Name: cmap scan mune (mscan) - a novel motor unit number estimation (mune) method
Uploaded: 2018-06-07T12:30:00
Description: Watch this Scientific Journal Video about CMAP Scan MUNE MScan - A Novel Motor Unit Number Estimation MUNE Method at JoVE.com

This study was financially supported mainly by the Lundbeck Foundation.
Additionally, Knud og Edith Eriksens Mindefond, S&#248;ster og Verner Lipperts Fond, Fonden til L&#230;gevidenskabens Fremme, and Aage og Johanne Louis Hansens Fond supported this study.

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 &#8220;TRONDNF&#8221; recording protocol, which is a part of the software (see the Table of Materials). Other equipment used is a bipolar s...

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E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Electrophysiological+estimation+of+the+number+of+motor+units+within+a+human+muscle.">Electrophysiological estimation of the number of motor units within a human muscle.</a> J Neurol Neurosur Ps. 34, 121-131 (1971).</li><li>Oge, A. E., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Motor+unit+number+estimation+in+transected+peripheral+nerves.">Motor unit number estimation in transected peripheral nerves.</a> Neurol Res. 32, 1072-1076 (2010).</li><li>Doherty, T. J., Brown, W. 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P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Statistical+motor+unit+number+estimation:+from+theory+to+practice.">Statistical motor unit number estimation: from theory to practice.</a> Muscle Nerve. 28, 263-272 (2003).</li><li>Unlusoy Acar, Z., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Decline+of+compound+muscle+action+potentials+and+statistical+MUNEs+during+Wallerian+degeneration.">Decline of compound muscle action potentials and statistical MUNEs during Wallerian degeneration.</a> Neurophysiol. Clin. 44, 257-265 (2014).</li><li>Henderson, R. D., Ridall, P. G., Hutchinson, N. M., Pettitt, A. N., McCombe, P. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Bayesian+statistical+MUNE+method.">Bayesian statistical MUNE method.</a> Muscle Nerve. 36, 206-213 (2007).</li><li>Ridall, P. G., Pettitt, A. N., Henderson, R. D., McCombe, P. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Motor+unit+number+estimation--a+Bayesian+approach.">Motor unit number estimation--a Bayesian approach.</a> Biometrics. 62, 1235-1250 (2006).</li><li>Nandedkar, S. D., Nandedkar, D. S., Barkhaus, P. E., Stalberg, E. V. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Motor+unit+number+index+(MUNIX).">Motor unit number index (MUNIX).</a> IEEE Trans. Biomed. Eng. 51, 2209-2211 (2004).</li><li>Neuwirth, C., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Motor+Unit+Number+Index+(MUNIX):+a+novel+neurophysiological+marker+for+neuromuscular+disorders;+test-retest+reliability+in+healthy+volunteers.">Motor Unit Number Index (MUNIX): a novel neurophysiological marker for neuromuscular disorders; test-retest reliability in healthy volunteers.</a> Clin. Neurophysiol. 122, 1867-1872 (2011).</li><li>Jacobsen, A. B., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Reproducibility,+and+sensitivity+to+motor+unit+loss+in+amyotrophic+lateral+sclerosis,+of+a+novel+MUNE+method:+MScanFit+MUNE.">Reproducibility, and sensitivity to motor unit loss in amyotrophic lateral sclerosis, of a novel MUNE method: MScanFit MUNE.</a> Clin neurophysiol. 128, 1380-1388 (2017).</li><li>Maathuis, E. M., Drenthen, J., Visser, G. H., Blok, J. H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Reproducibility+of+the+CMAP+scan.">Reproducibility of the CMAP scan.</a> J. Electromyogr. Kinesiol. 21, 433-437 (2011).</li><li>Sleutjes, B. T. H. M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=CMAP+scan+discontinuities:+automated+detection+and+relation+to+motor+unit+loss.">CMAP scan discontinuities: automated detection and relation to motor unit loss.</a> Clin Neurophysiol. 125, 388-395 (2014).</li><li>Bostock, H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Estimating+motor+unit+numbers+from+a+CMAP+scan.">Estimating motor unit numbers from a CMAP scan.</a> Muscle Nerve. 53, 889-896 (2016).</li><li>DeLong, E. R., DeLong, D. M., Clarke-Pearson, D. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Comparing+the+areas+under+two+or+more+correlated+receiver+operating+characteristic+curves:+a+nonparametric+approach.">Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach.</a> Biometrics. 44, 837-845 (1988).</li><li>Hanley, J. A., McNeil, B. 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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 ...

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 activity or motor unit potential (MUP) changes does not correlate with the degree of denervation.
Overall, there is no electrophysiological technique that allows for simple, direct measurements of motor unit number. Instead, an estimate of motor unit number (MUNE) is used to assess lower motor neuron loss2. Several MUNE methods have been developed since the implementation of the first method, incremental stimulation MUNE, which was introduced in 1971 by McComas3. Most methods have been based on measuring several surface-recorded motor unit potentials (sMUP) and dividing the maximal CMAP by the average sMUP amplitude. Such methods include incremental stimulation4, multiple point stimulation (MPS)5, and spike-triggered averaging6. Other MUNE methods have used statistical techniques based on the probabilistic nature of the firing of a motor unit in response to a stimulus7,8,9,10. This variability means that firing different combinations of motor units leads to variability in the size of the CMAP responses. Motor unit number index (Munix) is a more recently introduced method, which uses the surface interference patterns recorded during voluntary contractions to estimate the average size of sMUP11,12.
These MUNE methods all suffer from one or more limitations, such as the presence of subjectivity, dependence on the absolute CMAP amplitude, bias in the selection of units, the long time needed to sample enough units, or the long time required to analyze the results. A new MUNE method has recently been developed, &#39;CMAP scan MUNE` (MScan), to overcome these limitations13. This method avoids the problems inherent in unit selection by taking account of the contribution of all units to the CMAP, as measured in a detailed stimulus-response curve, or CMAP scan14,15. It also avoids the extended analysis time of a similar, model-fitting method9,10, by using new algorithms16. In a recent study, the reproducibility of MScan in estimating the number of motor units was better than two more traditional methods, MPS MUNE and Munix13. Additionally, MScan could show motor unit loss in earlier stages of Amyotrophic Lateral Sclerosis (ALS) than MPS MUNE and Munix. MScan was faster than MPS MUNE and as fast as Munix13.
This paper describes the methodology of MScan in detail. It also summarizes the previously reported intra- and inter-rater reproducibility of MScan in patients with ALS and healthy control subjects13, which may enable the reader to judge whether the method would be appropriate for a planned study.

<table>
	<tbody>
		<tr>
			<td>QtracW software</td>
			<td>Digitimer Ltd (copyright Institute of Neurology, University College, London)&#160;&#160;</td>
			<td>QtracW</td>
			<td></td>
		</tr>
		<tr>
			<td>MScanFit</td>
			<td>Digitimer Ltd (copyright Institute of Neurology, University College, London)&#160;&#160;</td>
			<td>QtracW</td>
			<td></td>
		</tr>
		<tr>
			<td>DS5 bipolar stimulator</td>
			<td>Digitimer Ltd&#160;</td>
			<td>DS5</td>
			<td></td>
		</tr>
		<tr>
			<td>D440 amplifier&#160;</td>
			<td>Digitimer Ltd&#160;</td>
			<td>D440-2 (2 channel) or D440-4 (4 channel)</td>
			<td></td>
		</tr>
		<tr>
			<td>HumBug Noise Eliminator</td>
			<td>Digitimer Ltd&#160;</td>
			<td>Humbug</td>
			<td></td>
		</tr>
		<tr>
			<td>Analogue-to-digital (A/D) board&#160;&#160;</td>
			<td>National Instruments</td>
			<td>NI-6221&#160;</td>
			<td></td>
		</tr>
	</tbody>
</table>

cmap scan mune (mscan) - a novel motor unit number estimation (mune) method

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 &#39;Bayesian MUNE,&#39;&#160;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 &#62;0.98 and a coefficient of variation averaging 12.3 &#177; 1.6%. There was no difference in the intra-rater reproducibility between the two observers. Average recording time was 6.27 &#177; 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.

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 ...

Watch this Scientific Journal Video about CMAP Scan MUNE MScan - A Novel Motor Unit Number Estimation MUNE Method at JoVE.com

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

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.

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

Like other methods for motor unit number estimation (MUNE), compound muscle action potential (CMAP) scan MUNE (MScan) is a non-invasive electrophysiologic ...

The overall goal of this procedure is to describe MScan, a new method used to estimate the number of functioning motor units in a muscle. MScan is a non-invasive method used to estimate the number of functioning motor units in a muscle. MScan works by fitting a model to a detailed stimulus-response curve, or CMAP scan.This method has several advantages. It can be completed quickly, it's easy to perform and analyze, and it has excellent reproducibility. To begin, request written consent from the subject.All subjects must give their written consent prior to the examination. Then, explain that the subject will experience a tickling sensation in their hand and wrist and that the examination can be halted at any time should they experience too much discomfort. First, use skin prep gel and alcohol to clean the subject's hand and forearm.Position the active recording electrode over the abductor pollicis brevis muscle, and then place the reference electrode on the metacarpophalangeal joint of the thumb. Place a ground electrode on the dorsum of the subject's hand, and connect the electrodes to the pre-amplifier. After positioning and connecting the electrodes to the pre-amplifier, tape the subject's fingers together to reduce noise and artifacts caused by voluntary movement.To start the semi-automated computerized system, use the standard protocol for motor nerve excitability tests. From the main menu, select MSCAN-R recording protocol and accept default settings for the pre-amplifier and the stimulator. In the Select recording parameters form, enter a two-to three-letter operator prefix in the Output file box.Then, click OK to continue. When the screen displays the raw EMG input, accept the default parameters and click OK.To find the site of lowest threshold at the median nerve of the wrist, position a repositionable stimulating electrode. Continue to adjust the position of the electrode until the largest EMG response has been achieved.Once the site of lowest threshold has been located, click OK to continue. Next, the modified response will be displayed with the window where the response is measured. The magenta line indicates the response measured in the window, while the short green line immediately before the window indicates the baseline.Replace the repositionable electrode with a non-polarizable adhesive stimulating cathode electrode, and place an anode two centimeters proximally along the median nerve. Encourage the subject to find the most relaxed position for their hand to minimize spontaneous activity. Click the OK button to continue.Manually increase stimulus intensity by steps of 3%by pressing the Insert key. Click the OK button to continue. Make fine 1%stimulus adjustments until the stimulus current is above the level for the maximal amplitude of the CMAP.After the responses to 20 supramaximal pre-scans are recorded, the stimulus intensity will automatically decrease with the frequency and percent steps selected previously. Once there is no longer a response from the subject, click the OK button to finish the recording with the series of 20 CMAP post-scans. Finally, click the OK button in the lower right corner to finish the recording and save the data.To do analyses offline, start the analysis program and select the MScan recording to be analyzed. Select Fit MScan on a QZD file from the menu. Then, the program will automatically generate a preliminary model and optimize the fit.The program will continue to run without user intervention until the multicolored progress bar in the Optimization box is complete and the Stop button is gray. The original scan, in black, can be plotted next to the scan generated by the model, in magenta. Make serial adjustments to minimize the difference between the recorded and simulated scans and optimize the model.In the Plot type box, different plotting options may be used to track the optimization process. A multicolored progress bar will also be displayed in the Optimization panel. Use a contour plot to assess the accuracy of the model by selecting the Diff and Contour map displays.These displays show the differences between the recorded and modeled CMAP scans as a contour plot. As the optimization process runs, these differences will be minimized. When the optimization process is complete, view the analysis results in the MScanFit text display.Finally, click on the OK button to save the model in a MEM file. In this study, MScan MUNE is used to derive an estimation of the number and sizes of functional motor units by fitting a model to CMAP scan. This technique is tested for sensitivity and specificity in both healthy controls and ALS patients.As expected, the median number of motor units in patients with ALS is significantly lower than in healthy controls. As shown by the ROC curve, the ability of MScan MUNE to distinguish the healthy controls from ALS patients is compared to that of CMAP. Area under the curve, or AUC, is used to measure the ability of both techniques to distinguish between ALS patients and healthy controls.The AUC of MScan MUNE is significantly higher than that of CMAP. Once mastered, this technique can be completed in six minutes if it's performed properly. The analysis process is also fast and should take less than five minutes.When attempting this procedure, it's important to remember to achieve adequate relaxation of the subject. MScan is a method that may have the potential to be implemented in a clinical setting for diagnosis and monitoring of neuromuscular disorders such as ALS. Further studies with other neuromuscular disorders and larger study groups are warranted.Studies on the application of MScan in different muscle groups should also be conducted. After watching this video, you should have a good understanding of how to perform and analyze MScan examinations.

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