Transcript
Hi, thanks for having me and it’s great to see so many friends in the audience. So I don’t have any relevant disclosures. I hope I can see my slides. Okay, but this talk does talk about the off-label use of fibrin sealant.
So many of you were back at a meeting in Freiburg, great meeting in 2023, when I talked about fibrin glue then, and pretty much what we were showing was a lot of case examples, anecdotal evidence. So two years is a long time in the world of SIH, and we know more now. We have more published data that has been multi-institutional, that has guided our practice and has changed how we manage some of these patients and how we select cases appropriately for treatment. And also we know from this great paper from Eike that targeted treatment is favored. So many of you who are already in leak centers are already doing this for targeted treatment.
So this is what I’m going to cover today. I’m going to talk about the background to fibrin glue use. We’re going to look at what is the actual evidence for the different leak types and the patient selection appropriately. We’re going to look at how I do my technique and some example cases. Then I’m going to finish up with some pearls, pitfalls, maybe some mistakes of mine.
Fibrin sealant is basically mimicking the end product of the coagulation cascade. Thrombin acts on fibrinogen with the help of factor 13 to form a meshwork basically, and that meshwork acts as a sealant. This is available in different preparations. I use the pre-filled frozen syringes. I find them easier, but they can be made up and reconstituted from scratch. They come in a variety of different sizes depending on how much you’re going to inject. And really the image-guided use for spinal CSF leaks has been around for 30 years. It was first starting off with the post-op leak literature, and then we had smaller case series from Wouter. Then we’ve had more targeted use for specific types of leak from the Duke group and Mark Mamlouk for CSF-venous fistulas. But we’ve had more and more data in the past two years.
So what can fibrin sealant be used for? Well we know some of the data for our type 1, type 2, and type 3 leaks, but really we can use it for really any type of CSF leak in an appropriate setting. I’m going to be showing examples of the various types of these.
What is the evidence that we have at the moment? And I think before we start talking about the evidence, we’ve really got to look back to some of the principles that Jürgen mentioned. We know that epidural fluid with dural tear type leaks is very diffuse when it’s in its acute setting and becomes more organized over time as those membranes form. This was really nicely put into the paper most recently by Andy Callen and Mark Mamlouk. That really impacts how we select patients for this treatment.
And Jürgen showed this picture earlier about the membranes forming. And really, if you’re going to treat these leaks via an interventional neuroradiology basis, there’s no point, I don’t think, being outside the leak. You will very rarely cure the defect in that way, which is why non-targeted blood patches ahead or remote from that time, particularly after that first few months, are in at least our experience, very unlikely to cure the defect.
So what has the evidence showed us from Mark and Andy’s most recent paper on traditional epidural patching? In terms of the fluid resolution, which is what we can imply is a dural defect closure, it’s 25% overall, which is pretty low when you compare it with surgical repair. But if we break that down into the different types of collection, when it’s unorganized, i.e. when it’s acute, there’s a much higher chance of success. And here’s the thing, if it’s organized, you really want to be inside those membranes. If you’re not inside, you are really going to struggle to be successful with closing that. So I would assume from that that therefore this is best for acute leaks with diffuse fluid, which is what we see in the acute setting.
Now, we also saw this about lateral leaks, about it’s not the cyst that leaks. It’s actually a lateral dural tear and it’s leaking from the margins. We’ve had some great papers in the last year from Cedars-Sinai group and Freiburg group that have really helped us understand the anatomy of where this leak is occurring. That’s important when we consider how we treat these leaks as well, also from an interventional perspective. And we have just come out with this paper which looked at the outcomes of CT-guided targeted patching for lateral leaks. Again, the actual defect cure in terms of fluid resolution was around 25% overall, and this is significantly altered when there is or isn’t the presence of a pouch. We’re assuming that from the radiological issue, or seeing this radiologically, but also from some of these cases that went to surgery.
So when there’s a bigger pouch, you’re going to have a lower chance of success. These pouches, you can see these on MRI. Niklas Lützen has really nicely described this bottom branch sign. We’ve got really great examples, I’m not sure if they’re projecting that well, which show us and can point to where these leaks are on MRI.
We did not find any difference whether you injected inside the pouch or outside the pouch. That was not a predictor of success.
Now in terms of CSF-venous fistulas, we’ve now published multi-institutional data on this. I think the most important take-home from this is that this is not just a transforaminal patch. Your needle placement does really matter, and therefore I really do think it needs to be CT-guided so that you can actually target and look at the fistula, look at the anatomy of it and the drainage. From our paper, the two most important things are that when the glue spread matches the fistula drainage pattern, that really increases your chance of success. Again, time to treatment matters.
So will it help? Because this is all that really matters here—does it actually help patients? Well a lot of patients get complete relief or some kind of relief, but some get none at all. But Some of this is also similar to some of the surgical data, and there’s slightly more effectiveness for CSF-venous fistula. But what I would say with this is that there were patients who had complete relief of symptoms and they still had fluid left on their MRI. So we need to be careful about what we’re judging as outcome measures here. Is it clinical resolution, radiological resolution? Does a defect there imply that the patient is still leaking? We think that, but clearly you need to follow up your patients.
So why do I like fibrin glue patching? Because we do everything in the same sitting. So when we have a patient, we find the leak, we treat them straight away within 15–20 minutes, which is the time it basically takes fibrin to defrost in the open or in a water bath setting. We always have a discussion with the patient before, and we say this is the kind of leak you’re likely to have and there are different treatments that we can offer. In the UK, most patients are scared of surgery, so they want to often go for the least invasive option first. But the great thing is when you work as part of a multidisciplinary team and we work collaboratively, we can offer all options to the patient.
We always think—could another treatment be better? There haven’t been any trials that have directly compared fibrin with transvenous embolization and surgery. There was this recent systematic review comparing surgery and transvenous embolization, but we do need more data on this. But what I would say is that fibrin glue is a low-invasive method that can be tried pretty much the same day, and it doesn’t preclude escalation to the other steps. We can have great results with it.
But I think the key thing is being honest and open with the patient about your own success rates, what the literature shows, and giving the patient that autonomy of choice as well once they’ve to make an informed decision.
So let me tell you my technique and give you some example cases.
Firstly, it’s preparing fibrin sealant. Don’t overheat the glue. You don’t want to put it in the hot water bath because it will cook literally like an egg, and it will look white in the syringe. If it’s looking clear, you’re okay.
We put contrast into the hub of the syringe. The manufacturers say don’t do this, but I want to know where that glue is going. So we put contrast in there, and we use a 20-gauge needle because this allows us to give an incremental step of fibrin. I don’t like to give the whole lot. We give small aliquots to see where this is going so that we can reinject. I always give bupivacaine because fibrin is painful, and this tends to give a good perineural blockade.
So I’m going to talk about the different needle tip positionings for the different types of leak. But in general, we place the needle. I always inject a little bit of air first because I find that contrast can really muddy the field first. After air, then we check with contrast as well.
So where do you need to be if you’re thinking about a ventral leak? Well we want to try and target that anterior epidural space at the level of the leak. This may need a bilateral approach.
So this was a patient who came in acutely. She was three days from her ictus. You can see here this is diffuse unorganized fluid. You can see here that she had a ventral dural defect at the T10-T11 level. We’ve advanced bilateral needles into that ventral epidural space. We give test doses of contrast. We give a double tap for this because the ventral epidural space is very vascular, and we don’t want to be in a vessel. You can see the post-glue appearances have filled that anterior epidural collection. But the most important thing is obviously does the patient get better, but is there still fluid left? Because if there’s still fluid left, in my opinion, that’s not been a successful glue. In this patient, there was no fluid left. So when we can get to these leaks within a short amount of time, we can cure them.
For lateral leaks, like I said, we don’t know which is better. We know from the data that this didn’t make any difference. So you can target the epidural space at the neck and/or the outpouching itself. So this is one of my earliest lateral leaks. I just want to show this because this patient had a very small arachnoid outpouching. We position the needle, we give contrast to check that we’re in the epidural space, and then what we do is an incremental glue. We give 1 mL aliquot, we check the deformation, and then we increase that to as much as we can, usually up to 4 mL. You can see in this patient the brain MRI findings that dural thickening resolves and their brain sag. You can see the very marked tonsillar descent before, the pituitary distension. You can see that that has resolved. But most importantly, has the fluid gone? Yes, the fluid’s gone. That’s what’s most important – image the spine.
This was a patient very recently. It was an emergency physician consultant. She has a very diffuse lateral leak. You can see that contrast pouring out of the foramen. This was at the T10-11 level. We place the needle, we give a test epidurogram, and again we give this staged glue injection. When it’s acute, we’ve also been giving some dorsal blood at that level because we feel that helps wrap around the glue. That’s not really scientific. In the lateral leak paper, we found that there wasn’t actually any difference for what substrate you used for that.
Now, in terms of fistulas, Mark Mamlouk’s going to talk on this a bit later, but generally we tend to target the junction of the vein, diverticulum, or the fistula network itself. We can puncture the diverticulum—that’s painful if you do it—so obviously give a perineural blockade. You want to try and really map the drainage because that’s what we have shown tends to give you the highest indication that you’ll be successful. This is a classic example of a two-needle approach and how we stage the glue injection for this.
But I want to show you my favorite case because this was a case that has been under the neurosurgeons at our institution for over 10 years before I found out about this case. She kept coming in and out with worsening Chiari syrinx. Eventually I found this case and this is SIH. This syrinx is related to the sag related to SIH. We found a CSF-venous fistula left T9-T10. We did a two-needle glue for this targeted at the fistula and the drainage. This was her follow-up MRI 6 weeks later, and she’s completely symptom free. The neurosurgeons love this case because how many syrinxes can you resolve with just putting a couple of needles in.
Now, sacral tear leaks. We’ve learned a lot about sacral tears from Niklas Lützen’s great paper on sacral tears. Since I started working with him, I have seen more and more of these tears and I’m pretty sure I missed quite a few of them. This was also missed from an external institution. You can see that this patient initially she has signs of SIH: subtle brain sag, pituitary distension. What you can see here is that she has the dorsal epidural fat edema. She got a little bit better but came back, and her MRI at follow-up was read as normal because there wasn’t that much fluid left. But what was missed was the small amount of fluid in the sacral cul-de-sac. When we reformat that, you can see that there’s still epidural fluid in that sacral region. Like Jürgen said, we really love to patch these leaks because accessing these leaks surgically can be more challenging, and they get really great results. So what we did with this was that we matched exactly where our needle position was into the collection that was remaining of that fluid. We did that both at the dorsal epidural space and also into that little focal bleb that we’re seeing here. And most importantly her epidural fluid completely resolved and she’s completely symptom free.
So I’m going to show you some pearls and pitfalls now. This was actually a very recent case from a couple of weeks ago, came in very acutely. But we had difficulties placing the needle into the ventral epidural space, and that can often be the case. Sometimes you have to really reposition a lot because you’re getting a lot of vascular contrast, and you really don’t want to be injecting glue into the vascular space. But what we did was we persisted for a while and we managed to get some contrast. It’s quite subtle, but it was just about here going across the midline. So we injected a small volume of glue and then we followed this up with some dorsal blood as well. Because this fluid is unorganized, that was wrapping around the defect. And importantly, the collection that was there before has completely gone. So you can treat ventral leaks without surgery, but it’s timing that matters.
Now this lateral leak was a patient who came, and you can see she has venous distension, the dural thickening, and she has this classic bottom branch sign. So we knew what we were going to find. You can see the fluid collection here, and we found this lateral leak as we assumed we would at right T11-T12. We injected glue at this location, no blood, and she’s now completely symptom free. Her brain MRI is much better. What is interesting is the fluid has gone, but the arachnoid pouch remains. That can be an appearance after patching of lateral leaks, that the arachnoid pouch has remained. Maybe there’s scarring at the neck of the arachnoid pouch, but there’s no fluid left.
This was a case from last week. Wouter very carefully described in his paper, that you can get this rarer type of leak called the pedicular leak, which occurs slightly remote from the nerve root sleeve. On the MRI you can see she has circumferential fluid. I was very suspicious of this because that looked like a little bit of an irregular area, and it’s at the level of the pedicle. I opted for a left side down because I was confident that it would be at that level of the pedicle, and that’s exactly where that leak was. It was a very subtle leak. You can see it just ejecting here, and you can see this little pool of dense contrast which has layered here.
So how do we treat this? This was within two weeks of presentation. When we turned her prone, you can see that there’s that little leak of leaked contrast here, and it’s right next to that facet joint. So I thought I’m going to try a trans-facet approach to get to that exact point of leak. We managed to get the needle into a great position, which looked right next to the leak, except the contrast was filling the facet joint. So at that point I thought I’m not going to be a hero. I’m going to actually reposition behind the pedicle. And that’s what we did. We gave contrast here. It was filling here nicely. And then what we’ve done here is staged increments of the glue until it’s nicely wrapped around that defect. And we finished it off with some dorsal blood at that level to also wrap around that.
Glue can also help in your acutely unwell patient. This was a young patient who came in, had their subdural hematomas evacuated three times, was getting progressively worse. They had very bad brain sag. They even developed a Duret hemorrhage as a result of worsening brain sag. Now I think in these patients the emergency management is to do a high-volume epidural blood patch to stabilize them, which we did, and then we went on within the next few days to find the leak. Now he was young, he was only 27, he had no fluid, but he had this massive fistula, and he was still relatively sick. So even though it was a massive fistula, we did incremental fibrin here as well, and the patient did really well. He’s completely symptom-free now and his brain MRI has resolved.
I haven’t had experience with this, but Andy Callen and Mark Mamlouk have also used fibrin for CSF vascular malformations and Andy recently published a case with CSF lymphatic fistula as well. So this can be used for other indications. But there are risks of glue treatment, and these do according on which type of leak that you’re treating. When you’re treating these ventral dural tears, we obviously consent patients that this can be very serious risks including risk of hydrocephalus, chemical meningitis, and arachnoiditis. Those are rare but they are very serious, so we do tell them about that. Lateral leaks we haven’t had any adverse incidents reported, but we still speak to patients about this being an off-license indication for the technique and we are honest with them about our results.
Within our cohort of the CSF-venous fistula group, there were three patients who developed radicular pain, and sometimes that can be seen with transvenous embolization as well. We have seen asymptomatic pulmonary embolism. And rebound intracranial hypertension was actually similar across all three types of leak. Interestingly, it doesn’t predict outcome.
So this can be a bit of a worrying sign, or at least when I first had it I was worried by this intrathecal spread of injectate. We have never had a clinical issue with this, but this is also why I only incrementally do the spread to make sure of our positioning. Usually when we’ve had this, these patients are followed up without clinical consequence and the fibrin has usually dissolved. I think blood is actually much more toxic than fibrin is. So it looks alarming but the sequelae are relatively rare.
This is often a concerning thing. Intentional intravascular injection of fibrin is not something that we advocate for. That’s why we always do test epidurograms with air and contrast. But sometimes you can have some fibrin in the vascular system. So this was after 2 mls, we see that there is actually some filling of the basivertebral vein, and also you can see some venous filling there, and that does increase the risk of a hypersensitivity reaction in the future. You can see that there. And you can also get pulmonary embolism from that. I’ve only noticed this once. Mark has noticed this a couple of times, but these have been asymptomatic.
Duke have recently published on this paper for hypersensitivity reactions. It occurs in roughly one in 200 patients, but usually on a repeat injection, never before that, and is associated with a lower BMI and a younger age. This is something to be extremely careful of if you’re doing a repeat glue. We get everything ready in the room. I’m very meticulous about this. I make sure the anaphylaxis kit is ready. We premedicate with an H1 and H2 agonist because having this reaction is a serious problem if you get this.
I want to finish up with a final case, and I would say that I have had more and more of these cases. This was actually one of the first patients we ever treated. This patient came with actually years of symptoms. You can see she has a layered calvarial hyperostosis, the brain sag, and you can see she has this fistula at T5. It has this beautiful transosseous vein. We treated this. This was one of my first glue patches, and she did really well. She was completely symptom-free for two years, and then she had symptom recurrence two years later. We imaged over that CSF-venous fistula at T5, and I did four runs because I was convinced it was going to be there. No CVF left there. But she had a new CVF, and it’s a big CVF at right T9. No residual recurrence at the old site. So we gave her a new glue and she was well for six months, and then her symptoms came back. So we imaged over that right T9, and you can see that the fistula that we’ve glued has gone, but she has a new one at right T6. I could have chosen several cases to show you this. And we glued that as well.
That begs the question: when it’s like this, why use more invasive methods first? We are still relatively young in the course of this disease, and we haven’t had a lot of long-term follow-up for how many of these patients will recur – and what is driving this? We are finding more and more bilateral fistulas, multiple fistulas. I’d say we found at least six in the last few months alone. Ajay Madhavan from the Mayo Clinic has recently, in the last two days, had this paper which has brought together several institutions to look at these multiple CSF-venous fistulas. This is even more reason for us treading lightly.
This is my amazing team and my amazing international collaborators who I’ve learned a lot from. Thank you very much.