I want to welcome all of you who are joining in with us for the Peds Rehab Community Session. I'm sorry that we can't have it in person. I know it's 730 on the dot and that folks will be jumping in as we continue moving forward, but wanted to get things moving so we can get to the wonderful presentations that we have today. And for those of you jumping on, again, Pediatric Rehabilitation Community Session, we're going to be talking about cerebral palsy challenges, dystonia, sexuality and intimacy, and mimickers. And with that, I would like to recognize our pediatric community leaders, I guess myself as also chair and session director, David Burbrare, who's joining us today. He's vice chair and co-session director. Mary Dubon, who's chair of education and one of our moderators, and Mike Green, who's chair of communication and moderator. And David and I will be stepping down, and there will be others who will be taking our place. Hannah Azizi will be jumping in as chair. Kim Hartman will be stepping up as vice chair. And Amy Teniglia, I'm sorry, Amy, I do that every time, she'll be coming in as our vice chair for the fellows. So really appreciate that. And with that being said, I would also like to bring about, for those of you who are on, please join in the other community sessions. If you've missed some, they're available on demand. The Central Nervous System Group had a lovely one on transition that is now available on demand. Our session is starting now. Tomorrow at 6 p.m. Central Time, the PEED Sports Medicine Group will be doing one on concussion management in children with and without disabilities. That'll be a great talk to attend. And then on Friday, I think finishing out all the community sessions will be one from the Cancer Rehab Group looking at pediatric cancer, building a program, and multidisciplinary case studies. So please join those either live, and if you can't, please look for them on demand to watch later. So without further ado, I'd like to get to our presentations. We have a wonderful lineup today. Our first speakers are going to be talking about severe dystonia in cerebral palsy. Is it a medication side effect or dystonia? That'll be presented by Dr. Larissa Pavone and Dr. Mary Keene from Mary and Joy Rehab Hospital and Dr. Stacey Stibb from Children's Hospital of Wisconsin. This will be followed by a video recording from Dr. Kim, who couldn't be with us today, unfortunately. But she'll be talking about sexuality and intimacy of people with cerebral palsy. And lastly, when it looks like CP but it's not, will be presented by Dr. Sally Evans from the Children's Hospital of Philadelphia and Dr. Brian Wishart from Spalding Rehab. And with all of that, I would love for you to put your questions in the Q&A box. I know we've all seen that. Please try to do that. I know sometimes we forget because we're in the chat, but it's easier to keep track of questions if they're actually put in the Q&A. Please feel free to use the chat. Please chat with your friends. I know we can't do this in person, so it's the closest thing we're going to have to that at this point in time until we can get back to those live meetings, hopefully next year in Baltimore. And Larissa, I would love to hand everything over to you. Great. So let me get our slides pulled up here. All right, so if all went well, you should see my first slide there. I just want to start by thanking you all for being here. I'm just so excited to present this topic and really honored to be amongst such great colleagues. So as was said before, it's going to be me starting things out, followed by Dr. Stibb talking to us a little bit, and Dr. Keene. So we're here to talk about severe dystonia and cerebral palsy. Is it a medication side effect or the dystonia? So the disclosure that I have is that we're going to be talking about off-label use of the medications. So the objectives of this talk is we wanted to start out by reviewing a couple of cases. We want to identify the medications that are commonly used in the treatment of dystonia and identify side effects of the medications. Also, what we really want to have is a discussion about these symptoms and side effects. And I really want to hear from our community the experience that other pediatric physiatrists have had. These are really challenging cases and would love to have a great discussion if we have time. If not, we could carry it after this talk. So our first case is a 17-year-old with quadriplegic dystonic cerebral palsy. He had a history of a Chiari decompression at 14 years of age and was admitted to acute rehab unit with status dystonicus. Prior to his presentation to us, he was hospitalized in an acute care setting with entero and rhinovirus. So there we have our trigger, most likely for this episode. I thought it was interesting to mention the Chiari decompression because when Matt presented at about 14 years, three years prior to this presentation, he had very similar findings with the increased dystonia. I was not treating him at that time, but I can't help to think if it was truly the Chiari at that time or maybe there was some exacerbation of his dystonia at that time. So I wanted to go through the medications that he was on while he was in acute rehabilitation. So when he came to us and was admitted, we did a lot of tweaking of his meds. So he came in on trihexyphenidyl, which was one milligram three times a day, and we increased it to two. We had started some gabapentin at night just to help with sleep. We were really aggressive with the clonidine, starting at 0.2 milligrams every four hours and eventually did need to titrate down on that as his body started to respond and he started to calm. We also increased his baclofen during that time. Just for completeness sake, I listed some of the other medications that he was on while he was with us. I put on dates here just to give you an idea of the timeline. So while he was inpatient in acute rehabilitation for almost 10 days, I followed up with him about four days after discharge from the hospital. At that time, he was down to clonidine 0.1 milligrams three times a day, trihexyphenidyl two milligrams three times a day, and the baclofen 20 milligrams three times a day. Because this was a challenging case and probably one of my first cases that I had like this, I had sent him to a movement disorder specialist just to make sure that we were covering all of our basis and there was no management change and they agreed with what we were doing. Interestingly enough, we did wean him off the trihexyphenidyl and he remained on the clonidine and he had a lot of anxiety and obsessive thoughts during that summertime in the summer of 2016. After the episode of his body calmed down, he was really having a lot of stress related to as well as his family and related to some of the mood symptoms that we were seeing. Mom and I talked about this and the only thing that was remaining was the clonidine and I had never really seen anything like this and her and I both thought like, oh, it's probably the clonidine, you know, because we got off of it and, you know, then those thoughts and the anxiety had stopped at that time. And you know, his body was also calmer at that time, that's why we could wean off the medications. We also had done Botox in the fall as well and all kind of resolved at that time. The reason I brought up this case, and we can discuss it further at the end, was, you know, his obsessive thoughts and anxiety at that time were attributed to the medications. I know that's not a common side effect, so, but as you all know, working in our field, we see things that are not common happen to our patients, so I'm really open minded to different things happening. You know, and right now he's really on, just on Baclofen and he's on amitriptyline for migraine headaches. And it's really interesting because the timing couldn't be better, but a week before this presentation I saw him last week and he had surgery on his feet in June and he didn't have any issues with severe dystonia, worsening dystonia after the surgery, but since surgery has had obsessive thoughts and anxiety. And also because it's been a couple years since that time, I have seen him have, you know, kind of cycle with these anxiety and obsessive thoughts when he's having more dystonia. So I thought the relationship was really interesting. The next case that I want to bring up is a nine-year-old with quadriplegic CP. Again, giving you some dates just so you have an idea of the timeline. In November, he had underwent multilevel orthopedic surgery. His postoperative course was significant for severely worsening dystonia. So I won't read you the exhaustive list of meds, but I kind of outlined there his preoperative medications and then his postoperative medications. And so as you can see, we really went up on the diazepam significantly, the baclofen was increased. You know, we increased his Sinemet, changed around his trahexyphenidyl, and then added clonidine, a good amount of clonidine for him, and benzotropine to really get his body to calm down. He had a complicated postoperative course. In the few weeks after being discharged, he was readmitted with pain. And then about a month later, he was readmitted with drainage from the wound, which he was treated for an infection. I don't believe they had to go back in for any hardware exchange or anything like that. And then because he had such a complicated course before, he was admitted to inpatient rehabilitation. And I had shown his meds before that we had him on while he was inpatient rehab. So a lot of inpatient rehab was spent positioning, comfort, and weaning down the medicines, because once his body started to calm, then he couldn't handle the load of medications that we had him on during that time period. And it was interesting because it was really the balance between his being awake and alert and his body just getting really tight and really dystonic. We did notice that when he had these episodes of dystonia, he really responded to deflection positioning and cuddling. So we used to joke that we would give cuddles PRN, because it actually did calm his body and we didn't have to use the PRN medications. If we just got him in a cuddling position, really flexed him up, he would respond nicely to that. But after his rehab course, he wasn't quite ready to go home and went to a home for medically complex children. And that's kind of a transition place, where we had weaned down on his diazepam and had placed him on a clonidine wean, had decreased the semen at that time as well. He remained to have complications, he was treated in pneumonia in the beginning of March, which resolved. But then mid-March, from this transitional care, he was sent to the ED because, you know, starting to have abnormal vital signs. In the ED, from the first hospital that he was sent to, the ED was unfamiliar with him. And he had gastric dilation, so couldn't take any of the oral medications, and it was probably about a 12-hour period of time before he could be transitioned to the hospital that was familiar with him. You know, in that hospital, you know, he was found to be hypoperfused and acute renal failure and rhabdo. He did not have an infection at that time. So I don't know if this was status system, because that was untreated, it's hard to say in hindsight, and I wasn't there in the ED. But one of the, I guess one of the things I always thought about is the clonidine wean that I put him on and not being able to follow him, and wondering if, like, at the other center, if they were recognizing if tone was increasing. You know, hindsight is everything, but I still think about if that could have contributed. And unfortunately, his child care was withdrawn four days after admission. So you know, a pretty complicated case requiring a lot of different medications. So with that, I am going to hand it over to Dr. Stibb to talk to us about the different medications we use to treat dystonia. So we just wanted to take some time to kind of go over the medications that we use in dystonia. There's lots of different medications I would say we try to use, and it seems like different combinations work one time, and then a couple months down the road or with growth, that same medication regimen does not work as well. So we're going to kind of go over the various medications that have been written in the literature that have been utilized, and then go over some of the side effects to discuss, you know, is it the medications that are maybe causing some of the side effects in dystonia worsening it, or are we actually helping the dystonia? Larissa, can you move forward for me, because you're in charge. So this is our big kind of algorithm of various dystonia treatments. So we'll just go briefly down each class. So under our dopaminergic agents, we have our tetrabenazine, our carbidopa, levodopa, heloperidols on there, and pimazide. So those are more used when we're really in a status dystonicus situation and really need something to break that dystonia. On the same, on the flip side, withdrawal of some of these medications can lead to worsening dystonia as well. So we always have to keep that in mind. Under our gabinergic agents, we have our benzos. Everybody probably has their favorite benzo. We have our diazepam, lorazepam, planazepam, all acting the same way, but different length of action. We have our baclofen as well and chlorohydrate. In the literature, this is used more to sedate and let the patient be able to sleep to kind of decrease some of that dystonia and hopefully stop some of that rhabdo that could be occurring. We also have our anticholinergic agents, so your trihexafenonil and your benzotropine. We have our calcium channel blockers with gabapentin, alpha-agnes as well with clonidine. I didn't list on here, but with one of my patients, I actually used lupranolol, so beta blockers can be utilized as well. And then looking more at some of the other options, we have our injectables, of course, with our botulinum toxin and alcohols, and then various surgical procedures with your baclofen pumps, deep brain stimulators, and anterior cervical rhizotomy. And so we're going to look at some of these medications. So all of these side effects were pulled from Lexicon, and actually these first few slides, these side effects that are listed are the most prominent side effects that are reported. So in our first case, we talked about our patient having anxiety, so is it the medications or is it hormones or is it what he's going through? But when we're looking at a lot of these medications, tetrabenazine, what's our biggest side effects that are listed? Drowsiness, sedation, depression, extrapyramidal reactions, anxiety, carbidopa, the same thing. We can have orthostatic hypotension, constipation. We know our kids, if they get constipated, if they have urinary retention, anything that's causing discomfort is worsening the dystonia. So we're giving this medication to help with dystonia, but on the flip side, is it causing some side effects that is then in turn worsening the dystonia? Heloperidol, you have your extrapyramidal reactions as well, hemazide, sedation, drowsiness, behavioral changes, dry mouth and constipation, again, all things that can irritate a child and worsen their dystonia. Next. Looking at the benzos, as you guys can imagine, you can get confusion, sedation, ataxia, so causing other movements besides the dystonia that can worsen our patient's clinical picture, dizziness, hallucinations, and anxiety. A lot of the kids that we deal with that we're giving these medications for for dystonia, a lot of them aren't able to communicate. So not all of them are able to tell you if they're feeling anxious or if they're seeing anything, but their body could still be reacting to things that are happening to them from their medications. Baclofen, we know, can cause constipation. We know withdrawal of baclofen can be something that can worsen spasticity, dystonia. Gabapentin can cause ataxia, dizziness as well. And quinidine, you can have pain, dry mouth, dizziness, drowsiness, and headache as well. Next slide. And then these medications on Lexicomp, they did not have kind of the top percentage of side effects, so these were just ones that I pulled out that seemed more relevant to our patient population and things that could annoy them. So chlorohydrate, increased middle ear pressure in infants and child that could cause pain and lead to dystonia, airway obstruction, laryngeal edema, somnolence, trihexaphenidyl, again you have agitation, confusion, dizziness, all these things that we're trying to avoid in our patients, we are giving them medications that essentially could cause it. And then finally, benzotropine, again, confusion, depression, disorientation, some numbness, constipation. So all these medications, again, that we're trying to use to help, are they helping or are we having issues with the meds and they're actually worsening? And we're going to look at a little bit of how some of these medications actually can interact with each other as well. So we've got lots of medications and potential for lots of interactions. The particular combinations can counteract one another and other combinations can actually exacerbate symptoms. Haloperidol and pimbazide can cause Q2 prolongation, pimbazide and alprazolam have an enzyme interaction in the liver. Carbidopin and haloperidol can work against each other and pimbazide and carbidopa can work against each other. Our baclofen, benzodiazepines, gabapentin are all sedative agents, as we've mentioned, and many of the pimbazide, triaxofenadil, cause anticholinergic side effects. Clonidine and propranolol can be synergistic and cause bradycardia and can be a limiting side effect. So many interactions, many complicated potential scenarios. It has occurred to me, as I've cared for these patients over the last 10 or 15 years, there are a lot of similarities between status dystonicus and sympathetic storm, and I've actually had some disagreements with other care providers. What are we actually dealing with? I think they may be part of the same spectrum. They have very similar manifestations and they have overlapping medication treatment strategies. The other thing I wanted to point out is, as we've talked about the side effects of anxiety and depression as another manifestation of a brain disorder, what is the mechanism for all of these things, and are there overlapping mechanisms? I was not able to find any literature that talks about OCD or anxiety and depression having too much synchrony, but I bet you there will be if I looked harder. This slide demonstrates two examples of pathophysiology in which there is diminished synchrony compared to normal. On the left side of the slide, there's a normal young person's brain working on memory all the way to the left, someone with dementia in the middle, and then someone on the right is getting electrical stimulation to synchronize brain circuits and you can see memory is improved. If we go all the way to the right, there are cortical circuits for schizophrenia versus the normal brain. Gamma activity is more synchronous in the typical brain and it's asynchronous with schizophrenia. What might be the mechanisms for causing dystonia or status dystonicus? Well, Hebb's Law, 1949, neurons that fire together wire together. When a brain practices seizures, the seizures get worse. If a brain practices dystonia, the dystonia gets worse. There's temporal spatial integration of neural networks that results from new synaptic connections and neurofiring. When you fire a nerve, it turns on the genetic machinery to cause the brain to change the internal connections, to cause new synapses to form. We really have a mechanism built in. The more dystonia there is, the more neurofiring, the more they turn on the genetic machinery, the more synchrony and more harmony, more resonance of these brain cell circuits. We have some complicated situations here. We've got multiple medications that can have side effects. Accommodation probably occurs with some of them. We want to get them off medicines before we start more. Side effects are plentiful and overlapping, and sometimes medications actually counteract each other. Medications may be causing side effects that are related, and it may be that the status dystonicus is related to anxiety or depression with synchronous circuits. Some questions. We are interested in hearing from the community about what your experiences are. One of the things that we were hoping to do with our community presentation was just talk to our community about this and see if anyone had any experiences that they wanted to share, different medications or side effects that they've seen, unusual circumstances, maybe some unusual triggers. Also one of the things that came up for conversation was if there was a standard workup that anyone did for that. I don't know if there's anything in the chat, any questions there, or if anyone wants to speak up at all. Thank you guys so much for a wonderful presentation and some challenging cases that I think resonate with a lot of us. There is a question in the chat just about the first patient case that Dr. Pavone had presented. Have the first patient ever received mental health screening as the causes of their anxiety or obsessive thoughts noted during rehab? Just a commentary that there are a lot of missed mental health diagnoses in this population, and Dr. Elizabeth Martin said she's currently working on quality measures that include mental health and pain screenings in this population. That's such a wonderful point to make when we're talking about that. I have, because this, well, I guess he's a teenager, a young man now. He is now 20, I think, and in college, very bright. He's a GMFCS level five, four to five, and I did send him to neuropsychology because I thought he can't control his body, but he can control his mind, and so he did do some work with a neuropsychologist on just some strategies to help manage anxiety, and I actually just had a conversation that the young man that I'm talking about, his dad is a family practice doctor, so his dad and I have had a lot of conversations, and we're talking about different medications, and I told dad we were going to have this group today, so I said, I'll see if anyone has any good ideas, but we did talk about sending him to psychiatry because one of the experiences that I've had with, and I'm sure some of you have had with children or adolescents with cerebral palsy is when they're depressed, if you choose, if you do or someone else puts them on an SSRI, I've seen a lot of worsening tone with that, so that always hasn't been the best option for that, and I haven't done the SNRIs, kind of assuming that I would have the same outcome with that as well, but yeah, we're going to send him to psychiatry, because now it's, you know, it's been a constant thing, like before it would come in cycles and waves, but now it's been pretty consistent since his surgery with pretty significant personality change, and I also noted, you know, weight loss that's associated with it now, so he really needs some help, but thanks, that's an excellent point and a great conversation we need to continue to have. Awesome, and it looks like there's some chatter about different medications, which I know was some of the questions that you guys were trying to spark here, so Dr. Josh Bova mentioned that tantraline is sometimes underutilized, especially in the case that you mentioned, Dr. Bravon, where the patient had a high CPK. Yeah, that's an excellent point, and I think I don't use it enough, admittedly so, especially in the older population. Sometimes I've been hesitant to use it, obviously, because the liver, you know, when we're monitoring the liver function, I don't know why I didn't use it in this case, but I think that's a really excellent point and something that I should utilize more, for sure. And then Dr. Martin had mentioned, Elizabeth Martin had mentioned in the Q&A, too, so we trained in the same place at Seattle Children's and Severe Estheticist, and I guess we did wind up using Benzodreps in the PICU, too, so that's just another option, and some pediatric neurologists tend to avoid Artane, she mentioned, because of the cognitive side effects as well. Yeah, we definitely, I think we've all seen those cognitive side effects from Artane. I've had, I don't know if anyone has had, for me, I feel like, and I think I learned this from working with Dr. Keene, Clonidine's been, like, usually is my, like, fix-it med for some of these real severe cases of dystonia. I don't know if anyone else has had a similar experience or has a different, obviously, Benzos are great, too, but if there's a go-to med when they're at home that you like to utilize. I think to stay on that part. While we're waiting to see if anyone has comments on that, there are some other comments also, I think, agreeing with Andrea as well, and then some gratitude for a great review of the drugs and the side effects, and this might be good for Dr. Stibb, like, any sense of the frequency of some of the side effects from those medications? Yeah, and kind of on my review, unfortunately, there was just kind of general side effects. All those ones I listed in the first couple slides were listed as the more frequent side effects, but how often those happen in our patient population, I don't have that information. From my personal experience, I say that's hard to tell, too, because like we said, all these kids are on multiple different medications. You try to stagger it, but if you're in a spot, you also have to throw everything at them to kind of break it, right? So, what could be causing the anxiety? I had another patient just like Dr. Pavone with kind of during adolescence and change from high school to graduating high school and probably hormones and things where the dystonia was very difficult to control, and then after his life outside of medical stuff settled down, his tone also settled down. But I don't know how many of our kids can actually tell us what they're feeling, too. So, a lot of it, I feel like, is a little bit of guesswork in our field, unfortunately. And sorry to put Dantrolene on there. That's my bad, but I agree. And I don't use it that often either because I'm probably too lazy to check labs, but I should. You know, on the list, obviously, and I don't know, you know, they listed Pimazide, but I've never used Pimazide, the side effect profile, or Haloperidol. I mean, we did that for a complete mistake, but I don't think that's something that we commonly use. But I would say, experience-wise, and I think, Dr. Keene, I don't know if you have anything to add to that, anticholinergic side effects, the retention, especially when you have on some, a couple of meds plus benzos, urinary retention, constipation, those are some of the major ones that I tend to see. Yeah, I think that was an awesome review and obviously a lot of conversation points here because certainly there's no one right treatment answer. So this was really excellent. I think time-wise, we are probably a good time to transition over to our next talk, but thank you guys so much. And I will pass it along to Jolene to help us out for the next one. Thanks for having us. Thank you, Larissa, Mary, and Stacy. And Larissa, can you unshare your screen for us, please? I'm working on it. Here we go. That's okay. That's usually the thing I forget to do. So with that, and thank you all for the questions in the chat and in the Q&A and the discussion. I know it's hard to do this when we can't all talk and discuss in person. So really appreciate you all being so engaged. Our next talk is going to be by Dr. Kim. It's going to be a video recording because she couldn't be with us today. Hello, my name is Hye-Kyung Kim. I'm a pediatric physician at Columbia University Medical Center. I know most of you guys are here today, but unfortunately, I'm not able to join you guys. So today's my topic is sexuality and cerebral palsy. I like to share my disclosure. This is my disclosure. And these are my learning objectives. We should be able to understand the importance of including sex and sexuality in assessments, and learn how to initiate meaningful conversation relating sex and sexuality, and be able to understand physical challenges and limitations that people with cerebral palsy experience related to sexual activity. And last one is be educated on available treatment options for management of medical conditions that people with cerebral palsy experience related to sexual activity. Cerebral palsy is the most common or most frequent childhood onset physical disability. And cerebral palsy is still seen as a primary pediatric disease. However, there is a significant increment in their life expectancy. So life span care is necessary at this time. When they were young, we were focusing on functional improvement, medical management. Sometimes they come with significant gastroesophageal reflux, seizure disorders, or their parents asking us to develop their motor skill or functional improvement. And we have to address the bracing, physical therapy, occupational therapy, or spasticity management. As they get older, their main problem is pain and discomfort, then managing spasticity. And they also complain about a lot of balance issues, losing their function. And mental health has also become significant issues. We did a retrospective study in our hospital, which showed that more than 50% adults with cerebral palsy were taking psychotropic medications for their anxiety disorder and significant depression. And they also want to discuss about their independency. And however, we are not really addressing their sexual activities or sexuality. So now we know that they live longer, we have to focus on their quality of life. So there should be a paradigm shift on cerebral palsy care, pediatric-focused care, to lifespan care. So I'd like to address a little more about sexuality in people with cerebral palsy. Recently, I was able to find out this article on adults with SCP, which is a review article. There's twice as high risk to develop stroke in adults with cerebral palsy, and eight times as high risk for them to develop cervical myelopathy, especially for people with dystonic cerebral palsy. And then more than one third of adults with cerebral palsy, they already lost or losing their ambulatory function by middle 30s, like about 35 years old. And then they feel chronic fatigue and they have significant pain. These older things should be addressed when they come to our clinic. And then this is another interesting and important article, which is showing the healthcare use in individuals with cerebral palsy. The left side graph is for the ambulatory participants. The right side graph is the non-ambulatory participants. Interesting enough, when you take a look at this graph, the green color graph is going up with the aging. And then the green color, except the green color, the brown, blue, and red color graph is going down. So the green is use of the medication, especially psychotropic medication and analgesic drugs. The use increases. However, visiting the rehabilitation services, using the orthosis, or using therapy has been going down as they get older. So there was some transition from childhood to adulthood involves significant changes in healthcare use. Interesting enough, using the botulinum toxin did not decrease with age. So I reviewed my own rehabilitation clinic. There were 86 participants in this retrospective study. The GMC was evenly distributed and the average age was 30 years old. And most common cause or reason for chemoneuralysis was pain control and gait-related problem and spasticity management. But fourth reason for chemoneuralysis was sitting position or sitting posture, which is related to proper position for sex. So let's talk about sex. There are very few study has been done for sexuality or sexual activity in adults with cerebral palsy. So this is launched in a study over four years with 103 adults with cerebral palsy. This study was done in the Netherlands. And then they have normal intelligence. GMC was between 1 to 3 and their age was 16 to 20. As time goes, they were able to see a significant increase in dating and sexual experience in these young adults with cerebral palsy. However, there was no increase in romantic relationship or sexual activities. But their sexual interest was equal to normal children. And they did another publication and they reviewed 74 adults with cerebral palsy aged between 20 to 24 years. And they reported that they had a high rate of orgasmia and physical problem with the sexual activity due to cerebral palsy and emotional inhibition to initiate sexual conduct. They required more information related to sexual activity or reproduction. Interesting enough, 90% of these participants never had the sexuality discussed in rehabilitation setting. Can you imagine? We only talk about spasticity, talk about walking, talk about pain, but we never addressed sexuality in people with cerebral palsy. So, there was one study addressing the quality of life with 75 adults with cerebral palsy. It was published in 2018. And then their quality of life was a 56th percentile. The lowest mean score was sexual activity. So, the question was, has a satisfactory sexual life? It was very low, which is also connected with their depression. So, we decided to conduct a sexuality survey study at our institution. Our motivation was there are very few, very little information on sexuality in cerebral palsy. And prior research has neglected the quality of life concerns. Therefore, this survey aims to bridge some of the gaps by investigating how people with cerebral palsy feel about their sexuality. The study design was a descriptive, cross-sectional, and non-interventional survey. And the age was between 18 to 65 years old. The diagnosis was cerebral palsy. Who should be able to complete the survey without having any communication through their caretaker. We collected data including their gender, level of education, type of cerebral palsy, and type of movement disorder, and mobility, transverse hand function. And we also brought the questions related to sexuality and intimacy. And we created and consented via phone and administered online through the Red Cap. So the results showed that type of movement, of course, most common movement problem was spasticity, 57.5%, restopedema, mixed tone, dystonia, acetoid, and topographical distribution, quadriplasia was the most common, 19, diplasia 11, hemiplegic 9, and others 1. I didn't mention, but 40 patients responded out of about 200 survey sent because the inclusion criteria, uh, they should be able to complete the survey. Therefore, we had 40% responded. So GEMSS was, uh, three was most common, but there was almost evenly distributed. And then sexual orientation, heterosex was 32, homosexual 1, bisexual 4, asexual 1. So our question was, where did you receive a sex education? That was number one. And mostly 29 responded at school and internet. Friends, healthcare provider, we educate, three people only had education by a healthcare professional. It's very shame. And whom have you been able to talk about sex and sexuality? Of course, it's friends. Thank God, healthcare providers, they were able to discuss with them and their family members. How have your sexual experience impacted your self-esteem? So if someone who had a history of a past sexual experience, they are more positive, or they stayed the same. But if they did not have sex in the past, they are more like negative or they didn't stay the same in their self-esteem. So they could be low. It could be high. Next question is, are you sexually active? That was our questions, but we're curious if they are sexually active, is this related to, is there any relation on their GEMSS or topographical classification? So when we take a look, GEMSS one and two on the left side of the screen, 75% was sexually active. GEMSS three was 50% that was sexually active. GEMSS four was sexually active in 10%. When we take a look at the topographical classification, diplegia 55%, hemiplegia 60%, quadriplegia 32%. The 7% among these participants, three reports that they needed assistance with the initiating positioning, and then one reports assistance with the transporting, undressing, and positioning. So any relationship between topographical versus functional versus education classification and the sexual experience. So when you take a look, the left top has the sexual experience education level. If they graduated graduate school and bachelor, they had a more sexual experience. If they are diplegia, hemiplegia, they had more sex than no sexual experience, but quadriplegia was they had 42% that had sexual experience. So topographical classification was less impacted on their sexual experience than educational level. And then when you take a look at the GEMSS, if they were GEMSS one to three, 85% had a sexual experience. If they were GEMSS three, 69% had a sexual experience, and then GEMSS four, 31%. So GEMSS also matters on sexual experience. So I already addressed this one, and then let's go current relationship status with the education level. So if they were more educated, they have more significant others, and they were married. As you see on the left side, and GEMSS, if their GEMSS level are lower, which means more functional, they were married or they had significant others than someone who had low function. And then topographical classification showed quadriplegia had stayed as a single more than diplegia and hemiplegia. Here, you can take a look. And then we were asking which physical challenges do you experience during intimacy activity? As you can see, the positioning difficulties was most high frequency we can see it. However, here you have a pain and discomfort. If you put together with the pain and muscle spasm, vagus anemus, which is more pain and discomfort. These things are actually higher than positioning difficulties. If you sum 15 plus 14 plus nine, which is 1938, right? 19 plus 9, 28, I'm sorry, 28. The 28 versus to 26. So pain was more problem for their intimate activities, pretty close with the positioning difficulties. Rest of them are an orgasmia, they don't have a sensation, and the ejaculate dysfunction. And the other question was a physical challenges during intimacy activity based on GNSS versus topographical distribution. If you look at it, a positioning difficulties in all GNSS level and positioning difficulties is more in the quadriplegia, but all of them actually having problems with positioning and pain and positioning and pain. So you really have to pay attention to their pain, muscle spasm, or pain during intercourse, as well as a positioning for their sex when you take your patient with it, adult with cerebral palsy. Here, and you can see here. So we actually asked them to write their suggestion for healthcare providers. So they were asking, please ask questions about what is successful or problematic related to sexual experience. Be more body and sex positive. And being overly focused on problems negatively impacts self-esteem. And then they want us to conduct research on aging with cerebral palsy, a quality of life, and slow the decline process. And discuss the technique or position to decrease pain and discomfort during sexual experience. Educate patients on how CP can impact their sex life, pain management for overall pain, pelvic floor physical therapy, and provide comprehensive care and guidance for child planning or parenting. And provide the parents with resources related to sex and sexuality, and provide proactive care related to birth control and STD. And then we also asked them what kind of treatment or technique reported by patients to cope with the physical challenges during sexual experience. They told us that they are using the desensitizing gel, or discuss challenges with doctors or psychologists. Sometimes they use a glass of wine. They talk with the gynecologist to talk about the complex pelvic pain, or using the lubricant or masturbation to activate the climax, or they are using medication such as gabapentin for vulvodynia, or muscle relaxant to coincide with the sexual activity, or nerve blood injection around the clitoris, or botulinum toxin injection to generate spasticity, or diazepam, vaginal suppository, or they do oral sex, or pelvic floor physical therapy. They're also trying to do good positioning with the wedge pillow, have sex in chair, or leaning against the surface, or time sexual activity to certain times of bad day based on fatigue or activity levels. And they also talk about vaginal dilator, or vagissimus. So actually patients are teaching us, then we are teaching patients. I think we have to really think about how we're going to educate ourselves before we educate our patients on sexual activities. So our survey study on sexuality in people with cerebral palsy was a test training, and we concluded as follows. Any relationship between topographical classification and sexual experience, yes there is negative correlation between extent of body affected by CP and sexual experience, and any relationship between GMF-CS and sexual relationship, there was not much association between dating, overall sexual activities, and GMF-CS level. Most common physical challenges during sexual activities were muscle spasm, positioning difficulties, and pain. In educational level and marriage, higher level of education is more related to higher marriage rather than higher level of function. Summary of outcomes, there is no correlation between GMF-CS level and likelihood being sexually active. GMF-CS level is not an adequate predictor for physical challenges experienced during intimacy activity. Muscle spasm, positioning difficulty, and pain discomfort are the most common physical challenges experienced by people with cerebral palsy during intimacy activity. So I'm going to discuss briefly about my case, two cases. One case is 27-year-old school graduate, and he lives with his parents. He tried to get out of his family and tried to be independent, and he does have sex with a surrogate partner, who was provided by his psychiatrist, and his chief complaint for initial visit was he doesn't want to have a jumpy body during sex. So after I did the examination, I recommended botulinum toxin injection to his quite spastic both legs. So my intervention was chemoneuralysis to his both legs, including hamstring, tensile-facial adductors, glastylis, iliopsoas adductors, and rectus femoris. And the goal was improving jumpy legs and relaxing stiffness in his legs. So actually, the goal was achieved. He was able to have sex without jumpy legs. And after then, we supposed to have a follow-up. I was getting email from him, and he was asking me about the positioning. He said one position would be lying down spine, her own top facing me or facing away. How can I sustain any elevation of my head to see my partner instead of looking at the ceiling? He was asking me. He wants to look at his partner. How can I prop myself up in bed so that my trunk won't slip down into a supine position? Should I use chest to stretch? When I am able to visualize her in position, I tend to ejaculate quickly. Can we try increasing my baclofen dose as needed? Unfortunately, I couldn't have any discussion with him during clinic visit because his parents wouldn't leave the room. So I did some literature. I found that antispastic drug does effect on sexual function. So diazepam, baclofen, even intrathecal baclofen pump does cause sexual dysfunction, erectile dysfunction, ejaculation problem, and ribosomia. And then these all the antidepressants, including SSRI, antipsychotic drugs, is a quite impact on sexual activities and libido. And as we all know, cerebral palsy has high blood pressure, 10-10 high blood pressure, and all, most of antihypertensive medication does cause erectile dysfunction. So case number two, she is 28-year-old, very intelligent lady who used to be GMSS 1 and 2, become 3 after the osteotomy. And her chief complaint was, I love to have sex, but too much pain during intercourse, so I cannot have sex. So she was using supposedly diazepam, which was provided by her GP, but she cannot still have sex because she's having too much pain. So I did the literature, but I found that for the normal people who had the vegecinimus, were getting the botulinum toxin injection to their vagina, there was one or two case reports out there. So I recommended, how about we do botulinum toxin injection to your vagina? And she got scared. So I recommended that botulinum toxin diffuses, so why don't we do injection to perineal muscles? So she agreed. So we did the injection to medial hamstrings, hip adductors, gracilis, gastrocnemius. And she also complained of back pain, so I did the injection to quadriceps lumbar. So this, along with this, she's still using the supposedly diazepam suppository to her vagina, and that improved her vegecinimus and hip abduction, decreased her back pain, and she was able to remove her long leg brace. It was successful, so I did not need to do injection to her vagina. And then I started the Google search, and there was a handful of women was complaining about physicians. They had a cerebral palsy, they have a cerebral palsy, but they have a quite significant vegecinimus intercourse. So one patient is complaining that when she reported to her physicians about her problems, initially they recommended lubricant, which didn't work. They recommended a dilator for vagina. Also, they recommended psychotherapy and pap smear to find out any source for the pain, or surgery to dilate the vagina, and keep on trying this, all the stuff, or they say keep on trying to have sex, but they weren't able to, she wasn't able to have sex. So she was in big trouble at that time. So our conclusion is, please address sexuality is essential for adult care. I like to insist that sexuality should be included in the reviewable system for people with a cerebral palsy, and we should offer specialist management for proper positioning, safe sex, and other problems such as a vegecinimus, and then we should have a different concept of adaptive equipment for adults with a cerebral palsy to improve their sexual activity, and we should be mindful with prescribing medications for people with a cerebral palsy, such as antidepressant, antipsychotic medications, antihypertensive medication, and antispastic drug too. These old medications cause all sexual activity or sexuality problems, and then we need to provide better access to inform on sex for people with a cerebral palsy, sex education for people with a cerebral palsy at clinic and school is extremely important, not only through media. This is my last slide. I hope that you guys can learn a little about sexuality in people with a cerebral palsy. I'd like to encourage everybody to ask a question on sexuality to people with a cerebral palsy when you see them in the clinic, and please enjoy your rest of the days and enjoy your pediatric rehabilitation community day. I hope to see you guys in next year meeting. Thank you so much. Bye-bye. Thanks a lot. That's a wonderful talk from Dr. Kim, and it's hard not to smile when you see her talk and hear her talk. She's amazing. We are going to put Dr. Kim's email address. We have her permission to do this, but her email address is in the chat. If you have further questions, please reach out to Dr. Kim. I know I was on a discussion group with also Dr. Jill Gettings. I don't know if she's on tonight. She's at Gillette. She does quite a bit also with adults and with sexuality too. It sounds like I have a lot of homework that I need to do in my own clinic and preparing the teens that I see for this discussion with regards to sexuality and I guess as a mom of a teen with cerebral palsy it sounds like a discussion I need to start thinking about having rather than avoiding and move on from just talking about puberty. So thank you Dr. Kim for all of that. With that we would like to bring on Brian and Sally to finish up our discussion tonight talking about things that may mimic cerebral palsy. So thank you. All right thank you Dr. Brandenburg. So my name is Brian Wishart. I am a pediatric physiatrist up at Spaulding Rehab in Boston and also at Mass General for Children. I'm doing this talk with Sally Evans who's the chair down at CHOP. We're both involved in the patient communities and some of the academic aspects of leukodystrophies and I'm going to talk today a little bit about some of the different diseases and approaches to treatment for things that are like CP but maybe have a little bit of a different underlying aspect and a different progression. There we go. So these are our key objectives. I'd like to kind of talk a little bit about a few of the more common common leukodystrophies. It's sort of a oxymoron but we'll talk about some of the ones that we do see and how they present in terms of different degeneration aspects compared to our static insults and diseases. And then we'd like to talk a little bit about how approaches may differ when we're looking at our spasticity and hypertonia in these patients. Both myself and Dr. Evans do have some financial support from Leukodystrophy Care Network and we will not be discussing any medications. So what are leukodystrophies? These are a group of inherited white matter diseases that affect our myelination and really affect that white matter within the central nervous system. So affecting particularly the brain as well as there are certain diseases that do affect the spinal cord and give us that central issue. Incidence overall when you combine all the diseases is actually relatively common. We will see these. You do see these come into clinics. So 1 in 7,600 live births worldwide. As you look at more individual diseases, they do get significantly more rare. And so that, you know, does affect when people are looking for community and other patients that they've seen and as well as providers having experience with individual diseases. I think it's challenging at times. Currently there's about 50 identified genetic causes for leukodystrophy, but it's been growing dramatically over the last couple of years, particularly as genetic testing is becoming more common and we're seeing different genes identified for each individual leukodystrophy as well as naming new leukodystrophies, which we've seen up here. And you have these, you know, new leukodystrophies that are 12 patients worldwide and that sort, but with the internet and with how the testing is done, we're able to actually connect the patients and see these patterns and actually, you know, identify these well. Most of them are progressive, but they do have different rates of progression. And so you may see a very slow progression at times, or there's certain diseases, one of which we'll talk about, which may have a rapid progression early on and then actually have a relatively stable presentation or static presentation moving forward. And there can be different types within one leukodystrophy and different presentations. And I think that's a really important aspect. We've seen this in multiple diseases where you have patients within the same family, so they have the same genetic disease, but their phenotype is very different than what their genotype is coming out. And so it's important to know kind of the spectrum of disease as you're going through these patients, because it may be very different from patient to patient. So we'll talk about a couple that are on the more common side. The first one I'd like to go over is called Aicardi-Gutierrez syndrome. This is a relatively rare disease. It is something that is due to a number of different gene defects. I think there's seven different genes that can cause this, and it is a interferonopathy is what they call it. So it's something that affects kind of viral signaling, but it does have these white matter changes. Typically you see this acute or subacute encephalopathy that comes on before one year of age, so typically in the six to 12-month range. There are a range of phenotypic and clinical presentations. So, you know, you can have a very severe disease, and it's probably the more common aspect where there's been some studies looking at what type of milestones these children meet, and the most common is smiling for all the patients to meet, and then it kind of goes down from there. So it's a very severe disease at times, but you certainly have a range, and I have a number of patients, a few that are in power wheelchairs and not very interactive and dependent for all needs versus other children that, you know, communicate and do well. And I have some patients that are on the far end of the spectrum and working to become a rabbi is what she's doing right now. So it's a systemic disease, and it does affect the brain, and you get mild degeneration. So you see spasticity, dystonia, axial hypotonia at times, and regression often in that kind of encephalopathic stage, but you also have other effects. So you can see hepatospegaly, you can see issues with the with the skin, and you get these chill blades, which is a fairly debilitating aspect of this disease. Most children present in that way where it's after about 6 to 12 months, but there is a small percentage, about 20%, that will present at birth, and often they'll have more of that systemic presentation. So they get elevations in their liver enzymes, you see thrombocytopenia, and a lot of this stuff can present similar to a congenital infection. And so this has been known as something that mimics kind of viral infection, congenital viral infection, but no infection is found. So yeah, so these guys are important to know and important to see because it is something that you can see a very kind of wide range, you can have children that are on a very severe end, but also kids that are much more mild in terms of their presentation. Another one is Pallesius Merzbacher. And so this is a disease that's a little bit more common than than our Chiardic Gutierrez. So our Chiardic Gutierrez, recent studies have shown that it's probably much more common than we're seeing secondary to that that more mild presentation. And as they're doing more whole genome sequencing, we're seeing this this come up more frequently. Pallesius Merzbacher does come up in about 1 in 200 to 500,000 males. It is X length and secondary to this PLP gene, which is related to our myelination, and it is affect both our central and peripheral nerves. And so you see the PLP protein more centrally, and then there's one called DM20 that's in the peripheral and it has to do with binding that that myelin to the nerve. So you get symptoms on both sides. Obviously, it's predominantly male, but you can see symptoms in females rarely. And majority of people have the same genetic defect in 80 to 95% of patients. There are two different cause types of this. So there's the classic form, which typically you see in the first year of life presents initially with hypotonia. And then as they go through, you often will see some delay, but there they do continue to develop through adolescence. And that's, I think, one of the challenging parts for these these patients, where they're continuing to make gains actually early on both cognitively as well as in their motor aspects. And that classic form, often these kids will be able to walk with some sort of assistive device. The other type is our conatal type, and that's a much more severe type. And often these patients aren't able to walk at any point. Just to look a little bit at the imaging findings. So when we look at these findings here, the top one is our T1, and it's a very prototypic imaging finding of our hypomyelinating disorders. So you lose that that clear delineation between the white and the gray matter, which you see in this bottom left one, where you kind of come through from the periphery. And it all sort of blends together. And this is a fairly classic finding when you think about our hypomyelinating versus our demyelinating images. So when we think about our presentation for these kids, you get both brain and spine involvement. You also can get some peripheral involvement as well as we were talking. And as we said, so you get that early hypotonia. Often early on, there's this nice stagness and weakness. They will often get spasticity and ataxia. But the challenging part is that they do develop as they go through early childhood and into adolescence. And then after that point is when you start to see this regression. And so that can be a little bit challenging to identify as different in that we're not seeing that classic regression early on. A third one here would be Alexander disease. This is significantly more rare, I would say. So 500 cases have been described in the last 60 years or so. I've seen it reported as being one in a million or so at that point, there's a couple different types of it. Genetically, it's caused by a GFAP gene, which has to do with the astroglia. And so you see these Rosenthal bodies that are that are being formed and causing this accumulation and abnormal function of these astroglia within the white matter. And so you get effects from that. There's been a couple different ways of describing it. So infantile versus juvenile, and then there are some late onset forms. But there's another way of describing it, which is type one and type two, and they kind of split that at age four. The infantile and type one is probably the more common that we will see. And with these, you can see failure to thrive is a very classic thing for these patients. You do see some macrocephaly moving through and often you get this kind of classic steady regression as they're going through. Seizures can be a big form of these patients as they're as they're starting to become more severe. But the reality is, is it's a bit of a continuum as you go through our later onset. Often they'll they do describe lack of pure regression in these patients, but you also can see kind of a mix of both both presentations as you're going through them. Often you'll see pseudobulbar issues and ataxia. You can also see some spasticity in our type two patients and our older ones. It's about a third of those patients. And then you'll see a little bit of spasticity. On MRI, you see the symmetric brain lesions, brainstem lesions. I'm sorry, that's very clear. I think in kind of the this one all the way on the left and over on the right. And it can be a fairly debilitating disease. We'll talk a little bit about treatment after this. So CRAB-A disease is a is the last one I'm going to kind of present briefly here. It is about one in 100,000. It's also known as globoid cell leukodystrophy. It's secondary to a gene defect in the GALC gene, which is something that caught that codes for the galactocerebrosidase. With this, you get accumulation of these sphingolipids, this galactosaramide within the lysosomes. And then these globoid cells is that doesn't get broken down. It can come on very early in life and often does come on within infancy. Most kids will have it come on under a year of life and it can be really devastating early on. So this is this picture on the right here is Jim Kelly. He was a Hall of Fame football player for the Broncos or no, sorry, it wasn't Bill. I'm forgetting exactly who he played with. And I can't see that picture well. But he started Hunter's Hope for his young son is one son that was diagnosed with CRAB-A and I believe 1997 actually did survive for a number of years until he was about eight, I believe. But typically we see these patients being diagnosed at about a year. And I believe our one year, two year and three year survival rates are about 60, 26 and 14%. So very devastating disease. You can see quick developmental delay and regression early on with these patients. Often you see significant spasticity and dystonia. They can have seizures. There are some late onset forms of this that can come on much slower, but a challenging and difficult disease as we go through. One of the things that's kind of specific for these, and I would say a lot of our leukodystrophies have very common symptoms. And then there's also some more specific ones for each disease, but GI issues are something that we often see. And often these kids present with irritability that's put up to the GI issues. Yes, the Buffalo Bill is like. So how do we care for these patients? I think, you know, it's often a challenging diagnosis from the beginning. It's something obviously that patients aren't looking to see, and it's something that we really need to make sure that we're addressing in a very interdisciplinary approach. And I really like this figure as we go through, because I think the key here is that it starts with the patient and the family. And I think early on when we're having these restarting care and initiating care with these patients, especially from the rehab side, discussing your goals and discussing what their expectations and what they want for these patients is really important. Often you get this regression, and as you're going through, you want to make sure that you're staying in line with what the family's wanted early on, and not just chasing down symptoms or chasing down different goals that may not be realistic at that time, even though you may have had that discussion early on. A lot of these other providers often come in depending on the type of leukodystrophy. So, you know, endocrinology is a great example. We see that in adrenal leukodystrophy. They have adrenal insufficiency and present with Addison's often. You know, urology is a classic one that we often need, and whether or not these patients need some sort of catheterization program or if we move on to any surgical things is important. You know, our pulmonary colleagues are really important in a lot of these diseases as they move through, and they have issues with secretions and pulmonary management and that sort of thing. So it's important to kind of go through, and then obviously our therapies and our equipment providers and everything. So as I was saying, there's often a common set of symptoms that we see, and spasticity is very common. We often see issues with impaired ADLs and self-care and mobility. Our more active kids and our kids that are up, scoliosis is something that comes out pretty frequently and is always a challenge. Our neuromuscular scoliosis patients are always a challenge to sort of figure out exactly where racing fits in and what else we can do for them. So in terms of diagnosis, you know, there's a number of ways of going through. In the past, it was often on clinical presentation, and then there's these very pathognomonic MRI lesion patterns that can come up. So there's certain ones that you see that are really diagnostic for certain diseases. XALD with the contrast enhancement and that posterior aspect is very classic. Metachromatic leukodystrophy, you see this, the sparing of the U fibers and this kind of confluent white matter disease, and then so on and so forth. You know, this is something that having a good neurologist that knows this well is always very helpful as you go through. There's a number of treatments out there. So GRAB-A is one of them that stem cell treatment has been used for. The challenging part is it's often, it depends on where they are in their disease. So as these kids start to be symptomatic, because these are often very quick-moving diseases, the outcomes are less beneficial. And you do still see some progression in these patients, even if they are treated before the disease has started. So a challenging decision often, but the earlier we can diagnose them, and if they've had siblings, or there's a big push to get a lot of these diseases put onto the newborn screen, and there's been some success with a lot of them, can be really helpful. There's been a big push in terms of gene therapy. We actually just treated the first patient with antisense oligonucleotides for Alexander disease up at MGH last week. And so we're hoping to see some improvement there. We have gene therapy for ALD, and there's been some other treatments that have been pushing through. There's certain clinical, there's a number of clinical trials and other compassionate use trials that are out there. One for A. cardigutierrez down at CHOP that's ongoing and seems to be showing some benefit. And yes, and then in terms of our other management, I think is the important part for today. You know, so this is kind of where we fit in. I think that when I think about these kids, this top part is important. You know, we think more often, a little bit more about this episodic care type model, where we're really looking at what are our goals for this course of therapy. We're going to see, often we're going to see regression, we're going to see progression of that disease and being specific about what we're aiming for. When we, when we send these kids to therapy and making sure that we're not just filling their time and, and filling their life with, with time and therapy, I think is important. The DME and equipment, I think is a challenging aspect. One of the things that we want to make sure we do as we go through this is think about where these kids are going to be. Um, it takes a while up here at least to get our equipment. Um, and I've definitely been burnt once or twice where I've gotten something for a patient. And then by the time it's come, it really wasn't appropriate for them. Same thing with bracing and splinting. I think thinking about our goals and what our, what our current function is, is really important as we go through, um, in those, so tone management, I'm going to quickly go through this, um, to make sure I can get past, but, you know, I think one of the things that I've kind of transitioned from is this sort of idea from the left where we're just start with our very, our very, um, conservative measures of stretching, bracing therapy, then move to our oral medications and focal tone management, and then to our surgeries. And more to this kind of wheel of, of how much of each one do we want and picking as we go through and making sure that we're, we're treating them as appropriate at that time and not necessarily just in, in sort of a stepwise manner. Um, so I've had some kids that we've jumped, you know, not necessarily the surgery, but definitely to injections much earlier, um, we're often, you know, bracing and that sort, but I also have had some kids, particularly in the more severe stages of metachromatic leukodystrophy and that sort where they really haven't tolerated the braces and, and our goals are much more pain control, um, and cares and they are actually maintaining range of motion and that sort. So I'm going to pass this over to Dr. Evans and let her talk about some of the other aspects of maybe the ethics and decision-making here. Brian, thanks so much. Uh, and thank you everyone for attending and sticking with us through the wee hours of the morning here on the East coast. Um, they're just with regards to tone management, I think just from the first lecture that you heard from, uh, Larissa and Stacy and Mary that, um, tone management isn't easy. We it's, it's our area of expertise and we have a, um, a system of drugs that we can use, but it's not easy to know what to use when, and I think that becomes even more difficult when we're treating patients who have a, an etiology that is not, um, static, similar to treating patients who have cerebral palsy or treating patients who have other static causes for their hypertonia, but there's not any, any evidence that says that one way or another is a better way to manage tone hypertonia in patients with leukodystrophies. And again, as Brian highlighted so nicely, one leukodystrophy is not the same as the next. So what we recommend is that you start with the algorithm that you would use to treat patients who have static lesions, but then pay attention to the pace at which you adjust medications, um, and pay close attention to what's happening with the patients as you adjust their medications, because some of these patients, at least in our experience have been a little bit more sensitive to, uh, to the drugs. And some of them require much higher doses or much more, uh, much higher frequency of the use of medications than, uh, than you might imagine for some of your patients with cerebral palsy. And I think that, um, the, in, in the absence of really good, uh, testing to see how patients will, um, metabolize drugs, which the only one of us who probably knows that consistently is, uh, Matt McLaughlin and, you know, one day we will all know how to use his information and be able to be, um, more specific in terms of how we treat our patients, but in the meantime, just follow these patients very closely. And then other things that are important to remember is that, um, as Brian said, patients with like cardiac uterus have an immune mediated response, uh, disease. And so patients with autoimmunities may react to the protein loads and toxins. That's not as true as it used to be since the, um, since the protein load has been significantly decreased since about the turn of this millennium, um, in all of the, the botulinum toxin products, but it's still important to remember that there is some protein in all of them and patients with autoimmunity may, or with an immune mediated disease may have set off an episode of, uh, worsening neurodegeneration in response to that. So you just have to be careful. Um, the other thing that is important to remember is the patients who have degenerative diseases will not react the same to a permanent solution as someone who has a static problem for, uh, as the underlying etiology for hypertonia. So a permanent solution such as a selective dorsal rhizotomy, which I have seen used to manage hypertonia in patients with Polesius Merzbacher before it was clear that the diagnosis wasn't spastic diplegia will not be effective long-term and the patients will look just as bad in a year or two as they did prior to the selective dorsal rhizotomy. So it's important to be aware of what you're dealing with and what you're trying to accomplish. And then the other thing that's really important to know for all of these patients with leukodystrophies is that they may have an increased risk associated with the use of anesthesia. And so it's just important that the anesthesiologist with whom you work are aware of the fact that the patient has a leukodystrophy and pay a little bit more attention to anesthesia that, that may be necessary for surgery, or that will be necessary if surgery is indicated so that, that, um, if you're taking care of these patients, you can let the anesthesiologist or probably more importantly, the parents know that this is a risk. Next slide. The sort of the flip side of that, or one other thing that we feel like is really important to highlight is that just because these patients have a degenerative disease for which there is no cure for, for any of these diseases right now, that does not mean that we should not be paying attention to caring for these patients. And I think delaying caring for these patients, which we've seen happen when, uh, surgeons are reluctant to operate on a dislocated painful hip or reluctant to operate on a rapidly progressive scoliosis in a patient who has a neurodegenerative disease, but who may live for another five, 10, 20 years, um, not approaching those patients early on and treating them as though they're going to live can really mean that, uh, that things deteriorate quite rapidly for these patients to the point where it's not possible to intervene and be helpful, um, other things to pay attention to, uh, just as, as Brian has highlighted already are the things that you see listed there, which are complications of a neurodegenerative disease that also may be a complication of a disease that's secondary to a static lesion, but that may be more common and that may show up more frequently over the course of the patient's life. Um, as with all of our patients, we think it's really important that you continue to ask the question of how can you add life to the years that remain for these patients? Next slide. And just a quick list to memorize, um, before, uh, we finished this talk about all the things that could have a problem and the, uh, and things that, that might go wrong in those areas, but things that you might be able to do something about. And one of the classic things that when you hear the Kelly's talk about their son Hunter, who had crevice was that they felt like his neuro irritability or his irritability might have been related to the fact that he was aspirating everything and that he was starving. And that once he had a G2 placed, even though they knew that he was going to die within a relatively short time, he was much more comfortable and they were more comfortable, uh, managing him because he, he was more comfortable. Next slide. So the, one of the important things that we think, um, you should be paying attention to is that since these patients may show up in your clinic diagnosed with cerebral palsy, or come in with, with a diagnosis of cerebral palsy, as you take a comprehensive history and physical, remember the things to be looking out for. And most of this will be in the history that are warning signs that this patient may not have cerebral palsy, even though he may have been diagnosed with it by another provider. So there, there are things that you already know, things like a full-term pregnancy, um, a history of cerebral palsy that runs in the family, um, pretty significant developmental regression, which we don't expect to see in our patients with CP, uh, and, um, then the, an abnormal MRI, especially one that a neuroradiologist can point to and say that, uh, that this is, is consistent with a lupid dystrophy. And I think the other thing that, that those of us who are used to telling patients that, um, an MRI isn't going to add anything to the management of a patient who we see with cerebral palsy. That's true that if a patient actually has cerebral palsy, having an imaging study of the brain will not add much to the way that you manage the patient. But on the other hand, if that's going to tell you that this patient doesn't have cerebral palsy and has a lupid dystrophy, uh, it will be very valuable. And I think for those of us who based on the, uh, based on the frequency that we see that have been listed for these diseases, those of us like who work in lupid dystrophy centers feel like we've seen every single one of these patients, but it makes us quite nervous to, uh, to diagnose a patient with CP without having had an imaging study of the brain. Next slide. And then finally, just things to, to remember are listed here on this slide. Um, that lupid dystrophies are complicated. Um, we've talked about rate of progression and contraindications for, for common treatments for hypotonic hypertonia in CP. Um, but what's important to know is that research is ongoing and that there may be cures down the road. Um, also that the research that's been done to try to identify natural history for some of these patients shows that, uh, these patients have low to normal IQ, which is much higher cognitive status, a much higher cognitive status than the patients may be able to express. So that's something that's important to keep in mind and then consider what you're prescribing, uh, and, and why that might be helpful, um, as highlighted by the interdisciplinary diagram. And then finally, as with many patients whose parents and families have not been able to, uh, find a cure or find a way to slow progression of disease, be aware of complimentary and alternative medications that might be used by families and try to develop a relationship with your patients and their families that has them telling you what they're using so that you can be aware when you are prescribing perhaps other medications, what they're doing and, or so that you can be aware of any absolute contraindications for the use of a particular complimentary or alternative medicine for patients who have leukodystrophies. And then finally, on the last slide, we've included, um, some references to, to, uh, community groups that are support systems, um, for families, patients and families who have leukodystrophies, and these can be really helpful for your patient. And sometimes for you, if you're looking for more information, there are also ways that you can go to sometimes look for funding for, uh, research projects that you have in mind, because these are groups that have formed to try to take care of, of their own in the absence of, um, information in, uh, in the medical community that they find helpful. Thank you very much. Thank you, Sally. Thank you, Brian. Um, there are a few comments and questions in the chat. Um, if you'd like, I can read them out to you, or if you want, um, to do it yourself, I I'm happy to read it to you if you'd like. Oh, you're on mute, Sally. We'd love to hear your voice. So go ahead. Oh, great. Okay. How do you balance quality of life with medical treatment, a progressive disease, and who decides child parents or healthcare provider? And are you adding years to life or life to years or both? When is intervention harmful versus helpful? Sorry. That was a lot of questions. So I, I can start with the first one. I think that it's really important when you're trying to come up with the appropriate balance of, uh, therapy or any kind of intervention to do exactly what Brian suggested in the beginning, and that is keep the patient and the family at the center of decision-making at all times. And, um, this is important both when you're working, um, remotely with families, but also for, to, to keep in mind, if you are providing consultation for, for local providers, uh, for patients who, who might be coming to see you from a long way away to a specialty clinic, and I think different, I mean, all of you all have seen this. All of us have seen this, that different families are going to want different things, and there's some families who really want permission to stop going to therapy so they can go to the zoo or go to the pool, uh, or go to the beach with their families. And there are other families who want to be able to take their children to therapy as frequently as possible in order to feel like they've done everything that they could for the family. I think, um, again, it's important to be honest and open about what you anticipate to be, uh, the likely trajectory of, of the disease or course of the disease, but, um, it is, uh, it has to be driven by what's going on with the family and what their goals are. Um, and I forgot the whole, all the rest of the questions. Um, I think you kind of answered the gist of all the questions for that one. David, if you disagree, please chime in. And then there's another question from Jolene. What do you do for a patient with a change in tone? How do you discern if it is related to disease progression versus something else like severe constipation or abdominal pathology or fracture? Yeah, I can, I mean, I, I run through the same process that I do it would for our patients with cerebral palsy. I always will run through and make sure that there's not a UTI, you know, that there's no concern for an acute fracture, um, making sure that our bowels are moving, that we're, we're emptying our bladder and that stuff, um, before I start to increase our medications and go up. And I think, you know, as Dr. Evans was saying, you know, sometimes you can have progression pretty quickly and you can have issues with aspiration or other things that may be causing that tone to be going up on its own, um, in that same period. And so sometimes it is a little bit challenging, but being a little bit slower, I think sometimes with, with going up on the medication is important because you may, you may be dealing with a little bit of both. Um, but it, it's often a little bit challenging depending on, depending on the underlying disease, disease. And I would agree completely. Um, but say also that, you know, just, we, we have no idea. I mean, none of us, I don't think I have any idea about what what's causing what, at what moment. But I think that, um, when you're dealing with a patient who has a degenerative disease, who may be changing quickly because of the disease, that it perhaps drives you to stay in a little bit closer touch with the patient and, and that it perhaps drives you to stay in a little bit closer touch with the patient and to reevaluate more frequently. And I think that that was, that has become perhaps easier to do with, um, telehealth and maybe not, I mean, you certainly can't put your hands on the patient, but you can see if, you know, if he was stiff as a board, when you saw him and then you did something and now he looks happy and playful, you probably did well, and if he's still stiff as a board, you probably need to try the next thing. So, um, that's, uh, I mean, Sue Epcon used to say the worse you are, the worse you are. So, um, so you can tell a little bit from that, but I think close followup can be really important for these patients and then small changes. Words to practice by, um, excellent talk. How do providers find out about where leukodystrophy centers are? Uh, the hunt, so Hunter's Hope, the website has a leukodystrophy care network. Um, and so does list out all of the major centers that they support, um, as well as some of the, uh, ancillary sites that are, that are kind of working towards it as well. And I think that's true for the other, for, uh, the United Leukodystrophy Foundation, which is the ULF and, um, GLEA, which is the global, uh, global leukodystrophy something initiative around the world. Um, I forgot what the, what the letters stand for, I'm sorry, but, um, the, I think, uh, all of those sites can be helpful in terms of where, where to refer patients. Um, and I think the other thing that, um, that is helpful for some of those sites is the different centers have, um, experts that are even more, have even greater expertise with particular disease. And the people in those groups can tell you the very best person for this disease is in X place. Now going to any of the centers, I think people are connected enough that, that they can help with any, any sort of, um, diagnosis. But I also think that I, in the cases that people, that if someone wants to know, where is the world expert, that all of those centers can be fairly helpful. Thank you. Oh, thank you, Brian and Lisa, Brian and Sally for joining us and for wrapping things up for us. Thank you, Mike, for asking the questions. Thank you to all of our presenters, um, who agreed to talk at this very late hour, especially those of you on the East coast, I'm well aware that it's after 10 o'clock and those of you on the West coast who have been able to join us because we are hopefully doing it after your clinic hours. So thank you so much. I'm looking forward to seeing you guys as we start the actual annual meeting and with our PEDS pre-day that will be at Vanderbilt that will precede that meeting this year. So take care. We will see you all soon. Thank you so much for joining us. Thank you, Jolene.

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