So, welcome everyone to what should be a really intense, dense, but highly informative session on neuromuscular updates. You might be wondering why we've got two directors here. I guess, you know, Sean and I are wondering that too. But what happened was we had a two-part series that we had proposed. They gave us the acceptance note for one of them, and then we decided to keep the group together and just make it work with a 75-minute session. So that's why it's going to be a little bit of a whirlwind, but you'll see why it was worth it when you see all the speakers we have today. Some quick housekeeping due to the density of the session will be keeping presentations to 12 minutes. What that means is, you know, if speakers finish a little early, we'll take a question, usually probably just one from the audience in real time. We may not be able to take a question if we go up to the 12-minute mark, and we'll just sort of flip over speakers, but no one's in the room after us at the end of the session, so we will be able to talk to the audience at the end of the session. So if you have any questions that you miss out on, we'll get to them hopefully later. Now I'm going to get things moving along, so I'm going to introduce the first three speakers just all in a row, and then we'll introduce the other three with Sean going next. So Dr. Etta Ways, a physician scientist at Shirley Ryan Ability Lab in Chicago, she's going to provide us insights into nerve transfers, electrodiagnostics, and how that pertains to the management of patients with tetraplegia. Dr. Daniel Cai is an assistant professor at UT Southwestern Medical Center in Dallas. He'll be talking about the challenges and what's new with managing neurologic hematopoietic syndrome, or Parsonage-Turner syndrome, and Dr. Enzrud at the University of Missouri, who serves as the director of the MDA clinic down there, and the ALS Center of Excellence. And he'll share his approaches to managing myasthenia gravis. And now I'm going to introduce my co-director, Dr. Jorgensen. He's a clinical professor at Albany Medical College, known for his expertise in both neuromuscular medicine, sports medicine, electrodiagnostics, and ultrasound, and he's going to take over and introduce our remaining speakers as we try to stay on time. All right, thank you, Dr. France, for that introduction and for co-directing this session with me. So let me take a moment to introduce Dr. Colin France, our session co-director. He is an associate professor of PM&R and neurology at Northwestern University, where he subspecializes in neuromuscular medicine, electrodiagnostics, and neuromuscular ultrasound, and he co-directs the Interdisciplinary Clinics in Complex Nerve Injuries, Diaphragm Muscle Paralysis, and is the EDX Lab Director at the Shirley Ryan Ability Lab Hospital, formerly RIC. All right, let's meet our remaining speakers. Dr. Sandra Hearn, an associate professor at Michigan Medicine, will discuss advancements in diagnosing and managing peripheral neuropathies. Dr. Ileana Howard, from the University of Washington, who co-directs the ALS Center of Excellence at the VA Puget Sound, will share insights from recent ALS clinical trials. And finally, Dr. Nassim Raad, an assistant professor at the University of Washington, will review approaches to spinal muscular atrophy from pediatric to adult care. All right, please join me in welcoming our first speaker, Dr. Adewoye. All right, thank you for that introduction. And, oh, excellent. And we've got our laser pointer hopefully working here. Yes. It's kind of faint, but there it is. Excellent. And so, as I mentioned, we're going to talk a little bit about electrodiagnostics as it pertains to neurotransfers and tetraplegia and how they can be valuable. And so, I have nothing to disclose. Hopefully from this talk, you guys are able to understand the benefits of having timely electrodiagnostic evaluation in individuals with cervical spinal cord injury and understand a little bit about how low motor neuron loss affects the reconstructive surgical options that are available for these individuals after their injury. And so a lot of you may be familiar with nerve transfer surgeries, but just to make sure we're all on the same page, the idea of nerve transfers has been around a while, as early as 1948, and it was initially used to restore function after brachial plexopathies. And so imagine if you have an injury to part of your brachial plexus, right? And so that's just what that's demonstrating over here. You could have, once you have that injury, resulting in denervation of the muscle. Now in a nerve transfer, that involves surgically moving a healthy nerve from a muscle to a paralyzed muscle, right, as that is demonstrated there. Oh, rewind. And so now after that transfer, you have recovery of that low motor neuron. You get re-innervation of that muscle. And so in spinal cord injury, it's kind of the same idea, right, except now the injury is within the spinal cord and not outside of it in your brachial plexus. But that same procedure still makes sense, where you can now take a transfer, you can transfer above the level of the injury, right, to below the level of injury that is paralyzed, such that your paralyzed muscle is now under volitional control and you have restored specific function. And so there are certainly many things, many options in nerve transfer surgery. Specifically in spinal cord injury, there are particular surgeries that are done commonly and that are helpful depending on the level of the injury. So for example, if what you want to restore is elbow extension for someone with a C6 injury, right, a common donor is to take the axillary branch to the posterior deltoid, right, which is supplied by your C5-C6, and then transfer that to the radial branch to the, say, one of your triceps, right, to restore elbow extension. If you wanted to restore wrist and finger extension, right, so your recipient would be your posterior interosseous nerve that innervates your wrist extensors and finger extensors and your donor, right, could be the radial branch to the supinator, right, or the brachioradialis, which is C5-C6 and is under volitional control. Similarly, if you wanted to restore wrist flexion or finger flexion, your recipient could be your anterior interosseous nerve, right, that's in charge of your, you know, your thumb and your finger flexors, and your donor could be your musculocutaneous branch to your brachialis, which is, again, a C5-C6 muscles. Hang on there. And so this is an important concept to grasp, right. So I talked about, hey, we're taking, if you can see that, a branch, right, super lesionally above the injury, right, and then we are grafting it to a nerve muscle group below the level of the injury, right. And so you might wonder, you know, how do we figure out what is above and what is really below, right? So we have our neurologic level of injury, and as I'll talk about a little bit later, it doesn't really represent this intermediate level, this lesional level, right, which involves upper and lower motor neuron loss, which we'll talk about actually right here, right. So when we think about spinal cord injury, right, we know you have loss of your descending corticospinal inputs, and at the level of the injury, right, and saying this C5-C6 translocation there, right, and so we have mixed upper and lower motor neuron, right, and presumably above level of lesion is normal, and below the level of lesion, presumably intact lower motor neuron bodies, and they just don't have that descending input. But really, how extensive is this lesional area, right? And so this is actually some pretty similar work by Christine Thomas that showed, so here are these sections that we're taking post-mortem of individuals with spinal cord injury, and this upper left corner is what a normal section looks like, right. B, C, and D are sections across the epicenter of the lesion, right. You can clearly see there is loss of the architecture to both the gray and the white matter. And so when we actually look at E, this section over here is taking at somebody with a T9 injury at the level of the injury. And so for reference, for those of you who haven't seen this kind of staining before, which is staining the myelin, so you can see the large myelinated fibers, oh, okay, great. Oh, that's better. So this stain right here, I just want to show you this over here on the left. It's what it should look like, right. And so you can see your myelinated fibers clearly, right, surrounding your large axons. And what's clear here is that you lose that, right, you're losing your large fibers. But what's interesting is that F is a section taken from the same individual, the T9 injury, but now this section is at the L1 level. And you see maybe a couple of more myelinated fibers, but not that much, right, comparing it to the normal section. And so when she quantified that, saw, let's say for E, represents the epicenter, right. You're looking below the epicenter and above the epicenter. You see loss of motor neurons both above and below. And this was done in just a few subjects. And so some recent work that we've done where we've tried to use electrodiagnostics to sort of quantify the extent of the injury. Here's a study that we did, collaborated with some of the folks out in UBC, where we looked at the presence of fibrillations in positive sharp ways, so active denervation, as a marker for abnormal, marker for low motor neuron abnormalities. And so here, right, is this injury level, it's what we're pointing to here, right. And then we are then quantifying how frequently are we seeing these evidence of active denervation below the level of the injury. And I think what's important here is even five segments down and below, right, almost 50% of muscles that were tested had evidence of active denervation. But what does that even mean functionally, these fibs and these positive sharp waves? And so some of my recent work here, where we've actually quantified using more advanced motor unit and number estimation methods, what is the change in the number of motor units in these infralesional muscles? So these are control subjects, orange SCI subjects in the C7, C8, and conius and EI, where we see a clear reduction in the number of motor units, right. So it's not just active denervation that we're seeing, but also actual loss of motor units, motor units, infralesionally. Okay, and so why is that important, right? So when we think about timing of nerve transfer surgeries, and all of this data we take from the brachial plexus, brachial plexopathy literature, surgically, if there is no lower motor neuron loss, right, we don't see much denervation of the muscle. And we think that when we restore the, when we use that nerve transfers, we can actually do that, you know, nine, 12 months is an okay time to wait to do this surgery, right. So it's not as time sensitive. But if you have lower motor neuron loss, and that's demonstrated in B, there is this now a time component, right, where we know that three to six months is a better time for us to surgically intervene, oh, we're gonna close there, in order to get good outcome. And let's continue on here so we can get through all our slides. Now when you have a surgeon ask you to do electrodiagnostics, what do you think about when you're doing your ADX, right? What do you evaluate? And so obviously it's important to evaluate both your donor and your recipient, but also think about evaluating the redundant muscle. So I talked about the brachialis as a good donor muscle. So you want to make sure you evaluate both, not just the brachialis, but the biceps and the brachioradialis, right, so that you have your redundant muscles left over. And as well as evaluating the recipients to see how much lower motor neuron loss you have there. And the final part is you really need to tailor your electrodiagnostics to what functions you are trying to restore, right, and so that means you might be needling muscles that you don't typically needle, right, you might have to needle the supinator if you think that's gonna be a donor, right, or the brachioradialis. And I think we're near the end here, so that's great. And so I know this was quick, but hopefully we've talked about how lower motor neuron loss generation after spinal cord injury is important and something to think about when you're doing electrodiagnostic evaluation of people with cervical spinal cord injury, because this can influence their ability to be nerve transfer candidates, something that we should do early, right, after their injury, and that it's important for us to differentiate between upper and lower motor neuron patterns of injury in these individuals. So thank you everyone there, I'll end, and we have one minute for questions. Any questions from the audience? Yeah, please come up to the mic, or I'll bring a mic to you. And then while we're doing that, can we get the slides up for the next speaker? here. In the patients you're doing for spinal cord injury, did you do nerve conduction studies on both sides? Correct. To look at the CMAP amplitude? Yes. Okay. Yes. So that would also be a good way of looking at the axon losses. That was one of the things. It is a good way, right. Because sometimes fibrillations and positive waves could be confusing. And so that's one of the things which I usually end up doing, and so that's what I was trying to bring that point across, that not just the EMG, but also nerve conduction. Okay. Why don't you respond to that? And we have 10 seconds. 10 seconds. All right. Okay. Exactly. So we do look at the CMAP. But something to know is that you can have a 50% loss of the number of motor units and have a normal CMAP. So the CMAP alone does not tell the story. Comparing the opposite side. Well, we'll talk about that after. Thank you so much for your question. Thank you. All right. Thanks, everybody. My name is Daniel, and I'm here to talk about neuralgic amyotrophy. I have no disclosures. So neuralgic amyotrophy, it's a disease entity that's kind of changed names multiple times throughout the years. You know, I think it was first called Parsonage-Turner syndrome, and colloquially, that might still be the most common name. And so I'm here to talk about neuralgic amyotrophy. I have no disclosures. So neuralgic amyotrophy, it's a disease entity that's kind of changed names multiple times throughout the years. You know, I think it was first called Parsonage-Turner syndrome, and colloquially, that might still be the most common name. For a while, we tried calling it idiopathic brachial plexitis to be a little bit more scientific, but now there's been a little bit of a paradigm shift that we recognize that the lesions are not just in the brachial plexus, but in the individual peripheral nerves after they come out of the brachial plexus. So the most popular name now is neuralgic amyotrophy. Classically, it presents with sudden pain going into the arm or the scapula, followed by areas of patchy weakness afterwards. This is a fairly under-recognized and under-diagnosed etiology. We used to think it was very rare, but now we think the incidence can be as high as one in 1,000 patients. Oftentimes it can mimic radiculopathy or shoulder pain, so it's probably pretty under-diagnosed. In the classic presentation, the patient has non-traumatic, severe pain going into the shoulder or the scapula. This can often be very, very uncomfortable, greater than 7 out of 10, possibly the worst pain they've ever had in their lives. Usually about days or weeks afterwards, you can develop weakness, usually in the proximal arm, but there's certain nerves and muscles that are preferentially affected, which separates this disease from other etiologies like radiculopathy. A lot of times you get long thoracic involvement or medial scapular winging. You can get a lot of phrenic involvement or diaphragm weakness, as well as in the distal arm. It classically affects the AIN and the PIN innervated muscles. Lots of times you see sensory deficits on the lateral upper arm or lateral forearm. One of the tricky things about this disease is that we like localization. We like putting things to a certain part of the brachial plexus or the nervous system, but a lot of the times the pain, weakness, and sensory distributions don't necessarily match up, don't necessarily localize well. Here is some thought. There's an autoimmune process involved. About half of patients have some kind of antecedent event. One of the things that you want to look for is medial scapular winging. You take a look at the patient's scapula. You have them abduct their arms, put them above their heads, and then with forward flexion, you see the scapular come out towards you and then rotate medially. This is very classic for Parsonage-Turner. Again, you can have phrenic neuropathy. So in the picture on the left, the left diaphragm is significantly elevated. You can have shortness of breath or arthopnea. You can diagnose this with x-ray or ultrasound. And classically, a lot of times you see anterior interosseous weakness. So you can have the patient try to do an okay sign. If they're not able to get their fingertips together, that might be due to weakness of the FPL and the FTP. So we have our classic phenotype for neurologic amyotrophy, but there's also more atypical phenotypes that we're recognizing as well. You can have the pain and then just weakness in one nerve distribution, be it the AIN or the PIN muscles. Sometimes you can have just sensory findings or just distal findings. So clearly it's a pretty hard diagnosis to make already when you take into account all these atypical phenotypes. A lot of the times these patients get extensive workup, MRIs of their neck and brachial plexus, electrodiagnostic studies, workup for vasculitis, and it is a little bit of a diagnosis of exclusion. For pathophysiology, we think it's probably autoimmune, though we're not quite sure. There is a little bit of a genetic predisposition. There is a certain gene called CEPT9, where if you have it, you have recurrent episodes, and there is possibly some involvement in environmental factors or biomechanical disruption. On electrodiagnostic testing, needle EMG of the muscles that are clinically weak should show axonal chronic neurogenic changes, Fibs positive sharp waves, chronic neurogenic changes, but sometimes the findings are not as convincing as you would expect for the amount of weakness. We always teach our residents and trainees that in brachial plexus injuries or postganglionic disorders, the sensory nerve conductions should be affected. However, in Parsonage-Turner, that might not be the case. Some studies show that in as many as 80% of patients, they are normal, even if you test a nerve that should be in the distribution of the sensory deficit. So overall, a lot of the times, Parsonage-Turner is a clinical diagnosis. EMG can be supportive and helpful, but you may not get as convincing findings as you would like. For medical management, there is limited evidence that high-dose prednisone within the first month of symptoms may help with the pain and speed up recovery. There's not too much evidence in immunotherapy past the first month. Oftentimes, the pain is pretty severe, so you can treat that with NSAIDs, gabapentin, opiates if needed. I think the traditional thinking of Parsonage-Turner is that it's something that's very self-limiting. Pretty much everybody makes a complete recovery within a few years, but recent evidence shows that that might not necessarily be the case. About 50% of patients continue to have some kind of issues with their ADLs. About 50% continue to have persistent pain, primarily in the scapular region. A fair amount of patients, even after 12 months, 18 months, still have complete weakness in the muscles that are involved. And particularly, you can see this in the distal muscles like the AIN or the PIN. Scapular dysfunction is a big part of pain and reduction in function in these patients. What happens is when the patient is in pain, what happens is when you have weakness of your serratus anterior, your other parascapular muscles like the trapezius and the levator scapula have to overcompensate. The muscles get very tight and painful. So, you want to send them to a therapist with experience in treating scapular dyskinesis. A lot of this revolves around teaching the patient how to evenly distribute their periscapular load as they're doing things. Traditional therapy, just doing a lot of exercises, trying to strengthen the serratus anterior is typically not effective and it may actually worsen the pain and weakness. And then some of the most exciting things that are coming out now that we have more neuromuscular ultrasound and now that we have more MR neurography is that we're finding lesions that are outside of the brachial plexus. On ultrasound, oftentimes you find enlargement of the peripheral nerves themselves or even individual fascicles of the nerve when you have this disorder. I think some of the most classic presentations you see is you can see enlargement of the main median nerve or the anterior interosseous nerve in the upper arm. Same thing with PIN and radial nerve. And what we're seeing sometimes is there's reports of these things called hourglass constrictions. What that is is the nerve is actually twisted in on itself like a twizzler. On ultrasound, as you're scanning across, the fascicles actually rapidly rotate like you would expect. On long axis, you can see those focal areas of constriction. And sometimes if you refer them to a peripheral nerve surgeon, intraoperatively, it actually looks like the nerve is twisted in on itself. So sometimes the surgeons can use a very high power microscope, go in there and cut the individual layers of connective tissue to try to untwist the nerve. I think these hourglass constrictions is still an area of hot debate in neuromuscular medicine as well as in peripheral nerve surgery. Some centers, they find these hourglass constrictions in a fair amount of their patients. I think in other centers, you see them once every few years or possibly never. So I think that's kind of where we are with Parsonage-Turner right now. We see these evidence of mostly swelling on imaging. Sometimes we see hourglass constrictions, but neuromuscular ultrasound, it's a new technology. A lot of it is very user dependent. So I don't think we quite understand exactly how often we should be seeing them and which patients we should be referring to surgery. So I believe we have about one minute for questions. Any questions? I can bring the mic to you. Oh, yeah, way in the back. Come up. Do you have an explanation for why the sensories are normal? Do we have an explanation for why the sensories are normal? I do not. So, but one of the possibilities, this is a mixed axonal demyelinating lesions often. So do you think that the sensories are just, you know, conduction block phenomena? I know it doesn't resolve in the kinetics of a, we think of like with trauma, but do you think that could be one of the reasons you would have a snap? Yeah, I think that's definitely a possibility. I think classically we think of NA as just, you know, purely axonal, but you know, I think there's a strong possibility there's, it's a mix of both axonal and demyelinating. Any other questions? Here you go. I heard you mention at the end, it's hard to determine which patients to refer for surgery, but I was wondering what would surgery, what was the, what would surgery accomplish? So I think there are some centers that are very, you know, interested in seeing these hourglass constrictions. There's some literature that shows if you have these severe constrictions, like maybe that makes it more likely that even after 18 months, two years, you don't have any recovery in that muscle. So sometimes they go in there and they try to release these lesions so that you have some kind of recovery, you know, in other centers like mine, usually we watch these patients if we, and we see if there's any kind of natural recovery. If there's not, other options is you can graft across the segment where you have damage or you can do nerve transfers, which work quite well. Awesome. Thanks. We're going to have to stop it there. Awesome talk. We'll get on to the next speaker. Sure. Thanks. Originally, as Colin mentioned, we were going to have twice as much time and I was going to tackle the management of myasthenia gravis, which has become a much more complicated and fortunately successful endeavor because we have so many new agents like complement inhibitors and even cell-based therapy like CAR T. But I just have a short amount of time, so I thought how could I pivot and make this section more helpful for people, give you some pearls by any chance, and really, before we can treat myasthenia gravis, we've got to identify it. So I'm trying to give you, the thing I love about physiatry is how we haven't given up on the exam and when we're all replaced by AI, so much of what we do, AI's not going to replace the exam. So I think it's an important thing for us to continue to focus on. So this section is, does the patient have myasthenia gravis, and how to do a quick and accurate bedside assessment of that. So MG diagnostic tests, if you're a Tom Petty fan like me, you know that the waiting is the hardest part. So how can you test? You can send the antibodies, they go to an outside lab, that takes days to weeks to come back, they're not always positive. You can do an EMG study, that's going to take time in nearly every location to get set up and to do, so you kind of got to take it on faith or take it to the heart. But I think we can do better than that. And we can do an exam bedside within minutes that is research-based, backed by data, and is really quite accurate. So just to review the features of myasthenia gravis, it's actually not an uncommon disease. When you look at epidemiologic studies of the incidence of these antibodies, it's really not that uncommon, but it presents in such a kind of nebulous fashion, it's really hard to identify sometimes, because weakness and fatigability have a million factors that can go into that. But there are some more specific things, ocular, we get ptosis, or droopiness of the eyelids, you can get diplopia or double vision, you can get dysarthria, dysphagia. And then there's a weakness that often occurs in myasthenia, which is kind of a myopathic or a limb-girdle distribution, usually more proximal than distal, but the unique factor of it is that it's fatigable, and that's very unique. And then you can also, of course, get respiratory muscle involvement. So here's just a couple of pictures of ptosis. So again, so we're gonna focus on, for the purpose of this quick assessment, on ptosis and extremity weakness. So ptosis can have multiple etiologies, and there are powerful forces who want us to diagnose everyone with myasthenia gravis, we've all seen Vivgard commercials, there are drugs that are quite effective, but you know, about $800,000 a year, and once you start them, you're on them for life, okay? So it's important to recognize that there are lots of things that cause ptosis which aren't myasthenia, the most common being, and I'm so proud of being able to pronounce this, dermatocoliosis. And that's when you have degeneration of connective tissues and you get a static, loose, reductant skin, and you may even get dehiscence of the muscle, the levator palpebrae, and that's right here. So ptosis, rather than being static, it's variable, it'll change on the same patient over time, and it only involves the upper eyelid. So some of you may be familiar with this ice pack test, and the idea is there's better neuromuscular transmission at cooler temperatures, but to do this, if you see a patient, say you're on an inpatient rehab unit, this has certainly happened to me, you think, this patient's not doing very well, maybe they've got myasthenia, you've got to find ice. Anybody who's ever used one for an injury knows that those squeeze packs really don't cool down much, but you apply it, and if you do that successfully, you can see, going from the left to the right there, that cooling can actually improve the ptosis, but you know, that's kind of a hassle, it's not very efficient to do in clinic. So I want to make sure everybody's familiar with the Bienfang test. If you don't like eponyms, they're not super trendy, although I know Don Bienfang, he's a wonderful person, he used to walk down the hallways of my hospital holding chicken eggs, because long before chickens became hip, he had his urban chickens, so I have an affection for him. But you can also call it the FECT, or the forced eyelid closure test, and don't we love in physiatry, we've got agonist and antagonist muscles, so if you contract an antagonist, you rest the agonist, right? So this takes advantage of this, you can see this patient on the left has ptosis on the right. So you ask them to not simply close the eyes, I always tell patients, imagine there's soap on your face and you don't want to get it in, I model it for them, and then I kind of coach them to keep doing that for 30 seconds, and then just open their eyes, and you can see that 30 seconds of contracting the orbicularis oculi has rested the levator palpebrae, and right there at bedside, it took you less than a minute, you've identified there's this ptosis that resolves with rest. And that is, in this great paper here from neuro-ophthalmology, the sensitivity and specificity of that test is 94% sensitive and 91% specific. So it's a great test, you can do it very quickly at bedside. So what if there's no ptosis, or what if you're wondering about, you know, what other kind of weakness? What about arm abduction? And you could always do, and I see different people do this different ways, oh, we have them do the chicken dance like this. And that, yeah, and then I see people, oh, I have them put the hands up and go like this. And I find that a little disturbing, if you've ever been to like a bat mitzvah, or a wedding where they did a Bhangra dance, and they invited participants, and somebody's mom or dad suddenly breaks out in this bizarre move, and you're like, where the hell did that come from? So I did a little dance history, I'm like, where did this come from? And I actually found it came from Tony Montero, and Saturday Night Fever from 1977. So that's the arm spin, and here we go. So unless you want to dance with your patients in clinic, and some of you may, I mean, we have great dance medicine experts, maybe you want to try something a little more sensitive and specific. So this is a test we developed in Boston called the MG-SAFE, shoulder abduction fatigue exam. You can do it very quickly. First you check shoulder abduction, and you check both sides to ensure they're symmetric. And then you model for the patient, you do 31 hertz, or one per second, full abductions, and you do them at a constant, or isokinetic, so that they have exercise from the, or physiatrist, from the eccentric contractions as well as the concentric, right? And then at 30 seconds, you test both sides again, and we found this to be very sensitive and specific. You can see in 11 myasthenic patients, 10 were positive, and other neuromuscular diseases, none were positive. But don't believe me? Try it on your next myasthenic patient. So here we have, very quickly, in two minutes, we've looked at the eyes, and we've looked at the extremity weakness. And these are both very sensitive and specific, so we can come much more quickly to an answer about what should our level of suspicion be in someone with myasthenia. Well, why is this important? So for such an indolent disease, this is an electron micrograph, and it shows the nerve terminal here, and then the postsynaptic membrane. And ideally, postsynaptic membranes look like a delta, you know, where a river goes into a sea, and you have a tremendous amount of shoreline, a tremendous amount of surface injury. And what happens, unfortunately, in myasthenia is that you get an abnormal neuromuscular junction, you get loss of invaginations of this postsynaptic membrane, and it's kind of timely. We've had a lot of hurricanes this year and so on, which have been devastating, or floods, and this causes irreversible damage to the postsynaptic membrane. So you can cause long-term irreversible fatigue in people with myasthenia, and actually even fixed weakness. Some of you may have seen there are some untreated myasthenics who their diplopia never resolves. So it's really important for us to identify these patients so we can get them on these newly much more successful agents, and hopefully become like, you know, MS used to be just a horrible disease, and it's really becoming more like diabetes now in many, many patients because of more effective medications. And we'll try and get there in myasthenia as well. So think about utilizing the Bienfang test, or if you'd like to call it the FECT, and the MG-SAFE. Thank you. You have one question or else move on? No? Okay, great. Great, thank you, Eric. I'll ask the question, Eric. Yeah. Since we have, we have two minutes. Okay. So I guess with that test, if you're concerned that sometimes some people have maybe some fatigue and weakness, but you know, the sensitivity, but like specificity for someone who you have concern about like maybe doesn't actually have a neuromuscular junction disorder, but who may, like what's the threshold? Cause you know, four out of five is sufficient to call that a positive test for the shoulder? Oftentimes I call it what I consider a four plus out of five, where it's definitely asymmetric with the other side, but it's not developing moderate weakness, but it's developing an asymmetry because you have the advantage of checking the rested side at the same time that you don't develop in a 31 Hertz contractions with any other neuromuscular disease. Excellent, thanks. All right, our next speaker is Sandra Hearns speaking about managing and diagnosing peripheral neuropathies Thanks everyone. This is great stuff. I'm learning a lot from each speaker. I'm gonna take 12 minutes, give you a lightning update on neuropathies and hopefully give a few things you might be able to bring into your clinics or electrodiagnostic lab. Distal neuromuscular function. When we're thinking about peripheral polyneuropathy, we really need to understand this as a spectrum. It's not a disease or lack of a disease, black and white. Early in life without other disease processes, people start out with pretty good distal neuromuscular function. And what we see across the population over time and with age is divergence. There are people who remain having excellent function all the way up through their 60s, 70s, 80s, 90s. These great sural nerve conduction studies that we see. And then we also see people for whom that function tapers very rapidly. The challenge for us is that there's a gray zone in between. And we all see in the clinics and in the electrodiagnostic labs, people with varying degrees of a gradient of distal neuromuscular decline. And the challenge is, regardless of whether they hit the diagnostic criteria for neuropathy or fall just shy, it's clinically relevant for this group. And they're a group of people we can help. How do we know this? And why does it matter? Well, we can ask older adults, maybe every two years or so, about whether they're falling. This longitudinal cohort study, done by Dr. Callahan et al, did exactly that. What you see here on the x-axis there is time, years, and it's centered up on the moment where someone is diagnosed with neuropathy. On the y-axis, you see the percentage of the population in the cohort saying, yes, I have fallen down recently. And what you can see with the cases in orange and the controls in blue is that, not surprisingly, people with neuropathy fall more than people without neuropathy, and that divergence increases over time. But what's particularly interesting is if we look back, if we look back before the diagnosis of neuropathy, you see that functional divergence happening as early as two, maybe three years before the diagnosis of neuropathy. What this shows us is people are experiencing a clinically relevant distal neuromuscular decline that is associated with falls, and it's happening before that point that we as physiatrists can pinpoint that they have a neuropathy. We need better measures. I'd argue that we kind of have better measures. Early and meaningful functional loss is actually electrophysiologically measurable. My colleague and mentor, Dr. Richardson and his group looked at distal sensory and motor function, looking at ankle proprioceptive precision, that's a distal sensory measure, and ankle rate of torque development, a motor measure. Both of these are correlated with fall risk. And they looked at how these aligned with fibular motor amplitudes, something that's readily accessible to all of us in the electrodiagnostic lab. What they found is shown here. In a sample of older adults with a range of peripheral neurologic function, they found that the fibular motor amplitude, which is plotted on the x-axis, predicts almost 60% of ankle proprioceptive threshold, which is plotted, you can see, on the y-axis. Now remember that for this, for threshold, the lower the better. A low proprioceptive threshold means that the ankle can detect tiny fractions of a degree of motion. And so what you see there is that even among patients with a fibular motor amplitude greater than 2.0, that's that origin point on the graph, all of these people have fibular motor amplitudes above the threshold that many of us use for diagnosing axonal neuropathy. And yet, even in this population, we see a range of distal sensory function. The data suggests, really looking at it, that it's not until the fibular motor amplitude is greater than about maybe five millivolts that we really see optimal distal neuromuscular function. So thinking about that deep fibular motor CMAP amplitude functionally, and not just as a disease cutoff yes or no, can help us identify our patients who may be at greater risk for falls and for distal neuromuscular decline. Number two, what else can we use? If we know we need better measures of distal function, is there anything else in the electrodiagnostic laboratory that we can harness to our advantage? I'd like to put forth that we can actually go deeper, or perhaps I should say we can actually go more distal. The Searle Sensory Study is not the most distal nerve that we can test. And if anyone has experience with some more distal nerves, one of them is the medial plantar mixed nerve conduction study, in which we're stimulating in the sole of the foot. Gives us a more distal segment of the nerve to test, as shown there. Some considerations with this. First of all, diagnostic utility can be quite good when appropriately used. What we see here is a study looking at 86 patients with a mild neuropathy-type phenotype, not much weakness, and then 204 controls. And using cases and controls, the group looked at a receiver-operator curve. So if we recall how these work, ideally for an ideal diagnostic test, we wanna see that curve go all the way up towards the ceiling and across. And what we see there is that the two curves for Searle and superficial fibular kind of run very close together. And that curve that's getting much more up toward the corner, that excellent diagnostic utility is actually the medial plantar mixed nerve study. So it does have enhanced diagnostic utility. Here's the catch though, in the consideration I offered you in the lab. The lower limit of normal for this study can be quite low for amplitude. People in their 50s and 60s may have a lower limit of normal of two or one microvolt. So how do I use this? I use this in the younger populations, people who are less than 60 years of age with a mild neuropathy phenotype. In other words, a low or borderline normal Searle snap and a clinical picture that fits with this. In other words, if I've done the usual stuff, it's a youngish patient and a mild distal neuropathy is still on the differential diagnosis for their main impairment, that's when I might use this. Second tool in the basket for distal studies is EMG of a distal dorsal foot muscle. EMG is great because it's sensitive for small amounts of axon loss. It doesn't rely on a normative data curve. It doesn't rely on comparison to others in the population. You can use that needle to see, are there fibers that are actively denervated? Are there motor units that are actively reinnervating, suggesting an active neurogenic process? Shown in the picture there, it's the fourth dorsal interosseous pedis, EMG. The EMG needle is inserted just proximal to the metatarsal heads, number four and five, 30 degree angle pointing towards calcaneus. Some practical considerations for this one, don't overcall. Distal foot muscles, they can have a little bit of increased insertional activity and some abnormalities. For me, I look for two plus positive sharp ways in fibrillations before making a diagnostic call and or motor unit action potentials with polyphagia and long duration, suggesting that there's a process that's more active. So now between interpreting the fibular motor nerve conduction study amplitude functionally, the medial plantar mixed nerve study and a distal dorsal foot muscle, we have a few extra tools for assessing those patients with potentially a mild neuropathy. But you know what, as we foray more into teasing out the borderline and the mild, because of this, I would argue that our clinical acumen and our history and physical examination become all the more key. Ultimately, it's the patient's clinical history that guide us whether to go deeper down this pathway to look for potentially mild disease or whether either way it's really not on the differential. And these patients come in with sensory complaints, right? They don't come into your office saying, my foot intrinsic muscles have stopped working. And so on the sensory exam, it's nice to have a tool that can quantify things a little. If you haven't tried using the vibratory tuning fork for testing sensation, I'd recommend trying that out. You can hit the tuning fork, 128 hertz tuning fork and acclimate the patient, show them what it feels like on their finger. And then I put it on the MTP joint of the great toe. Tell me when the feeling goes away. As soon as they say the feeling's gone, I pick it up, move it to the malleolus. Tell me when it goes away. So with one hit of the fork, we can establish, is there a vibratory sensory deficit and is there a length dependent gradient? Both of which are things that we're looking for when considering is this a distal neuropathy type of phenotype or not so much. So one physical exam tool for the toolkit. If people are curious about thresholds and cutoffs, studies suggest that if people can feel the tuning fork for less than about eight seconds at the great toe, that probably correlates with a little bit of relevant, relevant sensory decline. Doesn't mean they're neuropathy threshold, but you might have found something relevant. Moving on. Our CIDP diagnostic criteria were updated in 2021. There are a couple of good takeaways that we can carry back to lab. Some of the major changes, atypical CIDP is now no longer used. We call out the specific CIDP variants, multifocal CIDP, motor, et cetera. And that reflects our emerging understanding of the variants. The common thing underlying all of the CIDP variants is that the pathophys is demyelinating and they generally respond well to immune therapy. That's the common route. Number two, between definite, probable, and possible CIDP, the definite and probable have been lumped together and we just call it CIDP. So it's CIDP or possible CIDP, depending on whether criteria are met in at least two nerves or just one nerve. And finally, sensory abnormalities on nerve conduction studies are now included in the definition of CIDP, if it's a variant that involves the sensory nervous system. More details are in that 2021 guideline, but these are overarching framework considerations that are changed. That's the detail. I print this out and pin it on the lab so that we have it posted if there's someone borderline. Lastly, this is a little bit of a paradigm shift in how we think about some of these neuropathies. We now have a greater understanding of a category of neuropathy that we call notoparanodopathies. And these are neuropathies that present primarily with the hallmark of conduction blocks. If you see the diagram in the top side of the screen there, top left, we can see an axon and the various nodes of Ranvier. And you can also see the thick internodes that are heavily myelinated. So traditional demyelinating diseases like CIDP, they attack the internodes. And studies have shown that you can lose about 95% of that myelin thickness at the internode and still have adequate conduction. However, if the losses occur at the perinodes, and you can see the perinodes zoomed in right there, even small amounts of loss can lead to a failure of conduction, what we call conduction block. And so this means that we can have disorders where there's not necessarily a whole lot of slowing or temporal dispersion and the hallmarks of demyelinating disease, and instead we just have conduction failure. And these are the notoparanodopathies. As you see there, these are some of the ones that have been largely reclassified. This really disrupts our binary classification of neuropathy as demyelinating and axonal. So if you've in the past thought of it more like this, you have focal demyelination that can present with slowing, can present with temporal dispersion and phase cancellation, or can present with conduction block. Now we add that there's this concept of reversible conduction failure that occurs with problems at the nodes or internodes. Sorry, the nodes or perinodes. And that can give rise to conduction block directly. Okay, so some of these multifocal motor neuropathies and what's thought of as the acute axonal Guillain-Barré syndromes are actually those. That's five updates in neuropathy for you. Thank you. Thank you. Thank you so much. And next up is Dr. Eliana Howard, who's gonna talk about insights from recent ALS clinical trials. Good afternoon, everyone. Okay, so I've been tasked in giving a lightning ALS update in 10 minutes. I have no financial disclosures. This phrase was recently represented to me. I'm told that many medical students are told at the beginning of their medical education that half of the information that they will learn over the course of medical school will turn out to be incorrect. And yet we're unable to tell them which half of that material will be incorrect. And I was further intrigued to know that this phrase actually was first recorded in the 1940s when they said that medical education was changing and medical knowledge was changing so rapidly. I wonder what they would think if they would see where we are today. So this is certainly true. The things that I learned about ALS during my medical education turned out, many of them, to be quite untrue. So today I'm going to present five untruths about ALS. And then do just a rapid overview of some of the highlights of clinical trials from this year, which were mainly disappointing. And then wrap it up with some positive news about how physiatry really can make a meaningful difference in both quality and quantity of life for individuals with ALS. The first thing that I learned was that ALS is a rare disease. And while it's true that there are only about 30,000 individuals with ALS in the United States because of the poor prognosis, the lifetime risk of ALS is one in 400 individuals in the United States, with an increased risk of one in 350 men in the United States. So that means that every person in this room will likely know someone in their personal circle of family, friends, colleagues, classmates that have ALS. And once you meet someone with this devastating diagnosis, it's hard not to feel compelled to want to help. And I think in physiatry we are best trained to be able to support these individuals. Of course veterans are also at an increased risk over the civilian population with about 1.6, the risk of developing ALS compared to civilians. The second untruth that I learned in medical school was that ALS was a disease of painless weakness. And while it's true that neuropathic pain is not a common presenting feature for someone with initial signs of ALS, the majority of individuals with ALS will have pain at all stages of disease, from early to mid and late stage disease. This is generally nociceptive pain, which is exacerbated by weakness. So shoulder pain, neck, low back pain, joint pain are all very common. And I would argue are some of the most easy things to treat and improve quality of life for someone who has ALS. It's much easier to treat than the primary disease. The unfortunate news is that even in specialized centers and MDA clinics or ALS centers, surveys have repeatedly shown that these symptoms are poorly identified and poorly managed in this patient population. So we could do better. Moving along, more good news. If your medical education was like mine, you learned that ALS is a motor neuron disease. Advances in neuropathology and imaging have now shown us that some of the hallmark pathological inclusions associated with ALS, like phosphorylated TDP, are widely disseminated through the central nervous system. And this explains a lot of the phenomenon that we see commonly in clinic, including autonomic nervous system dysfunction. We know that ALS presents along a very broad spectrum of phenotypes, but we do see patients with bladder and bowel dysfunction, as well as gastroparesis. We also know the majority of individuals with ALS will have some form of cognitive dysfunction, as well. So this is more than just a motor neuron disease. Another damaging stereotype about ALS is that this is a disease of old white men. And I say that this is damaging because we've seen in recent studies that have come out in just the past year that black Americans are more likely to have a delay in diagnosis beyond the average one year delay for all comers with ALS. And they're often diagnosed at a more advanced disease state, which can preclude them from participation in clinical trials and prevent access to disease-modifying therapies at a stage of disease when it would be most effective, when they have higher functional levels. And finally, the last untruth, and maybe the most outrageous one, is that there's nothing that we can do to help people with ALS. I had the honor of being able to participate as the only physiatrist in the National Academies work group for ALS over the past 18 months. And a report was published this summer called Living with ALS. The QR code is listed here, which provides actionable suggestions for lawmakers, for nonprofits, and for the community for short-term and long-term actions that can be taken to meaningfully advance development of disease-modifying therapies and improvements in quality of life for persons and families affected by ALS. And I want to go into a couple of those things that we can do now in the next couple of slides. So I mentioned I'd talk about some of the clinical trials. We got a fair bit of bad news this year. We had four FDA-approved medications for ALS at the beginning of 2024, and we now have three. Relivrio, or sodium phenylbutyrate tarsodile, was withdrawn from the market by the manufacturer in April of this year, after a phase three clinical trial, multisite trial, found no improvement over placebo control. And that leaves us with three remaining drugs, Rilisol, which was approved in 1995, Idaravone, which has very modest effect on slowing function. There was a negative phase three trial of Idaravone in Europe that was published this year. However, the US manufacturers of the medication said this was a different formulation that was tested in Europe, and so this is still available in the United States. And then finally, we do have precision therapy for SOD1 mutation familial ALS, which is Tofersen, which was approved last year. It's an intrathecal therapy, which did show effects in reducing neurofilament light chains, however didn't show an effect in gross outcome measures during the clinical trial. So what we can do, which is more effective for extending life and improving quality of life, is to manage ALS comprehensively using a physiatric approach. And the way that I present this to my residents and a general approach to any patient as a physiatrist is to ensure that we address three main categories, and that is prevention of secondary complications, remediation of the impairment when possible, and then provision of compensatory strategies when that's no longer possible. These different categories carry different weights depending on the phase of disease from early stage through end of life. But one of the most effective interventions for extending life expectancy and improving quality of life is interdisciplinary care. And this is considered standard of care by the American Academy of Neurology Clinical Practice Guidelines for ALS. However, this is not currently reimbursable by Medicare or commercial insurers in the United States, which is absurd given the fact that this can extend life expectancy by almost four times more than the disease modifying therapies that we use. Therefore, one of the recommendations from the National Academy's report that I think is most important is ensuring that individuals with ALS have access to this standard of care, which is interdisciplinary management. There is related legislation that was proposed in Congress last year called the ALS Better Cares Act, and this simply asks for reimbursement of $800 as a bundled payment for an ALS interdisciplinary clinic visit, which would meet the requirements of having specific disciplines that should provide the service in typical ALS clinics. Another one of the top recommendations that has the most potential impact for extending life expectancy is management of neuromuscular respiratory impairment. We know the majority of individuals with ALS will pass away from respiratory failure or aspiration pneumonias. And the pathology in ALS is simply muscle weakness. Who is better suited to treat muscle weakness than physiatrists? I don't know who. This is simply a pump problem. There's no concern with the lung tissue. Unfortunately, the main tools that we have to provide respiratory support are limited in that Medicare will only reimburse when someone has already lost half of their force vital capacity, which is simply too late. So one of the recommendations I have circled here is to ensure access to these respiratory assist devices for patients with ALS. However, that's just one part of the pie. That's a compensatory strategy. An optimal management of neuromuscular respiratory weakness includes prevention of complications. So all things such as pulmonary hygiene, vaccines, oral care, as well as advanced care planning to ensure that that individual's wishes are respected. Remediation of impairments, and there's ongoing research into strengthening of the respiratory muscles with inspiratory and expiratory muscle strength training, as well as the compensatory strategies with PAP devices. So to sum it up, ALS is more common than we think. It is a complex, multi-system neurodegenerative disease with a high symptom burden for which physiatrists can provide the most comprehensive and compassionate care to improve both quality and quantity of life for these patients and families. Thank you so much for your attention today. All right, and thank you so much. And last but not least, Dr. Nassim-Rod, talking about SMA, Pediatric to Adult Care. Thank you everyone for sticking through it. I honestly thought I was gonna have no time, so thank you to all my co-presenters for doing such a wonderful job and hitting all these wonderful learning points. I'm gonna wrap up today's session with some advances in care in regard to spinal muscular atrophy, also known as SMA. I think there is probably, this segments very well after Dr. Howard's initial slides, talking about everything that you learned in medical school and how it might not be relevant now. So I have a lot of trainees that come through my clinic and are surprised when I say, today's my SMA clinic day, and I am adult rehab neuromuscular provider. So what does that mean, and how has the landscape changed for SMA? So just as a refresher to remind ourselves, what is SMA? SMA is a process that involves the alpha motor neurons in the spinal cord. Degradation of these alpha motor neurons leads to progressive muscle atrophy and weakness. The most common form results from a defect in the SMN1 gene, and this is important given the landscape of new treatment. But there are some lesser forms that make up less than 5% of SMA. These include the non-SMN infantile SMA forms, as well as the distal SMA phenotypes. The incidence is one in 11,000 live births, and more recently, over the last few years, SMA genetic testing is now offered as part of the newborn screen in all states. And this has just become a recent addition to the newborn screen. So the genetics behind SMA are quite important when we think about the therapeutics and the evolving landscape. So I'm gonna take just a second here to review what it is that causes SMA. So before, when people were diagnosed with SMA, oftentimes they had EMG testing, they had muscle biopsies. When genetic testing first came around, they were focused on the defect or the absence of the SMN1 gene, which is highlighted here in red. So this SMN1 gene, when it's transcribed and translated, produces SMN, or spinal motor neuron protein. It is this protein that is what causes SMA, the lack of this protein. And so this protein is highest concentration in the motor neurons, but it is actually found ubiquitously in all cells, even though we call this a motor neuron disease. Over time, people started testing for an SMN2 gene. We like to refer to this as the backup gene. There is, as you can see here, or maybe you can't, there's a little marker for a T on the SMN2 gene, where on the SMN1 gene, there's a C. What ends up happening when this is transcribed is the SMN2 gene, 85% of the time, doesn't include its exon 7. So when it's translated into SMN protein, it forms a truncated and non-functional SMN protein. So why this is important is when we start talking about phenotypes of SMA. Okay. So in medical school, what you probably learned and what we still use, but probably aren't gonna be able to use for a lot longer, are what are the subtypes of SMA? So we typically define this based on type, type 1 through 4, and this was based on the age of onset, as well as what was the maximum motor function achieved. So type 1 patients were very weak, hypotonic infants, onset are less than six months of age, who could never sit independently. Type 2s could sit independently, onset between six and 18 months. Type 3 could ambulate with symptoms less after 18 months. And type 4, which I'm not talking about in this presentation, is the adult onset. So typically they present in their 20s and later. Now, over time we've learned that there's a strong correlation between the SMN2 copy and the severity of the disease. It's not perfect, and we don't use it for predicting, but if we understand how the SMN2 gene works, we can kind of understand why there's a correlation. So I said that the SMN2 gene only produces about 15% functional SMN protein. The more copies you have of it, the more functional protein you're gonna make. So as you can see here, the type 4s have about four to six copies, and the type 0s have one copy. There are other genetic modifiers in play, and so this isn't a perfect model. So what does the natural history tell us about SMA? And the truth is is that the current available natural history is really historic, and that the novel therapies are really changing this landscape. When we talk about type 1 SMA, we really highlight the natural history based on survival. So surviving to age 40 is nonexistent. When we talk about type 2, surviving to age 40 is about 52%. When we move on to type 3, you have a normal life expectancy and so we talk about the ability to remain ambulatory, which really depends on how aggressive your symptoms are and when you present it. So what is it that these advances in treatment, and I'll highlight just two of them very briefly for time's sake, but what does it mean for us, and what does it mean for us as physiatrists? And I think the things that should be highlighted are we will see more adults with SMA. So those type 1 patients whose life expectancy was up to two years of age without any treatment option are gonna live to adulthood now. Our type 2s are gonna live longer. Those severe phenotypes are now gonna mimic some of the more milder phenotypes, and we really have to focus more on management of chronic disease. So I mentioned this was a disease that we think of as a motor neuron disease, but it's found in every cell. So as we start treating with novel therapies, what are we gonna see in regards to the other systems in SMA that have been affected? So just like we highlighted with other neuromuscular disorders, a multidisciplinary approach to treatment is now needed more than ever. This is no longer just a pediatric disease. This is an adult disease as well, and I don't mean just the adult type of SMA. I mean the type 1, 2, and 3 that are gonna live to adulthood, and who's better equipped to take care of a chronic neuromuscular disease than physiatrists? So targeted areas of concern as kind of bullet points right now. We know that our type 2 and type 3 patients in adults have on functional rating scales. So when we look at physical evaluations using functional rating scales, we don't see much functional change because it's hard for us to capture that, and there are plateau periods in this disease process. But the things that we see in other neuromuscular conditions and I can argue just in general in rehab clinics are what is gonna lead to loss of function in our SMA patients. These include worsening joint contractures, worsening scoliosis, weight gain from immobility. These will all lead to worsening function and mobility in SMA patients. And so really the focus of care by guidelines for type 2 and type 3 patients fall under monitoring weakness, contractures, respiratory dysfunction, and scoliosis. So I have the privilege of taking care of about 55 adult SMA patients, and we have recently started in our clinic a multidisciplinary clinic. And oftentimes patients ask, what do you do in a whole multidisciplinary clinic for one diagnosis? So I thought I would do just a rapid fire, few slides on what it is that we need to do, and hopefully you can take away from it how much there is to do and actually how little time we really have. So in terms of function, we're taking each patient uniquely, talking about orthotics that can be used for upper and lower limb support, talking about regular stretching for joints that are at risk for contractures, how to support them when they're ambulatory and how to transition them to power wheelchairs or lightweight manual wheelchairs, assessing for need of PT and OT in a chronic disease is quite challenging because they don't have ongoing PT and OT forever. And then caregiver training, how do we train caregivers to support their loved ones with transfers and Hoyer lifts? In terms of respiratory function, respiratory function and dysfunction is a little unique in SMA. It's not, typically the diaphragm is relatively spared, which is unlike other motor neuron conditions like ALS. And so there's a lot more emphasis on weakness from the intercostal muscles. And so a lot of times when you're reviewing their lung function tests, they may have quite low percentages, but still be able to get by with that. We wanted to still talk about secretion management and respiratory infections and keep them up to date with vaccines. We wanna make sure that we utilize functional respiratory testing, understanding that this is not a condition that's as progressive as other motor neuron disease. So you may see periods of plateau with respiratory lung function and stability throughout their lifetime. Jaw contractures are quite important in these disease population. They have limited opening of their jaws. This also makes it very difficult should they have acute respiratory needs for there to be emergent care. So getting an emergency airway support is quite difficult and making sure that we understand their goals of care and access. Swallow evaluations and when they need to have pegs, discussing with them that SMA also puts them at risk for metabolic derangements because of the SMN gene. And then on top of that, as they are able to have decreased mobility, what do you do with that increased obesity risk? I could go on about bone health. So in addition to just non-weight-bearing function that we see in people with mobility deficits, the SMN protein itself interacts with the osteoclast stimulatory factor. And what this means is that it puts them at increased risk for osteoporosis, even if they are ambulatory. Everything else, mental health, from anxiety to depression screening, to talking to our pregnant patients who are living into adulthood and now starting families and what we need to counsel for that, to continuing to drive and continue to address their other needs. I have five seconds left. So I'm gonna kind of wrap up, because I won't get to everything, by just saying that the landscape is changing because we have new available treatment options, which include an antisense oligonucleotide, nusinersen, and a small molecule that alters splicing the BSMN2 called Rizdoplan. Studies are ongoing for new therapies. So this landscape is gonna continue to evolve and all my slides are probably gonna be outdated the next time I talk to you. So. Thank you. Maybe the whole panel could come up to the front here and then we have just a couple minutes if there's any questions for Dr. Ratt or for any of the speakers. Sure, I'll run the microphone around. And I guess whoever he talks to will go up there, I guess. A quick question for Dr. Cowell. I thought it was a great presentation. Is the, do you think it's possible that the lack of sensory abnormalities, you say 80% of the sensories are normal, could that be because there's such a large range of, for example, normal amplitudes that somebody could be dropping from the good end to the lower end and we're just reading it as normal? I think that's definitely possible. They've done a few studies where they actually compare side to side and even then, sometimes, like clearly they have sensory deficits. You compare it to the other side, they don't see a clear difference in amplitude from side to side. So I think our normal values is part of the equation. I think part of it could be that it's, there might be more demyelination than we normally think in Parsonage-Scherner. I think the etiology, we just don't understand that well. Any other questions? If I could speak to that point just briefly also. Dr. Cai showed us really nicely how neurologic amyotrophy is often a fasciculopathy. He showed us how you can see selective fascicular dilation in the main trunk of the median nerve and how that goes to AIN. What do we think would happen with our sensory nerves if there's a fasciculopathy therein? I think that the concept of if there's a small deficit in just one portion of the nerve, can we pick it up electrophysiologically might be where some of the black hole lies. And the other piece of it is just which nerves tend to be involved is a big piece of it too. It's not always the ones that we're recording to still be in the hand. There's a nice study by Paul Searor that does show that when we test the right areas, there are sometimes sensory deficits that correspond. Here we go, one more question. So one of the arguments against that is the fact that there was sensory deficit. So the sensory deficit, if it is there, it has to be either a postganglion lesion or a conduction block lesion, right? Only two things which cause a sensory deficit. So it's a possibility that it's a conduction block lesion we are not picking up, right? Not necessarily a pure fasciculopathy because there is sensory loss in these patients. Yes, provided that we can record the right fascicles. True, that's true, I agree. But the thing is though he mentions that there were comparison to the other side as well. And so is the amplitude differences not necessary? Because I have seen patients with conduction block lesions and that's the reason why I was trying to point that out. Thank you. Thank you. All right, and we'll wrap up. I have one question for Dr. Rad. So I love all the new advances in SMA and some people here probably have heard of CRISPR-Cas9 gene editing. So, and this applies to the ALS population as well with the mutations, but what's keeping us from having gene editing like they have for the people with sickle cell coming to, for a population like SMA where we could correct the mutation and maybe be dealing with the fact that in addition to motor neuron loss, you mentioned that there's multi-system, multi-organ involvement as they get older. So yeah, what's keeping us from gene editing? Yeah, absolutely, I think that's a great question. Thank you. So this is not an area that is currently under study for SMA, but I do think it has potential. There is, which is not using CRISPR, but since I was only talking or was highlighting the adult focus, there is a gene therapy, so truly aimed at the SMN1 gene using adenovirus vector in children under the age of two. That goes by Zolgensma, so a one-time infusion. Anecdotally, some of this, and from some of the studies, those children do still need some of the more gene-modifying treatments as well, continuing forward. In regards to the adults and how CRISPR may benefit, I think that the multi-organ effects would be interesting. Unfortunately, none of the therapies, nor would CRISPR, reverse the neuron loss that has already occurred. So a lot of times when we're talking about these therapies, and I should highlight here, because I get a lot of patients that are like, great, so I'm gonna regrain strength, and we have to focus on, the goal is to maintain strength, and sometimes even slow it down, based on what the natural history would be. So we're not, unfortunately, regaining strength in adults as we would if we started super early in children. Wonderful, should we wrap it up, Dr. Yergesen? We should. Thanks, everyone, for staying late with us. Thank you. Come up to the front if you wanna chat, and.

neuromuscular disorders

innovative treatments

nerve transfers

tetraplegia management

neurologic amyotrophy

Parsonage-Turner Syndrome

myasthenia gravis

ALS

peripheral neuropathies

SMA

multidisciplinary care

diagnostic tools