Urodynamics - Case Discussion

Mm, these will be cases that are probably gonna comment more on sort of formal invasive urodynamics, rather than, uh, sort of the non-invasive, uh, variety here. All right. So, uh, this is a lovely six year old red-headed girl who, uh, presented to an outside hospital, basically acute, uh, lower bilateral paraplegia. Um, at the same time, she had loss of bowel and bladder continence. Um, upon admission to the hospital, they had given her a diagnosis of basically, uh, Guillain-Barre. They had started her on a course of some plasmapheresis. Um, interestingly, that seemed to, um, occur prior to some type of imaging, as much as I've dug into the chart. So, when the imaging was there, um, they ended up finding that there was a spinal cord vascular malformation. So, a little bit of a misdiagnosis of what the cause of her acute change was. And uh the family was kinda not pleased and said, can we come see you? And so, this is her spinal MRI and it had, um, as you see with the arrows, some of these uh central lesions that uh were um diagnosed as, uh, like I said, AVMs. Um, just a general, uh, poll question for our audience. Make sure they're still awake as well as asking you first there, uh, Doctor Yerkes. Um, this patient had their inpatient, uh, care, um, being rendered for a, a little bit of time before they came. Uh, just asking you, what kind of neurologic testing, if any, is below, uh, would you, would you want, uh, if this four-week session? So, and, and she previously was completely neurologically and neurologically normal, is that right? Complete and toilet trains of bowel and bladder, yep, no UTI history. Normal little girl. So I think with the, you know, acute presentation, um, You know, it's, it's routine. We would get an ultrasound on everyone because that's easy, but you're probably not gonna find much on the ultrasound and acute presentation nor on the serum creatinine, um. If she were, let's say, a, a spinal cord injury, I probably would wait a bit longer to get the urodynamics, but I think since we have a little bit of a different situation here with this, uh, vascular lesion and, um, you know, and, uh, an acute presentation with that. I mean, obviously, the vascular lesion didn't just turn up, um, but she just became symptomatic from it. So I, I think this would be a reasonable time to go ahead with her urodynamics, and I probably would get a video study. For this. Well, um, our polling results, somebody can, uh, share with me what we did, but, um, we'll, we'll keep going on and wait for some people to vote. So, the polling results, um, majority of them are saying that they get all three, all of the above. OK. Um, fortunately, um, this patient started to have some improvement in her lower extremity, uh, weakness. Um, she definitely did not return to baseline with her, uh, bladder and bowel incontinence. And that was uh very bothersome to this six year old girl. Um, as you anticipate, her renal ultrasound was stone cold normal. Um, and, uh, given the AVM and its complexity, she had actually kind of started to go to some other centers as well about what was kind of going on. But as, when I became involved, uh, I decided to do a, uh, baseline formal invasive urodynamics. Um, As you can see here, her, uh, systemmetric capacity was 27 mL. Uh, she did have some leakage measured at 27 mL instilled. And as you can see, I would describe this as there was a sustained single sort of tonic contraction. Our EMG leads, uh, as you can see, uh, it's probably compressed. You know, I think Doctor, um, Franco brought up a good point on how some of these graphs are presented to me to interpret or anything, cause if you stretch everything out, or even better, if you're in the room when it's done, uh, you may pick up certain things, cause some of these EMG tracings get compressed. So, to the audience on the slide, it may look completely like there was zero change in the EMG. But, um, At this point, uh, I could see that there was, you know, quite a lot of uh high amplitude measured detrusive contraction there. Doctor Franco, how would you have interpreted this? Oh, it looks like exactly like you said. Um, this is a big high amplitude contraction. Um, definitely, um, You know, you would not expect to see this at 27 mLs in a 6 year old. So, um, something obviously is going on and you have a disinhibited bladder. So, this little girl, like I said, was kinda like, hey, I wanna get better. They, they very much understand that there's a uh neurologic condition that has maybe given them a little improvement with lower muscle, uh, you know, motor function. But where, what would you kind of counsel them on there, Doctor Doherty? Ways to maybe manage this, uh, Your dynamic urinary incontinence picture. Um, so, you said she's still fecally incontinent as well? Uh, I would wonder how much her constipate if, if there is elements of constipation as well that might be exacerbating some of these findings too. Um, but I think depending on what their goals would be, if the goal is try to get back to normal, I would want her likely to be on an anticholinergic, uh, but at the same time, I would like them comfortable with cathing before we'd start to do that more consistently cause I don't like to start anticholinergics without a reliable way to empty the bladder either. Great. Doctor Yerkes, what is your thoughts about the obvious, the effects of the anticholinergic causing uh lower detrusive pressures, but, uh, you know, obviously, we as urologists don't wanna walk around making retention. So, how do you usually uh prescribe anticholinergics in the neurogenic bladder population and you're watching for bladder emptying? So, I'm sorry, in her particular case, did you say, did she leak to completion or did she just leak a small amount? Uh, she leaked with a, there's a residual of 10 mL. OK. Which, you know, given how little she held is, you know, still a decent percentage retained, but, um, and, and what did, was there a video study with it? Uh, not. Oh, there was, OK. Um, so I, you know, you look at high pressures like that, and, and certainly it ought to benefit from anticholinergics. Um, and it's hard to imagine that even if you started like a low dose of, of anticholinergics, I suspect you would see some benefit and not likely go into retention. Uh, however, um, if, if they have high resistance, you just really don't know what's gonna happen. And so, um, I think that you likely could start low with anticholinergics while you're working on intermittent catheterization. Um, but they would need a lot of support with the intermittent catheterization, but you can see, um, here, uh, non-relaxation of the external sphincter, which you mentioned the low amplitude activity, or that it was difficult to see the activity on the EMG, but But it looked like it corresponded with your contraction, or at least the peak of the contraction. This patient for their initial exam had a separate VCGs and separate urodynamics, so they're not performing concomitantly. Yeah, so, I mean this, this is a pretty compelling um cystogram for either fixation or non-relaxation of the external sphincter, whether it's You know, in this acute presentation, neurologically mediated rather than fibrosis of the sphincter, but your radiograph, you know, just tells you that it's narrow. Um, you know, so I obviously you have to proceed cautiously with anticholinergics. I think if you ease into it while you're, um, working on catheterization and work earnestly with them, I think it would be reasonable, um. Just as a side note, before we were a part of, of the umpire protocol where it's, where it's regulated who you give anticholinergics to. I learned from Bill Kaplan a number of years ago, he would give a quote-unquote whiff of Ditropan um to patients who had severely overactive, uh, bladders that were, um, had normal compliance of the bladder just to kind of take the edge off of those contractions and not all of those patients were on intermittent catheterization. So, so a low dose, very reasonable to start. Ryan, uh, one of the questions, uh, that, um, Miky alluded to is the impact of constipation. The question from audience is, uh, do you any of you have a standard protocol before any urodynamic study for a bowel cleanout? Yeah, we clean everybody out, um, so, you know, pick your clean out, whether it's gonna be a peristine or uh fleet's enema or Dulcolax or Dulcolaxapod. Everybody gets to clean out whether they're neurogenic or non-neurogenic. OK. Go, Brian, can you go back to the previous, uh, study? I want to point something out. Um, which sort of tells me that this is You know, there's a certain long-standing neurologic, uh, and, and whenever you see, uh, these, uh, these low-level contractions that are present in the abdominal phase of the curve, you're always, the, the likelihood that you're looking at a neurogenic or a neurologic component, it goes up, OK? So, uh, disinhibition, central disinhibition tends to be associated with that, assuming that you don't have somebody that's just full of poop, um, and, but, so if you clean somebody out and you're seeing, uh, uninhibited abdominal contractions or, or contractions in the abdominal phase, Um, you can almost bet that you're dealing with some type of neuro neurologic problem, OK? And so, uh, and usually it's gonna be, uh, upper motor neuron, uh, related, um, so, yeah. OK. So, um, I'll, I'll, I think we kinda start to get around this and, uh, what, what would we kinda do, I think, um, Doctor Defour, uh, my other partner in crime, what do you, um, What, what, uh, where would you go from here? As I said, this bothersome urinary incontinence, that's cystographic findings, and the urodynamics. Yeah, so, um, so typically I would, I would make sure the family was pretty comfortable with the catheter program before ramping up the anticholinergic. The cystogram here looks more chronic than sort of acute. I mean, the, the bladder was pretty trabeculated. There was already looked like dilating reflux on the left, um, with some dysynergia there with the sphincter. So I, I'm not sure exactly what the time frame was between the acute presentation and The, uh, when this test was obtained. But it does have that sort of neurogenic bladder appearance thinking at some point she's probably gonna need CIC to be continent. So, I would, you know, I, I definitely would, would, uh, have the family comfortable with it. Whether or not you could maybe ease up on an anticholinergic just to kind of Help with the symptoms and then check PVRs pretty carefully, um, as you did that to see if she was retaining. Uh, I don't know how far away she lived from our institution. Sometimes that sort of prohibits that side, that kind of intensive management. But I don't think that's unreasonable. If she's able to empty and you're basically trying to treat the symptoms and her upper tracts aren't being Damaged by the reflux and or recurrent UTIs, then you could sort of easy does it and kind of ease into it, um, and sort of have the CIC in your back pocket, uh, to start if you saw upper tract changes or, um, you know, damage to that kidney. OK. Um, I just wanted to point out to the audience because it's always so hard, I think, depending upon what device you're looking at. There's a little wisp of some, uh, left-sided, uh, reflux here. It was non-dilating, but, uh, Not surprising given some of those pressures we saw. Um, so, um, I took your guys' advice. We had a long conversation because this beautiful little girl was peeing and, you know, continent, and now she's, she's, she herself is very unhappy. Um, they were hesitant about anticholinergics. I mean, there's still, uh, to answer your question, Doctor Delore, the time frame from her diagnosis, uh, or presentation with the paraplegia and that urodynamics was probably no longer than 4 to 6 months. So, obviously, something was going on before the acute presentation of paraplegia. But, uh, they were hesitant about anticholinergics. Um, They kind of said, hey, let's just see what this is. We can add it on, do all this. I didn't put her on any antibiotic prophylaxis. She's, had never had a, a UTI, um, I think we would all agree that anticholinergics, uh, I mean, a catheterization program alone was not going to change this pattern. Uh, she needed some type of pharmacologic intervention. I put this on, not to tell everybody, uh, oh, you can get them better. But just, uh, sometimes we've all been there with the families may need to, um, Either they go to a different doctor and they're gonna tell them what they want to hear, or sometimes you repeat the study so that they'll all know this is a really bad bladder and I'm sorry, it's gonna need a lot. But, um, once again, we can kind of see exactly what we saw in the first kind of urodynamics for the subsequent slides. It will be the preceding one is in the bottom left. It's once again, another one of these high pressure, uninhibited detrusive contractions. And uh so, Basically, we talked about an oral anticholinergic for her. But, uh, Doctor Franco, what's your preferred medication for managing neurogenic detrusor overactivity? So, I'm going to um Sort of come in completely different with nothing that's on your list, OK. And it's, it's I would have put that girl on Hytrin, OK? And um the reason is, is that when uh we were doing the um The Uroxatral, uh, clinical trial. What we found was that, uh, even though the, the, the data never made it to, to the FDA, um, that bladder pressures were markedly reduced using alpha-blockers, and there's plenty of data. In, in the uh experimental literature that it does, and I've been using it ever since that study and uh I killed two birds with one stone. I can reduce bladder pressures and I could, in her case, have reduced outlet resistance, um, and in that, uh, posterior in that whole urethral complex, OK. It, there. Both males and females, the whole urethral complex is, does have alpha receptors in it. And I can lower her outlet resistance because that's why she has this uh reflux and that's why she has a thick walled bladder. Um, and In some cases, I'll add an anticholinergic to the regimen, OK? So at the same time, I can reduce the pressure and then allow them to empty better. You may or may not be able to get away with, without CIC in this situation. Um, but if we were looking to vie to completely paralyze the bladder, then I would, uh, the next step would either be, you know, jack up the oxybutynin as high as we can or, or go to solafenesin. Uh, Mira Begran, we've had fantastic results. In, uh, getting some kids whose bladders were on the verge of being pickled, uh, to hold enough urine. So, you know, uh, I don't think it matters what anti, I, I'm not a big fan of, uh, tolteridine because I think it's the weakest of all the anticholinergics, um, so, uh, oral Ditropan is probably the, the best. Uh, but we've had great success with Miror Begron. So, just for the, uh, fellows out there, uh, Mirab Begron is gonna require a, um, prior authorization because most third party payers, especially, um, governmental insurers, are not gonna pay for that upfront. They usually have to fail two other anticholinergics before at least the ones that we deal with will allow that. Yeah, it's the same thing. So you put him on, I put him on oxybutynin, Hytrin, and this girl, I keep her on oxybutynin, Hytrin. Doctor Yerkes, what's the maximum dose you'll push on uh uh with the Ditropan? Milligrams per kilo. Oh, like, usually 0.2 per kilo, 0.2, 3 times a day, 3 times a day, yeah, and I mean if there were a child who was a little bit older, you know, 5 TID, but also, you know, we would use the Xcel in that pop in that setting, so 10 BP or have you got higher. Uh, we've gone up as high as 30 of XL. Yup, I have. So, can I, uh, take the, uh, prerogative of harnessing this brain power in that many of my young patients that cannot swallow pills are on a, say, 2 mL oral solution 3 times a day. So, if you add that all up, I guess there's 6 mg of Oxybutynin that's going in the patient on a daily basis. How do you, Doctor Yerkes, convert a TID oral solution to a once a day XL formulation that only comes in 3, values, 5, 10, or 15. Uh, it's, there's nothing scientific about how I did. I was on 5. If they're on 5 TID, I, I go to 11th. If they're a much older child, like, let's say a teen, and I was gonna switch them at that point, I would probably go to 15 1st. Got you. What about you, Doctor Franco? Was there some magic, uh, conversion formula? You were the formula guy. Is it on that giant erase board behind you? In, in, in this, it's usually gut, um, you know. First of all, uh, the big problem with, uh, the XL is, is it can't be chewed, it can't be broken up. Uh, so it usually makes my problem easier because the most six year olds aren't swallowing pills, but the ones who do, if I had that patient, I'd say, I, I would probably go with a 5 XL, see what the response was, and possibly even 10 of the XL, um, in, in this, in this girl, um, and go from there. Um, whatever my total dose would be, uh, I would probably just take that and either use 5, 10, or 15. OK. I know one thing about the Excel formulation for our international colleagues is that, uh, the Xcel is the extended release formulation of Ditropan or oxybutynin, and the pill itself doesn't dissolve the medicines inside. So sometimes the families will bring you the pill saying it's not working and tell them that's OK. That's how it's supposed to work. Can, can I ask a question about Mirra Beran? Cause we, we really have not used it much. What, um, what instructions do you give the family or what conversation do you have with their primary care provider regarding, um, hemodynamic follow-up? Like just, just yearly blood pressure screens or do you have them see cardiology? Do you, do nothing? Premier background, yeah, typically nothing, no, nothing, nothing, nothing, not a, not a word at all. No, but, you know, we haven't checked the BP after they start the medication. If it's normal, that's it. Yeah, I've, um, I think maybe uh some of the members in the audience or on the panel were, uh, asked to participate in that, uh, I think it was Estela, right? That's who makes, uh, Mirabere. Yeah. That they tried to do a pediatric and it went nowhere. But by the same token, some of those pilot data in Europe showed a very low incidence, but we're talking sample size of like 9, 10 kids. But I tell them that in the adults that, you know, there's that, uh, reported adverse effect of hypertension or tachycardia. Um, I personally have not had a tremendous amount of um experience prescribing it. Uh, but when we do, I do kind of, that's probably one of my Only times I'm really looking at blood pressure last visit to this visit, which sounds terrible as a urologist if you're supposed to be screening for hypertension, but, um, uh, but I have not experienced any of the hemodynamic consequences from that. Got it. Thank you. So then back to the question about the alpha blocker. Sorry, go ahead, Mickey, go ahead. Um, for the alpha blockers, I mean, what dosing do you use for this, for this purpose of your starting if you're trying to help the bladder relaxation in the outlet too? Do you have a different starting dose or is it the same as you would for anything else? Oh, yeah, it's pretty much the same, but, uh, in a 6 year old, I'd probably start at 2 mg and push it up to at least 4. Um, and you're using, uh, doxazosin, Cardura, or I'm using terazosin, terazosin, so the dosing ends up being the same thing for oxy, uh, for terazosin and doxazosin. Um, Izzy, why not Flomax? It's, uh, it's easy to use. You can open the capsule, um, less human dynamic side effects. Well, the, the, the thing is this, right? So we want to capture alpha-1D activity. Um, we want to get the, that alpha-1D activity which leads to bladder suppression and reduction of bladder overactivity. And, um, you get that with terazosin, you don't get that with Flomax. You actually get it with alfuzosin. OK, um, because alfuzosin has more alpha 1D activity and less alpha-1A activity than Flomax. Flomax is more alpha 1A and then Rapaflo is the highest alpha 1A with the least amount of alpha-1D. That's why you have the least side effects with Rapaflo, um, OK, Systemic side effects, and it has the best. Effect at opening the bladder neck, the Rapaflo. So when I wanna take care of and lower pressures in my uh spina bifida kids, in my neurogenic patients, and I, first I put them on um uh Ditropan, and then if I don't see what I want, uh, they all go on Hytrin and we've had very good success in reducing. Now, the one downside to that is They can start to leak on you, you know, the ones that are dry, and then if they start leaking on you because they're dry, a lot of them don't wanna be wet, so you gotta back off on the Hytrin and you gotta find something else, and that's when I'll go to Mirraberon or Botox to uh final, finally drop their pressures. But you would be amazed at how well the alpha-blockers work at dropping pressures in kids who have neurogenic bladders. And uh with your example right there, Izzy, of that uh neurogenic bladder patient, uh, if you said 100 of those theoretical patients, how many of them are in a catheterization program? Uh, if they're my patients, about 100 of them are. OK. I just didn't know if not, it's 99 out of 100. I'm, I'm a disciple of Bill Kaplan, so, uh, everybody was on CIC. So, as you can see here, um, with the repeat exam, uh so, urodynamics #2 for this presentation, bottom left, like I said, that'll be, I'm gonna show you the preceding one that was without the oxybutynin. The larger one is with it. Uh, there was a, uh, improvement in the system metric capacity. The reflux, uh, was present at 75 mL instilled. And, uh, as we can kind of see, this was with a quite an elevated detrusive pressure, and the max detrusive pressure was 75. Um, so, some improvement in at least the early filling phase. Um, I'm gonna jump ahead here. Uh, catheterizations were occurring 5 times a day. Actually, the patient started to recover some, um, sensory of this, uh, urinate, but not very consistently. Uh, the frequency of daytime urinary incontinence decreased with the Ditropan, but still there, uh, half the time. Wasn't very, um, happy with, as all of our patients, 100% dryness, especially when you were toilet trained before. Um, we ramped up the Ditropan as, as high as she could kind of tolerate. Um, remember I told you her sort of peculiar AV malformation. She went to an outside hospital, seen by a neurosurgeon. Uh, they actually also designated, uh, diagnosed her with a distal tethered cord from this. She underwent spinal cord detethering, planned to have basically a repeat urodynamics after the tethering. I won't go into this, but she's also seen by another pediatric urologist, by their local neurosurgeon who had, um, Still showed left grade 2. Kind of a similar picture to what I showed you. Uh, because of the difference in, uh, I should say, the non-resolution with the Ditropan, that outside urologist had changed her, uh, from oxybutynin to tolteridine. And then she ends up kinda coming back, uh, in our house. So, what I'm gonna show you is, now we're a year out. Uh, you kind of might have stole my thunder here, Doctor Franco, and my own personal experience has been kind of similar to this. Tolteridine might give my patients less adverse effects, but it definitely makes the urodynamics less effective. So, um, Here, once again, uh, this is a urodynamics on the Ditropan, where the overactivity was seen around 60 mL and, and as we can kind of see on this, uh, Y axis, around 40 mL, we're starting to see this. Uh, interestingly, there was no reflux on this, uh, exam, but basically, I think we can all see that the compliance of the bladder was, uh, less on this study on tolteridine versus oxybutynin. Doctor Yerkes, have you seen some of the same, um, urodynamic profiles in the same patient with one anticholinergic versus the other? I'm also not a huge fan of tolteridine. Um, I will say that our, you know, our consumers, the, the parents and secondary the patients are, seem much more fearful of anticholinergic therapy. I mean, they read the internet, they talk to each other. Um, it's not as easy to get them to accept Ditropan. Not, not every patient, but the ones who, who push back a little bit, it's harder to get them to accept it. But, um, so I have like a minimal handful of people on tolterodine. I was not the outside urologist in this case. And, um, Uh, yeah, I mean, I, I think Ditropan is just superior. We, we use intra I don't know if I'm stealing your thunder again. We use oxybutynin a fair amount, but you have to obviously have a certain, um, you have to reach a certain threshold of storage volume before you could be putting an intravescal medicine in and expect it to work. So we may ramp them up on, um, on oral Ditropan, and then if we're still not, we wanna be adding intravesicle to it is Is not the way to push the dose or using it as primary therapy if they have symptoms. Yup. Um, Doctor Deford, what's your been your experience with intravesical oxybutynin? Um, do you use it as an adjunct, a substitute? Sorry, the mailman came and my uh dog is going crazy. So, um, I hear a lot of barking in the background. I, I apologize, man. So, I'm sorry, ask the question again, Brian. I was saying, what's been your experience with intravesical uh oxybutynin? Do you use it as a substitute for oral and adjunct? That would be, that would be a 0. I've never done it in 20 years. So, um, I, I, I think we read some studies and learned about it when I was a fellow, and, and, and my mentors never used it. So I have zero experience with it actually. Got it. I've, I've used it more as an adjunct to when oral isn't achieving or in that subset where oral oxybutynin is inducing, uh, Sort of intolerable side effects. Uh, interesting, as you know, that the Chicago group many years ago wrote a paper that's just basically saying a lot of the side effects that patients were experiencing with oral oxybutynin started to be noted with the intravescal oxybutynin as well. So, uh, at least I think I remember Palmer writing that paper. That's before my time. Sorry. You got it. What, uh, the one thing about the intravascular Ditropan is that you have to use a tablet. You can't use the Ditropan liquid. You have to crush up the tablet and put it in the liquid formulation. For some reason, the bioavailability doesn't absorb. Well, plus I'm sure the sugar content is in the liquid is probably great, uh, growth medium for our chronic bacteruria too. Um, where, uh, Doctor Doherty, where would you go now? Um, this girl's not as dry. We've done, you saw the monotherapies. We're not exactly controlling. Where would you go? I would talk to the family about the different options of either adding Myrbetriq to it as an option, uh, in addition to the anticholinergic that she's on, uh, or Botox would be my first things I, I don't normally like doing the double anticholinergic for. I'd rather do the Uh, the Mirabbergon and the anticholinergic or Botox for him. I mean, she's already on a catheter regimen, so I think the Botox makes sense, but at the same time, it's not a good long-acting, it's not a lifelong cure for her either though, but at least it'd be a trial run to see if it would help. Brian, um, before you go on, uh, was she having any sort of worsening upper tract changes or infections, any other clinical deterioration? It's a good point. I did not, uh, uh, annotate that. Fortunately, her renal ultrasounds have been showing up to this date and currently, uh, growth. There's been no increase in, say, hydronephrosis or ureteral dilation. There was one time where there was, and then it kind of, we repeated it on similar and it, and it, uh it went away. So, it's kind of some dilation and went. Uh, there's definitely been some symptomatic, smelly pee kind of hurts that, uh, has instigated the use of a daily prophylactic antibiotic. So I'd love to, you, you, you were the catalyst for a great, um, Question that I want to ask the panelists. When a patient that is on a catheterization program has uh with a neurogenic bladder, has uh vesicoureteral reflux, what would be your indications for starting a prophylactic antibiotic? I'll start with you, Doctor Franco. Well, with reflux, I probably would, uh, and, and this girl especially, you know, you're still in that transition phase, you're trying to figure out if you can get lower her pressures. I'd leave her on suppressive antibiotics. Um, once I know that I've accomplished and gotten to a baseline, um, then in this case, this is what I would have done. I would have done Botox on her, uh, which And if she wasn't gonna get better, I would have reimplanted her at that point, uh, or if I didn't get the volume expansion that I expected to get, um, if I was still waiting to buy my time before, uh, possibly an augment, but, um, You know, you say reimplant before the bladder was stable or after the bladder was stable? As soon as I know that I got the bladder stable, then I would reimplant it, you know, once I had stabilized and the reflux hadn't gone away. Then I would take care of it. The last thing I want is a neurogenic patient having persistent long term, uh, reflux. What's your indications, Elizabeth? I think sometimes the um hard parts of these are, you know, the, say, grade 2 reflux, and there's definitely some neurogenic detrusor overactivity, so we worry and, but obviously, they're not enjoying us selling them an anticholinergic. Now, we say, hey, you want some more meds? Yeah, I, I mean, I would agree with Izzy that, um, I think you have to, to break the family into the new routine and make sure that they're, uh, with the program, compliant with the program, and that we're starting to see some of the results we want. Um, but generally speaking, once I feel like we're in a good place, I would not keep them on any, um, sorry, I would not keep them on antibiotic prophylaxis, uh, even if they still have reflux. So if I had gotten control of the bladder pressures, I'm, I'm not really afraid of reflux as long as we have safe bladder pressures. Um, uh, stop the prophylaxis. Got it. What I'm gonna do here is then let you see once again, kinda, this was our bottom left-hand corner, the urodynamics on the tolteridine. This is our urodynamics 8 weeks after Botox. Uh, the systemmetric capacity. Uh, a little bit, actually smaller. I think this, the previous one was 130. There's still leakage. There's still frequent, uh, high amplitude, uh, detrusor contractures measured. And, um, my question at this point, discussions for everybody. Um, let's talk about Botox. We've got a lot of allergen, uh, investigators. Doctor Defour, um, how do you do? Uh, Botox. Do you spare the trigone? Do you intentionally? Are you an intradetrusive, submucosal? Yeah, so, um, so I, I don't usually inject the trigone, but I, I was involved in the allergen study, so I kind of do it sort of the way that they, um, Uh, recommended sort of, uh, you know, two rows on the back wall of the bladder. Uh, I usually just go right underneath the mucosa. I'd like to see a little bit of a bleb, um, and then maybe just kind of into the detrusor a bit. Um, I've always kind of pushed the dose a little bit. I, I tended to always use 300 international units on everybody. I know the FDA limit was lower. Um, and I think, uh, if I remember correctly, um, some of the early data from the Allergan study showed that you didn't really have to push it that high. So, um, so I think I've backed off now, down to about 200 for, for your older patients. Um, Doctor Franco, um, Trigone sparing, intentional trigone. So, being involved in the Botox study from its inception and involved in the development of the study, um. I'm sure the elegant people will, uh, wanna kill me, uh, for what I say now. Which doesn't, uh, fit. That's why these are great conferences to ask you these questions while you're being recorded. Yeah, I mean, you know, you know me very well. It really doesn't matter, OK? I always say what's on my mind anyway. So, um, the bottom line is, is I believe it, it. Botox works by a sensory mechanism, OK? It's very clear, uh, that it's a sensory medication. It's not working by a motor mechanism. So to inject into the muscle is a complete waste of time, OK? And, um, you're actually getting the minimum effectiveness by injecting into the muscle and the possibility that you're And, and studies that have been done have shown, clearly shown that uh muscular injections actually will tend to go outside the bladder. Um, but, so I inject submucosal. A huge bleb into the trigone, and then as much uh above the The ureterral orifices submucosally as well. So I want to effectively cover the whole floor of the bladder, which is where we know the highest concentration of receptors are in that submucosa that are ace acetylcholine, but remember Botox doesn't work just on acetylcholine. Botox works on. Uh, ATP, OK, and it also works on alpha agonist receptors as well. So, its effects, and I could tell you in, in my own controlled studies, I was doing those injections uh back in Westchester and when I came on board, I showed Adam how to do this, and Adam had been injecting some patients who he had very poor results with, um, and switched over to doing it in my way and, uh, the patients actually had much better results. As far as the, um, numbers go, um, I use 300, OK. The original study that was done in adults showed very clearly that there was no difference in efficacy at 200, but there was an increase in duration of effect, OK, which was associated with the 300 dose. That data did not go into the publication. OK, so, uh, this is data that I'm privy to, uh, so that's why I use 300, OK? And I think it extends the length in between my injections in my patients. Uh, so that's, uh, the, the, the, the long and short on Botox injections. Doctor Yerkes, uh, how often do you repeat, uh, if you are, is it one and you're done? Do you say, let's step up to the plate, uh, when, uh, will you offer Botox again if you're getting underwhelming results? Uh, obviously, I told you there was a Change in the urinary incontinence. Um, but obviously, urodynamically, uh, I've showed you a bunch of urodynamics on tolteridine, it's kind of a, a mixed bag. And obviously, we haven't really talked about bladder augmentation, but, uh, would you offer another Botox before jumping to the nuclear option? Uh, yes, I definitely would offer another injection before I would jump to augmentation. Um, just that does seem like a very extreme step. So I have a quest, a question I guess pertinent to this patient is, is, you, she had a tether cord release, but is there any other treatment on the horizon or planned for her AVM or are we just managing her bladder in the setting of what'll be a chronic? Maybe a progressive lesion. Um, the, so she's getting treated at, uh, by Boston Neurosurgery. So, I kind of get some information per mom, uh, cause sometimes, you know, those faxes don't always come through for you to get the, the letters. Um, there is in the future, uh, some form of, uh, treatment, uh, as well as obviously surveying her cause it's just, she's now 7, growing with a tethered cord. But, uh, as far as the, the primary AVM lesion, she hasn't had any type of operative intervention or, or vascular intervention. They're kind of watching. Um, so, uh, do you, um, Sorry, you were also saying about repeating. When, how many have you done? Like, while if the patient's happy and we're kind of going, have you Every 90 days, put you on the schedule kind of deal. So, I think it varies with the clinical scenario. So we, um, you know, you may have a patient who has, you know, really strong neurogenic detrusive activity who, um, you know, leaks with each of those contractions, will have an excellent response to treatment, um, and you can use, as long as you're periodically getting your dynamics, like, you know, not, not after each treatment, you certainly wouldn't be getting them, but you can use their, um, Uh, return of continence or return of incontinence as a, a marker of when to do it. And I, I feel like it's pretty variable for that particular population, how often they would need to be injected, but we have a, a pretty large group of patients that we're working on a publication right now that, that are non-compliant bladders and actually, you know, have, have been able to prolong time to bladder augmentation safely in, in that group. Um, and those kids, I, I pretty much inject them every, every 3 months. OK. How much volume and like what's the concentration of the Botox she makes up, Elizabeth? So, um, so I, I cap out at 200. I do 10 units per kilo up to 200, and it might be that there's a member of the panel who spoke on this a few weeks ago who told. Me a number of years ago that you can't go above 200 because there's no difference in efficacy, um, but it's good to know that, um, that it lasts longer and, uh, it's good to have the inside information, um, and so, so I would do 10 units per kilo up to 200 how much volume. I do, I do 100 units in 1010 10 mL, 10 mLs of injectable saline, and then I usually do 1 cc increments when I put it in. And um I love submucosal. I love to see a good blob. I hearing Izzy and Adam Hiddleman present on um the, uh, injecting the trigon. I'm, I'm a chicken, so I don't put a huge blob, but I've, I've worked myself up to 2 cc's, uh, into the trigone. Um, it bleeds a lot anyone doing this in the office like with, uh, just under local and secure nonsensate. Yeah, I've been doing it in, you know, adolescence and no big deal. They do you use a flexible scope or do you use a rigid scope? Um, some, the, the males I use are flexible and the females, it's, I find that it's much easier for me to inject in the females with a rigid scope, um, you know, and. Sometimes it, the nurses will hold them and Twist them a little bit and, uh, but I, I can do my injections uh in those young girls uh easily with a rigid scope. Um I remember when the, we were doing the allergen study and the defflux needle was unavailable for a short time, we had to use the flexible needle. I didn't like that at all. I didn't like how it punctured the mucosa. I just, I just didn't have the same feel. Uh, I didn't like it. I don't know if that's been your experience. Which flexible needle do you are you using? I don't remember because it's been a few years and we never used it again, um, but, you know, we typically just use the delux needle with an offset scope. When, when it was on backorder, we trialed a couple different flexible ones, but the, the one that I believe is made by Labury, it's blue. It actually injects very nicely. The other one was very flimsy. Yeah, the, the Labore needle works pretty well. Um, it's not, not bad. Yeah, we, we must have had the flimsy one cause we hated it. Yes, well, I, I agree. I agree with Bob. It was terrible. So, in the interest of time, um, I did not go to augmentation. This patient has not been augmented, uh, to date. Um, she is, as I said, she's, she is incontinent between catheterizations, maybe 1 to 2 times a day. Uh, she's preferred to wear a pull-up, but we've talked about transitioning to a pad because the severity of her incontinence, Mom thinks is Her bowels are managed with an oral laxative. Uh, her infections are much improved. Her reflux from the last cystogram, uh, resolved. But, um, this was our initial Botox, uh, urodynamics. And then the second time I did that. So, um, Uh, I agree. At this point, I'm not confident this is gonna be a lifelong plan. But just like you said, Doctor Yerkes, I have, and I think Doctor Defour and Doctor Reddy, lots of patients where we are trying to use this as an alternative to augmentation cystoplasty. Um, and it may delay, uh, obviously, with the Riley group showing 50% of them need another operation within 10 years, if you can. Move that 10 years post augment later and later, possibly minimizing. But I worry about uh Upper track fate with maybe a less effective control of this. So, this would be where your, your dynamics, uh, tool of what is the work of this bladder. Is it just cause I'm looking at this curve, these pressures, it, I, I, I fear that some bladders that I'm using. Historical or traditional measures of urodynamics may not be showing how much this bladder is working. Well, this bladder actually improved dramatically, OK, in comparison to the other bladder, OK. The, if you look at these, um, there's been a marked improvement. You have contractions occurring as early as, uh, at the 40 mL in the smaller one. OK. Even though they're low pressure contractions, they're still contractions. That means this bladder is, you haven't optimized this patient yet, OK? You, you, so even at low volumes, this bladder is still contracting. And you, you've done a better job in this, in this, in the bigger curve because you actually see elimination of the contractions and your volume has increased. So the total work that this bladder is doing is significantly lower. With that, I can tell you that just by looking at the curves. If you applied the program. It would. Um, me, what I would be doing at this point, I'd either be adding, uh, Hytrin or I'd add Mirrabegron and I would continue to Botox this patient. And I've, I, I could show you in other studies that I've had where the multiple Botox injections, the bladder continues to change, uh, Brian, and it, it loosens up. As they've been, they continue to be injected and um, I, I would not declare um a defeat um after just one injection. After 3 injections, I declare defeat, but I, in my study, I, I had all the slides that I could have shown. I have a perfect example of a boy like this who Botox, Ditropan, Mirraberan. I got him now to 300 cc's and low pressures. OK. I got him at 7. OK, and with 120 cc's. I got him up to 300 ccs, which is a, you can, you can live as an adult doing CIC on low pressures with 300 cc bladder. OK, so between Ditropan, Miraberan, and Botox, that's where he's living. Is it feasible? The answer is, is yes. Um, so I, you have more room to work with this patient than you think you have. Well, I, um, at least as far as this, uh, segment of the workshop, I'd like to wrap it up. Thank you, Doctor Yerkes, Doctor Franco, Doctor Defour, Doctor Doherty.