Okay. Welcome, everyone. We're going to go ahead and get started. It's so nice to see friends in the audience and new faces. I'm Kimberly Heckert. I am the Director of the Specificity Management Fellowship Program at Thomas Jefferson University in Philadelphia. And I'm delighted to be the Session Director for this talk. And I'm especially delighted to be accompanied on this stage by people who are not only my colleagues, but really people I consider to be friends and who I genuinely enjoy hanging out with, talking to, and discussing cases. So what we thought we would do today is discuss how management of spasticity more often than not typically requires more than one method to accomplish our goals. So we're going to talk about various combinations that we might use for spasticity management and when we might do so. So I'm joined today by Dr. Andrea Toomer, who comes to us from the Colicchia Neurological Institute in New Orleans. I'm also joined by a prior fellowship, spasticity management fellowship graduate and dear friend, Dr. Jessica Mulhern, who practices at the Center for Tone Management in Paoli, Pennsylvania. Next, we will hear from Dr. Michael Salino, who has been a mentor and a colleague and a friend for nearly 20 years, who is the chair of the Department of Physical Medicine Rehabilitation in Cooper in New Jersey, Camden, New Jersey. And finally, we have Dr. John McGuire, who is joining us from the Medical College of Wisconsin. And they say that... What do they say? That if you copy someone, that's the highest form of flattery. I know there's a better way to say that, but anyway, you know, I looked very much to his spasticity management fellowship program when I was building my own. So I'm delighted to have them by my side for this presentation. We're going to save all questions today for the end of the presentation, but please do save them and ask them. The menu for today... I'm having a little trouble advancing this slide. Do I need to point it to someplace directly? I'm not sure where to point it. Is it on? It might not be on. It's on. Oh, I think I have the menu memorized. So while we're... You got it? Okay, here we go. So the menu for today is going to begin with me. I'm going to talk about combo option number one, which is going to be modalities, oral therapy, and the use of neurotoxin. After that, we'll be discussing neurotoxin with the use of intrathecal baclofen therapy, followed by neurotoxin and neurolysis techniques combined, followed by intrathecal baclofen with other intrathecal drugs, and finally intrathecal baclofen with DBS. And I hear that last part of the presentation has been described as riveting. So we'll see if that is indeed the case riveting. So don't leave early. Do not leave early. These are my disclosures. If I do discuss the use of an off-label medication, I will say so. Okay. This is a real case. Case one is a patient of mine from years ago named Bill who had a chronic stroke with left spastic hemiparesis. When he came to me, he was ambulatory. He used an AFO and he had hand as a holder function for ADLs with his left hand. When he came to me, he had never before received any prior treatment for spasticity. He had only recently learned to understand that he had this condition called spasticity. His chief complaint was predominantly stiffness and also low back pain. That was a stiffness description of the pain. He's 61 years old and additional comorbidities include hypertension and longstanding but controlled epilepsy. On exam, his fingers were flexed with hypertonia using the modified Ashworth scale. I graded them as two. Worse at the PIPs and MCPs. His thumb was flexed but with minimal resistance to passive stretch. He had a neutral wrist at rest, no skin breakdown of the palm or elbow crease. His axilla was accessible. He had a very stiff knee gate with reduced passive dorsiflexion at the ankle. When his knee was flexed, his ankle could be moved to neutral, but it was less than neutral in terms of dorsiflexion when his knee was fully extended. And when he would get up from the exam table to stand without his shoes on, I could see that as he stood, his toes went into flexion. Also, I could induce ankle clonus when his knee was flexed, but not when his knee was extended. When he would stand, his lumbar paraspinals became taut and tender to palpation and his elbow when he stood up was brought in more into flexion. So I think I'm probably describing a patient that you two have met somewhere along your path. He was a little overweight, not considered obese. Systolic blood pressure on the first visit was in the 150s. I show this slide for us to remember that spasticity at its very core is rooted in a reflex that has gone rogue. And so we need to understand that our treatments can be targeted anywhere along this reflex arc, meaning we can choose to target the afferent signals, we can choose to target the efferent signals, we can choose drugs that act in the periphery on the muscle tissue itself, and we can choose drugs that act centrally. We just need to understand what it is that we're using to try to get a better sense of why it would be the right treatment or why it's not the right treatment. So for Bill, his treatment plan goals included to reduce stiffness and back pain and enhance the functional use of his hand. I immediately sent him to physical and occupational therapy and I started him on oral therapy and I was considering focal therapy. So that's my initial treatment plan. So let's talk about what I could have chosen for him. He had never been on any oral therapy. I could have considered a medicine called medicine baclofen, which as most of us know, it's a GABA-B agonist. So GABA is our main inhibitory neurotransmitter. So baclofen agonizes or increases the inhibition. That's how it works. It works centrally on the spinal cord, predominantly is excreted by the kidneys. Common side effects include sedation, dizziness, weakness, and seizures and can be used orally and intrathecally. One thing that we must understand about baclofen is that it's only absorbed in the upper portion of the small intestine. There is no colonic absorption. That means that there's a potential for a saturation phenomenon to be seen where by increasing oral doses after a certain point is not going to result in more effectiveness. It's not suitable for rectal use. So those of you who are in training, when you get that call at your IRF, that the patient's NPO, could he have baclofen as a suppository? Your answer is... Nope. Nope. No, he cannot. I mean, that's just mean. It's okay for a G-tube, not a J-tube. It was too late. It's not available IV yet, but I'll say that it is in the works and some people have used intrathecal baclofen intravenously in some cases. That would be an off-label use. When that is done, it tends to be a three-to-one potency compared to oral. Also intrathecal baclofen, yes, administered in an emergency. And then the oral preparations include the tablets that we're familiar with, granules, and also a couple of oral suspensions. These are the granules. The brand is called Levispa and this does have an indication for use in the G-tube. It comes in 5, 10, and 20 milligrams and I believe it comes flavored strawberry. There's also Ozobax. The prep is one milligram per mil, milligram per mil. There's no formal indication for use in G-tubes, although off-label I can surmise that that could be done. It requires refrigeration. This is in contrast to Flexuvi, which comes as either 300 or 120 milliliters. It's either 25 milligrams per 5 ml, um, excuse me, 5 milligrams per ml and there's no formal indication for G-tube use here either. In contrast to Ozobax, the Flexuvi can be stored at room temperature. So that might be important for certain practices that have frequent storms and lose power. Suspensions can be compounded. With the compounded suspensions there has been observed a sort of erratic absorption where there might be a mild overdosing or underdosing observed. So just something to be aware of. Moving on to Tizanidine. This is an alpha-2 adrenergic agonist. Pardon me as I've lost my voice a little bit from a lot of talking over this conference. That's the fun of being in person, right? Lots of talking. In contrast to Baclofen, Tizanidine prevents the release of excitatory neurotransmitters, mostly Norepi. So on one hand with Baclofen we had an agonizing effect of the inhibition and with Tizanidine we have a diminishing of the excitatory. But regardless of which way you go you come to the same end point, which is a reduction in spasticity, which is with some side effects of weakness. Differentiating it from Baclofen you can see hypotension. And we also have to be aware that it can raise the liver function tests. So I tend to just make sure that somewhere in the medical record in the, you know, not too distant past the patient has had a comprehensive metabolic panel. And if they haven't I would order it before initiating therapy. And then I will usually check it within three to six months. And then after that I'll check it yearly if the patient is on it chronically. Klonidine, similarly to Tizanidine, is also an alpha-adrenergic agonist. Differentiating it from Tizanidine it has alpha-2, but it also has a little bit of alpha-1 agonist activity. And it can be given orally. And we know from its use as an antihypertensive that it can cause hypotension and that if a patient misses a dose what happens? You get that reflex hypertension. So if Klonidine is to be used and there's any concern that that might happen you could consider using it in its transdermal form which is the cataprest patch. We have the oral drug Dantrolene which works on muscles by blocking release of the calcium from the sarcoplasmic reticulum which will reduce the force of contraction. This is also metabolized for the liver so requires LFT monitoring and has a very similar side effect profile. It's not supposed to because it's not central acting. In my clinical experience it causes just as much sedation as the others. We have the benzodiazepines. Predominantly Valium and Klonopin have been used for spasticity pretty widely, but they're not FDA approved. We know that these drugs have a high potential for dependence. We know they can cause other problems in our patient populations that might need spasticity management, particularly our brain injured patients. They can be helpful in scenarios of intrathecal withdrawal and have sedation, ataxia, and weakness as side effects, but also a high addictive potential. So we want to be very careful about using benzodiazepines. Falling out of favor perhaps more recently is Ciproheptadine. I used this a lot when I was training. It's an antihistamine described to be helpful with spasticity in spinal cord injured patients without as much weakness. And this would be an off-label use as it is an antihistamine. It's actually indicated for rhinitis and conjunctivitis. I'm going to put this category called other muscle relaxants. I'm talking about the flexorils, the sclaxons, the methocarbamol, the centrally acting and very poorly stood drugs. Centrally acting meaning they cause their relaxation similar to a martini. So I put that martini there and I say, frankly, if it were me, I'd rather just have the martini. These are not considered first-line oral therapy for spasticity of central nervous system origin because there's no direct action on skeletal muscle, motor end plates, or peripheral nerves. I just wanted to mention briefly a medicine called Zytase, which is zinc plus phytase. This is not an antispasmodic medicine, but it has been used recently to increase the absorption of zinc, iron, and copper. That's phytase and then zinc tends to potentiate the effectiveness of botulinum toxin, it's surmised. So some people have used this for cosmetic use before getting Botox for cosmesis or a neurotoxin for cosmesis. They might use this to sort of potentiate the effects so they won't have to come in and pay for it as frequently since that's typically not covered for cosmesis. And the reason that it's proposed to perhaps potentiate it is because botulinum toxins are zinc-dependent endoproteases. And if we think back to the toxicity literature, sometimes that was done for chelation. Some drugs could worsen spasticity. So it's important for us to see that before we prescribe something additional for a new patient. Maybe we want to think about counseling our patients that some of the medicines they're taking could be making their spasticity worse. I'm talking about SSRIs and tricyclic antidepressants. In theory, it could be from any medicine that increases serotonin because serotonin will increase the alpha motor neuron excitability. And I have an old reference there from 1999, but I wanted to include it because I read it a long time ago and it was really a nice description and I liked... It helped me understand why this phenomenon could happen. St. John's Wort also is said to increase serotonin in the brain. So in theory, it could also make spasticity worse. Let's go back to our case of Bill. What did I do for Bill? His goals were to reduce stiffness and back pain, to enhance the use of his hand, we did physical and occupational therapy. On the day I met him, I prescribed Tizanidine. Why did I choose Tizanidine? Well, he had a history of longstanding but well-controlled epilepsy. So it's not that Baclofen would have been an absolute contraindication for him, but Baclofen has been known to lower the seizure threshold. So why chance it? Also, you may have remembered in that first slide that Bill's blood pressure, systolic blood pressure was running in the 150s. So he wasn't the most well-controlled antihypertensive man. And so I thought if he did get a little hypotension from Tizanidine, it might not be the worst thing. We did counsel him accordingly. Then I did treat him with chemodenervation with botulinum toxin. Initially, I chose the FDS, the lumbricals, the gastrocnemius, the soleus, the flexor hallucis longus, and the flexor digitorum longus. And then in subsequent cycles, I placed a small amount in his brachialis so that when he stood up to walk, we didn't see so much elbow flexion. And that did help with the balance and the ease of gait. So the outcomes for Bill, he had improved hand function beyond hand as a holder. I'm not saying that he was typing, but he had improved use enough that it was worthwhile for him even to have me inject the lumbricals. He had reduced back pain. And I should note that he had a little bit of improvement from his back pain even the first time he came back to me in the office before I gave him chemodenervation. So I surmised that that was probably either related to the PT or OT or the Tizanidine treatment. And then he got additional improvement with his back pain as his gait improved. So I added the brachialis treatment. He had reduced stiff knee and his gait was less effortful. So he reported taking longer walks with his wife. So in summary, there's absolutely a role for stretching, for therapies, for modalities, particularly with the way that they can influence that reflex arc through the afferents. And focal treatments are for focal problems. So if we're really wanting to target a certain focal problem for our patient, we might want to think about one of the focal treatments. It's very difficult to sprinkle a toxin over multiple areas. Multifocal is okay, but sprinkling is less effective. And oral therapy is more helpful for widespread spasticity that would be difficult, right? Remember, he had back stiffness. It's off-label, but I've certainly seen people pepper it up and down paraspinals. That's a little harder to do and judge and see how your patient's gonna respond to that. So oral therapy worked very well for him. And then lastly, remember that certain groups of patients are more sensitive to side effects and that we should be very careful with side effect tolerance, particularly in the elderly. And with that, I'm going to turn it over to my colleague, Dr. Andrea Toomer. Thank you. Hi, I'm Andrea Toomer. I am from New Orleans and I'm in private practice. I'm in a multi-specialty group, so I have a few other physiatrists with me, but also neurologists and neurosurgeons. And so we're gonna talk about combo platter number two, which is the combination of intrathecal baclofen and toxin to treat spasticity. Yeah, no. It's not going. Okay. No problem. So I'll just say I have a few disclosures. I am a speaker and have done a little bit of research for some device and pharma companies. That was the next slide. So we are going to talk about using combination therapy to treat spasticity and obviously this combination is treating intrathecal baclofen with intramuscular botulinum toxin. So looking at patients who have global spasticity that we want to treat but then also want to target with some focal toxin treatment as well. So, I can tell you about my case before we get to the slides. So, my case is a lady who presented to me for an initial spasticity evaluation. It was... Here we go. Perfect. Whoops. Now it went too fast and now I can't back it up. We are there. These are my disclosures. Thank you. And we already kind of talked about objectives a bit. So, this is a 65-year-old lady who came to me for an initial evaluation in February of this year. So, she had had a stroke just a year prior. She was treated in inpatient rehab. At the time she left rehab, she was ambulatory and functional using either a quad cane or a rolling walker. She was using both. She said that her spasticity kind of started in July of that year. She noted limited active range of motion, limited use of her left arm due to that spasticity. She was put on oral back with him by her neurologist who was the person who referred her to me. She was really only able to tolerate it at night. It did cause a little bit of sedation, but she was using that to help her get her arm relaxed and help her to kind of go to sleep at night. So that was... And she was in ongoing physical and occupational therapy, but the only treatment she had really had so far was oral back with him, which she was able to tolerate very minimally. So she does have left spastic hemiparesis. There's resistance to passive range of motion, but I can reach full range of motion in the arm and the leg. She's modified Ashworth score of two. She does have brisk patellar and biceps responses. She has three beats of clonus at the left ankle. She's able to ambulate. She wears an AFO. The first time I see her, she has a quad cane. In the video, she brought her rolling walker that day. So she's got a wide base of support. Her left arm is flexed at the elbow, adducted at the shoulder. There's no swing when she ambulates. She's slower advancing that left leg, typical gait pattern that we would see. So here she is here for her physical therapy assessment, and they're using a rolling walker. So we can see not just that she's, and we see when she let go there, no volume please. When she let go there on her right side, she's really not holding on to that rolling walker very well with her left hand. She's not able to flex that wrist at all, so she can't get a good grip on that walker. So she's really just using it to help balance on that side. She's not putting as much weight through that left side. She's very slow to swing through, a little bit of a wide base, a little unsteady. So this is kind of her baseline pattern. Now again, this is a functional lady who's doing very well and doing lots of things, but she recognizes that her spasticity is limiting, and she wants further treatment than just the oral medication that she's tried. So we talked about options, and obviously adding other orals would always be an option, but she's a little bit not tolerating what she's taking now, and that's only one pill at bedtime. Also, she's not getting a great response with that oral medication, so we know we need to move further. And spoiler, we know that this is about intrathecal baclofen and intramuscular toxins, so that's obviously what we decided to do. So I talked to her about options. She does have diffuse spasticity affecting her arm and leg. My thought in a lot of these cases is to start with intrathecal baclofen and see what we can relax by doing a screening test. So she did undergo a 50-microgram intrathecal baclofen screening test. So at baseline, she's got a timed up and go of 39 seconds using a rolling walker. She's got modified Ashworth of two in the arm and leg. At the two-hour assessment, she actually did her timed up and go with a quad cane rather than the walker. She was more stable, and time cut down to 29 seconds. Modified Ashworths decreased down to one. At the four-hour assessment, Ashworths are even going down further. She's at modified Ashworths of zero in the arm and the leg. Timed up and go about the same at 30 seconds, again, using the quad cane rather than the rolling walker. So subjectively, she tells me she felt so much better. Not only passively could they move her arm and leg much better, but she could move them a whole lot better. She says when she walks, she felt like she could never get her foot flat. Even with that brace on, that foot just wasn't going where she wanted it to go. And the day of the screening test, she could get that foot flat. That felt a whole lot better for her. And she was really happy with the way that she was able to walk after that screening test. She told me that she really enjoyed the benefit, but she felt like the benefit wore off too quickly. So she felt what it felt like to have less spasticity and really liked that. And then it didn't last, obviously, because it's just a screening test. So that was kind of a letdown for her. So she definitely had a positive response and wanted to move forward with intrathecal baclofen. So we implanted a Flow Onyx 20 milliliter pump. We got the catheter tipped to T3, so we wanted to try and go higher because we wanted to affect the upper and the lower extremity with the response. I started her at 100 micrograms per day because I was banking on that statement she told me, you know, that benefit went away, it really didn't last. And I'm thinking, you know, I know at four hours it was still kind of working, but she went home, it wore off. I wanted to really give her that benefit of the medication that she'd felt so good the day of the screening test. However, it was too much. So she felt like her leg felt too loose, it was going to give out on her. She was relying on some of that tone that she had had for, you know, about eight months at this point. And it just felt different, and she didn't feel as stable when she was walking. So for that first visit, I lowered her dose down. We went down to 75. Now, of note, she did note that her arm was a whole lot better and felt a whole lot looser at the 100, but of course it was negatively impacting her feeling of stability when she was standing, so we had to lower her dose down. We went down to 75. Her leg didn't feel any better. She still felt that looseness and unsteadiness when she was standing. And her arm already started to get tighter. So she wasn't getting as much benefit in her arm that she was at 100, but then the leg was still feeling too loose. So we had to keep going down on the dose. So I'm thinking she got a great response to the 50-microgram screening test, and we sat there and we talked about that screening test day. That day, she did not feel any unsteadiness in her leg when she stood and walked. No looseness, no unsteadiness. She felt like she walked great. So I knew she could tolerate a bolus of 50. I knew it didn't last the whole 24-hour period, but I knew she could tolerate a bolus, and I knew that was going to get her a period of time. So my thought was, maybe I try to replicate what we did that day of the screening test and give her boluses with nothing in between and see how that goes. So I knew she could tolerate 50, but I knew it wasn't going to get her a whole 24-hour period. So I thought if I took 50 and divided it up in half and do 25 and 25, let's see what that gets us. And that was a decrease from 75 to 50, which was a reasonable decrease in dose. So I just picked 6 a.m. and 6 p.m. Let's try those for the doses and 25 micrograms each time. So her leg felt a whole lot better. That helped her feel more stable. She wasn't having any spasms, so we didn't have a return of her increased tightness in her leg. She felt good. The leg responded well. Her arm was tighter, especially at bedtime. So this is kind of what we're seeing, her baseline pattern when she first came to me, that arm was so tight at night, it was really difficult for her to get comfortable. That's why she was taking that oral baclofen at bedtime. So now she's kind of feeling that bedtime dose. But she's overall very happy with daytime control of spasticity. She feels more functional. At this point, she's using her quad cane. She's out in her garden doing things throughout the day. So daytime looks really well, but nighttime is still an issue. So I'm thinking we play with the dose of the intrathecal baclofen again. So I tried to increase that nighttime dose, and I actually took that morning dose down just a little bit. So I did 20 micrograms of Ebola's in the morning and then 40 micrograms at bedtime. So it was an overall increase from 50 micrograms to 60 micrograms. I knew when she'd up at 75, it was too much, so I didn't want to go that high. So I was kind of trying to see where do I inch between where I am and where she was and try to get that best control. So when we went up on that dosing, leg got too loose. She was starting to feel that unsteadiness again. And she didn't really feel any benefit with the arm, even though I had given her that 40 microgram bolus at bedtime, that higher dose. So I wasn't getting anywhere by doing that. So the thought is she's responding well to the bolus as far as the leg, but we've got to add something for the arm, because the arm is just not going to respond well at the lower doses that she needs for her leg. So at that visit, that's when we talk about let's do some intramuscular toxin, let's target the arm with toxin, and let's continue adjusting this dosing for the intrathecal baclofen and get that leg exactly where you want it to feel. So what I did was I decreased her dose of intrathecal baclofen to 35 micrograms, a single bolus only at bedtime. I moved it to 8 p.m., try and get a little bit later, get it something that would last her throughout the next day. And then the plan was also to move forward with botulinum toxin injections. So we did focal botulinum toxin injection. I did Dysport. I used a total of 600 units, a little bit of off-labelness mixed in there, and a lot of low doses. So if you look at package insert of what you can do in muscles, this is a lot lower than a lot of things. But we're really not, we're not treating muscles that aren't being treated. We're treating muscles that aren't being treated fully and effectively, because we've already got that intrathecal baclofen on board, so we can use a lower dose than what we would typically use. So objectively, there's improved active and passive range of motion after we do the intramuscular botulinum toxin injection. Subjectively, it's amazing for her. She tells me her arm, for the first time since her stroke, feels like a normal arm. She has better active range of motion. She's much more functional. She tells me that toxin was a miracle. She can hold her rollator. So she really wants to ambulate with a rollator, but she's never been able to get that good functional grip with her left hand to hold and be able to break. So she's never been able to do that. Now she can do that. She can hold a rollator. She can walk more smoothly. She feels like this combination of treatment for her has been the thing that has changed her functional level tremendously. So I thought, well, maybe we could decrease that intrathecal baclofen just a little bit more. So I lowered her to 25 microgram bolus at 8 p.m., and that didn't work out. Her legs started jumping again. So she was having these spontaneous spasms when she first came to me in her leg. We had eliminated that through everything. Once I went down to the 25, they came back. So she was unhappy with that decrease. We went back to the 35 microgram bolus. So that, this is her stable dose now. She's now gotten her second dose of intramuscular toxin, and we remain at that 35 microgram bolus at 8 p.m. So again, just a reminder of what she looked like at baseline. Let me just do this for a second. Compared to, this is what she looks like now. So she's much smoother. She's faster. She's much more stable. She's incredibly pleased with her ambulatory ability and with her functional use of the left arm. It's made a tremendous improvement in her function and quality of life. And of course, combined with all of these treatments, she's continued in physical and occupational therapy. So treating spasticity obviously can improve functional potential. We should always think about treating spasticity when it's impactful for function. We don't need to look at patients who have modified Ashworth's if they're, only if there are three or four, and consider these kinds of treatments in patients. She's certainly not as tight as many of our other patients, but she certainly got a great benefit in function and quality of life by reducing that spasticity and improving her function. Combining intrathecal baclofen with focal toxin treatment can be a great benefit when we have patients with that global spasticity. And then using different programming abilities in our intrathecal baclofen devices can help us to really fine tune and get the best treatments for our patients. Thank you. So I'm not Dr. Ketchum. I'm Dr. Mulhern. I practice at Center for Tumor Management. I'll be talking about chemo-denervation and chemo-neurolysis as my combo. So no real disclosures, possibly some off-label use of the medications and I'll discuss that when it comes up. So my case involved a 28-year-old male who has a history of a severe TBI that happened about seven years ago and resultant moderate to severe spasticity affecting all four of his limbs. He lives in a group home and has like excellent care, but he is non-verbal and has pretty significant dysphagia, absolutely nothing by mouth, and he has a GJ tube. All of his meds are via the J tube. He came to me only on an oral regimen for spasticity and it was baclofen, 10 milligrams, four times a day. They said it's not really working as we discussed, because it's going through the J tube. So he's not really having any of that absorption for it to work. He's previously tried some of the other agents, but they didn't like how much of the sedation that it was having on him. So they just had him on the baclofen, obviously wasn't helping him too much. As you can see, pretty significant spasticity in the lower extremities and moderate to severe spasticity in the upper extremities, pretty much affecting everywhere. Like I said, he lived in a group home. I finally got to see him on his fourth visit. He no-showed three times. Very inconsistent transportation. They didn't really call to say that they weren't coming. I didn't know he wasn't coming, but finally when he showed up they said transportation is totally unreliable to getting to the office. So the goals of the treatment that the aides mentioned are improving his positioning in bed and trying to get him into a chair during the day, ease of hygiene care, because they had lots of difficulties performing hygiene, getting him dressed for the day, and he was starting to get some evidence of skin breakdown. So they wanted to reduce that and he was having lots of discomfort when they were trying to position him for certain things. So plans for the treatment. His oral agents, they said he's been tried on numerous. They don't like the side effects. He has the J-tube, so the baclofen's not going to work. The intrathecal baclofen, he is globally being affected, but he no-showed three times and they couldn't really tell me why. They never called. So that kind of nixed that therapy for him. So that left me with the options of chemo-denervation and or chemo-neurolysis. So a little bit about chemo-denervation, the type of toxins that are available. We have the type A toxins, so Botox, Dysport, and Xeomin, and type B myoblock. So they're taken up at the axon terminal block, acetylcholine release, resulting in muscle weakness or paralysis. You inject it directly into the muscles that you want and you can adjust your dosages based upon the severity of the spasticity, the size of the muscle, or the effects for your goal. You can use various forms of guidance, either anatomical, EMG guidance stimulation, or ultrasound. And all the type A's do require reconstitution with preservative-free and Botox and Dysport require refrigeration. So the pros. I always weigh pros and cons. We talked about them for the oral and the intrathecal. So the pros for chemo-denervation, it's reversible. The effects will wear off in three months if we're not liking the effects. We can get spread, which we can use as a benefit or a con, depending on how you look at... If you want to use less toxin, you can use the spread to do so based upon concentration. Lots of patients are familiar with botulinum toxin. You can use it more for the small muscles, so the hands and confined compartments. If you're worried, we'll talk about some of the side effects for chemoneuralysis. You're going to want to use more of your toxins there. The cons, it's an expensive medication. It requires them to come back in. Transportation is already an issue for him. You can have spread, so you can have some effects elsewhere and you're limited by the dosages insurance coverage-wise and obtaining them. So this is kind of just... And whenever I see and evaluate a patient, I write down every single muscle that I think is affected and then I have a general idea of the range that I want to go based upon whether it's mild, moderate, severe. So for this patient, this is what I was thinking. I generally don't pick my toxin brand. I try to be pretty broad when thinking of the dosage range and kind of do whatever insurance allows me to. So you can see the total dose down at the bottom is just for one side that you're already way above what you're allowed to get and that's just one side of the body. So treating this patient solely with chemodetermination is just not possible. So we looked for chemoneuralysis for this. So we use phenol, but you can also use ethyl alcohol. Phenol also has some anesthetic properties, whereas ethyl alcohol doesn't. So there's a little bit more soreness post-injection, but they both act to non-selectively denature proteins. Our target is the nerves, but they're non-selective. So anything that they go around, they will denature. So you could have myonecrosis. You could have destruction of blood vessels. So you really want to make sure your guidance is on point so you're as close to that nerve as you can be. So we use electrical stimulation because we primarily do motor point or motor nerve branch blocks. But if you're using ultrasound for more of the full nerve, like musculocutaneous nerve, and then you're going to use the transcutaneous nerve stimulator, which we use to localize the nerve on an XY axis, then we use the transdermal needle electrode to find it on the Y axis, how deep it is. This method does require a bit additional training. I think this was probably the method I was most afraid of as far as spasticity management because it can be so non-selective in what it destroys. So having that extra training through the fellowship I thought... Nice little plug, but I thought it was really awesome. So the pros of this, it is immediate effects. The patients are so happy when they see as soon as... The five minutes we were able to inject like a couple motor points and assess if all the spasticity was removed, do I need to go back in and hit a couple more motor nerve branches to really get the effects that I want because it is going to act that quickly. It's pretty... Relatively inexpensive, especially when compared to the botulinum toxin. The effects in our office, we have noticed that they last a lot longer, lasting several years or months, and you can use this for large muscle groups, which would be ideal in this patient. Cons, it is a higher risk procedure and you do have that local tissue destruction. So for this case, we did do chemoneuralysis kind of in a lot of areas because he was so broadly affected. So this took kind of a while to address all the areas because we don't want to inject too many areas for the theoretical risk of having the potential intravascular uptake. The more areas that you do that, there's a higher risk. So we targeted his elbow flexors, again did the motor point branch blocks, not so much the full nerves, and then in the forearm it is a smaller, more confined compartment. So again, we did the motor point branch blocks to reduce the risk for any compartment syndrome due to the swelling or necrosis that you might have. And then we did do obturator. This is the only one that's not motor point blocks, more so the whole nerve for the adductor spasticity and we addressed his quadriceps and his plantar flexors with chemoneuralysis. So he was a lot looser after all these procedures, but he still had some difficulty with the positioning and the skin breakdown and some of the more intrinsic muscles. So then we were able to do chemodenervation and we typically practice... We always do toxin towards the chest wall because of the effects of the phenol in the hand, that's a confined compartment and then in the deep compartment of the leg, any time that you can do toxin versus phenol, that's kind of what we'll try to do. So we had those areas left and addressed that with the chemo denervation and I think, if I recall correctly, we did use Dysport for him. It was like 1,500 units, the max dose in addition to the chemoneuralysis and we'll continue to see him for repeat chemo denervation so we can monitor all those areas that we did the chemoneuralysis and see if any of them need to be touched up with a couple more motor branch blocks with phenol. That's not too difficult to do. So the take home training and numerous procedures like the chemo denervation, the intrathecal baclofen pump management as well as chemoneuralysis really allows you to treat all patients that come in with spasticity. Like this guy could have easily been treated with other ones but due to his circumstances, the GJ tube, a lot of his options were cut. So having training in everything really allows you to be able to treat everybody and you can hit your goals with the patient and the patient's goals can be met as well. That one's quick. Thank you. Uh, it's a real honor to join the tone bosses and tone boss ladies up here. My name is Mike Salino. I am a physiatrist at Cooper University Hospital in Camden, New Jersey. Go ahead and... There we are. Whoops. So my part of the combo platter and I will certainly plagiarize my colleague from Milwaukee, Dr. McGuire, for actually trademarking the combo meal spasticity approach. He was the first one that I ever heard use that term, but we use it all the time now. So these are my disclosures and practically everything that I'm going to tell you is off-label. Combining agents for intrathecal drug delivery is off-label, including the combination of on-label medication. So mama could be on-label, daddy could be on-label, but the children are all off-label. So also following the lead of my colleagues, I'll start with a case presentation. This is a real case. I did change some of the details to protect the innocent and obscure the guilty. 50-year-old female with primarily progressive multiple sclerosis. She has been an active patient of mine for 12 years. Initial presentation was a left lower extremity extension synergy, both at the hips, knees, and ankles. She was intolerant of oral medications, very minimally responsive to peripheral techniques like hemodenervation and neurolysis, like Dr. Mulhern talked about. Had a really nice response to a back of a trial, went on to get implanted, used the therapy, smooth sailing for over 10 years, was on 800 micrograms a day. Everything is just totally marvelous. Life is happy. All of a sudden, with no specific inciting cause, not instantly, but certainly relatively progressive over a few weeks to months, the left lower extremity begins to look like it did on initial presentation. There was also at least some associations of paroxysms of neuropathic pain, kind of diffusely in the left lower extremity. She described it as my whole leg is icy. I'm just being immersed in an ice bath from my hips to my toes, not really dermatomally specific. So we did the usual things that we normally did. We had been using the same on-label branded product throughout her course. Her workup was very unremarkable. We did imager, make sure that there were no new lesions involved. From an MS perspective, there was no granuloma at the catheter tip. We did a side port aspiration that was completely unremarkable, including the aspirate being positive for beta-2-transferrin. CT myelogram was textbook. There was no arachnoiditis. There was no subdural encapsulation. Everything was the way it should be. We tried complex programming. We tried patient-directed delivery. Dosing changes wasn't making much of an effort. So while we were working this up, we also hit her with two rounds of botulinum toxin injections, one at speed limit and one well above FDA speed limits, and not much change at all, you know, I mean maybe a little bit. So we offered her a couple of different options. We said, you know, why don't... maybe you're tolerant to intrathecal baclofen. Why don't we wean you down, we'll put you on saline for a while, and then we'll reinstitute therapy. We'll remove that tolerance, and she really declined on it. The other option that we talked to her is that maybe you have micro fractures. Maybe you have tiny little fractures along the longitudinal length of your catheter that you just have a thousand little pinhole leaks, and we're not picking it up on any of our imaging studies. Again, let's wean you down, put you on saline, and we'll do a complete system replacement. She declined that also. She had a pretty tough time on initial trial and implant with some spinal headaches. She wasn't in a good mood for an empiric catheter revision. So what do we do? Well, what are our options? So first I'd like to talk to you about intrathecal morphine, and if you take a look, what is the original date of this? 1989. The first intrathecal drug that was utilized for spasticity was intrathecal morphine. The idea perhaps that if spasticity being driven by noxious stimuli, morphine would work well. And this paper actually by Erickson is actually a pretty good number of patients followed by some other papers. The rate limiting step for most of the patients trialed on intrathecal morphine was constipation. Shocking, right? We give someone an opiate who has neurogenic bowel, and they got constipated. My goodness, who would have ever expected that? There's actually a report... This kind of fits exactly with our case study. Maybe someone who was tolerant to baclofen, and you swap out to morphine and regain control. Patient was pretty reluctant to go the morphine route, mostly for constipation reasons. There are some papers that actually talk about simultaneous utilization of baclofen and morphine, including this crazy guy in Philadelphia who presented on a 10-year clinical experience. Dr. Siddique is a neurologist in New York City who does a lot of work with multiple sclerosis patients. Again, a nice case study. So maybe we add some morphine into the mix. Intrathecal clonidin. So intrathecal clonidin is technically on label in the perioperative world, not for chronic infusion. Again, this is off-label. This was a really intriguing option, especially when I heard Dr. Perdome... I forgot to put his reference here. I first heard Michelle Perdome, who's a neurosurgeon in Halifax, Canada, present a number of case studies on the utilization of intrathecal clonidin as a first-line agent for intrathecal delivery. In fact, there are a number of Canadian centers that use clonidin as their first-line agent in the ambulatory folks. Folks get good spasticity reduction, perhaps with less concomitant weakness. And this has been repeated by some others. Intrathecal bupivacaine, while, again, off-label and of relative commonality in the pain world, does have a little bit of exposure in intrathecal spasticity. This is one case series that described the additive effect of intrathecal bupivacaine in a multiple sclerosis cohort. So, again, relatively old paper, though. 98, not much more in the literature since then. Ziconotide. Ziconotide is an approved agent for intrathecal drug delivery for pain, but not for spasticity. Mark Wallace's group at UCSD reported on a number of patients with spinal cord injury who had reduced spasticity. Really, really high doses. Maybe four to five times the typical dose that we utilize with ziconotide. A more recent paper described this spasticity reduction effect in a patient with PLS. Pretty expensive medication and often limited by adverse effects, so you have to use with a little bit of caution. We also reported on about 17 cases in combining ziconotide and baclofen together. More for the additive effect of pain. Didn't see much in a way of change with spasticity. So we did have a couple of options open for us and luckily this was a pretty high-level patient that we can have a high-level conversation. It's also an interesting family dynamic. She has a son who's a physical therapist, a daughter who's an anesthesiologist, and a daughter who's a pharmacist. So talk about your stressful family conference when you're talking about off-label indications. So what did we choose? So we chose a baclofen-clonidine mixture and I am going to this combination more and more often. At this point, her baclofen dosing was 1,000 mics per day. We started her at 12.5 mics per day of clonidine. Dr. Perdome, in his work at Halifax, started most of his patients at 25 to 50 micrograms a day. So I was being a little bit more conservative. I know that will be shocking to my former and current fellows that I was actually a little bit conservative with something. But this lady's blood pressure did run on the low side. She lived alone, even though she had good family supports. I'd rather start her off slowly. Ultimately, she was titrated to 60 micrograms and really this all melted away. So we're not really sure, was it the synergistic effect of the baclofen and clonidine together and was it the clonidine by itself and she's truly tolerant? Another thing that my fellows will tell you that I believe in, if it ain't broke, don't fix it. If she's happy with the combination, we're going to leave it where it is. Although I could probably make the argument that we could probably wean the baclofen and maybe convert her to clonidine monotherapy. But again, she's doing okay. Biggest risk of clonidine therapy is hypotension and especially in a population who might be prone to orthostasis. Also, if someone does go into a withdrawal, withdrawal from intrathecal clonidine is not pretty. Maybe not as ugly as intrathecal baclofen withdrawal can be, but you could get pretty recalcitrant hypertension and you need to work with your ICU team on getting that pressure down. It also did have a little bit of a backdoor effect on her pain. She's a little bit easier to control and we're actually thinking about actually giving her a triple combination, giving her a little bit of intrathecal bupivacaine on top of this. So right now I would say that my biggest add-on therapy, if it's just spasticity, is probably clonidine. We probably have 40 or 50 patients on a baclofen-clonidine mixture that we're always adjusting at some point. So this is my combo meal. People may know that McDonald's actually came out with an adult Happy Meal and sold out ridiculously well. If you were invested in McDonald's, your stock went up the week that the adult Happy Meal, they're practically sold out across the country. You could get your own adult Hamburglar. This is where I work, a great place to work. I will now hand the baton off to the originator of the combo meal, my colleague from Milwaukee, Dr. John Maguire. That's a little delicate of it. Now, what I was thinking we could do, just for fun, if everyone sits really still, maybe all the lights will go off in the whole room. Wouldn't that be cool? Because obviously, we're not moving enough up here as the lights go off. In our clinic, I don't know if your clinics are like this, but they have motion detectors in there, and literally, they're wheeling quadriplegic patients, and they'll open the door, and they'll be in pitch black. And like, oh my God, it's like pitch black. And they're going, you know, they can't move, but anyway. So now, we're gonna do a little more stimulating talk on deeper, anyone here, first of all, thank you for inviting me. I love being in a room with people who are passionate about spasticity management. Spasticity management is quintessential rehab medicine. You have to use all your tools and your bag of rehab tricks to manage these patients, and that's why I like it. But obviously, you wouldn't be here if you weren't somewhat passionate about this, because, I mean, it's Saturday, and it's beautiful out. It's really not that nice out. I heard it was raining, and it's really cloudy, and windy, and that sort of thing, but I'll try to, anyway, anyone here have much patience with deep brain stimulators? Oh, good, so I'm gonna just review a bit about deep brain stimulators, and how, where it's used, it's said mainly in Parkinson's, and if you have Parkinson's patients. Oh, and I'm gonna go in case after case, because I have two cases, right? And I've done work with pretty much all the usual players, Medtronic, AbbVie, Mertz, Ibsen, and Sale, but shouldn't conflict with this talk, and I'm just gonna briefly go over deep brain stimulation, and then two cases. So hopefully this'll work. So this is a Parkinson's patient, and you can see before DBS and after DBS. I mean, it's like lights out. It's sort of like the videos you see, and I was gonna show the video of ITB, too. Interthecal backup and lights out for spasticity. This is lights out for tremor, and so it's really, when it works, it's a beautiful thing. And so it's approved right now for dystonia and Parkinson's disease, stimulating the globus pallidum and the subthalamic nucleus bilaterally, or for epilepsy, tremor, and OCD, believe it or not. So, but there's also been reports about using it for other conditions also, off-label, of course. And so a lot of stimulating things happen in the brain right now. But of course, it is brain surgery, so you have to be a little careful. But anyway, so for the effectiveness for essential tremor, like I said, it's almost like ITB and spasticity. I mean, it's lights out for tremor. It's really very, very cool when it works. And for Parkinson's disease, for reducing tremor and rigidity, and they can actually hopefully improve their walking and balance, reduce dyskinesias. And a big thing is they can reduce their oral medications and reduce, with Parkinson's, a big thing is that on-off time when they're on and off. And so you can, they'll be on more than they're off without the dyskinesia, which is really, it's really been a very effective management for that. But you can do bilateral, if they've got symptoms on one side or both sides, you can manage it that way. It's reversible in the same way the pump, you can take it out if it's not working. And you can do non-invasive dose adjustments, same thing with the pump. And it works 24-7, just like the pump does. And you can use it with other treatments, and that's what we're talking about today. Of course, it is brain surgery, and it's from the package insert, so there could be surgical risks, there could be device issues, and then also from the therapy itself. So you can actually get a stroke, you can get CSF leaks, seizures, and surgical complications. The risks are generally low, but it is, like I said, you are putting electrodes deep in the brain area, and so there are risks for complications. The leads can break, but again, the incidence is low. And then for actually, when you adjust the stimulator, you can actually have more neurologic symptoms. And there's also, can make some of the behavioral issues worse also. And some people feel shocking stimulation, or it may just not work, so. All right, so at our, I'm at the Frayter Medical College in Milwaukee, Wisconsin. And so we have about a little over 400 patients with DBS, and most of them fall in the Parkinson's or tremor category. And we have probably, well, we have 300 stroke, or 300 ITB patients. And so you would think, so how many patients do you think would have both, right? Already told you, two, right? So of all those patients, we only have two that have had both at the same time. But most of our ITB patients are spinal cord and cerebral palsy, believe it or not, which is kind of interesting, so. So thanks to the medical affairs group at Medtronic and then doing literature search up until last October, we did it again, and nothing's come out since 2020. But there's only been, in the literature, there's only 16 case reports. So if you have any, it's really like case report kind of thing, this combination treatment. And so anyway, I should probably report my two cases. That'd be 18. Get it up to 18. So most of them are in the pediatric population, and in our institution, we probably have 60 pediatric pumps and we have none with DBS. But anyway, and so the reports are ages from very young, like two to 18, and seven of the 12 had PKAN. Does anyone know what that is? I didn't either, so I looked it up, but we're gonna talk about that later. Five of the 12 had primary dystonia, eight had ITB, and, or eight had the ITB place first and then DBS. And their dose ranges were low and very high, of course. And then in the adult population, three of the four had dystonic CP, and one had dystonia-related Parkinsonism. And so three had the ITB place first and then DBS, and their dose ranges were 140 to 800. So, and only half the cases actually reported complications. Unfortunately, a lot of these cases had long-term follow-up when they reported them. It was just, and so, but anyway, I just thought I'd throw this in here because I thought it was interesting because I didn't know what it was. And for residents out there, that it may be on your board exam, maybe not. But anyway, it's pentothenate kinase associated neurodegeneration. It's a rare one in a million, one in a million autosomal recessive disorder of brain iron accumulation in the basal ganglion. And so you get progressive abnormal involuntary movements, my favorite diagnosis, and increases in muscle tone and abnormal posturing. But you get this characteristic MRI finding, which is the eye of the tiger, which really got my attention. And so the mutation is off the PANK2 gene, of course, which you're all familiar with on the chromosome number 20. And so you got the P-K-A-N, the PANK, and so it's sort of cool acronyms. But anyway, so you got the CLASSIC, which is early onset and rapidly progressive. They become non-ambulatory about 10 to 15. And you got the more atypical, which onset later is more slowly progressive. And they usually stop walking anywhere from 15 to 40. The atypicals can live up to 60 or 70. The CLASSICs usually only live to, can live up to, may only live a few years after that, the diagnosis, or can only live up to about 30 years old. It's about half that. And so, and some have mixed things. But they get this characteristic eye of the tiger. So now, so see if you can see the tiger in the MRI scan. So you get this, you get hyperintensity in the globus pallidum, and the surrounding sort of, so there's the hyperintensity right here, and then the hypointensity around. So you kind of get the eye of the tiger. Isn't that cool? That's how they wake you up a little bit. All right, so the potential benefits that they reported, that they were talking better, less drooling, swallowing better, improvement motor skills, and their care was easier, sitting better, again, better, better, reduced pain, improved quality of life, and they were able to reduce their ITB dose. Now, the reported complications from this case series were a wound dehiscence from the pump implant, meningitis, someone had fever after the surgery, erosion, and then status dystonia, that's a very acute sort of a medical emergency where they get really horrible dystonia, and it's actually, DBS is actually used to treat that too, so, but anyway, or worsening of their dystonia. So I'll get to my two cases, and, oh, we gotta hurry. And so a 30-year-old woman with generalized DYT1, negative dystonia, had spasticity in all four extremities. She initially had her DBS planted in the globus pallidum, and she was doing good for about six months, but then her spasticity became the overriding problem, and so we decided to do a trial of intrathecal baclofen, and you could see her ASHRAE scores, you could see before the trial, twos and threes, and like I said, ITB lights out for spasticity, goes down, we put the pump in, her stable dose of about 240, and she still has some residual spasticity, which most pump patients do. And so the catheter was placed at T4, she combined therapy, she was doing great, but then she started getting side effects of more orophacial dystonia and neck pain, so we shut off her DBS, and that seemed to fix her orophacial dystonia and also her neck pain. And so she opted to, her dystonia with the pump, it just turned out that she was happier with just the pump and not the DBS anymore. And so, and she was able to continue with a more stable gait, and her dose maintained at the 240, and then she woke up and left the Midwest, and I haven't seen her, so. So she had both for about a year, and then now she just has the DBS, or just has the pump. And so, but it did work for a bit, so gets to my next case. So this is a case of atypical Parkinson's. And so she's a 48-year-old woman, and her symptoms started about 10 years before they actually made the diagnosis, and with frequent falls, loss of balance, rigidity, and bradykinesias. And then she also had porphyria, which made oral medications delicate, and she didn't tolerate them very well. So she underwent bilateral DBS placement, in the subthalamic nucleus, and her symptoms got better, and she felt like she was like 100% better for about two to three years, which is kind of amazing. So, but then her lower extremity spasticity seemed to get worse, and she was having more trouble difficulty, and so we did the usual omega doses of neurotoxins, and I was becoming more frustrated because, you know, I mean, toxins. But anyway, so overall, she was about, now is about 60% better, but just the DBS and toxin. And so we decided to do a trial of intrathecobaclofen, and you can see that she's fours before the trial, and then twos after the trial, and now she's on a stable dose. Her stable dose of ITB is 154 mics, so a relatively low dose. And so this is gait speed. So normal gait speed for a 56-year-old woman, for your information, is 1.26 meters per second. You can see she's already half the normal gait speed, you know, and so her gait was actually getting worse right before we implanted the pump, and then we implanted the pump, and we got very excited because all of a sudden, hey, it looks like she's gonna keep getting better, right? And so I wish I could show you that, but unfortunately, she tanked, not tanked, but she, her catheter was implanted at T11, and she was doing great for about two years, and overall about 80% better, but then unfortunately, her Parkinson disease progressed, and she was having more trouble with trunk control, and her ambulation was getting worse and more back pain, and then she basically became non-ambulatory. She was able to take a few steps around the house, so she couldn't even do the six-meter walk anymore, and so she basically fell off the curve, and so we decided to wean down her ITB dose, and because her replacement date was coming up, and she opted to have her pump removed because she felt, because we weaned her down to minimum rate, and she felt like she was able to stand easier, and her sitting balance was improved, and she was still able to just take a few steps with the help from her husband, even though she was more rigid overall, and her speech was worse, and she was still on her toes, she felt better with just the DBS, and opted to have the pump not replaced because she just felt like it wasn't worth it to her, and it's her life and not our life, but anyway, that's the way it goes because the window, the therapeutic window for these patients is pretty narrow for most of these patients, and it's really up to them on what they wanna manage, and how they wanna handle it, so, but anyway, ITB and DBS can be used together in more severe complex movement disorders, and it's pretty much case report sort of situations. It's not for everybody, of course, and it seems to be more common in pediatric patients, but we, not to say that it can't be used in other conditions potentially, but that's for further study. So, those are all the references. You can quick jot them down, and that is an art museum in Milwaukee. It's not just about beer and cheese, so. Okay. Have a good time. Thank you. I always appreciate a good Rocky reference. So we had Eye of the Tiger and then we had Porphyria. So we had a werewolf reference too and it's almost Halloween. So I already consider this a success. Understandably some of our speakers may have to leave and that's fine, but I will stay and take questions and you can stay as long as you're able pending your other commitments. There's a microphone in the front here. Oh, and there's one in the middle too. Hi, my name is Dr. Cole. I'm from Northern Michigan. One thing I've noticed at this conference is quite a few people are circling back to using phenol for spasticity. I didn't get a lot of experience with that. And I'm just wondering if you guys experience a significant amount of weakness when you use it with patients or how you avoid that. So why don't I let Dr. Mulhern take that answer. Oh, well, I grew up with phenol. That's the first thing that was available when I was a fellow. And so if it's done, I would encourage you to use diagnostic blocks. But it's better to start with lower doses and try to block more motor nerves and avoid mixed nerves as much as possible But you can avoid that excess of weakness and it's really like I always look at phenols like a cannon So I've got a fair number of patients that get pumps phenol and neurotoxin injections all the trifecta and so Just because a phenol is a great drug for the I always think of it more for the bigger proximal muscles And you can do it without making them too weak, but you have to be careful. That would have been the happy meal the happy meal I'm wondering if dr. Mulhern could touch on her technique and how she avoids weakness I think he kind of touched on it. You do more of the motor branch blocks Using the transcutaneous nerve stimulator. That's what we'll always go back in We usually start like if we're doing the biceps We'll start to with one or two points and see if we can eliminate The spasticity and we'll try to have them move the arm if they were previously had any volitional function Same thing with the quadriceps We'll have them raise their leg up or even stand up and see if they feel like their knees buckling if the spasticity is still Impairing them then we can go back in and do a couple more branches or if Everything has resolved and you can we stop it as few branches as we can and we always do Diagnostics to to set patient expectations. That's like we've had a couple people who decided not to proceed based upon the blocks And so what she's talking about is not doing whole nerves doing motor branches dr. Alfaro interesting Selection of cases one of the most difficult things that I've had to treat with is the dystonia Whether it be the dystonia for patients who have had for example a stroke or a TBI upper motor neuron lesion they have spasticity for me It's relatively easy to treat the spasticity but a number of them then develop a dystonia Boy, that's a bear to treat. I've done phenol nerve blocks Sometimes it works Sometimes it doesn't I've not had a lot of success with the ITB pumps Mike do you find adding any of your other? clonidine or anything going to help and Boy with the Parkinson patients Have you had any experience with the I know there are a few studies with botulinum toxin Mixed results. How about with phenol for the Parkinson patients? so the both of you share your Difficulty with the dystonic patients, I would say the best dystonia Category that gets treated with intrathecal baclofen is the dystonia related to CRPS those respond relatively well to intrathecal baclofen often as adaline therapy, but The dystonic CP patients the dystonic brain injury patients some respond really well Others don't and I think it It represents the heterogeneous heterogeneous nature of what dystonia is And on that I've been burned because we did a trial They did great under the trial. We put the pump in boy. They just did not do well. How do you explain that? Well, you know, it's a great question about Why is there even a correlation between the trial? You know, there's a number of different Factors there you typically inject 50 micrograms in one CC with the force of your hand and Even at the maximal flow rate of the pump that is seven orders of magnitude more velocity When you do a LP injection then with chronic delivery Is there something about the mixing of drug the concentration of delivery that affects the patient's response to it? You know sometimes when I think about it Like how does it even work to begin with you know that you you were able to inject such a dilute? Solution so quickly that you'll almost always get good carryover. There are exceptions like you mentioned I think it's one of those situations that is at a concentration Flow velocity component that doesn't carry over from trial on to Permanent delivery. I've all you know defer to doctors tumor and McGuire if they have a different opinion about that use them on lower concentrations and giving them bigger boluses, just to increase that flow rate. And sometimes that works. And so they may have to come in more frequently to get refills, but sometimes you go up on the dose and you change it to a 2,000 concentration, and that really dilutes it out, and it doesn't work as good. And you think, well, why aren't they, why isn't that working? It's because, like you say, that 50 might work great, but you have to sort of do it We have three intraventricular patients right now who all happen to be dystonic CP patients, but they're not intraventricular because of their dystonias. They're intraventricular because their spines are a mess. They're all, they are like arachnoiditis city, and the only place that we have free-flowing CSP. it was there. Question from the back. Hi. My name is Melissa. I'm a Pediatric Rehab Doctor at Children's National in D.C. This was an incredible talk. Thank you so much for doing this. My first question is about phenol and specifically dosing. Whether you're using a 5% or a 6%, will that affect how much volume you put in? And more generally, like, what volumes are... I've been pretty impressed by the variety I've seen among different practitioners. Some will use, like, you know, 0.3, 0.4, and some will use, like, 1 mL, 2 mLs. It just seems like there's a lot of variability. I was wondering if you could comment on that. So we get our phenol compounded, and we use 6%. The percentage can affect how much volume you're going to use, but if you use the same percentage, that's how you're going to base your volumes. And because we do the motor nerve branches, we are those people that you only use 0.25 cc's at each site, but like you said, there are those that are targeting more of the musculocutaneous, like the full nerve. There's some as low as, like, 2 cc's, and some as high as I've heard. So basically a quarter cc, a quarter cc per site and you're done? Yeah. 0.25 cc's at each motor nerve branch that we do. When you get the desired effectiveness, then you're done. Yep. Yep. And so we probably never use more than a total of like three to four, or actually no, like two cc's in an injection. Dr. Mullen brings up a really important point. Dr. McGuire and I are the old heads at this end of the table. It used to be that there was this big bottle of phenol that you just kept in clinic and drew out of it and injected into it. You can't do that anymore. There was concerns about microbial growth. God, if there's a microbe that's growing in phenol, the world as we know it, it's done. So you do have to use a compounding pharmacy to do it, which can be challenging in certain situations. The limit of solubility in water is about six and a half percent at room temperature. You stored it in a, like some people will put it in a refrigerator, but you're five percent. Six. You're six percent. You know, you have to worry a little bit about, if you, if there are people who use 10% and if you put a 10% solution in a refrigerator, you're probably going to precipitate out. But I share Dr. Mulhern's, in the anesthesia world, if you're doing it for like neurolytic celiac plexus blocks and stuff, even to a big nerve plexus, less than a half a cc. Wow. Yeah, I'll echo that too. We use six percent also. I mean, you can. The bigger the volume, the more it's gonna spread, so. And phenol doesn't care if you're a nerve, a muscle, a vessel, it doesn't care. It's gonna, the nature's proteins are just gonna dissolve everything in its path. And so, which is always like when we're learning, they say, well, if they've got dysesthesia, just inject a bigger dose. And I go, that's pretty hard to convince them that I'm gonna do the same thing again. My arm's on fire. Question from the back. Oh, can I go again? Can I ask another question? For folks who are using botulinum toxins, if you're injecting someone who has an upper motor neuron issue due to an autoimmune process, like a CNS autoimmune issue, do you worry about giving them a foreign protein load? Is that something that crosses your mind? I've not seen it. I haven't worried about it. If others wanna comment. Yeah, exactly, if you wanna. In theory, based upon that, if you do have a lower motor neuron load, I've obviously had the least experience, but haven't seen that. Has anyone injected like a stiff person syndrome with toxin, or? I have not, I mean, yeah, I mean, we have a couple of pump patients with stiff person syndrome that do fine on pumps, but I've never, that's a good point, I never thought about that. Yeah, that, where I practice, we have a white matter disorders clinic for kids with leukodystrophy, and you know, folks who have A-cardi-Gutierrez syndrome, it's a genetic problem, but there's thought to be a CNS autoimmune component to it, and families that are active in like the Facebook, and kind of the, you know, the patient community groups reported back in the 90s when Botox was like a less purified product, it had like a higher protein load that those kids would have flares of disease after their Botox, and so even to this day, we have a lot of our AGS families will say like, get away from me, don't offer me Botox, I'm not going to do it, so just curious how that applies to other, you know. Well, thank you all for your attention.

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