Hi. Good afternoon and welcome to the AANS-CNS Cerebrovascular section. I'm Mandy Binning. I'm Bernard Fennell. And we'll get started. We'll be your moderator for this afternoon. Go ahead, Bernard. First, I'd like to introduce the Donaghy lecturer, Dr. Adnan Siddiqui. Thank you very much, Mandy and Vern, this is great, it's great to see you. I'm merely the introducer of the Donaghy Lecture, not the lecturer himself, but it is my privilege and honor to introduce the 2021 Donaghy Lecture, Dr. Sepideh Amin-Hanjani of the University of Illinois at Chicago. A little bit about Dr. Donaghy himself, Dr. Raymond M.P. Donaghy was born in Quebec, but very early on in his childhood, migrated south of the border and grew up in Vermont, where he actually went to school, got enlisted in the army in World War I and World War II and was instrumental in developing neurosurgical service during his time in the military. And then after he finished his military service, he came back to Vermont. He had received training at the Montreal Neurologic Institute and Mass General Hospital. Wilder Penfield was a major influence on him, but he was really fascinated by microsurgery. In fact, it was happenstance that somebody suggested that they could actually use microscopes and ENT were starting to use these microscopes during surgery. And so he was the first one to really use a microscope. And guess what? He used an open microscope to do what we're doing endovascularly now. He used it for an MCA embolectomy back in 1960. He was able to get Carl Zeiss and their engineers to really focus on neurosurgical needs and develop a binocular microscope. And with one of his first real microsurgical neurosurgical disciples, Dr. Gazi Yasagil, in 1967, he introduced the concept of an SDMC, a bypass for occlusive disease. There are some of the pictures from a paper from 2010 describing his laurels, including the first OPMI microscope with a beam splitter to engage both. You can see some recording equipment as well as a source of light and camera. And 1967, that's him and Gazi Yasagil doing a bypass in the lab. And you can see by 69, he was really the principal person training everybody in microsurgical techniques. And so I could not think of a better person to really commemorate Dr. Donaghy's legacy than Dr. Amin Hanjani, who I've known for a few decades now. Dr. Amin Hanjani was born in Iran, in Tehran. And her early childhood, she moved after the revolution to Scotland, where she went to this Morrison's Academy, where the motto, strive to the highest, has been something that really is exemplified by her career. She graduated in three years summa cum laude from University of Massachusetts at Amherst, and was one of the youngest entrants at Harvard Medical School, where she graduated and just went down the street to Mass General, where she did her surgical internship, and neurosurgical residency with Nick Zervas and Robert Martuza. And then she clearly was inclined towards neurosurgery and decided to pursue an open and skull-based cerebrovascular fellowship with none other than Robert Spetzler in Phoenix. Shortly thereafter, she has pursued a very productive career at UIC with Fadi Charbel as chair and her partner in neurovascular surgery, where she's the program director and a professor of neurosurgery. Dr. Amin Hanjani is one of the first leaders that really welcomed me into the fold of cerebrovascular surgery as the chair of the joint section. She has been absolutely instrumental in the guidelines that have come out, particularly in regards to neurosurgical disease, which is probably the area where we have about the greatest depth of knowledge in neurosurgical disease, and I think a large part of that has to do with Dr. Hanjani and what she has done in her role as the chair of the guidelines committee, as well as at the American Heart, where she is the chair of the scientific oversight. Dr. Hanjani is extremely productive, over 200 papers with thousands of citations, and the ones that are most cited is this critical paper which really changed spine surgery of laminectomy plus fusions versus without, but the one that is near and dear to my heart is her work on athero-occlusive cerebrovascular disease in the posterior circulation, where the work led to the publication of this paper, which was an NIH-funded trial, which showed demonstrable significant differences in natural history, depending on flow, and this is something that remains really an important part of her academic career and really demonstrated a major difference in the natural history, demonstrating quantitative flow MRA as a main technique. I did not know that she drives motorcycles. I knew she was on TV a lot. I also did not realize that she gave lectures to Vikings, but she is a woman of many talent, a dear friend, and I'm just absolutely delighted to introduce to you the 2021 Donahue lecturer, Dr. Sapita Amin Hanjani. Thank you. Thank you so much, Adnan, for that very kind introduction. It's really a pleasure and an honor to be serving as the Donahue lecturer. I do want to thank the CV section, the AANS and the AANS Scientific Program Committee really for the honor to be able to do this. I want to take a moment to really thank and acknowledge Adnan for his phenomenal leadership in the CV section. He's really been seminal in a number of really key achievements of the section, including his role in developing the training guidelines for endovascular neurosurgery because it had a real big impact, I think, on the field currently and going into the future with some of those efforts. I do want to really also acknowledge just the role of the CV section in general and how impactful it has been for me personally in my professional development, but also in recognizing how big a role that plays in teaching advocacy and in its thoughtful interaction with organizations that are outside neurosurgery but relevant to the care of our cerebrovascular patients. With that said, I do want to start off just by acknowledging at the get-go my own mentors in the cerebrovascular space. As you heard Adnan mention, I trained at Mass General where my mentors were Chris Ogilvie and Robert Ogiman, who really were, again, very impactful in the development of my interest in cerebrovascular and in microsurgical skills. And then the time I spent at the BNI as a fellow with Robert Spetzler, who's undeniably a giant in the field of cerebrovascular surgery. And of course, Fadi Charbel, who's the chair of the department I've been in and a colleague and mentor for the last 15 years or so, who's not just a master surgeon, but really a thought leader in the field of bypass surgery. It's certainly been an honor to work with them. And also to be following in their footsteps and giving this lectureship is truly an immense honor for me. So I do want to take a moment just to acknowledge the trainees I've had an opportunity to work with, not just the residents in the program, but our cerebrovascular fellows over many years, as really trainees are what formed the foundation of the future of our field. And to acknowledge the many excellent colleagues I've had an opportunity to work with. This is our current team that takes care of neurovascular patients here at the University of Illinois. Really a pleasure to work with them day in and day out. So this topic of this lecture is really focused on Donahue's legacy. And as you already heard from Adnan, regarding his background, I think it's always fun to look back our field being a small one and seeing where we interface with our idols and role models of the past. And in this case with Dr. Donahue, my closest degrees of separation are related to our common training at Mass General Hospital. But as you also heard, he then ultimately went to become the division chair of the University of Vermont. And one of his major achievements there that has been, I think, impactful now through the years, subsequently, is his development of the first microsurgical research and training lab that you heard a little bit about already. And he worked with a colleague of his in vascular surgery, Jacobson, in putting this lab together. And as you also heard, they, as a team, performed the first MCA embolectomy and published that series, which frankly didn't have the greatest outcomes. Two of the nine of the MCAs that they did an embolectomy on in their first series, only two were patent. So it reminds us that procedures sometimes need refinement and development. And ultimately, this procedure has become what is now routine in endovascular thrombectomy. And even that has only developed in the last number of years through trials that demonstrated its efficacy. Importantly, as you also heard, he was really seminal in disseminating the technique to other neurosurgeons through training in that microsurgical lab, and notably, Dr. Yasser Gill, as you also heard in the introduction. And importantly, that's an important component of the legacy of the development of bypass surgery, and particularly STA-MCA bypass, with the idea having been conceived in order to try and correct cerebrovascular insufficiency in the context of carotid or intracranial vascular occlusive disease. And the first operations were performed both by Yasser Gill and Donaghy in quick succession within 24 hours in the 1960s. And this really launched a period of what could be considered eminence-based neurosurgery as relates to bypass, the idea that this procedure could be done, that early successes and bypass patency were seen, and the idea that this would correct cerebrovascular insufficiency. But as we all know, at some point, one has to move from eminence-based care to evidence-based care, and the evidence around this procedure really came ultimately from a couple of trials that I'll mention briefly, especially for those perhaps younger in the audience who may not be as familiar with these studies. The first of these in the 1980s was the ECIC bypass trial, and surprisingly failed to show a benefit of that bypass procedure, which had been so carefully conceived and developed in the previous years by Dr. Donaghy, Yasser Gill, and others. And really no difference was found between the medical and surgical arm of patients with either stenosis or occlusion of the IC or MCA by performing that procedure. And the conclusion was that there really is no benefit of this procedure, although the trial garnered a fair number of critiques for a number of things, including the notion that many patients were treated outside the trial, so there may have been selective blood flow enrollment, is an STA's blood flow really adequate for the type of revascularization needed, and the idea that the patients were not selected based on any hemodynamic criteria. This physiologic argument took most traction, leading to a number of years where people were interested in evaluating this further, because of the notion that some patients may have natural collateral pathways through the circle of Willis, through lateral or extracranial anastomosis, and others don't. So naturally, there may be patients with occlusive disease who are well compensated hemodynamically, and others which are not. That era then became the era of defining patients who are hemodynamically compromised and potentially at higher risk as a target for revascularization with bypass. And the studies that were probably most impactful led to the adoption of using PET, positive emission tomography, and looking at oxygen extraction fraction as a way to determine patients who are particularly compromised and may benefit. And notably, the St. Louis carotid occlusion study, published in the late 90s, seemed to demonstrate that if this test indicated a high oxygen extraction fraction, that was a marker of high risk, and would suggest that those patients are most in need of revascularization. And ultimately, that formed the basis for the carotid occlusion surgery study, a study that was initiated in the early 2000s as a prospective multicenter randomized trial, looking particularly at this subset of patients who are hemodynamically compromised, based on OEF, and performing STAMC bypass surgery. However, and again, to much disappointment, the trial was actually halted early, because there were no signs of benefit from the surgical arm. In fact, both groups had a very similar risk of subsequent stroke over two years, despite what had been projected when designing the study at about 22% in the whole group. It's worth taking a closer look at these results and looking at the Kaplan-Meier survival curves shows us that the surgical group had a high event rate that leveled out, and that the medical group ultimately had a lower risk of events on modern medical therapy than had been originally anticipated. And the conclusion of the study really was that ECIC bypass surgery fails to provide an overall benefit, even in this hemodynamically selected group. But again, it's worth looking a little bit more closely at the results. That perioperative morbidity of 15% certainly had an impact on the outcome of the study. If it had been lower, closer to 8%, certainly surgery would be very likely to have been beneficial. So that was an important element of the lack of benefit seen from the study results. Interestingly, after that period of perioperative risk, what was evident is that hemodynamics did in fact improve with restoration of more normal oxygen extraction fraction in patients that underwent bypass. And this really translated into a lower stroke risk in that period, past the perioperative period. So the other category of patients that really wasn't well addressed in the trial was the more infrequent, but more unstable patient who is having crescendo, postural, or recurrent symptoms, because the trials, basically inclusion-exclusion criteria was such that it effectively excluded patients who were particularly unstable. It allowed enrollment of patients who'd only had a single event and had a pretty broad enrollment window, which is usually the window in which recurrent strokes can occur. Now, to be fair, the COST group has gone back and analyzed their data in reference to patients who had only single events versus recurrent events, which is about 50-50 in the trial, and similarly saw no benefit of bypass. But again, even those patients aren't necessarily the unstable patients that are failing optical medical management. So I think that the COST study results really do demonstrate that there is not proof for routine use of bypass in cerebrovascular occlusive disease, but we can state that there is an improvement in hemodynamics and that beyond that perioperative risk or complication window, there was definitely evidence for benefit in stroke risk reduction. So what does that all translate to taken together? Well, I think the 2021 guidelines, our sources for gleaning evidence-based recommendations really I think state it fairly in stating that there is no benefit that's been shown for STAMCA bypass performed as an initial treatment because really that's what COST and the ECIC bypass study had looked at. But in that context where now the evidence has not shown us routine use is useful, is there any role to go back to our eminence-based approach, at least for patients who were not included in these trials? Certainly a smaller cadre, but arguably ones that are very high risk like unstable patients with recurrent symptoms. I think in considering that, we have to look at some of the lessons we've learned from these prior trials, one of them being that idea of who really is someone who might benefit and will these severely compromised patients that really weren't included in the trial who really failing all aggressive medical therapies where there's no options left, should we still consider bypass for those patients? Again, not an evidence-based approach because those patients weren't included in the trials, but based on knowledge of lack of other options available for them, but also keeping in mind that these patients may well have a higher risk of perioperative events as well. So we have to factor in risk in both regards. Now here's an example of a patient that might fall into this category, MCA occlusion, small stroke, large territory at risk, recurrent symptoms, hemodynamic imaging that shows clear compromise in the hemisphere, and a strategy to revascularize with STAMC double barrel bypass which resolves the symptoms and allows the hemodynamics to return to normal. Now we also, I think, recognize this issue of perioperative morbidity is extremely important ultimate outcome, and we have to recognize that volume outcome relationships both for the surgeon and for hospitals are relevant to bypass surgery. Back 15 years ago, we published data from the nationwide inpatient sample, and this was in an era where bypass was more common, that demonstrated a clear volume outcome relationship with higher volume centers having lower discharges to long-term care facilities and mortality. And this kind of data has been reiterated in more recent analyses of NIS samples, again showing that patients at high volume centers tend to have lower mortality and neurological complications, and obviously the strategy to deal with that would be centralization of this care, but beyond centralization, we have to also maintain the standards of surgery through microsurgical training, something that obviously Dr. Donaghy was very well aware of and very involved with, and we have to recognize that because of the relatively low frequency in which the procedures performed, the training becomes all the more important, and training outside of the OR as well. So there's a number of excellent models that can be used for bypass training from more complex, like this one that involves use of cadavers and can really simulate blood flow, to more kind of tabletop versions. This is a turkey neck model that still has pulsatile or has consistent flow in it that can be used for bypass training, or actually the one I like the most is the simplest version of this, the chicken wing model. Easy to get, low resource, just a trip to the grocery store, and you have really an excellent model for performing anastomosis. So I think all of these are critical to use in training for bypass. And in the context of meeting that low perioperative mortality and morbidity, we need to be thinking always about methods to optimize the surgery. Again, the last couple of decades, fluorescence angiography intraoperatively plays an important role in that, but what I think has been relatively underutilized is the use of flow measurements, and these were concepts really introduced by Fadi Charbel using this ultrasonic quantitative flow meter intraoperatively that can provide important information for optimizing bypass surgery. And some of the concepts you may have heard of are using these kinds of flow measurements to measure something we call the cut flow index, essentially a very simple index between what the bypass flow is after an STAMCA bypass compared to the cut flow of the supratemporal artery, the STA, when it's free flowing, and it gives an indication of how much of the flow of that STA is being utilized once the bypass is in place. So here's just a short case example going back to that patient with an MCA occlusion that I showed earlier. Here's how that concept would be applied during surgery. Here for this particular patient, because it's an MCA occlusion, it's a double barrel bypass being performed. There's a vessel above and below the sylvian fissure that's been isolated. First step is just to measure the flow in those STA branches using that flow meter. And then after an astimosis, which is the standard end-to-side STAMCA bypass, can be performed a number of ways with either running suture technique or interrupted technique. The key next step becomes measuring the bypass flow. And as shown on this slide, if the bypass flow equals or is around the cut flow, you know that you have a very robust and durable graft if the cut flow index is close to one, which is what you expect it to be if the brain is in need of blood flow. And we actually, a number of years ago, showed that a cut flow index more than 50 percent predicted long-term and short-term graft patency. And more recently, Chris Stapleton, a couple of years ago, who was our fellow at the time, now at Mass General, demonstrated with further follow-up data that that holds true, that a cut flow index greater than 0.5 predicts long-term success with bypasses. And so I think incorporating these kinds of concepts helps us improve our bypass surgery. I think other lessons we got to keep in mind is the need to track results objectively in databases and registries. Now, when the COST study came out, a number of us in the CV section, led by Carlos David at the Leahy Clinic, thought it would be a good idea to start collecting our outcomes from any cases that were still deemed to be appropriate for bypass that fell outside of those criteria that were used within COST. But I mean, I have to admit, this effort has not been very successful because even collecting this kind of data meets regulatory barriers, requires resources and funds, and we've not been particularly successful at getting a large number of patients into this registry. My hope is, as registry efforts with organizations like the NPA through the AANS and the NVQI QOD, which is the outcomes database that the CV section and other cerebrovascular organizations are involved with, become more and more and more commonplace, we'll be able to collect data on even these rarer procedures that have more limited indications as well. And then finally, we may be needing to look beyond just stroke prevention. There is some data that suggests cognitive and functional impacts of carotid occlusive disease and of bypass. There's been a lot of small series that suggest improvement in cognition related to bypass, although to be fair, the ancillary study to COST, which was called Recon, failed to show a benefit. It was very underpowered. And functional outcomes intriguingly may be impacted by bypass. There is a concept at least, just as there can be hibernating myocardium in the cardiology sphere of hibernating brain in patients who are oligemic, and the idea that cortical thickness or brain volume can actually improve post-bypass. Again, small kind of innovative and thought-provoking series that deserve further attention. Now, way back when COST came out, a group of us within the cerebrovascular section analyzed all those results and proposed that rather than completely abandoning the surgery, we got to keep an eye out for these kinds of further developments and try to improve the surgery so that it can be applied to appropriate patients safely. And in the end, we have to still ask the question of, is bypass still necessary? Well, it may be that a more limited cadre of patients with occlusive disease require it, but we have to remember there's other conditions like moya-moya and aneurysms that can benefit from bypass surgery too. And where do they fall on the spectrum of evidence versus evidence for being performed? Well, in moya disease, especially in ischemic moya disease, there's a lot of observational data that suggests the benefits of bypass. And there's been many series, both retrospective and prospective, the aggregate of which really show a benefit of surgical intervention for symptomatic moya-moya that comes with strokes or TIAs. Unclear if that's as beneficial in asymptomatic disease. And there's a prospective study in Japan and Moray that's analyzing this currently. So we'll probably know more about this in coming years. And arguably, it might be said that, well, you don't necessarily need to do an STA-MCA bypass in moya because indirect bypass seems to be a successful strategy to develop collaterals. But ultimately, the combined approach of direct and indirect bypass, if you look at the literature and the observational studies that have been done, seems at least in adults to be a superior option, both for secondary stroke prevention, for angiographic outcomes, and for long-term outcome. Again, arguing for maintaining the skill of STA-MCA bypass surgery for those indications. And keeping in mind that for hemorrhagic moya-moya, which is more prevalent in adults than in children, direct bypass has actually been shown beneficial based on the JAM trial, the Japanese adult moya-moya trial, which showed a benefit of that intervention in terms of reducing recurrent events over time. How about aneurysms? Well, here we're squarely back in the eminence space domain because these are, again, relatively infrequent indications for bypass. And these are, I've listed here some of the scenarios that I think still engender at least the thought process about the need for a bypass. Complex, giant, or partially thrombosed aneurysms, distal or serpentine aneurysms, the more complex lesions that we see. Of course, we have to entertain and keep in mind that for all of these indications, there have been additional and ongoing developments in endovascular strategies that may supplant for various indications that bypass were appropriate 20 years ago, may no longer be necessary or appropriate. So, here's an example of a patient I treated back over 15 years ago or so, a 73-year-old who comes with progressive ophthalmoplegia as this giant partially thrombosed cavernous aneurysm. And with the idea of treating that ophthalmoplegia and treating the symptomatic aneurysm that was getting progressively troublesome for her, she had failed balloon occlusion testing. And therefore, what was offered and what I performed back in 2005 was a proximal occlusion with the SDA-MCA bypass. No small surgery for a 70-some year old, but really the best we had to offer at that time. In the current era, no hands down, this patient would be referred. I'd refer to my endovascular colleague for flow diverter rather than doing a bypass for this kind of case. But I'm going to show a few cases where I think we still should be entertaining and utilizing the full spectrum, including the spectrum of surgical revascularization for treatment. So, here's a different patient, a 67-year-old who has giant ruptured ICA aneurysm with visual decline from optic nerve compression. And for this kind of case, I would argue the best strategy is going to be a revascularization and trapping or clipping of this aneurysm. And here's just a short video of that. Here's a saphenous vein graft being placed onto one of the MCA branches. The size mismatch can be accounted for with that end-to-side technique. Here's the proximal anastomosis. Once the graft is in place and revascularization has happened, the aneurysm can be explored. See if it's clippable, see if it requires trapping. In this case, it looked like trapping would be the best option, but there was backflow coming from the ophthalmic artery that prompted then doing an anterior clinoidectomy. And once the anterior clinoid was off, I could dissect the full neck of the aneurysm, trap the aneurysm successfully, and completely decompress it, also reducing any tension, as you can see there, on the optic apparatus as well. And with that strategy, the aneurysm is secured, the patient is revascularized, the optic chiasm is decompressed. And I think it would be challenging to treat this with endovascular strategies like pipeline or coils and not encounter problems in the subarachnoid hemorrhage setting where anticoagulation and antiplatelets can be problematic. Here's the post-operative angiogram, and this patient develops spasm. As many patients with subarachnoid hemorrhage do, the advantage of a large vein graft in that setting is the ability to be able to treat the vasospasm, even endovascularly, through the graft, which was done in this case and helped to relieve that vasospasm. Here's another case, which I think is still challenging from an endovascular standpoint, a distal ruptured MCA aneurysm. Probably the only option endovascularly would be to sacrifice this vessel. And I think even the stents that are suitable for smaller vessels would be inappropriate here or would have a high risk of thrombosis. And again, in a ruptured setting are not ideal. So for this kind of case, it's a fairly simple bypass solution, an end-to-end anastomosis. Here's the dissection in the distal fissure that shows us where the fusiform aneurysm is, measuring blood flow so that we know that after bypass, the flow is maintained, cutting out the aneurysm, which has a big thrombocytoaneurysmal portion to it as well. Once that is cut out, and in cases like this where there's enough laxity to the blood vessel to perform then what I call a beveled end-to-end anastomosis with the same techniques that are used to perform STAMCA bypass, just applying them to re-anastomose the vessel together. And once that's done, the final key step again, using flow measurements is to confirm that the bypass has been successful, not just anatomically with ICG, but with flow measurements to make sure that there's not an introduced stenosis or problem with the vessel itself. And here we're going to see the final ICG run and flow measurements that confirm that that's been successfully performed. And here's the angiogram where it's hard to identify the vessel where the aneurysm was because it's been excised and re-anastomosed. And then finally, here's another case where sometimes an unexpected situation warrants using those same microsurgical bypass skills. Here's a small ruptured aneurysm, really not well suitable for any endovascular therapy, broad-based, multiple lobules, small size, taken to the OR for clipping. And expected to be a fairly straightforward clipping, but unexpected things sometimes happen. In this particular case, there was an intraoperative rupture and you can see that there's a tear really at the base of the aneurysm. And despite multiple attempts of different clipping strategies to both secure the aneurysm, but maintain patency of the vessels, because of the location of that tear at the base of the aneurysm, that temporal M2 branch was occluded. And with that, the quickest solution to salvage that becomes a bypass. And it could be an STAMCA bypass, but in this case, the quickest strategy, seeing the vasculature of the M2 branches coming close together more distally was to perform a quicker side-to-side anastomosis, taking those M2 branches, again, using those same skillsets that are used in an STAMCA, but applying them to suture the vessels together. And once the back wall and the front wall have been anastomosed and removing the clips, we can then confirm immediately with flow measurements that flow has been restored, as well as confirming that with ICG. So a mechanism to salvage what otherwise would be a situation that leads to an ischemic stroke. And here we see the post-op and the avoidance of an ischemic stroke in that territory with the side-to-side bypass in place. So in conclusion, I just want to emphasize that I think bypass remains useful. In some cases, more based on eminence than evidence. There is evidence, I think, in the treatment of MOIA. I think there are still some patients with occlusive disease that can benefit from it, but we should be careful in tracking our outcomes and monitoring our perioperative morbidity in those cases. And I think there are still complex aneurysms where we want to be able to apply the full range of options across the endovascular and surgical sphere. And that includes the notion of revascularization and bypass surgery in selected cases. And I think ultimately that is Donahue's legacy, as I see it. The idea, as Professor Yazergill noted in an article he published in the late 1990s, is that Dr. Donahue demonstrated how arteries can be precisely reconstructed under an operating microscope using micro-instruments and applying meticulous patients and skillful micro-manipulations. And I think all of that still holds true and is something that we should aim to continue to train future vascular neurosurgeons so that we maintain all range of options for the very complex lesions that we can encounter. Thank you very much. And thank you again for the honor to serve as the Don Lee lecturer this year. That was a great lecture. Thank you. I do have a question for you. Since COS, I think a lot of physicians in the neurology community don't see any indication for bypass. And so a lot of times, even for Moyamoya or some of the vaso-occlusive disease where they may be pressure dependent or having these languishing watershed infarcts, we're not necessarily seeing those patients. How do you reach out to your neurology colleagues to let them know that there are some indications for bypass? Yeah, Mandy, I think that's an excellent point. And unfortunately, it can be the situation of you don't know because you never see the patient or you don't know who's not being referred. For us, it's been kind of an ongoing process of really speaking with and trying to educate our colleagues about particular cases where there may be indication for it. I think the most powerful, of course, is if they do happen to have a patient that they send and they see how the patients can benefit from the treatment, that becomes a big trigger for them to recognize that those patients at least warrant a workup. And we go through a very kind of, I would say, a paradigm we've developed over many years of a staged approach to evaluating the patients. Every patient gets imaging that's very focused on identifying the level of hemodynamic compromise. We look at their medical regimen, optimize that. And so I think we're giving the neurologists an indication that we're not cowboys that are just rushing into every case that happens to have an occlusion on angio, but really carefully selecting those patients. And I think in, again, keeping those results and being able to accumulate those over time and publish those is another way we can disseminate that kind of to the larger population beyond just the neurosurgical community, but to the vascular neurology community as well. Thank you. Thank you. I don't see any questions on the slide, but I also have another question for you, Dr. Ganjani. With, what are your thoughts on kind of quantifying some of those out of the operating room experiences in terms of being able to further advance your microsurgical skillset for bypass? Yeah, I mean, I think there's a lot of opportunities for that that we probably don't take as good advantage of. I'll make a shout out to one of our colleagues in Madison, Mustafa Buskaya, because I was there at a course he was giving once, and I saw that he had developed this very kind of structured paradigm for how he would let residents advance to doing bypass or putting stitches in the OR that required demonstration of very specific skills along the way, including a number of repetitions that would be done in the lab and then viewed by him as videos to kind of get feedback. It's just very time intensive, right, to do that kind of training. But I think that it may not be realistic to be doing that with every resident, but I think certainly for folks who go into cerebrovascular as their chosen field and during cerebrovascular fellowship, it makes perfect sense to kind of incorporate that kind of progressive structured paradigm of training, one that is not just practice, but deliberate practice. I think many people are very familiar with that concept now, the idea of you're not just practicing something, but somebody is actually giving you very specific feedback, monitoring that practice. And I think in the context of fellowship, even though it's a time intensive kind of model, it is worthwhile and really should be implemented to help folks really gain those skillsets and the confidence and the comfort with using them in the OR. Great, well, thank you. I think those were our questions. Excellent lecture. All right. Next, I'll be introducing the top abstract presentations. Our abstract authors are Kevin Shaw, Teneri Barak, Sarah Chang, Seth Staggers-Teclair, and Joshua Catapano. Hi, everyone. My name is Kevin Shaw. I'm a PGY-6 neurosurgery resident at Northwell Health. Today, I wanna talk about some of my previous work and some ongoing work I've done on understanding the role of the trigeminal nerve in modulating cerebrovascular tone and really using stimulation of that nerve as a therapy for spasm and DCI for subarachnoid hemorrhage. So you all know that angiographic spasm affects up to two-thirds of patients after subarachnoid hemorrhage. But even though for a long time, we thought that vasoconstriction was the main driver of spasm, even in my short career as a resident, a patient like this in the bottom right that comes in with subarachnoid hemorrhage can have no symptoms. And it really begs the question, is there something else going on? The fact is there's a lot of other things going on. And over the past few decades, we've kind of come to the understanding that there are a number of things besides just vasoconstriction, but things like oxidative stress and inflammation, spreading to polarizations that all contribute to this cycle of increased neuronal vulnerability to injury. I think most of the interventions that we have and we've tried are single target therapeutics, meaning that they act on a single effector molecule to try to break this cycle of spasm. But really a more ideal therapy is going to be something, an intervention that affects multiple arms of this cycle. And that's what I'm gonna talk to you guys today about. This is where the trigeminal nerve comes in. So the trigeminal nerve innervates the strip of vasculature. We know this, but what you might not know is that it innervates or it has very strong connections to autonomic brainstem nuclei. And those brainstem nuclei relay to the cortex where we've shown it can interrupt cycles of ischemia and cerebral inflammation. And so I thought maybe we can use this to interrupt cycles of DCI, meaning we can interrupt or we can augment cerebrovascular coupling and reduce cerebrovascular inflammation. And so we designed a model, well, we used a model, an endovascular puncture model, subarachnoid hemorrhage, where we introduced a sharpened threoperline suture into the cervical ICA and then placed it into the brain where it was used to perforate the ICA terminus, causing or replicating aneurysmal subarachnoid hemorrhage, which you can see here in the top right image. And then these rats that had subarachnoid hemorrhage were brought back during their peak vasospasm period and implanted with electrodes, measured electrocorticography, laser Doppler flow probe for cerebral blood flow and a number of other vital parameters. And we put a bipolar electrode into the peripheral branch, the interorbital nerve of the trigeminal nerve and simulated it. And three days after subarachnoid hemorrhage, the rats were euthanized. So spreading depolarizations are a very underrecognized and underdiagnosed, I think, component of DCI. And we always see this patient that, you know, for some reason it's not waking up and all the tests are negative and we don't really understand why. And I would say that we should consider spreading depolarizations. They are, if you don't know, slow, self-propagating, low-frequency waves over a population of neurons that rapidly increases their metabolic rate. And during this time of depolarization, repolarization, these neurons, which can encompass an entire lobe of the brain, are rendered inactive. And they're very hard to pick up on the scalp, e.g. But with direct corticography in rats, you know, we can pick it up. So normal response to CSD or spreading depolarizations is that with every CSD, which you can see here in the left-hand graph, there's a compensatory rise in cerebral blood flow. Significant amount of cerebral blood flow. I'm talking like 100 to 200%. And so with successive CSDs, there's, you know, a compensatory rise in cerebral blood flow in healthy brains. But in the injured setting, meaning in subarachnoid hemorrhage with successive CSDs, there's a decrease in the baseline cerebral blood flow. So after about 45 minutes, we found that these rats dropped under their baseline cerebral blood flow and maintained, you know, a state of low blood flow throughout the entire reporting session. And this renders neurons susceptible to ischemia. With trigeminal nerve stimulation, we found that this baseline of cerebral blood flow was maintained and the rats were able to mount a appropriate compensatory response to every successive CSD. And then when we repeated this and we quantitated it, we found that, you know, this was in fact the case with a high degree of statistical significance. We also found that these rats also experienced fewer CSD events. And we don't really understand why this was the case, but you can see here that the rats that got TNS, trigeminal nerve stimulation, had a fewer number of CSDs. We think that this may be related to the entire neuroinflammation component, just kind of this nebulous concept. So we measured kind of these nebulous parameters like reactive oxygen species, IL-6, TNF-alpha, and we found that all of these parameters were decreased after rats received TNS. And more than that, we found that TNS can reduce vasoconstriction or cause vasodilation in large arteries like the left M1 segment, which is here in cross section, but also small arteries. So the peel arterioles of the left hemisphere, and it can also reduce microthrombin. And this was confirmed with two assays, CGRP, calcitonin gene-related peptide, which is a vasodilatory molecule of the trigeminal nerve and ICAM, which is a sensitive marker of vasoconstriction. And we measured hypoxia-inducible factor 1-alpha expression in hippocampus. So in control rats, you see a high amount of expression of hypoxia-inducible factor, but with TNS, you can see that this factor expression significantly drops off. This corroborated by tunnel staining, which is a measure of apoptosis and similar result, right? So a lot of tunnel staining in control rats, but not a lot of tunnel staining in rats that received TNS. Same thing with neural behavioral scores. So a day after TNS, the rats that received the treatment were doing much better than the rats that didn't. So in conclusion, I think the trigeminal nerve has a role to play in modulating the cerebrovascular tone. But more importantly, what I didn't list here is that I think in order to treat this very complex disease, we need something that can attack multiple components of this cycle of DCI. And I think that trigeminal nerve, really trigeminal nerve stimulation can do that. And because of this, we've kind of been moving on to try and devise a human clinical trial for trigeminal nerve stimulation. And with that, I'll take any questions. Okay. Hi, everyone. Thank you all for having me. My name is Tanyer Barak. I'm working as a scientist with Professor Murat Minal at Yale University. Today, I will be presenting our latest research in the intracranial androgenetics. And in the lab, we have been studying the genetic risk factors of IA for more than 15 years. And over the last 15 years, we applied genomic technologies for the identification of risk regions using genomic association studies first. And more recently, to discover causative genes in IA pathogenesis using polyxome sequencing, which helped us identify the role of PPL4 gene as one of our first findings in our research. So in this study, we first polyxome sequenced large families five or more affected individuals and used polyxome sequencing result of over 400 index European cases as replication cohort. And we found significant enrichment of rare and damaging variants in PPL4 gene in IA cases compared to control cohorts. And to study the biological impacts of PPL4 loss, we generated CRISPR-Cas9-induced loss-of-function model in zebrafish. And using a transgenic line, as you can see here in the figure, where the endothelial cells were tagged with GFP, we were able to visualize and quantify the morphological changes in PPL4 depletion. And we found, actually, there was a significant impact of PPL4 depletion localized to brain and more predominantly, actually, interestingly, to midbrain, while the trunk mass, which was not affected at all. And that was a very interesting result for us because it was suggesting that PPL4 might be involved in regional specific androgenesis. Next, we wanted to assess whether PPL4 loss has an impact on mastoid integrity. And we induced hemodynamic stress by treating zebrafish embryos with epinephrine and found that the homozygous PPL4 zebrafish showed hemorrhage significantly more frequent in hemodynamic stress, under hemodynamic stress, compared to wild type. And these hemorrhagic events were prevented by overexpressing wild type in PPL4, in PPL4 homozygous background, but not with G132S mutation that we identified in the familial case. And of course, from the basic science perspective, we asked how PPL4 regulates the normal cerebrovascular function and regulates the development of cerebrovascular network. And to address these questions, we first assessed the expression profile of PPL4 in arterial tissues. And we identified that PPL4, although not specific, but predominantly expressed in enriching endothelial cells. And we found using another transgenic bias, you can see here where you can visualize and quantify the number of endothelial cells, that PPL4 depletion has an impact on endothelial cell number. And again, where we observe the phenotype more predominantly in the midbrain area in different embryonic stages. And my most interesting experiment, most striking experiment that we actually performed to address the question whether or not PPL4 is an endothelial cell autonomous effect was the overexpression of human wild type PPL4 in endothelial specific manner in zebrafish embryos. And we found the cerebrovascular phenotype observing homozygous PPL4 mutants were significantly prevented and restored in endothelial specific overexpression of PPL4, which suggested that these phenotypes we found in PPL4 depletion is associated with endothelial cell pathology. And we next wanted to assess whether heterozygous PPL4 mutants show any impact on cerebrovasculature, and especially during adulthood. And we induced hemodynamic stress again with epinephrine, but this time via retro-orbital injection for four days. And we found that heterozygous PPL4 zebrafish showed a significant increase in hemorrhagic events, especially around a circle of Willis area, and some of these vessels actually exhibited aneurysmic dilations. So next, we mechanistically assessed how PPL4 might be functioning, and we found that the wild-type PPL4 is binding GMG86 protein, which is a non-regulator of Wnt signaling and androgenesis. And interestingly, the G132S mutation prevented this interaction with GMG86. And then we wanted to see whether or not these two proteins have any synergistic effect on Wnt signaling activation. And we found in using Luciferase experiments in vitro, we found that actually these two just are potentiating each other's effect on Wnt signaling activation, and this interaction was lost with G132S mutation, we identified in the figure case. And they also show that the in vivo PPL4 depletion has an effect on PPL, Wnt signaling activation by using a transgenic report to liken a zebrafish, both in brain parenchyma and endothelial cells in the brain were actually showed a reduced number of endothelial, reduced number of cells reporting TCF. In conclusion, I can say our study showed that rare and deleterious mutation PPL4 are enriched in IE cases, but I think more interestingly for me, at least, is PPL4 emerged in our research as a known regulator of brain androgenesis and cerebrovascular integrity. And PPL4 mediates Wnt signaling activation through binding GMG86, where this interaction was lost with G132S mutation. I would like to thank my, first of all, my PI, who, Dr. Grinald, who I had the chance to work with for seven years, our collaborator, Stefani Nicoli, and several collaborators, contributors, and scientists who were involved in this project. Thank you. Hi, everyone. My name is Sarah Chang. I'm a medical student at WashU, and today I'll be talking about the importance of cerebellar white matter integrity in motor recovery after chronic stroke. It's been shown in the literature previously that white matter integrity correlates with recovery after acute stroke. The severe the damage to the white matter, the more severe the motor deficits are. Diffusion tensor imaging, or DTI, is a noninvasive imaging technique that provides several measures of white matter integrity. These measures have been used to show the importance of white matter in acute stroke. One DTI measure of interest is mean diffusivity, or MD, which I've overlaid on the right, where higher values indicate less constrained diffusion, such as in pathological states of demyelination and edema, which can be seen as white in this image. It also inversely correlates with axon count. DTI can also allow us, through tractography, to track the individual fibers throughout the brain, as can be seen in the image below, where the arrow indicates an area of disrupted fibers due to stroke, which you can see correlates to the MRI as well. Historically, recovery is thought to not occur after six months post-stroke. However, this is no longer the case with novel brain-computer interfaces, such as the recently FDA-approved IpsyHand by NeuroLutions, which consists of an EEG headset and a robotic exoskeleton fitted to the weak hand. However, the underlying white matter changes in these patients with chronic stroke and how they affect recovery have yet to be fully elucidated. Here, we seek to determine if white matter integrity correlates with or predicts recovery in chronic stroke patients. Our study consisted of nine chronic hemiplegic stroke patients who underwent a 12-week brain-computer interface rehabilitation program that's previously been described by our group, which trained patients to utilize the ipsilateral brain to regain function in the weak arm. Patients underwent DTI scans at two time points within two weeks of initiation of therapy and within two weeks of its completion. At these times, motor function was also evaluated using the upper extremity portion of the Fugl-Meier assessment, or UEFM. We performed a variety of analyses on these diffusion tensor images. Firstly, whole-brain voxel-wise analysis was performed to look for group-level changes in white matter before and after BCI therapy. Next, region-based analysis was performed, where we segmented the brain into ipsilasional and contralasional cerebral and cerebellar white matter, as you can see in the outlines on the right. The average MD was calculated for each of these regions for each patient, and the correlations between these regions and the Fugl-Meier changes were then calculated. Similarly, tract-based analysis was performed, where rather than calculating MD only within the outlined region, it was calculated throughout the length of all fibers that originated within that region. This becomes more relevant in our smaller regions of interest. Our results showed that there was no group-level change in MD after therapy as compared to before. That is, there was no one area in the brain that changed consistently across all the subjects over the course of rehabilitation. However, some regions of interest did correlate with motor recovery, which I'll show here. We can see here that the pre-therapy mean diffusivity in our four regions of interest, and we can see that the pre-BCI ipsilasional cerebellar MD was the only one that correlated with the change in Fugl-Meier score. We then further analyzed within the ipsilasional cerebellum to identify the responsible regions for this difference. Three regions within this hemisphere showed strong correlations between pre-therapy mean diffusivity and Fugl-Meier change for both region-based and tract-based statistical analyses, Lobule 5, which we'll also call the anterior cerebellar lobule, and Lobule 7b and 8a. You can see these here with respect to the contralateral motor cortex. Similarly, you can see the fiber projections that we found using tractography that connect the ipsilasional Lobule 5 to the contralesional motor cortex, providing motor communication between these two portions of the brain. We then performed correlations between region-based and tract-based analyses in all of these three lobules to confirm our findings. However, only Lobule 5, or ACL, was found to be significant, while Lobule 7b and 8a were not. Similarly, a multiple linear regression using Lobule 5 was used to classify patients into motor recovery or non-recovery based on the Fugl-Meier score. Lobule 5 was the only one to correctly classify each patient as having achieved or not achieved the minimal clinically significant Fugl-Meier change. You can see that here. To summarize, in this study, we found that pre-therapy ipsilasional cerebellar mean diffusivity, a measure of white matter integrity, correlates with motor recovery. When we dove deeper to identify the specific regions responsible for this, Lobule 5 demonstrated significant correlation to motor recovery and could predict clinically significant recovery. Lobule 5 has previously been shown to play a role in execution of voluntary hand movements and sensory motor processing. Here, we suggest a mechanism of this association between Lobule 5 and motor recovery. Normally, on the left, the anterior cerebellar lobules maintain bidirectional communication with the contralateral motor cortex and receive motor-related sensory inputs mostly from the ipsilateral spinal cord. However, on the right, in chronic stroke patients, a lesion in the motor cortex inactivates the contralesional ACL. As the BCI activates the contralesional motor cortex, the unaffected ACL is activated, ipsilasional to the stroke. The ipsilasional ACL receives afferent signals from the spinal cord and engages in a motor loop with the contralesional motor cortex, which is supported by the tractography we showed earlier. This provides a possible mechanism of the importance of ipsilasional cerebellar white matter in recovery after chronic stroke. I'd like to thank you all very much for your attention, and a special thank you to Drs. Leuthardt, Carter, and Shimony, as well as Sid Rana and Joey Humphreys for all their help on this project. It would not have been possible without you all. Thank you. Yeah. Hi there. I just want to start by thanking the AANS for having me present here. My name is Seth Tegeler and I'm a third-year medical student at Stanford working in the Department of Neurosurgery with Dr. Steinberg. I'm going to talk a little bit about Moyamoya disease, some of the incidents and outcomes of posterior circulation involvement. Moyamoya disease is a progressive disease of the vessels that supply the brain. That word Moyamoya just comes from a Japanese description of a puff of smoke because that's what it looks like. You can see that in the bottom right of the slide here, it's like a puff of smoke. These vascular networks get increasingly narrow and they form small, weak blood vessels that are prone to rupture. Similar occlusive diseases in the PCAs have been reported but really not well-characterized. The natural history of that PCA disease in patients with Moyamoya is not well-known. Here at Stanford, we've been able to have access to one of the largest cohorts of patients treated for Moyamoya disease in the world. We sought to characterize the effects of PCA disease in those patients on their outcomes. The objectives of our study were to determine the effect of steno-occlusive changes in the PCA on outcomes in patients with Moyamoya disease, and then characterize the natural history of Moyamoya disease patients in one of the world's largest cohorts. Then we wanted to quantify the complication rates in patients with PCA disease compared to those with Moyamoya disease but without PCA involvement. We retrospectively reviewed 686 patients. We have just under 2,000 total, but we're providing an update here on about 700 of those. Those were patients treated between 1987 and 2019. We collected demographics and perioperative outcomes. Then we looked at and scored radiologic phenotypes. We scored the PCA disease. Sorry, I'm just going to go back. We scored the PCA disease between 0 and 3, where 0 was considered normal and 3 was complete occlusive disease. This table is just for people's viewing. I'm not going to go through each line, but feel free to screenshot it or look at it later. We'll go through those. In total, we had 197 male patients, 489 females with a mean age of 32.7 years. This was across all Moyamoya disease patients. Then we had a mean follow-up of six years. Of those 686 patients, we had a total of 1,090 bypass surgeries. 282 of those patients had singular revascularization procedures, and 404 patients had two procedures. I was mentioned earlier in one of the previous presentations, the differences between direct and indirect revascularization and the effects of that. That's something we're still looking at, but here in this cohort, we had 981 patients that had direct revascularization and 106 indirect. Then 107 patients had field-type PCAs. That was interesting, and that's mostly consistent with what literature has reported. In total of those 686 patients, we found about 40 percent of those showed occlusive changes in the posterior circulation. Again, 60 percent had no posterior circulation involvement, and then it was between 15, 10, and 16 percent that had mild, moderate, or severe disease in the posterior circulation. In patients that had severe posterior circulation disease, they presented significantly earlier than all other patients. They more often were males that had severe PCMD and they resulted in more post-operative ischemic complications. Patients, we then compared the severity of PCA disease to the Suzuki grades, which just describes the intrinsic reorganization process of Moyamoya disease on a scale of 1-6. We identified higher rates of PCA disease in patients with higher Suzuki grades. Then we also looked at whether patients had bilateral PCA disease, and that was present in 89 patients or about 13 percent of those. When we looked at how these patients, once they present and the time after their initial surgery, how likely they were to progress or worsen or develop new PCA disease, about 50 percent of our patients ended up developing worsening PCA disease at about seven years after their initial surgery. Big proportion of patients tend to worsen over time. Then particular risk factors included smoking, patients that had a history of tobacco use, progressed to worse stages of PCA disease faster or earlier. Then patients that had a history of hypertension also showed earlier disease progression compared to patients without hypertension. We're able to really be fortunate in having this cohort of Moyamoya disease patients. Really so far, what we're able to show is that PCA disease is highly relevant in patients with Moyamoya disease, and worth investigating. The involvement of the PCAs is associated with higher rates of ischemic perioperative complications, worse functional outcomes, and that's probably due to reduced collateral flow. Then patients with severe PCA disease present significantly earlier compared to all other patients. Risk factors for PCA disease include tobacco use and hypertension, and while it's always recommended to advise about these things in PCA disease, it might be even more important. Then progressive worsening really occurs over the lifetime of these patients and is really something that's probably worth doing long-term surveillance on these patients and keeping an eye on their posterior circulation. We're continuing to go through a lot of this data. It's a massive data set and a ton of patients, and so please stay tuned for more results that come in the future. Otherwise, I'd like to thank the organization, AANS, and these funding sources for supporting this work. Thank you. Hi, I'm Joshua Katapong. The current PGY6 is at the Baroneological Institute. I would like to thank the Society for inviting me to speak today on this manuscript titled Cannabis Use and Delayed Cerebral Ischemia After Aneurysms and Subarachnoid Hemorrhage. I have no disclosures. So there's growing evidence leaking cannabis use to cerebral vascular diseases. Recently, aneurysms and subarachnoid hemorrhage, the incidence was found to be twice as high in cannabis users as in non-users in a young cohort study. However, the pathophysiology largely remains unknown. We do think multifocal intracranial stenosis, oxidative stress, and cerebral mitochondrial dysfunction may all be contributors. Given the recent legalization of cannabis use in many states in the U.S., it's essential to continue to evaluate the risk and benefits of this drug. This study analyzed the effects of cannabis and other commonly used recreational drugs on delayed cerebral ischemia. So all patients with aneurysms and subarachnoid hemorrhage from August 1st, 2007 to July 31st, 2019 that were treated at the Barrett Neurological Institute were reviewed. The predictor variable of interest was substance use. We looked at methamphetamines, cocaine, tobacco, and cannabis. Our primary outcome was DCI, and this is defined as cerebral infarction identified on CT or MRI after exclusion of any procedure-related infarctions. We also performed a propensity score adjustment. The propensity score was computed from baseline covariance. This included age, sex, pre-existing comorbidities, GCS, Hunt and Hess, Fisher grade, aneurysm characteristics, including location, size, and type, and treatment. We used the covariant adjustment in the binary logistic regression analysis. So here's table one. These are the demographics and clinical characteristics of the 1,014 aneurysms and subarachnoid hemorrhage patients that were treated during that time period. And this is dichotomized for patients with cannabis use versus without cannabis use. As you can see, the patients with cannabis use were younger. They had a higher percentage of them were male, and a higher percentage of them had other substance use, including cocaine, methamphetamines, and tobacco. We also saw the radiographic vasospasm was significantly more common in the cannabis users than non-users, and this was 90% versus 70%. We performed a subgroup analysis of patients with radiographic vasospasm, and 50% of the cannabis users, only 39% of the non-users had DCI. Here's table two, showing the demographics and clinical characteristics of those same 1,014 patients. But now we've dichotomized into delayed cerebral ischemia versus no delayed cerebral ischemia. As you can see, less than 40% of patients had delayed cerebral ischemia. And in the delayed cerebral ischemia patients, there was a much higher percentage of patients with cannabis use versus no cannabis use, 6.5% versus 3.4%. The DCI patients also had a lower GCS, a higher Hundert Hess, and a higher Fisher grade. Here's table three. This is a binary logistic regression analysis where we did a propensity score adjustment, and we found cannabis use was an independent predictor of DCI. So an additional multivariable analysis looking at DCI, we found that it independently predicted mortality with an odds ratio of 2.2 and poor long-term outcomes defined as an MRS graded 2 and odds ratio of 2.8. So in propensity score adjusted multivariable analysis, DCI was 2.6 times more likely in cannabis users. Patients with DCI were significantly more likely to experience poor functional outcomes defined as MRS graded 2 and death. There was no association of tobacco, cocaine, or methamphetamine use. Similarly, in a study published in 2017 in Stroke, they analyzed 108 patients with aneurysms and subarachnoid hemorrhage and found cannabis use was associated with DCI. However, that study was limited by no urine drug screen for other drugs, such as cocaine or meth, and it was also limited by small sample size, and there was no adjustment for potentially co-finding covariance. Pathophysiology for cannabis-related ischemia is still under investigation. It may directly increase a person's vulnerability to strokes, altering the brain's maximum oxidative capacity by impairing the mitochondrial respiratory chain, by increasing reactive oxygen species and free radicals. It may also induce cerebral vasoconstriction and multifocal angiopathy. Interestingly, in our study, we found a higher rate of angiographic vasospasm cannabis users, but we cannot exclude the possibility that cannabis users have a lower threshold for DCI as well. Limitations of the study include retrospective analysis. It was a single-centered design, and we didn't have any cannabis-specific details, including timing, route, frequency, or quantity. So in conclusion, our results indicate that DCI was 2.6 times more likely to develop in cannabis users hospitalized for aneurysms and subarachnoid hemorrhage. Patients with DCI were significantly more likely to experience poor long-term functional outcomes. Given the recent legalization of recreational marijuana in many states, it's essential to continue evaluating the risks and benefits of cannabis. Future studies are warranted to quantify the dose-dependent relationship between cannabis and cerebral vascular disturbances. I'd like to thank Dr. Lawton, Dr. Albuquerque, Dr. Ducre, Dr. Zabransky, and Dr. Jada for the help with this study, as well as for their continued mentorship in other studies. Those are fantastic talks. Thank you very much. I don't see any questions that are in the Q&A box. I will reiterate, if there are any folks that have questions, feel free to put them in the Q&A box, and I'm happy to ask them. I have a question for our last speaker, Dr. Carapano. In my practice, I've seen a lot of patients, younger patients, presenting with marijuana-induced RCBS, or reversible cerebrovasoconstrictive syndrome, and I didn't know if you had seen any correlation with that in your research as well. I know you're doing subarachnoid-induced vasospasm, but we're seeing it spontaneously. Thank you for the question. Yeah, you know, we didn't look at that specifically, but just being in the vascular service right now, we are seeing some younger patients as well coming in with RCBS, with marijuana use, so that'd be definitely something interesting to take a look at, whether prospectively or retrospectively. It could be something there, too. It could be causing, you know, increasing angiographic base, a spasm, et cetera, whatever mechanism can, this is causing it. And Dr. Cheng, if I was understanding your abstract correctly, you saw a more robust remodeling in the cerebellum, is that correct? Yeah, that's correct. The cerebellum was the only part of the brain that we saw that had any change at all with the BCI therapy, so either we didn't capture the true remodeling in this analysis, or it had something to do specifically with the cerebellum. Do you think it has anything to do just with the cerebellum has so many other inputs, you know, with sight and hearing and everything like that? Is there any way to test for that being confounding? Yeah, that would make a lot of sense. I would guess that because the contralesional cerebellum didn't show any changes, that might support the fact that this is specific to the new connections with the contralesional motor cortex, it's lateral to the hand that is weak. Those were our reasoning. Seth, I had a question about your patient cohort as well. Were these patients that had Moyamoya only in the posterior circulation, but also in the anterior circulation as well, or just posterior circulation? Sorry, can you say that one more time? Were these patients that had Moyamoya changes in just the posterior circulation or both anterior and the posterior circulation? Yeah, so initially anterior, so this was all our patients that had that anterior circulation, Moyamoya, and then we had to review all those angiographs to find and score the posterior circulation. I see. Yeah. Still no questions on the chat here, on the Q&A. I suppose if there are no questions, we should probably move on to the next section. Thank you all very much for wonderful talks and all your and all your great work. Yes. Great talks. Thank you. Great research. Good afternoon. I am very pleased to introduce this year's 2021. Yes, your lecturer, Dr. H Huntington major. We all know him as time. In describing hunt, we can talk about chair chair president president chair leader. It's very hard to not come up with a superlative when we're talking about him. But I think probably best we should understand that hunt has impacted students faculty and colleagues alike through his thoughtful teaching his dedication to translating research concepts into clinical care, and his persistence. This is the reputation and legacy has cultivated since his training began at UT Southwestern Medical Center. He carried that reputation and Northwestern University in 1993 where he was the chief of the division. And subsequently in 1995 name the chair of the new department of neurological surgery at Northwestern University. He maintained that position until 2012 and he returned to UT Southwestern as the chair. During his career he's held all new neurosurgical leadership positions you might think of. And that is really a reflection of the commitment that he demonstrates and the commitment that others demonstrate to him. As a past president of the WNS this WNS award and lectureship is very pertinent and very appropriate for. As I've learned through working with his diligence and focus and commitment to training are unmatched. He's careful in the operating room, but he's also very careful on the road, so do not drive behind. I'm pleased to see hunt join the ranks of other yesterday lecturers, who we feel in the CB section exemplify the drive and search will excellence of Dr. I'm pleased to tell you that my favorite word in Spanish is in order. Right. That means congratulations, but the translation is appropriate for this and that's a good hour. We look forward to your lecture and the time you spend with us and we appreciate your leadership more than any words can say. Congratulations. I'm very pleased to be with you today. I was honored when Dr. Welch approached me on behalf of the CV section to deliver the 2020 yesterday lecture. And unfortunately, the COVID-19 delayed our presentation by nearly a year and a half, but we are here. I want to thank my co-authors, Drs. June Kim, Mario Corona, and Tarek Al-Amadea for their excellent help in stimulating my memory. I chose a topic that I think Dr. Gassergill would approve of, and that is to trace the impact of the endovascular evolution over decades of development and how it impacted us as cerebrovascular surgeons and what we need to be thinking about in terms of training our next generations. Well, I first give credit to Dr. Pirdon-Donaghy, who had the wisdom to recognize the genius in a young neurosurgeon from Turkey, Dr. Ghazi Gassergill. He brought Dr. Gassergill to Vermont, to his laboratory, where modern micro neurosurgery was founded. I'm pleased to report that that's about 100 yards from where I was born as well. Together, they worked with our representatives from ZEISS and worked on the illumination and magnification that we all enjoy today. The Contravis Microscope was really, the Contravis component was the stand and the balance, and his forethought resulted in industry helping us to create a weightless microscope controlled by three large wheels that were manually adjustable. And that is the microscope stand that I grew up with as a resident and early attending, early in my career. Dr. Gassergill's incredible scholarship over many decades will be a lasting legacy that will enrich the careers of many generations of neurosurgeons to come. So let's go back over the decades and trace how this all occurred. Starting in the 1960s, Dr. Jun Wada developed a way to test hemispheral dominance by the injection of dark barbiturates into the carotid. Charles Drake pioneered basal aneurysm surgery with unique surgical approaches and some tests that he worked out with John Alcock to assess collateral flow when it looked like sacrifice of major arteries would be needed. Uline is generally credited with the hypothermic circulatory arrest procedure with extracorporeal circulation. Charles Donner reported intravascular stenting for extracranial vascular disease in the 60s. John Gallagher did something that you would never get through your IRB, and that is to take a pneumatic gun, as you see here, and shoot horsehair and dog hair into the lumen of large aneurysms to induce thrombosis. Tom Speakman used a technique of carotid cavernous fistula trapping surgically with injection of radiolabeled gel form. John Oxney used another technique, a very pioneering, where he magnetically migrated iron microspheres into the lumen of aneurysms to induce thrombosis. Al Lessenhop from Washington created an embolization technique using handmade microspheres where he shot those into the carotid and they lodged either in the feeding system of AVMs, the nidus itself, or in the pulmonary circulation occasionally. Sean Mullen, a man with great creativity, took horsehair and injected that material into the lumen of aneurysms, and I saw many of those angiograms because he performed a number with Dr. Drake when I was in London, Ontario, and the initial post-op angiograms were fantastic. CLIP technology made major strides during the decade of the 60s, and I'm always amused to see the Suntke's CLIP, which saved a number of my early patients with intraoperative rupture from usually dorsal carotid wall blister aneurysms. In those days, the endovascular treatments were done by open neurosurgeons. With very entrepreneurial and with the culture, we've got to do something about this. In the 70s, Drs. Steiner and Lexell pioneered stereotactic radiosurgery to obliterate AVMs. Serbanenko used balloon catheterization, creative angiography, and temporary occlusion of major arteries endovascularly. Yasser Gill, of course, founded microneurosurgery, multiple instruments, bypass procedures, and scope. Jim Turco first described steel coils for arterial occlusion. Chuck Kerber, who was the father of North American endovascular neuroradiology, embolized these lesions with IBCA, which was a very hard crystal and almost quartz-like material, very tough for surgeons to compress the AVM during resection, and it tore up all of our scissors and instruments trying to take these out. He converted that to N-butyl, or NBCA, which was much more malleable and surgeon-friendly. Osabuchi treated carotid cavernous fistulae with electrothrombosis using copper wires introduced through surgically exposed superior ophthalmic veins. The decade I consider really the Wild West, where we were confronted with difficult problems and had to make it up on the fly, and if you had an idea, we tried it. The challenges were that we had rare diseases with rapidly developing neuroimaging platforms, but not much natural history to go on. Our therapeutic folks, neurosurgeons and interventional radiologists, felt compelled to try anything because of the threatening appearance of these lesions angiographically. We would learn over the decades that many of these were more benign than therapeutic alternatives if left alone. The 1980s, Braun first described coiling of an extracranial carotid aneurysm. Randy Higashida, detachable silicone balloons filled with a polymer 2-hydroxyethylmethacrylate that was a permanent embolic material. Ilal used platinum diachron fibers with a high thrombotic reaction and also short, pushable coils for endocyclic treatments. These were primitive and too stiff and very difficult to retrieve or control. In the 1980s, endovascular care was owned by interventional radiology due to their ownership of the Angiot suite. In the 90s, Taki reported embolization of AVMs using a liquid agent, EVAL, and subsequent modification of this compound gave rise to Onyx. Guglielmi, major transformative experience with detachable platinum coils. Turchman and Guglielmi used a swine model to do stent coiling of Braun-based aneurysms. Jacques Moret balloon-assisted coiling in humans. In the 90s, it was all interventional radiology. Neurosurgeons were excluded quite actively. One of those neurosurgeons was a young man from Buffalo who had a lot of ideas about endovascular opportunities and tried to get trained. He was not allowed to be trained in his institution and later sought training largely through invasive cardiologists. Those loyalties remained throughout his career. 2000-2010, the decade, LILAC reported the first series of aneurysms treated with flow diversion. This case represents a laser ablation of deep cavernomas. This case was done at the Emory Clinic, but not published during this decade. It was published the next decade, which I will show you. In the 2010 decade, it was interventional and neurosurgery as pretty much equal footing in terms of numbers. Dr. Hopkins and others had trained many neurosurgeons in this field. That's equal footing, equal participation. It didn't work out so well. It was open warfare because we didn't have a financial model to deal with this. We didn't have a financial model to deal with disruptive new technologies. People fought over the control of these patients, and it was not pleasant. There were some bright lights, however, and one was Bernard Bindock. He had done his undergraduate training with us at Northwestern and then got his endovascular training in Buffalo and came back. At that time, we were having very high morbidity rates endovascularly due to the goal of obliterating every lesion completely. When Bernard came back, that was not his philosophy at all. When he was in the suite and the endovascular risks were growing throughout the procedure, he would stop, abort, and bring the patient back for a safer surgical approach. In that decade, also up to 2020, many new technologies, the web device was done. We had the stroke revolution in 2015 with four prospective randomized trials that were positive for thrombectomy. Another great technology was the PulseRider 2016, a major new technology which dealt with bifurcation lesions. This is the paper that came out of the Emory Clinic, authored by Dr. Barrow and Bob Gross, which was a really great new idea for ablation of deep cavernomas. In that decade, neurosurgeons actually outnumbered the other participants, but neurology, due to the stroke revolution, had made major gains in numbers and interventional radiology also still strong. But something had changed, and that is we had a new business model. Service lines proliferated into stroke centers, where downstream revenue was brought back into this stroke paradigm, and it created mutual support and synergy amongst all participants, regardless of their background. And that will be going forward a major leg up. Dr. Welch asked me to address a question. Are neurosurgeons relevant to cerebrovascular care in 2020? My answer then and now is yes. Neurosurgeons are expert in diagnosis, differential diagnosis, wide range of options for patients, including surveillance, a culture of empathetic advocacy for patients, not procedures, and a culture of innovation that I've alluded to. And the most important one, continuity of care. From the time you get a phone call until the time the patient is back to family and work. That is what neurosurgeons do best. This is a procedure, the Dallas technique for retrograde suction of giant periclineoidal lesions. That's an example of how neurosurgeons ran into difficulties and created opportunities actually for endovascular surgeons in the process. In this case, the giant periclineoidal, the normal circulation is as you know. When you trap such a lesion to soften it for surgical correction, the blood flows retrograde into the sac through the ophthalmic and three cavernous branches. Dr. Sampson and I noted that many times, and particularly in ruptured aneurysms, the turner of the sac actually worsened after trapping than before. And on one day, I was doing the craniotomy. Dr. Sampson was in the neck, had the carotid exposed for temporary occlusion and angiography after the clipping. And I forced a clip application into a very tight aneurysm and ruptured it. And he grabbed an angiocath, stuck it in the internal carotid and hooked it up to wall suction. And the results were dramatic. The aneurysm collapsed and was secured uneventfully. This is that technique in a video, showing a giant spear hop of steel, and you can see how it collapses with a cervical carotid suction after trapping. This lesion lent itself very nicely to fenestrated clip occlusion with a series of clips. Over time, that was very durable for her. I have a 10-year follow-up angiogram, which is perfect. This is the first case we did in our new UT Southwestern hybrid operating room, which was an NGO suite as well. 64 years old, visual failure on the left in hemiparesis. Her sac, you can see here, largely thrombotic with a lot of frontal lobe edema, obvious grossly on CT as well as MR. At exposure, this is her lesion, left-sided, it's trapped now with an endovascular device in the high cervical carotid. In opening the sac, I always like to leave a large cuff or cup to be clip reconstructed once the thrombus is removed, and that's being started as you see here. Once the cup is formed and amputated from the upper aneurysm, the pancake dissector, the sonopet, cavitron can also be, or cousa can be used to evacuate the clot quickly. Then the pancake to dissect the remaining clot, which is decompressed with exercise and great care around the osteo into the carotid as an intimal dissection can be created and the loss of the carotid occur if you're not very careful. In this case, once the clot was out, I had not yet seen the optic nerve, but it's being exposed in this clip. You see the medial neck of the aneurysm there being dissected free. Once that was completed, a very large Mizzou giant aneurysm clip being applied with gentle treatment of the optic nerve. These are extremely strong clips. Once the aneurysm was secured, we came back and restored flow. The carotid was briskly pulsatile, did a great Doppler flow and so forth. We then took our time and removed the thrombus from the anterior fossa being shown here. Once it came out and we had it fully decompressed, we then looked back at our carotid into our chagrin. The carotid was now non-pulsatile, soft, and no Doppler signal. A quick angiogram confirmed either a tight vasospasm or a dissection at the side of the endovascular device, which was treated immediately with an angioplasty, with restoration of flow, and a great result for the patient. What are our challenges looking forward to maintaining relevance and leadership in this field? There are many implications for our board and the ACGME, and some questions that our vascular surgeons have to answer. Should all ABNS diplomats be endovascularly capable, or at least acute stroke capable? Should non-emergent thrombovascular care be centralized? Are hybrid trained dualists symmetrically capable or interested? How do we manage highly challenged technical problems as their practice or the open surgical experience decreases? Should programs training the next generation of vascular surgeons have a faculty advocate for open surgery as Dan Barrow has proposed? Next, how accurately can we predict what our future is going to be? Remember, our residents will be practicing in 2060. These are entering residents today. What will that world look like? You could ask Yogi Berra, he knew a lot of prognostication, but might not give you exactly the answer you're looking for. That was tried in France in the late 1890s, when Jean-Marc Côté, an artist, was approached by a small firm, and they asked him to imagine the future 100 years in advance, in hopes that his artwork could be used to celebrate the new century, starting in the year 2000. He did his work and he put his artwork on a set of cards. The company that commissioned him went out of business, and those cards, unfortunately, were lost for 25 years. Isaac Asimov and his wife were shopping in Paris at an antique toy store and found them in a warehouse. He took the cards, bought them, and studied them and used them to illustrate his book, Future Days. Many interesting things were noted in that series, and one was the helicopter for military purposes, and this was way in advance of the Wright brothers' first flight. He envisioned aero cabs. That was pretty remarkable, and the folding wings. If you're aware, the aero cabs are going to happen in about 2025 in the great state of Florida. He correctly imagined how we would move our aircraft around during decades of misery coming forth. But he made a mistake that we often make, especially in technological fields like ours, where you think about the future in a one-dimensional format, the aero cab. It had progressed, obviously, but the rest of Parisian life was frozen in this card in the 1890s. We have to remember, everything moves forward, but not at the same pace. Progress may be out of our control. There are accelerators to progress, usually other industries. Think of all the developments in our field that came from the military or NASA, neuro-navigation, for example, biotech. Who would have thought that COVID-19 would have accelerated many areas of our economy, which it did. There are decelerators, economic, economic hardships, geopolitics, global pandemics, COVID-19 hurt us in many ways, and changing health priorities. This is a 25-year study. Looking at the causes of death and disability in Americans across the 50 states, the seven top causes are as follows, tobacco, obesity, dietary risk, alcohol and drug use, diabetes, hypertension, cholesterol. Nothing related to neurosurgery or neurology there except indirectly. Times of hardship, we may be left out as society, some to think about. If you think about the future, say in 25 years, it is likely that the word personalized appears numerous times in this slide, that we will be able to individualize therapies like stem cells, neuromodulation, and so forth. But whatever the future brings, still unpredictable. Will we be ready? Why do I say that? Well, think about the ACIC bypass trial. Will our future trainees be capable of doing this operation? Will they have enough exposure? Jim Osman predicted the death of Andrews in surgery in 1995. Where are you now? Well, it's not dead. Will it be dead in 2045? It's hard to know. I doubt it. Ruptured aneurysms and eyesight. Will our trainees be able to handle the tight brain, especially after hemorrhage, and deal with complex microsurgery? The stroke revolution alerted us to a whole new set of issues, and that is economics. When you take the understanding that 800,000 people in America suffer a stroke every year, only 10 percent are hemorrhaging. The rest are ischemic. Wonderful devices like this, the pulse writer. If you consider, I said, patients, only 13 percent of them would have been amenable to a device like that, and not even thinking of it being individualized for specific aneurysms. There is no economic plan for that. On the other hand, thrombectomy, economics are very good, and that is not missed by our colleagues in the industry. Technological advances are occurring and will occur, such as this one, a new study showing intra-arterial chemotherapy for retinoblastoma is effective, endovascularly deliverable. In this case, a very bad condition, a fusiform giant basilar aneurysm, not thrombotic, was treated, and Dr. Welch evaluated this patient with us at UT Southwestern and ultimately trapped it surgically for a good deal of deliberation. That trapping was followed by a neurological decline. As you saw, the MRI showed no ischemic changes. Sam Barnett from our institution had the idea that, what about going transnasal transclival to decompress it? I'll show you a bit of that procedure that Sam did very elegantly. As the clot was being removed, sac deflated, you can now see the trapping clip. After it was completely deflated, the closure was done with a nasal septal flap. The post-operative MRI looked absolutely spectacular, as did the patient, so a clear save using that technique that I offered to you. The exoscope, another interesting technology, and that has many great things. The visualization is great, the ergonomics are great, maneuverability, and what I really like is the surgical assistant is back in the case. Robotics are highly energetic. This is a Google Scholar search showing in neurosurgery how rapidly that's come along. What about neurosurgical training? I'll study it from 100 years ago. I don't think so. The idea of having a single mentor and a room full of learners is not going to work in a minimally invasive world. What about core competencies? Think about this. In the past, you can see the areas that needed to be mastered in present, a lot more. In the future, this builds on itself dramatically, and the surgeons of the future are going to have to be masters of all of these things. How are they going to get that done? Do we increase duration of training? I vote no. Simulation-based? Yes. Virtual simulation? Absolutely. With simulation, we've lagged other specialties in that the haptics of brain and spinal cord, particularly in diseased states, is expensive and difficult to reproduce, but we're making progress. I'll show you a model that was developed at Northwestern by two of our wonderful fellows that went to join Bernard Bendok. They created a system using micro-anastomosis of objective structured assessment of technical skills, NOMAD. They used two different sized graphs, and they looked at elements which includes virtually everything that goes into the conduct of that operation that you can see listed here, completed anastomosis, and so forth. What they did is they used each of these elements and graded them in a Dreyfus sense with a scale of 1-5. Then as you can see in the surgical videos, the needle handling on the left by a novice, one-handed wonder, and an experienced surgeon on the right scores 1 and 5 respectively. I failed anastomosis on the left with a score of 1, and an excellent 1 on the right. This was shown by those investigators to improve, as you would hope, with increasing training through the training program. I was exposed to virtual reality in neurosurgery at Dr. Bendok's program in Scottsdale, and putting on the goggles and walking around a room, walking through the circle of Willis, going behind an aneurysm is truly incredible. Augmented reality is going to be huge in spine, but also in brain disease. 3D printing, you can give a model that a patient can hold in their hands and look at their pathology, but we can also use to simulate an operation to be rehearsed for the next day. But I think the real opportunity here is in big data. AI and machine learning together with big data is illustrated in an article in Nature Medicine, January 2020, to get down to patient-specific recommendations. But we have to have robust registries, and Epic is not it. Epic has a business plan to be a billing tool, and that's what it is. ICD-10 guarantees that we will never have registry-specific accuracy for it. But once we get that, the idea is to put those databases into a machine learning model, where the machine, the computer, tries different associations, refines, they discard the ones that don't work. They get better and better and better, and finally down to the individual patient. You know that you've seen that in your online shopping, how it gets refined to save you a good deal of time. It's been used by our neurosurgical group at the Brigham for outcome prediction neurosurgery, and our colleagues in vascular surgery have used it for aortic aneurysms to great advantage. The bottom line is, over time, knowledge demands will increase dramatically. Technical demands will change dramatically. Open surgical experience in many areas will be reduced. Complexity of open surgery will increase. AI, machine learning, advanced simulation, will improve training and conclusions from practice. We must embrace each new technology as it comes along, or it will be to our peril. Our best days are ahead. If, as we're confronted in the future, when we need change, is it going to be incremental change or will it be transformational change? Those decisions will have to be made, and we would do very well to heed the words of the great Nelson Mandela. May your choices reflect your hopes and not your fears. Thank you for your attention and best wishes. Okay. Well, that was a wonderful lecture, Hunt. Thank you for that. In the next half hour, we're going to talk about clinical quandaries and aneurysm surgery. I'm Michael Lawton, and I want to thank the program committee for allowing me to be a part of this panel. So I looked up the word quandary just to make sure that we were on the same page, and it's a state of perplexity or doubt. So what I'm going to do for you in the next 10 minutes is just share with you four cases, an aneurysm rupture, an iatrogenic injury, an arterial occlusion, and a dissecting aneurysm, and just take you through those interoperative moments to give you a sense of how I dealt with those. This is the first case. You can see it's a standard post-decommunicating artery aneurysm here on the left, and it's an example of an interoperative rupture. So the frontal lobe is to your right. This is my resident operating, and you can see that with a little brush of his sucker, he went across the dome and got the aneurysm bleeding. He was able to place two proximal clips, but you can see that the bleeding is still quite brisk and not controlled. So at this point, I stepped into the chair, and I just wanted to take you through some of my reactions to this. The clips are actually serving no purpose, and so they really just get in my way. So the first step is to take them off, which is counterintuitive, but you can see that with a very accurately placed sucker, and note there's no patty over the hole here, but just an accurately placed patty, I can dry the field, and I can get proximal to the aneurysm origin here and work in that little crevice that was under-dissected by the resident initially. And this is where that first blade of the clip needs to go, right there where my number six dissector is located. And you can see that I'm managing that just with my sucker to keep things dry and to keep working. With that defined, now I need to go and transition to the backside of the aneurysm. So I've placed a little cotinoid over the leak there, and I'm tamponading with my suction, and you can see there for the first time back here, the distal supraclinoid carotid, and there's the inter-carotid artery at my number six tip, and that's the other key finding. So we have to work proximal, get in front of the inter-carotid artery right there, and that's the place for the second blade. Now it's time to clip, so the cotinoid comes out, you can see the clip going in, and now with that precise application, the aneurysm is dry, and the problem is essentially solved. And that is really meant to demonstrate the steps. Even though you've got torrential bleeding, you're just doing the same steps you normally would if you could see. Here you can see, I'm just going to reposition the clip here, but that sequence there just showed how under-dissected the proximal carotid was. There is a little clip advancement, and that takes care of our problem here, the temporary clip comes off, and we've averted a catastrophe. So this case is an example of what I would call hands, which is the technical response to a problem. You can see the use of suction, the use of a tamponading pledget, proximal control when it's safe and add something, distal control if necessary, communicating with your anesthesia team for high blood pressure and cerebral protection, and most important, speed and efficiency as the surgeon. Now this next case is an example of an iatrogenic injury that I caused. You can see it's an anterior carotid artery coiled aneurysm. It is recurring. That coil compaction and aneurysm regrowth is progressive. Here we are at surgery. As you would expect, the carotid right down the center of your screen, the neck here to the left of the screen, and you can see some of the coils herniating through the wall. Notice here as this clip goes on, the mass of coils is so big that it ramps the clip down. It's going to slam into the carotid artery with a little bit of movement here, right there. You can see that artery ramped down on the coils and slammed into the carotid and tore into the neck. So you can see that we now have a rupture and a tear. I'm going to place a temporary clip on the proximal carotid, and that does very little to control the bleeding. Again, I'm using my application of suction right at the area where the bleeding is from, and now I'm trying to go on with a clip on the neck in a slightly different place above the carotid and the perforation. You can see it's just not working. I apply a distal clip, see if that helps, and still quite a bit of bleeding, and I can't get the clips in the right place. There's still that ramping effect. Here you see my next move. I've escalated at this point to entering the aneurysm, transecting the mass of coils, and separating the compacted coil mass from the neck. The neck, you can see there, is completely free. Now, with a little wisp of cotton, I'm going to cover that tear in the artery, and I'm going to use my clip to anchor that wisp of cotton right on the site of the tear, which you can see here. The clip now controls the neck. You can see immediate control of the bleeding. You can see the carotid there in the distance. I'm going to go on with just a stacked booster clip in this tandem configuration, and that completes our clip reconstruction. You can see how I was responsible for that injury due to the ramping of the clips, but I quickly escalated when my easy options failed, and I used both the transection technique and the little cotton wisp technique. This is a case example that I would call the head or the mental response, and that is you've got to envision every conceivable disaster. You want to pre-prepare to deal with that, with all of those disasters. You want to prepare to deal and execute at the time of the problem, and that has to do with control and temporary clips. You want to track the bleeding, visualize your anatomy, and quickly solve the problem. What's important is you've got to keep thinking through this, and so it's really no time to be conceiving of these disasters for the first time. You have to just go about a plan of working through contingencies so that you can adjust to the information that's coming very rapidly at you. This next example here is a case of branch occlusion, and you can see from this slide here, it's an MCA aneurysm. It was coiled, and the coils once again had compacted. I actually was asked to clip the aneurysms around the coiled aneurysm at the time of the initial subarachnoid hemorrhage, and that's what those clips are, but the coiled aneurysm is what occurred. I'm now going back in to clip this aneurysm, and you can see, as we often do, a lot of scar tissue around the shanks of the clip blades. We have to dissect through all that scar tissue. This is now the trunk coming off the frontal side of the aneurysm here, and you can see how densely adherent. You can see filling of the dome of the aneurysm with icy green. You can see actually three trunks from behind the aneurysm. This is the frontal trunk. There's a middle trunk, and there's a third temporal trunk, so it's really a trifurcation aneurysm, and this aneurysm sits right in between the frontal and middle trunks. Now, I'm going to use a picket fence technique, which means applying fenestrated clips over the dome because that gives me a nice tight squeeze at the tips of my clip, and it jumps around this massive coil. With the picket fence, I like to start in the center and work my way out to the sides, so you'll see the center post and the additional clips going on to the sides, and it's creating a nice closure of the aneurysm sac here with these four clips in our picket fence. It looks good on the frontal side, but as we look over here, this is our middle trunk here, and it's very pale, and when we do icy green, it's not filling. You see a little bit of retrograde enhancement there, but the artery is limp. It's not pink like these other trunks, and on yellow 560, again, we confirm the fact that that is not filling, so we've got to then go to plan B here, and the plan B in this case is to take the middle trunk off of the aneurysm and do a reimplantation, so this is going to be a standard reimplantation, which means excising the trunk from the aneurysm, fish-mouthing the orifice to widen the anastomotic area. This is the donor that's prepared here, and now we're going to just reimplant, and so what's interesting about this case isn't so much the suturing, so I'm going to jump ahead. Although it is interesting, it's an intraluminal suturing technique that's now, we're now at the extraluminal suture line, but you'll see that the wall thickness on the middle trunk was starting to fray. The layers were coming apart, and when we take our clips and we examine the bypass, what we learn here, again, with yellow 560 is this middle trunk is not filling. You can see not so well in that icy green that the middle trunk is not filling, which means that we have failed in our reimplantation, so what's interesting is we now have to resort to plan C, and that is we know that this frontal trunk over here on the other side, sorry, the temporal trunk on the other side is viable, and that is a much better donor vessel. You'll see when I cut the artery free, it wasn't the bypass. It wasn't the anastomosis that was the problem. It was the poor health of the tissue in this proximal segment here that was not allowing for flow, so in order to circumvent that, we need to do what's really a side-to-side reimplantation, so I'm going to use artery that's a little bit further downstream that's more healthy, and it's going to be, instead of an end-to-side reimplantation, it's going to be a side-to-side reimplantation, so this is what I would call a fourth-generation or type IV-B reimplantation because it uses an unconventional anastomosis here, specifically a side-to-side, so here's the sewing. It's the interluminal suturing first. The extraluminal suturing comes next, and I'm going to just jump ahead here to show you the final result here. We finish our anastomosis. We come off with our clits, and we close off the stump distally to that reimplanted trunk, and now we've created this reimplantation construct here that is widened patent, and we've salvaged that middle trunk, so this is, again, an overview, a rescue of that bad situation and a successful outcome here for this lady who ended up doing quite well, so it's an example of what I call heart or the visceral response. There's a rush of emotions whenever something's not going right, and you can see all of the different emotions. You've all felt this when things don't go right, but I think the key is remain calm, find your clarity and composure, and over time, as you go through these experiences, you become numb, you develop an intuition, and you also, importantly, develop a confidence that you'll get through this. Last case, a very unusual one shown angiographically to the left and also artistically to the right. It's a dual origin of pica with a distal aneurysm just beyond its confluence, and this turned out to be a dissecting aneurysm with an interoperative rupture, and so I used, at the time of escalation, this limb, this proximal limb, to swing over to the distal part of the pica and do a reimplantation using that variant anatomy as its own graft. So here is the view interoperatively through a far lateral exposure. Your vertebral artery is up in the upper right here. This is the aneurysm. You can see it's covered in clot, and I'm going to try and clip this, as I always do, and you see that the tissues here are so fragile that with a little manipulation, it's going to rupture here, and so the clip slides off of the artery. We're left with a hole in the artery here, and once again, we are forced to escalate to a bypass strategy. The temporary proximal clip goes on, controls our bleeding. This is our distal temporary clip. You can now see very clearly this hole in the artery. There really wasn't an aneurysm there. It was just this hole, and now we swing into action with our contingency plan. This is that limb of pica, which we can trap. We can now swing it over to the distal pica. Notice the oblique transection, important to widen our anastomotic area. We can fish mouth it a little further to make matters even better for us, and here, once again, I'm just going to move this along to the end here, and we've now completed our anastomosis here. We've got that internal jump graft. The aneurysm is completely trapped. I'm just transecting the parent artery here. Our bypass is doing its thing there. You can see an overview, and again, a salvage situation successfully managed by resorting to bypass. This brief talk was meant to demonstrate these concepts, preparation, study your films, envision worst case scenarios, and make your contingency plans. I can't stress enough that you want to do your thinking about a case before you operate because when things go bad, you just don't have sometimes the luxury and the clarity to think as clearly as you would otherwise. Escalation is the next concept. You always want to start with the simplest solution because it's usually best, but recognize futility and failure, react, and move on. Lastly is execution. I think execution, it's all about your attitude. I think if you have the indication to do something more, as I had in these cases, then enjoy the ride. These are some of the fun things we do in vascular, doing all these reconstructive things, and when you're given these indications, I think the attitude changes to enjoy it and not fear it. To conclude, I'll leave you with these quotes. Uncontrolled bleeding is the one thing above all others that unnerves surgeons in the operating room. The corollary to that is if you can handle these situations, you can deal with anything. Whether you're an aneurysm surgeon or a tumor surgeon or whatever, I think getting comfortable with bleeding is the key, and it's head, hands, and heart. With that, I'm going to stop, and I thank you. Hello. Thank you for having me and for the organizer of the WNS. It's tough to follow a master surgeon like Mike, but I'm going to try my best. I'm going to be showing you some cases where hybrid techniques were used, and hopefully I'll be able to show you how important it is to stay really disease-oriented and not procedure-oriented or device-oriented. This is a 50-year-old female presented with acute right third nerve palsy. She has this right-sided PCOM aneurysm. As you see here on the 3D, it's a dysplastic, ugly aneurysm with a lot of excrescences. You see here this big PCA. Actually, it was a true fetal PCA. Because the patient was a good candidate for surgery, and she presented with a third nerve, I decided to clip the aneurysm. I went to the operating room, and after I exposed everything, it turned out that there was a big plaque of atheroma and some calcification that goes from the neck of the aneurysm all the way to the takeoff of the PCOM. This acted as a whole piece, where whenever I placed my clip, regardless, I tried multiple clips, multiple directions, but if I want to have a complete occlusion, I'm going to lose the PCOM. Then at the end, I decided that at this point, I'm going to have this small residual, and I can let the patient recover, then take her to the angiosuite and coil this residual and follow it. This is a way where I think it was a technique that would complement what I did in the OR. This was the 3D, and you see the residual there. This is the coil that I did, and then this is a three-month follow-up angiogram showing that we have adequate, good, actually complete occlusion. The whole aneurysm is gone, and the calls are here, and we don't see any filling. This is a case where I think, could I have done any heroic things in the OR? Maybe, but I manipulated so much where I thought that if I'm going to keep on manipulating, I may break an atheroma or cause the carotid to occlude or have an embolus or something. This is a case where I think because I'm dually trained, I knew when to stop, and I used the other technique to complement what I did. I was able to push the envelope one way or sometimes maybe not push the envelope the other way and try to complement with a different technique. Another case of a 60-year-old patient with headaches and familiar history of aneurysms. I don't have the pre-op angiogram. It was done at an outside facility, but the patient had a wide-neck ACOM aneurysm, and if you see here, there's some calcification. Same thing in the operating room. The contralateral A2 would occlude unless I'm partially clipping the aneurysm. Tried with fenestrated, tried with perpendicular to the aneurysm, but the whole thing was calcified and the same thing. At the end here, the options would have been either to keep it clipped completely and then do a side-to-side bypass here of distally, or I decided to just clip it this way and then bring back the patient and then treat the patient with a stent-assisted coiling of the residual. You see here the clips, you see the coils, you see the stent, and then this is a five-year follow-up angiogram actually showing complete occlusion of the aneurysm and everything holding nicely. This is a case of a 63-year-old male who originally presented with a subarachnoid hemorrhage grade 3. We don't have the original angiogram. This was 15 years ago, so the patient was clipped, but we have an op note saying that it was an ACOM aneurysm 9 by 7 millimeters. So this was the patient's five-year follow-up angiogram. This is when we got involved. The patient came in and followed up with us, and this was an adequate, good follow-up angiogram showing complete occlusion. We don't have the pre-op, but it was a 9 by 7 millimeter ACOM aneurysm. Then we followed the patient. Then the patient presented 10 years later with headaches, and this is what the patient had. So this is now 15 years post-clip, 10 years post-five-year follow-up angiogram that showed 100% occlusion of the aneurysm. So you see this big recurrence. In this case, I think going in to clip it would be high morbidity. Another option is to go from the left side and try to clip it, but in this case, I decided to go and use a flow diverter and flow divert the recurrence. So as you see here, this is the filling. This is the aneurysm sitting there, and then my micro catheter going from the A1 to the A2, and this is the pipeline being deployed. That's the pipeline. This is the stasis of contrast that you see here, and this is a six-month follow-up angiogram showing that there is a complete occlusion of the A2, but it was filling from the other side, and the patient was asymptomatic, and this is a complete cure of his aneurysm. Another case of a 57-year-old female with headaches presented with this PCOM aneurysm, we decided to do a web device. Here's the web. You see a lot of stasis. If you look at predictors of aneurysm occlusion with web, it's whenever you have really stasis all the way to the venous phase. You see it here. Then the patient came in with a six-month follow-up angiogram with this recurrence. At that time, I decided to clip the aneurysm. I'm showing this to show that, you know, web devices are clippable and we can crush them. It's not as bad as the coil. Here I'm using a lot and scissors actually. Here's the web. This is how it looks like intra-op. This is the clip being applied on the neck of the aneurysm. This is initially with the stasis. Then this is the recurrence. This is the intra-op angiogram showing 100% occlusion. I'm going to show the last case of a carotid cavernous fistula. I want to show it's not an aneurysm, but you can argue it's a venous aneurysm here. This is a CC fistula. It was a type D. You see here all the drainage pattern was toward the sylvian veins. I tried to treat it transvenously. No IPS, no SOV, couldn't get it. We needed to get to the venous side. With those sylvian veins there, I decided that I would go in, do a burr hole image guided on the sylvian vein and catheterize the sylvian vein. This is what I did. Here it is image guided, a burr hole. Those are the arterialized sylvian veins. This is the angiocath that I'm inserting in the arterialized sylvian vein. Then the microcatheter is going in, as you see here on the screen. We're going to advance the microcatheter all the way to the cavernous sinus. Here it is. That's my microcatheter going from the sylvian vein all the way in. This was done in the hybrid room. Then I'm going to inject onyx. This is the angiocath. I'm injecting onyx all the way. Then I'm pulling the catheter 100% occlusion. Then just some gel form pressure on the vein and then a burr hole and the case is done. I think we should be able to accept all those and stay open-minded. If you look at this slide I'm showing you, and if you are fine with all what I'm showing you, as I said, it's not about a technique. It's not about a device. It's about just treating the disease. If everyone accepts all what we're seeing, I think we're all on the same wave. I'm going to end by saying some people would make fun of us saying hybrids, a mule is a hybrid. A mule has the best of both worlds. It's better than a horse and better than a donkey. A BMW i8 is a hybrid. It's better than a completely electric car and better than a regular engine car. It has the best of both worlds. I think, like I said in the beginning, if you're hybrid dually trained, you're able to really know when to push the envelope and when to stop and complement what you did with the other technique that you're also trained in doing. Thank you very much. Hello. It's a great honor to be able to be part of this panel. What a fantastic group of speakers. Excited to get a chance to follow Drs. Lawton and Jabor. I was asked to talk on complex aneurysm cases and in specific endovascular approaches to them. I'm going to try to cover some interesting cases and hopefully give you some insightful options. These are my disclosures. I actually don't think any of them have any relevance to this talk. I don't touch on them. Complex aneurysm cases dealt with endovascularly. The first case is a 65-year-old gentleman who is obese. He's an active smoker. He has cardiac disease. He's extremely scared of having any kind of surgery. He had an episode of chest pain and dizziness, which led to incidental aneurysm workup. He has an ACOM aneurysm and a 9-millimeter MCA bifurcation aneurysm, which you can see here from the outside. I actually first recommended surgery to him, but I told him I thought it could be treated endovascularly as well. He very much wanted endovascular options. You can also see as a small pericallosal aneurysm on this side, certainly doesn't need treatment. After that discussion, he decided he wanted an embolization of that right MCA aneurysm. Here's a picture. You can see quite clearly how the quite large intertemporal artery really comes out completely distinct from the aneurysm itself, from the aneurysm neck, and is really in the dome of the aneurysm just off. This poses a bit of a problem. At first, I went in and said, well, maybe I can just get the coils to lie nicely, which was wishful thinking and just a waste of time really. When realizing that wasn't the case, it became time to get creative. This shows I was able to take a wire and catheter loop around the dome of the aneurysm into the outgoing outflow artery and out distally, and then go up and deploy a stent retriever to provide an anchor and reduce the entirety of the construct. You can see here from before and after, you can see on the picture on your right, the stent retriever well positioned with the catheter in good position. Then this was able to be a buttress to protect from the coils entering into the neck of the aneurysm. This allowed us then to coil the aneurysm and then deploy an atlas stent, which is delivered through the same micro catheter, 17 micro catheter of the vessel. This allowed excellent reconstruction of the aneurysm and complete preservation of the branch. At his six-month follow-up, you can see that there's complete obliteration of the aneurysm and excellent patency of the vessels. You can also see we coiled his just almost six-millimeter ACOM aneurysm. Here's his 18-month follow-up, clearly a durable result, no neurologic events. We didn't have to take this large, overweight gentleman with severe cardiac disease to the operating room with an excellent result of the treatment of his aneurysms. Here's another case of a 68-year-old woman with a very large left ophthalmic aneurysm, nearly giant. She has a little bit of vision problems in her left eye. She went to a different hospital where they performed a flow diversion procedure. Unfortunately, during that procedure, she suffered a stroke. She had some left-sided weakness and a moderate aphasia. She went to rehab. She actually made a fantastic recovery from that injury and was doing quite well. Then she noticed she began to have progressive vision loss. These are little notes from the ophthalmologist who saw her and then referred the patient to me. I don't mind when they misspell my first name, but he wanted her to see us right away to try to salvage her vision. Her vision was extremely and severely lost and detrimented. She felt that she had no functional vision whatsoever by this point. She had had a series of MRIs by the other hospital that was managing her, who kept telling her just to wait, it'll get better, it'll get better. There was clear demonstration of increased edema around the aneurysm and very substantial aneurysmal growth during this time. We did an angiogram where she had an angiogram to evaluate that. Again, she was told, don't worry, this is fine. That's when she saw the ophthalmologist. She referred to me. What I want to highlight is this in review of this. You can see that the flow diverter that was placed has zero apposition to the wall. Hopefully, you guys can see my mouse. It's actually pointing into the side of the ICA, the backside of the ICA, nowhere near the vessel. Really, this has zero chance of ever curing this. As you can see from the growing thrombosis, it's clearly making it worse. This was frustrating to see this because my original plan was that this should definitely be treated surgically. We could rapidly decompress the aneurysm and the thrombus, trap the aneurysm, decompress the aneurysm and the thrombus, reconstruct the neck and be done. That would certainly be my first choice. However, seeing that there was this flow diverter going all the way from the peaches carotid all the way up to the ICA bifurcation, floating in the breeze, not adhered to anything, I had real concerns about what that would mean in terms of trying to trap it, in terms of trying to put a clip across it, or even if I trap the MCA and the ACA, what am I going to do and what thrombotic type process is going to happen with this stent just floating there in the middle of the ICA? As a result, we brought it to our cerebrovascular board and we decided, let's see if we can salvage this endovascularly. What we did is went through, used aggressive angioplasty to try to open up the stent, reorient it a bit. Then we dropped additional flow diverters of a different brand from the MCA all the way down. She had a good ACOM and tried to reconstruct the whole structure. This is our post-op. By the way, you can see from the time the outside hospital did that diagnostic and the time we brought her back for her treatment, the aneurysm had even further recanalized and grown, but we were able to get really good wall apposition and re-approximation of the stents through these vessels. More importantly, on her follow-up, and we've subsequently stopped her double antiplatelets, and my expectation is this will be completely gone, but you can see a really great result, a dramatic reduction in the aneurysm. More importantly, she's had dramatic vision improvement. She now has a complete return of nasal field in her right eye and her left eye is also markedly improved. She's quite happy because she now can get around her house and move and do things and doesn't feel completely blinded. This next case is a little different, 68-year-old woman with migraine headaches and hypertension. She has a 6-millimeter PCOM aneurysm that's incidental. What you're going to notice when you look at this is there's a very steep ICA that cuts up. The space between the end of the aneurysm and the beginning of the A1, there's only a millimeter or two of error for placement of your flow diverter to treat that aneurysm. Honestly, I think in retrospect, this aneurysm would have been better treated with a stent and coils and or surgery, but we went in, placed the flow diverter. We're very happy with the result and initially had a good amount of stasis, which made me happy. I like to plasty the stent so that it has really good wall apposition as was evidenced in that prior case. Here's the stasis before we do it. We go and do our plasty, but afterwards, there's no more stasis. What we see looking really close is that the stent has just barely dropped into the aneurysm right here. We don't have a good seal from flow diversion. I go with a second flow diverter, drop it as well, a little more aggressive about being a little more distal, get really great plates and do the post-plasty. We have good stasis in the aneurysm, but unfortunately, we have another issue. We've got overhang of the stent over the ACA. The question was, do I leave that? Do I try to completely seal off the ACA because there's a good ACOM or do I try to rescue it? In this case, I think the best choice was to rescue it. We slipped a wire by and then brought up a balloon, inflated it and tracked it down to pull the flow diverter to the proximal edge of that orifice. We were able to dramatically change that. Happily, on follow-up, the aneurysm is 100% gone. There's a little bit of narrowing to the origin of the A1, but there's overall a really great technical result. She's done very well. Now, this is a complicated case where you have a 69-year-old woman who back in the 1990s had a left ICA aneurysm takedown for giant aneurysm on the left side. She also had aneurysm on the right side and she had clipping done. This was before I had completed my training. This was somewhere else. You can see this is what she's had, but what you can also notice is she began to have growth and dysplasia of her right-sided aneurysms, which are the only source of flow for her vessels. This is a great picture to show the dramatic progression of those right-sided aneurysms, which are much bigger. You can see on these pictures. This was one. She's got no left sided vessel. She's filling both of her cerebral hemispheres from the right side, but she has dramatically growing aneurysms on that side. What do you do? We opted to perform a bypass to the left side in anticipation of then performing flow diversion on the right side. You can see the flow has been taken over on the left side a good bit by the bypass and the flow diverters are in good position. We're currently following her and looking for aneurysms. They've already shrunk a bit. We're waiting for them to completely go. The next case and the last one to try to keep us on time, I think it's the last one, is a woman who had an essentially giant right pica aneurysm that ruptured. I think this is an important and viable way to approach aneurysms and a good way to advocate for endovascular. She was ruptured. We know that from BRAT, picas often have some of the worst outcomes surgically. She was coiled acutely with a small medium neck residual, but excellent dome protection. She did wonderfully. She recovered, resumed all of her normal activities, but she had substantial recurrence in the aneurysm. I would submit to you that I think that's okay, because at this point, you can deal with it any number of ways. The first indication or first thought was, well, let's flow divert it. The only thing that we didn't like about that is if you look, you can see that the pica really comes out of the aneurysm. That's something we don't want. It's unlikely that's going to make the aneurysm go away if you put a flow diverter across in the ICA. This is one where, although endovascular treatment got her through all of those acute phases, we're able to instead take her for a far lateral, identify the neck of the aneurysm, cut open the aneurysm, pull out the coils as you saw from Dr. Lawton earlier, use a picket fence type reconstruction to get rid of the aneurysm, she ends up with an excellent result. This is done in a non-swollen brain in an elective fashion. Most importantly, she makes an outstanding recovery. This is her the next day with my awesome haircut I gave her in the ICU. With that, I'll say thank you very much. I think complex aneurysms need the full skill set of endovascular and all the different options that are available. Certainly, we want to continue to use the surgical tools that we have as neurosurgeons. Thank you very much. Those were great cases. That's Gail and Jay. Thanks for sharing those. Do we have a fishbowl discussion now or should we open this up for feedback? We can hear you. Okay, great. Thank you, Mike, Pascal, and Jay for really great cases. I think for the panelists, we have enough food for thought and a lot of great cases to have a discussion. I've been taking some notes and we can go in order starting with Dr. Lawton's cases. Stacey, your thoughts? I know the first case I'll just quickly review. It's the most dreadful situation in the OR. You're not on the captain's seat and you have a resident. Unfortunately, we have a proximal paraclinear aneurysm with minimal control and intraoperative rupture. Obviously, in master hands like Mike, within a few minutes, the aneurysm is perfectly clipped and controlled. I wanted your thoughts in terms of some of the junior attendings when you're first starting out. Obviously, you can't prevent that, especially in a teaching institution, but are there any other steps to gain proximal control before you're even closer to the aneurysm? What are your thoughts on prepping the neck? When do you cut down the neck for a PCOM aneurysm? I had the privilege to train with Dr. Hiros. He was certainly a proponent of always making sure that you had access at the neck. I routinely, if I'm going to be doing that, I'm fortunate to have endovascular as well as open surgical skills. If it's something that I'm going to be doing operatively, I'm always going to either be thinking, okay, can I get balloon access to the neck or just having the neck prepped and available? One thing that comes to mind are things to not do. And so, we actually had a situation when I was a senior resident that I will always remember. Rupture in the OR, it happens, right? And I was a resident at the time. And so, the fellow that was there, very calm, said, okay, no problem, let's get compression on the neck. And they switched seats and what have you. The junior resident ran, put pressure on the neck. After we kind of got things under control, we all realized he had pressure on the wrong side of the neck. And so, making sure that these small details, I think it takes a second to prep the neck or at least to have things exposed. And it's worth just even going through those steps so that you're available. But I think the biggest thing is honestly staying calm, communication with your anesthesiologist. When you give the oral boards, you hear everybody say, I have two large boar suckers. But I think all of us in practice know that that's not really what, it's focused, it's identification of the bleeding point, some cotton, some pressure, get proximal control. Yeah, great. And I know in my cases, every PCOM gets the neck just prepped in case you need something in the case of a catastrophic event. And really take a look at the native view of your lateral angiogram. There are PCOMs and then there are really proximal PCOMs, not every PCOM. You could have this really proximal posterior paraclinoid and you may struggle or have to do a clinodectomy. So, those are the ones if you're a hybrid that you may want to consider and a flow diverter or something like that. And I think using the technique of extradural clinodectomy as well, when you do look at that lateral unsubtracted view and say, oh, it's a little close, there's no reason, especially kind of at those junior levels and when you have residents operating, you don't necessarily need to take the chance. We can be skull-based surgeons and we should use those tools. Great points. Thanks, Stacy. So, the next case of Mike's was that choroidal aneurysm rupture at the neck. A question for Demetrius, what are your thoughts? Are you aggressive at removing coils in a previously treated aneurysm? Certainly, the coil mass effect there was significant and unfortunately caused the clip rupture at the neck. Or do you try to fit the clip before considering removing coils? I think flow diversion was great in there. No, the main thing is that I think you have to tailor to the need of the tissue. At that point, he couldn't mobilize everything. He seemed very scarred down and I think at that point would call for this. I think it's even from Dr. Bacher's talk earlier, you have enough of a cuff, you know, so whenever you make the decision to take the coils out, always think about the reconstruction of whatever is going to be left there. We have seen situations that you can try to crush through. I think Pascal showed the web that he was able to crush through. So, I think that a lot depends on how much of scar tissue you have. I think if you can do without, it'll be better. I think every time you get into that scar, you are more prone to potentially have an avulsion of the neck of the aneurysm and that could be very complicated. I tend to also have sun clips available. So, call for that tray if you don't have in your room ready to go and I think, you know, have the cotton paddies to place your clip and any tears you may have in the artery. All these things are really important to as you're putting the suction on top, making the decision. If you're going to go for the coils, have those things available because you never know if the tear could get bigger, then you'd have a way to get around this. The discussion of proximal control will be crucial before you do anything like that and proximal and distal actually. So, I think that those are the things that we'll do before you embark into taking coils. Make sure you have a really good plan of control of the flow and repair the vessel in case you lose a lot of tissue. Yeah. Great points, Dimitris. And also the location of the choroidal, you know, if the coil mass and the choroidal are coming off from adjacent tissue in the aneurysm, then really be very hesitant to remove the coils. The next one was just a masterpiece of, you know, the branch occlusion and MCA salvage with a double bypass, fourth-generation bypass in Mike's hands. Greg, as another master open surgeon, what are your thoughts in terms of salvaging that situation and what would you have recommended in a similar scenario intraoperatively? I know a lot of us would have considered coiling, because I know Mike mentioned the dome, the interstices of the coils we're filling. What are your thoughts on that nasty aneurysm with scar tissue post-subarachnoid? Well, I think it was obviously an outstanding and creative solution that, you know, hopefully I would have thought of it in the operating room the way Mike was able to do that. But, you know, I think the main thing is you've got to prepare going in for bypass and make sure the both STAs are available and think through, you know, options that you may have, you know, under those circumstances. I think that, you know, my own approach when the initial bypass failed, you know, it's not infrequent that it's kind of that, I mean, you can try to reopen the anastomosis, irrigate out and try to salvage it, but once that initially has happened, often that's not going to fail. I guess the side to side with another branch was a great idea. I just wonder, you know, looking through things at the time of the surgery, was there a more distal component of that branch where that either in retrospect or as a revision could have been another option if, for example, you couldn't swing in the, I think it was a temporal M2 or temporal M3 that he brought over, if that wasn't an option, if the side to side with a neighboring branch wasn't an option, what else would you have tried, Mike? I'd love to hear your thoughts there. One thought I had was going more distal on that branch where perhaps it was less diseased might have been a different approach under certain circumstances. And that's another excellent point. In any vascular case, always preserve the SDAs because you'll never know when you need it for reconstruction. The last case of Mike's was the distal pica aneurysm, nasty aneurysm, perhaps dissecting aneurysm considering how friable the tissues were. Matt, what are your thoughts in terms of as a dual trained neurosurgeon, flow diverting something like that, would you consider doing, for example, a Fred Jr. as opposed to, you know, something so technically challenging? I think that that's always an option. The thing that bothers me kind of in the distal pica is just the diameter, the very small diameter of the parent artery, which I think lends itself to kind of more technical complications and limitations with, you know, with very small flow diverters. And then obviously you're, you know, once you place a flow diverter, you're committed to dual antiplatelet therapy, you know, in the setting of a subarachnoid hemorrhage if that is the situation. So I think that I think that that case was expertly handled. I think it's important to kind of have all your options available. At least in my hands, the occipital artery is a very difficult artery to dissect out and prepare for a bypass. So I think if there's any question that you're going to need that up front, it's, you know, to kind of devote the time and dissect that out or an in situ bypass kind of similar to what was done there. But I would probably try to stay away from flow diverting in that case. Demetrius, what's your lower aspect of diameter of a vessel to consider a small flow diverter for a vessel like that? Yeah, I know. I think we've seen the first case I did with Silkvista was that one was the Silkvista baby. If it's really meant for that vessel, you actually don't even change the shape of the vessel as you go inside with a micro catheter. We're talking about now a micro catheter, like, you know, the lowest profile micro catheter we can deliver a flow diverter, so you don't even change the shape of the pike. I think that's the territory of those flow diverters. The vessel we did was about 1.5 millimeters. So it will get bigger as the flow diverter is a little bit oversized in that location. And I do think that it saves you a lot of headaches. I think we can, Jay showed a case also with a recurrence. I think if surface modification becomes, you know, we'll see how the advantage trial goes or, yeah, no, sorry, advanced trial goes, I think we'll be able to potentially that surface modification in a small vessel like this could even be an acute use. But on Jay's and Mike's case, I think both bikers, I think today, SilkVista baby will be the way to go in most places in the world. Yeah, I would agree with you. Now we don't, back in the day, we had to use an O2-7 micro catheter to develop, to deliver a flow diverter. Now you can deliver with O2-1, 17 micro catheters, so definitely something to consider. 17, and the other thing, I think the comment of the distal, the most important is not so much the size of the vessel, sometimes it's also how much length you have for the wire to go forward. So without getting vasospasm, the distal anatomy, and these are coming now with very short distal wires, so, and very soft. So you're able to deliver right in position without having too much of a distal purchase. Yeah, and great point about surface modification coming up real soon. So moving on to Pascal's lecture, Greg, I know his first case, we've all been there, atheroma at the neck. And again, the most challenging case was the size of the aneurysm and the proximal location of the aneurysm as opposed to something, you know, like an MCA. What were your thoughts, and not being a dual-train hybrid, what would you have done different to try to salvage it by an open approach? I know Pascal handled it perfectly and, you know, utilized his second tray to coil the residual. Yeah, so that was the PECOM, right? That was the PECOM where we left the residual associated with the fetal vessel, obviously. You know, frankly, I have a great relationship with my interventional colleagues and have had that situation where you have a larger, wide-necked, complicated aneurysm, and with a clipping, you wind up with a narrow-necked, simpler thing that can ultimately be completely treated after surgery with a coil. So I probably would have done something similar, I just wouldn't have been the one coiling it myself, but I would have involved my interventional colleagues and, you know, have a great, you know, have a conversation in the operating room. They come, you know, very quickly and, you know, as do I to the angio suite to have those kind of conversations. So it would have been, you know, a different approach with two different people involved, but I think I probably would have taken something similar in terms of an approach. So you would have called a friend? Yeah, well, I just, I mean, you know, there are, you know, you could consider, you know, trapping and opening up the aneurysm, trying to take atheroma out in, you know, in a generation past or years past, that's the kind of approach you'd have to take. You could, you know, you'd have to think about those things in past era, but nowadays I just don't see why those kind of techniques are required in most of these situations. You just got to have a good relationship and a good setup, you know, where you have people that you trust and you can have those conversations and either it's an individual, we have two of them now who do both and they can make those decisions on their own and do both techniques or in my situation, I would, I would ask my endovascular colleagues what their thoughts are and if they can, they can take care of something narrow neck like that with a simple coiling after, I personally am not going to push it to be heroic. I'm okay with two procedures to fix the problem. Yeah. And again, the association with a fetal PFAM really limits you endovascular, obviously you cannot use a flow diverted stent, A, you have a fresh craniotomy and B, you've actually published this fetal circulation, flow diverters do not really work, you wind up still having the residual. Next case is the ACOM clip following a coiling embolization and I don't know if you guys remember the case, but I know Pascal mentioned an A2 to A2 bypass and side to bypass, you know, versus taking the patient to, to coil the secondary dome. Any thoughts on, on that case, Greg or Stacey, would you have done anything different there? I think, you know, there, there are options and I, I like what Greg was saying, I tell my residents neurosurgery is very much a team sport and I think when you have multiple different techniques, you put them together and you come out with the best outcomes so that you're not doing aggressive maneuvers that, you know, have higher risk of, of stroke. And so, you know, I, I think you've, you've got good potential options here, you know, and so if you've prepared and you have an adequate craniotomy that's going to give you, you know, access to both of those A2s and they're of good size, you know, going ahead and fixing the problem right then is, is certainly feasible. You know, I think there's a lot of potential options. I will say one thing that we have definitely learned is you don't want to float avert across an ACOM from kind of one A1 across the ACOM to the other A2 because things that didn't exist will open up, you know, if you have a hypoplastic A2 and so you either really have to float avert kind of on either side, you know, or, or going in and, and trying to do a stent coiling is, is certainly possible. So I think there's, you've got a cavalcade of good options really. And there's always that concern, you know, of potentially compromising both A2s in the setting of an acute bypass there. Yeah. And what have you, what have you prepared for? I think that's always, you know, if you've prepared upfront and kind of thought, okay, three steps ahead, what are all the things that can go wrong and you're ready for it? Awesome. If you haven't, and you're trying to pitch it, things can get a little stickier there. Yeah. Which sets us up for his next case, which was a, an ACOM that had a really bizarre recurrence post clipping ligation at an outside facility. So unfortunately, you know, you don't really know the full story but some concerns there for a distal A1 dissecting pseudo aneurysm always, whenever you have these growing aneurysms following clipping, assuming that they didn't miss it the first time around. Matt, what were, what would your thoughts be? This was the perfect case where you had a distal A1 where you can land a flow diverter from ipsilateral A1 to ipsilateral A2. What if the recurrence incorporating the ACOM complex, what are your thoughts in terms of how would you address it with the understanding, you know, with what just Stacy said, you would never flow divert against an ACOM complex. A, it's not going to obliterate the aneurysm and B, you're potentially running risk of thrombosing either A1 or A2 on the other side. You said you, the question was that if you had- What are the options at that point? If you have an aneurysm filling from the left, recurrent from the left, not much from the right with recurrence that you're concerned about a dissecting pseudo aneurysm. Yeah. Yeah. That was certainly a very challenging case. I think to your point, I would be much more concerned about a pseudo aneurysm, you know, rather than kind of an aneurysm recurrence. And so I would think that surgically that would be a very, very dangerous situation. I mean, it would be possible to, you know, to, you know, to stent coil the aneurysm. I think that that would be a very reasonable thing. And then, you know, you could avoid the situation of placing a flow diverter potentially across the ACOM. But I think a flow diverter would be very reasonable in that situation as well. Yeah. But I'd probably want to add some coils, you know, just to, in either situation, just to ensure, you know, complete obliteration. Yeah. So don't forget, right, standard stent-assisted coiling you could potentially in a high-risk redo such as this one. I think most of us would avoid taking the patient back to the OR. And obviously, if you're right at the ACOM complex, not consider flow diversion and stent-assisted coiling, either one stent or sometimes wide stenting, I think this would be a great approach. We went to his next case, web recurrence. We're now starting to see them, and some of them need to be clipped. I've done two myself where one was the perfect case, beautiful dissection with a nice neck. Like Pascal said, they're very compressible. And oftentimes you can really clip right up and crush the web. And I've had another pericallosal recurrence with significant scar tissue in the interhemispheric fissure where the actual dissection around the neck took a lot longer than the clip. But what are your thoughts? And Dimitris, have you seen these recurrences, have you treated them, and how have they worked out for you? I mean, we definitely have seen the consequences of, you know, the learning curve. Of course, a lot of things we see, we start refining where the webs are going to fit maybe better to continue reproducing the results we saw in the trial. But yes, whenever that happens, how to deal. Question is always, should we go, if possible, to a, as you know, we're starting now a trial with, it's called NEC, N-E-C-C, which is looking at a contour device only at the neck. So we do have somewhat of a response to that with intrasacral potentially treatment at the neck level. The other possibility is to go for diversion in the parent vassal. So those are two endovascular options to the web failure, perhaps. But the other option with surgery, I actually haven't had to do that. So I've seen most of the cases that you guys have presented, and that's possible to clip. And I would say it's a, my hesitation is always that if it's going to be malleable and flexible, like you said, or soft, like you described, since that's the case and consistently, I would be very happy to do that. Another thing that is also growing, we just got approved for OCT in cardiac for the small catheters that potentially will be able to be using neuro to see the neck of the aneurysm after deployment of web will probably be a better predictor than the stasis of contrast inside of the web as if the placement or the sizing is good enough, or we should remove it because it's not going to heal well. So like predictors of healing, maybe that'll be the best approach is to avoid a failure. Great, a great option there with contour coming up. So that'll open up some additional endovascular choices there. Okay. Last case with the CC fistula. I mean, that was a master case. I don't know if anybody would have, if anybody on the panel is experienced with direct cavernous sinus puncture, I know we don't really do it here, but I guess that would be the only other potential. I don't know, Stacy, Matt, Greg, if you guys in your centers, if you did direct punctures or not, and your experience with that. We haven't done that. Usually you work with opto for cutdowns on the superior orbital vein to gain access is what we do. Yeah. And in his case, you know, all the drainage went through the Sylvian vein. So that kind of limits you there. But yeah, I think that would have been the only option. And you know, the main point there is you got to go for gold. You know, once you have puncture, these arterialized Sylvian veins, you have to cure the fistula. Otherwise, you know, it's going to be a real challenge even removing your micro catheter. So you got to go for it. Many times you can go try to find the inferior petrosus sinus, even if it's not, maybe you're not feeling, and then get to that compartment. So that's always an option too. And I don't know if you tried that. So you've tried it, even though there's no inferior drainage, you were still, was it marathon? Yeah, exactly. You try to get through it and then sometimes just the wire, and then you bring a micro catheter over and you'll find yourself into the cavernous sinus. And it just comes through the back door, even though it's not feeling, yes. Sometimes you end up not, not actually in the IPS, but there's many channels, you know, to the IPS. Sometimes you end up kind of working your way through the basilar plexus. For these cases, I actually don't heparinize them until I've gotten that cavernous sinus access because of that very thing. You can only imagine you're going in and out some of these venous channels when you're creating them. But it does where I actually just did a case like that, not for a direct fistula, but for an indirect. And I completely agree with you. When you have retrograde cortical drainage, you've got to, and you start embolizing, you've got to finish because you cannot block off your access and you just got to keep going until it's done. I think another underutilized option too, is going transfacial to angular vein, which you can do, you know, either through the radial vein or brachial vein or through a femoral vein. So, you know, the approach, the system has to be pretty stable. It's generally kind of a triaxial system, but you can kind of avoid some of the pitfalls of having, you know, orbital pathology and orbital injury by the direct carotid stick. Yeah. So all those great options for anterior drainage. I think, I remember this case, he did try to go through a non-dilated IPS and they weren't successful. So, but no experience in direct cavernous punctures, right, in this group? I know we don't do it. Yeah. Okay. Lastly, Jay's presentation. So great on the vascular cases. Dimitris, question for you, the embolization of the MCA with coiling, I know Jay did the really slick anchoring with the stent reaver, the anterior temporal, and then ultimately stenting through the microcatheter with an atlas. Would you have gone through all that extent and a lot of increased risk to salvage an assuming non-dominant hemisphere, I don't know about the lateralization of speech here, but on the right side to spare the anterior temporal or not? Well, I mean, I think this is, that all depends when the case was done. I'm sure Jay would have considered today, but the inter-cyclar flow diverter, or he did talk about the clip in, but the patient didn't want it to do that and preferred. But I think he did a great example how to do it. It is a level of complexity that we are decreasing to our surgery today. Also, I think that with contour and web, we are likely will be able to protect that branch and take care of the aneurysms like that. Or there's a controversial topic of just placing a full diverter in the MCA2, which is a growing field. But today, I do think it's too early stage on that. I think that inter-cyclar would be the way to go for me, more like a web or a contour. Greg, I saw you smiling, Greg. Can I make one comment about this? What's that? Can I make one comment about this? Yes, please. I saw you smiling. Well, I mean, that was an unbelievable result in Herculean efforts. It seems like you're throwing everything, every technical approach at it. But I just would say that, and I know the patient didn't want surgery, but my own comment is surgery has changed. You do a lateral supraorbital craniotomy or a mini-teriornal craniotomy through a, well, a lateral supraorbital craniotomy where you don't even, you have a very limited mobilization of the temporalis muscle off the superior temporal line. The patients, they go home in a day or two, they recover within a few weeks. I think that type of surgical approach for an aneurysm like that, you gotta kind of have that conversation with the patient and let them know that things have changed. It can be done in a way that's much less intrusive on the patient and they can get back to their life much quicker than a standard teratonal craniotomy. And actually, in my own experience, the results are even better, I think, because you have less brain exposed and manipulation that you can have really outstanding results. But the key is the cosmetic result can be, don't cut their hair, you don't mobilize their temporalis muscle, a small bony opening, the patients go home in one or two days and they recover within a few weeks. It's just not the same kind of craniotomy that they may be reading about on the internet and worrying about why they would not wanna have that procedure. So that, I think that that advancement and change in how an operative aneurysm can be taken care of could color the discussion with the patient in a way that they may be more open to a surgical intervention, which had been very straightforward for that case, rather than something endovascular. Right. Just a couple of thoughts there. No, I totally agree with you, Greg, and that consideration and having that, I'm sure that was going through Jay's mind, but patient is on aspirin, Plavix, apparently he had some comorbidities. So sometimes if you need to be on anticoagulation, things like that, these are all things that I think goes through our head at that moment. Yeah, and I think based on the pictures, it looked like an older case, so most likely endovascular wasn't really an option at the time. His next case was also a challenging case. It was a recurrence of an ophthalmic aneurysm filing coiling with a flow diversion and outside facility that went awry. The patient sustained an infarct. And that was, again, another very successful case where he had the guts to go through the older flow diversion stent and balloon angioplasty. Matt, a question in terms of what are your thought process concern about doing a balloon angioplasty on obviously not properly placed stent with no wallop position, and your concern about potentially balloon angioplasty something that may have thrombus in it? Yeah, I think that that was an extremely difficult case. I would be a little bit concerned about damaging the initial device by an aggressive kind of plasty that was beyond the nominal diameter. I think that what he did, which is basically just to try to re-catheterize through the initial device and make sure that there was wallop position before and after would be the appropriate thing to do. But in that case, it's easier said than done because it's very, very challenging to get through kind of a floating flow diverter in the crowded. But as Jay had said too, with a flow diverter already in place, I think that your surgical options would be very limited. I would be very concerned about temporary clipping in the setting of a flow diverter there. I think that that could potentially damage the device and cause an arterial injury. Steph, I don't know if it's stentactomy. That was really slick there. And sometimes the most challenging part of your case is to exit a flow diverting stent with that wallop position and really excellent skills there being able to do that. Another option, oh, take that. Just stentactomy may be another thought. I don't know how old was that device in there, but some reports on removal of flow diverters and that may be another possibility. We have had not great luck with a chronic angioplasty. So it's probably was somewhat fresh. I don't know how long after the flow diverter was placed to consider the angioplasty like that. But after a while, it's not that easy to do. How would you recommend removing it, Dimitri? I think that, I mean, the snare with the stent retriever, that's the most described technique. With that bed up position, I think it's pretty straightforward to place a snare in there. And then, of course, the problem is you still have to probably have a balloon guide approximately and stop the flow and aspirate to avoid any clot. Yeah, and obviously make sure antiplatelet is where it needs to be fully heparinized. These are high-risk cases. And I love his next case with a very slick move of bringing the flow diverter proximal from the A1 into the distal paraclinoid by inflating a balloon and dragging the balloon. So that was his next PCOM flow diversion case. Stacy, your thoughts on, I know Jay mentioned it, that he tends to do balloon angioplasty to improve wallop position. Do you always do it? Do you sometimes do it? Is the nemesis of good better sometimes and you kind of let things be if you have, because I know in Jay's case, he had great contrast stasis in the PCOM and then did the balloon inflation and lost a little bit of that. What are your thoughts on that? I am a big enemy of good is better kind of person. And so I don't always angioplasty. If we're able to lay the stent and you've done the appropriate technique and you get good wallop position, you have a little stasis, get out. We know that the longer that you keep your devices up there, the higher your risk of thromboembolic complications. But there are certainly cases that we've all had where you deploy it and there's just a part that you don't have that great wallop position, in which case, going back through it, bumping into the stent, getting a balloon up there with some gentle angioplasty, I think is very, very reasonable. But I agree, I've seen and I've caused several times where you try to make it just perfect and that's not adequate. I will say if there's any stenosis to it, that I would much more aggressively angioplasty and try to get open because I think we've probably all seen cases come into us where that wasn't done. And now you've got this situation where you've got an ongoing instant stenosis and trying to get that open in a delayed fashion is challenging, if not impossible sometimes. Yeah, another trick, the proximal most part of the stent, if it's not very well opposed, oftentimes before reverting to balloon angioplasty, I just take the micro wire, give a really nice J and try to abut the proximal tines of the stent and see if you can get it to open a little bit more in a freshly deployed stent. So that's also another option. Stefa, but sometimes angioplasty of the stent and its body will foreshorten and that would avoid having to go into the A1. I think a lot of times that may be a nice way to do it too. Or if you don't have good enough distal capture or apposition, you go ahead and angioplasty and you pull it down to proximal and then have a problem. So it really is, it's making sure that it's good and not trying to get fancy. Yeah, which is I think exactly what happened in Jay's case after the balloon angioplasty, he lost the stasis because the stent was barely covering the distal part of the neck. So tough cases. So last was the, we're almost out of time, the giant pica with the subarachnoid coiling embolization and recurrence. Demetrius, you're smiling, your thoughts on flow diverting that. I know Jay mentioned the concern of pica coming off of it, but obviously we've had the same issue with the large ophthalmic aneurysms with the ophthalmic artery coming off of it. Is it the same animal, pica and ophthalmic? And can you say that you can flow divert with reasonable results in a previously ruptured case? Yeah, no, I think that that case, I kind of commented before on this, but I do feel that the great approach, coiling in the early stage, a rupture patient recover well, comes back electively. I think flow diversion with the small, the baby flow diverters or EVO is the other device that may be really helpful for this anatomy. These are the, I think that would be the way to go. So that would be my approach. Demetrius, this was a very proximal aneurysm, was right at the take up of pica, unlike the other ones. So I think a junior, a small flow diverter will be a little more challenging because you do not have enough proximal purchase to land it, you would have to fall into the vert. So what are your options in the very proximal pica ones? Yeah, so, I mean, many times you have to come through the contralateral vertebral artery and come down into it. That angle, it seems to, you'll be able to size better. But if you have a challenge to predict where the end of this device will end up, I think that sometimes you may have to use flow diverter in the vertebral artery. And we have had a case like that. It shuts down the door to get in to the aneurysm. So I say, would not do that the way it is. You can recoil more to flush the pica and then come and place a blade, a small flow diverter into the pica short and then put one into the vertebral artery. That may be an option to that, but I wouldn't do that in one stage. I would do only if it fails, or if I feel that the pica flow diverter goes into the vertebral artery, I would still try to get into the pica alone without getting to the vert. Yeah, I've done a few post-seborrheic nerve occurrences where I'll coil any significant recurrence and leave a flow diverter in the vertebral artery. And so far they were actually pretty successful in obliterating the aneurysm. Greg, would you even consider a flow diverter here? Maybe it was a slightly critical about the lack of use of surgery earlier. And I thought this was the appropriate use of surgery in my opinion. So I'm on board. Sounds great. I think we're right out of time. If anybody has any questions or comments. Otherwise, again, I wanna thank Mike, Pascal and Jay for excellent lectures and my co-panelists here for a very engaging discussion. We managed not to have a huge disagreement in most of these cases. All right, thanks a lot. Thanks everybody. Thank you. Thank you very much. My name is Adil Malik and I'll be talking to you about the development of a biomimetic endovascular CSF shunt for treatment of communicating hydrocephalus. These are disclosures for both myself and Carl Heilman. We are both shareholders and co-founders of Cervasque. What I wanna talk to you today is really a team effort between myself and Carl Heilman that's really spanned over 11 years now. And it's really been kind of a work of challenging each other and bringing his experience with skull-based surgery and me with endovascular and catheter experience. The story goes, Carl was sad that he was losing all these aneurysm clippings to endovascular. As we got better tools for this ACOM, we spent COIL with an excellent result. And he felt that maybe we should also be taking care of all the other less glamorous cases, specifically BP shunting, which is really a surgery that hasn't evolved much over the last 60 years. And as you see from these various complications, it's still fraught with all sorts of mishaps that can occur. This is a case that a lot of us, when we are on call, would rather not have to deal with. A shunt malfunction in a patient with collapsed ventricles or an obese patient with a pre-peritoneal catheter. BP shunt surgery really has not improved much and it continues to have a great rate of complication, greater than 40%. So the question is, was there a less invasive way for treating communicating hydrocephalus? And the idea here was to see if we could really mimic the function of retinoid granulations. And the question is, can we produce an endovascular device that would effectively be a retinoid granulation? The thinking would be that we could place the device between the cistern adjacent to one of the sinuses, perhaps a sigmoid sinus. And by then, we had already started treatment of various pathologies through a transvenous approach. Here, one of our first venous stent procedures. And more recently, stenting for idiopathic intracranial hypertension has really become routine. This was our initial patent, that it took us a number of attempts to get, including a trip down to Washington. But effectively, we envisioned a corkscrew device that we could somehow screw into the sinus wall and effectively achieve a communication between the CSF space and the cisterns. We designed a specific balloon that actually enabled for continuous flow where we were placing the device. And we set up to try to get funding for this idea. Internally, there was no funds that were available. Externally, we pitched this idea to two VC firms. And despite my best attempts, there was no takers. I think we then came across a Massachusetts Life Science Innovation Grant, which would provide us up to a million dollars to get this going. And we actually partnered with Covidien at the time. This is now about 10 years ago. This is the review of the grant application. After praising us, and you've seen the P&S sponsors are one of the strong points, it said that the project was overly ambitious and unlikely to succeed, that we basically didn't have any data to support this, and there was still quite a bit of very high scientific uncertainty. But this was actually the reason why we applied for the grant, which was an innovation grant in the first place. And then serendipity struck. We really were very fortunate to have Dan Livangi, who is a serial self-made entrepreneur, having been chairman of the board at EV3 at the time, they acquired the pipeline stent, come across one of my patents that described the fluid diverting stent with shaping elements. And at the time he came, he was interested in this. It turns out that on that day, the patent on the e-shunt got approved. And after having spent so many years trying to get the shunt project funded, we basically turned his attention to that and told him to forget about the fluid diverting shunt stent. He did some market research, found that the rate of complication was very high in shunt, and that it basically had been stagnant surgical procedure and decided to go all in. And so CERV-ASK was formed back in 2014 with Carl and myself as co-founders. We started initially a process of ideation, beginning with anatomical specimens in the anatomy lab, then with frozen specimens, looking at various drill substitutes, 3D printing. At the bottom there, you see a skin of a chicken that I got from Chinatown. I'm trying to see if we can puncture it here with a enterprise stent that was using with a bipolar cautery. And then the process of device development with some smart engineers, we came up with a few different designs. And this is the team here with one of our first successful penetration of Dura. We tried to find an animal model. We spent a lot of time with different swine models. This is a pig that you see in the MRI, and you can appreciate how thick the skull is, but somehow using multiple triaxial, quadriaxial systems, I was able to get up close to the cistern and actually deploy an Elvis stent. But it became very clear that this was not going to be possible. I personally went back to MIT, my alma mater, to get an MBA to try to get the business aspect a little bit better squared. I know we've heard a lot about the disruptive innovation. Reg Haidt gave an excellent talk. We heard about Kodak and the iPod versus the Walkman. And we also heard about the importance of creative tension. Usually you have dual inventors or coworkers, and that's kind of what we had. But back to the real world, we made a visit to the FDA, and to our chagrin, it became obvious that we were going to have to get a full PMA. And so we set out to work. We had many collaborators or friends. As you can see, Radman Siddiqui came to Tufts and tried some of our prototypes, Felipe Albuquerque, and then, of course, Pedro Lilic up on the right, who visited us from Argentina. So the challenge was, can we mimic an arachnoid granulation function using an endovascular device? And really a big progress was made when it was realized the inferior pterosal sinus really had a nice Cervo-Gontine-Angle Cistern CSF space right next to it. And the inferior pterosal sinus, from everybody's experience, is well-traveled by the endovascular interventionalist. It is surrounded in bone, so it's a fixed structure, and basically has a very taut dura separating it from the CSF space. And it also can be many times coiled with relative impunity without developing a deficit. This is an example of carotid cavernous fistula accessed via the inferior pterosal sinus here with the dual catheter technique. And so with that in mind, we set to use the inferior pterosal sinus. These are a couple of the early prototypes that actually were made of nitinol, but it turns out that the best approach was a simple device. Always keep it simple. And this is what it looks like. It has what's called a malicot that is at the end there that enables to ensure that it doesn't get pulled through the dura, and has a slit valve to prevent backflow whenever the patient may cough. You may have a transient increase in the CSF pressure. This is what it actually looks like. It's a miniature, has an ID of 0.017, thousandths of an inch. And this is what it looks like when it's being tested under pressure. The valve performance allows for a flow by 10 millimeters per hour in the range of about five millimeters of mercury gradient. This is forward flow, and backflow showed excellent performance with the very little backflow, even at the pressure of 37 millimeters of mercury. Our next step was to actually traverse the sinus. This is going through the torcula and the sheep model and reaching a cerebellar cistern and try to see if that can be done without inducing a subarachnoid hemorrhage. As you know, the CSF pressure is greater than the venous pressure. And this was successful. In a number of sheep, we actually did not encounter any bleeding. This is the tubing that you see, same size as we use clinically. So then the next problem became, how do we deliver this device? We characterized the iPS anatomy of a number of patients in different age ranges, built 3D models, and actually published our initial results with this concept of where we would want to deploy the device, and came up with a two-component delivery system, beginning with a microcatheter that enables the delivery of an anchor that has a flat trail, and this enables a stabilization for the delivery. As you know, if you've ever catheterized the intraparietal sinus, once you get a nice path, you want to keep it, and this ensures that. And then a penetrating catheter with a needle that enables us to advance into the correct level, and actually take advantage of this angulation in the inferior pituitary sinus to enable what's called a straight shot approach. The microcatheter incorporates a flat trail that enables a very low profile, this is a forefront system, and it has a safety feature in that the flat trail exits at the point this enables us to limit the depth of penetration of the needle as a safety feature. This is the final intended target that you see there, and this is going to be an illustration of the deployment process, which can be done through a six French guide system, enabling first deployment of the stent anchor with the flat trail, which enables then the delivery catheter to advance into the position, unsheathing the needle, straight shot approach, and then delivery of the e-shunt, which is within the needle system. We then got to work on human cadaveric samples that we put on a cell frame for immobilization, access the internal jugular veins. This is the crew and the control room watching as I get radiated doing those experiments. We were able to really leverage what's called 3D road mapping, which I will show you in a second. You can see here the orange dot shows the target site of the inferior petrosal sinus, the ability to penetrate with the needle with the anchor in position in the cavernous sinus. This is the needle at the exit site, and you can see with Conebeam CT the continuation of the flat trail, and the malachite of the e-shunt, and this is what it looks like on the inside. We then used 3D road mapping along with high-resolution MRI contrasted to enable us to identify potential locations for deployment. As you can see on this side, we have a nice big CSF space right next to the IPS, and that's okay for proceeding. In this case, we have the vertebral arch screening right next to inferior petrosal sinus, and that's not a good candidate. Using Conebeam CT with its extremely high resolution and using registration, we're able to then proceed, and this is what it looks like. We first get the 3D road map through the micro catheter, enabling us to see the IPS. We select the exit site, which we cut out, and then we are able to transfer this single spot in space, and now we can actually use 3D road mapping in any direction and enable us to target. After deploying the anchor, we'll bring our shunt delivery system, and the goal is to actually puncture at the orange dot. Here we are, unsheathing the needle, pulling back, and then using the straight shot approach, advancing transdurally into the cistern and delivering the e-shunt. We then go back and retrieve the anchor. This is something that is actually feasible to do bilaterally, and is it retrievable? Yes, it can be retrieved. This is an example of using the snare that you can see to grab the slit valve portion, the distal portion of the e-shunt, and pulling gently, and we are able to retrieve it. This is what it looks like on the inside while it's being retrieved, as the malacot collapses. COVID-19 came, and this posed a big challenge to us. Unfortunately, we were not able to go down to Argentina to actually perform the first in human, but actually also it was a blessing. This is before COVID hit. Dan Lavangia and I visited Pedro Lilic at his superb clinic in Buenos Aires, and the ECHS trial was begun. It's one that relies on patients that have subarachnoid hemorrhage with an EVD in place who have failed a clamp test. This way, after placement of the e-shunt, we're able to constantly monitor the ICP. The primary endpoint is the ability to remove the EVD within 36 to 48 hours. After initial training session with a visit to Boston, we were set off to the races. This is our first in human patient, an 84-year-old lady with a ruptured MCA aneurysm that was coiled. She had a clamp test, which she failed, as you can see here, spiking over 30 millimeters of mercury. This is her study. You can see she has significant depth of the CP angle cistern. The size of the IPS on the right is acceptable for a French system. This is virtual segmentation of the IPS in purple and the adjacent vertebral artery and branches in red. You can see we have about 6.6 millimeters, which is sufficient. This is what the actual procedure, first in human case, looks like. I'm going to speed this up a little bit. You can see, again, they have a good position, pulling back, and now advancing the needle to go across the IPS into the CP angle cistern. And then you can see here a run shows there's no leakage. The e-shunt is delivered. And the microcaptor is then used to withdraw the stent anchor. What happened to the patient is the ICP, as you can see on the right, decreased dramatically. Overnight the ICP was six millimeters of mercury. This is the combium Ct shown with the malachite, and there was no evidence of hemorrhage. We can visualize the tip of the malachite in situ, and this is the ICP trend following the ischium deployment. You can notice that it dropped all the way down to five millimeters of mercury, and then stayed below 20 centimeters of water. You can also see there were a few spikes with ductwork change and trendelbert position for central line change, which is not unexpected. The Ct shows low contrast enhancement in the immediate post-procedural Ct with the decreased size of the ventricles. The MRI showed actual malachite, and that you can see where the red arrows, and you can actually track the body of the ischium at non-contrasted MR, as well as distal valve. We've performed four patients successfully, and they have all met their primary endpoint with decrease in the ICP and removal of the EBD by 36 hours. So we were able to achieve some important milestones in the first case of percutaneous endovascular transformal access to the central nervous system. It has implications for use of this approach as an access platform for gene or antisense oligonucleotide therapy, and perhaps as a platform to enter the CNS and perform endoneurosurgery. Transdural venous to cisternal puncture is safe, was performed in four cases without evidence of hemorrhage. We proved the concept of cerebral pontine angle to IPS with rapid and sustained ICP decrease. We had stable placement of the eschant and visualization using Ct and MRI, but the results are preliminary, and we're at the very beginning of clinical evaluation. This is the team in Buenos Aires with Dr. Lilik, absolutely superb, top-notch, and we're lucky to have the chance to work with them. And of course, we have to thank our mentor and friends, both Karl and myself, Bill Shuchart as a mentor, Chuck Kerber is Karl's father-in-law and a good friend of mine. My mentor is Randy Igishida, Van Halbach, and Christophe from UCSF, where I did my fellowship in the late 90s. And also thank our department, who has provided a very nurturing environment and enabled us to do this while maintaining a busy practice. Thank you very much. Great talk, Adil. I actually had the opportunity to see Carl speak about this last week or a couple of weeks ago, and I think anything that could maybe replace the shunt is very exciting. Do you see any patients who would not be candidates for this? Yes, I think patients that have a very small cerebral pontine angle cistern, at least with our current technology, you know, where we do require about a depth of about three millimeters, would not be good candidates. Any patient that has on both sides, the right and left IPS, you know, vascular structures at the exit site, would not be very good candidates because of the risk. But I hope that with time we will perhaps develop a trocar-like approach to puncturing safely without requiring that depth. So time will tell, you know, if we're able to further miniaturize it as well. How much follow-up do you have on those four patients you treated? Do you know the longevity of this shunt? So obviously we're still in the process. The first patient had multiple medical complications, unfortunately passed in delayed fashion from renal failure. The other ones have done well, and enrollment has been relatively sluggish, and so we are actually starting a new study that will focus on patients with NPH where we're able to better control kind of the consent process and hopefully the kind of enrollment rate. Do you have any, that was a really fantastic talk, and I think, you know, just very useful, you know, I think as Mandy mentioned, you know, not a lot of development in shunt technology, you know, over the past several years. And so with your particular device, is there anything in place that prevents, like an anti-siphon valve or something to prevent over-shunting or things like that? That's a very good point. So as you know, with over-shunting and with siphoning, usually there's a very large kind of a gradient, a rho GH, kind of the height of the water column. In this case, the water column is simply a few centimeters. There's always a gradient between the CSF and the venous pressure. So this shunt only drains when the pressure exceeds what's called the cracking pressure, which is a small pressure that is needed to open the valve. But when that pressure gradient decreases after you've drained some CSF, then basically the valve closes and you don't usually have an over-drainage problem. So theoretically we should not suffer from over-drainage or a siphon effect, but obviously time will tell, you know, this is quite novel. You know, this was the first case that this was, you know, implanted in, so we're still learning and we have quite a bit to learn in the future. Do you envision any down the line, any variations that may include variations of cracking pressure so that you can change the opening pressure somehow? Yes. You know, I think it's possible to have various cracking pressures, you know, with time and with the improvement of, you know, MEMS technology, you can envision having a pressure sensor embedded in it, or maybe some have a flow regulator in it and so on. But, you know, it's always best to keep it simple at the very beginning. You can also envision using this approach to actually travel inside the cisternal system to do a number of things. You know, you could imagine doing, you know, kind of a third ventricular, you know, procedure from below. You know, you can envision kind of other types of endoneurosurgery. So we see this as a platform moving forward, but we're just taking baby steps at this point and hoping that we can improve hydrocephalus treatment. And additionally, I don't know, there's another question here that's, can the device be eventually obstructed with arachnoid tissue or fibrosis from the puncture? This is from Orlando diseases. Yes, absolutely. You know, those are all risks that we don't know yet, but as you know, we don't have kind of a tissue in that location. You know, all the different modes of failure of the regular shunt are quite different in this location. You know, you're not likely to have a collapsed cistern, but certainly those are potential failure modes. And what I tried to show is the fact that the e-shunt is actually removable. It has been actually removed in one of our patients successfully, and it can be re-implanted adjacent on the same IPS or perhaps on the contralateral one. So it is kind of a slightly different way of thinking from a conventional shunt where, you know, we think that it's going to be possible to either remove or replace or potentially troubleshoot it should it get clogged. And, you know, one advantage of this is it does not preclude, obviously, using the old conventional VP shunt technique. So if a patient has this and comes to a hospital with a failure, it doesn't necessarily need to have an endovascular treatment in the acute phase. Well, thank you very much. I think we're just about out of time. Thank you very much for your presentation. And thank you very much for everyone who's attended this session and all the speakers. This has been a really wonderful and a fantastic session. And thank you all for coming. Yeah, it's been a great session.

cannabis use

delayed cerebral ischemia

aneurysmal subarachnoid hemorrhage

retrospective study

clinical outcome

long-term impact

endovascular treatment

flow diverter

aneurysm occlusion

comorbidities

biomimetic endovascular device

communicating hydrocephalus

arachnoid granulations

intracranial pressure

cerebrospinal fluid drainage