Transcript

- Colleagues and friends, thank you for joining us for another session of the Virtual Operating Room. My name is Aaron Cohen. Our guest today is Dr. Ed Smith, one of my most favorite. Ed is the vice chairman of Pediatric Neurosurgery at Boston Children's Harvard Medical School. He's also the R. Michael Scott Endowed Chair in pediatric neurosurgery. Today he's gonna talk to us about pediatric arteriovenous malformations. AVMs are among my most favorite operations by far. Talking about AVMs in pediatric patients are even more interesting and intriguing for me. There are three elements that I think we're gonna focus on today. Number one is the physiology of children and considerations in preoperative preparation of these patients for undergoing AVM surgery. He's going to talk to us about that, and how can we make sure in pediatric patients with limited blood volume, and other pediatric constellations the patient has to be optimized. Number two really refers to something very critical in surgery, and that's the embryology of pediatric and congenital arteriovenous malformations. Undoubtedly AVMs are not all congenital. They can form de novo, mainly in adults. However, congenital arteriovenous malformations often have the conical shape and originate very frequently from the ventricle. Therefore, to prevent recurrence of the malformations being able to get to the ventricle and really disconnect those choroidal or appendable feeding vessels is paramount to avoid recurrence. Number three is really refers to the recurrence rate of malformations in pediatric patients. As we all know, pediatric AVMs are immature AVMs, in quotation, and immature means that these AVMs could have part of them that are not evident on preoperative angiography, or they can recur later despite a clean postoperative angiogram on a pediatric patient. So all of these really relate to the embryology as well as physiology of a young brain. And Ed, so honored to have you, so much looking forward to learning from you. Please go ahead.

- Well, Aaron, thank you. It's a great honor to be here and you've really done a wonderful job, you know, making this atlas become a really revered repository. I hope I can contribute in some small way and I'm really gonna try to focus today on the key points that differentiate pediatric AVMs from adults. Many of the core surgical principles are similar and I'm going to highlight what I think are some of the differentiating factors for those of you taking care of kids, both in the perioperative assessment, but also with regards to the way the surgery itself technically is done, looking at some key points. And I'm gonna sneak just a little bit of science in at the end because I do think it's relevant to the pediatric population. So with that, again, thank you very much for inviting me to speak with you today about the surgical resection of pediatric AVMs. One of the things, and I realize that some of this may be a little bit of redundancy for the more senior members of the surgical audience, but it is worthwhile looking at the embryology of cerebral vasculature. And everybody knows there's three main components. You have your arteries, your capillaries, and your veins. And as a pediatric neurosurgeon, we look a lot at the embryology of these lesions and when this vasculature becomes abnormal. We look at the venous malformations on the venous side, the telangectasias and cavernous malformations in the capillaries, and then the focus of this talk really the AVMs, and as sort of a subset of that, the vein of Galen malformation which I'll sort of leave separately. But people tend to think of this as an arterial disease because the A is first. And I'm gonna try to make the case that in fact this probably is less an arterial disease than a disease of abnormal embryology, and that's relevant to what we do in the operating room as surgeons with kids. When you think about what an AVM is, again, while it may seem redundant, hopefully some of the later slides will illustrate why I'm talking about this in the pediatric group. There are direct arterial to venous connections with no intervening capillaries and importantly functional neural tissue, by and large, does not reside inside the body of the lesion. And again, that's sort of is an old tenet, but I think there's some embryology that makes that important and that it relates to the way we do the operation as surgeons. Many of these are embryologic, not always, as you heard Aaron say, but what's important is once they're there, they can grow. They will change over time. They dilate their vessels. They will recruit new blood vessels through angiogenesis and vasculogenesis. And these processes are really important in pediatric AVM surgery because as Aaron mentioned, these will come back, they will recur. And as a surgeon it's very important if you can, on the first go to really doing a curative operation, if that is presented to you. It is the most common symptomatic intracranial vascular abnormality in kids. An old autopsy series from decades ago puts it as high as 1.4%. That's probably overestimated in the general population, but symptomatic AVMs are about one in 100,000. Kids represent almost 1/5 of all AVMs. And the overall prevalence is about 0.02% of the pediatric population. Again, almost 20% of these symptomatic AVMs will present before age 15, so it's disproportionately a large amount of AVMs will present in younger kids. And the idea here is probably that some of these guys are presenting themselves as the bad guys that will hemorrhage or become symptomatic early on. So that does sort of tell you as a pediatric neurosurgeon, you may be getting some of the more aggressive AVMs presenting in the younger populations. There's no real sex predilection and risk factors are really hard to come by. There are some genetic forms we're learning. The classic one obviously is HHT, hereditary hemorrhagic telangiectasia. About 35% of of these kids with HHT will have CNS AVMs, but they tend to present a little bit older, sort of in the young adult life. And recent work has suggested that while there are the rare HHT AVMs that need to be treated by neurosurgery, many of these kids will actually get sick from their lung disease before the brain ones will become a problem. So we really have a very heavily weighted focus on the congenital AVMs in our practice. In terms of why they're bad, I don't need to tell this audience, bleeding not good. But in addition to that, a particularly important thing in the pediatric world is this steal phenomenon where in addition to the mass effect of them growing, the flow of the blood will essentially cause ischemia and micro-hemorrhages with gliosis. And this is particularly important in kids because you may have a wonderful neurosurgery operation, you may get a complete cure, but these kids will still have cognitive problems, the neurologic deficits and seizures even after a good resection. So this is something to think about in terms of caring for these kids and in their preoperative assessment. The rate of bleeding is about 4% per year for kids and the mortality rate is about 1% per year. So the other thing that's really important, and we've published this in others, is about one in four kids if they hemorrhage will die from the bleed. So this really sort of gives a heavy weight as a surgeon and in our population here and the senior surgeons as well, that for kids, there is much more of an impetus to be aggressive in treating these, given the natural history than perhaps in the adult population. And again, the adults, I'm not gonna wade into that, there's some great reasons to treat those as well, but I think it's a particularly important entity to treat in kids when it's found. The re-bleeding rate is about 6% for the first six months and 3% per year after. So these are bad things if you find them, and they're particularly bad in kids. So how do you treat 'em? Well, same things that you talk about in adults, you talk about in kids: surgery, radiation, embolization. And I know there's been a lot of back and forth about does embolization alone serve as a treatment? I'm gonna show some evidence that suggested in kids, except for some extremely rare cases, embo alone is probably not a good idea. And then in some cases, observation might be the least risky option. So that brings us as surgeons, our question is, you know, is surgery really a good idea? And even as a fairly senior surgeon, this comes up as something to debate quite a bit. And one of the biggest problems with debate recently a number of years ago, is this ARUBA trial, the Randomized Trial of Unruptured Brain AVMs. And at least my neurology colleagues pushed back pretty hard. They say, look, you've got an intact kid, you found this AVM, why are you going to treat it? And we published an analysis of this in "Lancet" a number of years ago. And as you can see here from this table, what's important to understand is that many of the kids that were in the ARUBA trial were often treated with embolization alone or sometimes embolization or radiation, very different than what we did in the United States. And these included Spetzler one and two AVMs fairly low risk AVMs, that were just treated with embolization. Why that's important is because those kids that were treated with this sort of methodology that is not, at least standard in North America, in our practices, the result as it seemed that the treatments in those cases were worse than the disease. It tripled the bleeding rate, it tripled, almost, or quadrupled the hemorrhage rate. And the fact is that type of treatment made things worse than the natural history. In contrast, if you had surgery, the way we would normally do it in North America, you had roughly equal risk rates to the natural history, but the added benefit that you get rid of this AVM, which reduces their bleed rate in the future. So I think that ARUBA, at least for kids, can pretty strongly be refuted. And I really mention this because we've gotten a lot of pushback from our neurology colleagues and I think there's evidence now to support that surgery is the right thing to do for kids in the proper cases, and this is the evidence to cite. Which kids get surgery? This is something again that's very, very important in the pediatric population and maybe a little different than adults. We've had our experience we've published here. The bullet points even amongst the most senior members are obviously if they're symptomatic, whether or not they've had hemorrhage, or localizing symptoms. I've mentioned already the numbers that support a much more aggressive surgical approach, I believe, and I think others do as well, that the younger age helps to justify aggressive treatment in these kids with surgery. Just for review, you know, the Spetzler-Martin grade in terms of size, venous drainage, and eloquence, those are all things to take into consideration. And certainly Spetzler-Martin one through threes are almost always surgical cases, generally speaking. And then there's the lot in young adjuncts with age, bleeding, and compactness as well. So by and large, if you have an AVM in a kid and it's a relatively low Spetzler-Martin grade, our recommendation and I believe the American Heart Association Guidelines, Stroke Association Guidelines for kids would support surgical intervention. So this is a population that's unique and I think very much helped by this. How do we work the kids up? Again, this is a little different in kids. If the kids, you know, they have their typical symptoms, usually headache or seizure, we try to get an MRI/MRA and catheter angiograms are very important in kids. We understand the anatomy and the flow and this is where high volume centers can be helpful. Clearly with a a hemorrhage we think about a CTA right off the bat. And I do emphasize with our team, we try to get a non-contrast CT before the CTA. It only takes usually an additional 30 seconds to a minute. And then if you have the history of multiple AVMs, we think about genetic screening for HHT and then RASA1 mutations are common if you have spinal AVMs or cavernous malformations in addition to the AVM. This is important because you might have other vascular lesions in the body and some of the mutations are associated with coagulopathies. And again, this is different in kids, but when you talk about surgery, you know, getting in to do the craniotomy is only half the battle. And if you go into that and you don't know if this person has other vascular lesions elsewhere, if they have a bleeding disorder, you really could get in over your head, especially in a small kid with a low blood volume. In terms of imaging, I think everybody knows this, the size, location, orientation of the nidus, the feeding vessels, whether there's stenosis. And if there is outflow stenosis, we will often not delay surgery, although sometimes if there is a bleed we try to wait a little bit to let the clot go down. And then the orientation of the clot versus the lesion. So if you have a kid ready for surgery, what happens next? This is again a very busy slide, but we have a very rigorous management protocol for AVMs. And these are some of the key things before surgery that I think make it a lot safer and differentiate this population from adults. We are fairly aggressive in the use of embolization and we try to do this with the kids sedated and not intubated after the embolization. They're asleep for the embo but then post embolization we will keep them overnight in the ICU. We really try to keep the blood pressure a little bit lower than baseline. Reperfusion or hyperperfusion is a problem in these kids. Following removal, when we do the craniotomy, we will get angiography either if we have a hybrid room, in our hybrid room or if they have to, they they go asleep to the angio suite and then we make sure that the AVM is completely gone with catheter angiography, the time of surgery, not the next day, not a week later, but that actual same anesthetic. And then we get a one year angiogram and then an annual MRI/MRA. So this is our example of our sort of hybrid intra-op angio where we had this, you know, a splenial AVM. I thought it was a big shot and had it all out, and this is an example here where you can see that there was, on the second so called intra-op angio, there was definitely some residual there. And this allowed me to go back and make sure we had a complete resection before we woke the child up. Had we not done this, this probably would've been left behind. And this is really important in kids. It begs the question, if you're gonna adopt this practice in a pediatric group where you have longer anesthesia, intraoperatively you're getting angiograms, maybe the results are nice but is it really necessary to do this? This is where kids are different than adults. The gradual reduction in AVM flow for particularly larger AVMs in kids where you do the embolization a day or two before and then the surgery, we think reduces the perfusion breakthrough hemorrhage risk. Really importantly, multiple papers have suggested there's up to a 24% likelihood of residual or recurrent AVM if you do not use perioperative angiography. So you take the AVM out, you know myself, I thought it was a big time surgeon, and yet many, many times prior to instituting this protocol, there would be leftover AVM 'cause we did not see it at the time of surgery, particularly if there was a hemorrhage that the child presented with. And that can obscure being able to see the full extent of the AVM. And this means that getting a good angiogram, not just any angiogram, but a high quality one can really help us to reduce that risk of residual AVM intraoperatively. How do we actually operate? So this is a little video here, which hopefully we can start up, and there are a couple of, I think, key points that we, you know, try to do in AVM surgery in kids. Diagnostic imaging, I mentioned. The urgency of the operation. This is something where if you have a big clot you have to go immediately. We tend to use the ultrasound with the doppler to find where the AVM is and take the clot out first. Having an MRI if we can for stealth is helpful. You may not be able to get a catheter angiogram in an emergency, but otherwise if you have an elective case you can. We do tend to wait several weeks after a hemorrhage if the child is stable to let the swelling go down, get better understanding of the feeding arteries. We call the team beforehand for kids having blood in the room. Getting everything pre-draped is so important for vascular cases. We have a routine set up and having everything ready before the case starts, including good micro dissection tools, I think is really, really important. Big craniotomies, you know, you can compromise on love, but you can't compromise on exposure, particularly with AVM surgery. And I think that these are one of the rare cases against microsurgery where you really wanna see everything. ICG can be helpful for a superficial AVM. It doesn't help for deep stuff. But it gives you a sense of where the feeding vessels might be, the time and the flow. And then the key thing under the microscope is, as everyone knows, feeders first, really working in an ice cream cone type approach just outside the AVM. As you know, if you get bleeding in the AVM, it's very hard to cauterize. These vessels are not fully loaded with the normal proteins. They will not cauterize well on the edge. You'll see here under the scope, as long as you stay on the boundary, they sort of cauterize well. At the end, if you have a superficial lesion, an ICG dye can be helpful. You can see that the, hopefully the big draining vein there has stopped. And then obviously you divide the draining veins last, same principles as in adults. I would highlight here sort of the circular or the wedge-shaped approach. And this is important later. I make my favorite tumor here, the pattyoma, but having a patty all the way around, making sure that the craniotomy is closed well at the end with a little piece of gel foam over the top. But make sure the brain isn't swelling or having other signs during the surgery that might suggest you've left something behind or something has been missed. And critical to this approach, and particularly when you think you're all done, I will talk in a moment about the importance of really understanding the anatomy, making sure that your preoperative imaging is the best it can be because in kids you may leave some behind. This perioperative imaging is so important and I think we can end the video here and get back to the regular slides. But Mike Scott, my mentor, really taught me some very key principles, whether you're just starting in practice or you're getting to be an old geezer like me. Everybody knows with AVMs feeders are first, right? You really have to obliterate the feeding arteries whether you use clips or bipolars. We tend to use bipolars and not leaving clips behind in kids many times, particularly with the smaller cranis. We like to have the working space around, but either are fine. The idea of what's called an ice cream cone or a water slide. One of the problems, even myself, as I've done a number of these, you tend to get excited and follow the depth of the AVM. And I mentioned earlier that many of these AVMs are wedge or cone shaped. And the problem is you'll get on one side, you've got a good plane, you're moving along, but the problem is you then get in deep hole. If you get into bleeding and you don't have good exposure, you get in real trouble. So the idea as I tried to show a little bit in the video there, is you really stay circumferentially around this, like a water slide circling around and around or an ice cream cone to retain an even depth of resection surgically around the lesion to avoid getting in a hole and to minimize retraction on the draining vessels during the dissection. This is a really critical part of the case and particularly for moving along, putting patties in, I find, you know, Sepideh Hanjani was one of my sort of senior mentors at Mass General for a while. She made the pattyoma the Irish tumor. These are things that are just so important, I think, for not losing ground as you go along these complex cases, especially if they bleed. I've had other mentors tell me that, apparently they think my surgery's like a traffic accident. The idea of being a helicopter over a traffic accident repeatedly inspecting the surrounding brain, not just where you're conned in on working for swelling or bleeding can be so important for poorly placed retractors or clips. And then don't dive in. If you do get a hemorrhage many, many times, especially in kids, you can control the bleeding simply by putting a patty and some gel foam on it rather than getting into the body of the nidus and aggressively coagulating where you may get yourself in a much bigger problem than you might've had if you simply tried to tamponade it off and then work around to disconnect the feeders first. So these are some very important principles, whether you're just starting out or you've done a whole bunch of these. And I think keeping these in mind for pediatric AVM surgery technically is a really important set of principles. The last thing here, which is so important is how do you finish? And this is a great article by Cormack Maher, who's now out at Stanford and my mentor Mike, Dr. Scott, where they made this observation as clinicians and as surgeons like the people watching this video, that many AVMs are long linear vein based AVMs. And you'll notice in this cartoon that the angiogram doesn't show it, but the MRI does. This AVM ends at the ventricle. You see the tip of that AVM is at the ventricle. And why is that important? Well, it's got this wedge shape or this linear shape to it. And when you look at that, I mentioned this picture earlier from the surgical video, the AVM has this like an ice cream cone. As you look at the lower right video, as you start to take this out, the AVM looks a little bit like a cone coming out of the brain. And why is this important, this cone shape? Well if you look at embryology, and this is where I wanna highlight why kids are different than adults. The arterial imaging on the left from the Netter Handbook and the venous imaging on the right show a very different pattern of vasculature. And even though we call these arterial, artery, AVMs, the V part is probably more important. 'Cause if you look at the shape of the nidus, what we're facing as a surgeon when we're under the microscope and operating, this pattern is much more like the venous pattern, not like the arterial pattern. Why does that matter? Well, we think it matters because it affects whether or not we're really done with the case. These types of cases are prone for normal perfusion breakthrough. This can happen in high flow AVMs in kids, so you really want to make sure that you get every last little bit out and you've gradually rolled down the blood pressure in a safe way. And this can be helped by the preoperative embolization that I mentioned with larger AVMs. You don't need to do this with every AVM obviously, but bigger ones, and rigorous blood pressure control. That said, you can have the best control in the world, the best embolization in the world, think you're the hottest surgeon, but if you don't get the entire AVM out, you're gonna lend yourself to being in trouble. And this is where postoperative management's so important. You know, the surgeons have to be in charge of these patients. This is not something you delegate to the ICU or to other teams. I think we really need to have a hand on these kids because their blood pressures are fragile, they have profusion breakthrough concerns, they are complicated kids. And then once you get 'em outta the hospital, the story isn't over. This is a growing kid. They have a higher rate of recurrence than adults as I mentioned earlier, so you gotta get that both perioperative angiogram and then follow-up imaging, usually a six month MRI, a one year catheter angiogram, and then you really need to follow, and there's good papers out from UCSF and from other groups including our own, talking about the need for follow-up that is so important in kids. It's not just what we do in the operating room that day, but it's how you follow them. How can we do better? So this is my very, very brief foray into science. And I know this is an operative video atlas and Aaron's wonderful at curating these, but I do think this is one of the rare times where just a few minutes of science helps to explain why the way we do surgery is different, why it's this need to get down to the ventricle. 'Cause if you don't, and I've done it, you can leave AVM behind, they can bleed, you can get into trouble. So I wanna just take a brief foray into science here to explain how this translational research affects what we do as technical surgeons in the operating room. This is what clinicians see. I showed this before. I mean Dr. Scott is one of the brightest observers of detail in the operating room. All the people on this site, the senior level folks, that Aaron has recruited to talk, other than myself of course, have been such amazing technical surgeons. But part of the reason is not just the ability to execute, but their ability to observe, to identify patterns, and to incorporate that pattern recognition into their surgical technique. And Mike and Cormac did this very well where they identified this linear based approach that ends at the ventricle. And I've spoken to the fact that if you don't get down there in many of these kids, if you don't look for this on your preoperative angiograms, if you don't plan for this in your surgical approach, there is a high risk you may leave things behind and you've got that last, what you think is the last five minutes of the case and then pow, all of a sudden you get some big bleeding down deep, it fills the ventricle, the brain swells up. Some of us have been there, I know I have. And this is the reason I think that we have to be cognizant of this 'cause it affects how we do our surgery. Again, we see this cone-shaped AVM and the reason for that is it's vein based. I showed this picture just before and now I'm gonna talk about the science behind this vein based approach. This is where the clinical observation we make as surgeons can really affect the scientific background and feed to being better surgeons down the road. Why is this observation important? Well, scientists, when we say, boy, this thing kind of looks like a vein, and I've seen that in the operating room, it kinda has that shape of a venous or a linear thing. If I say vein to a surgeon or an interventional radiologist, they'll talk about an angiogram and the shape of the pattern of blood vessels. If I talk about a vein to a scientist, they will think about molecules that develop the blood vessels in the brain. And a big one of those are called axon guidance factors. And I won't go in the weeds too much, I don't have a PhD, but I do talk a little bit of science. And these axon guidance factors are really important. They're proteins, they're secreted so you can measure them. And as a pediatric neurosurgeon taking care of pediatric AVMs in the operating room, this is really important for brain development. These are the things that create the problems that you and I have to fix in the OR. And they usually work in pairs with an antagonist and an agonist. It's kinda like, you know, those of us who are speaking here understanding, you know, what's pushing and what's the brakes and what's the gas? These are some of the canonical proteins. We've talked about the netrins and tumors, I wanna talk about ephrins and vascular malformations. These ephrins, particularly EphrinB2, is this axon guidance factor. I don't wanna get too deep in the weeds, but basically it directs where cells adhese, where they grow, and how they push brain tissue out of the way. So this is a classic example of the EphrinB2 on the cell and the EphrinB4 binding to it. And what does this do? Well it basically tells cells, are you gonna be an artery or you're gonna be a vein? And importantly it also repels neurons out of the way. Well this is exactly what an AVM is. It's a mix of screwy AVM arterial and venous differentiation, that's what an AVM is, and it pushes the brain out of the way, which is exactly what we see at surgery. The AVMs follow this venous anatomy and don't have intervening brain tissue. And this is where the embryology of the science people, you know, the nerds in the science world really influence what we cut in the operating room. And when we understand this, why this observation is important, is because these axon guidance factors may change how we do the surgery. It may be which ones are the bad guys. Are there other treatments we can use? How do we surveil these kids long-term for recurrence, which is a real problem in kids. And what we found is it seems to be a real imbalance in the pediatric AVMs where there's a lot more of this EphrinB2 stuff around than there should be. And without belaboring the science too much, what this seems to do is create an imbalance with this aberrant endothelium. And so again, brief foray in a science, these kids with AVMs that we're treating have too much of this EphrinB2. I mean, does it make sense? And so we looked in the specimens of these kids both in the pathology and in the urine. And I know I'm not supposed to be using urine, it's wrong into the body for a neurosurgeon, but it's actually helpful. And what we found is that there are markedly elevated levels of this chemical in kids with AVMs. And we've published this and this is important because it tells us not just what happened in the past, but if we didn't do a good job taking this out, maybe the AVM angiogram looks okay, but maybe this is a way going in the future that we could just check the urine and have an additional way to follow these kids non-invasively in the future. We found this as a biomarker compared to kids that don't have AVMs. And honestly, we've looked at this with other vascular diseases such as moyamoya and we can just with a urine test, have a much better sense of whether the AVM is present or not. Does it hold up in actual tissue? Yep. If you cut the AVMs out, the same imbalance of the chemicals exists in AVM compared to normal brain. And importantly as a surgeon, if you get rid of the AVM, if I do surgery and that AVM goes away, do these chemicals normalize? And the answer is yes. I realize this isn't the biggest AVM in the world, but this is a girl that was having seizures. She has the AVM, we take it out, her seizures get better. But importantly we can see that before the surgery, in the red there, her level was quite high in the urine. And when the MRI looks clean, the urine is clean. Why is this important? Well, it's an additional non-invasive way to check the recurrence rate in these small kids. And it's also a way that compliments imaging where you don't necessarily have to sedate these kids and and bring them to the hospital. We did a big national trial for this in tumors and we're trying to look at this now in AVMs. Genetically, and this is something you'll hear about a lot in the pediatric world, this is the complicated molecular slide. You get your CBE credits for science here, but this is where we see these mutations. So our group and others have found these KRAS and BRAF mutations in AVM specimens. This is the most commonly mutated gene. This is why these AVMs are there. And they're in the ephrin pathway. RASA1 we've talked about. This is why you have to screen these kids, and kids are different than adults, when you think about the fact that they are at risk of having mutations. Again, we published this almost a decade ago, where they are much more likely to have other vascular malformations in their nervous system. This is important because if you start an operation and you haven't thought to look for an AVM elsewhere, there have been reports of these kids having hemorrhages, intraoperatively and postoperatively from unknown lesions. So something to think about in the pediatric population, again, that's more than just the technical cutting and sewing. And lastly, the EphrinB4 on the surface, what you can see here is that the genetics of this are that patients with a vein of Galen, for example, about 30% of 'em have mutations in this same molecule. So this all ties together for this common pathway where you say ephrin is sort of the parent molecule that drives all the other things that grow AVMs. And this is so important because it suggests in the kids why are these AVMs growing and growing back. We now probably have a better molecular understanding of that. But equally important, it helps us understand why they have this abnormal protein that doesn't coagulate. The problems we have as a surgeon are explained by the molecular biology and that's why putting a patty on might be better than coagulating or attempting to coagulate these. And then the last thing is that this explains many times in pediatric patients why these go all the way down to the ventricle in many, many cases, not all of 'em, but many of 'em. And so this little foray into embryology, I think helps to explain the surgical tenets and principles I showed at the beginning in the video: Coagulation, patties, working circumferentially around it, the shape of the AVM. Divining your surgical strategy when you're thinking about the case the day before or even as you're rushing down from the emergency department, can actually be predicated on some of these core principles that may make you have a safer surgery, so at the very end, you're not coagulating an AVM that doesn't coagulate or you're not wondering why is there a big hemorrhage welling up from the bottom of my AVM cavity when I thought I got the whole thing out. And then lastly, getting that perioperative imaging is so important. So what do we have here for the finish line as we sort of wrap up in the final minutes? Well, I think the takeaways here, again, speaking as a surgeon, surgery should almost always be considered as a first line therapy in pediatric AVM patients when they fit the criteria. And the patient selection that we've published and, again, are in the American Heart and Stroke Association guidelines include kids that are of younger age, so teenagers and younger, if they've had hemorrhage in their presentation and that they have a Spetzler-Martin one through three generally. And we've tended to include this, even if the children are asymptomatic and they've found this for other reasons, they've hit their head from a trauma, they've had a an accident. I think that there's a good justification with the data that I presented here to warrant surgical resection, assuming there's a candid discussion with the family based on the bleed rates, the natural history and the concern for leaving these alone. Surgery should generally be protocol driven. And again, this is probably a little drier than the really cool surgical videos that Aaron has with other cases, but in large part because the pediatric population has a lot more complexity to the perioperative management and thought process, I think, than many of the adults. And as a consequence, using a protocol, controlling the blood pressure, pressure multidisciplinary management and perioperative or intraoperative angiography is so important in this group. Adherence to these key operative techniques that I highlighted I think are just really, really important things to think about. Circling around the AVM, not getting in it, you know, thinking about creating a patty wall around the AVM and really having a strategy. I mean I think one of the reasons that surgeons enjoy these operations so much, not only is because they can be curative if they're done well, but because each AVM is unique and it really entails some core thought processes and creativity to the surgery. And the creativity to the surgery can be a lot more successful if you use the principles that I've learned the hard way here, about the size, the shape, the embryology, the nature of these AVMS, because I think this is much more of a strategic operation in many ways, than a purely technical exercise. And if you think about the tactics, but more importantly the strategy, the outcome will do well. The last thing is I think there's some real need for ongoing innovation here to improve the outcomes of pediatric patients in translational research. But the researchers won't know what to do if there aren't good technical surgeons, the kind of people that that Aaron has created to watch these videos and learn from this site to contribute to this so that we can make the surgery safer for these patients in need and really be the leading core front for this kind of change and better surgical technique. Because this is a place, AVMs in particular are probably one of the most important and best and most challenging technical surgeries that we can do. And if done well, can have some of the best outcomes in all of neurosurgery. So the most challenging and the most gratifying and it has been very gratifying to have the chance to speak with you today. So I thank Aaron very much for his kind invitation and I hope this has been helpful a little bit in outlining some principles for management of pediatric AVMs in the operating room.

- Very thankful to you Ed. Beautifully done. Really a great lecture all the way around. Great science, which plays an important role in academic neurosurgery and it's always very welcome in this series as well. I think you really emphasize what's critical and that's pediatrics or children are not miniaturized adults, especially in AVM surgery, it's so true. The vasculature of the brain, the surgical response for removing the malformation in such an acute way through surgery can have a wide variety of different responses in an immature brain rather than an adult brain. And one has to really keep these in mind. This is not just, okay, well this is just another, you know, smaller version of an adult, I can take this out. It really requires incredible, thoughtful preparation and a very thoughtful postoperative management, including a certain set of skills for intraoperative surgical techniques. So with that, I wanna truly thank you. Ed, I've followed your career for many years. Couldn't be more impressed, couldn't be more proud, as someone who is not only an incredible surgeon, a great scientist, and truly an amazing friend to hang out with. So thank you again and look forward to having with us soon.

- Thank you, Aaron. It's been an honor and I'm very grateful to you and all the wonderful work you've done on your site. It's been really, really great. So thank you and I look forward to chatting with you more.

- All right, thanks again.

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