#24 Ehlers Danlos Syndrome & Orthostatic Intolerance in Chronic Fatigue conditions with Dr Peter Rowe

(upbeat music) Welcome to Make Visible, the podcast Shining a Light on Complex Chronic Elness. I am your host, Emily Kate Stevens. (upbeat music) Welcome. This week I bring you an interview that I conducted in person with Dr. Peter O, Professor of Pediatrics at Johns Hopkins School of Medicine. He has been leading research and treating patients with chronic fatigue related conditions for over 30 years and is a leading voice in orthostatic intolerance and Elis Dunloss syndrome. (upbeat music) - Dr. O. - Good morning. - Thank you so much for joining me. - My pleasure. - Your expertise in chronic fatigue syndrome actually predates when we started calling it ME CFS. - Correct. - And you became interested in these disorders that were characterized by fatigue and orthostatic intolerance. And that's really one of your areas of expertise is this orthostatic intolerance. Can you, first of all, for our audience, explain to us what orthostatic intolerance is and how it contributes to these fatigue related conditions? - Or so orthostatic just means upright. And if you're intolerant of upright posture, you can get a variety of symptoms that are mostly related to not getting adequate blood flow to the brain or the body's response to not getting enough blood flow to the brain, which includes a sort of high adrenaline state. Orthostatic intolerance syndromes can include drops in blood pressure so that you have orthostatic hypertension or a reflex response that leads to fainting. You can have increases in heart rate or you can have neither a change in blood pressure or heart rate, but still have big reductions in the amount of blood flow that gets to the brain. So the symptoms really count. - Why? If you've not got the drop in the blood pressure or the heart rate, what drives or what causes that change in blood flow to the brain? So it's likely to be a combination of things. One is that people who have orthostatic intolerance tend to have a greater gravitational shift of blood into the lower half of the body when they're upright. For reasons that are not entirely clear, some of them have very stretchy blood vessels. And so there's a connection between orthostatic intolerance and people who have joint hypermobility. The same connective tissue that makes them stretchy also is affecting the wall of the blood vessels so that they can pool a lot more blood in the lower half of the body. Other contributors can be a reduction in total blood volume. So our patients tend to have about a 10 to 15% reduction in the amount of blood they have in the circulatory system. Again, for reasons that are unclear. And then the third problem with patients other than the excessive pooling and the low blood volume is that they get an exaggerated adrenaline response. And by adrenaline, I mean both adrenaline and nor adrenaline or epinephrine and nor epinephrine. So the body sort of has a big reaction to that. And those cataclylamines can also cause rapid heart rate palpitations and a bit of a number of other symptoms. And that's particularly interesting in the conditions that you deal with because actually, I think, it was in the 1990s that you started early 1990s that you started to realize that your patients that were coming in with chronic fatigue syndrome as it was then known, even without the fainting, without the syncopy, were experiencing these shifts in heart rate, in blood pressure, and this orthostatic intolerance. You start noticing that as, would you say, it's a symptom of ME/CFS or it's a driver because it was so correlated. Yeah, both are symptom and we think it's a driver because if you can treat it effectively, almost everybody with ME/CFS gets better to some degree. Which is fascinating isn't it? Because the symptoms that you just mentioned in orthostatic intolerance are such primary symptoms in ME/CFS. And then it was in 1999 that you rate the paper where you connected the orthostatic intolerance, ME/CFS, and alistamolous, or this hypermobility. One of the things that we have not yet covered hugely in the podcast is alistamolous. And you are someone who has extensive experience dealing with that. And this idea that the flexibility in the blood vessels is the same as that hypermobility in hypermobility. It was fascinating to me when I started reading about it. Can you tell me about your work in that from 1999? Onward. Yeah, so we initially thought that the orthostatic intolerance was such a huge driver that we could get everybody better. And that was probably foolish thinking. But along the way, some of the people that didn't do as well, we noticed we're much more likely to have a pre-existing diagnosis of alistamolous syndrome. And we thought, gosh, let's look into this more carefully. And we looked at the next 100 patients consecutively. We found 12 who were confirmed by a geneticist to have alistamolous syndrome. And all of them had orthostatic intolerance and ME/CFS. So this was the first paper that really tied together those three diagnoses. We went on after that to say, all right, if they've got the full spectrum of EDS, what about people who have just joined hypermobility without meeting the criteria for alistamolous? And that study enrolled 58 consecutive patients and controls. And we showed that if you had a diagnosis of ME/CFS, you were three and a half times more likely to be hypermobile. That was not an accident. That's a genetic trait that was present throughout childhood. Why it then tends to appear as people reach adolescents, most commonly, is a bit unclear. So there are other factors you probably need a second hit, possibly an infection, or something else. Maybe the changes of pubertal development. So there's this genetic predisposition to the joint hypermobility. And that is genetic. That is from B. - Correct. - And then you're saying that what happens is there's the susceptibility there that when you take that viral hit, some kind of trauma to the system, it drives it into ME/CFS. Is that right? - There seems to be the case, yeah. - And then subsequently, sort of later work that you've done suggests that 60% of your ME/CFS patients actually have that joint hypermobility. So is joint hypermobility something that we can actually view as a marker for more of a predisposition to ME/CFS? - We think so, yeah, it's a risk factor. - That's what I was not interested in. - And it's important to recognize that not everybody who's hypermobile is likely or will to get ME/CFS. Many people who are ballet dancers and swimmers and other athletes are hypermobile, it gives them an advantage, think of Michael Phelps, for example, but he doesn't have ME/CFS, right? He's the hypermobility doesn't always confer a very high risk, but it's clearly much more common in our ME/CFS patients. - Okay, and tell me more about Alice Damna's, because I think it's one of these conditions that is much underrepresented and not necessarily understood, and there might be a lot of people who are moving through the world with these two comobidities or three comobidities, if you look at orthostatic intolerances, a separate thing, and might not be aware of it, because Alice Damna is so complicated, it doesn't hit with the number of different, which of course, strains and not strains. - 13 types. And 12 of the 13 have a genetic defect in one of the collagen proteins or the enzymes that affect collagen. Collagen provides the structural support to all of the organs in the body. So if you've got a problem with that collagen, you're likely to have multi-system symptoms, which is often the case, and that's why many of the patients with EDS are quite complicated. - Yeah. - They can have a spinal fluid leaks because the dural membrane is thin. They can have temperamentibular joint dysfunction. They have the orthostatic intolerance, lousy gut motility, venous congestion, because the veins get easily compressed. And so there's a whole host of things that you can then know to look for if you recognize that they have the EDS. - And that's across all of the different types, that's similar to-- - Most similarity. - There are. They have skin, stretchiness, and the ligamentis stretchiness, and cutaneous fragility. The skin is easily injured. The most common types that we've got, We see in those with ME/CFS are the hypermobile type, which is by far the most common. It affects women way more than men as ME/CFS does. And that one is the only one that we don't know the gene defect in. The classical form patients are likely to have more skin problems, easily bruised, and they can get changes in the shins and the knee caps, where there's a deposition of iron, hemociderm in the skin. So they can be recognized through that. But they also have a lot of orthostatic intolerance. I was talking to someone who said that they have seen an uptick in EDS, the non-genetic, the HDS, post-COVID, with all of the increase in infection associated chronic conditions. I think it was actually Mickey Tal at MIT, who was suggesting that there might be with that form of EDS, a suggestion that the viral insult could be the thing that actually triggers the symptoms. Is that something that you. For our audience to understand, you actually deal with pediatrics. You work a lot with adolescents and young adults. Correct. Being people from quite early in some of these conditions, you're not getting to them when they're people like me who got sick in their 40s, you're seeing these as children. What's your understanding of that EDS onset from the viral condition? Yeah, just that we don't know exactly the mechanism by which the infections bring them to a symptomatic state. And that's a very interesting scientific question. What is it about having loose connective tissue that has an interaction with an infection to lead to these really profound symptoms? So some of the time, people are carrying this EDS with not so many symptoms until you have this second. Correct. Okay. Yeah. So that is something that you're seeing even in these young people. Yes. Okay. Can you talk to me. about the way that you approach these children young adults? Because you believe that you can move the majority of patients from bed bound to house bound to actually back to living life. And some of these people, as you say, are having incredibly complex pictures. I've also heard you say there are lots of treatments. These people do not necessarily need to be suffering in the way that they are. Tell me how you approach, obviously all very tailored and individual, but how do you approach a patient who presents to you with this complex picture of orthostatic intolerance? Perhaps you've got infection associated chronic conditions. You've got EDS. How do you start to get a handle on those symptoms? Yeah. I mean, the history is key for us. We sit down and go through with patients the long list of symptoms. And I'd point out that it's not a random list of symptoms. These are, we call them, monotonously similar for more patient to the next. They're not being made up. They're associated with the problems that they all have. We get a sense of an average day. We look at the family history. And we dig into whether they might have one of the other problems that we see in our patients. So do they have ringing in their ears? Do they have terrible headaches when they look up? Really hunting for the kinds of problems that we recognize to be treatable? We focus a lot on the orthostatic intolerance. We do a 10-minute pass of standing test in everybody with bad chronic fatigue. And we are interested not only in the heart rate and blood pressure changes, but also do they get symptomatic standing for 10 minutes leaning against the wall? And is that sometimes immediately symptomatic rather than a delayed sort of patient settlement? Immediately during that 10 minutes. They usually, for example, on Friday, we did a standing test and the person started getting an increase in fatigue from 5 out of 10 to 8 out of 10. Their lightheadedness got worse. They started feeling a bit sweaty. They couldn't think and respond this quickly. So it's often a very prompt increase. And they might feel worse the next day, so there's a post-exertional component. But we're looking for the change in symptoms as they stand. And that contrasts with the average adolescent who would be bored, but have nothing else going on for 10 minutes. So it's often a very clear difference between the patients and those who are healthy. And that's important for the parents to see as well. When we start treating them, we focus on what we think is the biggest problem for that individual. So we don't have a one-size-fits-all program. But we feel that treating the orthostatic intolerance is a key piece of it. 30% of our patients have a delayed reaction to milk protein. It's not a true allergy, but two to four hours after exposure to milk, they'll get upper abdominal pain, reflux. They feel full easily. Those patients can be treated by removing milk protein from the diet. That's not everybody in our clinic, but it's a big number, 30%. Is that also-- is that something that you see right from when they're babies? They often have a history of being very intolerant of a cow's milk formula. Or if the mother was nursing, if the mother's eating a high cow's milk diet, the baby can react to that with diarrhea, a colic, spitting up. And sometimes that milk intolerance clears up by the end of the first year. And they're fine until they get another infection in an adolescence that not only causes the onset of their MECFS, but also reverts their immune system back to being intolerant of milk. We've seen that a number of times we can't explain it. I mean, I'm not-- I'm not going to ask you if you-- Can you explain why that happened? Yeah, it must be the return of intolerance to the milk protein. But we don't know the mechanism for that. But we've seen it time and time again. Is that time with the Marcel activation? Is that something that you see with your patient? Yeah, I mean, Mass Cell activation was something that wasn't really even on anybody's radar until about 15 years ago. But as we have learned to look for it more carefully, that's another thing that can be present in our patients. And the Mass Cell activation symptoms overlap almost completely with MECFS. And Mass Cell's have been found to cause orthostatic intolerance. They give you-- we recognize it often by the skin flushing, the redness, and the rashes, and the hives that patients have. But treating that is a very important part of getting people better. So that really has become a big component of your-- Absolutely. Yeah, we were focusing on just milk protein intolerance in the past. But as other clinicians described better ways of recognizing Mass Cell activation, and I credit Larry Aferin, one of our colleagues, with a lot of the insights in this area, as he has taught us what to look for and how to treat these patients, we are seeing much more success in our ability to get people at a more functional level. You had asked earlier, how do we manage over the first year or two? In one of our cohort studies, we asked people, what is your wellness score? Zero means dying. 100 is as good as you could imagine feeling. The mean score in these 55 patients that we brought into a two-year study was a 50 out of 100. Most healthy kids are up around 85 to 90. So there was a vast difference. By the end of the first year, their wellness score on average had gone up to 70. And by the end of the second year, it was closer to 75. I would point out that that's an average. And there's still a few people in that cohort study that we did who really were still housebound. And that's the challenging group. We need better understandings of what perpetuates their illness, because they sure as heck don't want to be sick. Yeah. And that's-- that is a really good point, isn't it? Because I think there is so much-- there's a lot of stigma attached to conditions like MECFS. And that's historically from when people would just say, well, they're lazy, or they don't want to do something. But the big difference is you're treating kids. And kids don't have that-- I don't feel like going out and playing. I don't feel like doing that. So you're treating people who you know-- this is not made up. They're not. Yeah. No. And the understanding that this was somehow a psychosomatic disorder was really based on a number of fallacies. One was that there was nothing wrong with the physical examination. Well, that's nonsense. If you know what you're looking for, you find joint hypermobility in 60% orthostatic intolerance in nearly 100%. We've worked with our physiotherapy colleagues, and we find that many of them, even though they're hypermobile, also have restrictions in range of motion of the limbs and spine. 80% have abnormalities on their examination, just looking at that alone. So it's complete nonsense that the exam is normal. It's quite abnormal if you actually know what you're looking for. What about in terms of bloods? You've mentioned that with the EDS, you've got stretchy blood vessels. But do you see anything in the actual blood tests of-- Not really. Most of the standard blood tests that we use in clinical medicine have not been adequate to distinguish healthy people from ME/CFS patients. there. a lot of research studies that showed differences, but that hasn't yet translated into something we can use at the bedside in a standard clinical setting. - Yeah, because a lot of the time it's going deeper, it's not just you're looking at sort of proteomics and things rather than-- - Right, I mean, if it was that easy, we would have found the blood work 40 years ago. - Since the big uptick in infection associated chronic conditions with long COVID, and obviously, MCFS is not long COVID. Long COVID is not MCFS, but the two do correlate and some people with long COVID do fulfill the criteria for MCFS. You have-- This year, you've actually called, I believe, for children to be included in the long COVID trials. Talk to me about what that means for you and the work that you do, especially with the MCFS patients, to have children included in those trials and children included in the science that's being done. - Yeah, and I would start by saying that, in the patients that meet MCFS criteria after COVID, they are indistinguishable from our pre-pandemic MCFS patients. So while long COVID is a broad category, and you don't-- not all patients meet criteria for MCFS, the ones who do look very much like the ones we've seen before. They're hypermobile. They have a lot of the comorbid conditions that hypermobile people have. They have orthostatic intolerance. We treat them using the model that we've developed over the last 30 years for treating the pre-pandemic patients. And I think it's led to some very nice improvements in terms of the kids, and enrolling people with pre-pandemic MCFS in trials. They're a perfect control group, other than the duration of illness. You can't match on that, but they provide a very good control group for any long COVID studies. And that's for kids as well as the adults. So I think there's a danger that we would further neglect the pre-pandemic patients by not having them be-- having the services that we are now bringing forth for the people with long COVID. We also need to treat the pre-pandemic patients with the same level of interest and energy. - Virtue. In December 2024, I believe that you did a study or you wrote a paper looking at the cerebral blood flow in MCFS. And concluded that there's an absence of compensatory vasodilation. - Can you explain for our audience what that study revealed or what is happening there with this cerebral blood flow? - Yeah, so I was invited to a conference in Bristol in 2017 and two people that came from the Netherlands, Franz Visser and Linda van Kampen were also there, and we were all talking about orthostatic intolerance. They had come up with a technique. They're both cardiologists, and they run an MCFS clinic outside of Amsterdam. They came up with a technique where they use their Doppler ultrasound probe to measure the blood flow through each internal carotid artery and each vertebral artery. Takes about 30 seconds to acquire the data. But those are the four vessels that bring blood flow to the brain. If you add that the flow through each of them up, you get total cerebral blood inflow. And they compared people who were healthy with over 400 MCFS adults. And they've also done some work in kids to confirm that it's also present in them. The average adult who's put up on a tilt table with their head up for 30 minutes has a 7% reduction in brain blood flow compared to when they're flat. In the MCFS patients, it's a 26% reduction, which is huge. And you think, well, no wonder they're lightheaded and they can't think and they're tired all the time. If you break out the ones who have pots, they're at 28, 29%, or low blood pressure. But the vast majority of the adults that they studied, close to 60% had a negative tilt test for an abnormality in heart rate and blood pressure, but they still had a 24% reduction in brain blood flow. So greater than three times the reduction of a healthy person. And they've found the same thing in long COVID. So that's where I think our measures are suboptimal right now. This technique of measuring the blood flow with an echocardiogram device isn't adopted everywhere. It hasn't been adopted everywhere. But it should be the gold standard for defining a reduction in brain blood flow. We are using these fairly coarse measures of heart rate and blood pressure to infer problems with brain blood flow. But we're going to miss 60% of them if that's all we go by. If you say to somebody who's had a normal tilt test, but they've been quite symptomatic. If they have no change in heart rate or blood pressure, you cannot tell them you're fine, get out of here. There's nothing going on. We have to pay attention to their symptoms. A symptoms of lightheadedness, brain fog, fatigue. Those are really commonly provoked by upright posture in this population. So in terms of the cerebral blood flow, you're actually what you're saying with that. Is it actually a better marker to look at what is going on internally, rather than doing the tilt test? Is the NASA lean test also something that is. We don't call it the NASA lean test. What do we call it? We call it the passive standing test, which is what it was first called in the literature. People thought, colleagues of ours in the MECFS world thought that this would be a catchier phrase that would give it more legitimacy. But the initial study was done on prisoners in a California Correctional Institute. Not NASA astronauts. Nothing's doing NASA. No. I mean, the guy was funded by NASA, but it's a pet peeve of mine. We ought to call it what everybody else calls it. Passive standing test. But yeah, what you're. No, so tell me about the passive standing test, and whether that has any relevance here with the orthostatic intolerance. Yeah, so in studies, where you're really trying to bring out postural tachycardia syndrome or syncopy, you want to have a standardized test. That's where the tilt table test comes in. But it's expensive. In this country, it's about a $1,500 examination. It's not easily available. There's often a long waiting list, whereas any doctor can do a 10 minute standing test in their office of the blood pressure machine and a heart rate monitor. So we think it's a much more available test. It gives you much of the same information. And if you're looking carefully for the provocation of orthostatic symptoms, you don't need to go any further and spend a lot more money on the formal tilt test. Really? So something as simple as that. Passive standing test, which is essentially standing against the wall, can give you a huge amount of information. Absolutely. So you then coupled that with the acochocardi graph, did you say of the, which is not so widely? Right. But that would give you so much of the information that you need. Yeah, yeah. I mean, and the patients are also presenting this information to us. They come in and they give us the same range of symptoms. Yes, I get light-headed. I can't tolerate going to the shopping mall. And our joke with the trainees is that if you've got an adolescent who can't be in the shopping mall for five minutes without wanting to go home, you've got a real problem on your hands. You know, they get tired in the shower. They have to sit down in the shower. But if you don't ask them, do you have to sit down in the shower? They won't tell you that. They think everybody sits down in the shower. That's one of the things with these conditions, though, isn't it? You don't necessarily know what's normal and what's abnormal. Right. So until you're faced with someone like you that actually is armed with full knowledge of how one should be at that age or should be operating at that age. Yeah. Another one that we're focusing on in our current studies is a thing called thoracic outlets in Rome. This is the area where the nerves coming out of the neck have to intermingle with blood vessels to get down into the arm. And people with a narrowed thoracic outlet will have problems when their arms are overhead. So we-- Is the brachial plexus study that we do? Yeah, brachial plexus abnormalities, where the nerves are getting compressed as they go through this area. Well, in order to screen for that, we ask the kids, especially if they have a bit more hair than me, how do your arms feel when you're shampooing your hair? And if you have a bit more hair than I've got, these kids will tell you that their arms get tired and tingly. And we've learned by paying attention to that, that they all think everybody has this. So they don't offer it as a symptom or a report. They think this is just what all adolescents have. So if you're not asking about that, they aren't likely to volunteer the information. But we've noticed that when they have their arms up or arms extended like driving a car, their arms have to be down low on the steering wheel. They wash their hair in two-minute increments. And they accommodate to this. But we've also noticed that with their arms up, we do a three-minute test called an elevated arm stress test. And during this time, they get systemic fatigue. They get brain fog. They get lightheaded. Things that have nothing to do with the traditional focus on just-- the arms. So this is another examination abnormality that is turning out to be quite common. Our current study will give us better data on the exact prevalence of that. But that's a problem that can be treated with targeted physical therapy. We've had a couple of patients who've needed surgery to make more space in the thoracic outlet. They take out part of the first rib. So it's something to do with where that artery is moving through? So it's the nerve, typically the nerves in the brachial plexus. So all of these nerves coming out of the cervical spine, interweaving, exchanging braids like a rope, down under the clavicle over the first rib and into the arm. They are getting compressed in that region and the compression is worse if you've got your arms up or your arms extended. So we have to ask about that. How, where do you put your hands on the steering wheel? How do you do washing your hair? That's absolutely fascinating. It's because- It's treatable. I've always assumed that this was something to do with the heart and how hard the heart has to work because this is something that's been quite prevalent in long COVID is people having this onset of not being able to elevate their arms. Is it all said to do with the heart? So do you think it's no money to do with the nerves? I think it's mostly to do with the brachial plexus nerves, but there are connections between the nerves of the brachial plexus and the sympathetic ganglia, the control heart rate and cardiac function. So there are some of our patients who have come in to do this three-minute test and after 30 seconds they're about to faint and they have to lie down. So there's some interaction we don't know exactly which what connections are present, but we see this a lot that patients often will faint when they're doing something fixing something in a cupboard overhead. So there's an interaction between the brachial plexus and the cardiac function. Okay, and that's the actual heart that's affected or it's the autonomic nervous system? More the autonomic nervous system. Okay, because obviously you're looking at nerves. Yep. The heart is structurally normal in the vast majority of people with any CFS. There are some groups that said that the heart was small. My colleagues in Amsterdam have done a thousand echocardiograms. Don't find that to be the case. Okay, are there any other physical structural abnormalities that you see in ME/CFS? Like if you're saying there's not a small heart or it's so much fit driven by the autonomic nervous system? Well a lot is driven by the autonomic nervous system, but you also have to do a very careful neurologic exam. We've had subsets of patients who have crowding at the skull base with either a chyari malformation or a ligamentus instability at the skull base that leads to autonomic dysfunction because that area is unstable. They can have cervical spinal canal narrowing or stenosis from a disc bulge or from a congenital narrowing. And those patients aren't going to get better with our usual medications. They need surgery. And the trick is and the challenge is to find the right people for the surgeons and not send people who don't need it to them. So that's an evolving area but it's an area where physical therapists can have a role as well as surgeons. Is this also another overlap with the EDS? Yeah. EDS is a risk factor for having a chyari malformation, for having the ligamentus stretchiness at the skull base. We had a girl who was a medical student who was fainting and falling into the beds of the people on her clerkship rotation. So she was being removed from her medical education because she was a bit of a danger to herself and others from sudden fainting. Turns out she played gaelic football and it had a number of concussions. After one of them she developed pots and then the fainting came on after the most recent concussion. She had terrible instability at the skull base and needed an occipital to see three fusion after which she was able to resume her education. She's now a resident with us doing a great job. But that's the kind of history that we need to pay attention to as well. Do they get into trouble moving their neck to either side doing a neck flexion? Does their head feel heavy and unsupported? That's a key complaint of people who have the instability of the ligaments in the neck. So you know that's another thing we see of a further one is that people with EDS and joint hypermobility are much more likely to have these vascular compression syndromes that give you what used to be called pelvic congestion syndrome. Terrible chronic pelvic pain that gets worse the longer you're upright associated with urinary urgency and for women terrible pain within her course. They were regarded in the 1940s as being emotionally frigid. All of this was due to varicose veins in the pelvis from obstruction of flow and there's nothing wrong with their intimacy or their emotional state. They just had lacerating pain. And so these different problems that cause pelvic venous insufficiency are much more likely to occur in people who have connective tissue laxity. So these are again non accidental comorbidities. They're not random things. They're understandable based on the connective tissue physiology. And this connective tissue link with the stretchy blood vessels is absolutely fascinating. Yeah. And just about every other group in the world has confirmed the findings that we first published in 1999. And so this is a very active area of investigation and people with joint hypermobility seem more likely to have mastell activation. Well why would that be? We don't know the answer to it but we can treat both problems without even understanding the mechanism. Do we understand the mechanisms of any of these related conditions? Not really and that's it's kind of humbling right? We don't know all of the things that go on in this very complex autonomic nervous system with COVID or prior to COVID. We don't know what changes the control of circulation to the extent that it does. You'd think with overlapping systems in the body the body would be able to fix this. It would be able to fix the blood volume problem. But we don't have an understanding of that but that doesn't make you a therapeutic nilist. We have lots that we can do that we borrow from other areas like we don't stop treating migraines in people with ME because there's no formal randomized trial of a migraine treatment in ME. That would be insane. We just use what people have learned from migraines in non-ME patients. I mean that's the other thing isn't it that there is still no FDA approved treatment for ME/CFS. Right I would rephrase it there's no single drug that's effective for everybody but we have 15 medicines for orthostatic intolerance. We've got lots of things for pain. We've got treatments for migraines. We've got interventions for people with pelvic congestion syndrome. There's a lot you can do. So there are a lot of interventions that you can use on the individual symptoms. Yeah. Yeah. Rather than one drug that treats it because we can't remove the mechanism particularly the long-havid is different chronic Lyme different because we know the triggers but with ME/CFS we still generally do not know what the underlying pathogen was that that triggered that. Right or how it did so but we often find when you dig in the people with long COVID that they did have some symptoms as adolescents that this wasn't a completely denobo problem after COVID that they were dancers or gymnasts or cheerleaders. They had the flexibility that that but it hadn't manifested as a problem at that point. Or and in my case mast cell activation really realized only later that oh I had the history of that the whole way through. Well it's interesting that one of the thoughts we had at the beginning of the pandemic was that our patients would be really at risk for terrible troubles after COVID and what has been fascinating to observe is that nobody in our clinic of over 500 patients nobody who got COVID had prolonged worsening of their symptoms. Really? And part of that is because we were already controlling their circulation we were treating their allergies we were treating their mast cell activation and a number of observers have noted that people with treated mast cell activation sail through their COVID infection much more easily than people with untreated or unrecognized allergic inflammation from their mast cells. So the mast cells always start reacting when we get infections of any sort. So they may be a key player in the pathogenesis of these syndromes both of what's static intolerance and the broader ME/CFS group. So that work is only just beginning. That's amazing. You just mentioned inflammation in you mentioned allergic inflammation. What's your understanding of inflammation as a driver in these chronic fatigue conditions? Yeah it is likely to be a driver but it's it's interesting that the typical blood tests that we use to test for inflammation the erythrocyte sedimentation rate or ESR and the c-reactive protein they're usually normal in our patients so you're not getting a big sign lighting up saying go for the infection. inflammation, but many of the things that are involved, like the milk protein intolerance, gives you some sort of inflammation. The mass cell activation does. The orthostatic intolerance may, because if you get a reduction in blood flow to the brain, there's a thing called perfusion, reperfusion injury that we know about from heart disease that probably contributes to some of the inflammation in the rest of the body. If your muscles are not getting the amount of blood they need at that moment when you're upright, maybe when you lie down and they get a lot of blood flow, something changes. Those are all questions that are worth investigating. What are you investigating currently that we have not yet discussed that you think might move things forwards in this space? So, we've used a lot of low dose Nell Trexone with good results, not in everybody, but broad enough improvements that we think that's a promising therapy. I know that's being studied formally in some of the long-COVID studies that the NIH is funding. We are focusing our current research on the association of our patients with ME/CFS who have these areas of physical restriction and movement, like the Bricoplexus abnormalities and the thoracic outlets syndrome. But we're trying to replicate, or we're seeing if we can replicate findings from about 15 years ago that showed that they had all kinds of problems with things like straight leg rays, you know, kids who are flexible, but they can't get their leg up past 20 degrees without getting stretch or other symptoms. That's a paradox that we need to explain. And it's not because they're overly sensitive, it's that they're tight in certain parts of the body. That work is important because it leads to very practical interventions by physios, not to exercise them to health, but to clear out the areas of movement, restriction, muscle spasms, myofascial tightness, using manual techniques that are quite gentle and well tolerated by even the really sick people with ME/CFS. I'm relatively accessible and you're talking about something that's overly complicated. No. Final question, there's what was the date. It was March 2024. You did an initial validation on the spider, which is a systemic symptom impact tool that's used for hypermobility-related disorders. But I thought this was an absolutely fascinating thing with spider because actually it is so relevant, the majority of the symptoms, which are eight things around a spider, are so relevant to so many of these conditions. When you map the symptom sets on this spider's web essentially, you've sort of validated that as a tool that should be used in adolescents with these hypermobile-related disorders. Is that something that we could actually employ more across the board to have a broader understanding of these conditions? I'll just one caveat. I had a very small role in that study, in a study, in a study, in a study, in a study by physiotherapy colleagues in Europe. But very well done and very detailed work. That kind of thing gives you a nice graphic representation of which body system is most affected. And that might give you a very good insight into which one, as a physician or a clinician, you ought to treat first. So I think your idea is a good one. Maybe we should expand that to a variety of other conditions, not just the hypermobile group. It was just reading your paper that made me aware of it. And then I went into look at it. It's used mainly with the Alzheimer's, isn't it? And I just thought that's such an amazing visual mapping of people's symptoms sets. And yes, then prioritising what is really causing the biggest impact. Yeah. Amazing. Thank you so much for your time today. What an absolute pleasure it was for me to have the opportunity to meet such a knowledgeable and empathetic doctor in person who has developed such a deep understanding of these conditions. And this idea that we have the tools, we have the ability to improve situations for patients even when we don't know the root of some of these illnesses, that's huge. I appreciate that it requires us being able to access doctors such as Peter Rowe who are able to treat with that knowledge and kindness. But I do hope that this conversation gives you hope that there are treatments out there and there are people out there who are striving to make a difference. I wish you all the very best week and look forward to talking to you again soon. Thank you for listening to Make Visible. Please do like, follow or subscribe to listen to our next episode where we'll be uncovering more insights into complex chronic illness. This was brought to you by the team at Visible, a group of scientists and engineers whose lives have been affected by energy limiting health conditions. We're building wearable technology that's helping 100,000 people measure and manage their complex chronic illness. To find out more about what we're working on and how visible could help you, visit our website at MakeVisible.com.