Dr. Kathryn Sigford presents "Indications for Botox Injections in Pediatric Upper and Lower Extremity Conditions" at the UCSF Pediatric Musculoskeletal and Sports Medicine Conference 2023 in Berkeley, CA.
So I get to introduce next doctor Kate Sig Ford. Um Kate went to med school at U C Davis and then they did their residency in physical medicine and rehab at Stanford a few years before Dr Mitsu, I did it. Um And then they did their, I don't know why I'm saying you his name wrong all of a sudden today. That's the nerves. I'm sorry. And then um they did their peas rehab fellowship at Gillette Children's Hospital in Minnesota. Ok. Thank you. Um I was telling doctor no, during the break that as her talk to got into the first slide about boulla talks and I worried a little bit that I'd be repetitive, but she very nicely left me. Uh some things to talk about here. Um So I will talk about not just upper and lower limb indications for botulinum toxin use, but more broadly, almost anything you can use it for in pediatrics. Um Most of the musculoskeletal, but we will diverge a little bit from that first though to start out. I have no financial disclosures, but I will talk about off label use of medications during the course of this talk um a little bit first about botulinum toxin itself. There it is pro produced by the cluster botulinum bacteria and there are eight serotypes. Um The human nervous system isn't susceptible to D and in our medical usage, we pretty much just use type A and type B. The mechanism of action comes back to the neuromuscular junction. You may remember that the um nerve does not actually touch the muscle, rather vesicles filled with the acetylcholine have to dump out the acetyl colline to activate the muscle. What the botulinum toxin then does is it breaks one of these snap protein or one of these snare proteins that allow the vesicle to dock and keeps the acetyl colon containing vesicle from docking with the cell membrane uh thereby keeping it from activating the muscle. This is both how it works and why it's temporary because the nerve is smart enough to figure out over the course of time that something has gone wrong, I'd better fix myself. And this is where we get the temporary uh duration of act, the temporary direction of action of the Botox um on set and duration of action. Speaking of which we go, we go by the rule of three, it's not uh which is that generally you don't see effect at the time of injection though sometimes patients will patients or their parents will say um that as soon as the medicine went in, it helped, that's not terribly common and it's also not alarming. If it doesn't happen, you can usually start seeing an effect of the toxin by about the third day after injection. And it may continue to increase in effect as it affects the nerves through week three. So it may keep getting stronger and stronger. Average duration of action is about three months. It could go more than that, it could go less than that. Um And for most of the formulations com commercially available in the United States, the FDA approved dosing interval is three months. So no reinjection, sooner than three months, there are a few exceptions to that, but they're all, they're all on the longer side than the shorter commercially available in the United States are four formulations right now. Um Of which Botox is probably is the original and probably the best known that's on a botulinum toxin. A and much like Kleenex has come to mean anything you want to blow your nose on. Botox has pretty much come to mean any sort of botulinum toxin. Um which sometimes drives me a little bit crazy when I'm talking about doing a say, doing a disport injection on a patient and somebody else. Oh, are you doing your Botox injection? No, I want Disport today. Don't bring me, don't talk about that because one of these days we're gonna screw up and bring the wrong medicine. Um So they're, they're the onum toxin. A Aboul toxin, a incobotulinumtoxina and RMA Boulin toxin. B that's the only, um that's the only B that's available in the United States right now and seems in many of the studies in pediatrics to have a slightly higher instance of adverse effects than the A S. Um There was a real nice review article in the journal of the American Academy of Physical Medicine and Rehabilitation. Uh I believe it was published in the September edition that talked about all the pediatric indications of botulinum toxin and which made updating this talk very easy um units. What are we measuring this in? Um all the formulations are measured in mouse units. Usually people just say units rather than mouse units and one unit is the amount of toxin that kills 50% of a group of mice if you give one unit to each mouse. Um Why, why do I say this when it's when it's morbid and uh when it's morbid and may and may not mean a whole lot. The reason is because they work differently. Uh One unit is a different amount in every, for every formulation. One unit of Botox is not the same as one unit of disport is not the same as one unit of Myobloc. So you cannot uh you cannot convert interchangeably, you have to know what the dosing recommendations for the toxin you're going to use are. And or what various folks who have done a lot of work with the different formulations have come up with as presumed approximate equivalent estimates. The, as long as the next couple of slides are gonna be about adverse effects and we're gonna get the serious things out of the way. First with the black box warning that is on all botulinum toxin pro products. Um This one is particular, this one specific is to uh on a botulinum toxin. A they're all very similar. It warns that there may be spread of effect from the area of injection to produce symptom. Con consistent with botulism or toxin effects anywhere in the body that is in the muscle, you inject it in, uh in on purpose, you in the muscle next door or in a muscle, anywhere else in the body. This has led to serious adverse effects very, very rarely, but it has led to very serious adverse effects with enough dysphagia that people needed feeding tubes while the medicine was was in effect or affected their diaphragm enough that they needed respiratory support. Um regardless of where it's injected, higher risk, of course, if you're closer to one of those, one of those muscles, but regardless of where it's injected, um, some of the studies have suggested that our G M F CS levels, four and five patients are at higher risk of these serious adverse consequences, but that hasn't been consistent. Um Other adverse effects include injection pain and bruising. Um I'm not actually entirely sure why some of the studies listed injection pain as an adverse effect and injection hurts. This is, um, so some of the studies have much higher rates of adverse effects than others, depending on whether they counted injection pain and bruising those sorts of things that are going to happen when you give a shot. Um, the other one that is the other one that is somewhat common is a post injection soreness, which I've had described to me from patients who's experienced, it is feeling like, feeling like after you get your flu shot. So it's not, it's not great, but it's not terrible except for one person who, uh, got it a little worse than everybody else and, and, and said, no, it's like a tetanus shot. It's not, it's worse than a flu shot. Um, other issues can be muscle weakness. Now, that's, again, is it an adverse effect or is it the effect of the toxin? This is what we're trying to do with our botulinum toxin. So I guess it depends on in what quantity and in what muscle is it, the one we're treating or the one we're not treating or did it go too far as I mentioned before, dysphagia, breathing problems, pneumonia. Um, and then last, interestingly, there is an incidence of fever and flu like symptoms after injections of botulinum toxin, um, which is postulated maybe to be a result of the immune system reacting to the toxin. This certainly was fairly likely in some of the early on a botulinum toxin. A formulations where there was a fair amount of, uh, extraneous protein. They're all much more pure now. Um And so it's a little bit more puzzling, especially since you don't see a dose, defendant effect in the placebo controlled, in the placebo controlled studies. Um, all of that out of the way, you're probably wondering why we would ever want to use it anyway, having just told you everything that can possibly go wrong. Um, Nevertheless, really, for the most part is very well tolerated with minimal adverse effects unless you're gonna count injection pain. Um So what do we use it for as doctor? No, alluded to earlier, we use it for uh upper and lower extremity, spastic or any hypertonia. In fact, uh for congenital muscular torticollis for cervical dystonia uh for birth brachial plexus palsy. And here's where we leave the musculoskeletal system, uh allora or drooling and uh emerging use in pediatric for migraine. It's approved an adult for migraine. Um but looking like it probably works for kids too. Here is in graphic format, the different, the different formulations and what they're approved for. Um And in there too, we get a couple of other uses of um botulinum toxin, which aren't gonna come up today like primary axillary hyperhydration. And actually, you can do with palms and soles too. Um and detrusor overactivity. Uh So first we'll talk about spas use in spasticity um to review, when do we consider tone management? We don't necessarily need to treat all tone and we don't necessarily want to treat all tone. Question is what is that tone doing? Is it interfering with some part of life? Is it causing trouble with function? Is it causing trouble with positioning? Is it causing trouble with cares? Is it causing trouble with comfort? And sometimes you have to pry a little bit into this because the parents have gotten so used to taking care of their kid that, oh, no, it's really easy to, it's really easy to change their diaper. And then like, and then you watch them do it and they're prying the legs apart and sticking themselves between and like, so I often say, is it easy for you or would it be easy for anybody? Oh, I guess we're just used to it. Probably nobody else could. Um, what can we hope to do in terms of tone management with our botulinum toxin first, decrease plasticity, decrease dystonia. We can make it easier to stretch because those muscles aren't pulling back so hard, we can reduce pain because these plastic muscles can be painful. Um, and we may be able to improve function. But most of the time the botulinum toxin injections by themselves will not improve function. You have to have a plan after that. That usually will involve your physical therapists or your occupational therapists to capitalize on the different balance of muscles to help learn how to reuse things. Like, for instance, we have someone who's had wrist and finger flexion contractures. I can loosen those up. But then the occupational therapist is key. What do I do with this hand now that I can use now that I can use it, I've loosened up the gas rock enough that your toes aren't pointing straight down. You can try to walk heel toe. But the physical therapist is key in actually working on that motor pattern. Um, What can't we do? We can't lengthen contracted muscles. We can only get rid of excess tone. If the muscle itself has a contracture, we will not change that with botulinum toxin. We may assist with an aggressive stretching program and brace and stretching, brace or stretching, cast wear, but again, needs some assistance. Um We cannot independently improve function and we cannot expect it to last forever. Um This is in one of these three areas is where I see a lot of the folks that I talk to who say, oh, we tried that once and it didn't work and why didn't it work? Well, it more often we had to do it again. Uh Yeah, that's, that's how it works. They didn't get, it wasn't, it wasn't well explained clearly. And so the family ended up disappointed. Um It didn't work because the knees didn't straighten all the way out. Well, that's because your child has had their knees bent for the last 15 years and you have a contracture and I think we um I'm gonna, this is, this is particularly gonna be for the, for the therapist in the room. Um But I think we as practitioners contribute to that sum because we have a habit of just talking about muscle stiffness and not distinguishing always in our casual conversations between contracture and spasticity. Oh The muscle is the muscle is stiff, the muscle is tight. We don't always do a good job distinguishing that. And so we contribute to this confusion. I'll make sure before I do uh botulinum toxin injections on anybody that I say, do you know what spasticity is versus what a contracture is? Because I can only fix, I can only even say I'm gonna try to fix one of those. Um Then next, uh a little slide of some of the common upper extremity postures that we might see in people that we're treating and muscles in the upper extremity, you could inject which you look at the slides pretty much all of them. Um And the lower extremity, this is a more limited, this is a more limited diagram. It shows the muscles that are officially approved in pediatrics for on a botulinum toxin. A use. Does that mean that's all we inject? No, it doesn't mean that's all we inject. We'll take a look at the patient and say what muscles are causing trouble and treat those muscles very often. In addition to these hamstrings and hip abductors are a lot of are causing a lot of trouble. Um Next indication is in brachial plexus policy, particularly birth brachial plexus policy for their indications for treatment are a limited range of motion. Usually at the shoulder or elbow. There are not a lot, there are studies on this are still uh not a lot but showing that it may have showing that it may be effective in this case, what you're using it, what you're using it on is actually a normal muscle. If you think about the imbalances, say at the shoulder with somebody with the brachial plexus palsy causing an internal rotation, contracture, you may inject the internal rotators so that you can stretch them so that that weaker external rotator maybe has a chance to win for a minute and the kid learns how to trigger, it learns how to use it. Um Studies thus far suggest uh that the risk of adverse events is low that active and passive range of motion is improved. Um And different studies have suggested different studies have said different things about length. Some only showed improvement for the three month duration you can expect from the talks and others showed it going on quite some time after that. Um Next, in the next thing we can use it for is congenital muscular torticollis. Um congenital muscular torticollis is caused by shortening of the sterno clio mastoid muscle, uh trape and scale may also be involved. It leads to a head tilt to one side and looking to the other and congenital because it's present from the time of birth, it's often accompanied either initially or after those muscles affect development of the skull and face by skull or facial asymmetries. Um We're gonna take a side trip here for just a second into the fact that physical therapy is the mainstay of treatment for this. And the uh and the success rate of physical therapy approaches 100% if you get it started before the age of four months. So do not wait for the kid to grow out of it. Do not delay, get this, get your kid into physical therapy. If you can't get him into physical therapy, get him into my office and, and we'll see and we'll see what we can do, but really don't, but really don't wait for me because who knows when my next appointment is? Um And that's actually, that's actually the most important point of point of the tour to call as part of this uh of this talk. Um The there have been studies there have been other studies about, do we, do we do P T or do we do a home exercise program for Tortola? And there have been uh one study showed that P T three times weekly led to much faster resolution of torto callus than stretching at home. And what's interesting about that is these kids only were supposed to only do their P T three times weekly, the parents were supposed to not do anything the rest of the time. Um, on the other hand, we know both from this study and from other studies where the family just was told do your home exercise program, if you have a question, call up your P T, they'll talk you through what to do that. Home exercise program. Applied well and consistently can resolve this but applied well and consistently I think is where a lot of families fall down. If you don't have a physical therapist involved, when do we use? So that said, when do we use botulinum toxin when conservative management has been tried unsuccessfully. So, physical therapy, home stretching program and sometimes you'll bring in an orthosis, the lightest weight, the lightest weight when I meant to get a picture in here, sorry is just called a tat collar, T O T collar. And it's two. If you've ever seen that clear aquarium tubing, it's two pieces of clear aquarium tubing with posts in between and you put tall posts on the short side of the neck and short posts on the long side of the neck, real lightweight, real, um generally, really tall, really well tolerated because it's uh lightweight and fairly cool with just a minimal structure to it. Um If you've been working on conservative therapy for three months without adequate uh results, you is when you start considering use of botulinum toxin and moulin toxin. Like I said, a minute ago, is not probably gonna fix this by itself. You still need your therapy afterwards. Um, moving from that to the other neck problem is cervical dystonia distinguished from torticollis, congenital muscular torticollis as being a dystonia in which the position is not fixed. It's, uh, any dystonia is a movement disorder characterized by twisting motions or fixed postures, but they do come and go caused by involuntary muscle contractions. You can have it anywhere. Um and it can be painful. I pull out cervical dystonia um from the rest of the upper and lower extremity injections because there are a couple, there are a couple of special things to talk about injecting botulinum toxin into the neck. Um And that is that as, as I we we said earlier, the proximity of the muscles you're injecting once you get up to working in the neck to the muscles of swallowing, raise the risk of dysphagia with injections. Um You need to make sure you have an injector who's going to use some sort of guidance other other than just like. Well, I think the sternum melas coid should be about there between the mastoid and the and the sternum. Use E M G, use ultrasound, use electric stimulation something. Um So that you know that you're getting, you're getting into the muscles, you need not other muscles and not stabbing any of the other important structures in the neck such as, oh the carotid artery um in cervical dystonia, most commonly involved muscles are the splenius Capus semis spinalis and the steroidal mastoid, but just like as in treating spasticity, look at the person and see what direction they're going and treat the muscles that take you that direction. Um moving on, staying in the, staying in the head for a minute. Um The emerging use in migraine, which in a way it does, I think come back to musculoskeletal because we're injecting it into the muscles and treating the migraines that way. Um It has been, it has been approved for adults for quite a while. And there is, if you look particularly at like the on a toxin website, they have a whole recipe, inject 10 units here and 10 units there and 10 units there and 10 and the with the picture of the head exactly where to put it. Um it there have been two randomized controlled trials for migraine and pediatrics, both of them since 2020. So this is very clearly uh still very new. The they've gotten different results. One showed that the botulinum toxin was not superior to placebo and the other showed that it was that it showed that it was now both studies had some issues. The non superiority, one um differed from the adult treatment recommendations in that one treatment group got half the recommended dose and the and the study was powered to detect a change of migraine frequency twice that of what was considered successful in adults. So kids had so for it to be considered successful in pediatrics. In this trial, the kids had to have way more reduction in their migraine than they had than the adults have gotten in the adult studies. Not entirely surprising that they didn't see that. But the other study that showed efficacy also had some issues. It was 15 patients and two of them later went on to get diagnosed with idiopathic intracranial hypertension. So they didn't truly have migraine, true migraine to begin with more to come. I hope then lastly is or drooling. Um This is, this is a, this is a vaccine problem for a lot of people. The um it causes perioral skin irritation, aspiration, respiratory difficulties, articulation, difficulties, social stigma. Um this but actually what I, what I hear a lot of is I just have to change their clothes so much. We go through like 10 bibs a day and then we change shirts three times and I can't and I can't keep up. I don't hear perioral skin irritation here in California. Nearly much, nearly as much as I heard it in Minnesota and South Dakota. In the winter, the weather is better. Um which glands do you inject, you, inject the submandibular glands because they're most active in saliva production at baseline and the pro glands because they're most active with stimulation. Um Risks include the same as we as always, but also chewing difficulties. What's next? What's next to the glands, the Massad uh dry mouth because we're getting rid of saliva and injury to the facial nerve. Because again, that's right kind of there. Um What I think that I'm gonna mention quickly though, I did not write it into this talk is some of the, is some of the additional studies that have been done on repeated use of boul itm talks and it used to be that you gave it every three months and you didn't worry about it. It was, it was great. It helped kids. It was perfect, it was wonderful. The longer um then it became clear that m muscles that were repeatedly injected did suffer from muscle atrophy. That does, that shouldn't be surprising because you're making the muscle weak. It can't, uh it can't exercise in the same way. And as it became possible to get biopsies of some of these uh routinely injected muscles, there's also a change in muscle composition with decrease in muscle fibers increase in uh fatty atrophy and ground substance. Um Some of these, some of these biopsies have come courtesy of the orthopedic sur, uh have come courtesy of uh generous parents of patients undergoing orthopedic surgery where the surgeon said, you know, do you mind if I just take a little bit of the muscle, I'm cutting for science. So it's for the most part, they haven't been just biopsies for the sake of biopsy. So I think now more carefully about how often these injections are needed about what the end goals are and what our alternatives are, um where it used to be, where it used to be. Uh Well, I'll just inject this person every three months forever. I even, even sometimes that, that got old now I think more about some of the other things like doctor. No, talked about the um, back and pump the rhizotomy which can be used just to decrease tone in the low G M F CS folks, even without thinking about how it's gonna improve function, it can be used just for quality of life and ease of cares. Um And that also is work that is still ongoing to, to see exactly where it's gonna, where it is gonna end up. Um And that I think is where I will wrap up.
