So we're glad you're here this afternoon. My name's Candy Dolan, and I'm the course chair for this talk today. And I'm rotating off as the co-chair for the Education Committee for Technologists. So I'm just going to introduce our two awesome speakers. First is Dr. Anne Little. She works in Ann Arbor, and she's ABEM certified in EMG. She has clinical evaluation and electromyography on patients with neuromuscular disorders. She is the electromyographer for brachial plexus and the peripheral nerve program of nerves with neurosurgery and involved in IOM, particularly of the peripheral nerve and plexus cases. She's involved in education of fellows, and I hear she is a big Pokemon player and runner. Yeah. I had my intel. Anyway, Dr. Clark Moser, who is one of my attendings, he grew up in rural Indiana. He received his degree in biomedical engineering from Rose-Hulman Institute of Technology. He went to medical school at Indiana University. He was the University of Utah chief resident in his residency there. He did his fellowship at the U of U. He's an associate professor and assistant program director for the neurology residency program, and he is the fellowship director for neuromuscular. And he and his wife have two cute dogs, and he enjoys baking pies. And I will throw in, makes really good homemade ice cream. So yeah, pies and ice cream after on Dr. Moser. Yeah. OK. So I'm going to turn the time over to Dr. We're going to save questions for the end for both, and you'd be able to come up here. Make sure you fill out your surveys and you get your checkpoints if you're a technologist. Out of curiosity, how many here are technologists? Good chunk. How many are physicians? Good. OK. I'm going to turn the time over to Dr. Little. Thank you. So our topic is everything you wanted to know about nerves and were afraid to ask, and mostly targeted for technologists, but also young physicians doing their own nerve conductions. And there's no way I'm going over anatomy. You know where to put your stimulating and recording electrodes and everything. But what I really want to talk about is more is pathophysiology, why we do what we do, so that we understand and don't make errors or send in bad reports to people. And so we'll be discussing the pathophysiology. I'll be doing basic nerve conductions, and Dr. Moser is going to talk about some more advanced nerve conductions. And if there's anything highlighted in red, it's kind of a pitfall you can pay attention to, but our main point is not pitfalls. So think about basic nerve pathology. And I like to think of nerves as a nerve as a cable of wires, axons. Now those axons are not all of the same sizes. They have different diameters. And the larger wires you can see in the large white spots are the axons. And you can see that many of them are very thick black rings around, which are the myelin, and then varying sizes with lesser rings of myelin. Now it turns out that when you apply an electrical stimulus, the largest fibers, the ones with the biggest diameter, are the very first that are activated, that respond to your stimuli, that depolarize. And they send the electrical current along their length. You have to keep increasing your stimulation so that you are stimulating all the wires in your cable, the small ones and the large ones. The very smallest diameter axons have the greatest resistance, and they're going to need the highest level of stimulation to depolarize. If any of you are still getting ready to take any of technologist exams, you're going to see on there somewhere, Ohm's law, that V equals IR. The greater the resistance, the more voltage you need to activate or depolarize that axon. And those are going to be the small ones. They're going to depolarize the last. So it's very important. It's why we increase the stimulation. We want to make sure all of the nerve fibers in a nerve depolarize. Why is it not advancing? Oh, there we go. Or did it advance too much? No, it didn't. OK. So basically, if we talk a little bit more about the electrical conductivity of axons, basically there's a difference between the inside and the outside of your nerve cell of about negative 70 to negative 90 millivolts. When you get down to about 55 or 60 is when you get depolarization. So you basically, with your electrical stimulus, you're depolarizing that axon membrane above resting membrane potential to create an action potential, which then travels down the axon. And if you do not have the myelin available, your nerve conduction velocities are only going to range from like 0.3 to 5 meters per second. And you're probably all going, wow, that's slow. Because we know that in our nerve conductions in regular EMGs, we're going to be seeing 40, 50 meters per second in normal nerves. So why do they conduct at such high speed? And it's because of the myelin and saltatory conduction. When you have a myelinated axon, all the ion channels tend to cluster at the nodes. The nodes are the spots between the bits of myelin created by the Schwann cells. So the Schwann cells wrap in myelin. There's multiple Schwann cells along the length of the nerve. And you have nodes between. And when you do that, what happens is the electricity jumps from node to node. And so we always make cartoons, as you see on the right, where we have to show the nodes. And we make them look like they're very close together. Well, guess what? They're not. So if you look down there at bottom left, you'll see that the arrows are pointing to nodes. And in your myelinated axons, you can see that the distances between nodes is quite significant. And so if you are jumping your electrical stimulus from node to node, it increases the speed remarkably. And when you depolarize the cell, we know that the electrical basis of axons is all based on the ions and ion channels. So when you depolarize, you're opening your sodium channels. And then there's a sodium-potassium pump inside the cells that try to repolarize it and close the ion channel. So I'm going to, and if you remember, the topic was all about questions and what you were afraid to ask. And you're probably not afraid to ask. But I'm kind of doing a question format. So why do you warm up a patient? So ion channels are temperature regulated. They open more slowly in the cold. And because they open more slowly, more sodium flows out, and you get a higher amplitude. And you also, because of the cold, you get a delayed latency. And it also takes longer for the ion channel to close down with the sodium-potassium pump. So you end up getting a much higher amplitude of electrical response. So look at the picture on the bottom. This is the same patient, cold and warm. So at the top, you'll notice that it's clear even from the back of the room back there that you've got a much higher amplitude response. And you may not be able to read from the back of the room the latency on the blue chart. In fact, I'm having trouble reading it right here. But it is quite a prolonged latency compared to the bottom one, where the patient has been warmed up with a skin temperature above 32 or 33 degrees centigrade. And you're seeing that then you have a lower amplitude, which is still within normal range, and a much faster latency, which, of course, will give you a faster or more normal conduction velocity. If you are not warming the patient enough or properly, sometimes it takes more in the winter, you may be giving the patient a diagnosis of having a demyelinating disease. And then they have to go through a lumbar puncture and a nerve biopsy. And they might get some horrible medications. So very important to make sure that the patient is warm enough that you've maximally stimulated the nerves so that you get an excellent response. And why do you stimulate at two points to get a motor conduction? Well, if you are depolarizing a nerve, the depolarization is going to move down the nerve. Then you're going to release acetylcholine into the neuromuscular junction. And that is going to diffuse and hit the muscle receptors at a different speed than the response down the axon. And the muscle depolarization itself is a very different phenomena and much different velocity. So you've got to get rid of the contraction speed of the muscle and the speed across the neuromuscular junction. So what you're going to do here is you're going to take, we know that velocity very simply is distance over time. I mean, that's it, distance over time. So when you are stimulating, we always measure the distance between our stimulation proximally and distally. So there's your distance. And that's the speed. That's the area of nerve over which you want to see what the speed is. And then the time, basically, your computer is measuring that for you with your latency. And you can subtract your latencies and know that the time it took to go across that measured distance. So distance over time. And that is, so any time you need a conduction velocity on a motor nerve, you must stimulate at two points. So why don't you do that on sensory nerves? Well, you don't need to. Because when you stimulate and record, you're only doing it over a nerve. You can get a conduction velocity. But sometimes it's helpful. And you can use two sites if you would like to. And particularly if you have a question about a lesion at a certain site. But be careful. This is one of the things we like to sort of drum into our fellows, is that if you do a proximal stimulation of a sensory nerve, you can get an amplitude that's quite low. Even 50% of the distal stimulation. And so why is that? Well, it's phase cancellation. Basically, because you do have slightly different diameters of axons, and they're conducting at slightly different speeds, the positive and negative deflections can cancel out. On the right, you can see a distal stimulation. And you see a nice pointy sensory response. And then when you stimulate proximally, this is in a healthy individual, you see that your response is, I don't know, at least 50% of the other one. And so basically, why doesn't that happen with motor nerves? Well, when you get a motor nerve response, the duration of the response is about five to six milliseconds. So you don't get, even if you get the responses a little offset, you don't get the phase cancellation. Sensory responses, the duration is only about one, one and a half milliseconds. And so it's very easy for those negative and positive deflections to start canceling each other out. So your normal compound motor action potentials don't have a significant temporal dispersion or a phase cancellation. And the amplitude drop distal to proximal is usually less than 20%. We'll talk about conduction block in a little bit. And that's all about the duration of the response. So be very cautious about that, because that's something that can be a problem. And also, think about it. Sensory responses are so small. Yes, they are. We're measuring the amplitude in microvolts, yes. And we're measuring the motor nerve amplitudes, response amplitudes, in millivolts. That's 1,000 times difference, folks. And it's probably been drummed into everyone here. You need to really sort of move your recording electrode. You've got to get a flat baseline on your responses. The picture there is where you have a dip before you see the negative deflection. And so if you move your recording electrode, you get it right over the belly of the muscle, where the most of the neuromuscular junctions are, and you get no dip. And that would be the correct way to do it. So if you don't have a flat baseline on a motor conduction, it's generally an error of electrode placement. And you can often, it's not unusual to get a dip if you have a particularly atrophied person, because where you think the usual belly of the muscle is, there's not much belly left. And you may have to sort of move that electrode around to get a good response. So moving the recording electrode is how you fix your dips on motors. What about sensories, though? Well, and sensories, remember, they're so small. You want to accurately record an amplitude and your latency. And you can see here in the picture on the right, you can see where we don't have a good baseline on the top response, or the bottom one particularly, but we have a nice baseline on that middle one. And this is not a problem with electrode placement. With sensories not being flat, it's really more an issue with stimulus artifact. And there are a number of things to think about in trying to fix that. You want to make sure that you've got the ground between the stimulating and recording electrodes. You want to make sure your cables aren't tangled up. You want to keep your G1 and G2 cables away from your stimulating cable. You want to, the two things underlined are probably the biggest things that are going to fix you. And that is decreasing your stem intensity. You might be stimulating, overstimulating. And most often, rotating the anode while keeping the cathode in place often straightens out your baseline. You can also, if you're still having trouble, you can increase the distance from the stimulator and recording electrode. And then again, patients do tend to put lotions and creams on their skin. And you may need to get an alcohol pad out and reduce the impedance by cleaning the skin. You may need to apply more gel to your ground. Check that your ground hasn't fallen off and other things. But usually with that either uphill or downhill baseline, rotating the anode while you maintain the cathode is a great way to go. So what's the difference between a motor unit action potential and a compound motor action potential? Well, the motor unit action potential is basically the response of all the muscle fibers that are innervated by a single nerve cell. And that's really only assessed on the needle EMG. So when the docs are performing the needle EMG and you see all those spikes coming in, each spike is just all the muscle fibers responding from a single nerve cell. That's still kind of, I find that still sort of remarkable. But in your compound motor action potential is what you're dealing with in nerve conductions. Basically you're trying to stimulate all the axons in a given nerve and you're seeing the muscle response of all the many muscle fibers connected to all of those nerves. Compound meaning you've got a lot of those. And that's, you're assessed on your nerve conductions. So we often think about amplitude as basically a measure of how many axons are in a nerve. And we have normal lab standards. But remember your sensory nerves are a direct measure if you do it correctly, because you are stimulating over nerve, you are recording over nerve. When you do a motor conduction, you're stimulating a motor nerve, but you're using the activation of the muscles as a surrogate response. So if you have an amplitude of a compound motor action potential and it's low, do you have a problem with that motor nerve? Do you have a lot of axonal loss? Could, but you don't have to. It depends. Because it's an indirect test, you are relying on the integrity of the neuromuscular junction and of the integrity of the muscle. So if you have any large abnormality or disease of the muscle, for example, your compound motor action potentials are gonna be affected. Or if you have a problem with the neuromuscular junction where you're not getting the stimulation, or you're not getting the release of acetylcholine, or in myasthenia gravis, for example, there's not enough receptors for the acetylcholine. So you would see quite low, you could see quite low amplitudes of your compound motor action potential, for example, in myasthenia, limbs, botulism, end-stage myopathy, it's gotta be pretty bad. Clinically, hopefully, you can already tell that. And metabolic dysregulation and also certain toxins. So does any, just a quick aside, once in our lab, we did motor, we did conductions on a patient with very bad diabetes and I think their sugar was up in the, I don't know, 700s, it was, how much? 800s? It was in the 800s. And they had very slow velocities. Kind of looked demyelinating. They went upstairs, got an insulin drip, came down the next day, and they had absolutely normal conduction velocities. So incredibly high glucose, for example, can, it affects how the depolarization is happening and the speed of conduction. So metabolic dysregulation can give you some problems. But sensory nerve conductions are a direct measure of intact sensory axons. Nothing there involved in the response. So does slowing of your conduction velocity then, does it always represent demyelination? Well, I kind of just gave you a clue. Could be metabolic dysregulation. So, no, and you have, and when the physicians write the interpretations of your nerve conductions and their EMG, I often see this mixed demyelinating and axonal process, which drives me nuts, because very few things, uremia and diabetes, and I think there was a case today where there was a mixed picture, but it's pretty rare. It's usually like primary demyelination with secondary axonal, but you have to be careful about this kind of thing. Remember, the axons with the largest diameter are the ones that are conducting the fastest, and therefore, when your response leaves baseline, that's a reflection of the fastest axons in your nerve. So if you have had loss of enough of the largest axons, you're going to slightly slow your conduction speed, and it might be just below normal. So if you look at this example here, you'll see that you have a low amplitude of the tibial motor response, both on the right and the left, and if you look at your latencies, they're pushing the limits. They are in the normal range, but they're pushing the limits, and when you work it out, your conduction velocity is slightly reduced on the right and barely normal on the left. You look at the peroneal, or excuse me, fibular response, you're again seeing a low amplitude below normal, and you're seeing, again, pushing the limits, but still a normal latency, but you're seeing velocities of 39 and 37 meters per second, and those should be above 41, or in this lab, apparently, 44. So they're slightly reduced, and so this is more likely to be the dropout of the largest axons rather than a demyelinating case, but some people will look at this and say, oh, it must be demyelinating, and then go off in a long workup unnecessarily. So what are the criteria for demyelination anyway? And there are many criteria, and you can get out your calculator, and I'm just doing thumbnails here, folks, so don't yell at me. Anytime your conduction velocity is less than 75% of the lower limit of normal on a motor study, or your distal latency is greater than 130% the upper limit of normal, then you are probably meeting criteria and perhaps need to pull out a calculator in the full criteria and figure it out. And if you're looking at it and you're not sure about 75% the lower limit of normal or 130% the upper limit of normal, an even more gross thumbnail is basically anything under about 35 meters per second in the upper extremity or less than 30 meters per second in the lower extremity, you need to start wondering whether there could be demyelination. So why does my proximal motor response look so awful? Well, we're sort of on a demyelination topic here. And when we have acquired demyelinations, and that would be something like Guillain-Barre, AIDP, CIDP, when you do your distal stimulations, you're going to find that you've got a fairly good-looking response because you are stimulating over a fairly short distance, and so there's not that many areas where perhaps there are chunks of myelin missing. So if you look at the top right photo, when you're stimulating you get a fairly normal-looking response. As you move proximally, though, you are then stimulating over areas of the axon where there's a number of nerve fibers that are missing maybe a little bit, maybe a medium amount, maybe a lot of myelin. And so you start having the responses come in at far different times, and therefore you do start to get phase cancellation in a motor nerve. And then in this sample, someone then went up to Erb's point, and you can see what I call kind of the rat bite phenomena. You see a tremendous dispersion in time of those responses coming in, canceling each other out at different points. So any time you see that, and that's not always something that the machine is recording for you. You need to take a picture of it and make sure there's comments and that everybody knows that's there because this is one of the pathognomonic features of acquired demyelination, not hereditary but acquired. And I should point out the lower picture on the right is actually a teased fiber preparation of someone's nerve who has AIDP or CIDP, and you can see it's with a myelin stain. So you can see that the dark brown are well myelinated axons, and you can see that there's a couple that are stripped bare, and so they may not be conducting at all. And there are several others with just patches of myelin missing. And so when the patches of myelin are missing, the saltatory conduction may not get across that block, or it goes saltatory until it gets to that area and then proceeds at 5 meters per second until it gets to the other end and then goes saltatory again. So if I get a low amplitude of my motor response, is it always axonal loss? Well, no. I mean, it could be. Alternative explanations are, for example, if you have a problem with a presynaptic neuromuscular junction, that would be something like Lambert-Eaton or botulism, and that's when we sort of our eyes light up and we have the patient exercise their muscle. If they can't, if they're in an ICU, we might apply 50 Hertz stimulation. And on the right, you can see that the initial stimulation was very, very low motor amplitude. And then the patient can be exercised. If you're doing the ulnar nerve, just 15 seconds of abducting or pressing your fingers apart will result in that second waveform, which if that's who I think it is, that's 1,000 times facilitation. So typically, Lambert-Eaton, when you see facilitation, facilitation meaning that huge increase in amplitude with exercise, when you see facilitation in Lambert-Eaton, it typically is over 100%. Botulism, maybe not so much, about 70%, but it's usually pretty obvious. And the waveforms on the left are basically done with the person exercising and doing a single stimulation. The waveform down there on the right is what happens when you do 50 Hertz, what you would see. You would see the response very small and then very quickly, over a second or two, build up huge. And then the other reason that you might see low amplitude of motor responses is just end-stage myopathy. You just don't have the end-stage muscle to be able to give you that surrogate response. So I can't get a decent amplitude when I stimulate proximally. Why not? And we had just talked about diffuse acquired demyelination in an autoimmune disorder. This would be focal. And think about carpal tunnel. Think about an ulnar neuropathy at the elbow. Think about a fibular neuropathy at the fibular head, or any kind of entrapment. And this is where you are basically putting enough pressure on a certain portion of the nerve that you rub all the myelin off. And so what happens is some of those nerve fibers are not able to conduct the response across the denuded area. And so you end up getting a response when you stimulate proximally that may not be as big as your distal response. And typically, in our labs, we call a 20% drop in the motor conduction from distal to proximal for us as conduction block. Preston and Shapiro might say 30%, but 20% to 30% drop will give you a conduction block. And you can see if it's very focal, you don't actually change the way the response looks. You just change the amplitude. You still get a good response. And on the bottom left, there's a very nice picture of showing you that you still have well-formed responses, but you get a drop, and that's not a sensory. Because if it were a sensory, we all now know that could be normal. So this is something I pound into our fellows too because it shows up on all of our board exams, that the pathognomonic findings on nerve conductions for acquired demyelination are temporal dispersion and conduction block. Now, you don't always see it because patients don't always read the book, but it's something that you should always be aware of and look for. And again, that's that same picture I showed you that has both conduction block and temporal dispersion demonstrated nicely. So how do our sensory nerve conductions help localize lesions? Well, if you have a normal sensory nerve conduction study in a person that's having sensory loss, that suggests that you have a lesion proximal to the dorsal root ganglion. Remember, all the cell bodies and the nuclei are in that dorsal root ganglion that you can see coming off the spinal cord there. So if you pinch the nerve root proximal to that, you've still got living cells, and you're going to get a good response. But that patient's going to say, Oh, no, I'm numb. If you have abnormal sensory conductions, it suggests that there's something post-ganglionic going on more distal to that dorsal root ganglion, and that's where it's not real specific. You could have a plexopathy. You could have a mononeuropathy. You could have a neuronopathy with something actually damaging the cell bodies within the dorsal root ganglion or a peripheral neuropathy. But our EMG and nerve conductions are an extension of our history and clinical exams. So hopefully, if you put it all together, it will help you figure it out. This is just one slide. Sorry, Dr. Moser. When do you use repetitive stimulation? When you're concerned about a neuromuscular junction disorder. We talked about presynaptic getting facilitation, that huge response after a small response. And post-synaptically, myasthenia gravis, you're looking for a decrement, and I think you'll hear more about that. And finally, what are those proximal late responses? When do we use those? What are they? How do you do them? So F-waves are not a reflex, because a reflex has to have a synapse, has to have something in, synapse, and something out. And so the F-waves, basically, we are stimulating a motor nerve, and if you look at the bottom left, the response travels up, and it sort of backfires into the anterior horn cells, and then about 1-5% fire back down the pathway, and we record those. So you have to really turn up your gain, because you're only getting 1-5% back, and you've got to really increase your sweep, because people's legs and arms are long. We usually, at least in neuromuscular, our biggest use of F-waves, you can use them for any kind of proximal demyelination or injury. Our favorite time to use them is we will do an F response on any motor nerve that we can in a person when we suspect an acquired demyelination, like AIDP or CIDP. You can, of course, for radiculopathies, use them as well, or plexopathies. H-reflex is a true reflex. Got a synapse. Basically, it's equivalent to the S1 ankle deep tendon reflex, so it's kind of limited in what it can tell you, because it's usually done on the tibial nerve. You're stimulating the tibial nerve at the popliteal fossa with your cathode aimed up toward the body, and you're recording as the motor response comes back down over the gastrocnemius or the soleus. And what do they look like? Well, when you do F-waves, we do a whole maybe 10 of them, or less if the patient doesn't like them. And you measure the shortest latency, and that sort of tells you what your largest axons are doing. And there are normals for the upper and lower extremities. The H-reflex, basically, you're... I'm going to advance this for a minute, because... Nope, nope. Hang on, we're going back. So the H-reflex here, when you stimulate just a little bit, for some reason, the first thing you get is you get... You start to get the motor response. The sensory has gone all the way up to the spinal cord, come back down, and you start to see the motor response. As you increase your intensity, what happens is... I'm going to go back again. Oh, did I go back? No. Yes. As you increase the intensity, you start to send the electrical... You start to activate the axon that drops immediately just down to the muscle. So you start seeing the M-wave, or the muscle response. And when you stimulate high enough... And so as you stimulate high enough, you start to get collision of the responses going both ways in the motor axons. And so finally, as you stimulate at very high... At higher stimulation frequencies, you're only seeing the M-wave, and the H-reflex has been demolished. So... And then the other thing is we're looking at... If you notice on the F-waves on the left, you see there's something that keeps repeating at exactly the same spot. That's your axon reflex. And that's interesting as to what it actually means. Again, it's not a reflex, although it's called that. And it reflects reinnervation after denervation. Because again, if you look at a nerve cell coming down, you're just getting an M-wave. If you have reinnervated and sent off a little sprout of your nerve to pick up another muscle cell, you also... You have the M-wave, and then you have where some of your stimulation went proximally and then traveled down that extra little sprout, and then you get... And because it's always the same distance, it always looks the same. Now, if you stimulate even more, you will get rid of it again by collision. So what an axon... Oops. What an axon reflex tells you, it tells you that reinnervation has taken place, and it tells you you are not stimulating supramaximally. So you should be able to obliterate it by increasing your stimulation. Ooh, I have 45 seconds. So last two slides. You're having a bad day. Well, my waveforms, they're just no good. What am I doing? Well, have you maximized your stimulus? Because it is very important that you maximize stimulus. You don't want to overstimulate sensory nerves. They actually start going down in amplitude if you do. You get them tired out. But you need to maximize, certainly, your motors. Have you moved the stimulator to make sure you're over the nerve? Because you're going to have to give... If you're not over that nerve, you're going to have to really hurt that patient with a really high stimulus to get that nerve to activate. Did you replace your recording electrode properly? Is it over the end plate of the motor nerve with the reference over a bony prominence? Or is it over the sensory nerve with 2 to 3 centimeters between the recording electrode and the reference electrode? Measurement. Did you make a problem with measurement? Did you reverse your anode and cathode? Even small errors in measurement are going to really change your conduction velocities. Remember that skin distance doesn't equal nerve distance. When you're measuring your distances to do your distal and your proximal stimulation, you want to think about where is that nerve inside the arm or the leg. That can be particularly difficult, especially in chubby little babies. Finally, are they warmed up? Are they better than 32 degrees? Were you hurrying that day and it was winter and you just got the surface of their skin warm? Sometimes you have to, you know, put them under some warm towels for a little bit longer. Did you think about patient physiology? What if you have a basketball player in there? Nerves taper distally. It slows conduction velocity in people over 6 feet. It's not unusual to see a little bit of a slowed sural sensory response. And your F wave is going to take more time in a tall person because, remember, it goes all the way up and all the way down, and they have long legs and long arms. There are tables that do adjust for height, by the way, and then age makes a huge difference. Velocities can decrease by a half to 4 meters per decade, and this is due to axon dropout with aging. That's completely normal. There are, I think our lab has tables, sort of our averages are for people 10 to 60, and then we have some special values for people that are up into the 70s and 80s. You know, have you, you know, gotten that, are they, when you're in the ICU, do they have a lot of swelling? Is there, you know, edema? Are there skin lotions? How can you maximize what you're doing? And finally, you've seen those patients, especially electricians that are just jerk every time you stimulate them, and that's very hard to get a decent thing. And I had a case, and I'm going to tell you real quick because I'm out of time, is what's, and so if we do the conduction velocity here, what are we going to do? We're going to take distance. We've got 125 millimeters, right? No problem. Over time, so 5.6 minus 4.6, what's that? One. So is that patient, they're conducting at 125 meters per second. Anybody got a problem with that? Okay, so, and, but what do you notice about it? Look, the distal amplitude is less than the proximal amplitude. Well, so go back down, make sure you're maximized. You are. And so, basically, you've got more axons that you're stimulating up there proximally. Where did those extra axons go? Well, I think they jumped onto the ulnar nerve and bypassed the carpal tunnel because I think you've got a Martin Gruber anastomosis and a median mononeuropathy at the wrist. And I will now, at this time, turn this over to Dr. Moser after having stolen two minutes of his time. Thank you. And I realize now that I will probably do better if I have... Oh, it does work better now. Can you guys see this okay? Previously, at our angle, we couldn't tell it was working, but he must have warmed it up. Okay, so today I'm going to be talking about repetitive nerve stimulation and cranial nerves. I have nothing to disclose. That's right, I can look down here. So my two topics here, they're related only geographically. Philosophically, they don't really have a whole lot to do with each other. So they're going to be kind of two somewhat separate topics. We're first going to talk about the differential diagnosis for why you might perform a repetitive nerve stimulation test. I'm a little bit about the history of the test itself, how to perform the procedure, how to interpret the results, and what are the common pitfalls that you see when performing repetitive nerve stimulation. We're also going to look at cranial nerve, nerve conduction studies, and in particular looking at the blink reflex, the facial nerve, and the spinal accessory nerve. So thinking about repetitive nerve stimulation, what is the differential diagnosis? So there's three diagnoses. You've probably heard of all of them. Myasthenia gravis, I'm going to have just a few tidbits about each of them just to remind us. Myasthenia gravis is an autoimmune condition that typically has antibodies against the acetylcholine receptors, and these patients usually have oculobulbar more so than limb weakness. You've got Lambert-Eaton myasthenic syndrome. This condition is autoimmune or is more frequently perineoplastic, like autoimmune reacting to cancer. You have antibodies against voltage-gated calcium channels, and in contrast to myasthenia gravis, this one tends to be limb weakness more so than oculobulbar. And then for botulism, this is a toxin usually from dust, food, or wounds, and this is usually a pretty severe, abrupt onset of descending weakness that starts up in the face and then works its way down the body. Now I listed all three of these as different bullet points with approximately the same amount of ink on the page, but what is important to know is that when you're performing repetitive nerve stimulation in real life, 99% of the times you're going to be looking for and potentially making a diagnosis of myasthenia gravis, and these other two diagnoses are exceedingly rare, both in terms of how often you'll find them and also in terms of how frequently you're looking for them. I bring this up just to say that a lot of the data and stuff that I'll say about repetitive nerve stimulations has much more to do with the myasthenia gravis population than these other two because of how more common it is. So this is just a graphical representation of my description previously of patient's weakness in these three disorders. The shaded areas here are meant to represent more shade, more weakness. So myasthenia gravis, you typically get more oculobulbar symptoms than you do proximal weakness of the arms and limbs. Lambert-Eaton is kind of the opposite with an even higher emphasis more on the legs than on the arms. And then in botulism, the downward arrow suggests the time course of descending weakness, but it typically is very severe. In a lot of patients, they end up more or less seemingly fully paralyzed within hours. Maybe. There we go. So the time course for these disorders. So myasthenia gravis is in the black here, and there's actually two potential time courses with which myasthenia gravis might present. The patient might present with a subacute course over the course of weeks to months where they have kind of a slow worsening of their weakness that kind of ebbs and flows. Or you might have this abrupt downtrend here over the course of hours to days, and we would call that myasthenia crisis. Lambert-Eaton here is similar to kind of the slow course of myasthenia in the sense that it tends to be kind of subacute over weeks to months with a slow downtrend. And then botulism mimics myasthenia crisis where it's an abrupt worsening over the course of hours to a day or two. Dr. Little already mentioned a little bit about the pathophysiology between postsynaptic and presynaptic neuromuscular junction disorders. I'll kind of highlight here. I feel like this gets tested at every level, like when I was a med student, when I was a resident passing my general boards and then my subspecialty boards. It's always an easy question to write to differentiate postsynaptic versus presynaptic neuromuscular junction disorders. So on the left here is just a reminder of basic neurophysiology of how the neuromuscular junction works with acetylcholine packets coming off the nerve terminal, going towards the muscle end plate, connecting with the acetylcholine receptors that change the muscle end plate potential and create action potentials within the muscle fiber and create strength. In myasthenia gravis you have blockade of this with acetylcholine receptor antibodies, so this is postsynaptic because it's on the muscle side, so this is the postsynaptic neuromuscular junction disorder. And then for Lambert-Eaton and also botulism, these are presynaptic disorders where either the antibody in the case of Lambert-Eaton or the toxin in the case of botulism affects the nerve side of the neuromuscular junction, and so we call that a presynaptic neuromuscular junction disorder. So repetitive nerve stimulation is a procedure that was originally described by Friedrich Jolly. This was back in 1895, and this was actually done using mechanical recordings of strength rather than recording voltages, so stimulations of the nerve, but then actually seeing how well does the muscle contract mechanically. It wasn't until the 1940s with Harvard and Maslund that this was recorded electrically and also around the same time, we're gonna talk a little bit about the frequency with which you can stimulate in repetitive nerve stimulation tests, but this was also the time that they very easily demonstrated that generally slower frequency of stimulations is better than faster. And then from the 1950s to the 2000s, there have been a lot of people who have contributed to the field of repetitive nerve stimulation tests with a lot of different positive outcomes in the sense of what we've learned about them, testing very different muscles in different conditions and also outlining the sensitivity and specificity, which we'll talk about today for myasthenia gravis. So this is just another pictorial in slightly more detail of the neuromuscular junction. So you've got an action potential that's coming down the axon of your nerve fiber here. It creates or causes an influx of calcium that allows release of acetylcholine into the neuromuscular junction cleft. That acetylcholine goes across, connects to an acetylcholine receptor, which allows influx of sodium from the exterior to the interior of the muscle fiber. And that creates and contributes to the overall end plate voltage potential of the muscle fiber, which will then dictate whether or not it creates its own action potential and generates strength. So when we're doing repetitive nerve stimulation tests and we're stimulating a given nerve four, five, six, seven, eight times in succession, that's what this graph here is going to represent. In particular, this graph is gonna represent not like what you would typically see for doing a standard repetitive nerve stimulation test, but what this represents is the end plate potential, so the potential down here of this single muscle fiber. So not of an entire study, not macro, kind of what we're looking at with our machines, but what this would look like microscopically with a single muscle fiber. It's important to remember that action potentials both in the nerve fiber and in the muscle fiber are all or none phenomena. So it either happens or doesn't happen. It doesn't happen just a little bit. So here, I just described, you come down here, you release all this acetylcholine, you allow an influx of sodium, and it changes the end plate potential of this muscle fiber. So if you do that the first time, and this is a voltage here, so your voltage is a certain amount, and this dotted line is meant to represent the voltage that is necessary to generate the action potential, to trigger the action potential in the muscle fiber. So here, it fires once, it easily crosses the threshold, so that would generate an action potential here in the muscle fiber. Similarly, you do it again and again and again. Each time you reach threshold, and therefore you generate an action potential. So every time that this fires, or sorry, every time the action potential comes down the axon, either from naturally, from the patient contracting their muscle fiber, or from you doing the test in the lab, you're generating an action potential each time, even though the end plate potential is actually getting a little bit worse, a little bit weaker every time. That's in a normal patient. In a patient who has a postsynaptic disorder, like myasthenia gravis, so here you've got your blockade of the postsynaptic cleft. Here in this example, the first time it fires, it goes above threshold, so this time the action potential fires, this time the action potential fires, but now we're suddenly below threshold because we're losing strength here in our end plate potential so these three times, there is no action potential, there is no strength generated. Then this last example of Lambert-Eaton, or botulism, a presynaptic disorder, very frequently, many of the fibers, not all of them, but many of them, even from the get-go, will not reach threshold, so every time that an action potential is coming down the nerve axon here, it is not correlating to an action potential in the muscle fiber. This is gonna be kind of a three-tiered diagram again, looking at, on the left side, will be what it would look like for a single nerve and muscle fiber. On the right side, it'll represent what an actual series of C-maps would look like with repetitive nerve simulation tests in the lab. The most important thing to remember here is that on the left is a single fiber, on the right represents a whole bunch of fibers, and in these conditions, not all fibers will be affected identically, and I'll try to illustrate what I mean by that. Here, I kind of already described this verbally how every time it meets threshold, and in general, for most patients and most muscle fibers, that'll do it in such a way such that the C-map amplitude remains consistent from firing to firing. In a postsynaptic neuromuscular junction disorder, again, in this single muscle fiber, these last three times, there was no firing, so if all the muscle fibers in a given nerve and the muscle fibers connected to that nerve were all identical to this, you would get two firings here and then none at all. It would go down to zero, but that's not actually what the population of the nerve and muscle fibers looks like. Some of them are more affected than others, and as a result, you get kind of a mixture where it starts out pretty good, and then it dips down and more reflects the end plate potentials, even though action potentials are all or none phenomena. This reduction in the C-map amplitude is what we refer to as decrement, and is how we define a positive test in the majority of cases when we're looking at neuromuscular junction disorders. For presynaptic disorders, here you've got, again, a single representative fiber, which would not generate any action potentials at all, but then there are other fibers that probably would in this muscle. As a result, the initial C-map here is low compared to the normal and compared to myasthenia gravis, but it still experiences a difference in decrement. Another thing I meant to mention about the decrement is that it's pretty typical for your nadir, your lowest C-map, to be at the fourth or fifth stimulation when performing repetitive nerve stimulation at two to three hertz. Okay, so on this slide, the left side will be what we just looked at, so we're kind of carrying it over, and on the right will be what we'll see with the same repetitive nerve stimulation performed, like at two to three hertz, but after 10 seconds of isometric exercise. So in the case of, if you were doing this on the ulnar nerve, for example, that would be 10 seconds of spreading your fingers very wide against resistance. So in a normal case, everything stays normal. Normal is normal, right? So in a normal case, the amplitudes stay normal throughout your first set of firings, and then after 10 seconds of exercise, they stay normal yet again. For patients with myasthenia gravis, we just showed how you have this decrement after your baseline repetitive nerve stimulation tests, and then after 10 seconds of exercise, you find that there is a partial repair of that decrement. So the decrement is no longer as bad as it was before, and the reason for that is probably because there is additional acetylcholine that is rushed down from higher up in the axon to try to come out into the synaptic cleft and overcome the severe blockade of the acetylcholine receptor antibodies. Then in presynaptic disorders, again, I wanna highlight that the initial CMAP here on the baseline repetitive nerve stimulation test is low compared to the postsynaptic and the normal examples. You still saw the decrement, and then after 10 seconds of exercise, you see an increment. So here, kind of similarly to what I just described as part of the repair mechanism, you have this huge influx of acetylcholine packets that are available at the synaptic cleft, and that allows much more acetylcholine to get across the synaptic cleft, depolarize more muscle fibers to action potentials in creating a larger CMAP. There is also a partial repair of the decrement here as well by the same mechanism. The last kind of exercise phenomenon I wanna talk about is something that we typically see in myasthenia gravis that's called post-exercise exhaustion. So these series here, this is a baseline CMAP like I originally showed you in a case of myasthenia gravis or postsynaptic neuromuscular junction disorder where you see a nice decrement. After 10 seconds of exercise, you see this partial repair like we just showed, but then this post-exercise exhaustion comes in when you're talking about doing 60 seconds of isometric exercise. So rather than 10 seconds, you're doing it for a whole minute. And that actually has kind of the opposite effect. Rather than repairing it, it actually makes the decrement worse. So here they've actually labeled, oh, I can see it better on the screen. Here they've actually labeled the amount of decrement in each of these scenarios. So it'd be like 32 and then to eight, and then this is 44%. Two minutes after the 60 seconds of exercise, you're at about 50%. And then three minutes later, you're at 60 some percent. So the decrement gets worse over time. We call that exhaustion. So let's say you're gonna actually do this test. How would you prepare to do it in terms of technique? So first of all, again, in the vast majority of cases, when you're doing this evaluation for the purpose of myasthenia gravis, the patient may have already had that diagnosis kind of preemptively made for them. And so they might already be on a treatment for it, which is pyridostigmine. And pyridostigmine helps keep more acetylcholine in the synaptic cleft. And as a result, it can at least partially or completely normalize the result of this test if it's still on board and working in their system. Fortunately, it doesn't have a super long half-life. So we only recommend that you hold the pyridostigmine for about 12 hours or so. So they don't have to hold it for days or anything prior to the testing. But if they took it that morning when they come in to do the test, there's a possibility that if the test is normal, it may be falsely normal or reassuring. It's important to choose your nerve and muscle wisely. Ideally, you would always choose a weak muscle because that muscle is probably more affected by the neuromuscular junction deficit than other muscles. Nerve and muscle combinations that have been historically used are primarily the facial recording at the nasalis or the orbicularis oculi, the accessory nerve recording at the trapezius, the axillary nerve recording at the deltoid, and the ulnar nerve recording at the ADM. It's also important when you choose a nerve and muscle to try to choose one that is not confounded by another known pathology. So say, for example, the patient has a history of an ulnar neuropathy at the elbow that was pretty severe, they had to have surgery on it. That's probably not the best one to choose because it might have a low CMAP to begin with. And there are also reports, although it's rare, that patients with a known non-neuromuscular junction disorder may have a falsely positive repetitive nerve stimulation test if they've had some type of severe axonal damage like that. It's important to immobilize the limb because this test, because you're doing these firings, they're not super fast, right? They're a couple times per second, but they're fast enough that it's pretty susceptible to motion artifact. So you wanna try to keep the limb as still as possible. It's very important to warm the patient up to a critical temperature. The ANAM actually recommends warming up to 35 degrees Celsius, which is quite warm. And the reason for that is that it increases the sensitivity and I've got a slide on this later, it increases the sensitivity to find the decrement when the temperature is higher. So you may have a falsely reassuring or a falsely normal repetitive nerve stimulation if you're not warm enough. You wanna perform a routine nerve conduction study of the nerve that you're going to examine for the same reason that I mentioned earlier, that you wanna make sure that there's no other confounding pathology. And you also want to ensure that there's a super maximal stimulation because submaximal stimulation can lead to both false positive increments and decrements. And then you set your repetitive nerve stimulation parameters to somewhere between two and five hertz, two and five shocks per second, and you wanna perform somewhere between five and 10 stimulations. So, okay, so now you're prepared. Now you're actually gonna do it. So what are you gonna do once the patients are all set up? So first you perform a baseline repetitive nerve stimulation test, and you look for some of the things we just talked about. It might be normal. The CMAPs might remain stable. If you see a decrement, you wanna look to see is there a U-shaped decrement? You're only probably gonna see this if you do enough stimulations, and I'll talk about the number of simulations you might choose to do more or less in a minute and the pros and cons. But if you do enough stimulations, you would ideally see this U-shaped decrement where earlier I mentioned that the nadir, the lowest point is usually on like the fourth or fifth stimulation. And then you typically see an increase after that. And the importance of seeing the U-shaped decrement is that it gives you a lot of confidence that the decrement you're seeing is truly physiologic and not potentially due to a motion-related artifact or other types of artifact. Okay, so you just performed your baseline repetitive nerve stimulation test. Then you perform your isometric exercise for 10 seconds. You may wonder why 10 seconds? Like who came up with that idea? And that was actually studied in 2008 by Dr. Oh and Dr. Hatanaka to show that for patients with LEMS, which is the primary reason you're usually doing the 10 seconds of isometric exercise to look for the increment. For those patients that they had the best increments in the five to 10 second range, and once they got to 15, 20, 30 seconds, the increment dies off. Which isn't terribly surprising because we also talked about post-exercise exhaustion. So somewhere between 10 seconds and 60 seconds, there is a significant decrease in CMAP amplitude. Okay, so we call this brief exercise, 10 seconds of exercise. You do the rep sim again, and then you do, if you wanna look for post-exercise exhaustion, you would do 60 seconds of exercise and then record your repetitive nerve stimulation at one-minute intervals for approximately three to five minutes. So there's a couple of variations in terms of how you could choose to do some of these parameters. So first of all, slow hertz, two to five hertz, you know, how do you choose? Two, three, two, three, four, five. The short answer is we don't know that one is necessarily better than another. Those early experiments I mentioned in the 1940s showed that this range was better than 10 hertz or 50 hertz or better than one hertz. But within this range, it's probably about equivocal. You may also have to choose between, like how many simulations are you gonna do? Are you gonna do five or are you gonna do 10? And kind of the trade-off there is that patients frequently don't find this very comfortable so doing five is fewer shocks, it's more comfortable for the patient. Doing 10 has the advantage of looking for more stability over a course of, you know, you might have to do a couple trials of this if you're worried that artifact is playing into it. And it also gives you a better chance of seeing that U-shaped decrement if you're seeing decrement at all. For comatose patients who are too weak to perform the 10 seconds of isometric exercise, you can alternatively do what is called fast hertz or fast frequency repetitive invertebrate stimulation, which is basically the imposed upon the patient electrical equivalent of them exercising. But it is quite painful and it actually probably doesn't work as well as physiologic exercise if the patient can do physiologic exercise. So we only do that in patients who, like I said, are comatose and can't follow commands or are too weak to perform it. And then the last thing I'll mention is I just outlined this, you know, series of tasks to do, you know, perform a baseline, perform a RepStim after 10 seconds, perform a RepStim after 60 seconds. You may not have to do all of these. If you have a pretty clear scenario where of all the three disorders we talked about, you know, myasthenia gravis, botulism, Lambert-Eaton, you're really only considering myasthenia gravis, which is gonna be most of the time. And you're not considering the other diagnoses. And you do your first RepStim and you see a clear decrement and it matches your hypothesis, you don't necessarily have to do the 10 seconds of isometric exercise to show that there's, you know, partial repair or something like that of the decrement or to look for increment. You may only need to do the baseline RepStim. Maybe? Come on. Ah, there we go. I'm worried I skipped too ahead. Oh well, we'll run with it. So this slide is talking about the sensitivity and specificity for repetitive nerve stimulation in particular with patients with myasthenia gravis. And this was a paper that came out a couple years ago and there's a whole bunch of numbers and I'm not gonna walk you through all of them in this matrix, because that's not really the point. But the main point is that this paper looked at a couple, it actually looked, it was interesting because it looked at several different parameters and how they may affect the sensitivity and specificity of the test. It looked at what muscle was investigated and the sensitivity and specificity of that. The patient's phenotype, whether they had ocular symptoms only or they had more limb symptoms as well. And then it also looked at, there's, I wouldn't say controversy, but there's reasonable debate to be had as to what should constitute a positive call for significant decrement. And so they looked at how changing the critical or threshold decrement for calling the study abnormal changed the sensitivity and specificity when you range that decrement from 5% up to 10%. And the basic takeaways from this are a couple of things. Number one is that the overall sensitivity of this test, no matter which way you slice it, I would overall describe as medium. It's not super high sensitivity, such that nearly everyone with myasthenia gravis, no matter which parameter you choose, is the test gonna be necessarily positive. It's also not crazy low sensitivity where it's only very rarely gonna be positive. It's kind of in the middle, maybe in that 50% range. Understandably, there's a trade-off in terms of what you call the abnormal threshold percentage between five and 10%. The more you go towards 10%, you decrease your sensitivity because you're requiring the test to be more abnormal, to call it abnormal. And you're simultaneously increasing the specificity by increasing the threshold in that same direction. The other two takeaways for this is that, not terribly surprisingly, of these phenotypes, ocular-only symptoms, more limb symptoms, more bulbar symptoms, it was the ocular-only patients who had the lowest sensitivity for this test, so you're least likely to find abnormal decrement in patients with ocular myasthenia with repetitive nerve stimulation. And that sort of makes sense because those patients are, at least from a distribution perspective within their body, seemingly the least affected. And then the last part is that doing the post-exercise exhaustion, so doing a repetitive nerve stimulation test after 60 seconds of exercise, increases your sensitivity of detecting the abnormal decrement by about 10%. So it's a modest improvement, but if you were really close, like let's say you and your lab decide that a 10% cutoff is what you need to call a test abnormal, and you suspect your patient has myasthenia gravis, and you do their baseline repetitive nerve stimulation test, and it was 5% or 6%, but you still have a strong suspicion, that may be the case where you choose to go kind of quote-unquote the extra mile and do 60 seconds of isometric exercise to look for post-exercise exhaustion. So I kind of just talked about this a little bit, like how are you gonna call it being abnormal? For the decrement, the AEM recommended guideline is 10%. There are experts, Dr. Stahlberg, Sanders, and Trontel, she's no longer with us, actually discussed this in a YouTube video, it's free, you can find it online, where they gave their opinions as to actually what they would consider abnormal in their labs, and they all basically agreed that if it was a lab where they had control over the study, and they were there, and they felt like the quality was very good, they would actually consider in most cases greater than 5% to be abnormal. For increment, more than 100% increment, which is the same thing as saying doubling your initial CMAP, so again, in the case of Lambert-Eaton, where your initial CMAP is usually quite low, if you were to double that or more, that's an increment of 100% or more, and that would be diagnostic of Lambert-Eaton, that's very specific to it. Having an increment of 40% to 100% is definitely abnormal, but you could potentially see this in either Lambert-Eaton syndrome or myasthenia gravis. And then zero to 40% increment is considered the normal range, is called pseudo-facilitation, that has to do with, to some degree, the normal physiology of how extra acetylcholine gets sit down the axon. And then for post-exercise exhaustion, there is no definition of what would constitute post-exercise exhaustion happening, but the importance of understanding the concept of post-exercise exhaustion is that if you do your initial baseline RNS, and again, your results are kind of borderline, you have the option to do post-exercise exhaustion to exaggerate the decrement and make it meet your criteria to make the test positive. There we go, okay, pitfalls. So we talked about limb immobilization, we talked about temperature, at least a little bit. So I mentioned that the AAN recommends that you try to get to 35 degrees Celsius. This was a paper on the right that was done in 1998 where they actually, they had a hypothesis that maybe super high temperatures would really exaggerate your decrement. And so they took seven patients who had known myasthenia gravis, so they, sorry, just to make that clear, they had known myasthenia gravis, not know myasthenia gravis. They had myasthenia gravis. They did a baseline RepStim, the top graph is the RepStim being performed at 34C, which is still pretty warm, right, nearly what the AAN recommends, and sometimes it's hard to get patients that warm. On the x-axis is the number of minutes after 60 seconds of exercise. On the y-axis is your decrement, and I apologize, I know you can't read the numbers, but you can certainly appreciate, I'll tell you the scales are the same between the two graphs. On the bottom, the top graph is 34C, on the bottom graph is 42C. They warmed them like way up to like super normal levels, and they showed that the decrement went wildly abnormal. You can see here even in one patient it went up to like 60-some percent decrement from previously being only in like the 20% range. And so I take this as kind of, you know, very strong proof of concept about how much temperature can affect the results of the test. The other thing to be aware of, if you're performing repetitive nerve stimulation for the facial nerve in particular, the facial nerve sometimes doesn't put out a very large amplitude, and as a result, it makes the calculation of decrement sometimes challenging, and you might over-call decrement. For example, let's say you do your facial nerve and your amplitude is only one millivolt. If your fourth stimulation drops down to 0.9 millivolts, which you wouldn't think of as 0.1 millivolt difference being that much, but when you calculate it, it's a 10% decrement. It sounds pretty significant. So you run the risk of potentially over-calling decrement or over-calling increment or any kind of change when your baseline amplitude is so low in the facial nerve. So it's very important if you are going to do a facial nerve rep stim to try to optimize your electrode placement so that you get your initial CMAP as high as you possibly can to avoid this problem. And then I already talked about supermaximal stimulation, and I'm going to run out of time, so I'm going to move on. So cranial nerve conduction studies, we're going to talk about the blink reflex, and then I'm only very briefly going to mention facial nerve and spinal accessory nerve. So blink reflex physiology. So I've kind of made this a little bit shorter, but the blink reflex is the electrophysiologic equivalent of the corneal reflex, which is an exam maneuver that we sometimes perform, where there is an afferent component, which is cranial nerve 5, and an efferent component from cranial nerve 7. So we're going to briefly walk through that. This diagram here, this is obviously a depiction of the left side of some guy's face. The diagram on the right is an anterior view. So you see that this is the left side of the guy's face, and then when you're looking from straight on, this is the same red line as the trigeminal nerve coming down into his brain stem. So the afferent limb of this is the trigeminal nerve or cranial nerve 5. It comes down into the brain stem, and it synapses in two important places, the nucleus of cranial nerve 5, which is the main sensory nucleus, that's the VM, as well as simultaneously going down to VS, which is the spinal nucleus of cranial nerve 5. Then there is a series of interneurons that go between the VM, the VS, and then also to bilateral cranial nerve 7s. Then you have your efferent arc of this reflex, which is from the cranial nerve 7 or the facial nerve that goes out to both eyes. So physiologically, when you either perform the blink reflex in the lab or you do a corneal reflex as part of an exam maneuver, you will give a stimulus to one eye, but you'll get a blink on both sides because you have the efferent output to both sides simultaneously. The importance, I think, of showing the complex interchange in the brain stem is to show that on the ipsilateral side to the stimulus, there is an option for a shortcut. You can see how the trigeminal nerve, as it comes into VM, then goes straight to cranial nerve 7 and then out, is a shorter loop than it going down to the VS and then going to cranial nerve 7 and then out. That has importance in what we look for on the blink reflex response. All right, so this is, we've changed models now, but here is the stimulator stimulating at the superorbital notch on the left side, again, just kind of like with that other patient. Stimulating at the superorbital notch and then the black circles are representing your recording electrodes. The red circles are representing your, and those are over the orbicularis oculi, a facial innervated muscle. Your red circles are representing your reference electrodes at the epicanthus of your eyelids. And then on the right side of the screen, which is the patient's left side, on the right side of the screen, which is the side ipsilateral, same side as the stimulating side, because of that shortcut, you've got two potential responses. You've got the R1 response, which is representative of it going straight through VM to cranial nerve 7. And then you've got the ipsilateral R2, which is the other loop, the slower loop, going to cranial nerve 7. So you've actually got two different contractions happening in very close proximity to our naked eye, but in an electrical world is reasonably separated in time. You can also see here that the R1 is very stereotyped. Like every time it fires, it looks almost exactly the same. The R2 tends to have, look a little, it's a little bit analogous to F waves. Every time it fires, it has a slightly different waveform. And then similarly, on the patient's right side, which is the left side of the screen, you get an R2 only. So you get no R1 on that side because you don't have the shortcut option of the R1 on the stimulated side. It's important to note that what are we actually looking for here? So we're looking for two things. Primarily one is, is each of these present, the ipsilateral R1 and ipsilateral R2 and the contralateral R2. And then also what are their latencies? And we have standards and I put them up here, but they're not important to remember exactly. So we'll move on. So now whenever you do a blink reflex, you're not just going to do it on one side, you're going to do it on the other side as well. And so here you can see basically the same response, but everything is flip flop. You've got your ipsilateral R1 and R2 on the patient's right side. And then your contralateral R2 only, no R1 on the patient's left side. So when you do this and it prints out your responses on your machine, it won't actually have the diagram and everything for you. And one thing that's really important to note is different manufacturers of the machines will put this matrix of these four responses potentially in different orientations. And so here it's important to note every time you look at it, how are they orienting? So here up on the top of the screen, I've got my side of stimulation, my right side and left side, which is like the x-axis. And then on the y-axis on the left side of the screen, you've got your side of recording. And so it's very important to keep track of what you're looking at. And you really, unlike a photograph or something, you really have to look at these one at a time and think what's being stimulated and what are you recording and what do you expect to find in a normal patient and what are you finding or not finding. So we'll go through a couple of localizations. Yeah, I think I have time. So only three that I wanted to do today. There are potentially more localizations that you could derive from blink reflexes, but these I think are the most clinically useful and ones that you're most likely to try to find. So the first is a trigeminal nerve. So imagine now that we were to take out this patient's left trigeminal nerve, what would you expect to see? So if you were to stimulate on the left side, then there's nothing getting in, right? So if you stimulate on the left side, nothing should happen on the right or the left side. If you stimulate on the right side, what should happen? Well, if you took out the trigeminal on the left and everything else is intact, the only thing on the left that you really need to be intact is the cranial nerve seven to have your output, your efferent. So when you stimulate on the right, everything should be normal. So let's see, is that correct? Yes, it is. So when you stimulate on the left side, you don't get any responses. And that's, again, I look at the side I'm stimulating on first. So I look at the right side of the screen now, which is the left side for patient. And then on the right side, when you stimulate, you get normal responses. So when you stimulate on the right and record on the right, you get the ipsilateral R1 and the ipsilateral R2. When you stimulate on the right and record on the left, the bottom left-hand corner, you get the contralateral R2 only. What about if you were to take out the facial nerve? So let's say, in this case, we're taking out the left facial nerve. What would you expect to see? So if you stimulate on the left side and you take out the left facial nerve, you should see no output on the left side. But there's nothing wrong with the right side. So all the right side responses should be normal. And when you stimulate on the right side and your left side facial nerve is out, it's kind of similar. Everything should be normal except the output on the left side. So again, stimulating on the left side, you see that there's the contralateral R2. So when you stimulate on the left and record on the right, you still get the R2 response, which is what you would expect. When you stimulate, but you don't get anything on the left side. When you stimulate on the right side, you get the ipsilateral R1 and the ipsilateral R2, but nothing on the left because you have no output on the left. And then the last is diffuse demyelination. Like you would see in Guillain-Barre syndrome or AIDP, my hazed circles here are meant to represent demyelination of all the peripheral portions of the nerve, at least. And so here, you just get prolonged latency. So everything is slower than it was before. Things are usually still probably present, but everything is slowed kind of like what Dr. Little talked about in terms of demyelination and conduction velocities. Okay, I have one slide each, and they're not very interesting because I couldn't come up with anything interesting to talk about with the facial nerves, the facial nerve or the axillary, or sorry, not the axillary, the spinal accessory nerves. They were part of the topic, and I thought I would find cool things about them, but I couldn't. The most important things to know are that the facial nerves, you can record from lots of different muscles. There are many muscles that your facial nerve innervates, like your frontalis, your nasalis, your orbicularis oculi, and your mentalis. It usually requires pretty small currents to generate these responses. And kind of like I talked about in repetitive nerve simulation tests, they generate very small amplitudes. And as a result, they usually require side-to-side comparison, assuming that you're looking at a unilateral facial weakness. Spinal accessory nerve is basically the same story. You're going to be doing this test if you think the patient has unilateral, like, shoulder abduction weakness or shoulder elevation weakness. And it's going to be very important to compare side-to-side. You would stimulate at the posterior sternocleidomastoid, and you would record over the upper trapezius with my recording and reference electrodes placed here with the black and red dots. Okay. I think that's it. Thank you. Are there any questions for either of them? Thank you for the excellent presentations. I have one question for each of you, actually. When I do a tibial nerve conduction study, I find that proximal stimulation often has a decrease in amplitude that is in excess of 20% in otherwise what I consider a normal conduction study. So in order to avoid overcore, I typically just kind of know that and then write it off in my conclusion. But I do want to get a little bit more thoughts from Dr. Little on that. And I think that's primarily a matter of the depth of the tissue. That basically, like, if you had a small candle and it doesn't light the whole room, you need a bigger candle. When you're stimulating, you just can't stimulate high enough to get every single axon in the tibial nerve at your proximal stimulation. And you'll find the same problem if you're going up. Sometimes if you have a, especially a patient with a large BMI, if you're stimulating at Erb's point, you may not, you may also have a significant drop. And you have to take that into consideration that this is a, you know, not being able to stimulate super maximally, you will not get as large an amplitude. So you have to take it in clinical context. If it's a huge drop, you know, it's 10% of what you see, well, that's probably more significant. But it's mostly because the tissues are so thick and you can't get the super maximal stimulation. Thank you. And a question for Dr. Moser. What is the physiological significance of the R1 waveform? I understand the R1 waveform is only on the urethral side of the stimulation of the brain reflux. And obviously, R2 is what gets brain, and I have always wanted to know exactly what R1 does for us. So, sorry, the question is, what does R1 represent? What does it do physiologically? What does it actually do? It contributes to your blink, like to your eyelid closure. But that, I thought, is kind of an R2 process when your blink is bilateral. So I'm wondering why. I understand the pathway that leads to R1 being urinatal, but kind of physiologically, how does it contribute to the blink itself? the r1 the interlateral r1 and r2 they look very separated like you know when you measure them in terms of latency but to our naked eye they're happening in such close succession you know in terms of like milliseconds that physiologically it's a single point. Okay thank you. Any other questions? Corey. Hi I'm a physiatrist in Orange County California. Sometimes we get patients a lot of times from podiatry asking about peripheral neuropathy in the feet and sometimes these patients have very flat feet and we'll get very small tibial motor amplitudes and I just wanted to see what you thought about that and what you might note in your study as far as that type of finding. We absolutely see that people with flat feet especially as they're older very low tibial amplitudes and if you've you know and and you know perhaps it's just you know compression of that particular nerve but if you don't find anything else that goes with peripheral neuropathy then you know I actually make a note in the reports that you know you know there was this one abnormality and it's likely related to you know the patient's body you know their their flat feet. That is totally something that is always seen with flat feet. So my question is for Dr. Moser. Do you have a preferential I guess standard protocol for your repetitive nerve stimulation when you're trying to diagnose myasthenia? And the reason that I ask this is because in our clinic one physician in particular he loves to do the ulnar and the perineal I'm sorry the common fibular at the tibialis anterior muscle but we had one patient in particular where we did the ulnar the common fibular the facial found nothing and actually went to the spinal accessory nothing and then went to the axillary and found it only on one nerve. We were able to find decrement even going through and searching so I'm curious do you does myasthenia in his disease process tend to be preferentially affecting specific nerves? Good question. So not necessarily. It probably does and the reason I just said two things that are very contradictory there's sort of a reason for one is so that paper that I showed that talks about sensitivities and specificities for doing different nerves in patients with different phenotypes and then also it also compared to the you know decrement level that you're going to find out that's not part of that paper did a pretty good job of showing that there isn't one muscle or nerve that's better than others. It didn't include the perineal. It only included the facial the ulnar and the accessory. So it didn't conclude that one was like the best one to do. You want to try to choose a weak muscle if it's possible because sometimes you don't have a weak one. Sometimes you're kind of fishing. And the other part I was going to say though is you know there are muscles that are preferentially clinically affected and most patients in my opinion but it didn't really bear out in that study to show that there's a kind of nerve stimulation test that would reliably more likely. Did you have a standard protocol for your studies? My standard protocol is usually in most people. It's hard to say standard but usually I would prefer to like just do an ulnar if I have a very low suspicion that this is somebody's diagnosis like if somebody refers them and I hear it's from my student. You know I don't want to struggle hard and do a whole bunch of nerves that are probably futile and also make you more susceptible to artifact and potentially having like bad results. Sometimes rough studies are hard. They are. And so I would prefer to do less but in the other case like you just described like the physician you were working with who wanted to do you know as many nerves as they could possibly do. I don't think it was so much that he wanted to do as many nerves as we could. It's just we were really convinced that this was the actual diagnosis and so we went to go find it. That's my point is that if you if you're on the hunt for it because you have this strong clinical suspicion I agree that if you if you did five nerves and you found decrement that you were convinced was true and not artifactual in a single nerve I would call that an abnormal study and make the diagnosis. Okay. So I would come for it just like you described. Sure. Thanks. Any other questions? All right. Thanks for being here. Have a great evening.

repetitive nerve stimulation

neuromuscular disorders

myasthenia gravis

test procedure

nerve stimulation

muscle response

frequency of stimulation

development of test

acetylcholine release

C-map amplitude

isometric exercise

test preparation

lesion localization