2024 Fetal Care Center Frontiers in Fetal Neurology Day 1 - Hour 1 Q&A

Uh, we have about 5 to 10 minutes for questions, so please, um, put your question into the chat if you have something you wanna ask any of this, uh, last, the presenters from this last hour, and I can start. I have a question for Doctor Benate Tessen. Um, Thank you for presenting the data that is not yet published yet from Children's. I'm wondering if you at all separated the patients with non-isolated congenital aqueductal stenosis into um patients who had additional CNS anomalies. Or only extra CNS anomalies. Because my question would be if there's something about the additional neurologic findings that worsens the outcomes or if it's something more global with the uh fetus. Yeah, no, that's a really good question. So the, um, The complex category was a bucket of any time we saw any other anomaly that fell into that complex category. Many of them had genetic anomalies, so there were, you know, endeloides, uh, you know, trisomy 1318, so on. We had, um, Uh, uh, extracranial findings, uh, and some of the syndromic findings as well. So, ideally, and obviously, so it's a, it's a very, um, heterogeneous group of, of babies, right, that fall in that category. Um, and it is important though, because when we're counseling, um, we tend to combine all of them, the ones who were really isolated, where we're there, we don't really suspect the genetic cause or even postnatally, we don't find something, and the ones who are likely complex in a very broad strokes approach, and perhaps that's not the approach that one should take. So. There, I'm sorry, no. Oh, I was gonna say that there's another set of questions in the chat, um, from Doctor Varela, um, and also Doctor Ford asked the same question, which is what size scopes are being used for the ETVs? I think that's a question for Doctor Scos. Yeah. Uh, the conventional scopes are usually about 6 millimeters in diameter, uh, but I know that, um, uh, Doctor Pierro and especially in these clinical studies are using smaller scopes for these fetal cases. Yeah, so for fetal, obviously it's small and we are using 2 millimeters, so 2.4, 2.4 millimeter scopes. So, actually, the Tor Peralta in humans are using the same scope we are lastly using in the animals. So, it's a 2.4 sharp tip, uh, phytoscope with a telescope. The camera is 1.3. Uh, millimeters is the same as we are using to place balloons in the trachea, uh, for PTO for CDH in fetuses. So, actually, it's the same. It's a very pretty good view, right? Uh, good quality of the image and there is a working channel, so you can pass, uh, any probe, any balloon or any other things or, or CSR, yeah. And Doctor Gonzalez is wondering at what gestational age will we be offering this procedure when we move to phase one studies in humans. That's a very good question. So, still, we don't know, but I ask everything in, in, in fetal as soon as possible, right? In a reasonable time. All right. So, I think with the diagnosis about 2021 weeks, I think just uh do the whole exam genetic uh selection and when you have a really, a good patient candidate, probably 24, 25 weeks will be the best as we do spina bifida, we do any other procedures, right? And try to decompress the brain and let more time in utero just to be uh in a better shape. But obviously, sometimes it's a delayed diagnosis. I think still between 25 and 30 weeks, I think it's a good, uh, it's a good time just to recover a little bit the brain. Sorry. Um, Doctor Pierro, follow-up question. How far, um, do you think into the, do you think this is the trials here will occur within the next year? Hopefully, we are working with Doctor Mangano, OK, yes, to join efforts and, uh, fetal and neurosurgery and also George Scott is very interested in the, in the hydrocephalus and the ATV as you saw before. So I think it's a, it's a collaborative, uh, work, OK. We are working with the FDA. We need an ID just special because it's a risky. Uh, we are not using any drug or leaving any device, but it's a risky procedure, so, it's good to have an ID, all right? And also, uh, IRE, yes, of, of course, yes, to complete all that and start the pilot, uh, uh, for safety and feasibility, hopefully next year. That's the, that's the goal. We'll see. So with that also in mind, um, question for, two questions actually for Doctor Scoach. The first is just the use of acetazolamide. How widely is that being used in this population? And really is, uh, uh, and a second part question is, um, given that the concern You know, is we're doing possibly some damage just shown by data that Doctor Perro presented. Should we try to actually even intervene earlier, understanding that ETV might not be the option in this particular population of congenital aqueductal stenosis, specifically, who are born with severe ventriculomegaly, oftentimes, Should we try to move that needle and just and, and do some kind of intervention even sooner than we are? Yeah. So the first part of the question about acetazolamide, I mean that that was a bullet point on my slide. I didn't really get a chance to talk to you about it too much. It is interesting. There hasn't been a whole lot of renewed interest in that. That was, um, there were some publications in the late 80s and early 90s about doing that. And I would say that it is something that's still used in practice. So best case scenario for a. Solemide, you can reduce the CSF production by about 15%. And so, on a case where you're kind of on the border, uh, and it's a slow progressing case, um, I, I do think that it might allow you to stave things off for another month or two to get you into a better category for, um, for ETV, uh, and I, I think that we have enough. Experience with acetazolamide and the monitoring of the electrolytes that um I think it can be used safely. So I, I am, I am pro cetazolamide or at least pro doing more studies to look at it as a temporizing measure in the right patients. You, you can't go for a patient that's progressing rapidly and expect it to be a game changer. Um, with regards to the The second part of your question, um, as far as, yeah, is earlier always better? I, I, I would argue, I, I don't think it's a linear pattern in the sense that I, I, I think it's very interesting, um, and I think that the primary benefits in, in my mind of what uh Doctor Pierro is talking about might be some of these developmental changes. I mean, again, because of the things we're seeing with um Uh, you know, early ETVs having a high failure rate, you know, I, I think I would expect that a lot of those patients may also experience that. But if we can change the developmental course of, of those patients, maybe it's OK even if they fail. Um, and so I think that's really interesting, but I, I, I have not seen convincing data that earlier is always better in a linear fashion on these newborns that are not showing any signs of rapid progression. Uh, and you saw from that, um, That Rus study where, you know, those type 2 kind of slowly progressive patients that were treated with ETV in a delayed fashion, um, had the same neurologic outcomes as the patients that were shunted, and the shunted patients were typically shunted earlier. Uh, so, um, I, I think you, you gotta make sure you're comparing apples to apples. If you're just continuing to wait on a patient that is showing signs of progression, actively moving along their hydrocephalus, causing more pressure, more damage, um, then, yeah, sooner is, is gonna be better. But, uh, on a stable patient, I, I, I'm not convinced postnatally that, um, it's not, uh, safe and, um, beneficial perhaps even to wait. Yeah, I agree with Doctor Scott in the terms of that a postnatal treatment, probably it's not as important to go earlier or a little bit later because the damage is already done. It's very stable. So, it's very critical when it's a fetus, right? It's a very critical time, then it's a critical time that you can Potentially avoid that pressure and let the brain to develop better, right? And also I am concerned about the closure of the hole, right, because in neonates is described also in fetus, right, but if I can keep the fetus for 67 weeks with that. Without pressure, right? So it's, it's a good thing and even postnatally, you need to do a redo ETV or even put a shunt, but the brain will be better. So the goal is not to fix completely, it's just to contemporize and have a better development of the brain, even if it's temporary as we describe it, yeah. Well, thank you both very much. This was a very, very enlightening and great discussion.