Spinal CSF Leak Foundation in conversation with Dr. Mark Mamlouk
Dr. Mamlouk took some time to discuss with us his most recent publication, “Factors Predictive of Treatment Success in CT Guided Fibrin Occlusion of CSF-Venous Fistulas, a Multicenter Retrospective Cross Sectional Study,” an important new study evaluating the clinical and radiologic outcomes of CT-guided fibrin occlusion across six international sites, looking to find a correlation among cure rates, fibrin injectate spread, and drainage patterns.
The paper concluded: “CT-guided fibrin occlusion is a safe and effective treatment for CVF, achieving a relatively high clinical and radiologic cure rate with a small adverse effect profile across multiple institutions. The alignment between the spread pattern of fibrin injectate and the drainage pathway of CVFs appears to play a significant role in treatment success, emphasizing the importance of preprocedural mapping and tailored needle positions. Additionally, the shorter duration of symptoms preceding treatment was associated with a higher likelihood of treatment success, highlighting the significance of prompt intervention in patients with SIH.”
Dr. Mamlouk is a member of the Spinal CSF Leak Foundation Medical Advisory Board, and neuroradiology lead of The Permanente Medical Group, where he is also director of the Spinal CSF Leak Program. He also works as a volunteer Assistant Clinical Professor of Neuroradiology at UCSF.
Transcript:
Andi Buchanan
Hi, I’m Andi Buchanan, Executive Director of the Spinal CSF Leak Foundation. And with me today is Dr. Mark Mamlouk, a Neuroradiologist and Spinal CSF leak specialist, here to discuss his recent paper titled, “Factors Predictive of Treatment Success in CT Guided Fibrin Occlusion of CSF-Venous Fistulas, a Multicenter Retrospective Cross Sectional Study,” published this month in the American Journal of Neuroradiology. Dr. Mamlouk, thank you so much for being here.
Dr. Mark Mamlouk
No, thank you for having me, Andi, and thank you to the rest of the Spinal CSF Leak Foundation for the invitation on behalf of me and our co-authors as well.
Andi Buchanan
First of all, congratulations on this paper. It’s so important and it’s groundbreaking for many reasons. Most notably that it’s an international multicenter study, correct?
Dr. Mark Mamlouk
Yeah, we had six institutions over the United States and UK with several different neuroradiologists who perform fibrin glue for CSF-venous fistula. And one of our main hypotheses was to see how well fibrin glue occlusion or patching did for CSF-venous fistulas.
Andi Buchanan
Have there been very many multicenter studies looking at anything in regards to spinal CSF leak?
Dr. Mark Mamlouk
No, it’s um, it’s a, well, it’s, it’s been challenging to date. Most of the, most of the papers, including a lot of ours have been from single-center institutions. And I think this is groundbreaking in the sense that we’ve essentially established a CSF leak community, and we’ve collaborated together to see if we can harness all of our data to help provide more accurate numbers on efficacy and incidents, et cetera. So I think it’s very exciting and I have no doubts that this should, um, will continue for other groups as well.
Andi Buchanan
I’m always curious about where ideas come from. What was the impetus for this study and why did you think it was so important to do it?
Dr. Mark Mamlouk
Yeah, I think that’s a great question. We, so I think we’re lucky, as a society and for CSF patients, now that we have three good treatment strategies for CSF-venous fistulas, one being surgery, one being fibrin glue patching, or occlusion, and one being embolization. And I think all of them are good treatment strategies.
However, there’s not a lot of data on each of the individual treatments. When we published our paper a couple of years back on fibrin glue patching for CSF-venous fistulas, it was novel in the sense that it was different than prior reports on how patching did for fistulas.
And I think a lot of that had to do with, there was just not a lot of information out there with respect to what type of modality was used, how much, and what type of agent, you injected, particularly where exactly did you inject. A lot of the prior papers were just, Oh, we did this. And there was a little bit, uh, there was information about the actual patching. So our paper on fibrin glue patching a couple years ago really sparked the discussion of how patching can be used. So our multi-institutional study with first author Dr. Callan, we led a multi-disciplinary, multi-group team and we evaluated to see how good patching did.
Andi Buchanan
Is there a difference between fibrin patching and fibrin occlusion?
Dr. Mark Mamlouk
No, there’s, there’s no difference between the actual, they can be synonymous. However, I will say that the term patching is used variably throughout the community and in the literature. And it really matters exactly where you inject. So not all patching is the same. So, but in the context of our paper, patching and occlusion are synonymous.
Andi Buchanan
Can you explain a little bit in layman’s terms maybe about, uh, where, where is it injected exactly?
Dr. Mark Mamlouk
Yeah, no, that’s a good question. So a lot of these, these fistulas are on the side of the spine in the, what we call the perivertebral space or the neuroforamen, and they course along the side of the vertebral body and then drain into the systemic bloodstream. So what we hypothesized in our paper was, we wondered if, it sounds pretty basic, but you want to match or inject the glue where the actual fistula is.
And where the fistula is, is actually in a different location because it’s often not in the epidural space, where traditional patches are performed. So sometimes people will say, “Oh, I had a patch for a CSF-venous fistula,” which could be a traditional patch with injectant into the epidural space.
But that’s not going to occlude the vein, because the vein is often not in the epidural space. So our main hypothesis was, if we match the glue spread or the glue location to the fistula, will that result in a good outcome?
Andi Buchanan
How were you able to assess that?
Dr. Mark Mamlouk
We assessed it from a few different standpoints. We first characterized the actual anatomic location of the fistulas and we identified certain patterns that most fistulas will have. Then we characterized the location of the glue injectant performed by all the doctors, and then we correlated them to see if they were concordant.
Subsequently, we then used brain MRIs before and after the treatment and assessed any differences. And lastly, from a clinical perspective, we evaluated patients by combing through the medical records to see if patients had complete or partial or no response to the fibrin glue patching.
Andi Buchanan
One question that’s come up in our community regards fibrin and the use of fibrin in itself. If fibrin glue dissolves over time, what’s the mechanism that keeps the fistula closed after the glue dissolves?
Dr. Mark Mamlouk
If the vein clots off, then even if the fibrin glue absorbs in your body, there is a high chance that the vein won’t reoccur and that the fistula can remain closed. What we’ve noticed that’s the case in the majority of cases, sometimes when you close off one vein, the other veins can sprout up and then the fistula can remain active.
And this has been the same phenomenon that’s been observed with embolization and surgery as well. So it’s important to make sure you target all the veins in the particular area, but also be cognizant that if the patient doesn’t completely improve, that you may have to do additional treatments or additional evaluation. And that’s the same going for the other treatment arms as well.
Andi Buchanan
Do you see subsequent fistulas forming after treatment with fibrin occlusion?
Dr. Mark Mamlouk
Often not, we would say, I would say the majority of the time, the fibrin glue remains closed. If the patient still has symptoms. It’s probably that not all the veins were closed, and additional treatment may be needed in that particular case.
Some patients rarely may undergo fistulas elsewhere along the spine, and that has been described with all the different three treatment arms as well. We don’t really know why that occurs. But I would like to convey that it’s not a very high incidence of that. So it’s more the exception rather than the rule that you develop additional fistulas. But it can happen.
Andi Buchanan
I wonder if you could comment on one of the findings in your paper about the statistically significant association between concordant spread and clinical improvement.
Dr. Mark Mamlouk
Yeah, that was one of the main findings in our paper, and the concordant spread between where the glue is and the fistula was statistically significant with clinical improvement. And that kind of makes sense in the sense that you want to inject the glue where the fistula is, and if the glue, for some reason, didn’t go where the fistula is, then clinical improvement wasn’t as good.
So that was one of the main takeaways from the paper, and the most chance for success is matching the glue spread with where the actual fistula is. And that just speaks to also the importance of accurately characterizing the fistula. Some of these fistulas are very basic with one vein, but sometimes they have multiple veins and very complex. It speaks to the necessity to accurately characterize that on advanced decubitus myelography.
Andi Buchanan
The other significant association you found was between pre-treatment symptom duration and clinical improvement.
Dr. Mark Mamlouk
Yeah, that was, that was an interesting one and I think we kind of somewhat intuitively suspected that, but it really was an interesting finding for us in that patients who have been leaking for longer, even if they had successful treatment, their improvement wasn’t as good as patients who were leaking less, and not as long. And this also correlates with another group that evaluated for ventral dural tears in that patients who were leaking longer, even if surgically corrected, had less improvement. I don’t think we really understand the reason that is, but I think one main takeaway is that it’s really advantageous to get evaluated and treated earlier than later.
Andi Buchanan
Could you speak to the perception that fibrin occlusion is a less effective treatment than onyx embolization? Do you have, do you have thoughts on that?
Dr. Mark Mamlouk
Yeah, I, it’s, uh, to be honest, there actually is no study that has compared surgery versus embolization versus glue. And I think a lot of it will depend on which institution you’re at and the doctors’ comfort level with each of those different treatment arms. What we have seen is that fibrin glue is very effective.
It’s minimally invasive treatment. It’s easy to do, as shown in our study across multiple different institutions, small and large. So I think going forward, we will have to do some multicenter trials to evaluate the different treatment arms. I think it would be a difficult study to actually do. In short, I think all treatment arms are helpful for this condition and I think we need to do more evaluation to see if one is better than the other.
Andi Buchanan
Given that this study was done across multiple institutions, were you surprised by the range in success rates? Or did you kind of expect to see the differences that you found from institution to institution?
Dr. Mark Mamlouk
I think it was, it was kind of what we expected and I think it was, so in our paper, approximately 60 percent of patients were curative from fibrin glue patching, 35 percent were, had partial improvement, and 5 percent had no improvement. And the numbers are a little bit lower than our initial study for fibrin glue patching for fistulas.
However, I think that could be related to just institutional preferences or provider awareness of the actual technique. And I think with more and more use of fibrin glue patching, that there could be a potential learning curve. Just like in anything in medicine, in any procedure, there could be a learning curve. And I suspect over time that those numbers can get higher and higher.
Andi Buchanan
Yeah. It seems like this study showed that early treatment intervention and the accuracy of the injection placement were the keys to positive outcomes here. So, so where do you, where do we go from here? What are the next steps in educating physicians in this technique to treat patients?
Dr. Mark Mamlouk
Yeah, I think, I think, emphasizing the, the— again, injecting where it matters. A lot of neuroradiologists and radiologists and interventional radiologists perform a similar procedure for patients with pain, spinal pain, and we inject the steroids into the spine for pain relief. And one of the traditional ways to do that is you want to inject the steroid medication around the nerve, and you also want to get medication going in the epidural space to maximize the patient relief from pain. And I think because a lot of physicians are so ingrained in that needle positioning and technique, that has led to, when they’ve tried this for patching for fistulas, they perform the same technique, and that has led to less effective success with fistulas, and then they say, Oh, well, maybe I need to give up and do something else.
However, we want to convey that it’s not the same as a traditional steroid injection, and you want to target the needle in a different location, and possibly even use more than one needle, if the fistula is complex. So I think education on actual needle placement. I think the good thing though is it’s, if you can perform these traditional spine interventions, then you can also do patching for fistulas, and I think that’s good for the whole world in general, given it’s a relatively easy procedure to learn.
Andi Buchanan
Wonderful. Was there anything else you’d like to mention about your study that we didn’t already cover?
Dr. Mark Mamlouk
I think overall, I’d just like to part with that, um, I think we’re very excited that we’re developing new treatments and further treatments for patients with CSF leaks. For us physicians that see a lot of patients with CSF leaks, we understand the pain that patients have come through.
We understand that they’ve been through many doctors and many doctors may not believe the symptoms that they undergo and, um, we just want to say that we hear you and we are here for you and we think the future is bright for CSF leak evaluation.
Andi Buchanan
Well, thank you so much for your time, and your dedication to helping everybody affected by spinal CSF leak.
Dr. Mark Mamlouk
Thank you. Thank you for having me.
Further reading: