AAN 2024 | EMBOLISE: middle meningeal artery embolization to prevent the recurrence of subdural hematoma

The fundamental problem we’re hoping to understand better is how can we prevent subdural hematomas from coming back. Subdural hematoma is essentially when you get a collection of blood between the dura and the brain. For the longest time, the only treatment that we’ve really had was to drain it: you either make a small craniotomy, two small burr holes, or you could do a bedside procedure to potentially drain the fluid. It’s an easy enough procedure; it’s one of the first things that my residents are going to learn how to do. But the vexing part is that they tend to come back relatively frequently. Reports in the literature range from 10 to even 30% recurrence. The big issue is that these subdurals tend to form membranes. Basically, you have inflammatory cells that come in, those inflammatory cells secrete pro-angiogenic factors that cause blood vessels to ingrow from the dura. Those tend to set up this process where you have these leaky vessels, exudates of fluid, and the thing just never goes away.

So, the hypothesis was: if we could devascularize these membranes, potentially we could dry them up, prevent the cycle from taking place, and reduce the number of times the patient might need surgical intervention. So that’s what we did. We designed a trial where we looked at two different patient groups: patients who had larger hematomas who needed surgery, and patients who had smaller hematomas, less significant symptoms, who fundamentally didn’t need surgery, at least not yet. Then, we randomized each of those to either get embolization or not. So basically, four arms in the trial. The part that we presented here today was the surgical cohort, where we looked at the patients who were either randomized surgery plus embolization, or surgery without. We wanted to understand how frequently they needed to go back to the operating room. Secondarily, were we causing them harm by subjecting them to another potentially dangerous procedure? Then, of course, a whole host of health economics and other kinds of outcomes that we were looking at.

We were excited to find that we had a 3-fold reduction in the rate of return to operating room in the patients who were treated with embolization as opposed to those who were not. In fact, the finding is probably a little bit more robust than even the data suggests, because in our intent-to-treat analysis, we had several patients who were treated out of the study (surgery only), and when they had a recurrence, instead of going to the operating room, the investigators were so enthusiastic about embolization that they embolized them as opposed to taking them to the operating room. So, they didn’t meet the official end point, and yet still should have caused that number to be higher in terms of recurrence. On the other side, we had two patients who were assigned to receive embolization, who had dangerous vascular variants so they couldn’t actually get embolized, and they ended up reoccurring. So that number probably should have been lower. This is a very robust finding.

Putting this in the context of the field, there are two other trials that were presented alongside ours at the International Stroke Conference: the STEM trial, which is funded by Balt using a different liquid embolic agent, and the MAGIC-MT trial out of China, which again uses the Onyx Medtronic Liquid Embolic. All three of our trials demonstrated the same thing: reduced problems if you had embolization. The outcomes were a little bit different, the patient demographics were a little bit different, but overall; if you dry up that membrane, patients tend to do better.

In our study that is ongoing, we are continuing with enrolment at this point. The other two trials, interestingly, kind of intermixed them. So, they had both surgical and observation patients in each of theirs, so it’s a little bit of a more heterogeneous group. But one of the interesting analyses Dr Adam Arthur (one of the PIs of the STEM trial), presented was that, although they weren’t powered to look separately at surgery versus observation, when they pull out those numbers, the effect size is much greater for the observation; meaning they were actually preventing even the first surgery at much higher rates than even we were preventing that second surgery. So, we’re really excited to be able to see what that observation cohort looks like. We’re getting close, but these trials always take time.

This is a paradigm shift. Absolutely. There are three trials that have already been reported, and obviously we want to see the final publication when it comes out to be able to assess the nitty gritty. There is a fourth trial, the MEMBRANE trial, that’s chaired by Chris Kellner out of Mount Sinai. They’ve completed enrolment, and they are in their follow-up period now. There is another trial in Canada. There’s another trial in France. We’ve got six trials. We suspect that this is going to be another 2015 kind of event: where all the stroke trials came together, all pointing in the same direction, creating a paradigm shift in how we treat stroke. Now, stroke is an interventional disease. We expect that when all of these data are fully available and everybody can evaluate them, that this is going to create a paradigm shift, that there will be guidelines. Our recommendation is that anybody who has a subdural ought to be considered for middle meningeal artery embolization, particularly if they’re symptomatic. We’re excited to see what all the data show in totality, and we have a bunch of different analyzes that we’re planning once that’s available, because for the longest time, we didn’t quite know some of the nitty gritties about what constituted an adequate embolization, what were some of the finer details. Now we’ve got 1500-2000 patients that we can bring together into a single meta-study to be able to look at.

So we’re really excited about the EMBOLISE trial approaching this problem of these middle meningeal artery embolizations. One of the big things that we found was that it is safe. The reason that’s important is because there are other disease states that we think we might be able to attack through a similar approach. For instance, about 13% of the world’s population suffers from migraine headaches. That’s a billion people. And there are some early data that suggest that at least some subset of those are related to problems with that same artery, the middle meningeal artery. So potentially, if we could go in and either anesthetize it, lidocaine infusions, or embolize it, as we’ve done here, we may be able to reduce the severity or even get rid of the migraines in some of these patients. Which could be a huge public health benefit, because we know that migraine causes a lot of missed days of work, a lot of pain and suffering. My wife suffers from migraines. I wish I could do this for her. I think that this is potentially a way of treating any number of other diseases as we sort of push the boundaries.