Slides
Transcript
Hello again. It’s nice to be up here again speaking at this incredible conference. I’ve learned so much. There have been such great talks, and I’m really honored to be here and to have been invited, so thank you to all the organizers for the invite.
So, yesterday I just sort of showed one of my complex cases, and I think all of us neurologists who are in this field can talk about complex cases until the day is long. But I think that what I want to really focus in on – on what makes them so complex beyond the fact that they are at high risk for a CSF leak. And so, I wanted to go through some different comorbid diagnoses, what they’re really about, how to think about them, how to think about them in the context of CSF leak patients. And like I said, I just have found this conference to be so incredible. I really have learned just a tremendous amount, and I’ve really sort of connected with all of the talks, including those from the patients.
I have been a patient myself. I was dismissed and gaslit for a long time, despite the fact that I was a neurologist. Everyone just told me that I was anxious, stressed, I missed my family, and I was working too hard. I ended up having a very large tumor in my brain, so I understand the journey that patients go through, and I really respect the fact that this conference included patients and allowed them to tell their stories. Because I think as doctors, we often forget what we’re asking patients to do. We often don’t realize how long the patient has suffered before they had finally presented in front of us. And so, I think it’s important also to understand that there are other things that were probably contributing over the years that may have led up to the CSF leak or may very well impact the way that we diagnose the CSF leak, the way we treat it, or even its healing and recovery.
So, no disclosures or conflicts.
So, Mast Cell Activation Syndrome – I think I get more questions about MCAS, no, probably about EDS than I do about MCAS, but MCAS is definitely a close second, about what Mast Cell Activation Syndrome is. So, it really – it’s a very hard syndrome to describe. It obviously focuses on the mast cells, which is part of our innate immune system. It’s a first responder – it’s fast acting, doesn’t care who the enemy is, it’s there to protect us. But ultimately, when the mast cells are overly activated, they become trigger-happy, and they just degranulate and release all of their mediators over and over and over again. So, it ends up becoming a very chronic multi-system, multi-organ illness.
And it could be very confusing actually because the symptoms are not just about the histamine. And I very regularly say like, we focus too much on the histamine, you know? So, all these patients come to me on antihistamines, and you know in neurology, we’re not huge fans of antihistamines because they lower seizure thresholds, they lower migraine thresholds, they impair nutrient absorption, which can cause whole other kinds of problems. There were some small studies that showed that long-term use can contribute to cognitive decline.
So, they were all on antihistamines and for long periods of time. But it’s not just about the antihistamines, because the mast cells actually have about 1,200 different mediators, and a lot of those mediators cause way more damage than the histamine does. And the histamine reaction is actually fairly easy to see, right? It’s allergies, it’s atopy, it’s – you get flushing, you get hives, you get itchy, you have allergies to, seasonal pollen. But it’s the other mediators that are somewhat obscure in their effects and are very hard to identify.
But I really do believe, because I’ve seen so many patients over the years, that it really – those mediators are more of the problem than the histamine, and the triggers can be anything. I mean, so it’s like we think, oh, it must be you got an infection, and so you have mast cell activation, but it can be anything. I mean, I have patients who are just sensitive to – I call them too sensitive for the world because their mast cells will activate based on a fragrance in the air or even mechanical compression. So, mast cells are just very finicky once they’re hyperexcitable, and once they’re hyperreactive, they can react to just about anything, so including anatomy where it shouldn’t be. And that would include fluids, right? So, if there’s CSF leak, if there’s extravasation, then that can actually trigger mast cells. And I have this on another slide, but if you think about the dura, it is connective tissue, and there’s lots of mast cells. So those mast cells, once they’re reactive, like anything can trigger them.
So, as I said, there are a lot of different mediators, and I don’t have a lot of pretty radiographic pictures as all the other speakers have had, so I tried to find some pictures. I borrowed this from a colleague of mine. But it releases TNF-alpha, the tumor necrosis factor, which is well known to be associated with macrophages and part of the immune response, elastase, and also – I don’t have on this slide – but also matrix metalloproteinases. These are two enzymes that – the elastase focuses on the elastin, and the matrix metalloproteinase focuses on collagen fibers.
And when we think about the components of the connective tissue – and I have slides on that – which is not just collagen but lots of other components – it breaks down the connective tissue. So, if you have mast cell activation and chronic degranulation of those mast cells, then you have further degradation of connective tissue. And that brings us to a whole conversation of whether this is truly like a genetic EDS-type connective tissue disorder, or if it’s an acquired one. I’m not going to even focus on that question today, but it is an important conversation that has to be had.
The histamine that I discussed – the heparin – so heparin is released from mast cells, and it contributes not only to vascular permeability but also contributes to the initiation of the bradykinin formation, which ultimately results in a lot of swelling and pain. And then the tryptase, of course, which is the marker that most institutions use to decide if you have mast cell problems. But it really is a bit of a folly because the tryptase marker can actually help diagnose something called mastocytosis, but it really is not useful in trying to diagnose Mast Cell Activation Syndrome. I have a lot of patients who come and tell me that they were told they don’t have MCAS because their tryptase was normal.
I should say that the labs in general to identify MCAS are notoriously difficult in terms of the technique to measure. And I very often will tell patients, you can’t rule out mast cell activation with normal labs, but you can certainly rule it in with abnormal labs. It’s a very large lab workup, I should say, and I’m not going to cover that today.
So, when you think about mast cells – where they are – they’re ubiquitous, but so is connective tissue, and they’re all over the body. When they are present in vascular spaces, and when circle the astrocytes, they release histamine, leukotrienes, and cytokines, and they have CD4 ligands, which is how they do it. The astrocytes themselves have histamine receptors, and it’s interesting because all these patients, as I’ve already said, are on antihistamines, which are H1 and H2 blockers. But as we know, the H3 receptors are unique to the central nervous system, and yet there are no antagonists for those receptors, so you have all this unopposed histamine now floating around.
I often wonder – and another important conversation – believe me, I’m going to bring up a lot of unknowns and uncertainties because I don’t really have all the answers, but I think these are important conversations to have for this complex patient population.
So, when the astrocytes – when their histamine receptors get their histamine – they release other cytokines, which further then provokes the mast cells, and there’s an implication for the blood-brain barrier here, right? When we think about the dura mater – again, packed with mast cells. And when they’re in contact with pathogens and the pathogen-associated PAMPs – the pathogen-associated molecular patterns – then they too release a lot of different inflammatory mediators. And then there will be glial activation, which then releases a lot of cytokines. Which again, this is an inflammatory cascade that I’m trying to describe, and I should have made a nice picture.
But the other thing, you know, just with regards to the nervous system, is that the mast cells also contain certain serine proteases that will break down collagen and myelin. And the interesting thing about that is that the myelin degradation products are further provokers of mast cells. So it’s this vicious cycle that the central nervous system gets in when there really is a true mast cell problem.
So, another diagnosis that these patients had, that some of the other speakers had mentioned, was, you know, different kinds of autonomic disorders, the most common one being POTS, of course, postural orthostatic tachycardia syndrome. I always say that, the autonomic nervous system is so complex that POTS is like the tip of the iceberg, right? And everyone gets a diagnosis of POTS because, at the very least, if you have an autonomic disorder, when you stand up, your heart rate will go up, and it’ll stay there, and you won’t feel well. But there’s so much more under the water, right? And so, I think that it’s important to recognize that POTS is just sort of a simple form of labeling. You have autonomic dysfunction, you know. As we all stand, there’s a small fall in systolic blood pressure, a small rise in diastolic, and then a rise in your heart rate, and that’s from the baroreceptors. It turns out that studies have shown that baroreflex sensitivity is higher in hypermobile patients, and of course, I’m leading into the connective tissue component to all of this.
So, it’s important to recognize that in these patients, their sensitivity to changes of volume and pressure are actually much more sensitive, and they have a lower threshold. There’s a higher incidence of orthostatic intolerance, which includes neurogenic orthostatic hypotension, POTS, and the blood pressure, of course, maintained by a compensatory tachycardia, increases cardiac output. And there’s very often a history – if you ask, “How were you with a blood draw when you were young?” You will very often get a history of vasovagal syncope.
So neurogenic orthostatic hypotension – on head-up tilt table test, you see a sustained reduction of blood pressure greater than 20 mmHg in systolic and greater than 10 mmHg in diastolic, and this is called passive standing. I know you all know this, but the reason why we do the tilt table head-up is because we want to remove the lower limb muscular pump, as we refer to it, so it’s like passive standing. So, there’s no additional muscle contraction to push the blood up. So, we want to see how the autonomic nervous system just does when it’s in free fall.
So, POTS, as we all know, is a sustained heart rate increase of heart rate when you stand, with at least a 30 beats per minute after 10 minutes. The criteria means that you have to be symptomatic, and I’ve had people just pass out on tilt table tests. You put their head up, tilt, and they’re out. I’ve had posts where they had convulsions even on the table. But they always return to baseline, and they resolve, but that’s clearly an indication of an autonomic disorder. And I, too, label it POTS. It’s really not a criticism. It’s just that I want to recognize how complex that autonomic nervous system is. And when you start looking deeper, and you do a full breadth of autonomic testing, not just the tilt table test, you can see other kinds of problems. And, like I said, there’s syncope, and a common comorbidity, once again, is joint hypermobility.
So, POTS symptoms can very much mimic symptoms of other things and this is a list of the more common symptoms, and I often say the dysautonomia drives disease. When your autonomic nervous system is not protecting you, then a lot of things can happen, and a lot of things can go wrong with the body.
I see a lot of autonomic disorder patients, and, there’s a whole list of symptoms. These, again, are the most commonly ones reported, and certainly the most commonly ones that are listed in literature. But it can run the gamut. In fact, there’s a lot of non-orthostatic type symptoms that include fatigue, circadian rhythm, gastrointestinal, interstitial cystitis – which is very commonly seen with mast cell patients because the bladder, of course, is lined with mast cells – exercise intolerance and fatigability. Though, I would argue that, we could make a connection that these are orthostatic symptoms because they often worsen with position change. And it’s important to remember in these patients, and especially within the CSF leak space, that prolonged recumbency can worsen these autonomic symptoms.
So, there are mechanisms behind POTS, there’s volume dysregulation – lots of hypovolemia and venous pooling, which results in capillary leakage. You know, the blood pools. People like to talk about how the blood pools in their lower limbs, which to some extent is true, but it really pools in the splanchnic-mesenteric bed, which is why compression of the legs is not nearly as effective as those lovely, attractive abdominal binders that I make my patients wear. But it really helps to provide improvement of blood returning to the heart so that the preload is appropriate. Otherwise, you have lower preload and lower cardiac output.
There’s impaired cerebral autoregulation. So, there is hypoperfusion basically due to reduction of cerebral blood flow because the blood isn’t in the brain, so you have impaired perfusion. So, it’s one thing for the blood flow to appropriately flow through the brain – which it doesn’t, because we’ve seen this in transcranial dopplers – but it’s the perfusion aspect that’s lost. So, you have cerebral hypoperfusion, which explains a lot of the symptoms.
And then you have this paradoxical arterial or vasoconstriction. So, sometimes I treat that almost as cerebral vasoconstriction syndrome, with calcium channel blockers, and sometimes patients respond, and sometimes they don’t.
You know, in hypermobility, Ehlers-Danlos syndrome, and other connective tissue disorders – and I like to point out, it’s not just all EDS – and I’m not even sure what we’re calling EDS when we say hypermobile EDS, to be honest. But we do know that there have been studies that have shown that there is dural weakness in connective tissue disorder patients. And having connective tissue disorder, or connective tissue compromise, I believe, is a risk factor for CSF leak.
And in this study – which wasn’t specifically on CSF leak patients. It actually was on patients with the diagnosis of ME/CFS, which does cover this population – they were looking at patients with IIH and hypermobility and CCI, and they found that joint hypermobility was definitely overrepresented in this particular patient population.
So, some facts about EDS – EDS is the classic inherited connective tissue disorder. There are defects in the architecture, metabolism, the fibrillar collagens, and the modifying enzymes, the extracellular matrix. Prevalence has been estimated to be 1 in 5,000. I’ve seen it reported as low as 1 in 500, but just of note, I think that connective tissue disorders in general are sort of now a little bit more mainstream in terms of its focus with regards to how it’s a risk factor for other kinds of diagnoses. In the past year, 284 research papers in hypermobility compared to 880 in between 2019 and 2023 – so there’s been an exponential increase in the amount of research that’s being done on connective tissue disorders, hypermobility, and what they are risk factors for.
There are, of course, several different types of EDS, but I think we’re referring to the hypermobile type. Those that have classic, known genetic subtypes are more easily found because you can do the genetics on them. Most of these patients don’t have positive genetics, but they have hypermobility on exam. But there are other ways of assessing for this hypermobile EDS that we refer to. I think it can be acquired as well, and I will talk about that a little bit at the end.
EDS, you know, it could be challenging to diagnose – I mean largely because of what I said. There’s really no biomarker, there’s no genetic subtype. Some labs have shown that they might be finding a gene. I believe, like I said, it’s either acquired, it’s either polygenic – I think it’s like the two-hit hypothesis. I think a variant is held that sort of sets you up, and some exposure does you in. And so, I think that there’s a lot more research that really needs to happen before we really know what we’re referring to when we say hypermobile type EDS. And the treatment of it is really difficult because it really does depend on the phenotype and what the manifestations are.
So, in terms of connective tissue disorders, it’s not just EDS, right? There’s over 450, and Marfan’s, which someone gave a slide about, Loeys-Dietz- I have several patients with Loeys-Dietz, Stickler syndrome – several patients with that, the osteochondrodystrophies – also very commonly seen, and the glycosaminoglycan disorders as well. These are all connective tissue disorders, and the connective tissue is not just collagen, as I said, it’s got lots of different cellular components. Specifically, the fibroblasts, which make the collagen, but there’s the adipocytes, the chondrocytes, the osteocytes, the mast cells – which are abundant in connective tissue – macrophages, leukocytes, and erythrocytes.
These cells sort of show you that the connective tissue is not just a mechanical and structural support, which is what everyone thinks it is. And obviously, it’s a very important role – it’s how we move, it’s what helps our mobility, for sure. But there’s so many different cells in it, and there’s also the extracellular matrix, which has a lot of other components. It’s dynamic – it’s got physiology, it’s got exchange of fluids, exchange of waste products. It actually has immune response. Antigen presentation takes place within the connective tissue because there are macrophages, there are T-cells, there are B-cells. So, it’s a very important tissue, and it’s everywhere, right? It’s not just our ligaments and our tendons, right? It’s everywhere. I mean, most pieces of us are some form of connective tissue, and there’s different types, of course, but it still is connective tissue and has a very dynamic, robust, critical role to our body’s pathophysiology.
And I will say that anatomically wise, the ratios of where our tissues are and our organs are really genetically predetermined. And if our connective tissue is failing to the extent where those things aren’t in the place they should be, even if it’s off by a millimeter, the cellular signaling and the communication among cells and tissues and organs just don’t work nearly as well. And that doesn’t necessarily mean that there’s a clear disease or profound pathology, but it just means that things just aren’t good, and that sets up, I think, patients for risks, especially with exposures to everything.
I mean, I can go on about how our environment is just getting dirtier and dirtier. My PHD is in environmental toxicology, and I did a water sampling study, and I can assure you that I would never drink the tap water. But the amount of infections that we’re exposed to – just take the recent COVID pandemic – but also all of the different environmental contaminants and toxicants in the air. So, I think that these connective tissue compromises our immune system’s ability to be resilient and to be protective as it should be. So, just recognize that even in our nervous system – the meninges, the glial cells, the vessel walls – they all contain a level of connective tissue.
So, the human body has four major types of tissues: muscle, epithelial, neural, and connective. The connective is most abundant, diffusely present. I sort of said most of this already. It’s just important to remember the human body is a cohesive network of tissues, and I think that’s somewhat lost. I think we sort of talk about silo in medicine, but I think we see the body as siloed pieces as pieces of anatomy, but it really is all interconnected, including the systems. And the most abundant fiber is the collagen protein, and a lot of patients often ask me, should I take those collagen supplements – will it help? I don’t know.
So, in CSF leak patients specifically, actually, Dr. Schievink did a great study showing that connective tissue disorders are common among patients with spontaneous CSF leaks. But the manifestations may be subtle, which is sometimes why it’s hard to decide on an individual patient whether this is truly a CSF leak and whether you want to proceed with what invasive imaging might be necessary, or you start with non-invasive and then proceed to what you might need to order in order to really see if you can identify the leak.
But also, just in terms of even identifying the leak, it can be really difficult. And again, I think it’s because the anatomy is not as rigid and as strict as it should be.
So, with connective tissue disorders, there’s a ton of spinal manifestations of the spine, and this is just from a slide that I’d given at a different conference. But I just think it’s interesting that, you know, I have 20-year-olds with spines that look like 70-year-olds, and they have connective tissue disorders. And I too call them hypermobile EDS just because we all know what we’re talking about when we say that kind of verbiage. But I see a lot of – obviously, in the Chiari EDS Center, we see a lot of Chiari, a lot of atlantoaxial instability, cranio-cervical instability. Cranio-cervical instability can result in what’s called cervicomedullary syndrome, which is the compression of the lower end of the brain stem which is not unique to CCI.
If you had any kind of mass sitting there, you would still have cervical medullary syndrome, but there is then direct involvement in the arteries and vessels and even the CSF compartments, and even the lower cranial nerves that are part of that neuroanatomy. You could see basilar invagination, which can also cause cervical medullary syndrome.
I see a lot of segmental instability and kyphosis – and that was sort of shown even in connective tissue disorders in two great papers – and this often causes myelopathy. In fact, a lot of my patients with CCI or AAI or other kinds of spinal manifestations present with myelopathic symptoms, tethered cord syndrome, and Tarlov cyst syndrome as well. I regularly see these diagnoses in these connective tissue patients.
Cranio-cervical instability is probably the third on the list that I get asked about. So, the ligaments are the major occiput-C1 stabilizing structures, and it is the most mobile portion of our spine, right? So, everything we do uses that particular joint. And don’t forget, the spine is just a series of joints. So, while I said yesterday, I’m not a big fan of the Beighton score because it just looks at these random peripheral joints because I see so much spinal manifestation, and that is not taken into account with the Beighton score. And I think that it should be. I don’t know how it could be, but I think it should be. Obviously, it would require imaging, but the C0-C1 is the most mobile portion: I mean, everything we do – me talking to you right now. CCJ contains a lot of very critical cervical medullary anatomy, as I already mentioned, and so it could really ultimately result in a lot of different kinds of symptoms, frankly. You know, when you think about the nuclei of the brain stem, for example, those can be compromised. When you think about the arteries and vessels – I’m going to talk about how we very commonly see internal jugular vein compression with CCI, which affects the outflow of blood from the brain – that has its own set of symptoms. You know, there’s a lot of different manifestations of this particular part of the anatomy, and when it’s compromised, a lot of things can go wrong and ultimately can lead to things like elevated intracranial pressure, which is thought to be one of the risk factors for developing a CSF leak.
So, Milhorat showed in 2007 that when he took patients with Chiari and EDS and compared them to just those patients with Chiari, he found that they actually had different morphometrics. So, there are certain morphometrics that we do and certain angles that we measure when we’re trying to diagnose CCI, and I listed them here: the clivus-axial angle, the atlas-axis angle, the clivus-atlas angle, the BDI, and the BAI. And so, there were different measurements in the patients with EDS and Chiari than those without EDS and Chiari, and so I found that to be very interesting.
We see a lot of EDS patients in the Chiari EDS Center, and when we do ICT – which is invasive cervical traction – we very regularly see these morphometrics change, and we see improvement in symptoms. And so, it’s just an interesting, I think, piece of information when we’re trying to think what really is CCI, and does it really exist, and how are we going to fix it. I think it’s important to recognize that there’s some literature – not a lot of literature – but some literature that really does support that this is a real diagnosis, and it could have greater effects on the EDS population than on the non-EDS population.
So, the jugular venous compression, as I said, which can lead to a variety of symptoms just from the impairment of blood outflow – again, most commonly is the elevated intracranial pressure. The symptoms usually are headaches, pulsatile tinnitus, dizziness, cognitive fatigue, a “brain fog” kind of description that patients will say, which is often a patient experience. So, I will ask them what that means to them. You can get very different kinds of descriptions to what brain fog is. Patients will very often have visual disturbances. People love to tell me about how they need new glasses, but it’s really that they get double vision. They don’t recognize that the vision – it’s not just blurriness, right? They have double vision, sometimes triple vision. They get a like a dimming of their visual fields, so they sometimes feel like they’re losing their vision, but then it’ll resolve.
So, I think it’s important to recognize that there could be visual disturbances with jugular venous compression. And in some cases, the autonomic nervous system is involved, and they get syncope, they have dyspnea, they have nausea with some vomiting, they have palpitations. Sometimes they feel like their heart is just sort of jumping out of their chest, and these symptoms will often overlap, because we also – coexisting with a CCI – we also see Eagle syndrome, which of course is the elongated styloid. All these things can compress the jugular vein. They can wrap up the glossopharyngeal nerve, causing crazy pain of the face, of the neck, intra-orally. Some patients have severe pain in the back of the oropharynx or in the upper part of their mouth.
And so, it could be a challenge to diagnose specifically what the diagnosis is that leads to the particular symptom that’s so troubling to the patient. But it’s important, right? Because how else are we going to help them if we don’t know exactly what it’s doing? So, we need the appropriate diagnosis so that we can better help them. But these things are also seen with spontaneous intracranial hypotension.
So, post-viral syndromes. I think that in the long COVID years now, I think that the post-viral kind of effect is really taking more of a mainstream acknowledgment, and I’m sort of happy about that. Because frankly, early on when I started doing this work, I saw a lot of patients with a diagnosis of ME/CFS. They had this chronic fatigue, they couldn’t get out of bed, they couldn’t be upright. Any minimal physical exertion sort of created this level of what they would describe as like unwellness and malaise, and they would call it a crash, and they couldn’t get better, and I couldn’t figure out what was going on. And their history was just wrought with like lots of infections, travel where they had some severe GI illness that took them weeks to recover. And you do a workup, and they have evidence of having been exposed to all the ubiquitous viruses, so at first, you don’t make anything of it. But then they also had other kinds of markers of immune dysregulation on their labs, and I started to realize that their system was just so overwhelmed with so many different exposures that their immune system just sort of couldn’t help, couldn’t protect them any longer. And they developed MCAS, ultimately, which I didn’t realize, but now I see it. And that results in this downstream effect of just complete, as I said, an inflammatory cascade, connective tissue degradation, further immune dysregulation, autonomic dysregulation. And then it all comes together, and it’s just this horrible syndrome for patients who no longer really have quality of life. And they would tell me about how they used to be, and it impacts their work life, their family life, their social life, their active life. Most of them were very active, and now they can’t be. And it really just breaks my heart because these people were productive members of our society, and now they are not, and that hurts them more than anything else. They don’t want to be on disability. They are embarrassed to ask me to sign the forms because they wanted to be part of this world. They wanted to be global citizens. They wanted to raise their families and raise their children into productive members of society.
So, I think that it’s really important. I loved the talk – I think it was Dr. Kranz who talked about “We don’t know what we don’t know.” And so, I think the idea of being receptive to like, “Okay, well, what’s going on here?” And maybe we can help figure it out together. Maybe we can all have more regular meetings and dialogues. It’s always my dream, and I was talking to my neurology colleagues here that like, I would love to just have regular meetings where we just bat around ideas about what’s going on with these patients based on different labs that come back and imaging that comes back. I loved the talk on the negative imaging because I get that all the time. And so, I don’t know, I find that we just need more dialogue.
So, the long COVID, the ME/CFS – I see a lot of post-viral – now I get referrals for a lot of different – I’m not an infectious disease doctor. I’m often looking up what’s that organism, and what does that organism do? And then I started to learn about Lyme disease and all these vector-borne diseases. I had to ask people about those and other post-exposure illnesses.
As I said, I don’t think it’s only infectious. I think – I know, not I think, I know – our environment is dirty. I always have to say our environment is trying to kill us. There’s so much out there that we breathe in, that we drink, that we eat, that we touch. I think that we have to recognize that we have to somehow find ways of, one, correcting the problem that the exposures caused, but then figuring out how we’re going to support our immune system so it becomes more resilient and more protective because we’re losing the war in some respects. But I do think that for some of us, the answers are in the genome. I do a lot of genetic testing of these patients, and I’m finding variants that really set them up for being more sensitive to a problem when there’s an exposure that either triggers that variant to be overexpressed or to be expressed at all. I think some of these variants would have just remained dormant and never posed a problem for this patient, but now there’s evidence of its expression because oftentimes, you can test for the enzyme activity or test for the protein level – not always, but sometimes – and you find, “Oh wow, there really is dysfunction of this gene because of this variant.” So, you can make those connections, but this takes a lot of time. This takes a lot of research because we’re out there on the limb doing this stuff.
I’m just trying to theorize why I’m doing this, but I would love research and data to support what I do. I’m vested in trying to help these patients get better, and as long as I know that I’m not doing any harm, I think patients just appreciate that you’re on this journey with them. You’re looking for ways of answering the question – like why, why this, why that, why now, why, you know? I have a lot of veterans from 9/11, first responders from 9/11, and then more recent veterans from the burn pits that I had to learn all about.
Again, I think that we have to recognize that our immune system is dysregulated. I get often asked, “Does this mean that everyone’s developing an autoimmune disease?” And I don’t really think so. I refer to it as the body’s being in an autoreactive state. One of my colleagues at UCSD, who’s a mitochondrial expert – I focus a lot on mitochondria, do a lot of mitochondrial medicine – we think it’s cellular damage. So, this inflammatory cascade is basically damaging these cells. These cells, then as they’re damaged, sort of release fragments, cellular debris, and the immune system sees that floating around and recognizes that, and says, “What’s that? That shouldn’t be here,” so it makes an autoantibody. But it doesn’t stay, and those patients, as far as I know – I follow patients now for almost 10 years – they don’t seem to develop that autoimmune disease that the antibody might be associated with. So, I don’t think it’s necessarily about an autoimmune disease. I just think our body is in this autoreactive state because it’s so inflamed. That sounds so vague, and I don’t think it answers any particular question, but it’s the best way that I can describe it.
I think it’s important to recognize that the dura mater is densely packed with a lot of immune cells and activity, and we know that the brain and the cord have their own unique immune system. The blood-brain barrier, as I said in the previous slide, is disrupted because of all of this. I think that this is something that is not very commonly focused on, but in my opinion, it should be.
We know the risks of poor healing. If we don’t recognize this and we don’t treat the leak, obviously, these patients are at great risk of developing life-threatening CNS infections, which I’ve seen a couple of times when I was at the hospitals. But I’m in private practice now in Seattle, and I’m just the medical director at the Chiari EDS Center in New York, so I don’t see that as often, but I had seen it in the past in my career. So, I’m very vested in making sure that these patients who have leaks – they are found, they are identified, they are treated, and they are followed. As we’ve learned, oftentimes patients will relapse. It might be six months, a year, five years. I think there was one case where it was 12 years later. I think it’s just important that we recognize that we’re caring for these patients – and yeah, that’s all I have to say.