Treating MCAS, POTS, and Long COVID can be difficult, and physicians must attack from various angles to get patients feeling better. Dr. Maxwell walks us through his thinking and how MCAS is linked to POTS and Long COVID. This episode is a must-listen for patients and practitioners alike.

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[00:00:00] Jill Brook: Hello, mast cell patients and lovely people who care about mast cell patients. I’m Jill Brook, and this is our fifth episode of Mast Cell Matters, where we go deep on all things related to mast cell activation syndrome or MCAS. We have a fabulous episode for you today where the brilliant Dr. Tania Dempsey will lead a conversation with our also brilliant guest. You’ll recall that Dr. Dempsey herself is a leading MCAS physician and researcher in New York State, educated at Cornell and Johns Hopkins. She specializes in complex chronic disorders and immune dysregulation, and she is so generous to donate her time today to help us educate people about mast cell dysfunction. Dr. Dempsey, thank you for hosting today, and who’s our guest?

[00:00:46] Dr. Tania Dempsey: Oh, I’m so thrilled to be interviewing my friend and colleague, Dr. Andrew Maxwell. Dr. Maxwell is a board certified pediatric cardiologist and pediatrician. He received his medical degree from Johns Hopkins Medical School, the same medical school I went to and a residency in pediatrics at the University of California at San Francisco, followed by clinical and research fellowships in pediatric cardiology at Lucille Salter Packard in Stanford Hospitals and Children’s Hospital of Philadelphia. His research interests include study of endothelial control of vasomotor tone, nitric oxide, sports, cardiology, dysautonomia, hypermobility syndromes, and mast cell activation syndrome, and their relationships to the environmental toxins. He’s won awards and has done research, and he’s published many articles and book chapters on these subjects. Welcome Dr. Maxwell.

[00:01:42] Dr. Andrew Maxwell: Well, thank you very much both Tania and Jill. Thank you very much for having me.

[00:01:47] Jill Brook: We are so excited to have you. Oh my gosh. I can barely contain myself.

[00:01:50] Dr. Tania Dempsey: Yeah, this is great. Let’s dive right in and let’s start with talking about mast cells and MCAS and how they’re relevant to cardiology.

[00:02:02] Dr. Andrew Maxwell: Right. Yeah. Well I think mast cells are relevant to cardiology in a huge way. And I feel like in the pediatric cardiology world, I’m sort of alone in that and that my colleagues don’t necessarily understand what I’m seeing or doing. And I think it’s very relevant, particularly these days in the age of COVID where we’re seeing more POTS, Kounis syndrome, myocarditis and even inappropriate sinus tachycardia, which I see a lot of, which is probably a localized version of myocarditis. So I think they’re more relevant today than they have ever been. But it was a problem even before COVID. Mast cells affecting the human organism causing dysautonomia and POTS. And in my opinion or view, that Ehlers-Danlos that’s very commonly associated with the, these other two entities.

[00:02:59] Dr. Tania Dempsey: Great.

[00:03:00] Dr. Andrew Maxwell: I can go on, I can

[00:03:01] Dr. Tania Dempsey: Yeah. Actually let’s, yeah, let’s, let’s build on that a little bit. Yeah. Talk about a little bit about the hypermobility.

[00:03:08] Dr. Andrew Maxwell: Yeah. Well, okay. So I mean, I think the big picture is some environmental exposure. And now that extra environmental exposure is quite often either COVID virus or the vaccine. And so that exposure, either it’s the very likely the spike protein from the virus, because that’s why we see it being mimicked with the vaccine. The only common denominator is the spike protein really is doing something caustic in, in the body. Now, maybe some of that is direct inflammation that doesn’t require mast cells, but I think a lot of it requires mast cells to mediate that inflammation. The spike protein, maybe some other component of the virus, is Activating mast cells. And mast cells are doing a lot of the things that we are seeing in these patients causing post COVID long haul syndrome leading to POTS with or without the post COVID long haul. I mean, it could be very specifically POTS, it could be very specifically Kounis syndrome. It could be very specifically myocarditis, could be very specifically inappropriate sinus tachycardia. But I believe mast cells are very frequently the underlying mediator of that inflammation. Now, it could be where it’s partly a mediator and something more direct or some other thing as being a mediator as well. But I see time and time again a pretty good response to full mast cell suppression. So that, that again informs us that very commonly it’s mast cells doing the mediation.

[00:04:45] Dr. Tania Dempsey: Yeah. Yeah. Well I absolutely agree with that. That’s what I see in my practice as well. And you mentioned Kounis Syndrome a few times, so maybe you can tell us a little bit about what that is and how it manifests, what people need to know about it.

[00:05:00] Dr. Andrew Maxwell: Well, I mean, Kounis syndrome is basically an allergic spasm of the coronary arteries. And so when you have a spasm of the coronary arteries, you have essentially all the signs and symptoms of the angina that might lead one to believe they’re having problems with coronary perfusion. And you are. But it is reversible with, with mast cell medications. So the Kounis syndrome can be suppressed with mast cell medications. And I see it very frequently, and I’m not sure If my colleagues are recognizing the chest pain that occurs in some patients that is reversible with mast cell medications. I think it’s more common than we have ever realized. And again, that was prior to COVID. And now with COVID being present, we even see it more frequently.

[00:05:50] Dr. Tania Dempsey: Are you seeing it in children, in in your pediatric population?

[00:05:54] Dr. Andrew Maxwell: Yes, I saw Kounis syndrome pre COVID and now I’m seeing it even more commonly post COVID. Now that’s not the most problematic issues I’m seeing in my practice with COVID. I’m seeing definitely seeing a lot of dysautonomia and POTS. I see a lot of inappropriate sinus tachycardia. And so there’s those issues that are even more frequent than Kounis syndrome.

[00:06:18] Dr. Tania Dempsey: So, what is your approach to these patients who have these various symptoms? And some of them you believe are rooted in, in mast cell activation, so how do you go about working them up and then treating them?

[00:06:31] Dr. Andrew Maxwell: Well a lot of it is definitely the clinical picture, the history taking, and you know, looking for evidence that maybe this was all started with a viral infection. And I don’t always, you know, demand that a COVID history be documented since so many times PCR and antigen testing has been negative. There’s been times in my practice where the whole family was sick and proven to have COVID, but that particular patient was negative on testing and maybe even negative with symptoms at the time. But then within a week or so of the entire family being sick, developed a long haul picture or a began to show signs of dysautonomia and POTS. And so there’s pretty high suspicion that they actually were infected even though they were negative. So that happens. And so looking for that history, then looking for the breadth of all their signs and symptoms. Looking for telltale signs that mast cells are also activated. And that’s sometimes hard to do in the midst of a dysautonomia picture. A lot of the symptoms overlap. What I kind of look, try to look for is the food sensitivities, the GI distresses that are a little bit different with mast cell activation. And then the one particular feature, what I call rushes of flushes, which is sure there’s tachycardia and palpitations, burst of racing heart palpitations, but you can find that in both the straightforward dysautonomia and mast cell activation. So how do you tell the difference between the two? You get the flushing and the rashiness with rushes of flushes. And that’s kind of how I say, okay, this is definitely a mast cell phenomenon going on. And then once I’m convinced of that, you know, laboratory evidence has not been to me a big important feature. Yes, I’ll go ahead and get some mast cell laboratories if it’s feasible. Meaning sometimes there’s patients come in with insurances that are just not going to cover it. So it’s not a necessarily a good way to spend their funds. And when I hear the clinical picture, I’m always going to manage it clinically no matter what the lab results show. So then the big question is, what’s the bigger issue presently? Are they coming in with really bad POTS symptoms that might need some bandaid therapy that’s directed toward POTS as a the very first thing to do, even though it’s not the thing that’s going to help fix them long term, but they really need help with say you know, orthostatic symptoms or really bad racing heart. So we might start with that type of therapy including fludrocortisone, midodrine, corlanor, beta blockers, pyridostigmine, that type of medication directed toward dysautonomia slash POTS. But either after that or very commonly before that, I do what I call my bicycle tire management strategy of mast cell suppression. And what I mean

[00:09:42] Dr. Tania Dempsey: brought that up. Great. Tell us about that.

[00:09:44] Dr. Andrew Maxwell: What I mean by the bicycle tire management strategy is you gotta consider mast cell activation like a bicycle tire with about seven holes in it. And those holes are you know, excessive histamine consumption in the diet. The GI tract as being a source of additional mast cell activation, so having the GI tract in order, and then mast cell action itself, both systemically and within the GI tract. And then those particular receptors of histamine, H1 and H2. So therapy would be an H1 blocker, an H2 blocker, mast cell suppression systemically with usually a lukast. Zafirlukast is what I prefer. I usually avoid montelukast and with a cryomolyn substance in the gut. So Gastrocrom here in the US. Finally, quercetin is a natural version of the systemic mast cell stabilizer. So I usually have patients on quercetin. I consider it kind of a freebie that not really being exposed to a med is very safe, so why not? And then making sure the GI motility is working well, making sure that there’s no evidence of what we call SIBO, small intestinal bacterial overgrowth, doesn’t necessarily mean I work them up for that in any way. I just mean I put ’em on probiotics. Make sure if they have any evidence of slow gi motility, put ’em on a burra, gass or ginger root extract. Rarely have to go something more extensive medication-wise with that. And then of course, put them on a low histamine diet, make sure they’re not adding histamine to their system. That’s usually the, the, in my view, patching all seven holes of that bicycle tire. And when you have all seven holes patched, You can expect a change.

[00:11:45] Jill Brook: Yeah, you mentioned that you don’t like montelukast as well as some of the other lukasts, so all of us on Montelukast are now wondering what’s wrong with montelukast.

[00:11:54] Dr. Andrew Maxwell: Okay. Well, there’s a bit of controversy in our little study group. What I see at least one out of every three patients, I put it on becomes significantly depressed on it. And I’m sure that that’s partly population based. That this particular population has a leaky blood brain barrier. The same way they have a leaky gut. And again, it goes back to my theory that an environmental exposure activates mast cells. Mast cells not only secrete histamine, but they secrete elastases and elastases breakdown the little proteins that hold things together, what are called cadherins and maybe other proteins too. But I really focus on the cadherins. Cadherins hold together, the gi epithelium, that’s the E-cadherin. So that’s where your leaky gut comes from and it holds together what are called VE-cadherins hold together, the capillaries, the endothelium within capillaries. And so if they break down, you get increased leaky capillary in general, but blood-brain barrier. And we see that with not only montelukast, we see it with a lot of the dopamine agonist antagonists like Reglan where patients will much more commonly have extra pyraminal effects being put on reglan and other types of dopamine modifying agents. So I think that’s the source of it. Now, it can’t just be population because again, my colleagues see a lot of these same patients, the same population. So maybe there’s an age issue here where maybe it’s more common in the pediatric age range. So I think combination of age and this particular disorder, because certainly Singulair is used very, very commonly for patients with allergies. And yes, now it has a black box warning because of the depression issue, but it took a long time to get that black box warning. So it must be much less common in the general population.

[00:13:56] Dr. Tania Dempsey: I really appreciate your take on that, Dr. Maxwell. And I’ll I’ll just add my 2 cents. I’ve certainly seen those side effects but I also have patients who have done quite well. And one of the tricks that I’ve learned along the way, not just for Singulair (montelukast) but for many other drugs, is that compounding it can make a difference in a subset of these patients. The Singulair brand, the the generic formulations have various excipients and dye. And I don’t know why that drug over, you know, some of the other drugs have more of that depression side effect. But I have a subset of patients when compounded they don’t have the same level of side effects as the commercially available. So there’s a small subset of that. And then I do think there’s a lot of individual variation. And so I sometimes have to, you know, try different drugs in this class to see, you know, which one works well. But maybe it is an age thing. So I don’t see kids as young as you do. And maybe that’s why I don’t see the same level of, of symptoms.

[00:15:00] Dr. Andrew Maxwell: All right.

[00:15:01] Jill Brook: I have one more question about your bicycle tire. You had mentioned quercetin as being one factor, and do you find that Quercetin works better than luteolin or do you ever combine the Quercetin in luteolin or use the Neuro Protect, or is there any one best of the flavonoid category in your experience?

[00:15:21] Dr. Andrew Maxwell: Yeah, I have no experience in comparing the, the different ways to do that. It would be great if someone has done that and, you know, could enlighten us to that.

[00:15:33] Dr. Tania Dempsey: Okay. So let’s talk a little bit, if you don’t mind about the septad. In our study group, our mast cell group, we talk a lot about associated conditions. You’ve mentioned some already but we’ve sort of put this term out, the septad. And I gave a presentation recently and I turned it into the decad had, because it just seemed like, you know, really maybe septad was even eliminating some of the other conditions. But I’d love to, to hear your take on it and talk a little bit about how those connections, you know, work and what are you seeing in, in your patient population?

[00:16:08] Dr. Andrew Maxwell: Sure. Well, I mean, it began with a triad. The recognition of the Association of dysautonomia, mast cell activation syndrome and hypermobile, Ehlers-Danlos. And, you know, the pentad came along basically as a way to recognize that GI is usually a very big issue in these patients. So GI dysmotility. So That isn’t a entity by itself, that’s really just a consequence of the other three things. And the same with the fifth portion of the pentad being, you know some sort of autoimmunity. And that autoimmunity may be the first thing and kicking everything off. Or it may be a eventual consequence of say, having leaky gut for a long time, where the gut becomes sort of an auto-antibody generator over time. And so those five entities were common enough together that, you know, whenever a patient arrived with all this, it kind of meant five different doctors were, were required to take care of these. So that was the whole idea of the pentad is, Hey, let’s set up your five different doctors that you’re gonna need, you’re gonna need someone who’s really good at dysautonomias, that’s either a cardiologist or a neurologist. You’re going to need your GI doc. You’re gonna need someone who manages the immunologic aspect of it. And someone who’s really good with Ehlers-Danlos. Now, you know, a lot of us can never find those five people, and a lot of us providers end up being those five people. But that’s the idea behind the pentad is kind of like, you know, you need the big five specialists. And then the recognition that a lot of the underlying causes were Infectious in nature. And so there was number six. And then I believe that the seventh of the pentad is sort of an ME/CFS picture. So potentially a lot of us believe that’s a mitochondrial dysfunction. So, you know, two more aspects to these. Not all patients, but many of the patients. Is this okay, is an underlying Lyme, babesiosis, bartonella. Et cetera. And is there also a chronic fatigue syndrome component to that? And just for anyone who might wonder, how does chronic fatigue syndrome differ from everything else we’re seeing? And there’s a whole criteria of course, for meeting chronic fatigue syndrome, but I think the big differentiating aspect is how do you respond to exercise and POTS patients and most dysautonomia patients have a improvement as you go through an exercise program. While chronic fatigue syndrome patients every time you try to exercise it just sets the patient back. And so it’s a much bigger struggle with that. And again, it’s probably mitochondrial based that’s explaining that.

[00:19:13] Dr. Tania Dempsey: Right. Yeah. That was

[00:19:15] Dr. Andrew Maxwell: to add Tania with that

[00:19:17] Dr. Tania Dempsey: That was a great explanation. And I think the other things that I think about, and the reason I turned that pentad to the septad to the decad was that I just added some other things that I think are just really, you know, sort of along the same lines of the things we talked about, but maybe just expand on it. So I included uh, small fiber neuropathy on my PowerPoint slide for this presentation. Because that seems to be something that we see, you know, fairly often now in some of the dysautonomia patients, maybe infectious patients and MCAS patients. I have cervical instability. Possibly tethered cord as connected to the connective tissue issues, but maybe also on its own related to MCAS, infection and all these other things. And this is where I think this podcast would be great if there was video, and I can show my slide, but, but in any case, I put autoimmune encephalopathy, PANS, PANDAS, cognitive dysfunction sort of as a class together, you know, just because that’s brain fog is not an uncommon symptom. But many of them have evidence of the sort of encephalopathic kind of stuff, neuropsychiatric stuff that, that really affects them dramatically. And then I put endocrine disorders because many of these patients do have, and again, it’s sort of chicken or the egg right? What’s driving what, but many have adrenal, thyroid and also sex hormone issues for sure. Women. We see a lot of menstrual issues you know pelvic floor issues, pelvic pain issues. So it’s actually not purely endocrine, but I put that all in, sort of that category. So it’s a lot to think about.

[00:20:56] Dr. Andrew Maxwell: Yeah. Well, I think, you know, this kind of reminds me of back in biology 101 when we were learning taxonomy of organisms and, you know, you had the, what were called the lumpers and the splitters. And so the lumpers were those who had smaller numbers of categories and lumped a lot of things in within small categories. And then the splitters say, well, I think these should be pulled out. And so, you know, went on and on about how to categorize organisms. And, I guess at some point they split the difference and and made everybody happy. But that’s kind of what’s happening here is, a lot of the things you mentioned, I would say are sub syndromes that are consequences of the big three. And so for instance, CCI cranial cervical instability really happens in a patient that may not be full on Ehlers-Danlos may not be full on hypermobile EDS, but may have what I call a localized version of EDS. And again, going back to this paradigm of environmental exposure, if that environmental exposure happens to be something that’s aerosolized and breathed in, and what happens is you have a localized nasal pharyngeal mast cell activation that then causes havoc in the nasal pharyngeal region, specifically CCI, TMJ issues, and then loss of airway. So the airway becomes floppy for different reasons. And so you see these particular patients and they’re kind of a setup for this phenomenon. I see and call spiky leaky syndrome. And so, Just getting back to this concept of CCI sort of being a sub syndrome as a consequence of Ehlers-Danlos and mast cell activation syndrome combined. And that’s the same way with the GI motility as kinda like, well that’s just a combination of the three big issues combined. And, you know, you mentioned PANS. Well, you know, PANS is kind of a form of autoimmunity. So that kind of is a sub syndrome under the immunology. So that’s again, just my way of looking at it. But certainly everybody else’s way of looking at it is just as valid.

[00:23:17] Dr. Tania Dempsey: No, it, yeah. maybe I’m a splitter. And you’re a lumper. Yes,

[00:23:21] Jill Brook: a question for both of you on this then. So of course what’s amazing about the mast cell stuff is how it seems like the same mast cell phenomenon can happen in so many different parts of the body and cause so many different symptoms. But I’m curious to hear if you are seeing symptoms in the heart, for example, versus in the endocrine system. Do you still go to that bicycle tire and treat those first or do you try to treat the specific symptom first or go to the general MCAS work first?

[00:23:53] Dr. Andrew Maxwell: No, I mean,

[00:23:54] Jill Brook: or reason.

[00:23:55] Dr. Andrew Maxwell: If I believe it’s mast cell mediated, no matter whether it is these CRPS type phenomenons that we see, Kounis syndrome, inappropriate sinus tachycardia i, I will go to my very same mast cell suppression routine. And then the only question is, is do they need more than that? You know? And so, you know, another strategy I have are IV infusions of mast cell meds, you know, getting saline along with Benadryl, Toradol, Ativan, and famotidine and IV form, and oftentimes on ondansetron as well. And so that often works much more effectively than the oral forms. Not always, but whenever the oral form is failing, that’s a strategy. The other is to just add on more LDN. And, you know, there’s a whole list of other mast meds we didn’t mention that, that are possibilities to add onto that. And as far as do I do it first versus second, it kind of depends on are there bandaid therapies that need immediate attention? And I already mentioned if they’re really, really POTSie then I might start with the POTS stuff. If you know, if they come in with, you know, angina type symptoms and you’re thinking the mast cell meds aren’t gonna work fast enough for that, you might try some antianginal type strategy, something like a nitric oxide releaser to open up their coronaries as quick as possible. And I think that list could be applied to, to almost anything where you need to jump with band-aid therapy to affect a change immediately.

[00:25:33] Dr. Tania Dempsey: Yeah. No, it’s complicated. Of course. Jill, did you have another question?

[00:25:38] Jill Brook: Well, I was just wondering if that’s your approach too, to start with sort of the central mast cell stuff.

[00:25:43] Dr. Tania Dempsey: Yeah, I think that we definitely have the same approach. You put out fires if there are things that are at the top layer that, you know, they’re really symptomatic from, but the MCAS part of it is really has to be at the same time, or, or sometimes first, again, similar to Dr. Maxwell, we’re trying to figure out, you know, what’s gonna stabilize the patient the best. But MCAS targeted therapy by far has been, you know, really a game changer for so many of these patients. It may not be the whole thing, right, as we talking about all these other conditions they have, but to get them to a place where they’re stable, not flaring, symptoms are better controlled is huge. So, yeah, I think we have the same approach.

[00:26:26] Dr. Andrew Maxwell: Yeah. So I think one of the things that we want to talk about today was how does POTS develop out of, you know, having had COVID or the COVID vaccine? I mean, what is the connection there? Right? And we’ll eventually talk about this paper that came out back last October. That there is clearly an association between either having COVID or the vaccine and developing dysautonomia in POTS and what, you know, what would be the mechanism behind that. And if you go back to this paradigm of environmental exposure leading to mast cell activation, what are the mast cells doing to create a POTS like situation? So, you know, I always like to kind of talk about exactly what is the pathophysiology of POTS itself. And this is also a good time to have slides and be able to show things. But, you know, POTS, I think the basis of POTS is this sagging away of the blood volume that’s returning to the heart. And so it causes orthostatic changes in how the heart fills. So when you go a sitting or standing position and the blood volume sags away from the heart, it’s not there ready to fill the heart when the heart opens up to ask for more blood. So it pumps empty. And in an attempt to keep cardiac output going, the body responds by increasing heart rate. And so that’s where you get your big rise in heart rate as the blood sags away. And so why is it sagging away? Well, you know, there’s basically two phenomenon going on that make blood sag away in a POTS situation. One is the function of the autonomic nervous system, which should control venal constriction and heart rate. And things that change the vascular physiology to keep that blood volume right there ready to fill the heart. But the other part is the structural integrity of the venous system itself. How compliant is your venous system? Is it like a saggy balloon or is it like a nice solid glass column where blood is filling that column and being up next to the heart? And so one of the phenomenon I believe happens is, you know, the spike protein or whatnot activates mast cells. Mast cells break down the connective tissue, the integrity of the venous vessels turning them from this glass column into a saggy balloon, so it sags away. So that’s, that’s the mechanical portion. But then of course, mast cells also can cause dysfunctional autonomic nervous system directly or in a different route, let’s just say. And that can be a couple different ways. One is that mast cells activated in the gut can then cause inflammation of the sensory portion of the Vagus nerve. It’s the information heading back to the brain. And so if it’s irritating and inflaming the sensory portion of the Vagus nerve, it’s as I consider it like almost like a CPU u you know, computer system with information going into the cpu, if it’s garbage in, it’s gonna be garbage back out. And so, it affects how the motor portion of the Vagus nerve works. And so you have a dysautonomia of the motor portion of the Vagus nerve that results from a inflammation of the sensory portion of the Vagus. That’s one way. And then the other way is going back to this idea of cranial cervical instability. If you have a tenderization of the ligaments right there where C1 is, you have C1 becoming a little jiggly and unstable. And I think it’s important to kind of differentiate the, the types of cranial cervical instability. In my view, there’s a type that I liken to carpal tunnel syndrome. And this is what I consider carpal tunnel syndrome of the neck. And the importance of that distinction is that this isn’t necessarily a cranial cervical instability that’s easily detected by radiology or different ways. This is almost entirely a clinical diagnosis of cranial cervical instability the same way carpal tunnel syndrome is oftentimes a, a clinical diagnosis, and it’s also a management strategy is kind of the same. You don’t go into carpal tunnel syndrome and do major surgical intervention, often physical therapy and correction of, you know, ergonomics and things like that will correct the carpal tunnel syndrome of the wrist. And I think that’s what’s going on at the level of the neck. Carpal cci. It doesn’t necessarily need major surgical intervention and sometimes not even prolotherapy, but correcting the inflammation, the mast cell activation that’s, that’s tenderizing that area. And then physical therapy that can restrengthen it. So now that we kind of talked about that, that it’s kind of subtle and it’s a kind of a carpal tunnel syndrome of the neck, say, okay, how is that hurting the autonomic nervous system? Well, the cervical vertebrae, number one, the atlas, slides forward just a little bit in this case, and there’s lateral processes on that that basically grab the the three major cranial nerves that are exiting right at that spot. That’s cranial nerves nine, 10, and 11. And it can injure that, it can basically compress them against the jugular vein, which is compressed against the stylo hyoid ligament. And chronically doing so can injure those three nerves. And cranial nerve number 10 is your Vagus nerve. And so there’s your dysfunction of the parasympathetic nervous system by way of a little bit of CCI. And you know this because you’re also seeing cranial nerve nine and cranial nerve 11 dysfunction at the same time. So when you hear a patient talking about tinnitus and phonophobia and hyperacusis and vertigo and what’s called globus feeling of a mast in the back of the throat and maybe even what’s called eagle syndrome type symptoms with turning the head and having pain upon turning your head. From side to side, sharp stabbing pains in the neck or pain at the base of the tongue. Those are all glossopharyngeal nerve findings. And then the cranial nerve 11 is a motor nerve to the trapezius and it innervates the trapezius. So when it’s injured, oftentimes will cause a knottiness something beyond coat hanger pain in the trapezius, but rather a knottiness in the trapezius. So when you hear these patients complaining of all these symptoms, that it sounds almost crazy that they’re related. No, there’s one place in the body where these three nerves are together and they happen to run right in front of the lateral process of c1. So when that slips forward and chronically does so, I think it causes this, this list of symptoms together. And so couple different ways. There’s the parasympathetic nervous system that becomes dysfunctional by mast cells being the cause of that. And then the increased elasticity of the veins together that creates a POTS like situation. And I think that’s what we’re seeing here with with COVID, post COVID post vaccine.

[00:34:27] Dr. Tania Dempsey: Yeah, that’s a wonderful explanation. I was actually taking notes cuz I love how you explain it. Of course I understand it, but it is just a clever way of putting it together. It makes so much sense. So then yeah. What is your approach to these patients then? Where do you start? If you think they have CCI you think they have vagal nerve involvement. So where, where do you start?

[00:34:47] Dr. Andrew Maxwell: Yeah. Well, I mean if I identify what looks like this form of CCI that I will get the physical therapist involved. And I’ll often assess their airway as well, because if they have that going on, they may have a floppy airway as well, and they may be losing it at night and showing what we call upper airway resistance syndrome, which is a subtle form of sleep apnea. So we oftentimes, I get sleep studies to look at that. Oftentimes I’ll get ENT and the oral airway doctors including oral surgeons involved to make sure that they’re not losing their airway, myofunctional therapists to help strengthen the musculature of the airway. And then there’s a class of physical therapists that are geared entirely toward CCI. So I will get them and get them involved. One of the things that I’ve found useful as a test of concept in these patients is what happens if they were to get some what’s called NUCCA therapy, NUCCA. And that’s a particular form of chiropractic therapy that focuses on the Atlas. And so these NUCCA chiropractors have been very, very helpful in putting C1 back in place. And these patients can respond right away to their POTS like symptoms. Their dysautonomia improves right away. Trouble is, it doesn’t last long. It’s almost as if the spinal column, the cervical column is like a Jenga block tower. And the Jenga blocks have been messed up and they’ve come along and straightened up the Jenga block tower, but that may not last very long. So, but it’s a very good test of concept. It may last a week, and, you know, they may be willing to go back on a weekly basis to get this done and get relief. But you’re looking long term and working with the CCI physical therapist to find a better way to strengthen that Jenga tower. So that’s a strategy I use.

[00:36:50] Dr. Tania Dempsey: No, that’s excellent. Is there a percentage of patients in your practice who wind up with surgery for that this condition?

[00:36:58] Dr. Andrew Maxwell: I’ve never sent a patient for surgery for this. I have sent a few patients for prolotherapy. These, these are not post COVID patients. These are patients that have had this issue long enough to know that physical therapy was not solving the problem that they had it for a while, that physical therapy was not the answer. The physical therapist usually weigh in on this. Andy, this isn’t something I’m being able to get any improvement on. I think it’s time to consider prolotherapy. And and then of course, the choice of how to go about prolotherapy becomes important. I usually have them all do the platelet rich plasma. So it’s injecting into the ligaments, materials from self so that you are minimizing the chance of creating a mast cell activation phenomenon by injecting something foreign. And but there’s prolotherapists who will inject only the peripheral ligaments that really aren’t the ligaments that are the problem. And they may be somewhat successful just doing that, but usually not. And then there’s the prolotherapists who will get in a little bit deeper. And inject the ligaments that are right there holding C1 and C2 and C zero, the base of the skull in place. And then finally there’s the prolotherapist who will go right in as deep as you can go to the transverse ligament. And that’s obviously a very specialized technique and they will strengthen that. And so a few of my patients have gone for those latter two procedures and had benefits with that. Again, those are not post COVID patients. I haven’t had a post COVID patient who has failed physical therapy to say that this is where they’re headed.

[00:38:47] Dr. Tania Dempsey: Well, it’s very reassuring actually, right? For those people who are struggling with post COVID, to know that some of the less aggressive methods of, of dealing with it are helpful. I’m reassured

[00:39:00] Dr. Andrew Maxwell: think so.

[00:39:01] Dr. Tania Dempsey: right?

[00:39:02] Dr. Andrew Maxwell: Yeah. So far the hope with a lot of these patients are you’re just giving bandaid therapy. That’s certainly what all the POTS therapies are, is bandaid therapy. And then, you know, a little bit more true therapy with a mast cell therapy. You’re interrupting the process by suppressing mast cells. But, in reality, you’re still waiting for the underlying phenomenon to dissipate oftentimes by the body taken care of either getting rid of spike protein on its own, or, you know, the other two theories, you know, that it’s still a, a chronic low level COVID virus that’s present. And of course sometimes we take that strategy well, well, maybe an antiviral will help. And then of course the third theory does it reactivate latent organisms in the body, whether it’s Epstein Bar virus, HSV six, or maybe one of the you know, Lyme, bartonella, Babesia and would attention to those organisms be helpful to eradicate and help speed the process of recovery. So I tend to, for the most part work with the first theory that we’re just waiting for Spike protein. I look for Epstein Barr Virus, I look for HSV six, and if the PCRs are positive or if the IGMs for those viruses are positive, I’ll try antivirals. But that’s a minority of patients. I haven’t turned to other organisms to consider them. Again, my theory is that we’re biding our time with all these symptoms while the bodies mainly taking care of the underlying problem. I dunno if maybe Tania wants to speak to some of that as well.

[00:40:44] Dr. Tania Dempsey: Yeah. No, I think you did a great job. I don’t have much to add. Obviously we think a lot alike, right? And our approach is very, very similar. And I think it’s about helping the body heal. The mast cells are gonna be a big part of that healing. So that has to be addressed. And then these other pieces, I mean, because of my specialty or expertise in vector borne infections? I definitely will test for that more often, right? That’s on my radar, particularly because of the area of the country that I practice in. So, and I see, you know, quite a few patients who have reactivated old infections that they may have had beyond viruses, these bacteria and all that. So I do focus on it, but really the mast cells are always number one. You know, patients get a little impatient sometimes because they wanna just feel better. And then we get a positive PCR let’s say on Epstein Barr, or we get a positive fish test for Bartonella or Borrelia or something. And, that feeling like, oh, we’ve gotta go after that. And usually that’s not my first place to start because I’ve gotta stabilize the immune system. And what I hope is that by stabilizing the immune system and and creating a more efficient immune system is kind of the way I describe it to patients, then maybe the immune system, which was handling those infections prior to COVID could just go back to handling it. You know again, that’s always my preference. But of course there are patients that have needed treatment for those infections post COVID, and I have a number of patients that have COVID multiple times. One patient had sat five times or six times now, right? It’s, oh my goodness. Actually, she’s rebounding. So three of them are probably just the same infection potentially over the course of two months with positive and negative, positive negative. So there’s immune dysfunction, clearly. It’s not clearing the virus. And she has a really, really significant history of, of tick-borne, vector-borne infections. And so probably what’s happening now is that, that all those infections are at the surface, the immune system can’t handle anything. And so stabilizing the mast cells and then the band-aids, sometimes the antivirals, sometimes antibiotics. In some ways they’re band-aids too, because we’re just trying to drop the load down on the immune system so that we can get the recovery. That’s sort of my approach.

[00:43:04] Dr. Andrew Maxwell: So that is a good segue, I think, into this specific article, this article that was published out of Cedar Sinai with Alan Kwan being the first author. And it had been noted prior to this that patients were developing POTS and dysautonomia and mast cell activation syndrome shortly after having COVID or the vaccine. I think that, you know, certainly in my practice, I witnessed it. I didn’t need an article to tell me this was happening. But it’s great to see that it was actually put to a rigorous Analysis. And they, you know, actually looked at a good 20,000 patients that had had COVID and about 250,000 patients that a had the vaccine and a asked what’s the frequency of developing a whole list of things that we’ve been seeing. Myocarditis, dysautonomia, POTS even, you know, lumbago, the you know, just pain in the lower back. The list is probably what 20 long on the things they looked at. But at the top of the list at least for the vaccine was the myocarditis we’ve all heard about. But right after that is dysautonomia, then POTS, the mast cell activation syndrome. And they looked at that for the vaccine and they looked at it for the post COVID infection, and they saw it, you know, maybe at a two and a half times relative risk of developing myocarditis, POTS, the dysautonomia with either the COVID infection or the vaccine. But then they kind of took it one step further and looked at, you know, the frequency that these occurred in the population at risk. And kind of parsed it out in a very interesting way that allowed us to compare a little bit the relative risk of the two together. If we’re hearing that we’re getting POTS and dysautonomia and mast cell activation from the vaccine, why would we ever be giving the vaccine? Well, it’s complicated by the fact that, you know, we’re also seeing these things from getting COVID. And if you put the two analyses together, what they found was, yeah, it’s probably about five times more common to get the, the onset of myocarditis or POTS or dysautonomia, or mast cell activation from COVID infection than from the vaccine. So, it really is this very complex metric or matrix that someone has to apply to themselves when saying, you know, do I want to get the vaccine or not? Versus, you know, do I wanna risk getting COVID? Yeah, you’re gonna potentially have a risk of one of those complications from either one.

[00:46:02] Dr. Tania Dempsey: Yeah.

[00:46:03] Jill Brook: And I would just encourage our listeners to listen to the episode with Marie Claire Seeley. Standing up to POTS actually funded their study on Long COVID, where they were looking at long COVID patients and the prevalence of POTS, and unfortunately, they were not able to see evidence that the vaccine was preventing people from getting post COVID POTS if they had a breakthrough infection. So just to complicate that picture, even more about

[00:46:34] Dr. Andrew Maxwell: no,

[00:46:35] Jill Brook: cost and benefits, you’d have to do quite a bit of math to do that analysis at this point.

[00:46:40] Dr. Andrew Maxwell: I certainly think that, you know the vaccine has definitely changed its relevance over the course of the past two years. We’re certainly in the early part it seemed like the vaccine was preventing transmission, preventing serious illness, hospitalization, death. But as the virus changed how important the vaccine was such that there was no longer any, in my view, and it sounds like there was some evidence to corroborate what I’m witnessing is you’re not preventing transmission with the vaccine so much anymore. You’re not preventing long COVID with the vaccine. We’re seeing that with or without the vaccine, sometimes causing long COVID with the vaccine. And so the smaller range that we’re seeing of the illness, you know, less hospitalization, less death, and so you’re working with a smaller range of illness. With anyone and the vaccine’s not clearly impacting that within that range. And so you gotta ask is it worth it? And I think there’s enough ambiguity in the studies and all that, that it still leaves people to say, yeah, but I think it’s worth it for me or my family. And I would have to respect that. And the same with the patient comes in and says, no way. I’m not, you know, having a vaccine. No, I would respect that as well. Either way. Our role as doctors is whatever the consequences of whatever choice you made, we’re here to manage the outcome of that.

[00:48:17] Dr. Tania Dempsey: Yeah, a hundred percent agree. Yeah.

[00:48:20] Jill Brook: You guys have covered so much wonderful, rich, amazing information that I almost feel like you are an advertisement for Johns Hopkins Medical School. I’m sitting here saying, wow, Johns Hopkins is special. This has been amazing. I feel like I wanna go listen to this again right now, and I would encourage listeners to listen again because that was so packed full of wonderful information. I just wanted to make sure that people understood in your bicycle tire analogy, why it’s a bicycle tire. Right, because you can’t, you can’t plug some leaks but not others.

[00:48:54] Dr. Andrew Maxwell: Yeah, that’s right. I mean, a bicycle tire is going to be completely useless until all seven holes are patched. That’s the whole point. And then you say, well, why not a car tire? I mean, have you seen car tires lately? Now they’re run flats and I mean, it would never work with a car tire analogy. Oh, it’s gotta be bicycle.

[00:49:14] Dr. Tania Dempsey: It’s perfect.

[00:49:16] Jill Brook: Perfect. I wanted to make sure nobody missed that, cuz I think that’s so valuable.

[00:49:20] Dr. Tania Dempsey: Andy, do you have any last minute, final words or messages for our listeners today? Is there anything else that we didn’t talk about that you wanna make sure that they hear?

[00:49:30] Dr. Andrew Maxwell: It’s the kind of final last words I always have in podcasts. And that’s for the patients seeking help, you know, find the right provider that works with you. Don’t let someone dismiss you. I hear again and again being told, you know, there’s no point in managing anything. You’re gonna get better with your long COVID. And you know, we’ve seen long COVID patients two years out who were just struggling, not everybody. And it’s great to see some patients getting better even on their own. But you never know who thoses are gonna be, and so you’re gonna want to try to modify what could be a very long road. And so you know, make sure you’re finding someone who’s addressing your issues that has a a pretty good handle on the underlying causes that can do it in a systematic way. And I think you’ll have some success.

[00:50:24] Dr. Tania Dempsey: Thank you for saying that. Your words are very similar to the words that I say at the end of the podcast as well. The same message, you know, so we’re definitely on the same page. I’m so appreciative for you coming on the show today and joining us and sharing your knowledge with us. Thank you so much, Dr. Maxwell.

[00:50:41] Dr. Andrew Maxwell: Sure. Okay. Talk to you guys later.

[00:50:44] Jill Brook: Dr. Dempsey and Dr. Maxwell, thank you so much for this incredible information. You guys are just amazing. I don’t know what more to say other than we just could not be more, more grateful to have your brain power and compassion on our team. So thanks a million million. I know you need to run. We’ve kept you long, so hey listeners, that’s all for now, but we’ll be back again next week with a normal episode. We’ll be back again next month for another episode of Mast Cell Matters. Until then, thank you for listening, and may your mast cells be good to you.