Well, good morning everyone, the ones that are here and then also the other ones who are attending virtually or the other ones who will be watching the recorded video. My name is Dr. Sankar Bandyopadhyay. I'm a neuromuscular electrodiagnostic provider in Penn State. Basically, if you look at the curriculum for this whole meeting, this is probably the most difficult or controversial topic because every day there are like two or three presentations and it goes on and still people come in. So as the program director for neuromuscular medicine and neurophysiology, this is what I've been doing with my fellows for over nine years. Also working with the technicians very closely. Basically, people have trouble understanding the repetitive nerve stimulation studies. There are books and there are nice cartoons but still the things are not very clear. I'm also learning. So I wanted to do an interactive session in a small room with a blackboard and with my cartoons that I will be making on the spot with complete understanding of the attendees and then move on. But this was the case. Now I was told that there will be an extra microphone over there. That was a special thing on the back but I don't think it is turned on so speak out. And then feel free to stop me at any point because as I said, this is supposed to be what I've been doing for over a decade is a one-to-one discussion so that at the end they get it. So my purpose will be for all of you who are present here physically or beyond to get it and I will try for that. So let me ask a question. How many of you are technicians, EMG technicians? Okay. And then how many of you are residents, BMR or neurology and fellows? Oh, there are fellows. And how many of you are beyond that? Okay. So we have a diverse audience here as well as virtually. So before any further ado, let's begin over there. Now, of course, you are here because you still have the hunger. You still want to kind of go to the bottom, the absolute rock bottom of repetitive nerve stimulation and I'm sure you still have questions that have not been answered because even if you read all the books on EMG which I have in position, there are many phrases like the mechanism is still not totally understood. So let's see, there will be cartoons and I did not copy and pasted the ones because as I said, it's like pancake meds before your eyes as you want, like a blackboard teaching. So I have my cartoons and I will go over there. So I'm not an artist, but bear with me. So I have no financial disclosure. Also, there was no involvement of artificial intelligence. Also, although I'm very much involved with artificial intelligences use and research, but for not this one. But I wonder in future, there should be some kind of additional intelligence where I will be having a small digital blackboard or whiteboard or writing paper and whatever I write or draw will be shown in a nice professional way. But now it is my bad drawing. So the learning objectives will be to understand how to do repetitive nerve stimulation study in a nice way, period. Because my goal is basically for, I'm aiming towards the technicians, residents and fellows who still might have some deficiencies or lack of proper understanding. They know what to do, but they might have some deficiencies. Why this? Why that? So the purpose will be to analyze every step of it. And at the end, when we have gathered enough, I will go again back to the methodology and I will ask all of you whether you have understood completely. Now, not everything is completely understood. So as completely as possible. So we'll go over the neuromuscular junction anatomy and physiology with the thought in mind that this is not a lecture on anatomy and physiology. This is for you to understand the REPSTEMS. Of course, the basics of REPSTEMS. We'll go over terminology such as decrement, increment, facilitation. And of course, the methodologies will take place. And we'll discuss the common mistakes and pitfalls. And then if time permits, which I think there should be, if still we haven't covered, we'll ask what and why of this methodology? Why you are doing this? And I will try to cover those as we go because this is kind of a live discussion. And feel free to interrupt me and raise your hands. So this is my hand drawing. None of the cartoons in any of the books or published journals, articles will do this. This is a surreal presentation. This has a nerve ending, which expands into this. And then there is the muscle. So this is the muscle membrane. There are three conditions. One is myasthenia gravis. The other one is normal. The other one is pre-ganglioning, Lambert-Ethan myasthenic syndrome. And there is also time involved. This is not a snapshot. This is what keeps happening. So I will walk you through this. So let's take the example of, you are doing a repetitive stimulation from a doctor, ADM muscle here. And you are stimulating the ulnar nerve. Okay. There are other nerves and muscles that you can check. So what does it mean? What are you doing actually? So you are giving a supramaximal stimulus and all of you know the minimum. So you keep increasing the amplitude, the current size as well as until the amplitude doesn't increase. Then you give a one last, about 20% or 30% higher amplitude. Make sure that the amplitude doesn't rise. So that is your supramaximal stimulation. And with that, you stimulate all the motor actions. And with that, you stimulate all the type one and type two fibers. So that nothing is bigger than that. So there are about 25,000 motor actions in an average adult ulnar nerve. And so at the elbow, about 25,000 actions, but they're in one bundle. And then there is flexor digitorum profundus, third and fourth fingers and, or fourth and fifth fingers. And then the flexor carpi ulnaris. So these two are big muscles, give them half of the thing. So you're left with about 12,000, 13,000 like that. Ulnar nerve supplies at least 14 muscles in our hand. So about a thousand actions, terminal branches for each muscle. So ADM, I'm going to stimulate the ulnar nerve. I have about one bundle, but eventually it will divide into a thousand branches. And now each branch will supply how many muscles? That changes. For biceps, one terminal action divides into about 200 branches with 200 neuromuscular junctions and 200 muscle fibers. But because we do precise movements, precision movements with the hands, say about 10 to 20. So 1,000 times, say 10. So when you are stimulating the ulnar nerve, you are stimulating the nerve bundle, which eventually will divide into 10,000 approximately, terminal action branches with 10,000 neuromuscular junctions and 10,000 muscle fibers. This is one of the 10,000. So one of the 10,000 going to ADM is there. So the nerve expands and here is the muscle and the muscle folds itself into as many folds as necessary and possible to receive in as good as a way that is possible. The green ones are the acetylcholine vesicles. So why do you need a vesicle? There is an enzyme cholinesterase and acetylcholinesterase that will destroy the acetylcholine wherever they find it. So there is acetylcholinesterase here in the neuromuscular junction. They also have here in the nerve endings. They're everywhere. So how can you store and use acetylcholine? Once they're in a vesicle, they're protected from the enzyme. So you have about 1,000 vesicles that are ready to go. Just say go and if it is above a threshold, they will go. In about two seconds or so, there are secondary vesicles. Each one is called a quantum. Quantum is single, quanta are plural. So you have about 1,000 quanta ready to go, jump into action, and then you have about 10,000 as the secondary vesicles. They can be released if you give them approximately two seconds. Now these numbers are not that I collected and I tried to make my slide richer because you know the purpose of this presentation is for you to completely understand whatever I understand and go even beyond. So this two second is important. Approximately two seconds because if we'll see later that once you get the maximal stimulation CMAP, you'll be doing a repetitive nerve stimulation and we'll go over each thing. Why two, why three, why not five, why not 20? But when you are stimulating a nerve over a rate of five per second or five hertz, then so if you are stimulating that over five hertz, you are going to, no, I'll come to that. So if you are stimulating in a repetitive stimulation for approximately two seconds or so, then you are going to get this secondary vesicles released. So if you're stimulating at two hertz, so then the first second you have first stimulus and second stimulus. Then in the second stimulus, third or fourth, the fourth one touches this two second margin. And if you're doing a three per second stimulation, so the first three happen in first second and then the fourth and fifth happen between one and two seconds. With the later stimulations, you release this secondary vesicles. And this is important for our understanding of why and what. And this is where, this is a roadblock. Particularly technicians, they just don't understand what's the difference between normal and abnormal neuromuscular junction function testing. So remember this about two seconds. So if you're doing it and you are into the two second margin close to that, you're going to have more vesicles and it means something. So normally, this is not dormant. We have over trillion synapses in our system. All the synapses are active all the time until we are dead. And this is the new AI model that has inspired about a decade ago to the new AI model where all the computers, all the electronic devices are continuously on. Even if you turn it off, there is some activity goes on. Which is this vesicles come to the surface and then they are released. The cover is dissolved, so bare acetylcholine molecule is released and they bind to the receptors. These are hypothetical. So let's take the normal one. So normally, I put only four. It's a completely arbitrary number. So a few vesicles are released all the time. A few acetylcholine is binding to the receptors and are creating local, very local and focal depolarization. Those are small. Those are called miniature end plate potential. The nerve and muscle junction is called end plate. So this is an end plate. When there is no action potential that has come through the action, they are released and they create this MEPP, the miniature end plate potential. Those could be measured. You don't measure it from the surface by the EMG machine, but you can put a microelectrode and you can measure those. So that's miniature end plate potential. Okay, it doesn't help us for our purpose. When an action potential reaches here, what happens is the calcium channel. These are the calcium channel, one on each side. This is the one in normal people. So calcium enters and whatever enters has to also leave. So calcium enters and calcium facilitates the release of the quanta, not just one here, two there, three there, but many quanta and we'll come to the number because that's important. And then calcium also has to leave. So calcium, the calcium that has entered leaves somewhere between 100 to 200 millisecond. If you multiply 100 by 10, that's one second. If you multiply 200 millisecond by five, that is one second. So if you are stimulating a muscle at a frequency of five hertz or five per second or higher, then we are going to cause calcium accumulation because the calcium that has entered before it leaves, new colonies of calcium will come in. So there'll be calcium accumulation and this is important. So remember the time, about two seconds, and remember the five per second rate of stimulation. Something special happens under these two situations. So there are about 1,000 vesicles primary and there are about 10,000 vesicles. These are rough numbers. And we have tertiary vesicles, about 100,000, where up to the cell body. So they are in various stages of storage and transfer. Now this is a calcium channel receptor which is blocked by an antibody. Technically speaking, the PQ type voltage-gated calcium channel antibody. So as a result, when action potential comes here, calcium cannot enter. As a result, the release of acetylcholine is greatly diminished. And this is important because when you do, when you're doing a baseline supramaximal stimulation in diseases such as Lambert-Eaton myasthenic syndrome, which is a disease of the structure before the synapse. So this is the presynaptic disease. Then you have low amplitude. Myasthenia gravis, on the other hand, is a disease of receptors binding here. So this is myasthenia gravis. So in myasthenia gravis, it is not just the receptors binding the antibodies, binding the receptors so that they are not available. There is a complement initiated inflammatory war going on. So as a result, if you look at the normal, compared to the normal muscle membrane fold, this fold is atrophied. And as the disease advances or goes on with time, they disappear. And so are the receptors. Instead of four, I have drawn only three. And one is blocked by this acetylcholine receptor. The other one is also blocked. So only one is left. A person who has this, with a 75% reduction of availability of binding of acetylcholine, would be in crisis. So this is an exaggerated slide. So this is myasthenia gravis. This is normal. And the opposite thing happens in pre-ganglion disease such as Lambert-Eaton myasthenic syndrome. The receptors are not getting the acetylcholine because calcium is blocked. They are not released. So there is something called like a denervation sensitivity. If you're hungry, then you can eat anything like that. So look at the number of receptors. Instead of four, there are one, two, three, four, five, six. They just say, give me acetylcholine, give me acetylcholine. But still, they don't get acetylcholine because there is a lack of supply. So this explains why the initial CMAP, the compound muscle action potential, is low. And we'll come back to that. So when this miniature end plate potential, MEPP, only of scientific interest, you can put an electrode and measure it. When an action potential comes, many vesicles are released. And you develop many MEPPs. MEP here, MEP there, MEP there. You don't have three diseases in the body. So this is supposed to be normal. This is supposed to be normal. This is supposed to be normal. And this MEPP is an arithmetic entity. 2 plus 2, 4. Add another 3, becomes 7. Add another 5, becomes 12, and so on. It is not an all or none phenomenon. When they sum up, it is end plate potential that is also an arithmetic or mathematical entity. 5 plus 7 is 12. Add another 4, becomes 16. Just keep adding. But then happens one phenomenon. We'll come a little bit later. So the terms that we'll discuss is decrement of amplitude and area. Which one is more important? Well, theoretically, they're both equally important. But culturally, I would say, the amplitude has been relied on, measured, commented on, attended to much more often than area. We'll discuss this disturbing term of increment and why it should be used cautiously. Isometric contraction, when you are done with the opening the supramaximal stimulation, you have chosen the nerve, first you prepare the patient, second you choose the nerve and muscle duo, and then you get a supramaximal stimulation baseline CMAP, and that's important because all your measurements will be in reference to that one. And then you do the two per second or three per second stimulation, but after that you're going to go for exercise. There are two types of exercise, the brief exercise for 10 seconds, and then the one minute exercise. Their purpose is different for this. The one minute exercise is to create or to see if you can create exhaustion. The one minute exercise is not to see whether the amplitude rises. If you put an electrode, recording electrode, into the muscle and you keep exercising, say one minute, 10 seconds, 20 seconds, 30 seconds, 40 seconds, you will see that the amplitude is rising, but you don't see that from the surface electrode when you measure the CMAP. What you see is at the end of the exercise, you again do these two per second or three per second repetitive nerve stimulation, and then what you see on the surface, what you measure is the CMAP, many CMAPs. And you compare the obtained CMAP after one minute exercise, after two hertz or three hertz repetitive stimulation with the original supramaximal CMAP. That is different. That goes down. So the one minute exercise is done to look for exhaustion. Exhaustion has no metrics. The metrics for exhaustion is decrement. But we'll also talk about facilitation and pseudo-facilitation, and we'll understand the difference between increment and how loosely these terms are used. It's okay, that's culture, but we'll understand the difference. Tetanic stimulation is nothing to do with the disease tetanus. Tetanic stimulation means if you are stimulating without break in between. So 10 second exercise is a tetanic stimulation. One minute, five minute, 30 minutes, whatever you do is also tetanic stimulation. The common culture for the common diseases is to do one minute exercise and 10 second exercise. There are esoteric situations where you can stimulate for five minutes. I don't think that is done routinely. I do not do that, and the yield is questionable. Safety factor is another thing that is a roadblock. I would say particularly for my residents and fellows and some technicians to say, what is being done? Like you're trying to find out difference between health and disease. Normal neuromuscular junction testing and abnormal neuromuscular junction testing. And then the question is, is it pre-synaptic or post-synaptic? But the first question is, is it abnormal? So we'll understand the safety factor. So let's go with the decrement. So remember one thing, which is a common mistake. And we'll show you the five waveforms obtained after repetitive stimulation. People think that the first one is the reference, and you see the lowest one, and you do a mathematical equation. Completely wrong. You have obtained the biggest line CMAP with the supramaximal stimulation. When you go to the program, the computer remembers that one. You don't have to obtain that. Remember that one, the area and the amplitude. So amplitude of the biggest line CMAP minus the amplitude of the lowest CMAP, whatever is the lowest, it's usually the fourth or the fifth one. But it could be the second one. It could be the sixth one. And then you divide that by amplitude of the baseline CMAP that you obtained. Multiply that by 100. So it is a percentage. And so that means your amplitude of the lowest CMAP, if it equals the baseline CMAP, then it is zero. So then there is no decrement. And that's what we see in the normal situation. Increment is kind of opposite, but you'll understand in a few minutes that actually we're not dealing with increment for the vast majority of the cases. Decrement is a hot topic, because that is the first thing to happen in both presynaptic and postsynaptic disorders, myasthenia, Lambert-Eaton myasthenic syndrome, as well as botulism. So we're looking for decrement or lack of decrement. But the increment is a complex topic, because you look at that amplitude of the highest CMAP that you have obtained, minus the amplitude of the baseline CMAP, divide by the baseline CMAP by 100%. So in normal people, when you stimulate them, the amplitude doesn't rise. So you don't see increment in healthy people. If it's a myasthenia gravis, there is decrement with repetitive stimulation. And with the 10-second exercise, which we'll see later, the amplitude increases. That means the decrement is repaired, but very rarely it exceeds 100%. So it doesn't become normal. And if it exceeds 100%, you have to think about technical errors, or whether the patient has taken the pyridostigmine, the medicine, or something like that. You have to repeat the test. So basically, you don't see increment, except for rare cases of myasthenia gravis. And I have a slide later down of in what situation you can see significant increment in myasthenia gravis. First is technical, patient took the medicine, your technique is wrong. But there is also a pathological condition. So increment, I will just say, we'll just discuss that, because people use that term. In your lab, somebody says, oh, what was the increment? A much better term is the facilitation. The facilitation just gives you, there is no, here you are, you have subtraction, and that is what makes it difficult. But here, it is just the amplitude of highest CMAP by amplitude of the baseline supramaximal CMAP, and you multiply it by 100, so it is a percentage. So in normal people, they are the same. So amplitude of the highest CMAP is the same of amplitude of baseline. But in myasthenia gravis, we're not talking about facilitation initially, but after doing exercise, which comes with a 10-second exercise, then we're looking for repair. Repair means 100 becomes 60, with 10-second exercise, it becomes 80. So you partially repair the decrement, but it rarely becomes 100 or goes beyond 100. Possible, sometimes I see that. So the facilitation, if the facilitation is 100%, means what? Means there was decrement, and with 10-second exercise, you have repaired it completely. So 100% means your CMAP obtained after exercise is the same as the CMAP that you had under baseline. What is the increment when the facilitation is 100%? The answer is 0%, because if you go back, the increment is the subtraction, which is zero. So this is confusing. You have a 100% facilitation, things like something good is happening, but your increment is 0%, and it has no value. So is this part clear, that technically, we should be using the term decrement, because that's what we're looking for, and with the repetitive stimulation. With the one-minute exercise, we are also looking for decrement, which is called exhaustion, but the metric for exhaustion is the decrement. And we'll discuss later why there is decrement on one-minute exercise. I just explained that. If you measure, if you put an electrode into the muscle, you will see, actually, the amplitude is rising much higher than the original CMAP, but here, on the surface, you can only see decrement. There is a term called pseudo-facilitation, and what is pseudo-facilitation? So there are different ways it has been defined. One is, which is the more popular definition, is when your amplitude is increased, but the area is not increased. What are the reasons? A, technical. B, it can happen in some athletes who can, when they exercise, they exercise in a very coordinated, very synergistic way. All the muscle fibers are activated at the same time, which is not the case for many. So it could be just individuals whose muscle contraction is such that you can get higher amplitude, but not a corresponding increase of the area. And why does it happen? Because the technology of the computer for amplitude, which is a height, from baseline to the peak, is a very clear-cut entity. But as the wave goes up and down, up and down, and up and down, the digital measurement of the area is nearly 100% accurate, but not 100% accurate. So it is possible, just for you to see, amplitude high, but not area high. We see that, I will say, once a week, probably. And it could be just be, it can be there. It's technical, it's artifactual. But it also could be there if you are stimulating at a frequency of five per second or higher. The interpretation is difficult, but if you're stimulating at five hertz, or five per second, that's what we do not stimulate, at four or even five, because then the area and the amplitude may go in different ways. So that's the pseudo-facilitation. So we'll just spend a few minutes on the safety factor. This looks complex, but again, we'll walk you through. So when one quantum of acetylcholine is released, it has about 1,000, let's say 10,000, 10,000 acetylcholine. Now, 10,000 acetylcholine molecules will bind to about 1,500 channels. It's like a fish egg. A mummy egg gives 10,000 eggs. If all 10,000 becomes 10,000 fish, and each one of them gives 10,000, pretty much this auditorium and the rest of the earth will be full of fish only. Nobody to eat them or do anything to them. So only 1,500 channels they bind to and they create miniature n-plate potentials, and if you add them, n-plate potentials. And their business, at the best, can create one millivolt of potential. This is inside, not the one millivolt from the skin that you measure. If you put an electrode into the neuromuscular junction, you will see one millivolt potential. How much do you need? You need 20 millivolt to generate a propagating action potential. So this is just a breakdown. In channel one, you have a miniature n-plate potential, one, and channel two, so and so, up to 1,500, so you have one millivolt. So this doesn't do anything on the surface. Nothing moves. When an action potential comes, usually 60 quanta, plural of quantum, is released. So that can cause 60 millivolt of potential changes, but you only need 20. So 60 quanta, they do what they are supposed to be doing. So it's not that you say, enough, stop, rest, you go back, no. All 60 quanta, they work, and they create a 60 millivolt change to create summation of this n-plate potential. And finally, once it is over 20, you get this muscle fiber action potential. Muscle fiber action potential, MFAP. So miniature n-plate potential is an arithmetic entity. Goes on, you add the numbers. N-plate potential is an arithmetic or mathematical entity. Keep going. But once it crosses 20 millivolt, then stops. Then becomes muscle fiber action potential. It's an all or none phenomenon. So what happens to the remaining 40 millivolt? We do not know. So imagine on your birthday you have 100 friends, but you only have 20 vases. So 100 friends come and they give 100 bouquets. You only display 20, because that's what you have. And a reporter comes and says, wow, all the flower vases are full. You are loved, well loved. Then you break up with 10 friends. You are 90, you get 90 bouquets. You still have 20. The reporter says, he or she is equally loved. Wrong, because this is an all or none phenomenon. When it goes down to 20, you still have 20 flower bouquets in vases, and the reporter reports, the reporter is us from the surface. The technician, the resident, the fellow, the neurologist, the electromyographer, still says everything is normal. But you don't know that it has, your friend size has dropped down from 100 to 90 to 80 to 20. Only when it goes below 20, then you say it is abnormal. There is a problem, which is the neuromuscular junction disease. So this is the safety factor. We need 20, we have 60. We have three times, or 300% safety factor. In normal people, that's why no matter what you do, you make them exhausted, you stimulate them here, this way, that way, you still see the same amplitude. But the amplitude inside does drop, and we'll see that. This is a simplified version from one of my favorite person's books, who is actually speaking now. So if you measure the acetylcholine molecules, and you can measure that, with repetitive stimulation, it does go down. In normal person and in a person with a disease of neuromuscular junction. End plate potential also goes down. If you put an electrode deep into the neuromuscular junction, this is normal, this first column. It also goes down, but it doesn't matter, because you had 100 bouquets, now you have 90 bouquets and 80 bouquets and whatever. As long as you have 20, the reporter from the surface, you or me, says it's normal, it's okay. But when you have a disease, your safety factor is decreased. Then, here it goes down, you don't see that. The end plate potential goes down, and some of them are below the threshold. Go to the muscle fiber action potential. In a normal person, you try to exhaust them, you cannot, because they have only accepted the threshold. And although this has gone down, acetylcholine, although EPPs have gone down, your MFAPs are an all or none phenomenon. You still have 20 bouquets, you are equally loved. Wrong diagnosis from outside, but that is our apparent diagnosis. But here, you will not see the third, fourth, fifth, sixth, and there will be abnormalities. What you are measuring is the CMAP, compound muscle action potential. In a normal person, exercise 10 seconds, one minute, it will remain the same. Sometimes you have a little increase in the amplitude, and that is pseudo-facilitation. Mechanism, more synergistic muscle action, technical factors, but nothing to worry about, or yeah. And so, but then in other neuromuscular junction disease, you see a decrease, and that is called decrement. Now, any decrement is a decrement, but when it is 10% or more, then we count it. So what about 8% decrement, 9% decrement? The culture is not to call it abnormal, but there are some books on neuromuscular books, particularly on myasthenia gravis. They have mentioned that, you know, we are worried about this 8% decrement and 9% decrement. We're gonna watch, keep doing and watching. And now we know the answers. If you do a single fiber EMG on those people who had any decrement, your single fiber EMG will be abnormal. So that question doesn't remain unanswered. But that's an interesting thing. So when somebody's decrement is, say, 6%, and you do one minute exercise, still you don't see anything, we call it a normal test, normal neuromuscular junction function. Technically, those patients still should have single fiber EMG, because that 6% decrement means something like this did happen, because you will see no decrement in a normal person. So we'll go into the methodology. Our purpose will be to do the test. So I'm a technician or a resident or a fellow like you. I work in this lab, which is AANEM hiring lab, Savannah Convincence Center. And by this way, I'm so honored to be on this podium with James Edward Oglethorpe, his name, outside and here. And he's such a noble soul. When I first, many years ago, 2014, or when I first came here, I was sitting where you are, and he removed slavery. He came from Great Britain, and he established the Georgia colony, the entire state of Georgia, here in Savannah. And there was no slavery. So 140 years before we had anybody called Abraham Lincoln. So 140 years ago, he was so advanced, he created a free society here who could practice their religion, and there was no slavery. And this is named after him. So I'm honored to be here. So we'll do a test. You have ordered and repeated a neurostimulation study. I'm going to do the test. First of all, it is ordered for not anginal chest pain. It is not ordered for depression. It is ordered for neuromuscular junction disorders. Commonly, myasthenia gravis, which we learned, is a post-ganglion disease. What is the sensitivity? About 70% in generalized, and about 50% in ocular myasthenia gravis. Lambert-Eaton myasthenic syndrome is a pre-ganglion disease. Not so commonly for botulism, because you diagnose botulism by other means, which is a pre-ganglion condition. I mention this unbolded, because I don't think REBS teams are the way to go for congenital myasthenic syndrome. Because congenital myasthenic syndrome could be pre-ganglionic, ganglionic, and post-ganglionic. There are over 20 genetic mutations that causes almost different subsets of the disease. And there's a slow-channel disease, which is very confusing from this REBS team point of view. And I also don't do that. My lab is mostly an adult lab. So I just mention, if anybody has any question, I have a slide later, but I will be focusing on these three. So if repetitive nerve stimulation study has been ordered for a patient suspected of motor neuron disease, ALS, or diabetic peripheral neuropathy, or poly or dermatomyositis, would you still do that? That's an ethical question. And I make questions for the neuromuscular board certification ethics. So the answer is, you don't cancel the test, and you don't do the test. You contact the ordering provider, and say, well, I see that you ordered the repetitive nerve stimulation study for suspected polymyositis, or mitonic dystrophy, or ALS. And is it okay, and I do that. And then the ordering provider, if you can contact, says, oh, no, no, no, no, that's just a mistake. I'm doing it to look for any myasthenia gravis that may coexist or be there, like that. Then it's okay to do that. But this test, repetitive nerve stimulation study, is not the test for peripheral neuropathy, almost all of them, or muscle disease, almost all of them. It's a test for the neuromuscular junction disease. If time permits, we'll discuss what we see if we do this by error, or not error, but if you do that, and you see the decrement, and is it still possible? So we'll talk about that. So the methodology three is selecting the nerve and muscle. Technically, if the board question comes, repetitive nerve stimulation study should be done from accessory slash trapezius, ADM slash ulnar, FDI slash ulnar, et cetera, like that. And then if there's an option of all of the above, which AANM has gotten rid of from this year. So there'll be no all of the above or none of the above. There'll be only one answer. So you won't get this question, but it used to come like that. The answer will be all of the above, because technically you can do rev stim studies from any nerve and muscle that is accessible, but in reality, you have to think about that you need to go for immobilization, because the exercise that we'll talk about, or we have talked about, is isometric exercise. Iso means same, metric means measurement. So your muscle is contracting, but nothing, the joint is not moving. So if I make my biceps here, that's not isometric, but if you force me, obstruct me, and say, try to bend your elbow, but nothing moves, that is isometric. So you have to immobilize the muscle. Otherwise, the electrode on the skin will remain where it is, and the muscle underneath will move somewhere else, and your baseline will drift, and bottom line, you will get a useless record or data. So it has to be isometric exercise. So we'll come to that. So more common practices is you choose the ulnar nerve, and either ADM or first dorsal intertia. It is somewhat a little challenging, not so difficult to immobilize the FDI muscle, but ADM is very easy. You can tell the patient to make a splint of the fourth and fifth fingers, make sure that the ADM moves the little finger at adduction, doesn't move. So the patient can do that, and then you can do the study. Or there are devices that you can see in various textbooks, fancy devices. If the patient is not following commands, has cognitive problems, or somehow disoriented, yes, you can do that. In our lab, we have a very sophisticated, highly evolved device that's called an additional technician. So an additional technician holds it, and it works. You can also do spinal accessory and trapezius. So which one is better? Tell me which one to do. For myasthenia gravis, the proximal muscles, like spinal accessory and trapezius, they have a higher yield, but it is also harder to immobilize them. Ulnar is easy to immobilize, but you have a lower yield. So why not doing the facial muscle study? They are closer. 96% of patients, say, with myasthenia gravis, within six months of onset, will have ocular and facial muscle symptoms. So why don't you do it here? There is no immobilization technique for the facial muscles. So technically better, if you can do that, but immobilization is not there. Now the most common facial muscles is nasoliz, where you put the G1 recording electrode on one side, and then the G2 is on the other side, and then the ground could be on the forehead, and you have to stimulate behind this thalamus to form in the facial nerve. By the way, there is a session today, later, by Dr. Laughlin on the techniques of REPS teams, including facial muscles. And this is important because Mayo Clinic tried this study with the masseter. And Dr. Ruben Devon just published, not just, but a few years ago, published a paper that the trigeminal and the masseter muscle duo is as sensitive, as useful as facial and nasoliz, although they are further down from your eye than the nasoliz, and they are further down. But the immobilization factor that makes this facial nasoliz test a theoretically superior test, but practically not so user-friendly, it takes care of that immobilization factor. So if any of you go and attend that, I think later is 10 o'clock or 10.30. Dr. Laughlin is the EMG lab director at the Mayo Clinic Rochester. So maybe just see if it could be demonstrated, the trigeminal with the masseter study, and whether the baseline looks fantastic or not, and if there is any practical demonstration of this facial versus trigeminal. The paper has been published, but you need to see that for yourself to believe. So the other muscles can also be done, but I will say for all practical purposes, ulnar with ADM as a distal muscle, spinal accessory with trapezius. If you are adventurous, facial with nasoliz, and if you have enough experience, trigeminal with masseter. I just checked before I left for this meeting, our technicians, we have ACGME accredited lab, and all the technicians are certified. They have not done trigeminal with masseter. A few weeks ago, they were doing a test ordered by another person. They came to me asking where to record nasoliz, and just a few weeks ago, maybe less than a month ago. So just to give an idea that it is not done. I didn't order that test, but I told them G1, G2, et cetera, like that, because I teach fellows and residents, and so I know this. So that's the thing. Any questions on selection of nerve and muscle? Any input, experience, disaster, great results? Feel free to share, okay? There is an extra microphone, which Mrs. Tracy Parks arranged just for me, for this room, for this hour. Normally, it is a one-way traffic. That's on the back. I don't know whether it's working or not. So immobilization techniques. If you open Dr. John Kimmerer's book, and he said that the spinal accessory trapezius patients will hold the bottom of the chair and will try to elevate the shoulders, shrug the shoulders. So if a patient is cooperative, not with cognitive impairment or disoriented, but I've never seen a chair in the EMG lab when I did the residency fellowship, which was not far from here, Medical College of Georgia, and I asked, where is Kimmerer's chair? And Dr. Kimmerer was still alive until a few years ago, and I said, there is no Kimmerer's chair. There are only stools. So in our lab, we have this, again, a highly evolved system called another technician, the second technician, blocking the shoulders. But if it is a muscular person, it is indeed a challenging job. So which one shall we do? The ulnar or the thing? It's obvious. The trapezius has a better yield. So only for me, our lab, and there are seven neuromuscular people doing it. Actually, seven neuromuscular, and then about three other neurophysiologists. So about 10 people. Only for me, the dictum is, if I'm kind of strongly suspecting myasthenia gravis or a neuromuscular junction disease, I say do the trapezius with two technicians in the room, because if that's normal, there is no need to do the ulnar, because that is more sensitive. If that's normal, the ulnar is not going to be abnormal. So we can have one repetitive stimulation study. And the others have a different logic. Both are correct. They say do the ulnar. And if you see the 10% decrement from ulnar, bingo, you are done. You don't have to go to this unpleasant stimulation here, which is very unpleasant. Ulnar is very easy. So it's a hit or miss. You could gain by just doing ulnar and seeing abnormality, you are done. Or doing the trapezius, and it's normal. You don't have to do the ulnar. It's normal, you are done. So there is no fixed algorithm of how to go there. But you have to have the awareness of immobilization, whether you have a two technician system, which we have, we have the luxury of technicians. But there are many labs where there is only one technician. Is that the picture for some of you? Yes, so you cannot have a second person unless you have a resident or a fellow or the attending himself or herself being present. So you have to come up with a solution of the immobilization. If you cannot, then ulnar is a good thing because you can easily immobilize. In fact, I have done, when I did the nerve conduction study, ulnar study all by myself, holding it. And with one hand, I'm operating the computer, and the other hand is immobilizing the patient. So that's important. So a common mistake is not to do supramaximal stimulation because remember, all the calculations is based on this supramaximal stimulation, stimulating all the 1,000 nerve actions here or whatever other nerves you are checking and obtaining the value. And the computer remembers that number. And for one-minute exercise where you do, after one-minute exercise, you do the repetitive nerve stimulation at zero, one, two, three, four minutes, and at the end, you do 10-second exercise. All of the amplitudes that you're collecting for one minute, it's the lowest that matters because you're trying to see the exhaustion or decrement. And for 10-second exercise, you're not trying to see the exhaustion. You're trying to see facilitation. So those amplitudes are going to be compared with the original one. In some places, the technician or the resident or the fellow does the test and calls the attending who is five minutes away or 10 minutes away in a complex institution and then say, I'm coming. You cannot use that value. You have to again obtain your supramaximal complex that the compound muscle action potential. So if you are stimulating a muscle at a frequency below five, it is called slow stimulation. And why is this holy finger five? Because we have five fingers, five toes? No. We discussed in some of the original slides that five per second is important because by that, the fourth or the fifth stimuli it causes the, if you do five per second, then it's less than 200 milliseconds. So there's a calcium activation that plays a role. So keep it below five. Now, when you exercise voluntarily, maximal voluntary effort, what is the frequency? The textbook answer is 10 to 50, but in reality, most studies have shown it's about 20 to 30 in a person who is not, who doesn't do exercise, but maybe up to 40 or 50. It very rarely exceeds 40 and almost never exceeds 50, but you can stimulate from outside at any frequency. So you can go for 10, but it's very hard to do a 10 per second exercise voluntarily. So that's about 20 to 50, the range, usually 20 to 30. So slow rep is two to three. Which one is better? So published paper says two and three, also from Mayo Clinic, says they are equally good. So two per second means in one second, you are giving two stimulus. Stimulus one, stimulus two, one second. Stimulus three, stimulus four, second second. Goes on like that. Then how many stimuli to be given? We used to do routinely 10 until probably 12 or 14 years ago when Dr. Neeraj Kumar from Mayo Clinic Rochester published a paper in Muscular Nerve saying four or five is as good as 10, but it's much more tolerated by the patient. So if you need to repeat the rep stims, the patient is not gonna walk out. So overall, actually, it's better because the patient tolerates it better. You can repeat it to see the reproducibility. You can check another nerve and muscle combination. So overall, it's probably better, but individually, piecemeal, four and five will be statistically comparable to 10. We have a cartoon here, and I will show you it's exactly not the same, but it's acceptable. And then repeat at one minute interval. So again, I checked with our technicians in our lab. They just don't look at the interval. They just keep doing. So it takes about 15 to 20 seconds. So you change the parameter in the computer and tell the patient, okay, I'm gonna give you some volleys of three or four rapid succession currents. You're okay, ready? And that takes about 10, 15, 20 seconds, but they don't look at the watch. But the book says do that at one minute interval. I don't think that is needed. Next is the 60-second exercise is post-tetanic. Tetanic means contraction followed by contraction without relaxation, like a status epileptica seizure followed by seizure without recovery. So something like a status contractus or something. So post-tetanic exhaustion, 60 seconds. If you put an electrode into the neuromuscular junction, you will see amplitude rising, going above the baseline CMAP. We are not doing that. We are measuring from the surface. We only see if there is any exhaustion. In normal people, we do not see any exhaustion. In a neuromuscular junction disorder, we may see exhaustion. So you do one minute of isometric. Now we know the meaning of isometric. The muscle should not be able to move the joint. So that means exercise that cannot be seen from outside. If I am exercising my ADM muscle, but nothing is moving as if I'm not doing it, that is isometric exercise. But then the question is how do you know that I'm exercising at all and not just say, mm, mm, mm, I'm doing, and that is a reality. And you will see that. There is no technicality to check it because when the person is exercising, in the textbooks, it will mislead you because they have put the diagram of electrode into the neuromuscular junction. So when you are exercising, there is something. So you know whether I'm exercising or faking. But in reality, you just wait for a minute unless you are putting the resistance. So that's why I like the resistance to be put by us, the technician resident fellow attending. So if I'm putting the resistance here for the trapezius, I know that the patient is trying hard and I am trying hard to make sure nothing moves. And the owner also, instead of using a gadget, we have the second technician or the second person, it could be a resident fellow or the attending, doing it so that you feel that the person is trying to push, but you are making it not happen. So you are ensuring that the exercise is actually taking place. Then with this one-minute exercise, the purpose is to see from the surface decrement called exhaustion, and that has to be followed by repetitive stimulation. So all the parameters are repetitive stimulation, except for that one original baseline CMAP. You are doing a two or three hertz stimulation, after that you are going for one-minute exercise, and after that you are not taking a CMAP, ACMAP, you are doing two or three hertz stimulation immediately, zero-minute, one-minute, two-minute, three-minute, four-minutes, and then you are doing 10-second exercise, after that you are not taking a CMAP, ACMAP, you are again doing two to three hertz stimulation to see a series of waves, which we'll see next. So the 10-second exercise is to see facilitation. So let's look at some of these things. So in a pre-ganglioning disease such as Lambert-Eaton myasthenic syndrome or botulism, this is normal when you obtain the CMAP. No, it's not repetitive study, it's just the single supramaximal stimulation. You see a low amplitude. You may not see that. If it is mild or early, it may not see that, but if you see that, this is very characteristic. Now don't you see decreased amplitude in neuropathy and myopathy? If the neuropathy has affected muscles, muscles have atrophied, don't you see decreased amplitude? Yes, but you also see increased latency. The amplitude just doesn't drop significantly without change of the latency. Latency is one of the first things to be affected because the fast fibers could be affected first, where the amplitude still remains the same, the latency is prolonged. But in pre-ganglioning Lambert-Eaton, your latency will not be affected. How about muscle disease where the latency may be normal and the amplitude is low? Well, it will require the neural EMG, which should follow REF stims to see whether you see myopathic units or not. So REF stims should not be done, in my opinion and many other people's opinion, just as an isolated, just go to the lab and check ulnar and accessory nerves. They should first have the standard nerve conduction study so that you know you're not dealing with peripheral neuropathy, generalized sensory motor peripheral neuropathy cases. And technically speaking, should the neural EMG be done? No. I mean, yes, do the neural EMG, but it becomes painful and then it might become painful for the patient to tolerate. So routine study followed by REF stim followed by neural EMG. So this is where you have obtained the compound muscle action potential with supramaximal stimulation. The computer stores that. You don't see that. Then you give, in this case, say five repeated stimulation. If it is a two per second, so this is one second. The fourth one is at the end of second second, and the fifth one goes into the third second. If you're doing three hertz, then this one, two, three happened, boom, boom, boom, one second, then boom, boom, and if there was a square of six, it would be the second second. We saw in normal people, the acetylcholine discharge goes down in normal people. The miniature end plate potentials goes down, potentials go down. The end plate potentials go down, but they're still above the threshold. You have 60 quanta released, you need 20, 20 millivolt. And so you have an all or none phenomenon. What you see on the surface is no changes. Sometimes you see amplitude going up, and that is called pseudo-facilitation. It can happen just without any reason, due to technical factors. It may happen particularly in athletes, due to maybe the person slept well, you explained the test well, and all the muscles contracted at the same time, things like that. Or it could just be of unknown significance. That's pseudo-facilitation. It's never over 40%. So that's normal, or also remember, in mild or early cases of myasthenia gravis, you can still have a normal study. So this is not normal, normal or early myasthenia gravis. So in myasthenia gravis, we have checked the supramaximal CMAP, it was normal. Then we gave, say in this hypothetical case is the old time, you get 10 stimuli, 1, 2, 3, 4, 5, 6, 7, 8. So if it is at 3 hertz, the first 3 was first second, fourth, fifth, sixth was second, second, seven, eight, ninth was third second, and you stepped into the fourth second. Here you will see decrement. This is one very common question in various board examinations, is the maximum decrement. And remember, decrement is not 10%, 10% decrement is regarded as abnormal. That if someone's blood sugar is over 126, you call it abnormal. But if the blood sugar is 98, it's no sugar. It's not called no sugar, it's called blood sugar of 98. So the maximum decrement takes place between first and second. But the decrement continues. And usually by the time it is the fourth, you see the lowest decrement. Why the lowest? You can understand, the acetylcholine stores get exhausted, further exhausted, further exhausted, further exhausted, no. Because you are at the two second mark. The secondary vesicles, 10,000 vesicles, they are released, they repair the decrement, make it about same, and then the sixth one goes up, seventh one goes up, the ninth and tenth goes up, but it never reaches the original value. That's a standard case of myasthenia gravis. It may reach the original value, it's still okay, acceptable, but there could be technical factors. I will definitely redo this test and look at the basement with my glasses on and redo this because I'll be careful if it exceeds. It can exceed in severe myasthenia gravis patients. But those severe myasthenia gravis patients should have the C-MAP, the baseline C-MAP will be low. And we'll discuss that in severe cases of myasthenia, it may look like Lambert-Eaton. You're obtaining a supramaximal stimulation and you are seeing a low amplitude. When you see that, then sometimes the facilitation could be over 100%, and this tenth one may be above the, not this first one, the baseline C-MAP. So myasthenia gravis, you may have a decrement of 9% and then you do exercise because you didn't see the 10%, so you do one minute exercise. After one minute, it got further worse, it did exceed 10%, that's good. I mean, bad for the patient, good for the diagnosis. Two minute later, 26%, three minute later, 32%. At the end, you do a 10 second exercise, your decrement is 11%. Decrement means compared to the baseline C-MAP, it is still 11% less. But compared to 32%, it is an increase. Don't call it increment. For increment, it has to be above the original value. So it is a facilitation or repair of the decrement. Those are acceptable terms, but not increment. So in a Lambert-Eaton, ignore some of these, baseline is low, but the latency is normal, you are on your guard. And then you see the decrement, just like you see in myasthenia gravis, then not always, but usually with the one minute exercise, you see the decrement getting worse. And then you have a 10 second exercise, and that is the main thing for pre-Gallian disease. You see over 100% increment. In fact, often we see over 200% facilitation, not increment, sorry. So with a 200% facilitation, the amplitude becomes double. Increment, if you use that term, which is better avoided, will be 100%. So with a 100% increment, your facilitation will be 200%. And in the botulism, you are somewhere in between. You are somewhere between 50% facilitation to 150%, around 100%. So quickly go over this. We have discussed that. Normal study, baseline C-MAP normal, repetitive stimulation, no decrement, one minute exercise, no decrement, 10 second exercise, don't do that. 10 second exercise is to see if you can repair the decrement. If there is no decrement, you do not have to do the 10 second exercise. In myasthenia gravis, remember in severe cases, the baseline C-MAP is normal, but decreased in severe cases. And then we discussed the repetitive stimulation in one minute. But remember, after a 10 second exercise, your facilitation is usually below 100%. If it exceeds 100%, possible, but redo it, and avoid check out for technical factors, or it could be a severe myasthenia gravis. Lambert-Eaton, we have discussed that. Botulism, one few difference. What's the difference between the findings in botulism and Lambert-Eaton, both are pre-eugandic? The baseline C-MAP will be decreased, that's the same. But when you do this two or three hertz stimulation, you don't see decrement in adults. You can see that in infants, which I do not do many, about half of them. So majority of the patients, you will see no decrement with the two or three hertz stimulation. How about one minute exercise, also you may not see any decrement. So that's very different. The real thing comes from the ten second exercise. When you can see about 100 to 150% facilitation with botulism, means the amplitude becomes same as the baseline C-MAP or goes up. And in Lambert-Eaton, it becomes double, that's 200% facilitation. I will just mention congenital myasthenic syndrome. Again, could be pre-ganglionic, ganglionic, post-ganglionic, over 22 mutations, it's all over the place. The diagnostic role is uncertain. The baseline C-MAP could be normal, REPSTIM could be normal. You may have to require ten hertz stimulation, which is extremely unpleasant. And for kids and infants to tolerate that, ten hertz. Normally we're doing two or three. And there's a study, can we do two, because three is unpleasant. And you're talking about ten hertz stimulation, and you have to do that for five minutes. This will be very difficult to be completed. So we'll go into the common mistakes and pitfalls. If somebody is on acetylcholine receptor inhibitor, that has to be stopped. When? The book says four to 24 hours, but I will say our lab says 12 hours, which is within four to 24 hours. Because acetylcholine ester inhibitor will slow down the breakdown of acetylcholine, and there will be acetylcholine in the neuromuscular junction. And it will increase the amplitude, so the decrement that you want to see, if there is a disease, will be masked. So you will miss a disease, your test will be false negative. Lack of warming, or cooling rather, what cooling does is, cooling also slows down the action of the acetylcholine esterase. So it's kind of a same effect as if somebody has taken pyruvastigine, or brand name, mestinone, and there is cooling. The breakdown of acetylcholine will be slowed, as a result there will be more acetylcholine for a longer duration in the neuromuscular junction, which will increase the amplitude, which will decrease the decrement that you want to see if it is 10%. It will be, what would have been 10% is now 4% or 5%, and you're gonna call it normal, so it will be a false negative testing. Choosing the wrong muscle from immobilization point of view. Lack of supramaximal stimulation we talked about. Immobilization failure is a very common failure. You need to have a strategy of what you're going for, and what challenges there could be, and how to overcome that. One thing is sensitivity adjustment. When you are going for the ten second exercise, and especially if it is pre-ganglioning, such as Lambert-Eaton. If you don't change your sensitivity or gain, your wave goes up, reaches the ceiling, and then it comes down. Not in all machines, if you change the sensitivity once it has been recorded, you don't see the continuation of the curve. Once you have a complete graph, you can make it bigger and smaller. And if you make it bigger, bigger, bigger, the peak gets cut off, but you can make it smaller, smaller, smaller, it comes back. But if you have not recorded that, you cannot make it. Computer is not going to project, this is how it should have gone that way. So that is one of the pitfalls. So we'll go over quickly the methodology. Patient selection, any questions? Who should have that test? Holding pyrostigm in 4 to 24 hours, selecting the nerve and muscle. Immobilization techniques, supermaximal stimulation, slow, repetitive study. 60 second exercise for post-tetanic exhaustion, and 10 second exercise for post-tetanic facilitation. So I thank AADM for giving me this opportunity, and also to Mrs. Tracy Parks, and to all of you who are here, as well as listening virtually. Sometimes it's just fun to look at things from a different point of view. So if you look at AADM, I see AAN and electrodiagnostic medicine. I can also see American Airlines, which I'll be taking while going back, and neuromuscular and electrodiagnostic medicine. So just for fun, to look at something in a different angle. In terms of our medical terminology, it gives you a room to look for another resource. There is a book that is very popular, and people think that's enough. Well, that's enough. That's a very good book. But there are books, and these other books have been written by competent people, and there are articles, journals, publications. It's important to expand and look the other points of views in this regard. And that's important. Just this latest neuromuscular muscle and nerve journal, there is an article from Professor Shinji Oh, about two patients who has myasthenia gravis and Lambert-Ethan. Mask-positive myasthenia gravis and Lambert-Ethan. So pre-ganglionic and post-ganglionic. So what do you see on the REVS team? So the REVS teams were kind of what you see in Lambert-Ethan, slightly subdued, and there have been so far 55 cases described. So it's interesting that what you normally expect, you may not see that. And before saying for technical reasons or uncertain clinical significance, you may redo the test. But you need to have the basic understanding of whatever you're doing. Why two hertz? Why three hertz? Why not five? What happens to calcium accumulation? What happens with ten second exercise that doesn't happen with 60 second exercise? And what I'm seeing from outside by our recording system is a synthetic, is an artificial way of looking at a disease underneath, where actually opposite things are happening. With one minute exercise, the amplitude is going up, but my repetitive CMAP shows exhaustion. So I think it is very important to understand the structure and the function and the abnormality, the pathogenesis, for good understanding. All of these I have discussed for years with my technicians, residents, that are interested, and of course, neuromuscular and neurophysiology fellows, until they have said, got it. So thanks to all of you, but I will take questions. Did you all get it, or do you still have some issues, questions, or anything that you would like to share? We have 13 minutes and 58 seconds left. Thank you. No questions, you all of you got it? I couldn't completely hear you. Can you come a little bit? Have I seen Yeah, so her question is whether the combined pre-ganglioning and post-ganglioning, myasthenia gravis plus, Lampard-Eaton cases are going up. The answer is, technically, we do not know, because I will refer you back to the latest Muscular Nerve and go for Dr. St. Joe's article. He added the 54th and the 55th patients, but until then, 53 patients were discussed, and you have the articles with those 53. So when the disease in the world has been reported only 55 times, it's hard to answer the question whether the prevalence is going up or not. I would say in our lab, we haven't seen, but how often we see Lampard-Eaton? Not very often. Myasthenia gravis, of course, is a weekly or sometimes daily phenomenon for me. So I cannot give you the answer, but only 55 cases have been reported. But it'll be important if you have a case it seems that you are seeing. So maybe those should be published so that we know that it's not just 55 in the whole planet for last 30 years, more than that. And so then the question will be, why are people developing antibodies to the calcium channel receptor, the voltage-gated, as well as the post-gallioning receptors? And then the question will be, can some of these be paraneoplastic? Because if you look at the individual diseases, paraneoplastic disease could be associated with acetylcholine receptor antibody, myasthenia gravis, just like that. And it could also be associated, of course, with the Lampard-Eaton myasthenic syndrome. So are we missing those cases as paraneoplastic syndrome where a tumor will come to surface two, three, four years later? Can we diagnose them? We have no, presently, no practice parameters or algorithm to do this. So that would be an interesting thing to know if all these cases are published, that would prompt further research to go for paraneoplastic antibodies or a cancer research. It is not done automatically. If I see a patient with myasthenia gravis symptoms and I diagnose with antibody testing, serological testing, as well as REVS teams, then we go into the treatment mode. Yeah, we do a CT scan of the chest, but I do not routinely check paraneoplastic antibodies. For LAMPS, yes, we do. And for the others, maybe that will prompt us to change our practice. So please keep that in mind to publish those cases. And as I said, Professor Oh published only two cases, and that got accepted in a muscle, and of course, his name is enough. But if you have the 56th case, please publish. Okay, thank you, yeah. Any more questions? There was one other hand up, no? So I will just briefly spend a few minutes for just a surface knowledge, I would say, is what will happen if you end up doing repetitive neurostimulation study in a diabetic neuropathy patient? Would you see decrement? Very unpredictable, probably not. Would you see facilitation? Nothing significant. If you end up doing this test on a patient with motor neuron disease, or ALS, would you see decrement? The answer is yes. Would you see further decrement with one-minute exercise? The answer is probably yes. Would you see facilitation? Probably not. And again, motor neuron disease is diagnosed in a different way. You need the needle EMG, and you need all of the various other things. There is another issue where people think about the myotonic dystrophy. So the myotonic disorders, again, this might be a little bit too much for some of you, but myotonic disorders are grossly into two types, the dystrophic and the non-dystrophic. The dystrophic one are the two potentially killer diseases, the type one and the type two. Will there be any difference in RepStim studies if you end up doing the test? The answer is yes. You know, the one-minute exercise causing the decrement is not seen in the myotonic dystrophy type two. So you see that on the type one, but you don't see that on type two. But you don't use this for diagnosis. You do a genetic testing, because this is a potentially lethal disease. It can affect the heart, and people usually die from cardiac arrhythmia or heart failure. So you are definitely going to go for the genetic testing for myotonic dystrophy type one and two. So this is just an intellectual information for myotonic dystrophy. For the non-dystrophic conditions, myotonia congenita, paramyotonia congenita, and other periodic policy cases, there is this short exercise and long exercise. Those are not to be confused with our RepStims. So those are short exercise, and you see the C-MAP, and the long exercise, and then you do the C-MAP. So, and again, we also have genetic testing for those situations. The RepStims that we discussed, I discussed today, is not the test for the myotonic dystrophies or the periodic policy cases. So, but those are there. The last few paragraphs in a textbook, it's optional, it's good for you to read, but they do not have any practical significance from the diagnosis and management point of view. Any more questions? We have seven minutes, but, yes. So her question was, you know, again, there is no standard practice. Even the, all the books are different, and I don't think there is any standard practice for this. So in her lab, you routinely do three muscles, is that correct? Facial and maybe one proximal, like trapezius and ulnar. So yeah, you're increasing the diagnostic yield. If you do three, you're increasing the diagnostic yield. Why not four? You increase the diagnostic yield further, yes. There is no doubt about that. But the question is, 95% of the patients with myasthenia gravis will be diagnosed and confirmed with serological testing. And so you have only 5% or 6% patients left. And there is this single fiber EMG waiting to finish the game. So with this, what's the role of doing three muscles, four muscles, five muscles, six muscles is questionable, but you're definitely increasing the diagnostic yield. And if you have good immobilization techniques and you're doing a facial muscle, you are doing the best form of repetitive stimulation in your lab. But still, that is not a standard practice because there are many labs where they cannot go for that. The depth of understanding is maybe not that deep. So immobilization may be a big factor. So that's the case. But a few years ago, there was an abstract and a few guys came from Japan, Tokyo, and my abstract poster was next to that. And they did four REF stims from four or six muscles on the face. And they showed that the combined efficacy was comparable to single fiber EMG from orbicularis oculi muscle. That was very interesting. But I don't think I have seen the paper coming out that if you do four, and you have some kind of a scoring system that is as sensitive as single fiber EMG, which still, the serological testing and the single fiber, they still remain yardsticks off. The single fiber EMG cannot confirm pre or post ganglionic, but can confirm a neuromuscular junction disease for sure. And then the serology will be the way to go. But you are doing a more than average job in your lab. You had another question, maybe four minutes? Yes, in fact I briefly mentioned that, but as a passing comment, is that if you look at the most commonly used textbook on EMG, it says everything that I mentioned should be repeated two to three times. But then just before a few days coming I checked with our technicians and they said no, we do not repeat. What we do is we know what we're doing, and I've been giving lectures every year, and then we see the baseline, we have extra person going for the immobilization, and our attending is always present in the lab. So immediately the attending looks and says got it. So you don't have to repeat two or three times because we got it. But there is no standard practice. If you are doing it, the CMAP obtaining two to three times, you are ensuring that you got the best results. So again, you are just like her, also running at a more than average accuracy level, whether that is absolutely needed, and if so, how much unpleasantness you have to create before you have one gain, I don't think there is any study on that, or at least it's not a widespread knowledge. But if you continue to get good results, that will require a publication so that we all can say, hey, change your modus operandi, do her way, your way. But that's a good time. Yes. Thank you. Might be the last one, two minutes. Baseline CMAP is flat. What do you mean by flat? I'm sorry, there's no amplitude. No, no, no, not for baseline. You have to have a sizable CMAP and in fact that's a question. In severe cases of myasthenia gravis or more commonly in lumbar-return myasthenic syndrome, the supermaximal CMAP is so low that it is statistically very difficult to show any decrement or facilitation and then the value of the question is questionable. So if you have a flat CMAP, go to another muscle until you have some acceptable CMAP so that you can do the RAP stims and then go for one minute exercise for exhaustion and 10 second exercise. But if you have a muscle, and that's why it is important to do the general sensory motor EMG before RAP stim. If your ADM shows nothing, don't do ADM. Go to trapezius. There should be something over the trapezius or go to the facial muscles. A flat EMG, that means you cannot do anything. That is the purpose. In many cases with myasthenia gravis, with the RAP stim, there is decrement but not 10%. So then you do one minute to accentuate the decrement to make sure now it goes to beyond 10%. So the one minute is needed. In fact, the opposite question is more relevant, which I was doing but the technicians were confused is A, suspected myasthenia gravis patient, baseline CMAP is normal. You just did 3 hertz stimulation and your decrement is 18%. Do you still have to do one minute exercise and keep shocking 0, 1, 2, 3, 4? The answer is no. You do a 10 second exercise and see how much is the facilitation. You are done with the testing and such a method is in use in University of North Carolina, if I'm not wrong, by a very eminent person who is also here presenting. But that is, I try to implement that and the technicians say let's do same way for everybody. So if you do not see decrement, then you have to do the one minute exercise to see if you can bring on the decrement and then go for 10 seconds to see if you can repair or go for facilitation. But if you have already seen more than 10% decrement, why do you do the one minute exercise? A big question. There is no standard answer. You do not have to do that technically. And some books, not all the books, not the common popular, most popular books, but some other publications have briefly mentioned that view. And I'm sure some of the big labs also do that. But you need the presence of the interpreter to be there so that you can look at that and say done, do the 10 second now. But if the attending or person says I'm coming and comes after five minutes, you have to repeat the whole thing. But the opposite is true. If you don't see decrement, then you go for a one minute exercise, of course. Well, I think thanks to all of you here as well as those who are present virtually. Thank you.

repetitive nerve stimulation

neuromuscular junction

nmj

myasthenia gravis

Lambert-Eaton syndrome

compound muscle action potentials

supramaximal stimulation

calcium channel function

electrode placement

decrement and facilitation

acetylcholine breakdown

test sensitivity

technical execution

clinical interpretation

nmj

neuromuscular junction