Far-field potential of the compound muscle action potential as a reliable marker in amyotrophic lateral sclerosis.

INTRODUCTION/AIMS: Reliable neurophysiological markers in amyotrophic lateral sclerosis (ALS) are of great interest. The compound muscle action potential (CMAP) amplitude has been a conventional marker, although it is greatly influenced by the electrode position. We propose the far-field potential of the CMAP (FFP-CMAP) as a new neurophysiological marker in ALS. METHODS: Patients with ALS and age-matched healthy controls were enrolled. We used a proximal reference (pref) in addition to the conventional distal reference (dref). Routine CMAP was recorded from the belly-dref lead and FFP-CMAP from the dref-pref lead for the ulnar and tibial nerves. Multiple point stimulation motor unit number estimation (MUNE) was also examined in the ulnar nerve. Inter-rater reproducibility was evaluated by two examiners, and some patients were followed up every 3 mo for 1 y. RESULTS: We tested 17 patients with ALS and 10 controls. The amplitudes of routine CMAP and FFP-CMAP in the ulnar and tibial nerves, and hypothenar MUNE value in the ulnar nerve were significantly decreased in ALS compared to controls. Ulnar FFP-CMAP achieved the highest inter-rater intraclass correlation coefficient (ICC) value (0.942) when compared with routine CMAP (0.880) and MUNE (0.839). The tibial FFP-CMAP had a higher ICC value (0.986) than the routine CMAP (0.697). In this way, the FFP-CMAP showed high inter-rater reproducibility because its shape was not much influenced by the electrode position. During 1-y follow-up, decline of CMAP, FFP, and MUNE showed significant correlations with the Amyotrophic Lateral Sclerosis Functional Rating Scale - Revised (ALSFRS-R). DISCUSSION: The FFP-CMAP shows promise as a reliable marker for ALS.

Feasibility and reliability of MScanFit motor unit number estimation in peroneus longus muscle.

INTRODUCTION/AIMS: Motor unit number estimation (MUNE) methods may be valuable to detect motor involvement earlier than compound muscle action potential (CMAP) amplitude. The most recent MUNE method, MScanFit, has been shown to have advantages compared with previously described methods. However, MScanFit has only been applied in a few lower extremity muscles. In this study we examined the feasibility and reliability of MScanFit in peroneus longus muscle. METHODS: Twenty healthy controls (16 males and 4 females; mean age, 36.05 ± 2.58 years) were examined twice within a 1- to 2-week interval. Fibular nerve was stimulated at the knee and CMAP scans were recorded from peroneus longus muscle. From this, MScanFit MUNE and size parameters were calculated, as was the CMAP amplitude. The reliability was examined using coefficient of variation (CV) and intraclass correlation coefficient (ICC). MUNE was correlated with CMAP amplitude using linear regression analysis. RESULTS: The CV between sessions was higher for CMAP amplitude (11.63 ± 1.88%) than MScanFit MUNE (3.13 ± 0.78%). Among the size parameters, mean unit amplitude (µV) showed the lowest CV (11.46 ± 1.77%). Using ICC, CMAP amplitude exhibited good reliability (0.787), whereas that of MScanFit MUNE was excellent (0.902). Reliability was good for all size parameters. There was no significant correlation between MScanFit MUNE and CMAP amplitude (R = 0.25, P > .05). DISCUSSION: MScanFit MUNE is feasible in the peroneus longus muscle, with high test-retest reliability in healthy subjects. Studies in patients are needed to examine the sensitivity of this muscle in disease.

Estimating the motor unit number of the flexor carpi ulnaris muscle with MScanFit MUNE.

INTRODUCTION/AIMS: MScanFit motor unit number estimation (MUNE) is a promising method for motor unit estimation and is reported to have good reliability in distal and small muscles. In this study, we investigated the reliability of MScanFit MUNE in a proximal forearm muscle, the flexor carpi ulnaris. METHODS: Twenty healthy volunteers were included in this study, and 15 participants were re-evaluated in a second session. The ulnar nerve was stimulated at the elbow and a compound muscle action potential (CMAP) scan from the flexor carpi ulnaris (FCU) muscle was recorded from each arm. CMAP, MUNE, and other motor unit parameters were obtained. Reproducibility was evaluated using intraclass correlation coefficients (ICCs). RESULTS: The average MUNE from 40 FCU muscles was 90.9 (standard deviation: 16.4). MScanFit MUNE and CMAP were not significantly different between the dominant and non-dominant sides. The ICC indicated good reliability between sessions for each side (0.81 and 0.8, respectively). DISCUSSION: Our results indicate that MScanFit MUNE is a feasible method with good reproducibility for MUNE of the FCU muscle.

Relation between the severity of liver cirrhosis and neurological symptoms, nerve conduction study results, and motor unit number estimation.

Liver cirrhosis is a global health problem that can be associated with several neurological manifestations. We aimed to assessment of the relation between the severity of the liver cirrhosis and the neurological symptoms, nerve conduction studies (NCS), as well as detecting subclinical neuropathic affection using motor unit number estimation (MUNE) technique. This cross-sectional study was conducted on 56 cirrhotic patients and 61 age- and sex-matched healthy controls. Neurological manifestations, Child-Pugh classification, Model for End-Stage Liver Disease score, NCS and MUNE using a modified spike-triggered averaging technique were studied. Forty-five (80.3%) of the cirrhotic patients had neurological manifestations. Muscle cramps were the most frequently reported manifestation, followed by fatigue and then numbness. NCS abnormality was significantly related to the presence of neurological symptoms (p < 0.001) and not only to peripheral numbness. Only fatigue was significantly related to the lower MUNE values (p < 0.017). Child-Pugh classification progression was significantly related to the presence of fatigue and abnormal NCS results (p < 0.001); no similar relation was detected between the Child-Pugh classification and the MUNE value (p = 0.103). Higher MELD scores were significantly related to NCS abnormalities (p = 0.014) and negatively correlated, although not significantly, with the MUNE values (r = -0.246 and p = 0.067). The progression of liver cirrhosis was related to the presence of neurological manifestations and nerve conduction abnormalities. Nerve conduction abnormalities may be present even in the absence of clinical numbness. A decline in motor unit number could explain the pathophysiology of fatigue in cirrhotic patients.

Compound muscle action potential scan and MScanFit motor unit number estimation during Wallerian degeneration after nerve transections.

BACKGROUND: Compound muscle action potential (CMAP) scan and MScanFit have been used to understand the consequences of denervation and reinnervation. This study aimed to monitor these parameters during Wallerian degeneration (WD) after acute nerve transections (ANT). METHODS: Beginning after urgent surgery, CMAP scans were recorded at 1-2 day intervals in 12 patients with ANT of the ulnar or median nerves, by stimulating the distal stump (DS). Stimulus intensities (SI), steps, returners, and MScanFit were calculated. Studies were grouped according to the examination time after ANT. Results were compared with those of 27 controls. RESULTS: CMAP amplitudes and MScanFit progressively declined, revealing a positive correlation with one another. SIs were higher in WD groups than controls. Steps appeared or disappeared in follow-up scans. The late WD group had higher returner% than the early WD and control groups. CONCLUSIONS: MScanFit can monitor neuromuscular dysfunction during WD. SIs revealed excitability changes in DS.

Motor unit number estimation of facial muscles using the M Scan-Fit method.

INTRODUCTION: M Scan-Fit, an automated method for motor unit number estimation (MUNE), was assessed in muscles innervated by the facial nerve. METHODS: Healthy volunteers were recruited. M Scans were recorded twice from nasalis and depressor anguli oris (DAO) muscles, and then fitted to a probabilistic model. RESULTS: Twenty-one subjects were evaluated; 38% were females and 62% were males, with a mean age of 34.71 years. The average number of MUs was 38.57 on both testing occasions (t ≤ 0.0001; P = 1.0) for the nasalis. For the DAO, results were 20.62 MUs for the first and 23.48 for the second (t = -2.12; P = .04). Pearson's interrater correlation coefficients were 0.96 (P < .0001) for nasalis and 0.87 (P ≤ .01) for DAO. Intraclass correlation coefficients were 0.88 (P ≤ .01) for nasalis and 0.39 (P = .37) for DAO. DISCUSSION: M Scan-Fit MUNE is an automated, accurate, reliable method of estimating MU number and size from facial muscles.

Parameters derived from compound muscle action potential scan for discriminating amyotrophic lateral sclerosis-related denervation.

INTRODUCTION: The objective of this study was to determine compound muscle action potential (CMAP) scan parameters and MScanFit motor unit number estimation (MUNE) in patients with amyotrophic lateral sclerosis (ALS) and to compare the results in the abductor pollicis brevis (APB) to those in the abductor digiti minimi (ADM). METHODS: CMAP scans were recorded from the APB and ADM in 35 patients with ALS and 21 controls. MScanFit MUNE, neurophysiological index (NI), step%, returner%, and D50 were calculated. RESULTS: CMAP scan parameters including the returner%, MScanFit MUNE, and NI can distinguish ALS with high sensitivity and specificity. The electrophysiological parameters, with the exception of D50 (the number of largest consecutive differences of recorded responses generating 50% of maximum CMAP), showed more pronounced changes in the APB than in the ADM, even though most of the patients had normal APB/ADM amplitude ratios. DISCUSSION: CMAP scan parameters and MScanFit MUNE can be used in the evaluation of denervation and reinnervation and may herald the "split hand" in ALS.

Following disease progression in motor neuron disorders with 3 motor unit number estimation methods.

INTRODUCTION: The objective of this study was to evaluate a recently developed motor unit number estimation (MUNE) method, MScanFit MUNE (MScan), as a measure of disease progression in amyotrophic lateral sclerosis (ALS) compared with compound muscle action potential (CMAP) amplitude and 2 traditional MUNE methods. METHODS: ALS patients were evaluated clinically using the ALS Functional Rating Scale-Revised (ALSFRS-R). MScan, multiple-point stimulation MUNE (MPS), and motor unit number index (MUNIX) were performed in the abductor pollicis brevis (APB) muscle at baseline (27 patients), 4 months (23 patients), and 8 months (16 patients). RESULTS: Of the 5 measures, MScan registered the largest decline (8.7% per month), compared with MPS (3.4%), MUNIX (4.8%), CMAP amplitude (2.0%), and ALSFRS-R (1.9%). Only MScan and ALSFRS-R registered significant decrements over 4 and 8 months. DISCUSSION: MScan may be useful as a sensitive, objective tool for quantifying motor unit loss in ALS. Muscle Nerve 59:82-87, 2019.

Electrodiagnostics: MUNE and MUNIX as methods of estimating the number of motor units - biomarkers in lower motor neurone disease.

Routine quantitative electromyography is used for the assessment of the presence of lower motor neurone involvement and its consequences, including primary denervation and compensatory reinnervation of muscle fibres. However, it is not useful for the assessment of the motor unit number reserve. The need for a valid biomarker to evaluate lower motor neurone disease progression in such diseases as amyotrophic lateral sclerosis, and for use in clinical trials, has led to a number of studies of the methods that allow assessment of the number of motor units. In this review, motor unit number estimation (MUNE) methods with incremental stimulation and the recently developed motor unit number index (MUNIX) method, along with their technical and clinical aspects, are presented as methods which reflect motor unit loss in neurogenic processes. These electrodiagnostic tests may allow a valuable assessment of disease progression and the efficacy of new therapeutic methods in clinical trials in diseases with lower motor neurone degeneration.

Crush injury to motor nerves in the G93A transgenic mouse model of amyotrophic lateral sclerosis promotes muscle reinnervation and survival of functionally intact nerve-muscle contacts.

Selective survival of small motor nerve fibers and their neuromuscular contacts in the SOD1G93A transgenic mouse model of amyotrophic lateral sclerosis (ALS) suggests that smaller regenerated nerve fibers are more able to sustain reformed nerve-muscle connections as functionally intact motor units (MUs). The sciatic nerve was crushed unilaterally in SOD1G93A transgenic mice at 40 days of age and contractile forces of reinnervated muscles and their MUs were recorded at 90 days in order to determine the capacities of the nerves to regenerate and to form and retain functional neuromuscular connections. Reduced MU numbers in fast-twitch tibialis anterior, extensor digitorum longus and medial gastrocnemius muscles and the lesser reductions in slow-twitch soleus muscle of SOD1G93A transgenic mice were reversed in reinnervated muscles: there were more reinnervated MUs and their contractile forces and the muscle forces and weights increased. In line with the contrasting ability of only small not large nerve fibers to sprout to form enlarged MUs in the SOD1G93A transgenic mouse, the smaller regenerating nerve fibers formed enlarged MUs that were better able to survive. Because nerve fibers with and without muscle contacts were severed by the sciatic nerve crush injury, the conditioning lesion is untenable as the explanation for improved maintenance of reinnervated neuromuscular junctions. Elevated neurotrophic factor expression in axotomized motoneurons and/or denervated Schwann cells and the synapse withdrawal from axotomized motoneurons are other factors that, in addition to reduced size of nerve fibers reinnervating muscles, may account for increased survival and size of reinnervated MUs in ALS.

Effect of very old age on anconeus motor unit loss and compensatory remodelling.

INTRODUCTION: It is not known how the process of compensatory remodeling through collateral reinnervation continues into very old age (>80 years) or whether there is a limit to effective motor unit (MU) reinnervation. Therefore, we explore electrophysiological properties related to motor unit number estimates (MUNEs) in very old participants (79-90 years of age) compared with young controls (25-29 years of age). METHODS: Decomposition-enhanced spike-triggered averaging was used to collect surface and intramuscular electromyography information from the anconeus to derive a MUNE. RESULTS: Young participants had a MUNE of ∼38 and ∼25 at 30% and 50% root mean squared maximum voluntary contraction (RMSMVC ) with surface motor unit potentials (S-MUPs) of ∼145 µV and 236 µV, respectively. Older participants had a MUNE of ∼23 and ∼16 at 30% and 50% RMSMVC with S-MUPs of 168 µV and 232 µV, respectively. DISCUSSION: In this muscle, an age limit to successful remodeling through collateral reinnervation, to compensate for the presumed ongoing losses of MUs, may have been surpassed. Muscle Nerve 57: 659-663, 2018.

Motor unit number estimation of human abductor hallucis from a compound muscle action potential scan.

INTRODUCTION: This study performed motor unit number estimation (MUNE) of the abductor hallucis (AH) muscle from 16 healthy control participants on the basis of the compound muscle action potential (CMAP) scan. METHODS: Muscle responses to electrical stimuli ranging from subthreshold to supramaximal intensity were recorded, and MUNE was determined from a model of the responses (MScanFit program). RESULTS: The average CMAP amplitude and MUNE of the AH for the right and left sides combined were 19.6 ± 0.75 mV and 127 ± 5 (mean ± SE), respectively. DISCUSSION: Findings of the study provide useful information about the motor unit number of the AH. Muscle Nerve 58: 735-737, 2018.

Muscle action potential scans and ultrasound imaging in neurofibromatosis type 2.

INTRODUCTION: The neuropathy in patients with neurofibromatosis type 2 (NF2) is difficult to quantify and follow up. In this study we compared 3 methods that may help assess motor axon pathology in NF2 patients. METHODS: Nerve conduction studies in median nerves were supplemented by deriving motor unit number estimates (MUNEs) from compound muscle action potential (CMAP) scans and by high-resolution ultrasound (US) peripheral nerve imaging. RESULTS: CMAP amplitudes and nerve conduction velocity were normal in the vast majority of affected individuals, but CMAP scan MUNE revealed denervation and reinnervation in many peripheral nerves. In addition, nerve US imaging enabled monitoring of the size and number of schwannoma-like fascicular enlargements in median nerve trunks. CONCLUSION: In contrast to conventional nerve conduction studies, CMAP scan MUNE in combination with US nerve imaging can quantify the NF2-associated neuropathy and may help to monitor disease progression and drug treatments. Muscle Nerve 55: 350-358, 2017.

A neurophysiological approach to nerve transfer to restore upper limb function in cervical spinal cord injury.

A successful nerve transfer surgery can provide a wealth of benefits to a patient with cervical spinal cord injury. The process of surgical decision making ideally uses all pertinent information to produce the best functional outcome. Reliance on clinical examination and imaging studies alone can miss valuable information on the state of spinal cord health. In this regard, neurophysiological evaluation has the potential to effectively gauge the neurological status of even select pools of anterior horn cells and their axons to small nerve branches in question to determine the potential efficacy of their use in a transfer. If available preoperatively, knowledge gained from such an evaluation could significantly alter the reconstructive surgical plan and avoid poor results. The authors describe their institution's approach to the assessment of patients with cervical spinal cord injury who are being considered for nerve transfer surgery in both the acute and chronic setting and broadly review the neurophysiological techniques used.

Estimating motor unit numbers from a CMAP scan.

INTRODUCTION: Compound muscle action potential (CMAP) scans are detailed stimulus-response curves which provide information about motor unit properties in neuromuscular disorders. This study assessed a method of automatic motor unit number estimation (MUNE) from 5-min CMAP scans. METHODS: A preliminary model, derived from the variance and slope of the scan, is refined to fit the CMAP scan more closely. The method was tested by application to 60 simulated scans, generated from between 5 and 160 motor unit potentials. RESULTS: The fitting procedure took an average of 1.5 min on a standard personal computer. Small unit numbers (5-20) were on average correctly estimated, but large unit numbers (>40) were slightly underestimated. Overall, the absolute MUNE error averaged 6.9%. CONCLUSIONS: This new MUNE method takes all excitable motor units into account and provides realistic estimates of unit numbers over the range 5 to 160. Validation as a clinical tool awaits further study. Muscle Nerve 53: 889-896, 2016.

Repeater F-waves are signs of motor unit pathology in polio survivors.

INTRODUCTION: The purpose of this study was to determine whether F-waves reveal electrophysiological features of anterior horn cells in polio survivors. METHODS: Forty-three polio survivors and 20 healthy controls underwent motor nerve conduction studies of the median and tibial nerves bilaterally, including sampling of F-waves elicited by 100 stimuli and the determination of motor unit number estimation (MUNE). RESULTS: A significant increase in abnormally stereotyped ("repeater") F-waves and a reduction of F-wave persistence were observed in both nerves in the polio group as compared with the control group. Repeater F-waves had a negative correlation with MUNE. CONCLUSIONS: These trends in F-wave persistence and repeater F-waves after motor unit loss are characteristic findings in polio survivors. Repeater F-waves are a sign of motor unit pathology.

Motor unit number in a small facial muscle, dilator naris.

A loss of functioning motor units underlies many neuromuscular disorders. The facial nerve innervates the muscles of facial expression, including nasal muscles, which also play an important role in the regulation of airflow resistance. It is difficult to accurately assess motor unit number in the facial muscles, because the muscles are difficult to activate in isolation. Here, we apply the manual McComas method to estimate the number of motor units in a nasal dilator muscle. EMG of the dilator naris was recorded during graded stimulation of the zygomatic branch of the facial nerve in 26 subjects (12 males and 14 females), aged 20-41 years. Each subject was studied twice, on separate days, to estimate method reproducibility. As a check on our use of the McComas method, we also estimated motor unit number in the first dorsal interosseus muscle (FDI) of six subjects, as the muscle is also small and has been studied with the McComas method. Reproducibility was evaluated with a rigorous statistical approach, the Bland-Altman procedure. We estimate that dilator naris is composed of 75 ± 15.6 (SD) motor units, compared to 144 ± 35.5 in FDI. The coefficient of variation for test-retest reproducibility of dilator naris motor unit estimates was 29.6 %, similar to separate-day reproducibility reported for other muscles. Recording and stimulation were done with surface electrodes, and the recordings were of high quality and reproducible. This simple technique could be applied clinically to track motor neuron loss and to monitor facial nerve integrity.

Anconeus motor unit number estimates using decomposition-based quantitative electromyography.

INTRODUCTION: Motor unit number estimates (MUNEs) provide important information in health, aging, and disease, and can be determined using decomposition-enhanced spike-triggered averaging (DE-STA). Discrimination of surface-detected motor unit potentials (S-MUPs) has been limited to contractile forces of ∽30% maximum voluntary contraction (MVC), which is insufficient to recruit a representative sample of the entire MU pool in most muscles. Unique features of the anconeus may permit MUNEs at high muscle activation levels. METHODS: In 10 men (25 ± 3 years), anconeus MUNEs were performed using DE-STA at 10%, 30%, and 50% root-mean-square of MVC (RMS(MVC)). RESULTS: The mean compound muscle action potential of the anconeus was ∽6 mV, and average S-MUP amplitudes were ∽100 µV, 145 µV, and 235 µV at 10%, 30%, and 50% RMS(MVC), resulting in low average MUNEs of 58, 38, and 25, respectively. CONCLUSIONS: Elbow extensor force-EMG relationships suggest full recruitment of the anconeus MU pool at 50% RMS(MVC), thus providing a representative sample for MUNE.

Influence of needle electrode depth on DE-STA motor unit number estimation.

INTRODUCTION: To assess a potential source of technique-associated error, we evaluated the influence of needle electrode depth on decomposition-enhanced spike-triggered averaging (DE-STA) motor unit number estimation (MUNE) and quantitative motor unit analysis in the upper trapezius (UT). METHODS: The DE-STA MUNE protocol was performed at superficial, intermediate, and deep needle electrode depths in 18 control subjects. RESULTS: Mean surface-detected motor unit potential amplitudes were significantly smaller for intermediate versus superficial (P<0.05), deep versus superficial (P<0.001), and deep versus intermediate (P<0.05). MUNE was significantly larger for deep versus superficial (P<0.001), with statistical trends toward larger MUNE values at greater depths for the remaining comparisons. No significant differences were found among needle electrode depths for quantitative motor unit potential parameters. CONCLUSIONS: These results demonstrate the important influence of needle electrode depth on DE-STA MUNE in the UT. Suggestions are made for improved standardization of the protocol.

Revisiting the compound muscle action potential (CMAP).

The compound muscle action potential (CMAP) is among the first recorded waveforms in clinical neurography and one of the most common in clinical use. It is derived from the summated muscle fiber action potentials recorded from a surface electrode overlying the studied muscle following stimulation of the relevant motor nerve fibres innervating the muscle. Surface recorded motor unit potentials (SMUPs) are the fundamental units comprising the CMAP. Because it is considered a basic, if not banal signal, what it represents is often underappreciated. In this review we discuss current concepts in the anatomy and physiology of the CMAP. These have evolved with advances in instrumentation and digitization of signals, affecting its quantitation and measurement. It is important to understand the basic technical and biological factors influencing the CMAP. If these influences are not recognized, then a suboptimal recording may result. The object is to obtain a high quality CMAP recording that is reproducible, whether the study is done for clinical or research purposes. The initial sections cover the relevant CMAP anatomy and physiology, followed by how these principles are applied to CMAP changes in neuromuscular disorders. The concluding section is a brief overview of CMAP research where advances in recording systems and computer-based analysis programs have opened new research applications. One such example is motor unit number estimation (MUNE) that is now being used as a surrogate marker in monitoring chronic neurogenic processes such as motor neuron diseases.