CMAP Scan MUNE (MScan) - A Novel Motor Unit Number Estimation (MUNE) Method

Summary

This protocol describes a new method to estimate the number of functioning motor units in a muscle, by fitting a model to a detailed stimulus-response curve of the compound muscle action potential. It is quick and easy to perform and analyze and has excellent reproducibility.

Abstract

Like other methods for motor unit number estimation (MUNE), compound muscle action potential (CMAP) scan MUNE (MScan) is a non-invasive electrophysiologic method to estimate the number of functioning motor units in a muscle. MUNE is an important tool for the assessment of neuropathies and neuronopathies. Unlike most MUNE methods in use, MScan assesses all the motor units in a muscle, by fitting a model to a detailed stimulus-response curve, or CMAP scan. It thereby avoids the bias inherent in all MUNE methods based on extrapolating from a small sample of units. Like 'Bayesian MUNE,' MScan analysis works by fitting a model, made up of motor units with different amplitudes, thresholds, and threshold variabilities, but the fitting method is quite different, and completed within five minutes, rather than several hours. The MScan off-line analysis works in two stages: first, a preliminary model is generated based on the slope and variance of the points in the scan, and second, this model is then refined by adjusting all the parameters to improve the fit between the original scan and scans generated by the model.

This new method has been tested for reproducibility and recording time on 22 amyotrophic lateral sclerosis (ALS) patients and 20 healthy controls, with each test repeated twice by two blinded physicians. MScan showed excellent intra- and inter-rater reproducibility with ICC values of >0.98 and a coefficient of variation averaging 12.3 ± 1.6%. There was no difference in the intra-rater reproducibility between the two observers. Average recording time was 6.27 ± 0.27 min.

This protocol describes how to record a CMAP scan and how to use the MScan software to derive an estimate of the number and sizes of the functioning motor units. MScan is a fast, convenient, and reproducible method, which may be helpful in diagnoses and monitoring disease progression in neuromuscular disorders.

Introduction

Motor system movement is dependent on the motor unit, which refers to an individual motor nerve fiber together with the muscle fibers it activates, and motor unit number is the number of anterior horn cells or axons innervating a single muscle¹. During the denervation and reinnervation processes, healthy axons take over the role of axons that are lost by collateral sprouting. Therefore, compound muscle action potential (CMAP) amplitude does not give the necessary information about the degree of motor unit loss. CMAP amplitude may only start to fall when more than 50% of motor units are lost. Similarly, the magnitude of abnormal spontaneous acti....

Protocol

All subjects must give their written consent prior to examination, and the recording protocol must be approved by the appropriate local ethical review board(s). All methods described here were approved by the Regional Scientific Ethical Committee and the Danish Data Protection Agency.

Note: The recordings are made with the “TRONDNF” recording protocol, which is a part of the software (see the Table of Materials). Other equipment used is a bipolar stimulator, a 50 Hz noise eliminator, an amplifier, and an analogue-to-digital (A/D) board (also recommended is an audio amplifier for feedback of elec....

Results

The following results were obtained in a recent study, in which the MScan method was compared with two established techniques: multiple point stimulation MUNE (MPS) and motor unit number index (Munix)¹³. The results show that with the technique described in this protocol, consistent results with excellent reproducibility can be achieved. The method can differentiate ALS patients from healthy controls in an earlier stage of the disease than CMAP and it is quick and .......

Discussion

Critical steps within the protocol: MScan is a highly automated procedure, but as with all EMG methods, care should be taken to obtain consistent results. In the preparation stage, it is important to achieve relaxation, since spontaneous activity or movement artefacts during the CMAP scan introduce spurious variance in the CMAP and confound the generation of the preliminary model.

Modifications and troubleshooting: We found that taping of the fingers, and use .......

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
QtracW software	Digitimer Ltd (copyright Institute of Neurology, University College, London)	QtracW
MScanFit	Digitimer Ltd (copyright Institute of Neurology, University College, London)	QtracW
DS5 bipolar stimulator	Digitimer Ltd	DS5
D440 amplifier	Digitimer Ltd	D440-2 (2 channel) or D440-4 (4 channel)
HumBug Noise Eliminator	Digitimer Ltd	Humbug
Analogue-to-digital (A/D) board	National Instruments	NI-6221