Slides
Transcript
Hello. All right. I’m going to talk about pressing issues in SIH. To be honest, I was a little surprised when I saw this as the request for the topic. I was kind of hoping for how to do a myelogram, but it’s okay. I appreciate it. Wouter, look for your invitation to lead the small group therapy session at the next Bridging the Gap. Here are my disclosures, none of which are relevant for this talk today.
Actually, I am very grateful for this topic because it gave me a lot of opportunity for self-reflection in terms of what are the things that are important to me when I take care of these patients. What are the things that I think we can improve upon? And I think that I tried to split it down into sort of two things. One was what could we do better and then what remains elusive and clinically important things that we don’t understand. And so I’m going to try to break it down into sort of systems issues and then issues of unknowns.
But before I talk about all the ways that we can improve, I want to just pay attention to how far we’ve come. In the late 19th century, this clinical syndrome of a leak was described after lumbar punctures, and it wasn’t until many years later that we started realizing this could happen spontaneously without someone having a needle in their back, per se. And it wasn’t until 1988 that in the ICHD-1 SIH wasn’t described at all, and Dr. Schievink really was the first one to pioneer this field, have us understand that these could happen non-iatrogenically, spontaneously. And then finally in the 2000s the ICHD-2 described the spontaneous CSF leak, and CSF-venous fistulas of course were described in 2014. And we’ve all seen a graph similar to this, the sort of rapid exponential increase in understanding and publications related to intracranial hypotension, really with an inflection point probably after the discovery of CSF-venous fistulas.
We’re all very excited to make contributions to the literature in this regard. But yet there still remain major issues in the care and research for our patients. From a systems-level issue I see this in four facets. There’s awareness, access, education, and then infrastructure as well. Now we all are aware of this to some degree that this disease is probably underestimated. We have these two papers that report their incidence between two and five per 100,000 per year. But this disease of course is very prone to underestimation. We know that most of these cases are misdiagnosed initially, that their clinical presentation mimics other headache disorders and other disorders in general and diseases in general. That these patients often have a delayed diagnosis and that the coding specific for SIH wasn’t introduced until 2018–2019. You can imagine that people aren’t coding this correctly even with the available ICD10 code. And so the true burden of this disease is likely much higher than we claim for it to be.
And then despite that we have this issue of lack of access. We know that there are these centers for intracranial hypotension, for CSF leak, around the world but there’s still large gaps in the care for these patients, and so it’s hard for these patients, who are there probably more than we realize are out there, to actually get the care they need. And this, when I was thinking about this and sort of like what patients are we seeing versus the patients that actually have this, it prompted me to want to look at our own data and say, is there a way that we could sort of counter-factually estimate the number of patients we’re missing with this disease.
So I enlisted one of our trainees to look at one month of patients in our CSF leak clinic and then compare that to the same month of patients who showed up to the ER who had a headache and who received neuroimaging. So their provider to some degree was concerned enough about their headache that they should get an MRI or a CT of their head.
And what we found were some pretty interesting things. In our CSF clinic there was a statistically significantly higher percentage of women. There was a statistically significantly higher percentage of English speakers, of people with private insurance, and they were traveling longer to see us, the ones in the CSF clinic. And their median household income was higher but this was not statistically significant. That surprised me a little bit. And there were many more white patients. Okay, 90% compared with 48%.
So this is not a perfect way to compare this but I really do think that it gets at the fact that there are patients who are particularly of lower socioeconomic status who may have lower health literacy or understanding who are out there suffering from this disease that we are not taking care of. So I think this is a pressing issue and I think that we’re underestimating the impact because of that. I like this comic where this guy is looking for his quarter that dropped and the cop asked him, “Well, did you drop it here?” He said, “No, I dropped it over there, but I’m looking here because the light’s here.” We’re where it’s easy to see. And it’s the same thing. We’re making all these sort of generalizations and inferences about our patients, but we’re not maybe seeing all the patients with this disease. And because we know that the impact on our patients is profound in terms of job and financial stability, etc., you can only imagine how much more of an impact that is on patients of a lower socioeconomic status, for example, than those who don’t get specialty care. So I would implore all of us to sort of focus on this a little bit more, to try to quantify missed SIH diagnoses and the impact in lower socioeconomic communities or non-English-speaking populations because I believe that they are out there.
But I just mentioned this CSF leak center thing a bunch of times and I think that it’s really important that you don’t need to be at a CSF leak center to care for these patients. And this was a message I got on the EMR during our first Bridging the Gap conference. We’re talking about all those sort of nuances of care and patients navigating the system and they said, “Hi, Dr. Callen. This is Mary from DocLine. There’s a hospital that’s requesting to transfer a patient to you because she’s postpartum with an epidural complicated by a CSF leak and anesthesia will not patch her because her spine MRI shows an epidural fluid collection.” Now, as we all know, we would expect to see an epidural fluid collection, but this is the kind of thing that’s happening out there where people who are equipped with the tools to take care of these patients, at least temporize them or improve them clinically, are not doing so just because of a lack of understanding. So maybe we don’t always need a center, we just need some education, right?
Another systems issue that I think is very important, it’s been alluded to partially in some prior talks, are issues of reimbursement and sustainability. So my department did me the favor of proving to me exactly how much money I was losing for them by doing CSF leak work. And through a series of complex calculations, they showed to me that I’m basically making 60% of the RVUs, the clinical productivity of a benchmark diagnostic neuroradiologist, by doing this work.
Now, my wife is sitting over there and you could ask her, do I seem more stressed on my diagnostic days reading cases or my procedural days? Here’s an example of a procedural day of mine, kind of seven to four doing cases and then a day with clinic and then procedures. I don’t feel like I’m doing 60% of the work, but nonetheless that’s what the hospital side is seeing.
And so to get our systems to sort of support us in doing this work, it can become very challenging if we’re not able to code and bill correctly. We don’t have the sort of CPT or CCSD codes for advanced myelography and targeted patching that we need. When I’m doing a dynamic myelogram which requires much more intense care and consideration, I’m billing it as a conventional myelogram, right? And we all know this is not the same thing. And similarly, when a lumbar fluoroscopic epidural blood patch is not the same thing as passing a very long needle by very critical structures to access a ventral leak to try to patch it in terms of the time taken, expertise required, etc. Nor is it the same passing a 15 cm needle through a patient’s nose with the assistance of ENT and our general anesthesia to treat a CSF lymphatic fistula at the skull base. Nonetheless, we’re just billing it as a blood patch, right? So this is a big problem and a problem if we want to encourage more people to take care of these patients, particularly in private practice. We’re very motivated by productivity. How could we really convince them to do that at all?
Now I want to move beyond systems. I felt like I had to talk about those things because I do believe they’re pressing issues. But these are the things that I feel very passionately about, that I get excited about and get very frustrated about.
And I want to step back before I talk about what makes me frustrated and remember why we’re drawn to this work. Why are we addicted to this? Why do we love taking care of these patients and figuring things out, contributing to the literature? And I think there’s three things that contribute to that.
Number one is the curiosity, right? The unknown. There’s so much, the fact that we discovered this type of CSF leak about a decade ago. It’s so young. What else are we missing? What else are we not seeing in these patients that perhaps we could discover? We could be a part of that discovery.
There’s also, of course, the altruism, right? The desire to help. It’s such an amazing feeling to change these patients’ lives, to take them from a place of suffering, a place where people weren’t believing them, for example, and then show them that there is something wrong and help them and fix them. It’s why we went into medicine, is to be healers, right?
But I think that a big, big driver of this, at least for me personally, is the frustration, is feeling that when we feel like we can help and should help, but we can’t help, why? And that’s what I want to talk about here. I’m going to progress through sort of the easy wins in terms of when we get that satisfaction to satisfy our curiosity, our altruism, and then when we get to the frustration.
We take somebody like this, right? This is a classic example of such a wonderful win for us. A 61-year-old guy who has carried these six different diagnoses for years: migraine, tension headache, TAC, TMJ, occipital neuralgia, supraorbital neuralgia. He had a regular myelogram in 2016, and then gets his lateral decubitus myelogram 5 years later. And we find this CSF-venous fistula. Incredibly validating for the patient, incredibly validating for us, and we’re all high-fiving, happy about this, right?
And then we have cases that are very frustrating, but they’re frustrating to different degrees. There are ones that I will call diagnostic dead ends, and they’ve been alluded to so far.
And so, we’ll have a patient like this, and I’m sure that if you’ve taken care of these patients, you’ve seen someone like this in your clinic before. Thirty-four-year-old woman. She had a sudden onset suboccipital headache. No prior history of migraine. She has neck radiation. She has muffled hearing. She has aural fullness. She describes ringing in her ears. She feels completely fine when she lays flat. She had a workup for POTS. It was negative. She had several migraine-directed therapies. They were ineffective. Her brain MRI does not show evidence of a leak. She has no epidural fluid, nor did she have any significant spinal meningeal diverticula. Nonetheless, we said we’re still going to look for a CSF-venous fistula. We didn’t find one. Nonetheless, we’re still going to offer her an empiric epidural blood patch, which doesn’t really help her. Maybe a couple days where she feels a little better, and then she’s back to baseline. And after that she undergoes a bilateral styloidectomy for concern for jugular decompression, an occipital-cervical fusion for concern of craniocervical instability, surgery for occult tethered cord, and she’s no better. Now this is devastating and horrible, but at least we can say we tried. Maybe she would have even gone to places where they would have said based on that brain MRI we’re not even going to look, or we’re not going to do a myelogram, we’re not going to offer you a blood patch. It’s frustrating and devastating, but we have our tools and our understanding, and we used them and said, “Well, these were negative and they didn’t work.”
That is not as frustrating to me as the following scenario, which I’m going to show some examples of, which has been talked a little bit about yesterday and today, and that is I’ve become obsessed with a little bit, which is this fix-failure paradox where we have technical success, we use our tools, we achieve our desired goal, but we have a clinical failure despite that. I’m going to show two cases that illustrate this.
The first patient, a 51-year-old woman, she had a sudden onset suboccipital orthostatic headache about a year and a half ago. She had severe vertigo and tinnitus. Her brain MRI was pretty unremarkable. There’s maybe some very subtle signs of sag there or prepontine is a little effaced. Maybe there’s a little bit of tonsillar downward displacement of her cerebellum, but no real venous engorgement and no dural thickening, nor are there subdural collections. Nonetheless, she has a big epidural fluid collection. So it doesn’t matter that her brain MRI looks like that. She has a CSF leak. We find the CSF leak. It’s on the left along the T9 nerve root axilla. It’s localized intraoperatively and repaired, and the fluid is gone, but she doesn’t feel any better at all. It’s exactly the same. And now, this is a couple years after her surgery. She’s not improved one bit. We repeated a myelogram. Perhaps there’s a CSF-venous fistula there that we missed, or one had developed at the operative site or elsewhere. It was negative. We patched her lumbar puncture site. Perhaps in looking for the leak, we gave her a leak and she now has post-dural puncture headache. No benefit. Perhaps this is an atypical manifestation of rebound, this thing we call rebound. And we tried her on Diamox. No benefit.
Here’s Patient B, 73-year-old man. He was actually a surgeon at our institution. He had one month only of a left-sided headache, which was worse when he coughed or bent over to tie his shoes, and he had right-sided non-pulsatile high-pitch tinnitus. He had diffuse dural thickening and he had a CSF-venous fistula on the left along the T7 nerve root sleeve. First we tried gluing it with fibrin. I tried twice. He didn’t feel any better. His brain MRI did seem to improve, but nonetheless he wasn’t getting better. He then underwent endovascular embolization with Onyx. Didn’t feel any better. And after that had repeat decubitus CT myelogram. It was hard to see things because of the Onyx, and then had a DSM repeat, still did not see any residual or recurrent fistula, and then still underwent surgical ligation. We thought, well, perhaps it’s still percolating there through the Onyx in some way that we just can’t see, let’s just go ahead and ligate that nerve root. And he’s not better.
So this drives me crazy, and I’m sure it drives others of you crazy too. And what is going on here? Is this central sensitization phenomenon? These patients now have rewiring of their nociceptive circuitry and they just are never going to feel better? There’s something wrong with the wiring? Do they have some persistent undetectable leak that we just are not yet able to find or see or understand? Or is this rebound intracranial hypertension, CSF disequilibrium phenomenon, that we’re sort of hand-wavy, oh, your internal thermostat’s been reset and now you’re kind of in this high-low state that we like to say. And I really wanted to try to understand, I want to try to understand can we predict the non-responders, rather than asking the question after the story is over, can we go back to the beginning and say is there something about these patients, a pattern in the patients who aren’t getting better after we treat them and radiographically it looks like we did.
So I went through 92 of our ICHD-3 positive definite leak patients who had documented clinical follow-up in our medical record. There’s 32 ventral tears, 14 lateral tears, and 46 CSF-venous fistulas. And the mean follow-up for these patients with their documented follow-up was 5.3 months. And again, we just used this self-reported patient saying, “I had either complete, partial, or no improvement in my pre-operative clinical symptoms.” We also looked at their brain MRIs and the Bern score subcomponents specifically, and looked at them just to see, is there anything on the brain MRI that can give us a clue as to what’s going on.
Now the very first sort of preliminary analysis here, which I’m showing, a couple of very interesting things stand out, and some of them may be intuitive. For example, the patients who weren’t getting better had a longer symptom duration, pre-treatment symptom duration. This has been described in several papers already. It kind of intuitively makes sense. The leak’s been ongoing longer. Maybe it’s that resetting of the internal thermostat phenomenon or what have you. But then there’s a couple other interesting things here. Patients who weren’t getting better seemed to have a higher opening pressure. And then patients who were getting better seemed to have more positive brain MRIs, a higher Bern score pre-treatment. And interestingly, in this subset of patients, women were doing better than men in terms of a treatment for their leak.
But the thing that was very interesting to me was the thing at the bottom – that none of the individual subcomponents of the Bern score were predictive on their own except for venous engorgement. The patients who had venous engorgement on the brain MRI pre-treatment seemed to be getting better at a way higher rate than patients who did not. And so it looked on the outset like shorter symptom duration, lesser opening pressure, higher pre-treatment Bern score, and venous engorgement were all seeming to be somehow related to complete clinical resolution.
But we did a couple adjusted multivariable models here to see if there were any effect modifiers, one thing causing, related to the other. And when we have a model that includes female sex, pre-treatment venous engorgement, symptom duration, opening pressure, and pre-treatment Bern score, everything except for female sex and pre-treatment venous engorgement drops out of significance, but those two remain strongly significant. And we have a model of female sex, symptom duration, pre-treatment venous engorgement, and then the change in Bern score. The only thing that remains significant is pre-treatment venous engorgement.
So I found this fascinating. One other relationship that I thought was interesting was that patients without venous engorgement were the ones that had higher opening pressure. So when accounted for in the model, that opening pressure dropped out of significance. But nonetheless, there’s this relationship going on between the venous engorgement and the CSF pressure that is not just a function of symptom duration. And is there something here that’s important?
Well, we did prior work that looked at this sort of elastance to the craniospinal compartment, or the reciprocal of compliance, right? So we’re infusing saline and how much does the pressure change in response to that infusion. And one of the things we found is that patients who had venous engorgement had more compliant craniospinal compartments. So there’s something about the compliance of the system and the presence of venous engorgement. Those two things are related to some degree.
And we also know that patients can present in sort of clusters of imaging findings. Patients like this one who have severe brain sag but don’t have venous engorgement or dural thickening, and other ones who present with the opposite, who have dural thickening and venous engorgement but no brain sag. And so these two co-occurring pathophysiologic mechanisms maybe aren’t just happening at random but reflect something underlying about that patient’s system that predisposes them or allows them to be normal again or be healed again. The plasticity of that system despite both of the patients having the same type of CSF leak, CSF-venous fistula.
This is just showing again that these findings do tend to cluster together in our experience. And that those clusters, those imaging clusters, also seem to relate to a clinical phenotype. We found that the classic symptom cluster of patients reporting a pressure-throbbing type headache with an occipital location, with relief when flat, and when they had comorbid neck pain, seemed to cluster with findings of brain sag with a brain sag imaging cluster.
Whereas this sort of atypical cluster, ones that I don’t think we’d associate with a CSF leak headache, a sharper stabbing frontal type headache, less orthostatic relief, and less comorbid neck pain, seemed to be not clustering with the brain sag, with the venous engorgement-dural thickening group.
So what have we learned recently about venous pathology, intracranial hypotension? What does this mean? What is this a clue? Is this just noise? Is there something here that is very important? Well, Dr. Schievink’s paper recently described that there are these patients who have this brain sag in whom we cannot find a CSF leak, and in a subset of those they have stenosis of their azygos vein. And that stenosis of this unique outflow conduit, the singular outflow conduit to the thoracic spine, resulted in that sag syndrome for them along with their behavioral variant frontotemporal dementia syndrome. And treatment of the azygos stenosis in three of those patients reversed the sag and improved their clinical syndrome.
So there was something about the veins in these patients and perhaps their compliance or their plasticity which was changing their CSF dynamics and leading to a very severe clinical syndrome. Does it stand to reason that that could be existing to a certain degree in other patients, perhaps not to the same severity?
And we also know that if we look at the sort of opposite clinical phenomenon, this rebound intracranial hypertension phenomenon, there’s something important about the veins there too. Patients who develop rebound intracranial hypertension are ones who tend to have hypoplastic or stenotic transverse venous sinuses. This phenomenon of RIH, patients always ask me this question. They’re like, if I don’t get rebound, that must be because the leak wasn’t fixed, right? And I think that they’re imagining sort of like a pipe under a sink that’s leaking out and the water is flowing out of the faucet to maintain that level. But then when it’s patched, it’s starting to overflow, right? It sort of intuitively makes sense, but that’s not really the model. We have three different multi-institution studies now on patching each different leak type. And in all three of them, rebound intracranial hypertension was not related to clinical success. So that is not what’s going on here. It is not just simply a CSF hypervolemia issue or however you want to call it. But instead, RIH is reflecting a phenomenon of venous dynamics in response to a change in CSF pressure.
Nonetheless, I think we should continue to keep an open mind with respect to this phenomenon because it is only with an open mind that we’re going to be able to figure this out. Perhaps a lot of the things that we are sort of stating to be true and dogma now we may prove ourselves to be wrong, right? That’s the best type of science.
So those are my pressing issues in SIH. I promised myself I’d try to make a pressure joke because it just seemed too obvious, but I couldn’t. So there it is. There’s a pressure joke. But yeah, systems pressures, right? And these I didn’t mean to minimize them. I’m less passionate about them, but it’s a little more boring. We need to get better access for our patients. We need to fix our building and infrastructure so that our colleagues across the world can do this type of work and not feel like they’re losing money for the department. We need to access our patients who are in lower socioeconomic status, in marginalized communities who are suffering from this disease that we’re just not seeing. And then the clinical pressures, right, when cure isn’t cure, when we’re using the tools that we have with our current understanding and nonetheless not able to help our patients. I think these are the two pressing issues for me.
With that, I want to say thank you. And I want to say thank you especially to my two awesome trainees who I really, really was hoping were going to get that prelim data for me before this talk, and they did. So thank you to them.