Hello, everyone. It's a pleasure to have you all with us today on this on-demand session called Electrodiagnosis of Brachial Plexopathy. My name is Sandra Hearn. I'm from Michigan Medicine. We have a fantastic panel of speakers today to go through with us the electrodiagnostic approach to brachial plexopathy. You can see our array of speakers here. We have Dr. Jorgensen, Dr. Rad, Dr. Arnold, and myself presenting with you today. I'm going to go ahead and introduce Dr. Sean Jorgensen as our first speaker. He's going to speak with us about the clinical presentation and electrodiagnostic approach to brachial plexopathy. Dr. Jorgensen is a clinical professor of physical medicine and rehabilitation at Albany Medical College. He's also a partner at Adirondack Rehabilitation. Welcome, Sean. Okay. Thank you, Sandra, for having me involved in this in the first place. Thank you, everybody, for joining us while I get my slides set up for you. My job is to talk about brachial plexopathies in general and really just how to approach them. The other speakers are going to get into a lot more detail. This is more of an orientation. I have no financial disclosures. We'll talk about anatomy, clinical assessment, and the general EDX approach. However, the anatomy, this is something we all learned. It was probably the first or second thing we learned in medical school and probably at least 12 times since. I have not yet discovered any new parts of the plexus. Other than just showing this for reference, I think we can probably skip that. It is important to know where the plexus lies in situ. The roots and trunks are superclavicular. The divisions are subclavicular, and the cords and branches are infratlavicular. That's an important thing. This is just kind of an annoying semantics thing, but we do say roots all the time. This area is technically where you have the dorsal and ventral root fuse is the spinal nerve. Anyway, enough of that. Clinical features of facial plexopathies, how frequent they are kind of depends on your setting. We estimate in my practices, which is more of a community setting, we probably diagnose one about every 200 electrodiagnostic studies that we do, which is pretty low. But if you looked at other practice patterns, it can be up to 10% of all peripheral nerve lesions. So they're not really that rare. As far as the history goes, the mechanism of action is actually going to be more helpful than it's going to be for a lot of other things. So for example, if someone has cancer or radiation in this area, obviously that's going to be a big giveaway. You really need to be thinking about plexopathies. And trauma and dislocation is going to be a lot more frequent than it will be in the general population. Unfortunately, beyond that the history really doesn't help you separate plexopathies from radiculopathies proximal or from focal mononeuropathies distal, both of which are much, much more common. Similarly, the physical exam does also not really help you distinguish plexopathies from these proximal or distal processes. There may be two exceptions that you don't see very often. One is edema, which is something you can get from compression of the neural structures and the vascular structures. And this is really one of the few places where the major nerve and vascular centers are all concentrated together. In fact, the cords are named for their relationship to the artery. So certainly an external compression here could give you edema, and that's not something you're going to see in a radiculopathy, for example. The other thing is Horner syndrome. So this is a problem you get because the sympathetic supply lives in the thoracolumbar cord. It's got to get to the sympathetic chain to be distributed throughout the body. And in this particular case, we're thinking of the face and the eye. And in the process, it has to hitch a ride on the T1 root and the inferior trunk of the plexus. So if that gets interrupted by, say, an apical lung tumor, you will have a deficit of sympathetic supply. Well, what does that look like? Classically, the main features are ptosis, meiosis, and anhydrosis, which you can't really see. So this is definitely something if someone has Horner syndrome, they're going to be thinking more about a plexopathy, and I have occasionally made the diagnosis or at least suspected what turned out to be a plexopathy because of the Horner syndrome. Okay, but beyond that, it's really about planning your study. And I would say for plexopathies, this is really a study that you want to kind of pause, take a breath, and plan this thing out. And in general, this is going to be a study that you're going to do more than you normally do. You're probably going to need to needle more muscles. You're probably going to need to do more stimulations, especially for side-to-side amplitude comparisons, which we'll be talking about later. The other thing that I have found is I have kind of subconsciously developed three different approaches for depending on the severity of the lesion. So mild lesions in my head are ones where I'm not even sure there's a lesion at all. Severe lesions are things that there is clearly a neurological lesion when you examine the patient, and a catastrophic lesion is something you can tell just by watching the patient walk or even sit down or fill out their paperwork. So let's start with mild lesions. So these are ones that after you do your history and physical, we're not sure there's even a neurological issue at all, much less a plexopathy. And so, for example, in my practice, we'll get a lot of these rule-out plexopathy from the shoulder surgeons because their MRI is normal or they scoped them and they didn't get better. And I'm not really very suspicious in these cases. So what this study really ends up being very different than the other types of studies, because this is basically a fishing expedition. You're looking for anything, because most of the time it's going to come up normal. And one problem that comes up here that does not come up in the other severities is selective sparing. So what do I mean by that? Well, if you had a complete lesion of a nerve, you would expect to see abnormalities in all the muscles that are supplied by that nerve downstream from the lesion. So for example, if we have this nerve and we have this complete lesion, we're going to see abnormalities in all of those muscles on needle EMG. But if this is an incomplete lesion, some of those facetules are often going to be spared and the muscles when you needle them, they may look fine. So for example, in this one, half of the muscles may be abnormal, half may be normal. And so you're going to have to be ready to needle more muscles in this case to really make sure you're capturing what might be out there. This is a common phenomenon that happens in the FCU and ulnar neuropathy. The elbow is something that's pretty well known and in the tibial division of the sciatic nerve and these stretch plexopathies that happen with hip surgery. So it's a pretty well known phenomenon, but it comes up really only in the mild lesions. The other thing that's different about mild lesions compared to severe or catastrophic lesions is that nerve conduction studies are not going to help you localize or determine the degree of the lesion, which sounds funny probably because we all learned that they do. Why can't we do that? We make the diagnosis of mild carpal tunnel syndrome all the time. Why can't we do it here? Well, as Dr. Dimitriou says, it's really hard to detect things like conduction block or even conduction slowing across the plexus. It's just technically limited that way. So if a mild lesion is only manifesting as conduction block or slowing, you're probably not going to see it. So you may be thinking, okay, that's fine, but I should be able to use my distal studies to detect axon loss, right? Yes, but probably not in mild lesions because even in our best technically adequate studies, we still have such a huge difference that's allowable side to side. If we did these studies on ourselves, we'd see huge amplitude difference side to side. So a little axonal lesion is something you're really going to have a hard time diagnosing with confidence in this setting. So that's what makes mild lesions kind of a different study than your other more classic plexus lesions. I would consider severe lesions more of kind of your classic plexus study that we're all kind of in the habit of doing. And in this case, your goals are to localize it to the plexus or the root. And other speakers are going to talk about that. So I'll leave that alone. Degree of damage. This is one where you can use the amplitudes side to side to estimate the degree of damage, but I'll let others talk about that too. And then the other thing you're going to want to establish is where are we? How old is this? What's the status of the re-innervation, et cetera, because that'll have huge prognostic implications. And then lastly, catastrophic lesions. These are, you know, again, very obvious lesions, almost always traumatic. And the goals here, again, are very different than the kind of more typical severe plexus injury. So for example, a motor nerve conduction study in a catastrophic lesion is often not super helpful because if it's this bad, it's either going to be either going to be gone or almost gone. And the studies when they're that low amplitude is really hard to interpret them well. So the motor nerve conduction studies won't help you a lot. Now the sensory nerve conduction studies will help you tremendously in localizing the lesion, but again, others are going to talk about that. And then the goal of the needle EMG here, unlike those mild lesions where you really are going to maybe capture something here or there, this one finding Fibs and positive waves is not your goal. You're going to see them everywhere. Every muscle that's affected by this lesion is going to show up with Fibs and positive waves. The difference is what you really need to find is motor units. Any motor units, one motor unit is going to tell you that this is an incomplete lesion. And this has huge implications for prognosis and even for treatment. So that's really the main thing you're trying to establish is there continuity in these really catastrophic lesions and is it a plexus or a root level lesion? Okay. So I'm going to let the other speakers do their thing and dive into the details. Here's my references and I will be on the chat available. If you have any questions, please put them through. And so I am going to introduce our next speaker who is Dr. Rad, who is an assistant professor of PM&R at the University of Washington. Thank you so much. So it's my pleasure to be able to talk a little bit about how do we differentiate plexus from root injuries. And to do this, we're going to go over a case-based approach. I don't have any disclosures to make. So we're going to dive right in with a case presentation of a 39-year-old male that was involved in a motorcycle collision accident six months prior to seeing us in clinic. He reports that he was the motorcyclist and he fell onto his left shoulder and immediately developed weakness or noted weakness with the ability to abduct his shoulder and flex his elbow. Over the past six months, he does not note any improvement. He states initially he had numbness and tingling over the left shoulder and thumb, but over the past few months, the thumb changes have essentially gone away, but he still continues to have residual numbness and tingling over that left shoulder. He's also had chronic pain over the entire left shoulder since the injury. The only medical complications during his acute hospital course that are notable were a left upper extremity blood clot for which he's still on anticoagulation. On physical exam, he is in quite a lot of pain with his left shoulder movement, but it's notable that you can passively range him fully, but he's only able to actively abduct to about 20 degrees. He's unable to flex his left elbow and unable to supinate his left elbow. This is despite his pain. He's giving a lot of effort distal to these muscles entirely intact. His sensation is diminished to pinprick over the left anterior shoulder, otherwise intact, and his reflexes are trace but symmetric throughout his upper extremities and negative Hoffman's bilaterally. So why is it difficult to localize a lesion to plexus versus roots? And as already was mentioned, this is largely in part due to the fact that clinically our history and physical exams are quite similar when we need to consider a cervical radiculopathy, a plexopathy, or multiple peripheral neuropathies. Even more challenging is when you're dealing with a polyradiculopathy or a panplexopathy because now you're having symptoms across multiple nerve roots and multiple peripheral nerves. The goal of nerve conduction studies and EMGs are to aid with localization, which can't always be done with our history and physical exam, and more importantly, aid in that severity of injury to help with possible treatment and or surgical planning. We're going to dive in a little deeper in the next few slides as to why sensory nerve conduction studies are of greater utility for localizing plexus versus roots than our motor nerve conduction studies. And also to throw in a little curveball, it's not always very clear-cut. You can have root involvement and things that are considered primarily brachial plexopathies. These are in the settings of nerve root avulsions in traumatic brachial plexopathies and cases where we can see root involvement in some cases of neuralgic amyotrophy. So let's take a moment and remind ourselves why is it that sensory responses can help us differentiate root versus plexus. So when we're dealing with a radiculopathy, we expect to see normal sensory responses. So in the schematic to the right here, we have figure A up top demonstrating a normal nerve, figure B demonstrating a lesion that's considered pre-ganglionic or proximal to the dorsal root ganglion, and figure C demonstrating a post-ganglionic or distal to the dorsal root ganglion. And as you can see here with the schematics for what the sensory nerve conduction action potentials and the motor action potentials, when your lesion is proximal to the dorsal root ganglion, our sensory nerve responses bypass that injury, never hit that injury, and so we get a normal response. Now distally, it's a different story. If your injury is distal to the dorsal root ganglion or post-ganglionic, we should have an affected sensory nerve action potential in the distribution of the nerve that was injured. The few caveats being that, you know, certainly if this was an acute injury and there wasn't any, and there wasn't time for valerian degeneration, we may not see that abnormal sensory response. And then if we are dealing with a more, you know, proximal demyelinating condition, we may also not see that axonal loss. The schematic here on the other side of the screen, you know, the most common type of RIDICs that develop are from herniated discs, and many people wondered, well, why doesn't the herniated disc affect that dorsal root ganglion? And the reason is, is that most herniated discs are posterior and lateral, and so your dorsal root ganglion is still actually distal to that herniated disc. And so again, nerve, these normal sensory nerve conduction responses are quite useful. So in any plexopathy study that you're performing, having a good understanding of the brachial plexus and anatomy is important. But when you're trying to differentiate root versus plexus, it's really important to have a good understanding of what muscles are innervated by cervical roots and not the actual plexus. And so as a reminder, the plexus is formed from C5 to T1. So there are three nerves that we should be familiar with that come from these root levels but are innervated directly by the roots. And so the dorsal scapular nerve here that we can see in this illustration comes directly off the C4 and C5 root levels. They innervate the rhomboids and the levator scapula. And then C5, with contribution from C3 and C4, I was just listing the nerve roots that are included in the brachial plexus, make up the phrenic nerve and innervate the diaphragm. And then the long thoracic nerve comes from the C5, C6, and C7 root levels, innervating the serratus anterior. Why this is important is any of these muscles, were they to have abnormalities, would suggest to us that these were occurring at a root level, so proximal to the brachial plexus. All right. So a lot of words on this slide. And we already had a wonderful introduction into planning these studies. So we're going to dive in a little deeper into how these studies can help us differentiate between root and plexus. So to begin with, while our history and physical exam may not help us decide if it's root or plexus, it should help you to localize whether or not you're thinking, you know, upper trunk, middle trunk, lower trunk, or what levels of the root may be affected. Know that your EMG plan may change depending on what you discover, as you may, you know, in mild injuries, find abnormalities that you weren't expecting to be there. So let's start with those sensory nerve conduction studies. Again, we would suspect that they would be normal in radiculopathies. So of the more commonly tested sensory nerve conduction studies in plexopathies, we have the lateral antebrachial cutaneous, the radial median ulnar, and medial antebrachial cutaneous. Certainly, this is adaptable. So if you had very low suspicion or no suspicion of a posterior cord, you may not do the radial sensory response. You always wanna make sure that you're comparing to the contralateral side. You know, we all routinely do this for the lateral antebrachial cutaneous and medial antebrachial cutaneous, but it's important to remember that what may seem normal and even the median ulnar or radial may not be normal when we compare it to the other side. The good thing is plexopathies are usually unilateral, so you got a great control built in for you. The other approach to the sensory nerve conduction studies divides upper, middle, and lower trunk, so commonly referred to as the 1-3-5 approach, one meaning testing the median to the thumb, examining the upper trunk, three examining median sensory nerve response to the middle finger to get that middle trunk, and then five for the routine ulnar to the little finger to get that lower trunk. So moving on to our motor nerve conduction studies, so of course, starting with our more typical median and ulnar, which reflect the medial cord, lower trunk, the radial motor response reflecting the posterior cord and lower trunk. As always, you wanna compare these to the contralateral side to identify any abnormalities. That being said, as you can see, our routine motor nerve conduction studies are really only looking at the lower trunk for us. It can be really challenging to identify these upper and middle trunk lesions on nerve conduction studies because you'd have to go to Erb's point and stimulate proximal muscles. And Erb's point has its own challenges. You wanna make sure that you're looking at supermax stimulation. At submax stimulation, you may get falsely abnormal responses. At supermax, you may be co-stimulating different nerves in the plexus. And so you're not gonna get as clean of response. Most plexopathies are axonal. So for motor nerve conduction studies, if you do see abnormalities, you're looking for low amplitudes, depending on how much axon loss, maybe mildly prolonged latencies and some conduction velocity slowing, but never in the demyelinating range if it's axonal. That being said, when there's a most, there's always exceptions. And so you can have demyelinating plexopathies where an F-wave may be helpful, especially in a radiation plexopathy, for example. Moving on to needle EMG. So we wanna make sure we choose muscles with different peripheral nerve innervations and different routes. You always wanna make sure that you're including clinically weak muscles on your needle exam. And then don't forget about the proximal muscles. So as a reminder, the paraspinals, the rhomboids, the serratus anterior, all of those are innervated at the root level. So identifying any abnormalities in those muscles can help you with localization to the root level. What is it that we're looking for on needle EMG? So we're trying to identify for axonal loss. So we're gonna be looking for active denervation in the forms of positive sharp waves and fibrillation. Certainly any other unique spontaneous activity that you see will be very helpful. So myokinemia, again, radiation plexopathy comes to mind with that. And then you're gonna be looking at the motor units themselves, looking for abnormal morphology that reflects chronic re-innervation and abnormal recruitment. And then most importantly, as already was alluded to in the last presentation, assessing for axonal continuity. So what does axonal continuity mean? Are there motor unit action potentials that you are seeing? Absence of axonal continuity typically looks like widespread, severe denervation and no motor unit action potentials, despite patient giving you good effort. So you wanna also make sure that they're giving you everything they can. You also wanna assess for nascent potentials. So that's gonna be something early on, what in those first few months post injury, they tend to have low amplitudes, are polyphasic, durations can vary. You wanna make sure you don't confuse them for myopathic looking units. This is a really helpful clue because if you see these early on, there is potential that if you re-needled them in a few months, you may see some positive re-innervation. So those are very helpful for surgical considerations. Let's go back to apply what we've kind of discussed to our case. And remember that our gentleman is coming to us six months post his initial injury. So lots of different numbers here pulled up from his actual report. Some of our normative data for our particular lab is included here for you. But I'm gonna highlight some of the abnormal ones just to get us moving. So his sensory nerve conduction studies are most notable for the fact that we don't get a response to the left lateral antebrachial cutaneous. And you can see that a response was generated and quite robust on the right side. Looking at his motor nerve conduction studies, those are all normal. And again, you know, the utility of, especially since we know his clinical history is affecting the more proximal muscles and we're looking at distal, you know, motor nerve conduction responses, not as helpful for us to differentiate is it root versus plexus with these normal motor nerve conduction. But at least we're not throwing any curve balls in here in his study. So moving on to his needle study, we can see that he has a wide variety of muscles in the C5 and C6 distributions that have increased insertional activity with positive sharp waves and fibrillation. Most notable, his deltoid and his biceps, despite good effort, we can't get any volitional units seen. And then in the infraspinatus, supraspinatus and rhomboid, we see increased amplitudes, one case of increased polyphasia in the rhomboid and severely reduced recruitment. Not forgetting about additional proximal muscles, his cervical paraspinal muscles also demonstrate increased insertional activities with positive sharp waves and fibrillation. So to summarize what we're seeing, based on our definition of axonal continuity, we're not seeing any axonal continuity to the left deltoid or biceps. We are, however, though, seeing chronic re-innervation changes to the left infraspinatus, supraspinatus and rhomboid. And we are seeing that there was de-innervation in the cervical paraspinal muscles. So is it root or is it plexus? What helps us favor the plexus? So that lack of response in the sensory nerve conduction study makes us think this must be post-ganglionic. But then we see that we have abnormal rhomboids and paraspinal muscles here, and those come from a root level. So what is going on here? Well, going back to those cases where we can see root involvement, you know, we are at this point suspicious in our electrodiagnostic testing is most consistent with an upper trunk plexopathy where we have nerve root avulsion. To just kind of clean up the case for you, this gentleman did get an MRI of his brachial plexus that demonstrated a left-sided C5, C6 pseudomeningocele, which is consistent with nerve root avulsion. Localized with presumed nerve root avulsion hematoma located in the dilated nerve sheet with extensive edema in the left scalene muscle and shoulder girdle. So in terms of severity and prognosis, nerve root avulsions typically carry a poor prognosis for recovery. The things that we should consider are the fact that he has no volitional motor unit six months out to his left deltoid or biceps, but positively he also does have some chronic re-innervation changes to some of those C5 and C6 muscles. I'm not going to dive into this because you're going to get a great presentation from Dr. Hearn talking about prognosis and how do you utilize the information similar to what was provided here for next steps. So thank you so much. I get the pleasure now of introducing Dr. Arnold, who's a professor at The Ohio State University. So for the next section, I'm going to talk about plexus or multiple nerves, immune-mediated disorders of the brachial plexus. So before I start, I have no relevant disclosures to make that are relevant to this talk. So I chose this case because it was a case that I still remember, even though it's been a few years since I saw this patient. It was a good case to choose because it is kind of a stereotypical, prototypical case to highlight the disorder that I'm going to spend the most time on talking about today. Actually, I'm going to talk about a few different things. But this patient presents to the emergency room. I actually don't normally see these kinds of cases in the emergency room, but I remember seeing this individual. He presented with severe shoulder pain. So this pain was centered at his shoulder, very, very severe, excruciating pain. It was worse than my movement of the shoulder. And it started the day of the presentation. He had also an interesting history as well with the two week prior to presentation, he had had a bicycle accident associated with a clavicle fracture, which requires surgical fixation. And he had noticed pain after the surgery, but the pain had actually started to get better. And what brought him to the ER at this point was that the pain had escalated severely. And in fact, was a orthopedics resident that put in a neuromuscular consult to see this patient. They were worried about nerve entrapment. On examination, this patient had very, very severe muscle weakness. In fact, you could not see any visible contraction in elbow flexion, shoulder abduction, or external shoulder rotation. Little bit of patchy sensory loss, lateral forearm, and absent reflexes at the brachioradialis and the biceps, but the triceps reflex was intact. So this case is kind of a unique type of what we're gonna say in air quotes, brachial plexopathy process. So some points that I think stand out to make it really a stereotypical presentation is the fact that the weakness and the symptoms start abruptly. The pain was very, very severe acute onset. And when you think about the differential, so peripheral nervous system involvement, spinal nerve root, brachial plexus, or distal, when you think of root, it's very uncommon to have this amount of weakness because muscles typically have at least two or three myotomes that serve those muscles. So to have absent muscle strength, it usually points to something that's more distal. So more in the plexus, because to hit both myotomes at the nerve root level or the spinal nerve level is very, very uncommon. So this already right off the bat makes you think plexus. And if you were trying to localize, you would think an upper plexus problem, upper trunk kind of problem, similar to the case we just heard about. So this case really epitomizes a group of disorders first described by Parsonage and Turner in 1948. A lot of people have heard of this disorder. They called this disorder the shoulder girdle syndrome, the neurologic amyotrophy. A lot of times people nowadays name this Parsonage-Turner syndrome, but it's gone by many, many different names. The etiology is actually uncertain. So while we're kind of lumping this under immune mediated, the etiology is actually not entirely clear. There are also, in addition to idiopathic forms, there are also genetic forms. And the genetic form is usually termed hereditary neurologic amyotrophy. A subset of patients with hereditary neurologic amyotrophy have a gene variant in septum nine, but a lot of patients that we think have hereditary neurologic amyotrophy, we can't find the gene or the gene is not known. And so that is one cause, but not the only cause. So this is the very typical presentation, abrupt onset, usually in the shoulder, sometimes in the forearm, sometimes in the upper back. This usually corresponds with which nerves are involved. Pain is usually worse with movement of the limb, not so much with the neck. Pain typically lasts at a very severe level for a week or a little bit longer, and then it generally decreases. But a lot of patients can have chronic pain that can be primarily neuropathic, but it also can be secondary related to weakness and joint problems related to severe, profound loss of muscle function. It's oftentimes the case that patients don't notice the weakness until after the pain has kind of abated because the pain is so, so severe. And whether or not that's related to the fact that the weakness is there yet or not, I think it's not entirely clear. It's very hard to study this condition because oftentimes people, if they've never seen it, they don't think about it. But once you know the presentation, it's very stereotypical and should be the first thing that comes to mind, but even this orthopedic surgeon that saw this patient in the ER was thinking this was some kind of compression of nerve or something like that. And when I heard the case and talked to the patient, it was clear that this was Parsonage-Turner neurologic amyotrophy. So it's very stereotypical in how it presents. The reason people attribute to immune-mediated etiology is it does have a tight association with the antecedent event, kind of similar to what we would see in Guillain-Barre syndrome and other immune-mediated neuropathies, and so 50% or so have an infection viral infection, trauma or procedure. And this patient had both trauma and a procedure that preceded this presentation. The epidemiology, there are roughly two to four per 100,000 per year, slight male predominance. Age of onset is typically second or third decade, but this patient was in his 50s. So that's not necessarily always the case. It is usually monophasic when idiopathic in etiology, but about a fourth of patients can have a second bout years after the initial bout of pain and weakness. When you look at hereditary neurologic amyotrophy though, a lot of those patients can have a lot of recurrent bouts over time, and that has actually been what has helped people identify these generic variants because they act a little bit different, although they're very similar in a lot of ways. So this is a problem of the nerves of the brachial plexus, and I'm gonna talk a little bit more about that in a bit, but the nerves that are involved are oftentimes not part of the brachial plexus proper, but they come from the brachial plexus. And that's the reason I still think it's helpful to lump these with the brachial plexopathy processes. But nerves that are often affected include suprascapular, which was infected in this visual, musculocutaneous, axillary, all three of those were profoundly affected in this individual. Long thoracic is very common, causing weakened scapula. Anterior and posterior and osseous are also involved as well as other nerves. Phrenic neuropathies and cranial neuropathies are less commonly associated with idiopathic Parsonage-Turner neuralgic amyotrophy, and more typical of the hereditary forms, but they can happen. One thing that is very, very unusual is involvement of the lower parts of the plexus. So the nerves observed by CHT1 typically aren't very commonly affected. So median to the thenar eminence or ulnar, those are not normally involved in neurologic amyotrophy. And if you see that, you really want to push back on the history, make sure it really was abrupt onset, make sure there's nothing else that could attribute this, like as mentioned earlier, lower plexus problems with cancer involvement are something you really should think about when you see the lower plexus involved. So I'm not going to go into this in great detail, but the electrodiagnostic approach is not as straightforward as typical plexopathies, because it is typically that there's more motor involvement than sensory. And in fact, in a large percentage of patients, sensory responses are not involved. Some of that has to do with which nerves are involved. And so if you're not testing a nerve that's coming from the part of the nerve that's affected, then you're not going to see it. And that makes sense, that lateral interbrachial would be involved because that musculocutaneous is a common nerve that we test, and it's observed by that nerve of the brachial plexus. The EMG typically will localize the lesions to name their branches of the brachial plexus rather than the brachial plexus itself. And this is based on studies that have looked at over hundreds of cases to show that this is a very consistent presentation. And so it doesn't typically localize to the brachial plexus proper. One thing that we've already talked about a little bit, amplitude is a key kind of parameter to look in electrodiagnostic studies. We can't conduct across the plexus. And so you have to wait until the axons degenerate. And if they don't degenerate, then you're not going to see it. But in general, there is axon loss in Parsonage-Turner, but there's a lag time with that. So just keep that as a caveat. And the reason I pointed that out is patients are typically treated with a tapering round of steroids, if seen acutely sometimes, even when seen chronically. So don't wait for the EMG, if it's a classical presentation. Don't wait for the MRI to rule other things out. If somebody presents with fulminant severe pain that abruptly started and they have weakness in the brachial plexus distribution, it's probably reasonable to start steroids as you're working them up to rule out other things. This patient that I presented actually did quite well. It took him a year to really see any real recovery. We did aggressive rehabilitation to maintain mobility of the shoulder because secondary complications of shoulder joint problems, decreased range of motion, I see as one of the biggest problems chronically in these patients. So that's really key. And we did that. And actually now he's four to four plus grade in most of the muscles, the last time I saw him a few years ago and doing quite well. So one thing that I wanted to talk about before finishing up is some recent work that have both shown that the lesions don't seem to localize to the plexus and this unique characteristic that's been found in peripheral named nerve branches of the plexus. So these focal constrictions in nerves that are involved. And so while the lesions aren't seen on the brachial plexus proper, the majority of the patients have been, in this study at least, have been shown to have these focal constrictions. The questions that these findings raise is whether this is cause or consequence. Is this a limiter to recovery? And in fact, this more recent study suggests that surgical intervention for these constrictions may improve recovery. I think this is a very hard thing to study because as I mentioned, the patient that I saw took him a year to see really any visible improvement. And we did repeated EMGs. And for sake of time, I can't go through those parts of that case. He did really, really well. So it's hard to design studies to study this, but this is something that we should be thinking about to understand if this is something that can be used to stratify treatments, get prognosis, and possibly do interventions to improve outcomes. So before I finish up, I just want to mention a few other potential mimics. So there are other immune and non-immune causes. So multifocal motor neuropathy is not painful but can affect the upper limbs to a predominant extent. That is an autoimmune condition that is treatable. Radiculoplexis neuropathy is usually associated with diabetes, normally affects the lower limb, is also painful, has a lot of characteristics aligned with Parsonage-Turner, and some people have thought maybe there's some of the same processes with a microvasculitic process. Lewis-Summer is a variant of chronic inflammatory demyelinating polyradiculoid neuropathy that affects upper limbs more than lower limbs, but it is a more generalized process. Lastly, this image here is a case with hereditary neuropathy with predisposition to pressure palsy, that's a variant of CMT, where they had a long thoracic neuropathy and a brachial plexopathy presenting with scapular winging, and this was genetically determined to be HMPP, and so that's something to keep in mind. The key there, they can present with brachial plexopathy, but almost never in my experience is that painful, so the pain is the key distinguishing factor. So I have the distinct pleasure to hand off to Dr. Hearn, who is an assistant professor at Michigan Medicine. Thank you very much, Dr. Arnold. Let's change gears, and next we're going to talk about how we can use electrodiagnosis to inform prognosis of brachial plexopathy. I have no relevant conflict of interest to disclose. When we step back and take a bird's eye view, we'll find ourselves learning something like this schematic. Overall, between upper and lower plexus lesions, upper plexus lesions carry a better prognosis, and when we look at the supraclavicular versus infraclavicular distinction that Dr. Jorgensen introduced, we find that the supraclavicular lesions, meaning of the roots and trunks, overall carry a poorer prognosis than infraclavicular, but that's a bird's eye view, right? Well, we say things like upper plexus lesions carry a better prognosis than lower plexus lesions. We're looking across all comers, and there are probably several factors that mediate this. Some of you in the audience may have some ideas. For one, the upper plexus lesions, on average, tend to be more demyelinating. We can see oftentimes a mechanism of traction when the head and neck are pulled forcefully away from the shoulder on the ipsilateral side. We have traction or stretch of the upper portion of the brachial plexus. So we see these in athletic injuries with collision type sports. We see burners, stingers, things like that. Overall, this group tends to be less likely a root avulsion, and the lesion is closer to key functional muscles because the upper brachial plexus generally innervate the more proximal muscle. So when we look at it this way, we can come to understand some of the subcomponents that underlie prognostication, and I would encourage us as a group to think about a practical tailored way to prognosticate for these lesions based on some of these approaches. So let's try this. I'm going to try to synthesize some of the knowledge that we have on how peripheral nerves regenerate and how lesions occur to put together perhaps four things that we can think about when trying to prognosticate. I'm going to borrow a fair bit from some of the concepts really well outlined in this invited review by Dr. Robinson from 2015 in muscle and nerve, how electrodiagnosis predicts clinical outcome of focal peripheral nerve lesions. That's some good reading on prognosis if you're interested, and there's a section that specifically addresses the brachial plexus. So stepping back, I'm going to encourage us to think about four things. One is the nature and severity of the lesion. That's something that electrodiagnosis is very powerful at informing. Number two, the distance between the lesion and the key functional muscles that we want to re-innervate. Number three is clinical, not electrophysiologic, but understanding the clinical process driving the lesion. Number four is an us factor. Where are we, the electrodiagnostician, along the continuum of the patient's injury and recovery? Let's take it one at a time. Nature and severity of the lesion. My colleagues have alluded to the concept of demyelinating versus axonal. If we can establish this, we should. This is valuable. A demyelinating lesion can potentially remyelinate or heal within two to 12 weeks. So this is a striking pattern. We can have a patient with very significant weakness that's actually attributable to neuropraxia or conductive block. We can get that strength back over the course of weeks or months. In contrast, axonal lesions, by definition, are going to rely on re-innervation of some sort to get recovery. So that's the first distinction we want to draw with demyelinating carrying a better prognosis. Secondly, what Dr. Rad taught us, are we seeing evidence of a root evulsion versus a post-ganglionic lesion? With a root evulsion, we have the little root that's pulled out from the spinal cord, meaning that we have no capacity for the body to spontaneously reform that connection. Nor is there ability right now, surgically, to re-implant those rootlets in, in a way where we can restore function. So root evulsions carry a poor prognosis for spontaneous recovery. Now, importantly, depending on which roots are evulsed and the situation, there are nerve transfers and other surgeries that can be done to restore function. So these are important to identify early and connect with that poor prognosis for spontaneous recovery. Finally, assuming that we're looking at an axonal brachial plexopathy, which as Dr. Rad said is the most common, we want to know if the lesion is complete or incomplete. Is there any evidence of axonal continuity through the lesion? And if the lesion is incomplete, we can also estimate the extent of axonal loss. A lot of people like to look at the number and density of positive sharp waves and fibrillations, but our most honest marker for quantity of axonal loss is looking at the compound muscle action potential and ideally comparing it to a contralateral unaffected compound muscle action potential where we can. Let's take a bit of a deeper dive into axonal continuity and why this matters so much. So for one axonal continuity across the lesion and having some evidence of axonal continuity to key muscles indicates that we can get some recovery by what we call collateral sprouting. That's depicted here. So you can see a motor neuron. We can see the axon extending out, terminal nerve twigs and muscle fibers. And here you see an incomplete lesion with one axon out of two disconnected. So collateral sprouting basically looks like this. We have reaching out of collateral sprouts to re-innervate our denervated muscle fibers. This process takes about two to three months to start. And it's been shown that each axon can actually innervate up to five times the initial muscle fibers that it innervated. What that means is we can get substantial gains in strength just by collateral sprouting alone. That's why having any axonal continuity at all, and especially if it's more than 20%, is a good prognosticator early in the lesion course before re-innervation has occurred. If there's no axonal continuity to a muscle, then we have a situation that looks more like this, right? We have our axons that are disrupted. We have lonely muscle fibers with no neighboring axons to sprout. So how do these people recover? These lesions must recover by what we call proximal distal regrowth, meaning that an axon has to grow gradually down from the site of the lesion all the way to the muscle fibers. The challenges with this are one, it's slow. The rate of regrowth is about one inch per month. Number two, it's not reliable. It depends on the viability of the supporting structures along the way, the endoneurial tubes, the connective tissue structures that form that track. If there's hematoma scarring in between, those little axons may never make it down. And finally, it's time limited because the muscle fibers and distal endoneurial tubes don't stay viable forever. It's been shown that, and there's a bit of a range here, but the muscle viability is probably about 18 to 24 months from the time of re-innervation. So we don't have forever to make this connection. Distance matters, pathophysiology matters. Let's take a little bit more of a look at why it is that any axonal continuity implies potential for more to come. I like to teach by analogies and the one I like to use for this is a train track. Consider the endoneurial tubes and supportive tissue structures like a train track, a requisite pathway for the train or growing axon to be able to come down from the site of the injury to re-innervate the muscle. So if we're sitting at the train station, we've got our needle inside the patient's muscle and we're waiting. If we see even a single train, even one motor unit firing, what we can infer is that the track does bridge the lesion. There's something there. More trains could come. We need to wait. But if no trains are coming at all, what can we infer about the track upstream? Actually nothing, right? We don't know. We can't tell that it's fully disrupted, but we also can't tell that the trains are going to come. So those are the patients that we follow closely. We may be able to follow them clinically to see if they're regaining function in those muscles. And if they're not really, we may need to follow them electrodiagnostically. And that's what we put our needle in the muscle and look for those tiny nascent units, right? And see whether we're getting any re-innovation down or any trains crossing the track. So in summary, axonal continuity matters chiefly for two main reasons. One, if it's there, you're going to have collateral sprouting. Two, if it's there, the track is intact, meaning that more axons may be able to grow down. All right, let's talk about distance from the lesion. And I think now that we've gone over some of the pathophysiology as well as the physiology of nerve regeneration, this race against time actually becomes quite clear to us. We discussed how the growth rate of axons by proximodistal regrowth is about an inch a month. And on the other hand, we have the fact that the muscle fibers remain viable for only about 18 to 24 months. So we're really looking at a balance between two processes, a race against time. So in this context, if we revisit and compare and contrast upper and lower brachial plexopathy, we can see how this concept applies in both lesions, right? In brachial plexopathy in general, the lesion is somewhere at or around this, this region of the neck, clavicle, and shoulder. And so with upper brachial plexopathy, you can see that all the key muscles that we want to re-innervate largely live around the shoulder area. That's about one year or less worth of re-innervation time. In contrast with a lower brachial plexus lesion, where are the key muscles that a patient wants restored? Largely in the hand, right? And you can see just looking at my arm all the way down, that's looking at well over two feet or two years, and the muscles just don't stick around viable for that long. So that's why lower trunk brachial plexopathy that are complete have a very poor prognosis for spontaneous recovery. All right, the underlying clinical process. Why does that matter when we're doing electrophysiology? Well, the underlying clinical process determines what's likely to occur. So far, what we've described so far has referred to the processes of nerve regeneration, assuming that the pathways are intact, assuming that there's no ongoing damage there at the brachial plexus. But we need to consider if that's true. Are we looking at a one-time static lesion? Or are we looking at something where ongoing damage is occurring? For example, if we're looking at a case that is likely a radiation-induced nerve lesion, radiation-induced brachial plexopathy, that's a disease process where we know it tends to be a late onset and it tends to be progressive. So that's a disease course where just because there's axonal continuity, we're not going to write that the patient has an excellent prognosis for getting their function back. Similarly, if we know that the underlying etiology is a tumor, and that that tumor is encasing and moving through the neural structures, again, based on the clinical situation, that's not a good prognosis for recovery. Sometimes we don't know, right? When we're doing the electrodiagnostic study, we don't know exactly what the underlying cause is. So those are situations where I might use phrases like, assuming ongoing damage to the neural structures can be avoided, the prognosis for recovery by the prognosis for recovery by spontaneous reinnervation is, and share. The other clinical piece that can be relevant is the pathophysiology of the underlying process with regard to the supportive structures. So the case that Dr. Arnold presented of neuralgic amyotrophy, that's felt to be an immune mediated attack on axons, meaning that the surrounding connective tissue structure should be largely intact. So those overall are going to carry a better prognosis than a situation where you have massive scarring and hematoma and other disruption of supportive tissue structures. Finally, point in time course. We talked about looking at the compound muscle action potential amplitudes to estimate axonal loss, but that process is for before reinnervation has occurred. If we're doing a study at a later time point, somewhere along the patient's trajectory from denervation to reinnervation, we need to keep in mind where we are in that race against time, how much remaining distance needs to be bridged, how much time likely remains for muscle fiber viability. Put another way, if I tell you that there's evidence of trace axonal continuity three months after the lesion, that may be a fairly promising prognosis for getting more reinnervation. But if I give you that same finding at the two year time point, we're up against a deadline there and the prognosis is going to be much less good. Other things that we can look at, we can look to see at any time point is reinnervation ongoing, or is it effectively complete? Signs like polyphasia and motor unit instability suggest that there's an element of ongoing reinnervation. It shows us that the reinnervation occur that has occurred has been recent, meaning that we're likely to see more. We can also look at some signs to see if the denervated muscle looks still viable. Some have looked at amplitude of denervating potentials of positive sharp waves and fibs. This is a little controversial. It's not very quantitative, but I use it at the very extremes. So when the P waves and fibs are tiny, tiny, tiny, that suggests that muscle fibers may be nearly atrophied. And similarly, when we're moving the needle through the muscle and the insertional activity is very, very low or absent, that suggests a minimal muscle fiber viability, assuming that you're in the right muscle, technically. So putting things together briefly, I had the privilege of following a patient over time. A surgical colleague asked me to perform some serial studies. And so I got kind of a unique window into what this regeneration looks like in real life. This is a 62 year old gentleman who had right upper limb weakness and numbness after a complicated shoulder surgery. I'll show you his initial study briefly, and we'll see that there is a plexopathy of the lateral and medial cords of the brachial plexus. And he had concordant numbness through the medial forearm, through all fingers and the palmar hand, the sparing of the dorsum as we would expect with this lesion localization. And then his weakness was in keeping with that, he had a hand of benediction type posture with a median weakness, and then also evidence of ulnar clawing. On his initial study, I'm just going to pick through highlights in the interest of time. You can see that median sensory is quite involved, lateral cord. Ulnar sensory looks okay here by normative standards, but probably actually does evidence some axonal loss. Medial antebrachial is out and the radial sensory is spared. So we can see a low median motor study that looks axonal. I highlighted on his initial EMG three muscles in yellow that we can use to basically follow his progress visually. So biceps is lateral cord, plexocarpi radialis is also lateral cord by the median nerve, and then abductor pollicis brevis or opponent's pollicis are both medial cord by way of median. And so we see on his initial study, profuse positive sharp waves and fibrillation through both cords and decreased recruitment, not a lot of reinnervation yet, except for an APB, which may represent a different lesion given the time course, or it may actually represent some unmasking of the larger motor units in the setting of significant axon loss. When we move out to 3.25 months after the lesion, well, we're still fibrillating. Okay, it hasn't been that long yet, but what we're seeing here is some polyphagia. We're seeing that reinnervation occurring, which is very promising. And I'll remind us going back to the initial study for a moment here, we had said that axonal continuity was really important for prognosis. And we actually see axonal continuity through all of the muscles tested and all of the cords. So even though there are four plus positive sharp waves and fibrillations, this is a promising, this is a study with a good prognosis. Looking out 6.25 months after the lesion, we are still fibrillating. It does take time to reinnervate so many muscle fibers. And now we're continuing to see polyphagia. There's ongoing reinnervation through the lateral cord. The recruitment is overall improved. And we know that clinically the patient is continuing to regain some strength up in the fours region. When we get out to 10.5 months, we have cessation of active denervation in all but the distal most muscle. There is less polyphagia now. We're seeing more maturation of the motor units with increased amplitude and duration. And if we go super, super far out to the two-year time point, what we find is that the motor units are essentially triphasic once again, with just the increased amplitude representing that collateral sprouting. I had a little bit of the unlimited study on opponent's policies, didn't really see units here, but we can see he's got good compound muscle action potentials, 6.2 up on his initial 2.2. So pretty good reinnervation through there. So that in a nutshell is a little window into prognosis. So to recap, we covered nature and severity of the lesion, demyelinating or axonal, is there a nerve root avulsion? Is the lesion complete or incomplete? And what's the degree of axonal continuity? Distance from the lesion, our race against time. Underlying clinical process, is this a one-time insult or a progressive process? And how much disruption do we think there will be to supportive tissues? And then finally, where are we in the time course? Are we seeing evidence of ongoing reinnervation? Are we seeing that muscle fiber tissues are still viable for reinnervation? So with that, I will conclude. I want to thank once again, our fantastic panel of speakers. I've worked with this team a few times now. We presented some neuropathy type updates last year and got some feedback that you all wanted to hear more about the brachial plexus. And so we built that in this year. So thank you to my colleagues, Dr. Jorgensen, Dr. Rad and Dr. Arnold for pivoting and building and continuing to try to identify interesting electrodiagnostic topics to share with you all. Thanks for tuning in and hope you enjoy the rest of the AAPMNR annual assembly this year. Take care.

electrodiagnosis

brachial plexopathy

clinical presentation

prognosis

demyelinating

axonal

nerve root avulsion

axonal continuity

upper plexus lesions

lower plexus lesions