Dr. Rania Habib (Host): Welcome to MD Cast by Tampa General Hospital, a go-to listening location for specialized physician-to-physician content, and a valuable learning tool for world-class healthcare. I'm your host, Dr. Rania Habib.

Host: Joining me today on MD Cast is Dr. Kunal Vakharia, an Assistant professor of Neurosurgery at the University of South Florida. Dr. Vakharia specializes in complex cranial and endovascular pathologies, and he is here to discuss the evolving treatment paradigm for cerebral arteriovenous malformations. Hello, Dr. Vakharia. Welcome. I'm so excited about this topic. How are you today?

Dr. Kunal Vakharia: Good. Thanks for having me, Dr. Habib.

Host: We're so excited. So to begin, what are the different surgical options for treating cerebral arteriovenous malformations?

Dr. Kunal Vakharia: Yeah. So, there's a lot of different options and a lot of newer options that are coming out into the world as well. So, I think the first question we ask ourselves is, when you have an AVM, which is an abnormal tangle of vessels between arteries and veins with a lot of what we call shunting or AV shunting between the artery and vein, the question is how can we take this out safely without injuring normal brain tissue?

A lot of times these have a higher risk of bleeding, so we talk about different modalities, and those are typically three, and that's what's always been talked about in the past. Microsurgical resection, so that's the typical surgery where we actually open up a small window in the bone in the skull, find the AVM, and work all the way around it and avoid taking out any vessels that are feeding normal brain with the goal to remove the AVM in its entirety. That is typically good for certain types of AVMs, particularly ones that are easy to access and lower risk. There's also options with radiosurgery, which is like radiation therapy for tumors or other things like that. It's a very targeted approach and we can give a pretty good dose of radiation to these as well. And over time, they slowly go away. That's also been proven pretty efficacious.

The one that's growing in popularity, be it across the world now more and more, is endovascular therapy are minimally invasive techniques. And I know there was a trial done recently called the ARUBA trial that really told people that interventions for AVMs have risk and actually argued that interventions for AVMs shouldn't be done. And what we've noticed, especially in the COVID era, is that we've seen a much higher rate of AVMs that are coming into the hospital ruptured because they're not getting interventions or treatments as outpatients are electively when they're found. So, endovascular is a situation where we actually go through the artery and either glue or treat high risk features of these AVMs, even if we can't treat them entirely. And a lot of that newer technology works on the venous side. So instead of the arterial side, we're actually working on taking out the entire cluster of vessels through the vein. It's a growing technique. Every year, we're seen more and more of it being done.

Host: That's incredible. So, talk to me a little bit about when a patient is sitting in front of you and they're trying to decide, "Do I want this AVM removed?" How are you helping them make that decision based on, they're saying, "Okay, the risk of the deficits based on the surrounding brain tissue versus risk of rupture"?

Dr. Kunal Vakharia: Yeah. That's actually a good question because I think there's a lot of different factors and each one of these modalities has their own grading scale to try to determine that risk. So, AVMs in general, we see them more and more in younger people. They tend to be there. They can form, you can acquire them, but most of the time they tend to be there and they have a rupture rate of anywhere from two to 4% per year. So if you have an incredibly young patient, a lifetime risk is pretty high, which is why we're more aggressive with these if we can be.

So, one, understanding what your initial risk of rupture is and its impact on the patient, be it if they found it because of seizures or any other semiology. And then, understanding how we can treat this with reducing that risk. So in certain situations, we have an AVM that's sitting right in the middle of the motor cortex or right in the middle of a speech area. And in those situations, it doesn't make sense for the patient to go through that risk profile and they're willing to consider radiation therapy or consider an endovascular option.

I know recently we saw a patient with a AVM within the brainstem and, neurologically, they were okay. They came in with this thing that was unruptured. But for a large part, there was no good way to say, "Look, if we open up a small window in your skull, there's probably going to be some deficits after a giant surgery like this."

Host: Exactly.

Dr. Kunal Vakharia: And that's a situation where we're still evolving from like an endovascular perspective. We ended up treating that through a transvenous approach or through the vein. And that risk profile is probably higher because it's a newer technique. But at the same time, one that left this patient asymptomatic even after we completely treated the AVM.

Host: That's fantastic. Now, with the evolving endo vascular therapy, how are you as a surgeon making that decision between the different modalities?

Dr. Kunal Vakharia: There's a couple different factors that take an important role in that situation, in that decision making process. One is it's always a decision that we make with our patient. It's one where we understand what their risk benefit profile is, what they're willing to take on. And radiation may be a good option with the understanding that it increases the risk of bleeding for the immediate interim after radiation starts. But that over time, it slowly gets rid of the AVM most of the time. And so, that may be a profile that a patient's willing to take and one that's a better option from a risk profile instead of a surgery. The flip side of that is also that, at a university setting, we have the ability to have a multidisciplinary conference. So, you have someone like me who's trained in all three modalities, and you have a team with multiple people who are trained in multiple different modalities. And everyone's weighing in saying, "Look, here are things that we may not have considered." and having that kind of situation and that kind of back and forth, I think really helps us figure out what the best treatment is for these patients, particularly because there's not a huge volume out there to give you a perfect answer for every patient.

Host: Right. Have you become like a center for tertiary referrals for AVMs because of that multidisciplinary care?

Dr. Kunal Vakharia: We have, and largely because we just see a relatively large volume. University centers in general tend to have that radiology background, the radiation background and have all those disciplines together to have that kind of a conversation. And so, having the ability to have novel imaging technology to help us understand, be it normal pathways around the AVM or the AVM nidus, I think are kind of the developing edge of technology right now, and one that universities really give us that upper leg on.

Host: Oh, absolutely. So, talk to me a little bit about the risks and benefits of radiosurgery for cerebral arteriovenous malformation treatment compared to the endovascular or the open approach.

Dr. Kunal Vakharia: So, radiation is a painless, you don't recognize you've actually had it done situation, where we take an MRI or an image or an angiogram and map out exactly where this AVM is. It's almost like painting the AVM out on a picture and then having a computer and a whole system that's dedicated to this target it and give focus ed radiation to that area. In fact, it's so precise that we're able to give a marginal dose of radiation to about 22 gray, sometimes to very complex AVMs, which is exactly what we expect with our technology exactly.

And part of that also is that we're starting to realize that there are good indications for it. Patients, they don't have, seizures right now, or no hemorrhage or mild hemorrhage, with a small diameter and they're located deep or in eloquent cortex, they tend to be great patients for radiosurgery. But the flip side is that that initial risk, so if you have an aneurysm associated with your AVM or you have a venous obstruction, meaning the vein is already starting to get blocked off, or you've had an AVM that's bled, all of those mean that if you get radiation, it may still treat the AVM over time, but the risk of that AVM bleeding again until it's treated is higher. And so, that's what we usually have to take into account.

Host: Okay. Is that because the radiotherapy is making the walls thinner and more friable?

Dr. Kunal Vakharia: So partially, and that's a great question that I think we're still working on figuring out. The challenge is we don't exactly know if it's necessarily sclerosing the vessel and making it smaller and therefore decreasing the area of the nidus and the volume of the nidus, or if it's actually causing scarring around the entire nidus and causing that to get smaller over time. The theory is that it impacts the artery and vein and the wall of the artery and vein and the blood supply to the wall of the artery and vein. And over time, it shrinks those, which is why we see a progressive decline in the area and volume of the nidus and the AVM over time after radiation and why we also focus on that marginal dose. But I'll tell you, the idea behind the radiobiological effect of our therapies on AVMs and the surrounding tissue is evolving year.

Host: That's incredible. And I mean, obviously, it's very new. What are some of the anticipated long-term deficits with radiotherapy? Has that even been studied yet?

Dr. Kunal Vakharia: It has. We do have good evidence for long-term therapies with radiosurgery in terms of It's something that's been a growing modality. So, we may not have treated as many early on with radiation, but we're starting to treat more and more. So from a radiation standpoint, we're seeing impacts from seizure, radionecrosis based on targeting around it, but a lot of that is changing over time. Again, I think it's only one of those modalities that we're talking about in treating these AVMs, and that's part of why we have growing knowledge as we say.

Host: Right. Absolutely. So, how is the effectiveness of treatment evaluated and monitored for the three different modalities, and is it even different?

Dr. Kunal Vakharia: The biggest challenge is actually differentiating treatment and followup plans between pediatric populations and adult populations. So in pediatrics, what we're seeing, even if we go in, make a window in the bone, take out an AVM and prove that we got everything out with a followup angiogram, MRI, the challenge is that over time throughout that patient's lifespan, there is a chance of a slight recurrence. And so, that still exists and there's no good answer as to exactly why.

And so from a pediatric standpoint, I would say we continue to follow patients usually with non-invasive imaging unless we see something new happen on non-invasive imaging. And then, obviously, the gold standard is a diagnostic angiogram where we actually put a catheter up and take a picture under x-ray guidance. And we do that because that's a gold standard of understanding the angio architecture of what we're dealing with. But a lot of the non-invasive studies help us dictate when we need to do that.

So from a surgical standpoint for adults, we can usually tell if it's been taken out in its entirety and we do perioperative studies, be it an intraoperative angiogram, postoperative angiogram to prove that there's no early venous drainage in an MRI. And then from a radiosurgical standpoint, again, we do the same thing, imaging with MRIs over time and an angiogram at a certain designated time points a couple years out from radiation to prove that there's no shunting.

Host: Okay.

Dr. Kunal Vakharia: And then from an endovascular standpoint, that's again an evolving question. So, transarterial embolization, I think is something that's still growing in popularity. It's usually more of an adjunct therapy with resection. But transvenous, I know our series so far has been several years out. So, it's something that's a growing body of literature.

Host: That's fantastic. And does the recurrence rate differ based on treatment modality as well? Like have you seen a decrease with one specific technique over the other?

Dr. Kunal Vakharia: So, recurrence is mostly in the pediatric population, and I can't say there's that many that we can tell you if transvenous approach or a radiosurgical approach is better for pediatrics. But we can usually get a sense that there's a pretty good cure rate if you get a cure from radiation. And there's usually a 90% chance of getting a cure from radiation. And then from a surgical standpoint, typically we have that kind of intraoperative control to tell that we got everything or we didn't.

Host: Right. So from a surgical standpoint, is there a preference in technique that you personally have?

Dr. Kunal Vakharia: I think the surgery for AVMs has dramatically grown in the last century. I know a lot of early literature and a lot of early anecdotes talked about these being pretty aggressive lesions because of how vascular they are and how much blood they contain. From a surgical technique standpoint, we've started to really hone in on location and the art of taking these out has become more and more standardized. And so, part of it is that we have better technology, better instruments and better outcomes because of that. And we're starting to see that more and more. And that's why there's centers of excellence that are growing their population of patients who are doing well and do well after surgery. But from a technique standpoint, I think it's a combination really depending on, based on what each individual patient's AVM looks like.

Host: Okay. Fantastic. From the patient standpoint now, are there any lifestyle changes or followup care that you specifically recommend after treatment for AVMs?

Dr. Kunal Vakharia: So after the treatment of an AVM, I don't think there's a specific guideline necessarily because there's so many different modalities. So from a. radiation standpoint, I tell patients that typically if they don't have a high risk feature, meaning an aneurysm, A venous obstruction or a prior hemorrhage, that their risk is okay and that they're going to continue to live with what risk they had. Typically, patients who have seizures, I tell them the goal of taking out an AVM is to reduce the nidus of the seizure and the focus of the seizure. And most of the time, we're successful in doing that. But there are cases where patients still have seizures postoperatively and have to stand medication. But in the grand scheme of things, typically when we have what I call cure, when we have that situation where we've actually taken out that shunting situation, resected an AVM or radio surgically cured an AVM, I typically tell people, "Look, you're normal, and go live life normally."

Host: That's awesome. So, no restrictions in terms of like having to limit contact sports, wear a helmet, anything like that?

Dr. Kunal Vakharia: Typically not, unless they have symptoms or an issue related to it.

Host: That's fantastic. Well, what you do is absolutely life-changing, so I really appreciate you discussing this with us today. Thank you, Dr. Vakharia, for all of your expertise. Thank you for listening to MD Cast by Tampa General Hospital, which is available on all major streaming services for free.

To collect your CME, please click on the link in the description. For other CME opportunities, including live webinars, on-demand videos, and local events offered to you by Tampa General Hospital, please visit cme.tgh.org. Thank you so much for listening. This is Dr. Rania Habib wishing you well.