All right. Let's go ahead and get started. I want to welcome everybody to the AAP virtual didactics for today. My name is Sterling Herring. I'm a PGY3 at Vanderbilt. Excited to have everybody on today. As always, I want to recognize and appreciate those of you who have been affected more than the rest of us by this COVID-19 pandemic. We recognize that that burden has not been shared equitably. So we appreciate those of you who have been most affected. If there's anything that we, your colleagues, or the AAP can do to support you further, please let us know. So the goals of this online didactic curriculum are to augment your ongoing home didactic curricula, to offload overstretched faculty due to some of the logistical challenges associated with this pandemic, to provide additional learning opportunities for off-schedule residences. I know many of us have been pulled off of clinical rotations or out of clinic to develop further digital learning resources and support physiatrists in general during COVID-19. We're going to keep everybody video and audio muted. If you have any questions, you should be able to click on your participants button and you'll see my name, Sterling Herring, up near the top of that list. If you double click me, you can send me some messages and I will pass them along to our presenter. If you have any questions about the series in general or suggestions or concerns, please feel free to reach out to Candice directly. Her email is there on the screen, or you can track her down on Twitter. And I do want to put in a plug here for the AAP RFC-led wellness days that are on, that are going to be held on the first Wednesday of every month via Zoom. You can find the information on the webinars page on the AAP website. So without further ado, we're excited for today's presenter, Dr. Alba Jarena from the University of Miami. Welcome. Thank you. Hi, let me see if I can video here. Hi everyone. So should I just kind of share my screen now? Yes, please. Okay. Okay. So here we go. And I'm going to actually mine, let's see, stop the video for me so I don't look at myself. And here we go. So my name is Alba Jarena and I'm an FSI address who did additional two years in neuromuscular medicine, wanting a clinical fellowship at UCLA and another research fellowship in clinical investigation and muscular dystrophy at Kennedy Krieger and Hopkins. So I am more than happy to talk a little bit about neuromuscular disorders since it's a field that I love so much. So disclosure is nothing to disclose. I will be talking about new developments in FDA approved medications and some of the newer neuromuscular disorders and how that has changed pretty much the field in the past decade. So the objectives for today are pretty much just to describe some of the most common neuromuscular disorders, how electrodiagnostics can play a role in terms of diagnosis for these diseases and also explain how PM&R specialists can be involved in the treatment of these conditions. Since most of the fellowships are actually under neurology and more and more you'll see us playing a really important role in the care of these patients. So I'm putting this slide up because of the limitations that we have in terms of time. There's a lot of neuromuscular disorders and I won't be able to discuss all of them. So I'm just going to highlight a few like I said that have had some drastic changes in terms of treatment in the past decade. So neuromuscular disorders, what does that mean? So we're actually talking about most of them coming out of the neuromuscular system. So any sort of dysfunction be it structurally and this you can think of your common radiculopathies or plexopathies or nerve injuries to diseases involving the motor neuron, the dorsal root ganglion and then down to the motor nerve or sensory nerve, the neuromuscular junction and the muscle. There are other things at play here including the autonomic system but that's outside the scope of what I'm going to be discussing today. So important here is the localization, right? So when we're dealing with neuromuscular disorders, where is it? So if you have someone coming in your clinic and saying hey I have muscle weakness, I've noticed this. So one of the first things that you will try to do is to identify where is it coming from. So the EMG and nerve conduction study certainly can do that but nothing ever will trump a good history and a good exam. And depending on what you find on those, then you can use ancillary tests like the EMG and nerve conduction study as an extension of your exam. The other two things to consider here are if the condition, the underlying condition is a hereditary condition or if it is an acquired condition. So these two things are different and it'll be treated differently also. As a whole differential diagnosis of neuromuscular disorders will be age-dependent. So both infants and children as well as some adolescents, they might have an overlapping and unique set of diagnosis that you won't see in the adult side. However, you will have those outliers that can present with a milder phenotype of a what we would consider a childhood onset disease on the adult side. So honestly we more and more we're seeing just kind of just a spectrum of these conditions as we go on with the genetic diagnoses. Also as a whole you will have some general complications and these can vary in severity but most of them will include some sort of progressive muscle weakness, limb contractures, and spine deformities. Likely this is how you will get a referral. However, those of us who are working with the neuromuscular disorders from the very beginning you likely will see also and have to kind of put in mind looking into the pulmonary function, cardiac disorders, and even neuropsychiatric disorders. So how do you go about all of those evaluations and you'll see that throughout the talk today I will make a point of plugging in those multidisciplinary clinics and if you don't have them at your center to see how you can potentially work on that if you're interested in seeing these patients. Not only because of the amount of things that they'll need to be evaluated on but also because it's we're dealing with progressive diseases it is important to do these evaluations in routine intervals. So as a mode I would kind of summary I actually looked over the talks that the AAP has had in the past through the virtual didactics and I saw really good presentations on radiculopathy and plexopathy, also mononeuropathy of the upper extremity with ultrasound as well as chemo-induced polyneuropathy. So I'm not going to touch on any of those but I will be talking about today more on some muscular dystrophies as well as motor neuron diseases. Okay so I lived in Montana for three years and this is Glacier Lake so I would say for everyone and this pandemic is over and if you have a any time off consider going to this National Park it's it's gorgeous and this picture was actually from last year May. Okay so the first case these are real cases both of them I've been involved in their care but this one in particular I just wanted to kind of give you a sense of what can happen when someone kind of forgoes the what I said a good history and a good exam. So this is a 66 year old male who was a lifelong cyclist, runner, hiker and he started to notice this tripping over his feet but actually the right foot more than anything else when walking. So he was evaluated at a spine clinic. He was found with weakness in the dorsiflexors and reflexes were diminished but present still. So he underwent an EMG nerve conduction study of only that right side and was diagnosed with an L4 and 5 radiculopathy. They did the MRI of the lumbar spine. They found some degenerative changes and because of the weakness and the findings on the EMG although the MRI was not as something that that would make you think of doing a surgery they actually treated him surgically. However the progression of the weakness continued on that right side and then on a subsequent evaluation he was found with weakness on the contralateral side. So he was actually sent to a neurologist and he was seen for an EMG. This neurologist actually did the two lower extremities and found because of low amplitude on the surals and this is the sensory nerve conduction on the lower extremities that he was diagnosed or stamped let's say with a sensory motor polyneuropathy of an axonal nature. Again they say axonal because they saw a lot of denervation already on the legs. So a few months later the patient actually was seen at a tertiary facility for a second opinion and there they did a comprehensive evaluation from head to toe laboratory tests and lo and behold he actually was diagnosed with a lower motor neuron disease with the EMG since the EMG can only test for that lower motor neuron part. But clinically they thought that he had ALS which is what he did have. So why bring this case to float coming from a radiculopathy to all the way to ALS? So the big thing here is that importance of accurate history and examination. Why is it that if you have someone that is complaining of painless muscle weakness right see from the very beginning he was not behaving like a common radiculopathy. So those are like little red flags that should tell you maybe something else is going on here. Now the lack of sensory deficits on history as well as this rapidly progressive course that again you won't know about the rapidly progressive course until you see this patient again in your clinic right. So these are things that are important to kind of keep in mind and when you're evaluating someone and the big thing here is that honestly the boundaries of what is and what it is ALS it's difficult to say early on in the course more if they're behaving not with an upper motor neuron issue but mostly with the lower motor neuron thing. So again what is ALS and how do we diagnose it? So ALS we consider it a multi-system disease and actually we consider it a spectrum. So and I'm saying a spectrum because now I'm looking into the familial ALS which are not the majority. The majority of patients will be sporadic ALS but by evaluating this familial ALS we've actually seen and noticed certain mutations that we've now found and tested for on the sporadic ALS. We also have found that there's some sort of spectrum going on where you have frontotemporal dimension on one end and pure ALS on the other and there's an overlap that happens. So if you're really good and you have really good instruments on your clinic to test for maybe frontotemporal dysfunction not the dimension but the dysfunction at least you could pick up some patients that actually have that and same thing with when you actually go and see the purely frontotemporal dementia patients you may pick up some ALS features on their exam. Now the main point here is that even though it is a a multi-system disease it's mostly dominated by issues with the motor neuron. It is rapidly progressive and the life expectancy in the majority of patients is less than five years after the clinic onset. So in the very very important thing here making sure that nothing else can explain the presentation because there are treatable conditions. So differential diagnosis when you're thinking about seeing someone and you want to make sure that which signs are present on the on the exam. So if it is and this is the classical right upper motor neuron and lower motor neuron issues you likely are dealing with something like ALS on the adult onset remember. Lower motor neuron only then you might think something like progressive muscular atrophy which most of these patients will become ALS eventually or if you only have upper motor neuron signs only then you may think of PLS or HSP. Now on your electrodiagnostic evaluation what do you do? How many parts and body parts do you do? So usually we want to do at least two or more limbs in terms of the nerve conduction portion of it and include lay responses because it is important that you rule out other causes that are treatable like multifocal motor neuropathy. Now on the EMG side you do want to do three limbs, mid thoracic, paraspinals and if possible the bulbar region. Now we tend to divide the body for this classification when it comes to ALS in four body parts the bulbar and I put here the hand but this means the cervical, the thoracic level and then also the lumbosacral level. Now on the EMG if it is a classic and this is a high yield concept on the EMG side you will find chronic neurogenic changes so you will find those spontaneous activity with positive short waves and fibrillation potentials as well as fasciculations. So that's the classic one. Usually you could find more on the denervation side. You do want to see some fasciculations be it physically or by EMG. Now diagnostic criteria important to kind of also keep in mind here. These criteria are mostly for research purposes but we do use them at the clinics and I'm saying that because about 10% of patients that die from ALS will not have actually been able to be classified under these criteria as an ALS patient. So they tend to be very stringent so they have sacrifice sensitivity for specificity. So we tend to be a little bit more open-minded when we're seeing someone presenting with what we think there's a lower motor neuron condition here and kind of make sure that you keep them under observation. Now epidemiology worldwide you have about two per 100,000 across all studies of patients in terms of the incidence mean age is in the 60 years old. It is rapidly progressive and it usually is the respiratory failure the main issue why they pass away. For a prognosis for those that are actually vulvar onset and overall like I said less in terms of survival less than five years from diagnosis. Now like I said before the pathophysiology we know now is mostly because of those evaluations done on documented cases of familial ALS and this is just to kind of give you an example here of what happens and they think this is a toxic mRNA issue and what you pretty much have is these inclusions right and this is actually taken from brain and spinal cord sections of patients that actually had ALS and you see that atrophy in the neurons as well as those the presence of cellular inclusions there which are pretty much just neurofilaments accumulated. Now I'm telling you all of this because as we go along in terms of treatment likely it'll have to do with something like this as well as biomarkers that they will start using to see how a patient is doing. So, the big one has been the C9-ORF finding where actually we found pretty much on the familial cases about 46% at the top that can explain or they have that mutation as well as on the sporadic side about one-fifth of the cases. So again, this is something a little bit more, again, exciting because we're getting to know a little bit more about the disease rather than just saying, oh, you have a motor neuron disease, so we can't do anything. So, important and again, you'll see me saying this, you know, throughout the whole lecture, it's pretty much multidisciplinary clinics. This has been proven already to help in the survival of these patients. So, I think, you know, plugging in, if you have someone and it's important for them to touch base at least with a multidisciplinary clinic, if you're unable to kind of have that locally. Now, same thing and this is pretty much, you'll see this graph in different diseases. It's the same thing. The patient will be in the center and as I said, you'll have, because this is multi-system disorder, you'll need a lot of different people engaged in this. In this case, in particular, family and palliative care is important to have them also involved in the care. It can be a little bit challenging at first because a lot of people are still having a lot of misconceptions about what palliative care is. So, I think sometimes it's up to us as physiatrists to kind of explain their role and then let the patient decide slowly but surely what they want to do and how they want to go about their treatment options. So, what can we offer these patients? So, Rilisol, as likely most of you know, it's been present for over two decades, is the only one that way back when was done a study where they saw that two to three month ventilator free survival on these patients. We still use it and it's not as expensive as the newer medications that, one in particular that came out. And it's thought to kind of help with that oxidative issue that happens when the motor neuron dies. So, Idarabone is pretty much the new medication. Now, this one, just so you know, it's only beneficial, it's only being seen beneficial in the early stages of ALS. So, we're talking about someone that can ambulate without assistance, self feeds and dresses. The functional rating scale is what we use to kind of follow them up. And, you know, the force vital capacity is still more than 80%. So, again, early, early on. Now, even with those, there's been some controversy in terms of the benefits. Some Italian studies have actually seen no benefit of using this medication. Now, the whole point of using this infusion is that it slows the decline at the early stages. And again, this one also is thought to neutralize the free oxygen species in the condition. Now, it is an infusion and it is quite a task to have the patients come in for the cycles of the infusion because it is daily for 14 days and then you'll have daily for 10 days, the first 14 days of each month. So, as you can see, it can take a toll on the patients also, the treatment with this infusion. Now, respiratory failure is important to kind of keep in mind. And the good thing is that we've been able to work on the noninvasive positive pressure, which is pretty much what has helped with the disease. And a lot of patients that start on it actually don't go on tracheostomy afterwards. The other one is nutrition, and you'll notice that it is an independent prognostic factor. So, those patients that don't get as much nutrition because of the Blovar dysfunction and opt out of doing something like a gastrostomy, you can see them not doing as well. However, I have to say that improvement on survival with gastrostomy, we think it's better for the quality of life, but in terms of survival, the results have been varied. So, other treatments that likely we can be involved in with cramps, spasticity, and pseudobulbar affects. So, there's medications for this. And again, being physiatrists, we are, I think, comfortable dealing with the spasticity and likely the cramps. And I can tell you, so the group that I work with at UW in Seattle was working on the maxillotine trial, and they were the ones who actually found that it really helped in reducing the cramp and frequency and severity. So, I think something to keep in mind. Okay, so this is Stewie. He was our dog when we were in Montana. He passed away about a year ago. I love that little guy. So, switching gears here, I'm going to talk about spinal muscular atrophy. And I'm kind of lumping in the motor neuron disease because it is a motor neuron disease, but this is more on that pediatric genetic side, although you will see spinal muscular atrophy late onset. But this is pretty much kind of targeting the anterior horn cells in the spinal cord. And this is actually a type 1, which is also called Virnig and Hoffman. And the whole problem here is with a defect on the SMN1, which is a survivor motor neuron. Now, this is high yield for you residents. It's important to kind of keep in mind how we classify SMA. And like I said, this is something that we have had different classifications, be it by the amount of SMN2 copies that you have. But the big classification that we actually do is by age of onset and maximal motor function achieved. So, the infantile onset or SMA1, you will have very weak infants, and they're unable to sit unsupported. And I'll make a point of this one because the medications that have come out in the past two years have changed drastically the natural history of these patients. The childhood onset one is the type 2, and they can sit independently but not ambulate. The juvenile onset, so they ambulate in childhood, but then again, all of these patients, because of the concern and the accumulation of toxicity within the motor neurons, the motor neurons die. So, in other words, these are progressive diseases that you will see progressive muscle weakness in them. And just as a point, Kennedy's disease is considered also an SMA type, and the mutation is actually in the androgen receptor. It's not on the SMN. Okay, so diagnosis is mostly genetics for the SMN type 1 and 2, potentially 3. Now, if you're looking at 4, meaning an adult onset, it is likely that you will be doing an EMG and nerve conduction study on these patients. If there isn't any sort of family history on any, you know, or any findings on the exam that might think or might let you know that you might be dealing with something hereditary. So, it might be important for you to kind of keep that in mind that the EMG is not done as much on the infants or children, but yes, on the adults. So, what happens? So, we all have SMN1 and SMN2. So, these are two genes. The SMN1 is our main gene that actually helps with the survival of the motor neurons. So, when this one is working, it produces actually from the DNA to mRNA, a full length protein, and it works well. And we have no problems with our motor neurons. The SMN2, again, we all have this one also. However, it only produces about 10% of the amount of the full length of what this one does, and it is because it tends to, when it comes from DNA to mRNA, it tends to actually splice this exon and not work as well. So, this is what we all have. However, so like I said, normal people will have, that don't have this condition, have both. And SMN1 is the one that takes over. However, when you have SMA, you don't have this one. So, you rely only on the one that kind of honestly makes a wonky protein that doesn't work well. And depending on the amount, since it only produces about 10% of a good protein, it depends on the amount of copies you have of this one to have the phenotype. So, it does correlate. And this is usually a question, a board question. But just to let you know, yes, it does correlate with the severity of the disease, the amount of copies that you have. Now, the other thing that is important to keep in mind, because this has actually changed now with the new medications, is that SMA1, by the age of six months, this is the really severe one, they have lost 90% of the motor neurons. So, you can see how difficult it is, right, to kind of work on these patients and why the survival was not that great with these patients, again, because of the loss of the motor neurons. Now, this is the exciting part. Two different medications, two different ways of delivery, but both of them consider SMN-enhancing therapies. And these have changed pretty much the outlook on these conditions. In particular, Solgenzumab, which is pretty much just an injection that they get. But you have to identify these patients right away, which is why the screening tests are now better at trying to identify it. But we're still missing some patients that do present with the hypotonia at birth. And the earlier you get them, the better, because again, you won't have, by six months, again, 90% of those motor neurons have died. So, you want to make sure that these treatments are done right away. Now, one of them, Spiraza, is actually for all ages and types of the SMA, but the Solgenzumab one is only for the up to two years, and that was FDA approved a year ago. As you can see, there's other treatments on phase one and phase two and three trials, but it is important to get, again, keep in mind that things have changed drastically for these patients. Now, the other good thing is that most experts have come together around the world, and these are international groups, and published care guidelines. So, if you at any point in time find yourself that you're not completely familiar with it, if you have access, it is important to just at least look at these, because they're really comprehensive, and they do make a point of, again, as you can see here, the graph. It is important to have a multidisciplinary team working with these patients, because again, despite the fact that this is a motor neuron disease, different systems do get affected, including nutrition, spine, we're talking about rehab, and pulmonary. So, you know, it is important to have that good communication between all the services. Now, multidisciplinary approach, again, the goals are to maximize the patient's independence and quality of life. So, plug in here, like I said, a lot of these teams sometimes are led by orthopedic surgeons and or neurologists. I think us with the training in physical medicine and rehab, because we do work so well with other services, we are at a good position to kind of lead these groups and help on the communication side. So, just to give you an example of how we see these patients, and how on the rehabilitation side they're evaluated. So, it really depends. Remember what I said before about the classification. So, the non-sitters will have different types of assessment and the interventions that we do with them, as well as the care conditions that we have to keep in mind. I'm not going to go over all of this, but I just wanted you to kind of get a sense, and this is out of that paper that I told you about, of the care guidelines. Same thing with the sitters, it's completely different in terms of the goals here. But again, it is because of where they're at at the moment, and those that ambulate. Now, just to kind of give a sense also why I think this is important, a lot of people will think that, oh well, I'll let the physical therapist do these functional scales and I'll just see the patient. Well, I actually gain a lot of knowledge about the functionality and how these muscles work and where they're not working by actually doing rotations with those physical therapists and occupational therapists in their evaluations with the patient. So, if you do have that opportunity to do that, I would say go ahead and do it because it is a wealth of knowledge that they can provide you from a functional standpoint, and it can actually even help you decide what to do next for the patient. So, supportive treatment in terms of what do we do with these patients. So, again, nutrition and respiratory assistance are the main thing. Physical therapy and bracing. So, the big thing with the spinal bracing, important to keep in mind. So, for the type 1 and 2, so these are the really young ones, infant and early childhood, it is important that those braces in the sitting position don't reduce the expiratory tidal volume. So, you have to keep that in mind. Now, important also I highlight here the respiratory part, that mobilization and clearance of airway secretions, and again, the non-invasive nasal ventilation can always be something to consider instead of tracheostomy. So, it really depends on where the child is and also the pulmonary evaluation and support. So, this is, again, Stewie, and this is at a lake house that we used to go to in Flathead Lake in Montana. Plugging in again when all this craziness is over, anyone that can visit the national parks, especially Western Montana, I would say you're going to enjoy it. Okay, so second case, and so this is a boy who was born normal pregnancy and delivery, presented initially with speech delay at age two, walk at 14 months old, but he was really poorly coordinated and able to run with difficulty and began to struggle with stair climbing. On his first grade at school, the behavior issues were significant, and he also was tripping and falling a lot. So, he actually was diagnosed with developmental coordination disorder, dyspraxia. So, this is something that is usually kind of like a bucket of diagnosis where anyone who has issues with coordination as a child will stand with that diagnosis. This is more frequently used in the UK, but it's something that it's sad that sometimes we kind of put that diagnosis in and that's it instead of kind of looking a little bit further. So, despite the diagnosis and doing therapy, so he started doing therapy, he persisted with the problems walking, and he was really unable to keep up with his peers in terms of physicality. So, it wasn't until he was eight years old that they did a CK level and they found that it was 20,000. And the concern that we have with this case in particular, which was a Duchenne patient was that because he was not recognized earlier on, by the time they did the CK on him, he was not ambulating at all. So he was behaving as the natural history of these kids when we were evaluating them back in the 1960s. So when you were seeing someone with speech delay and motor delay and maybe some neuropsychiatric issues, it might be a good idea to consider an evaluation. And again, it's not that it's nothing because honestly doing blood tests in kids takes also a toll on everyone, but doing a CK might be worth your while to make sure that you're not missing something else like Duchenne. So muscular dystrophies, in general, they're inherited muscle disorders and they are progressive. The necrosis is the big thing of that muscle tissue, which gets replaced with connective tissue and fatty tissue. And that is the main difference between that and myopathies. So I always make a point with my residents to kind of talk about the cell wall, the sarcolemma, and also seeing how important that dystrophin glycoprotein complex is because it helps a lot, not only for the structure, a lot of different issues in regards to the NNOS system. So it has not only that structural part, but also physiologic points of use that when it's not working well, get affected. So what is dystrophinopathy? It's a mutation that actually leads to either the absence or defect. So you actually have, this is an X-linked recessive and I'll make a point of talking about also the carriers. So here's the thing. Carriers of this X-linked or manifesting carriers, about 10% of these females will actually show with cardiomyopathy or cardiac issues. So no matter when I'm seeing the patient, I always make a point of talking to the biological mother and asking them to get evaluated and make sure that they know, hey, that this is something that they need to follow up with. But you'll see that there's the phenotype of the dystrophinopathies can go from the very severe with Duchenne muscular dystrophy to myopathies in only certain areas. So there's, like I said, there's a big spectrum there. So like I said, the functions of that protein complex and the protein per se of dystrophin, so stabilization of that membrane, but it also plays a functional role in different things when it comes to the muscle fiber. So two big things that you will hear every one of us talk about is the out-of-frame and the in-frame mutations. So if you go back to your genetics class from college, you likely will remember that out-of-frame mutations likely will cause some stop codons and then it's a really unstable protein that will get degraded right away. And potentially in-frame mutations may make the protein not as good or full length as it should be, but at least stable enough that it can potentially do some of its function. So this is another thing that I keep hammering my poor residence on. It's how the muscle biopsy looks. So this is a healthy muscle biopsy of skeletal muscle and this is someone with Duchenne muscular dystrophy in the actually early stages. And so on this muscle biopsy, it's important for you to kind of look at that and it's not only the morphology, but you can see here in different muscle fibers, the internalized nuclei, not only that, but you also see how you have here inflammatory cell infiltrates and the paramecium and endomecium and all of this becomes fibrotic tissue. So the cell dies and then your body will actually put something there to fill in the space. So that's usually that fibrotic tissue or fatty tissue eventually, and you cannot strengthen that tissue. So this is why we make a point of trying to preserve and tamper down that inflammatory response with the treatments, including the corticosteroids. So this is another one and this is high yield also for you guys. So important that this is a stain for dystrophin. So you can see how it actually stains around the muscle fiber because it is in the sarcolemna and you can see the absence here. So this is just to kind of give you a sense of what it is. Now, because of the spectrum of what I was telling you about, some patients will have a little bit of dystrophin. So you can see that. You can see on some slides where you can see some fibers with maybe one wall covered and not another, but that's not normal either. So the clinical course delayed motor developmental milestones is a big thing. So poor head control is a big, big red flag. But this is what we kind of expect when someone tells us about muscular dystrophy, right? But in the abnormal gait, including the tiptoe and this big one, the Gower's sign, which is important for you guys to also keep in mind. But these are the other things that I like for you to kind of remember. If a patient is, or a parent, because it's usually the parent who will come to you and say, Hey, my kid is complaining of cramps in the, in the calf. Or if they have Coca-Cola colored urine. If for some reason someone did liver tests on a blood draw and they were elevated, it is important for you to kind of follow that up. Learning difficulties and behavior issues. I cannot stress that enough. It's, it becomes a big problem when you're also trying to treat these patients with corticosteroids. As you probably know, corticosteroids at high doses will cause anyone to pretty much just walk up the wall. So imagine someone with already issues in terms of behavior and being on corticosteroids, it can become really challenging. So it's always important to kind of keep in mind that if you do see someone with maybe motor milestones that are not being met, and maybe on the autistic spectrum, it is important to get any, if they haven't already, get an evaluation. And again, you could do a CK just to see where they're at. Now, like I said, you can see also affected individuals that are on the milder side of those delayed motor milestones, because the phenotype is so different. And this is just because we're physiatrists, it's important for us to know kind of the functional part. When you have gluteus maximus weakness, what happens? And this is pretty much the same patient as he went on and grew older. And what happened with the issue with that gluteus maximus weakness is that he then didn't have that hip extensor stability. So he tended to then forward flex and then have that compensatory lower doses to keep himself upright. And you'll see here that he's already trying to tiptoe, and we'll go over that. So the quadricep weakness, which is also one of the big issues with these patients, it is important that you know that then because they won't have that help of knee extensor stability, they will actually shift that weight line anteriorly to the knee, and that's why they tiptoe. And why am I saying that? Because I would say we would have patients that would get braced, believe it or not, and that would just send them down. The tiptoeing is because it's the only way that they can actually move and stand up. So the bracing that happens, because this also causes a lot of shortening on the Achilles tendon, usually we do the bracing at night, we don't do it during the day. So the testing is genetic testing. You can do a simple deletion duplication, but if you still have a high suspicion that this might be a problem with the dystrophin gene, then you can either do the sodium blot or the sequencing. So diagnosis usually from two to five years of age, that's when they start. We see most of the patients getting diagnosed. But like I said, sometimes we do see those cases which break our heart where they haven't been diagnosed for longer. And like I said before, this is another case where you will need a multidisciplinary team to treat the patient. Now dilated cardiomyopathy is one of the big issues. The IQ on some of these patients is around 88, and they can't have night blindness, and that's because an isoform of dystrophin actually goes into the retina. So big things that you likely will have to deal with if you're doing a fasciatory care for these patients, contractures, and that's what I mean about the night splints. I can tell you some of these patients hate the night splints. They love the stretching exercises that their parents sometimes do for them. At night they love that, but they do not like the night splints. And then contracture really sometimes is done. Then also for the spine, I have to be honest, sometimes they do still do the surgical insertions of spinal rods for working with the scoliosis. So this is another one that was published in 2018. The original one was published in 2010, and it was a great care guideline. And I can tell you that two of the people that actually published this were involved. One of them, Dr. Sue Atkin, she's a great, amazing, brilliant pediatric rehab doctor. She's now at, I think, Children's in Colorado, and she was involved in this. And then my prior mentor, Kennedy Krieger, Dr. Wagner, she's a neurologist. But like I said, we as rehab doctors can have a lot to say when it comes to the care of these patients. And I'm plugging in here because I think we still need more of us in this field. So I would love to see more people involved in the care of these patients. Once again, as you can see, I keep hammering on this, but yes, multidisciplinary care is the best option for these patients. The treatment would be glucocorticoids, and that in and of itself would bring a whole lot of other issues, including endocrine issues that have to be also addressed. But it has been seen to help with the decline in that muscle strength. It helps slow down that decline. Now, when do you start the glucocorticoids? So we do not recommend doing that when the patient is still gaining motor skills. But this is why it's important to follow up with the patient and looking at how they're doing. So this is where, again, the different tests are done with a physical therapist to see the outcomes of them. And if they are at a plateau where they're not gaining any motor skills, that's when we like to start the glucocorticoids steroids. But that can be a window that's quite small before they start declining. So that's why follow-up is important. Now, the target dose, and if you see this, these are really elevated doses of glucocorticoids steroids. So this is why eventually you do have to deal with bone health issues, as well as hormone issues, which is, again, why endocrine has to be involved. Now, the exciting thing, remember when I was talking about that in-frame and out-of-frame, so what the new exciting thing is happening with the medications on these patients is actually the targeting of that pre-MS in your RNA. And what they're trying to do is pretty much convert or change that reading frame. So if you have someone that already has that mutation or deletion, let's say on exon 45 of that gene, they will cause a premature stop codon and then a non-functional dystrophin. So by using different things, not only the AON, but other means, they've been able to switch that reading frame. So what happens is that you have that pre-mRNA, and when it actually gets read, they skip that one, and it doesn't become a stop codon, but actually the reading frame gets restored, and you have a partially functioning dystrophin. And again, this is really exciting, but the problem, as you probably have figured out, is that not everyone has a deletion. That's a huge gene. Not everyone has a deletion on that one exon only. So this is a very targeted type of treatment, and it would only work on those that have this specific mutation. So that's why, again, corticosteroids, which work globally for anyone that has that problem with that inflammatory response, is still something that we do for these patients. But again, it just tells you that things have changed so much, again, in the past just 10 years. I actually would say in the past five years when these medications have been FDA approved, which has just, again, changed the outline for all of these patients. So as a summary, again, I could not—neuromuscular disorders are vast, and I didn't talk about any neuromuscular junction problems and the polyneuropathies in general, the acquired ones like Guillain-Barre or CIDP. But I just wanted you to at least have a sense of what's going on with some of these diseases and how things have changed. And again, we can all have a good, I would say, role in the care of these patients and advocate for them also. And that's it. I don't know if anyone has any questions. I'm sorry. I was working on the slide and got stuck and I couldn't get out. Thank you so much. That was a fantastic lecture, and not only do I think we all know far more about these neuromuscular disorders, but I also really want to go to Montana now. I hope so. It's just gorgeous there. No, thank you so much. I haven't seen any questions pop up. I know we are likely to get more. Many of our viewers are now watching them in a delayed format as they're kind of re-entries back to the clinic. And so many, in fact, at this point, I'd say most of our viewers are watching it later. And so as those questions come through, we'll make sure and just switch around. Yeah, I would love to answer. Yeah, yeah. More than happy to. Perfect. So there is your email address. Is that correct? Yes, that's the one. Excellent. Thank you so much. This has been fantastic. We appreciate you taking the time to teach us. You are a great teacher, by the way. So if we ever have the opportunity to teach at AAP, I will be looking out for you for one. Okay. Thank you so much. Hold on. I'm just checking one more thing. Getting notes here. Yes. From someone saying that your patients are very well. Again, thank you so much. Keep an eye on your email. I'm sure questions will come through. This is one of those topics that can be complicated to the uninitiated. Yes, yes, it is. If anybody has any questions, please feel free to email her directly. You can reach out to me or the AAP there on Twitter. Anybody that wants to review this or caught part of it or got paged out or has a colleague that wants to review it, all of these videos will be hosted live or will be hosted in the recorded format on physiatry.org slash webinars at least through the end of this calendar year. So thank you again. We appreciate you joining us today. Thank you for having me.

neuromuscular disorders

COVID-19 pandemic

online curriculum

motor neuron diseases

ALS

spinal muscular atrophy

Duchenne muscular dystrophy

multidisciplinary care

healthcare professionals