All right, hello everyone, my name is Ryan Wolfe. I'm a PGY3 at LSU. Welcome to the Physiatrist in Training, or FIT, session on spasticity. The wonderful president of the FIT program, Dr. Heidi Chen, wanted to encourage more involvement from the residents, so she devised a plan to have these FIT educational sessions during the annual assembly. I was lucky enough to have been included in this effort, where I had the pleasant opportunity to work closely with my co-director of this session, Dr. Emily Kivelhan. And we both had the privilege to work with some of the best and brightest in our field, Drs. Alter, Kim, and Patel. First off, thank you all for being here, especially at 8 a.m. Early morning lectures are tough, even at a big conference. We'll try to keep this concise and to the point with three lectures, each lasting about 15 to 20 minutes. The topic that we will be discussing today is spasticity. The recognition, diagnosis, and management of spasticity should be in the repertoire of all physiatrists, given its significant effects on function in many of our patients. With this session, we wanted to focus on one of the best and most evidence-based interventions, chemo-denervation. At one point, the most expensive substance per weight on the planet, botulinum toxin has become a staple in the management of chronic pain disorders, aesthetics, scialleria, bladder and urethral dysfunction, migraine headaches, and spasticity, to name a few. Research on the utilization of this master chemical continues to expand and show promise in other areas, such as plantar fasciitis, excessive perspiration, premature ejaculation, and more. With these sessions, we wanted to focus on some of the more nuanced topics involved in the management with botulinum toxin. We will discuss initial eval and proper dosing, as well as site selection, follow-up evaluation and adjustment of dosing and switching between toxins, and more invasive options for the management of spasticity. We're fortunate to have three fantastic spasticity masters speaking today, and we will introduce each as we go through the talk. Hi, everyone. I am honored to introduce Dr. Catherine Alter. Dr. Alter is a pediatric and adult physiatrist at the National Institute of Health in Bethesda, Maryland, where she serves as senior research clinician and as medical director of neuroimaging and biomechanics section within rehabilitation medicine. Prior to joining the NIH full-time in 2014, she was the medical director of rehabilitation programs at Mount Washington Pediatric Hospital and a staff physiatrist at the National Rehabilitation Hospital in Washington, D.C. She's board certified in pediatrics, physical medicine and rehabilitation, pediatric rehabilitation, and electrodiagnostic and neuromuscular medicine. Dr. Alter is a co-investigator on numerous NIH and multi-institute research protocols and is actively involved in the education and training of clinical fellows, PM&R and neurology residents and medical students. Her clinical interests include the assessment and treatment of neurological and musculoskeletal disorders in children and adults, including botulinum toxin therapy for treatment of movement disorders and muscle overactivity. Her research projects include diagnostic neuromuscular ultrasound, shear wave elastography, motion capture MRI, botulinum toxin therapy for movement disorders, non-invasive functional brain imaging and robotic exoskeletons for the treatment of Crouch-Gate. She is active in numerous professional associations and has presented nationally and internationally on topics within her field and has published numerous peer-reviewed articles and book chapters. In July 2022, Dr. Alter was elected to the position of president-elect of the International Neurotoxins Association. Dr. Alter. Thank you. So that just took all 20 minutes of my time. So I'll sit down. And I don't sit still very well, so I hope, or stand still very well, so hopefully I can stand back here. We kind of switched the order on this. If you looked at your program, I told what Patel was gonna go first, but since I'm talking more about the toxin molecules and the product themselves, we decided I would go first. And I wanted to talk a little bit about beyond mechanism of action and the products and talk about, and Atul may be talking about this as well, but some just basics. I'm not gonna go through all my slides. I may click through a lot of this quickly, but it's in your handout. I updated the presentation today because I found some errors. So key points here are that after patients receive their first toxin injections, up to 30% of them don't return back for a second procedure. And the question is, why does that happen? And there's a lot of different reasons, but I can tell you that it's very uncommon that it's the botulinum toxin product that was the problem that made the patient not come back. It's more often related to factors that we control. And the most important is inadequate pre-procedure planning. So you failure to identify who you should be treating and or which muscles may be contributing to whatever the patient's clinical problem is. And actually identifying what the functional problem is. It's also really critical, the inadequate patient discussion that we fail to tell patients how the toxin worked, that it doesn't work immediately, when to expect benefit, and to establish appropriate treatment goals so that the patient, if you haven't established with the patient what they think the goal should be, you've identified your goal, but you haven't talked to the therapist or the patient to identify the goal. You may think the patient's treatment was a success, but it really, from their perspective, was a failure. And then also critical that it may take three or four injection cycles to show the benefit that the patient is looking for. It's not like taking an antibiotic where you take 10 days of the antibiotic and your infection is gone. This takes, it's the art of dosing and getting the medication to the right muscle. Another factor is post, I'm gonna go into procedure itself, is another factor, how you perform the procedure. But post-procedure therapy, that you don't do these injections in isolation, particularly patients with upper motor neuron syndromes. They're gonna need therapy before and after, and you need to do this. And reinforce to the patient that going to PT or OT once a week isn't how this works. They have to have a home exercise program. If they don't do this, they're not gonna benefit. Then there's procedure issues, which is dose calculation and targeting errors, which Atul will talk about a little bit as well, so I'm not gonna go in at length. And then failing to see the patient back or look at the patient's videos after treatment. So there's all these little factors that are important. And with pre-procedure planning, you have to identify what the functional problem is and communicate with the therapist. This is a village. It's not us just performing the injections. And again, clinical pattern recognition, establishing goals for each individual patient. We tend to use gas or goal attainment scaling because you can individualize goals for the patient. And then it's product selection. Which botulinum toxin product are you going to use? And you're gonna calculate the dose correctly. Dr. Atul again will talk about dosage itself, so I'm not gonna go over this. But you need to be able to identify the minimum effective dose. How much do you need to put into an individual muscle to make it work? And how not to put too much into an individual muscle? And then what is the maximum dose per treatment cycle? The three month treatment cycle? This is really actually critical because now there are multiple specialists that are performing toxin injections. And you may have a patient with upper motor neuron syndrome that's also getting urological injections. And if you look at the label for the product, it says X amount max dose per three month cycle. And that doesn't mean your three month cycle. It means everybody's three month cycle. So you need to coordinate with other practitioners. I have patients who are treating for blepharospasm, have MAGE syndrome, which is cervical dystonia or medibular dystonia and blepharospasm. And they may go to an ophthalmologist for their eye injection or their orbicular oculi injections and then come to us for other injections. You need to coordinate this. Including the preauthorization for the toxin. Because that is really critical as well. You can't, in some states, especially Medicare and Medicaid you may not need preauthorization, but it's critical. So what about the product itself? I'm unfortunately a botulinum toxin geek. So you're gonna have to listen a little bit if you haven't heard about the history of botulinum toxin. So it is actually kind of fascinating. It was in the 1700s and 1800s, it was first identified. Justin S. Kirzner was the first person who talked about sausage poisoning. He saw this in a bunch of patients that attended a funeral and they all developed poisoning. He astutely identified that there was some type of toxin or poison within that sausage that led to this paralysis that the patients developed. But it wasn't until much later that we actually identified the bacterium. And then even later, the actual molecule itself, it wasn't until 1944 that Ed Schantz actually identified the 150 kilodalton botulinum toxin molecule. And that was done right up the street here at Fort Detrick in Maryland as part of a German warfare project during World War II with the federal government. From there, the leap between Ed Schantz and Alan Scott, who was the first clinician that proposed the use of botulinum toxin, because in 44, the toxin was identified, and then in 49, another researcher identified where the site of action of the botulinum toxin was and what its mechanism of action was. So Alan Scott, in 1968, decided that he wanted to do injections in children's for strabismus with the most potent neurotoxin known to man that had never been used in clinical trials on humans before. So he contacted Ed Schantz, and Ed Schantz purified a batch of toxin for Dr. Scott to use. And it was branded under the name oculinum, and then eventually purchased by Allergan, now AbbVie, and branded as Botox. But they did initial animal models, and then did their first patients who were children with strabismus, and then adults with blepharospasm. And that's sort of the beginning of all of this, where its toxin is now approved for multiple indications and where we are today with its ever-expanding seemingly use of the toxin. So the botulinum toxin is our biological product. There's actually eight, not seven, serotypes. As eighth serotype was identified about four years ago, botulinum toxin type A, H. Only the A and B serotypes are available for clinical use, but there is research today in botulinum toxin E, which is a very short-acting agent and will probably be released. There are engineered products, either approved or under development. So there's a couple of products, like doxybotulinum toxin A, or Revance, which is approved for cosmetic use, has an accessory or additional proprietary protein molecule that's added that increases its stability at room temperature and also extends its duration of action. And then the most recent development is this phage modification of botulinum toxins that's under clinical research. So for what we're talking about today is really just focal muscle overactivity or generalized muscle overactivity, but there's a variety of other conditions that we use this for, including pain indications. So I think I'm gonna skip some of these. So the mechanism of action, it's actually really fascinating. There's three steps, binding, internalization, and blocking. And different parts of the toxin molecule are responsible for different portions of this process. So the heavy chain, so remember the toxin is synthesized as a single 150 kilodalton chain, and then it is cleaved into a dye chain molecule bound together by a del sulfide link. And the heavy chain and the light chain have different responsibilities in the way the toxin works. The heavy chain, the C-terminus, the carboxy terminus is responsible for surface binding to the presynaptic membrane. And it does this by a conformational locking key mechanism where it binds avidly to these presynaptic receptors and then is internalized into an endosome. Once within the endosome, the light chain and the heavy chain have to be cleaved from one another because it's only the light chain that induces the activity. So what happens is within the endosome, this is actually kind of interesting, proteins normally denature under different acidic conditions. So under the acidic condition within the endosome, the light chain unfolds. And the heavy chain, the nitrogen terminus, actually creates a pore within the endosome membrane through which the unfolded light chain escapes into the cytosol. Once back in the cytosol, the pH difference allows the light chain to refold into the three-dimensional conformation that's required for the light chain to do what it needs to do, which is to block proteolytic cleavage of the SNARE proteins. So this is a pretty amazing process. And the fact that the research scientists and the basic scientists have discovered all of this in the last probably five or six years how this all works. But the serotype differences, one of the first parts of differences between the toxins is the site of blocking and action. So the SNARE proteins are responsible for docking and release of neurotransmitters, including acetylcholine. And the light chain of botulinum toxin A blocks the SNAP-25, and the light chain of B blocks the vesicle-associated protein, or VAMP, or synaptic brevim. So that's the first thing that's different between the A and B toxins. So all of the botulinum toxins work similarly. They block the release of acetylcholine and also other neurotransmitters like substance P, glutamate, and other pain-signaling neurotransmitters, which is how there are actions of botulinum toxin for pain indications. And the differences between the serotypes that you use, and even within the serotypes, the A serotypes, is based on intracellular targets, the complex size, diffusion, and particularly in the manufacturing process. So even though you may be using, there are three available A products for spasticity management, those products are manufactured differently, and so that's why their dosing is very different. Botulinum toxin, I'm not gonna go into this, because I hope all of you know this, it induces denervation and blocks the release of acetylcholine. It only lasts for a certain period of time, because over time, the neuromuscular junction regrows. And the peak effect is at four to six weeks, and onset is somewhere between three to five days. If you're treating a patient with a very small muscle, like for blepharospasm, the onset tends to be faster, because there's less diffusion that's required, whereas the onset may be, it may take longer for some of the bigger muscles that we treat. We don't use toxin in isolation. Dr. Kim does ITB and botulinum toxin, as does Dr. Patel. We also do, I do DBS plus botulinum toxin injections. The only time I use oral medications, I'm not a big oral medication fan. I use it mostly at night for people who have pain and sleep disturbance, but not as much for oral medications. And, oh, I sort of took this out because all of you are too young to remember this movie, Is It Safe? None of you remember, right? Do even any of the faculty remember this, Is It Safe? It was a movie with Dustin Hoffman and Anthony Hopkins, I think it was. And the FDA added a box warning for all the toxins and this was based on, I won't go into the details behind this, but it was the death of a number of children with cerebral palsy, very impaired children. And they added this black box or box warning to all the products to highlight safety issues and risks. They added a risk or REMS, risk evaluation management programs or product insert that you're supposed to hand to each one of your patients every time you do the botulinum toxin, you're supposed to give that to the patient. And they assigned unique generic names to reinforce the differences between the products, particularly in dosing and handling. And back before this happened, Dr. Patel, Dr. Kim and I were doing this, you would get a note from another physician that said they did botulinum toxin A injections and they gave you dosing. And you had no idea what product they used so you didn't know what the dosing was. So now that we use these unique generic names like ABOA, INCOA, ANA-A, REMA-B, this really helps us with when you see a patient's note and you know what the product was and you know where to start. The dosing is not like antibiotics, it's a unique biological product. And so the doses are calculated based on the product specificity and the LD50. So each unit is the LD50 of a, one unit is the LD50 of a 30 gram Swiss Weber mouse injected intraperitoneally. Dose calculation is really challenging for toxins because there's so much variability between the products but also between conditions. So if you're treating for, if I'm treating for focal dystonia, the dosing is very different than if I'm treating for upper motor neurons spasticity. And so you have to remember this. When you're talking about, people always ask me this question is how do you, how do I use a conversion ratio to go between the products? And the answer is, you know, there's unique differences between these toxins and while ANA and INCO tend to be generally equipotent, there isn't really a conversion ratio that's accepted. And they aren't interchangeable, the products are not interchangeable. And while these conversion ratios are utilized, they're not recommended by the FDA, they're not recommended by the manufacturers. And the current level of the evidence doesn't really support, it's unknown for using these conversion ratios. What's the recommendation is, from my perspective is additional head-to-head trials between toxins to establish these safe conversion ratio. Because you don't know if the conversion ratio is the same for blepharospasm as it is for upper limb spasticity. And so when people tell you to use these conversion ratios, you have to be cautious. So what I do when converting between toxins, and I gave you the conversion ratios that are published, there's some evidence about these. But again, it's not for every condition. What I do when I convert between products is I go back to the label. So I go back to the labeled indication for a specific product and restart at that beginning dose that they recommend. Because if you're switching between one toxin to the other, it could be because the insurance company tells you who you have to switch, because the product is no longer formulary that you were using. Or it may be because the patient has had a decreasing response to the product that you're using and you think they might have antibodies. And so you're switching to a different product. In that situation, if you switch from product A that you've been doing and they have antibodies, and you switch at a conversion dose to product B and they have no antibodies, they may have a much bigger response and you may develop weakness or side effects. So it's better to go back to the products labeled starting dose. And I said this about five different times. And then there's, I've got a whole bunch of extra slides in here that are in your handout. So I don't know how that got there. So what are other differences, similarities and differences? Again, I'm not gonna belabor this because it's in your handout, but there's, why is it different? Because they're manufactured differently. And their composition is somewhat different as well. The biggest difference, I think, is between Inco Botulinum Toxin A and the other A products. Because the molecule size for ABO and ANA is 500, 900 kilodaltons. Because there's accessory proteins that are associated with the Botulinum Toxin molecule. And those accessory proteins in the wild protect the toxin from being degraded in the GI tract when it's ingested. Or through the skin when it's, you know, if it's through a wound. But what Inco Botulinum Toxin A has done, or Xeomin, they've removed all those accessory proteins and you're injecting essentially just the naked toxins. So the protein load is different with this. There's differences in indications, approved indications. The approvals keep changing, so you just have to keep track of this. But all of the toxins, all of the A toxins are approved for upper limb spasticity in children and adults. And ANA and ABO are approved for lower limb spasticity in children and adults. And Rheumabotulinum Toxin A doesn't have any approvals for spasticity at this point. Again, this is, I put these tables in just for your reference. And it's talking about what the dosages are for the individual products. Same thing here, approved indications and dosage, for instance, for, because I don't know how many of you may be seeing patients with other conditions like blepharospasm or CD. So in addition to spasticity, I included the labeled indication and starting dose for those products as well. A reconstitution is very different for the different products. In part because, and I think it's, the biggest difference is between INCO and Rheuma and ABO and ANA. Because Rheumabotulinum Toxin B is provided in solution. So you can't concentrate it further. You can't make it more concentrated. You can make it more dilute by adding saline. But you don't have to reconstitute this. ANA and ABO, you're supposed to add all three of the A toxins. You use preservative-free normal saline and then reconstitute and follow their instructions. For ABO and ANA, they tell you don't invert the vial because you're gonna get some of the toxin, the liquid is gonna stick to the rubber stopper. And that's the opposite of what INCO tells you because INCO's a lyophilized powder that's in the bottom of the vial. You actually do have to invert that vial to make sure if any of the powder is stuck to the rubber stopper or the silicone stopper, you need to invert the vial. And you may have to let it settle for a little bit before you can get all the product out. Mixing instructions, this is like, I guess a martini, you're not supposed to shake it. You're supposed to stir it. So you gently swirl the vial. The reason you do this is because you're denaturing the protein when you shake it up. And every time you denature the protein, you're decreasing the efficacy of the toxin in that vial, but you're still injecting that protein as a stimulus to immune response. So you want to make sure that you don't, that you handle the product as labeled. Re-injection intervals are different as well for ABO and ANA. They all say a minimum of three months between injection cycles. But for ABO botulinum toxin A, it appears that the dosing interval is longer. For most of us, I don't know if, Hick, Young, and Atul, are you injecting at a longer interval for ABO? For Dysport? You don't, okay, so. It depends on the condition. Okay, yeah, so the labeled studies for pediatric and adult limb spasticity is the majority of the patients were treated at a longer interval than three months. So at four months or even longer. So there, and there's reasons behind that. There was somebody that actually did a study to look at why this was. And this is a kind of a long study, but he, Dr. Field, went through and did a number of different biochemical studies on this. And he calculated essentially the amount of toxin that was in the vial between the products. And based on his conclusion, that first of all, the bioactivity between all three of the products was exactly the same. One unit was the same as far as its activity. But that there was actually more product in the ABO vial. And when he calculated, then in the other two vials. And that when he calculated the FDA approved dose, it was just a higher protein administration when you're injecting ABO. And he proposed that one of the reasons for why it lasts longer is because you're actually injecting a higher amount of toxin. I've heard other people say that it's actually more toxigenic. But this study doesn't support that because he said that the bioactivity was the same. Immune resistance is, in my hands, in my practice, I don't know at all, Hank Young, what you see. I don't see resistance very often. But there are people who I would call hyper responders. Or hyper, they're hypo and hyper immune. They'd be interesting to study in other vaccination things. But I have a patient that all, he's a focal hand dystonia patient. All I inject is one lumbrical. That's it, one lumbrical muscle at like five units of anabotulinumtoxin A. And he developed resistance to ANA. And we weren't booster dosing him or anything else. And then we switched him to rimobotulinumtoxin B. And he responded for about nine months to a year. And he developed resistance to that. And then we switched him to INCO with the idea that because the accessory proteins were gone. And he responded for about a year to INCO. And then he developed antibodies. So now what we do is we cycle him in about one year cycles between three different products. And he responds. But over time we have to escalate the dose. So what I was talking about, a dose calculation. When we've escalated the dose because he's getting resistance to ANA. When I restart at RIMA I go back way down on the dose. I don't use a conversion ratio. All right, so neutralizing antibodies can be minimized by reducing the amount of toxin that you inject every month. That's why it's so important to be precise about where you inject. Because if you're precisely injecting the muscles you're gonna reduce the required effective dose. And you're not relying on spread and diffusion for effect. You're relying on placing the toxin where it's supposed to go. All right, and I think I'm gonna end here in a second. Most common risks associated with the product are adverse events. The most common that I see is dysphagia with neck injections or weakness in adjacent structures. Either too much weakness in the muscle that you injected because you miscalculated the dose or miscalculated how weak the patient was underneath their spasticity. Or I think once or twice I've had patients that have had, were using very high doses that had weakness in an adjacent limb. So it wasn't spread to the adjacent structure. It was to a different limb. So there was some type of spread. But I think that's once or twice in 20, I guess 30 years now of doing this. So to minimize this you wanna be precise. You wanna use the minimum dose that's required. And don't be inaccurate about placing the injection. I'm having problems with this, not advancing. I'm not gonna go into this whole diffusion. We talked about non-response. Other than if you see patients with non-response the way of testing for this. You can either do a neurophysiology test where you inject however many units in the abductor digiti minimi and do a C-MAP before and after treatment and measure if there's a decline in the C-MAP. But that's a pain in the neck and I don't think anybody does that other than maybe a few of us at NIH occasionally as part of a research study. We usually do a clinical test called the frontalis test where you inject X number of units in one side of the frontalis muscle. And then you have patients send you a picture back. And if the contraction in the muscle and the side you injected is, you know, they've responded to toxin they will have a change in the forehead wrinkling. So it decreases. But if they don't have a change then they're a patient that may be resistant to toxin. And then you might wanna consider are the neutralizing antibody tests, is it really worth doing? No, because there could be non-neutralizing antibodies. So just because the neutralizing antibodies are negative it doesn't mean that the patient doesn't have antibodies. So we never use the neutralizing antibodies. And avoiding resistance I talked about and why they're important is important. And pain indications, I'm only gonna talk two seconds because this is a spasticity talk. But Dr. Brin is the first person that kind of identified the pain response in patients with cervical dystonia that most patients with CD report more improvement in their pain than they do in their pulling or their muscle contraction. And that explored people to look at how botulinum toxin blocks the pain signals. Because remember these synaptic vesicles are full of multiple neurotransmitters not just acetylcholine. And so, you know, this receptor mediated blockage of releases of neurotransmitters also affects pain neurotransmitters. And so you can get decreases in pain. And that may be how it works for migraine, plantar fasciitis and some of the other conditions that we use for pain. And I think I'm gonna stop there. So there's some of the other neurotransmitters. Lots of them. And so my conclusion is for this, my portion of the talk is that it's important that you recognize there are differences between the products. All the products are, if used correctly, are effective in reducing spasticity. And it's important to, if you get, insurance companies may dictate which product you use because of the patient's formulary. But if they deny the product that the patient's been on and on a stable dose for, you can appeal to the insurance company. And you can ask them and tell them that, you know, the patient is on this stable dose and that converting is not in the patient's best interest. And sometimes they will approve the change back to the original product. And you need to be careful about all the approvals, storage and handling, and the dosage in units. And I think that's it. Thanks. Thank you. I can introduce Dr. Patel. Thank you, Dr. Alger. Dr. Patel is a practicing physiatrist and vice president of the Kansas City Bonin Joint Clinic in Pennsylvania. He is a research associate professor at the University of Missouri Kansas City School of Medicine. Dr. Patel received his medical degree from Baylor College of Medicine and completed his residency in PM&R at the University of Washington. Dr. Patel is board certified in PM&R, electrodiagnostic medicine, and has subspecialty certifications in neuromuscular medicine, brain injury medicine, and spinal cord injury medicine. Dr. Patel has been conducting clinical trials with botulinum toxins for over 15 years and has been using them in clinical practice for over 25 years. Dr. Patel is active in several professional organizations, including AAPM&R, AANEM, and ISPRM. He is currently a member of the Board of Governors of the AAPM&R. He has authored several journal articles and book chapters and lectures regularly on electrodiagnostics, sonography, neurotoxins, and various other subjects. Thank you, Dr. Patel. Great, thank you very much. Happy physiatry day. Good to see all these people interested. And I'm assuming that most of you are learners or early in your career or not necessarily using botulinum toxins as much, right? Am I correct in assuming that you're kind of new to the area? Nope. Some of you are doing it for a long time. I see somebody who I know does it for a long time. That's okay. So what I want to do is, Dr. Alter did a great job. And that's just the tip of the iceberg. There is so much to know about this. And we only have a few minutes. So what I want to do is go over a few things with you and give you a really high-level view of how to approach this whole area of taking care of patients. So first of all, let me just start with a thing that happened yesterday. I had lunch with somebody and he told me that he was admitted to the hospital a few months ago. He was in the hospital for 10 days. He had pneumonia. And of course, what did they think? That he had COVID. They kept giving him all different kinds of antibiotics, kept testing him. Everything kept coming back negative. And he was close to being put on the vent. Then one more test and they found out that he had fungal pneumonia. They started him on medication and the very next day he got up and walked. The day after that, he went home. So what's the point? You have to make the correct diagnosis. You have to have the correct dose or the treatment. And you need to have compliance from the patient in general to get a really good outcome. What's happening? There's so many people with spasticity. And as physiatrists, we are taking care of the majority of patients or we come close to taking care of these patients that have spasticity. And who gets spasticity? People who have upper motor neuron syndrome, right? So people who have insult to the brain or spinal cord. Now most of you may not necessarily take care of neuro rehab patients. But then I would say, I live in Kansas City. How nice would it be or how bad would it be if the orthopedic surgeon who lives like in the middle of Kansas says, all I'm going to do is take care of shoulders. And then has a nine-year-old kid that comes in with a broken forearm and says, no, now you have to go 200 miles to KU Medical Center in Kansas City to take care of that. Because all I do is shoulders. But that orthopedic surgeon could have easily taken care of that. And I think that's what we need to do as rehab physicians. That if you're in sports medicine, musculoskeletal spine, recognize spasticity. Either take care of it or find somebody to send these patients to. Because less than probably 5% of people who can benefit for the treatment of spasticity are getting adequate treatment. That's horrible. 95% are not getting it. And then Dr. Alter just said, 30% of people who actually get botulinum toxin don't come back after the first treatment. 50% don't come back after the second treatment. That's horrible. So there's a huge opportunity for us as physiatrists to make a big difference. And so I think all of us need to know how to properly diagnose, identify these patients, and then treat them, right? Or send them to the right person. So I'm going to go over three things today. How to assess a patient with spasticity. I'm going to talk about the importance of goal-setting and compliance. Because what good is it if you identify it and the patient doesn't follow through? And the third thing is dosing. So I'm going to just spend a few minutes on each of those things and just talk about it, okay? So identification. Upper motor neuron syndrome, you've got to make sure that the patient has spasticity. The next thing is, how is the spasticity affecting their function? Is it helping them or not helping them? If it is helping them, then maybe you don't want to get rid of that spasticity, right? And if it isn't helping them, then what is it? Is it the spasticity that's causing the problem? Or is it the complications of spasticity, right? So if somebody has increased tone and they stay in this position, then they're going to have stiffness and contractures. And when that happens, you're really treating not the spasticity. You're trying to avoid the complications of spasticity. I work in an orthopedic group, and when we put people in CAS for six weeks, they haven't had an upper motor neuron syndrome, and you take the cast off, they're a little stiff. So that is to do with positioning. And why do we get contractions and stiffening? Not because the tendon gets shorter, it's the muscle. The muscle, if you think of a little bricks, right? Each sarcomere, the length of the sarcomere gets smaller, and the number of sarcomeres decreases. So when you stretch muscle, the number of sarcomeres increases, and the length of each sarcomere increases. And that's what we're dealing with, right? So most of the patients you're going to see are going to be patients that have issues with complications of spasticity, and not the spasticity itself. The spasticity is putting them in that position, so you're taking care of that problem, so you're avoiding a complication. And that's a huge problem, and then there's much, much, so much more stuff to do. But even just starting with that would be so good. It would be just like saying, if you, every patient you see, there's such a high chance that the patient you're seeing has diabetes now, right? In America. And you want that to be taken. It's the same thing. If you're going to be taking care of pain management patients, whatever, there are chances that someone of, one of your patients has some kind of an upper motor neuron problem. You're going to see that on a weekly basis. And how can you help these people and identify them? So when you're assessing patients, and if you really want to treat them, or if you're going to pass them on, but at least, so first recognize that they have spasticity. And I'm assuming that you all know how to check reflexes and all this. I'm not going to spend time on that. But how do you decide which muscles you're going to inject? And that's so key, because you have to figure out how it is impacting their function. So you're going to get a good history, of course. Get a good physical exam. And then, on top of that, you want to get a really good functional history and a functional exam. What do I mean by that? You want to find out how is this impacting their life. You need to get in their shoes and walk in their shoes and see what they're going through the day, and how can you change that. So is it, is the tone affecting their ability to get out of the chair? Is it, are they losing their balance? What is affected? And I keep going like this, because the most common cause of spasticity in adult disability in the United States is what? Stroke. So it's going to be one-sided. Of course, you're going to have CP patients who are going to have both sides, or spinal cord injury patients are going to be both legs or both arms. But just let's stick with stroke. You know, there's so many people who have stroke in the United States. So you're going to, the more likely than not, you're going to see a patient with stroke. And let's talk about the simple low-hanging fruit, right? People are coming in like this. They're walking with a stiff gait. They've got increased tone in their leg. And you're going to have to figure out, is it, because our patient could be sitting, and they may look really good, and you check their tone, and everything seems okay. The moment they get up, they get synergy, and everything tightens up. And so you need to see what is impacting their function and how it is. And once you've identified that, and going back to Dr. Alter's point, right? It's so much, don't blame the drug. Don't blame the treatment. Look at yourself first. That's the first thing. So if a patient doesn't respond, it's not because the drug didn't work. You probably didn't find, identify the correct muscles. You probably didn't use the correct dose. Or you didn't tell the patient what to do. She said that you need to do other things, right? You can't just give somebody the drug or the treatment, and then expect a good result. This is so complex. It's not a simple thing. Like, you know, you got a broken bone, put a cast on, go play. You know, the cast is going to keep you immobilized, and the bone's going to heal. It's not that. They have to do therapy. You've got to stretch, and all that. So once you've recognized it, I think it's so important to get buy-in from the patient, and the family, and from you too. And you need to properly document what the goals are. And you have to make sure that these patients are going to follow through with this. And one of the best ways to do that is not only educate them, but you write down what the goals are, what they're going to do, and follow up. Even if you're going to treat, she said, most patients get treated every three months. So after the first treatment, bring them back in at four to six weeks. See how they're doing, and tell them. And they're going to say, some of these patients still tell me this. Well, doc, it didn't work. And I said, remember we told you, it's not going to work in one treatment. It's not even going to work in six weeks. Yeah, the botulinum toxin effect is going to take place in one to two weeks, but you're not going to get better in six weeks. And you have to reassure them, and educate them, and get buy-in, and make sure that they understand what's happening. So they don't say, you know what, this didn't work. I tried it, it didn't work. I'm not going to come back. All right? You keep trying, and you have to keep explaining it. So I think we need to drop, even though the few people that do come in for treatment, we want to reduce the rate at which they drop off. We can't. That's 30% people show up after the first treatment. That's just crazy. Sorry, 30% drop off after the first one, and then 50% total drop off after the second treatment. And I think one of the biggest problems might be education. The other thing is, if they're not seeing impact, then that's a problem. So that brings me to dose. If you just, if you have a big fire, and you just put a cup of water on it, it's not going to make a difference. Even if you cut that big fire in half, the patient's not going to notice anything. You have to make sure that the patient understands it's going to take a while, but you also have to show them that there is an impact with this. So appropriate dosing. You have to use a good and adequate dose. How do you decide what dose to use? If you haven't been doing this, and if you're going to go out into practice and start this, my recommendation would be start with one product. There's so many products out there, but they all come from the same bacteria. They're processed differently, they act a little bit differently, but those are nuances. Forget about that. You've got a diabetic, you want to bring the blood sugar down, it doesn't matter which drug you use, get the blood sugar down first. Don't be so involved in trying to figure out whether I'm going to use Glyburide or Glipper. You can figure all that out a little bit. Just try and at least just get the treatment going. So with these patients, the first thing I would do is just pick one, pick one toxin, and maybe the toxin is going to be picked for you anyway, because you're going to be in an institution or you're going to join a practice where the other physician is using one product or two or three. Pick one. Get to know it and get better. As you get better and better, then you start adding another one, and then you start looking at the nuances of what happens when you switch and all those kind of things. But those are all higher level things. First, just get to start with treating these patients. And there is a big difference in the numbers, but the numbers don't mean as much as when you're looking at an individual product. So onabotulinumtoxin, Botox, comes in 100 and 200 unit files, and the total dose with FDA approval on label is 400 units in one session. Xeomin, Incobotulinumtoxin, same thing, 400 units. And when it comes to Dysport, which is abobotulinumtoxin, is 1,000 units total for upper limbs plasticity, and if you're doing both upper and lower or just lower, the maximum dose is 1,500 units. So if you're going to be using for somebody with musculoskeletal pain, you're going to put them on aspirin, you're going to put them on Motrin, or you're going to put them on, sorry, ibuprofen or naproxen, you don't start thinking, okay, what am I going to do? You just know naproxen, and you know ibuprofen, right? You know them separately. Start the same way with the toxins. Just know one of them, get to know it, and then you can add other info because there's so much more to learn. Once you've picked a drug, then you want to make sure that you use the information that all these companies have with the doses, which many of us spend time figuring out, and there's so many papers out there, but just look at the package insert and it'll give you a range. Then once you've figured out the patient and you say, for example, this patient has no function, say for example, they come in like this, they're in a wheelchair. They're not using their arm. You ask them, what do you do all day? Do you use this arm to do anything? No. So you could start slow or you could start aggressively, but if you're scared, start slow. But then don't take forever to go up on your dose because you're wasting three months at a time. The soonest you can inject this person again is in three months. So don't go with a really dodo. Look at those things and see if you're getting an impact. Plus you want to get buy-in from the patient. So if they're really, really tight like this, negotiate with the patient. What's the goal? Because you're not gonna be able to treat all the muscles. So are you gonna open up the hand? Are you gonna open up the elbow? Are you gonna open up the shoulder? And you figure that out and then really target that appropriately with a high dose. And given all the other issues, I think you guys will agree, it's extremely safe. It's like water. You can drown and get killed, right? But if you use it properly and everything, it's just works really well. So same thing with potassium toxin. It's a very safe product if you do it properly. And I would recommend that you get to know the doses, look at the range, see what your patient is. And if you have never injected, you're just starting to, yeah, start out slow. But you'll quickly realize it's not doing much if you're using a very, the low end of the dose. And then also learn from your own patients and how they're responding. So I really would recommend that you follow those patients at six weeks, not at three months, when it's time to do the injection again because the effect is worn off. You want to see them at the optimal set because you are learning from your own patients and your confidence will go up and then you will figure out what dosage is to use. So if you're really trying to open up the elbow, you'll say, gosh, you know what? I need to go higher with the elbow flexors. And you need to know your functional anatomy. So if somebody's like this, this is just a simple example and you guys may already know that. If somebody's already pronated and biceps is a strong supinator, right? So if you inject the biceps and make the supinator weaker, they're gonna be even more pronated. So go for the brachialis. Open up the elbow with the brachialis and the brachioradialis and not with the biceps. But if they're supinated and flexed at the elbow, biceps might be a great muscle to target. So that's what I meant by functional anatomy. You need to know their functional and understand functional anatomy and how it's affecting the upper or lower limb and then go from there. With the lower limb, I'm just gonna say go with high doses from the get-go and don't be afraid. Why? Because physiatrists, what do we know? We know how to brace. If you brace the ankle, you can paralyze the ankle. You're gonna be fine. Put a brace on, the patient will walk. And the great thing about this thing is we're not cutting. Explain that to the patient. Even if somebody's super tight and you give them overdose, the only thing you have to worry about is if you stay on label, you're not gonna give them other side effects. You got to make sure it gets into the muscle. If it goes into the bloodstream, you just wasted the drug. It's not gonna cause a problem. So you don't want to waste drug. It's so expensive. Super expensive, somebody mentioned. And it's also very safe. You're not gonna cause any real big functional problem. And even if you did, you educate the patient. You know what? This happened. That's fine, but guess what? Good news and bad news. Good news, you don't have to, you know, we can wait and it's gonna come back. Bad news, you're gonna have to see me again because I'm gonna have to inject it and we're gonna have to lower the dose or whatever. So, but anyway. So, there's so many different ways to go around this, but you need to look at the whole picture. The botulinum toxin dose, and I'm not gonna go into any specific dose because there's so many different products. Pick one product, look at the label indications, start with the low to medium dose if you're really afraid in the beginning. You'll quickly realize it's not working as well. And even if you use a total dose, a total low dose, and you can say, I'm gonna get aggressive. I'm scared to use more than, I'll use Inco or Ana botulinum. I'm too afraid to use 400. Okay, start with 200. But if you're gonna start with 200, then figure out what you're gonna target appropriately. So, maybe you're gonna sprinkle a little bit in the elbow flexors and everything, but then go crazy with the thumb, extend that thumb out, get the flexor pollicis longus with the high dose. And see what happens. Patient will see a difference. You'll see a difference. You know you got it, and then go from there. And if you didn't make a difference, then you say, wait a minute, why did I miss? And that's when guidance comes in. You wanna make sure that you are using proper guidance. You're getting your drug in the right place. I am going to stop here. I think there might be more stuff, but there'll be questions and everything, and I'm gonna hand it over. Thank you. They may not have a question anymore. But the fashion disaster, right? Look at this. Anyway, my name is Hye-Kyung Kim. You don't need to introduce me. Let's run because we don't have that much time. But I'm a pediatric physiatrist. I work at University of Texas Southwestern. I'm the department chair. That's very, can I run? But today I'd like to discuss about surgical intervention, but I don't know where is my slide. But I'm going to discuss, oh, good. Okay, next slide. Do I have to do that? I like to stay here, so can you push the button? Because he did, so I want to do that, too. Something has to be different, right? So I have to move very fast, but since I'm the pediatric physiatrist, you have to think about three things. Spastic muscle is stiff and weak, and children are not growing. Next. So if you look at the picture, this person is 19-year-old. Left triplegic cerebral palsy, you can see. Left side of the hand is very small, right side of the hand is big. So growth really matters. Pediatric physiatrist, we work for catching up the growth. So bone has no spasticity, muscle has spasticity. Spastic muscle cannot grow that much, and bothers bone growth. So bone gets longer and shorter, and muscle gets shorter, too. But if you use any means to stretch the stiff muscles, we can prevent shortening of the bone and muscles. So all our life, we try to catch up growth, bone growth with stiff muscle by using all kinds of means, with the surgery or botulinum toxin, those things. Next. So when we're gonna think about the surgical intervention, so if the patient has diffused spasticity, toxin dose may not be enough. Or if they have a functional problem, if patient is dystonic patient, sometimes it's very difficult to isolate the muscle, and then they have a whole body contraction, so toxin injection or phenyl injection may not be enough. Those cases, or some cases, they have a severe pain, which cannot be controlled by any other means, by surgical intervention. Or a hip subluxation dislocation, those things can cause pain, right? So we can send patient for surgical intervention. Next. So this patient is dystonic child, and she is having severe dystonia in her both arms, but both legs has a severe spasticity. So if you see it, dystonia, she tried to tell me that her knee is hurting, but she cannot go to the point, right? But when she's relaxed, she's not trying to tell me what's the problem. She's almost hypotonia in her upper extremities. But lower extremity, spasticity is sustaining all the time. So spasticity causes contractures. Pure dystonia barely causes contractures, because it comes and goes. Dystonia, emotion and attempt. But spasticity, the resistance is always in their body. Therefore, if you don't passively stretch, they will develop the contractures. Next. My voice is very attractive, very husky. I couldn't talk one hour, because they were talking too much. Next. Intrathecal baclofen pump. Everybody knows intrathecal baclofen pump, right? Next. No, we have to move fast. So because we have residents and attendings, so actually I was doing lumbar puncture, right? With the LP and then we do trial. So you identify the patient. Once you identify the patient, you have to do test trial. But most of the children with spasticity or dystonia, they have scoliosis. Those cases, you don't want to do LP without the sedation. What patient who has too much movement, you cannot do LP without the sedation. So I'm doing, next. I'm doing LP with interventional radiology. So they don't let me do the LP, right? It's their motion. So actually my partner, she is doing LP for me. But as you know, the pump goes under the skin and then tip of the catheter originally stays in T10 because initially we know the GABA receptor is only in the spinal cord, right? Laminate two at that time. Later we found out that GABA receptor is in the brain too. So now we are using intrathecal baclofen for brain pathology patient too. But beginning, at the beginning, I was resident at Kessler at that time. First patient in the nation we did a trial and then the patient was incomplete paraplegia, spinal cord injury patient. Later we tried ITV patient for brain injuries. Next. So we are doing trial and this is the video. You can click the button for me, the left side. So the patient who has spasticity modified at your scale, I'm gonna push the button here then. It's not running? Oh good. So she's trying to bend her knee, his knee as much as she can. So I thought the knee was contractured, right? And then, can you click the next one? So one hour later. One hour. I actually have everything in my packet. Like a new dental mask, right? So it was not contractured. There was almost modified at your scale four, right? So you have to be really careful when you say patient is contractured until you put the patient under the sedation, you cannot really say that. Next. And then I'm trying the intrathecal baclofen trial for the hemiplegic CP. Some patient is very severe. If the patient has a thalamic stroke, they have very severe, like kind of a strange spastic dystonia. You cannot really say what they have. But you cannot really have a successful outcome trial with botulinum toxin injections or even phenol injections. It goes back, almost. So I said, why don't I try intrathecal baclofen? So let's click the left side. This is prior to trial. And he's walking speed is slow. And actually, I have to confess, he is not wearing shoes, so a lot of trend in lumbar gait, you can see it, because of also leg length discrepancies there more. So he was very stiff, and you can see his arm. But next. Turn around, come back. He does have a still arm, but still is a little bit looser, and his walking speed is much faster. As you know, intrathecal baclofen trial, the medication goes downstairs first by gravity, right? Then it goes to the upstairs. So he walks better, but arm is not, you don't see that much difference, right? We gave only 100 units at the time, or one in the microgram. What am I saying, units? Always toxin injections next. So it's okay for you to put the intrathecal baclofen pump for the hemiplegic patient very safely, no problem at all. This is a very interesting story I want to share. Just like Dr. Atul and Dr. Arthur, we really, we are very passionate tone management people, right? So this girl was my dearest patient who was unconscious over four months after the car accident, and she, the insurance company want to discharge her. They were pushing me to discharge her. I was thinking about how I can keep her in the room, or in the hospital, right? So I asked my case manager, how can I keep this girl in the hospital? I feel like there's something, right? She said, do some surgery. What surgery? I mean, she's unconscious over four months. She had all the subluxation, because so stiff, whole body stiff. Anyway, so I convinced a neurosurgeon. At that time, CHOP didn't have a pump program, so I convinced a young junior faculty, because senior is against ITV. I told him, Peter, you're a junior, right? Don't you want to be famous? I said, what is it? I said, just follow me. At that time, I barely spoke English. I barely able to convince him. Anyway, he was convinced. So we went to the hospital, DME committee, and then he and I supposed to present. And this guy had emergent surgery. He texted me, Hye-Kyung, I'm so sorry. You have to present. How can I speak English, you know? But your passion brought me to speak to the group. So I was able to convince them. They bought the $20,000 pump. But I had to try first. When I do trial, the patient didn't show anything. So I was very disappointed. And then the mom said, no, no, no, no. Yes, yes, there is. I'm Korean, so that's why I said no, no, no. But yes, yes, yes, there is some difference. So what difference is it? The difference was she was so comfortable. Oh, I wrote the page by page to report to the hospital. It was very effective. So they had to buy machine, right? The ITV. So I brought her one month. She had to go home because the insurance didn't allow us to keep her. One month later, I brought her back. And then neurosurgeon put the pump. Let's look at the video. She was unconscious, right, over five months. By the time I brought her to the hospital, she was minimally conscious status. So she was following commands with her great toes, up and down. That's the only one she was able to do. But actually, she was awake whole throughout five months. Can you believe that? She was locked in. She was so stiff, she couldn't talk. As soon as we put the pump, she was waking up. Now she's walking, right? Two and a half years later, we took the pump out. Next slide. I got the picture from mom eight years later. It's her prom picture. So please do not give up your patient until they give up. Patient give up, right? So you're not the one who's going to give up the patient. Next. So this is just a study. This is a famous guy, Dr. Mota in Italy. They did a study, which showed the fastest endostonia improvement. Next. And then common adverse event is hypotonia. You guys know this one, right? And the overdose is a problem. The more problem is, Reginus was the emergency department for the intrathecal bicarbonate, right? There's a lot of confusion comes, because we have two different, I'm going to briefly say that because it's very important. When you get called by emergency department, just run to the ED. Before you go to the ED, you have to tell them to put the IV, do the ABC. And then you have to start the benzyl, IV benzyl, right? You have to calm them down. Otherwise, they're going to go to reptomyelitis. They're going to die. So you have to relax them first. So while you're on the way, so you have to think. Troubleshooting, right? So we had one patient who had arachnoiditis. She's a grown-up CP. We put the pump for pain control. And she came with severe rigidity in ED. Looks like going through the withdrawal symptoms. So we did a whole troubleshooting. Everything was negative. Later, we read the MRI. It shows there's some arachnoiditis. But the symptom why she complained was exactly arachnoiditis, actually. She had severe leg pain on and off, but not constantly. But we got confused. But what I'm trying to make the point is, you're going to do troubleshooting later, but you have to relax the patient rigidity, solve the rigidity problem first. Next. So we did, one thing you have to know is the serotonin syndrome, right? Usually, serotonin may block the GABA. That's why, while they are having the pump, they have less GABA coming from their body. So when the intrathecal baclofen has a problem, GABA is not there. So now, serotonin has been blocked. So now, serotonin is gushing out. So they are going into serotonin syndrome. They're exactly same problem, like crazy people, right? So then, you can give GABA, you can give benzo, you can give everything to make them just relax. Next. Neurosurgery, deep brain stimulation. Next. So, as you know, you put the pulse generator underneath the skin, and then we go to the target area to put the stimulator to control the movement. So the only one thing that we have to know, the side effect is paresthesia muscle contractions, but we know that globus pallidum, we usually go there to control the chorioarthritoid movement, dystonia movement, but cerebral palsy is much less responsive to GBS. Why is that? Their brain lesion is dirty. It's not pure dystonia. It's not from the one focus. So outcome study did show only 23% is positively effective. Next. So when you take a look at the dystonia, primary dystonia is a genetic origin, which we call the DYT1, DY, DY, DY. This is all pure dystonia. So they are not cerebral palsy. They are progressive lesion. Second, that is due to hypoxic event or stroke, whatever brain lesion happened later. It's not genetic disorder. So that's the two dystonia we're talking about, and mobile dystonia and fixed dystonia. Mobile is there's no contractures. Some dystonia does have contractures. So if they have fixed dystonia, it's much less effective. Next. So DBS indication is mobile dystonia, and after you failed all kind of medication, and sometimes I was thinking, I don't know, I agree with that. You have to try Levodopa, try Hexanedil, Gabapentin, over 12 months. We try more than that, right? Longer than 12 months. But try everything what you can do. The best one is actually botulinum toxin, then oral medications, but the dose is so limited. That's why we feel like we are not helping them that much. So my patient had the DBS, and then what happened? Five years later, they really started to show more rebound dystonia. Not everybody, but they did. So they had to take the DBS out, and then, thank God that's temporary, right? You can take it out. And then we are doing heavily botulinum toxin injection and phenol injection to control the dystonia and pain. Was much successful. Parents prefer that way. But you have to do whole body injection every three to four months. So, as I said, primary dystonia is better, since secondary dystonia has different motor and non-motor problems from the involvement of multiple brain lesions, right? So you have to remember that when you discuss with your patient, if they are secondary dystonia, you may say that that may not be very effective. So we talk about target, and so as you see, the study showed that 20% patient showed positive outcome when they did the cerebral palsy patient. Next. And then, this is interesting because it depends on your mood, that's the way I teach you guys when I teach dosing of botulinum toxin, right? Same things with the DBS, depends on your mood, where you wanna put the, leave the tip of the stimulator. So if you leave that in cerebellum, what happens? Cerebellum is governing whole brain, actually. You have to study cerebellum, it's so fascinating area, but think about it, they stimulate the cerebellum, so what do they see? Spasticity improved more than dystonia, actually. Makes sense, right? So hypotonia, controlling the hypotonia. Next. So now, SDR, I have to move really fast, right? I condemned them, but five minutes. Okay, so, once we get the microphone, we don't wanna get, stop. So SDR, just, I would like to just talk about, we have SDR, right? Dorsal Rhizotomy, so you cut the sensory branches to stop the motor output, but now we do Ventra. Dorsal Ventra to control the dystonia, so we cut the motor and sensory together. Next. Next. In terms of indication age, there's no limitation anymore, whatsoever. Two and a half years old can go to SDR. 34 years old, like me, can go to SDR. So no age difference. I apologize, I was sleeping while I was making this slide, but update. So Dr. T.S. Park, my Jared Lubin, my dearest fellow, now he's in charge for the Pediatric Rehab. Over there, Dr. T.S. Park is there. He started, now he did not start this one, but he has the most cases. According to his long-term study, 20 to 28 years, they followed, which showed the patient, you know all those childhood onset spasticity? They have premature aging, right? So a patient used to walk, but about 50% of the patients end up stop walking because of mismatch of the bone growth and spasticity, sarcopenia, and then fibrosis in the spastic muscle. So when they followed this patient, actually they were able to stop the premature aging, or delay the premature aging. If you read his article, there's video in his article, they show from the little, like three years old to 30-something years old. So patient usually start walking at late teenage, 25, 35. By the time they become 35, 50% of patients stop walking, but his patient, or other doctor's patient who had SDR in younger ages, they were able to walk much longer period, and then they started to do SDR. When they stop walking, or when they deteriorate, walking by 35 years old, or 40 years old, they did SDR. They were able to go back to their baseline next. So don't stop giving them opportunity to improve, or prevent their functional deterioration. This patient next is not important. Orthopedic surgery, two more minutes. So the patient, the spasticity works as a pressure for the growing children. So they press down this growing bone, and then they prevent physiologic derotation. Therefore, Koch survival happens. And then chronic spasticity causes liver, arm dysfunction. So your patient usually start like this. Internally rotated, knees kissing, foot is rotating like this. Your patient walks like this, right? Then botulinum toxin doesn't work. ITV doesn't work. So what do you have to say? Orthopedic surgery doesn't address spasticity. It addresses bone and pain. So next. So this kind of condition. So we have to send them to orthopedic surgery. Next, next, next. Oh, can you, can I show, can you click this button? Oh my, he just, she's kicking me out. Okay, that's okay. But the, okay, that's all right. I think they understand everything. So what I'm trying to say is when we have this liver, arm dysfunction, you have to work with your orthopedic surgeon. They are not telling you what to do. You are the one who's gonna tell them what to do, right? So you have to know better. So I usually tell surgeon, time to bring your patient to surgery. So we talk, we discuss, and then you ask them to do osteotomies. So you have to do, you have to recommend a femoral osteotomy, tibial osteotomy, and then you can do triple isoarthritis in their feet or you can delay the surgery. So we have to have a multidisciplinary team approach, but physiatrist has to know more than anybody. Thank you. Thank you all so much. I think we may have time for like a few questions, possibly. Yeah, please, that'd be great. Okay. Questions. I can start with a question. So I know that you mentioned everyone kind of knows the three month interval, but now more and more of these toxins are being used for multiple indications. So sometimes we'll have a patient who's getting bladder or Botox. What is your timeframe for considering that as kind of the same, like does it have to be the same day, the same week for those other ones to be used until you have to wait for the next three months? I think we don't have, can you guys hear me? I don't think we have really good data on that. And I think one of the things I would mention, what is the concern? The concern is you're gonna have immunogenicity and then you're gonna have lack of response, right? All of us have been doing this for a long time and when we're educating our patients and some of them are by mistake getting treatment in between and we find out after the fact, I have not seen a single patient with true resistance. They might have antibodies, but they are not truly resistant. I do the brow test and it works. I clean them out and it works. So that's one. But we don't want people to have immunogenicity. So I always educate them. And you have to be really careful because if you're treating different areas, patients don't realize and other healthcare providers don't understand how botulinum toxin works. So they'll say, oh, Dysport. It's completely different from Botox. So you can have your Dysport for cosmetic today. I know you're getting your migraine tough in three weeks, but that's okay. And then the patient comes to me and cries because I said, I'm not gonna treat you because you just had botulinum toxin three weeks ago. So they don't understand. So we have to educate our patients. And I spend a lot of time making sure that they know all the different products, trade names, and that if they're getting injected somewhere, I need to know about it. And I think as a physiatrist or us who is taking care of more of these conditions, I actually take it upon myself to communicate with the urologist and say, I'll time it around your injection. I know I'm busy. I know you're busier somehow. So I will work around you. The good thing for at least the urological or the sialaria conditions is that toxin seems to last longer on smooth muscle and on gland. So that usually the urological conditions you're injecting every six to nine months and the sialaria, it's usually six months is what I'm doing. What about you, Hye-Kyung? Yeah, I do, I cannot say, dually. Salivary gland injection, initially we do every three months and then after that, according to our retrospective study, as we repeat, the duration of injection gets longer. So usually after four to seven times of repeat injection, you don't need to do injection that much often between the six months or even sometimes one year. So I think initially you should repeat every three to four months to prevent aspiration if that's the goal of the injection. If for the cosmetic, you do it every three months, initially, then later, you do. Same thing with the palm. I mean, the gland, the effect, as you repeat the injection, the effect lasts longer as you repeat it. So at least that's helpful is that if you're doing the sialaria and for those conditions, sialaria and bladder, they're already at longer intervals so you can try to coordinate. The ones that I have problems with are patients that we see for blepharospasm and other dystonia conditions and when we're not treating their blepharospasm. We try to, we're not trying to take the patient away from another provider. We actually try to do it within 24 hours and that's the way we view it. But remember the label doses, 400 units in three months, not 400 units for spasticity in three months and 120 units for migraine or 440 units for migraine. It's not 900 units per. Now all of us, you didn't hear me say this, we use higher doses but it's actually, I don't know what you think but it's actually become more difficult now that spasticity is on label. I never used to have denials for higher doses but now you get denials for higher doses because the insurance companies will say it's only labeled for 400 units so you can't have 600. Yes. Right. Because we don't get it or I don't get it in a month but when I see many pediatrics, they just routinely bring the patient every three months and they say, we are very busy. Busy for what? I'm sorry. Yes, sure. I'll just add one more thing. So I'm in a study right now. We're looking at real world data and the name of the study is synchronized. Hopefully we'll get the paper out in the next meeting and looking at people receiving botulinum toxin for more than one indication. And then we'll look at the time, the dose and all those things. That'd be great for all of us that are struggling with that. Another question I have is, as the PT philosophy kind of pushes towards goal-based and periodic, if you do have a patient that you are doing it on that three month cycle, are they essentially always in PT? How are you doing that therapy description? Yeah, I'll go first. The thing is, I think you have to look at the patient and all the situation. I mean, not everybody has the luxury of getting therapy all the time. So I do ration their therapy. It's a rare commodity and expensive. So you time it to the time when it's gonna make the most difference in the beginning and then you really educate the patient and family. And it's not a recipe, right? I think I also treat other conditions like cervical dystonia, where it is a little bit more of a recipe. They're gonna come every three months for the rest of their lives. Going back to spasticity, am I treating the spasticity or the complications of spasticity? Once I've opened up their arm and they keep stretching, do they need treatment every three months? Probably not, right? But some of them, there might be new goals. I'm going to some other area now. But depending on every time there's a new goal and can the patient learn it or not, but you do try to get therapy. It'd be nice if everybody got therapy, but you just can't do it. And it's really different in the States what is approved in other countries. I had a patient that moved here from Iran because they wanted their child to get better care. And when they got here, they were appalled with the amount of therapy that was approved by the insurance because the child was getting two or three hours a week of therapy in school and then an hour of private therapy every week. And now that they got an hour once a month in school. And so anyway, insurance isn't gonna tell you, unfortunately, how much you can have. They may have 30 visits per year or 60 visits per year. And if you use all those 60 visits up in one session, it's the home program that's the key. The therapist is directing the home program that the patient's supposed to perform. I would just add that I don't like to send patients to the PV regularly. I emphasize having patients. So dancing, all my patients need is to sign up for the dancing class or rock climbing. The podi-clay, they can have rock climbing too. And of course, actually, I have a beautiful video, but I cannot show today. But really, the moving full body changes. So especially all those patients, my patients are very prone to cerebral palsy, right? Therapists don't like that at all when they grow up. They refuse to treat them. So I send them to dancing class and they can meet up with a somebody and they can go out. The mental has to release the factors, you know? Yeah. Right. I mean, community-based activities are a form of therapy. I mean, just like exercise is medicine. So however you exercise, it doesn't have to be in PT doing range of motion. I mean, that's not really what PT is, right? If you have a good therapist, the therapist is doing activity-based interventions. Yeah. I have a very naive question about ITV. I was excited to hear... My question might be... I have a... I was excited... That's me, sorry. Telling me I'm supposed to be in another room. I was excited to hear about ITV on stroke patients because I take care of a lot of stroke patients. I was not... I have been hesitating to refer to ITV unless the protocols were being filled. I'm wondering... So, the reason is... I'm wondering if the ITV is also affecting the other normal limbs. I didn't see that at all. There was a patient... Weak in the... Yeah. No. It's not affecting the sound of life at all. I was... Actually, the father was a patient for years and we went up to 1,500 micrograms because he's so severe. But he didn't have any weakness of his sound of life at all. Right. And there's a good study that looked at this, looked at people with hemiplegia and spastic hemiplegia. It does not... It's a GABA receptor, it affects spasticity. It doesn't affect strength. It's the same with patients with hemidystonia. It exposes the weakness on the spasticity side when you decrease the tone, but it doesn't decrease strength. So, it does not affect the unaffected side. Right. How about the PO? PO's terrible. No. Same. It affects strength. Well, no, but PO medication, you have to use so much to get any effect because you got to get through the blood-brain barrier. Right. So, yeah, a hundred times the dose. So, by the time you get to the effective dose to reduce spasticity, you've already caused too many cognitive side effects. I don't know if they are really weak, oral effect, can they make anything higher? They don't care anymore because they're sedated. Very weak, very, very fatigue with the oral effect. And remember that it's also cognitive slowing that you see in these medications. So, you've already got a child that has a learning disability or a patient that has cognitive problems post-stroke or TBI, and now you put them on high doses of oral, you know, baclofen, you're going to, and patients, non-verbal patients, are going to be telling you that they're having cognitive slowing, right? So, that's part of the problem. And it's same thing with Trihexaphenidyl for dystonia. People say that children tolerate much higher doses of Trihexaphenidyl for dystonia. Well, it's because nobody asks the kids, how do you feel? Right. You know, or asks, you know, if you ask their teachers, you ask other people that see how the kid's functioning, they will tell you there's a problem with Trihexaphenidyl. Yeah, the only thing I would add to that is, think of clean ways to treat all conditions, right? So, when you put a chemical in your body by mouth and it goes everywhere, it affects a lot of things. Some things we know about, some things we don't. Something like a natural product like botulinum toxin or a very, very low dose of a medication in the right place in the spine has fewer side effects. Right, so think of it that way. Right. Very good. Thank you all so much. Thank you.

spasticity management

botulinum toxin

FIT session

pre-procedure planning

patient education

accurate dosing

risks and complications

assessment of spasticity

goal setting

compliance

individualized treatment

multidisciplinary approach