flexion and extension of the elbow performed with a velocity of 10μ/s. Motor unit potential trains were recorded from the branchial biceps muscle of 6 healthy females using a quadripolar needle electrode and a computerized decomposition program. Properties of the identified MUs were derived from concentric needle EMG. A total of 119 MUs were identified during dynamic contractions, 107 MUs during static anisotonic contractions, and 96 MUs during static isotonic contractions. The main result was that MUs recruited during different contractions showed similar properties and may belong to the same part of the motoneuron pool. This indicates that MU recruitment patterns during dynamic contractions may be almost as stereotypical as during static contractions and may even activate the same MUs.© 1995 John Wiley &Sons, Inc.     

Excitatory synaptic potentials in spastic human motoneurons have a short rise-time

This study assessed whether changes in size or time-course of excitatory postsynaptic potentials (EPSPs) in motoneurons innervating spastic muscle could induce a greater synaptic response, and thereby contribute to reflex hyperexcitability. We compared motor unit (MU) firing patterns elicited by tendon taps applied to both spastic and contralateral (nonspastic) biceps brachii muscle in hemiparetic stroke subjects. Based on recordings of 115 MUs, significantly shortened EPSP rise times were present on the spastic side, but with no significant differences in estimated EPSP amplitude. These changes may contribute to hyperexcitable reflex responses at short latency, but the EPSP amplitude changes appear insufficient to account for global differences in reflex excitability.     

Relation between location of a motor unit in the human biceps brachii and its critical firing levels for different tasks

Critical firing levels (CFLs) of single motor units (MUs) in the long head of the human biceps brachii muscle were determined in combinations of two isometric tasks: flexion of the elbow, supination of the lower arm, and exorotation of the humerus, as well as the corresponding antagonistic tasks. The MU activity was recorded by 25-micron bipolar wire electrodes. Four main patterns of MU recruitment, related to the recording location in the muscle, were found: (i) MUs active only when flexing the elbow were located mostly laterally. (ii) MUs active only when supinating were all located medially. (iii) MUs whose CFL depended on a linear combination of flexion and supination forces were all located medially. Some of these MUs could not be recruited during pronation. (iv) Nonlinearly behaving MUs, located centrally. The relative weights of flexion and supination input were constant for all units, whose CFL depended on a linear sum of flexion and supination forces, as well as for the nonlinearly behaving units. Supination and exorotation showed equivalent CFL changes when they were combined with the flexion task. Extension did not change the CFL for supination- or exorotation tasks. No clear difference was found between the ratios of the peak twitch forces in flexion and supination direction for laterally and medially located small muscle areas or single MUs. A simple model of the motoneuron pool organization is proposed to explain our findings.     

Discharge pattern of human motor units during dynamic concentric and eccentric contractions

Objectives: A total of 45 motor units (MUs) from the human biceps brachii muscle were investigated during isovelocity concentric and eccentric movements performed by means of a device implementing an external torque in the direction of the extension proportionally to the elbow angle changes. The effects of movement velocity on the recruitment and decruitment thresholds (RT and DT) and the corresponding discharge patterns were determined. Methods: A wire branched electrode placed subcutaneously was used to discriminate the potentials from a single MV. Results: The majority of MUs (91%) were recruited at lower torque values with the increase of movement velocity. The decrease of RT was statistically significant for 47% of the investigated MUs. A typical discharge pattern of short first interspike interval (ISI) followed by a longer one was observed for 93% of all MUs. After the first 2–3 spikes the rate of the MU discharge was approximately constant regardless of the fact that the muscle force gradually increased until the end of the concentric movement.Conclusions: There are differences in the muscle force control during shortening and lengthening contractions. For 82% of the investigated MUs DT was smaller at faster movements and for 21 MUs (47%) the decrease of DT was significant. The gradually declined MU discharge rate throughout the entire movement with a very long last ISI was demonstrated for 93% of the investigated MUs.     

Age-related change in motor unit activation strategy in force production: a mechanomyographic investigation

This study was designed to examine the effect of increasing age on the recruitment and activation of motor units (MU) in the biceps brachii muscle, using the mechanomyogram (MMG)/force relationship during isometric ramp contractions. The relationships between the root mean squared amplitude (RMS) and mean power frequency (MPF) of the MMG and relative force (% MVC) in the elderly (male, n = 10, age = 69.8 +/- 4.7 years, mean +/- SD) were markedly different from those in the young group (male, n = 15, age = 22.7 +/- 1.8 years). In elderly individuals, the RMS increased progressively with force up to 57.6 +/- 3.4% MVC, when a brief rapid increase was followed by a stable trend beyond 63.6 +/- 3.7% MVC. The MPF increased slowly up to 59.4 +/- 2.3% MVC; after a temporary reduction from 59.4% to 64.3 +/- 2.0% MVC, it then increased progressively again. In conjunction with absolute force (F(abs)), both the RMS and MPF in the elderly were smaller than those in the young group throughout the submaximal levels of force exerted. The results reflect an alteration in MU activation strategy, with a predominant role for MUs with slow-twitch fibers and an effective fused tetanus induced at lower firing rate of the MUs, resulting from age-related neuromuscular changes.     

Characterizing spinal muscular atrophy with electrical impedance myography

Electrical impedance myography (EIM) is a non-invasive, painless technique for the evaluation of neuromuscular disease, and here we evaluate its potential application in spinal muscular atrophy (SMA). Twenty-one SMA patients and 18 healthy children underwent EIM of biceps brachii and tibialis anterior using a commercially available impedance device. Hand-held dynamometry and ultrasound assessment of subcutaneous fat thickness were also performed. All EIM parameters differed significantly between both SMA patients and normal subjects and between type 2 and type 3 SMA patients. In addition, EIM had an accuracy level as high as 93% for correctly categorizing patients as type 2 or type 3. Multiple regression analyses confirmed a strong association between EIM and dynamometry. These results confirm that EIM can accurately categorize patients with SMA. Because EIM requires no patient effort and is rapid to apply, it may serve a useful role in future SMA clinical trials.     

Effect of age on muscle functions investigated with surface electromyography.

The purpose of this study was to investigate changes in the surface electromyographic (EMG) signal as a means of defining age-related central and peripheral mechanisms affecting muscle fatigue. Spectral and temporal variables of the surface EMG signal were studied during voluntary isometric contractions of the dominant biceps brachii muscle in a group of 8 healthy elderly men (age range 67-86 years) and a group of 10 healthy young men (age range 23-34 years). The maximal torque developed and the rate of decrease (slope) of spectral variables and conduction velocity (CV) were statistically higher in the young subjects than in the elderly subjects. Motor unit (MU) CV distribution was also estimated from the surface EMG signal and no statistical difference was observed in its variance between the two groups. These results confirm previous findings from the tibialis anterior muscle. Thus, changes in fiber type distribution and decrease in MU firing rate with aging may be factors determining the decrease in maximal voluntary contraction torque and in myoelectric manifestations of muscle fatigue.     

Sensitivity of motor unit potential analysis in facioscapulohumeral muscular dystrophy

Template-operated motor unit potential (MUP) analysis has made quantitative electromyography (EMG) feasible, even in busy laboratories, but validation of this approach is still necessary. In the present study, the utility of multi-MUP analysis was assessed in patients with a molecular genetic diagnosis of facioscapulohumeral muscular dystrophy (FSHD). Manual assessment of muscle strength and concentric-needle EMG of the biceps brachii and vastus lateralis muscles were performed. The sensitivity for diagnosing myopathy (mean values and outliers) was tested for eight MUP parameters and four of their combinations. The group comprised 31 patients. Elbow flexion and knee extension strength was normal in 45% and 52% of patients, respectively. The most sensitive MUP parameter was thickness, followed by duration. A combination of three MUP parameters (thickness, amplitude, and duration/area) was needed for maximal sensitivity. The study demonstrated a high sensitivity of multi-MUP analysis in FSHD. Myopathic abnormalities were demonstrated in all weak biceps brachii muscles, and in 77% of biceps brachii muscles with normal strength.     

Macro electromyography and motor unit number index in the tibialis anterior muscle: differences and similarities in characterizing motor unit properties in prior polio

Our objective was to establish the usefulness of the noninvasive method of the motor unit number index (MUNIX) in a large muscle and to study how macro electromyography (EMG) and MUNIX complement each other in describing the motor units (MUs) in prior polio. MUNIX and macro EMG were performed in 48 tibialis anterior muscles in 33 prior polio patients. In addition, the reproducibility of MUNIX was investigated. It is shown that MUNIX can be used to characterize MUs with high reproducibility, even in a large muscle. As judged by MUNIX values, the patients had a 25% reduction of motor neurons, whereas the macro EMG indicated a loss of 60% of the neurons. Macro EMG showed more pronounced changes compared with control material than the MUNIX. One of the reasons for this finding may be the difference in MU populations studied with the two methods.     

Analysis of double discharges in amyotrophic lateral sclerosis

Double discharges of motor units (MUs) occurring during sustained voluntary muscle contractions are observed occasionally in healthy muscles and more frequently in disorders of the neuromuscular system. In healthy subjects, double discharges are generated in motoneurons (MNs) and are considered to be a sign of their increased excitability. Therefore, an analysis of their firing pattern may provide information on the state of MNs in neuromuscular diseases, particularly in amyotrophic lateral sclerosis (ALS), whose etiology remains to be disclosed. Firing patterns of MUs capable of firing double discharges were analyzed in brachial biceps of 14 patients with ALS (184 MUs) and 8 healthy control subjects (102 MUs). The incidence of MUs capable of firing double discharges was significantly higher in ALS patients (28.8%) than in controls (3.9%). The majority of doublet interval durations (range 4-8 ms) as well as firing patterns of doubling MUs did not differ between subject groups. Although our data confirm the hyperexcitability of the MN pool in ALS, analysis of firing characteristics of doubling MUs indicates that doublet generation is governed by the same mechanism as in controls, that is, by delayed depolarization. Our findings may provide insight into MN function in ALS.     

Spasticity,weakness, force variability,and sustained spontaneous motor unit discharges of resting spastic–paretic biceps brachii muscles in chronic stroke

Introduction: The purpose of our study was to examine relations among spasticity, weakness, force variability, and sustained spontaneous motor unit discharges in spastic–paretic biceps brachii muscles in chronic stroke. Methods: Ten chronic stroke subjects produced submaximal isometric elbow flexion force on impaired and non‐impaired sides. Intramuscular EMG (iEMG) was recorded from biceps and triceps brachii muscles. Results: We observed sustained spontaneous motor unit discharges in resting biceps on iEMG. Spontaneous discharges increased after voluntary activation only on the impaired side. The impaired side had greater matching errors and greater fluctuations in isometric force. Spontaneous discharges were not related functionally to spasticity, force variability, or weakness. However, greater strength on the impaired side correlated with less force variability. Conclusion: Weakness rather than spasticity is a main factor interfering with voluntary force control in paretic–spastic biceps brachii muscles in chronic stroke. Muscle Nerve, 2013     

Superiority of sonographic evaluation of contracted versus relaxed muscle thickness in motor neuron diseases

ObjectiveTo compare the correlations of relaxed and contracted limb muscle thickness with clinical scales in patients with amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA).MethodsPatients with ALS and SMA were prospectively recruited from December 2018 to November 2019. All patients underwent clinical assessment and sonographic muscle thickness measurement of eight relaxed muscles (biceps brachii, abductor pollicis brevis (APB), first dorsal interosseous, abductor digiti minimi, quadriceps, tibialis anterior, extensor digitorum brevis, and abductor hallucis brevis), and four contracted muscles (biceps brachii, APB, quadriceps, and tibialis anterior).Results91 patients with ALS and 31 patients with SMA were recruited. Contracted muscle thickness compared to relaxed muscle showed higher reliability and similar or better correlations with muscle strength and clinical scales, especially in ALS patients with hyperreflexia. Strong to very strong correlations with clinical scales were observed with multivariate analysis of relaxed and contracted muscle thickness (0.64–0.87).ConclusionsSonographic evaluation of contracted muscle thickness is an objective measure that correlates with disease burden. It is feasible, quick, valid and reliable, and may be superior to evaluation of relaxed muscles.SignificanceSonographic evaluation of contracted muscle thickness is superior to evaluation of relaxed muscles.