Episode 90: POTS, Small Fiber Neuropathy, and Mystery Symptoms with Dr. David Saperstein

00:01 Announcer: Welcome to the Standing Up to POTS podcast, otherwise known as the POTScast. This podcast is dedicated to educating and empowering the community about postural orthostatic tachycardia syndrome, commonly referred to as POTS. This invisible illness impacts millions and we are committed to explaining the basics, raising awareness, exploring the research, and empowering patients to not only survive, but thrive. This is the Standing Up to POTS podcast.

00:29 Jill (Host): Hello, fellow POTS patients and super-duper people who care about POTS patients. I'm Jill Brook, and today we are hearing from POTS specialist Dr. David Saperstein. He is a neurologist at the Center for Complex Neurology in Phoenix, Arizona. He is board certified in neurology, neuromuscular medicine, clinical neurophysiology, and electrodiagnostic medicine. He is also a clinical associate professor of neurology at the University of Arizona College of Medicine. He is a veteran of the US Air Force. He attended the Boston University School of Medicine. He has so many impressive qualifications related to neurology that I can't read them all or it would take all hour, but he holds numerous professional memberships, sits on numerous national advisory committees, and was the 2021 recipient of a Community Choice Award from the Ehlers Danlos Society. Dr. Saperstein has cared for over 2,500 patients with EDS, POTS, and related conditions, including the toughest comorbidities like craniocervical instability, Chiari malformation, and things like that. And I could go on, but I know that you are dying to hear from Dr. Saperstein yourselves. So, thank you so much for joining us today, Dr. Saperstein.

01:48 Dr. Saperstein (Guest): Oh, my pleasure. Thank you, Jill.

01:51 Jill (Host): So, how did you become an expert in POTS, because they don't really focus on that too much in medical school, right?

01:56 Dr. Saperstein (Guest): No, they... they sure don't. So, I was a resident in neurology when Mayo Clinic first had the POTS paper. And so even as a resident I was interested in autonomic disorders, and we didn't have sophisticated equipment. I remember once having a patient in the hospital and I was running like a little EKG strip, so I was doing, you know, one of the tests for autonomic is looking at variations in their EKG with heart rate, and I was like printing it out and measuring and I was such a little geek doing my, my little testing. And then I went on and trained in neuromuscular medicine and certainly now there are - and there have been for awhile - autonomic specialists, but for some reason, I'm not really sure why, but a lot of these people who dealt with autonomic disorders were neuromuscular specialists, and probably most of neuromuscular specialists kind of did either begrudgingly or reluctantly, and then obviously there are people who specialize in it. And so, I had always been interested. And then when working with small fiber neuropathy, which I think we'll talk about more later, which became a significant part of my practice. I realized that a lot of those patients had autonomic disorders and specifically POTS, and so I started doing more of it and... and at my practice got, I guess it was a nice transition, got the state-of-the-art elaborate autonomic testing coming far from my little printing out strips of EKG and measuring them with the ruler days. And then in doing that, we're seeing more and more POTS patients and certainly seeing that connections between small fiber neuropathy and hypermobility and some of the other comorbidities, which again I'm also sure we will be talking more about today.

03:42 Jill (Host): So just for fun, I know that you kind of like eat, sleep, and breathe POTS and related conditions. You've seen so many patients. So, I'm curious, when you're at a cocktail party, if you get asked about your work, how do you describe POTS to people who don't really want to hear all the medical jargon?

04:01 Dr. Saperstein (Guest): There's two answers. Like, one is the answer and then the other is the answer I give based on how frustrated I am. Not, and I'll explain what I mean by that, not with the person asking me, but with how POTS patients get treated. So, the quick answer is, I mean really simply, something goes wrong in the coordination of blood pressure and heart rate. The way it's supposed to happen when we stand up doesn't happen and people get lightheaded and get rapid heart rate. The frustrating part is trying to explain why that concept is so hard for, you know, the medical community at large. And so, for all of us who... who treat a lot of POTS patients day in and day out, we're hearing these stories of or meeting these patients who like OK, so five years ago you started passing out and your heart goes really fast and your doctor said your tests were normal and then some doctor said, “Oh, this sounds like POTS.” Then you're like, OK, and then they did... Oh, they didn't do anything. So sometimes the cocktail answer would be I deal with patients that have an easily diagnosed condition that's, most cases, at least initially, easy to treat that nobody does anything about. That's my frustrated cocktail answer.

05:19 Jill (Host): [Laughs] OK, I like that answer. Well, I know that you do more for POTS patients than a lot of doctors do. Like you say, a lot of doctors might recognize it, but then just say, hey, drink more water or something like that. Can I ask, like once you suspect that a patient has POTS, what else are you looking to learn about that patient?

05:40 Dr. Saperstein (Guest): So again, two-fold - one is trying to understand as much about the POTS as we can. So, even again, I can't have it both ways. So I should be pleased when other physicians in the community identify somebody having POTS, and I I am. But then, as you said, I eat, drink and sleep it so there's... there can be an oversimplification of POTS, and so there's different types of POTS. Maybe those aren't as cleanly delineated as... as the textbook suggests, but sort of getting that information. So is this a person who's also has blood pressure issues in addition to their heart rate problems? They have hyperadrenergic POTS where their blood pressure is going to high or they have too much drive in their sympathetic nervous system. So those are things are going to affect how I treat their POTS. And then definitely in terms of what do I want to know about them is what sort of comorbidities there are? So some patients develop POTS and that's really... you can't really find much other explanation for it, but certainly in the population I see in part of its how patients come to me and what we call referral bias, lot of them have EDS or other hypermobility conditions. They have mast cell activation syndrome and it gets very interesting in figuring out all those things into your interlap, and you mentioned Chiari and craniocervical instability. So, it's... I guess what I tell patients is we know that a lot of things can be involved with POTS and people with POTS, in addition to lightheadedness and tachycardia, can have GI symptoms and temperature tolerability issues. And all of that can fall under POTS, but then there can be like two or three other reasons why similar sorts of symptoms happened. And it took me just relatively recently to realize this, it's like, wow, this is really complicated. A few years ago, it’s be like you have POTS. Boom, there we go. We're off to the races. Let's treat POTS. I mean, that's... that’s a good starting point and in some patients, that's all you need to do but then you realize, Hmm, OK, well, you have GI symptoms. Some of that may be what we usually see in POTS, but you might also have mast cell activation syndrome and if we change your diet or we treat your mast cells, I always tell we need to sort of map out exactly what's going on, and we may not, and fortunately often do not need to hit every one of those points, but usually at the beginning if... if we don't sort of get as clean a picture as we can, then when we're down the road getting into trouble, then it kind of wished we had that little road map. It's like, OK, wait, we did that test. At the time we didn't act on it, but now I think we need to treat you for this or that and...

08:32 Jill (Host): Yeah, I think you also specialize in neuropathy, right? I think in fact, you do a lot of speaking and teaching about neuropathy, yeah. Can you talk about neuropathy and how it relates to POTS?

08:44 Dr. Saperstein (Guest): Sure. So, when I started in neurology, we always knew there was something called small fiber neuropathy. I mean, we know that nerves have fibers of different sizes. So, there's little ones, larger ones, and then larger still, and they all do different functions. We didn't have good ways of testing for small fiber neuropathy. So just around 20 years ago, the technique of doing a skin biopsy became available, but was mostly a research tool. About a dozen or so years ago it became, you know, easily available where you could just order it. And so, we've learned more about it and why there's a subgroup of patients, you know, why is it a big deal that it's purely small fiber? Again, part of it is the diagnosis, because our standard task nerve conduction studies – EMG - will be normal in somebody who has a small fiber neuropathy. So, there are these groups of patients where, OK, some of them you really seem like you have a neuropathy based on your symptoms and other factors based on your exam, but it was harder to prove. But then we realized there were patients with what would seem like odd symptoms, symptoms would come and go, numbness and tingling. It would be multifocal. Most neuropathies start in the feet and move their ways up. When we did more and more of these skin biopsies and could demonstrate small fiber neuropathy, we realized that that was part of it or that could be part of small farm neuropathy. And then it's like what do small nerve fibers do so? They're in the nerve endings in our skin and involved in pain and temperature transmission sensory transmission of those sensations. But then they're also, they play a big role in the autonomic nervous system. So some people will just have sensory features. Some people will just have autonomic. More often than not, people can have both. And so, we came to realize that small fiber neuropathy was very often associated with autonomic conditions and we know there's a link between POTS, although we're not exactly sure. So, you know, if you test people with POTS do a skin biopsy test to look at their small nerves, close to half, maybe not, you know, a third or some studies, a half of them will have a small fiber neuropathy on that test. That led to this term neuropathic POTS, so this idea that in some people with POTS, the nerves that control how tightly the veins and arteries squeeze aren't functioning right. And so, this idea of blood pooling, you stand up and you get purplish feet and you're getting too much blood collecting in your lower body when you're standing and that's why people have POTS. And that certainly is a factor in it and there are some patients where that's probably the... the whole or main factor. We're still trying to sort out that story and we know that if you biopsy POTS patients, some of them will have an abnormal test, some will have normal, and... and their symptoms can be very similar. So, patients can have sensory symptoms or do often have sensory symptoms with their POTS, and you would think those are the ones more likely they have an abnormal skin biopsy, but not always.

11:44 Jill (Host): OK, fair enough. Do we know if those small fiber nerves can heal? And if so, are there any tricks to get them to heal faster? Or are they just damaged once they're damaged?

11:56 Dr. Saperstein (Guest): So, we don't know. Well, part of the problem is we don't know if we have a treatment that heals nerves. So, in some situations we might. So why... we were just talking about this, doing testing the small nerves, you know why do we often do that? Sometimes we don't know why somebody has a small fiber neuropathy, but sometimes there is a reason we can detect. Our Holy Grail, or one of them, is to find an autoimmune disease because that's one of the subsets of diseases or disorders that we can potentially treat, and if we give something that causes the immune system to better behave itself or the stop attacking the nerves, sometimes IVIG is intravenous and [inaudible] is used in that regard. And there seem to be patients who respond to that. So there have been small studies, and I've done similar small studies, where you repeat the skin biopsy. And the nice thing about skin biopsies is you can do them multiply. You treat somebody who seems to be better - their POTS are better, their sensory symptoms are better - and you repeat that skin biopsy and maybe just a little bit next to where you did the original biopsy. When you do a skin biopsy, you literally count how many nerve fibers there are per millimeter, and we have normal values. And you can see in some of these small little series, big increases. So they only had like one or two fibers per millimeter, and they should have at least five. And then, you know, you repeat it and they've got 7, 8, 10 per millimeter, which is pretty impressive. Again, nobody has done a good natural history study like over time, if you just took a patient with small fiber neuropathy and didn't treat them six months, one year, two years later, does their nerve fiber density - that's our fancy word for the count, the number of nerves they have per millimeter - does that increase? And there was one study that shows that over time that definitely gets less, you know, most small fiber neuropathies. Certainly, we don't have a precedent for them spontaneously increasing. So that's impressive indirect evidence. There have been studies, or I think recently been completed a study, that looked at placebo versus IVIG that looked at pre and post treatment nerve biopsies or skin biopsies and so then we'll actually have some more high-level information. And it's an intriguing area. So, I think the question was, can they get better? And the answer is we think so. We hope so and like everything, depends on what's damaging the nerves.

14:38 Jill (Host): OK, so we've got to wait for a few more studies to get done.

14:41 Dr. Saperstein (Guest): Yeah.

14:42 Jill (Host): OK. So that's interesting. You know, we're hearing about some small fiber neuropathy after COVID and also POTS since COVID. Are you seeing very much of that, and do you think it's teaching us anything new about POTS?

14:56 Dr. Saperstein (Guest): Yes, yeah. So definitely seeing it as others are. And so, skin biopsies again are in the news, so to speak, with post-COVID, with long-COVID. As I alluded to, the big question is, what exactly does that mean? We know that a significant percentage of people with POTS will have abnormal skin biopsies. And again, obviously we have many ways of diagnosing POTS and related conditions, but the skin biopsy is nice because it gives us an objective measure. So, there are... again, it's still early stages, but there are studies that are showing that patients with so-called long-COVID with multiple issues of stamina issues and brain fog, a decent percentage of them have abnormal skin biopsies. So they would have, by definition, small fiber neuropathy. So, along the lines of what we're learning about POTS... So we've always known that a viral illness or some sort of acute illness can be a trigger for POTS. So we weren't surprised when COVID turned out to be. So, you know, it's definitely an interesting time because I think it's... it's making awareness of why certain people get POTS after infection via COVID or others, and it's still early to tell, but what I've noticed is that the post-COVID POTS patients, to me, seem different than POTS patients in general. Obviously there are exceptions, but I talked about our tools and our tests of measuring the autonomic nervous and they're still just lacking in what we really need. You know, if you do a tilt on somebody, you'll see an increase in heart rate. You know, you'll see similar things on your post-COVID POTS patients than your non-COVID associated POTS patients. But the post COVID patients, seeing much more heart racing. They try to exert themselves and their heart goes really fast and they get short of breath and they get chest tightness, which certainly anybody with POTS can and does experience, but that seems to be the main feature and the less so in tolerance of standing, where most typically when you talk to your POTS patients who aren't post COVID, they're like, I stand up and I get lightheaded. Certainly, they do get rapid heart rate and all those things, but it... it seems much more, again, to use a very scientific term, heart racing. And, you know, I've talked to colleagues and not everybody... we're not all in agreement about that. And again, it's it's very interesting times, you know, of trying to tease out what's post-COVID and COVID can and cannot do. So I definitely think it's all going to be to the betterment 'cause POTS, although in and of itself a very common disorder that's treated as a super rare disease, obviously COVID is sexy and it's going to get the funding and headlines and attention and so I think it can't help but bring non COVID related POTS and autonomic disorders since they are very similar, I think it's... it's only going to be a net plus to sort of help at the very least, at least get awareness so then instead of people looking at our patients like, Huh? Why can't you do that or why do you have this chronic diseases?

18:25 Jill (Host): Right. As far as what you're seeing, do you think that a lot of it is autoimmune after COVID? You had mentioned that being one main driver of neuropathy that sometimes can be treated?

18:37 Dr. Saperstein (Guest): It may be. Again, I think it's too early to tell. It's definitely an intriguing thought, one more on the topic of stuff about POTS that we don't understand it nearly as well as we'd like. For many years it's become clear that if you look at people with POTS, they have different antibodies, antibodies that make sense in this in respect to antibodies that affect receptors of the autonomic nervous system, different aspects of it, parasympathetic, sympathetic. And nobody's been able to figure out exactly what role they play, and there's been a bit of a setback in a recent study. When I talk about studies finding these antibodies, mostly it's been in research spheres. So they're at university laboratories that do this and you can't order them. You can't go to your local lab and get them, but there is a lab in Germany that would do testing. And then some people sent samples from POTS patients, but then sent samples from healthy control subjects and the incidence of antibodies was no different between the two groups. So, finding the positive antibodies, at least from that lab which used methodologies that were different or are different from what the research labs do, which is why the research techniques aren't so easily translated. So, it doesn't mean that the antibody theory is all bunk, but we're still, again, need to sort of figure that out. And just as I mentioned, there's study been completed in looking at IVIG and small fiber neuropathy with certain antibodies, there's ongoing studies of looking at IVIG in in POTS, and again, hopefully we'll... we'll learn more about that. I think there's a lot of post-COVID patients with small fiber neuropathy, whether it's autonomic or sensory, who I think are going to get treated for autonomic issues and it's... it's just hard. I mean, obviously you got to do the best that you can with the information you have, but you also want to study it as rigorously as you can to kind of figure out if we're on the right track.

20:42 Jill (Host): Right, and I know in this space is probably frustrating that people always have the most questions about things that don't actually have any answers, [Laughs] but if I could ask you a couple more, we always have patients who are asking us about symptoms, weird symptoms that are kind of feel neurological. They're just curious - do we understand why this happens or what the mechanism is, or what's going on here. Could I run a few of them by you and see if you have any thoughts on them?

21:10 Dr. Saperstein (Guest): Yeah.

21:11 Jill (Host): OK. The first one is that one that you said a moment ago, brain fog, do we know what causes that?

21:15 Dr. Saperstein (Guest): No. No, though I mean, obviously there's lots of theories, but that's what makes it so hard, and that's why it has at the same time such an imprecise name, but it also like a great name 'cause it I think it conveys it well and I think physicians and patients alike kind of get it what you're talking about. But, you know, simplistically, we think that poor blood flow to the brain, which certainly is a part of POTS, you know, suboptimal blood flow, and that probably plays a role. But I think I think there's other factors as well which may have to do with mast cell activation dysfunction in of itself can contribute to brain fog under the right circumstances. And then we get into the cranial cervical instability, and we used to think of that as, OK, it's just there's a structural problem and maybe the brain's getting pulled or tugged and... and then certainly that may be a factor. But now we're learning more that maybe it's not so much that as shifts in how the skull rests on the... on the spine is impeding how well spinal fluid gets cleared out of the brain, and that's causing maybe not brain fog, but some of these other neurologic symptoms that happen or the venous blood, it's flow, is being affected. And so the bottom line is we just don't know and I think that's what frustrates... well, obviously frustrates patients, but it frustrates clinicians and I think particularly neurologists, 'cause if a patient had just one symptom that we couldn't really understand but then they've got multiple and so then unfortunately in patients where they get blamed for having unexplained symptoms. And you, you asked, you know, just to go back, it's like, how do you learn this? Nobody teaches it, and that the single most instructive thing was when you start seeing lots and lots of POTS patients and you realize the patterns. So every neurologist sees lots of POTS patients, you know, they're seeing them and they're calling a migraine. They're seeing him and they're calling them dizzy. They're seeing them and they're calling it small fiber neuropathy. And it's just when you realize that these symptoms are uniform and you have your list of questions that you're prepared to ask and you can predict what the answers are going to be, but a patient has this, this, and this going on you’re like, there's a pretty good likelihood that you're going to have these symptoms present. And it's frustrating because colleagues may look skeptically on... on those of us who are deep into POTS and you just want to say, well, you know, you just... just look at the patterns.

23:54 Jill (Host): So that's so interesting. I have a couple more symptoms to ask you about, but if we could maybe just go down this rabbit hole for a second. I do sometimes wonder what is different about the doctors like you who seem to really believe patients and take some flak, probably from your colleagues, versus the doctors who don't. Do you think that it's where you're trained or just your nature or anything? Is it just what you said, noticing the same pattern so many times that you cannot deny it?

24:27 Dr. Saperstein (Guest): Yeah, I think it's a combination of things. I definitely don't think it's where you're trained. A large part of neurology training, because weird stuff can happen and you could see a patient having some sort of seizure-like episode or they're... they're not using their limb correctly, and, you know, as a non-neurologist it can be unclear what's going on, and they don't necessarily have the tools. And so neurologists are like, OK. Well, based on this and this, this doesn't seem like they're truly paralyzed. And so then we assume that then it's psychogenic or something like that. And... and so and I'm, you know, recovering from that, and I I used to think in that way. And then, you know, you realize that, again, it’s part of the picture, it's part of the spectrum of problems that we see and... and we don't understand it, but there's there seems to be reasons for it. But to answer your question, I don't know why some people choose to take an interest in POTS and deal with a lot of POTS. And so, like I said, a lot of neurologists see it, a lot of physicians, cardiologists or other physicians or clinicians see it, but I think they're playing defense and they're just getting barraged by patients with... with a lot of symptoms and it's hard to see the pattern. There was just this situation where I saw patient with POTS and I diagnosed Ehlers Danlos Syndrome and then she set up a support group and started sending me patients and I was just seeing lots of patients with hypermobility and POTS and a lot of... lots and lots of symptoms, and then I was kind of at the point where, you know, what am I doing? Why am I seeing these patients? What expertise do I get? At the beginning of the visit, I would scribble down sort of my questions I was going to ask and I realized this is my approach and I recognize the patterns. And so, you know, I stuck with it and then sort of came through the other side. And understandably, you know, there's so much time pressure in medicine and you're trying to do so much. But POTS and diseases like that, you can't do it quickly, or you can't do it well, quickly. And so, the idea is to kind of get the picture and I think just that being my strategy in general is to try to get as big a picture as I can. I think that's when you're going to be more receptive to seeing those patterns.

26:53 Dr. Saperstein (Guest): Well, lucky for us, that you did and that you followed it. Can I ask you about a couple more symptoms that patients are confused about?

27:01 Dr. Saperstein (Guest): Of course.

27:02 Jill (Host): One is ear ringing. Why on earth does ear ringing happen? Do we know?

27:06 Dr. Saperstein (Guest): We don't, although I mean we have theories for tinnitus or ear ringing. So 2/3, ¾... really high numbers of patients, they seem to clench their jaw. They have some sort of temporomandibular joint dysfunction, TMJ. And it's well known that that can cause tinnitus. If you go to an EMT with ringing ears they’ll often, you know, say, “Oh, you have problems with your jaw.” So that may be part of it. Again, there's why is clenching your jaw issue so common? Again, many of these patients have hyper mobility and there's issues with their neck and I think if your neck moves too much, it makes your jaw clench. If your jaw clench, it makes your neck out of whack, and there's this sort of yin and yang of of interaction there. I keep mentioning mast activation syndrome and it's interesting 'cause I deal with that, and I view that as something that happens in patients with POTS and hypermobility, whereas the hardcore mast cell people view mast cell as this problem that causes these others. So we're all like seeing the same things, treating the same things, coming out of the same playbook, more or less. But then some of those are like, “Oh yeah, the MCAS is part of POTS and hypermobility,” and others are like, “oh, POTS and hypermobility are part of MCAS.” Again, we don't know, and it may be different in different patients. They all sort of have a big interplay, but you talk to a lot of the MCAS people and they'll say, you know tinnitus is a very common symptom. So, does that mean that mast cell dysfunction causes tinnitus? Maybe, or is it that these comorbidities like hypermobility, like POTS are so common? So, it's a distressing symptom and it's one we don't have great treatments for unless it is related to the temporomandibular joint dysfunction. When we think of neuropathy, when we think of nerve problems, we're very biased towards extremities, numbness and tingling in the extremities, or at least in the skin, but obviously our auditory nerves are nerves, our hearing nerves are nerves. And so, it may be another manifestation of neuropathy. But I talked about having inadequate tools to assess the autonomic nervous system as well as we like. I mean, we really can do a hearing test and that's right now about the only test we can do of the hearing nerve.

29:40 Jill (Host): Oh, interesting. I hadn't thought about auditory nerves as nerves. And one interesting memory I have is that six years ago, when I started IVIG, the first thing I noticed was that my screaming tinnitus of 10 years just disappeared. And that was kind of the first sign that something was changing. And I don't know if that was just a coincidence or if it had anything to do with it, but just another mystery.

30:01 Dr. Saperstein (Guest): Yeah, I mean, again, there's a lot of mysteries, but again, we need to figure out how to string those mysteries together into a narrative.

30:09 Jill (Host): OK, so I have a really mysterious symptom, at least to patients. Maybe it's not mysterious to you, but we get asked all the time, what is up with that POTS symptom of body vibrations or buzzing or feeling like your phone is going off inside your body. Do you know what I'm talking about and do you have any idea what this is?

30:28 Dr. Saperstein (Guest): Yeah, no, that's actually, I think the hardest one. That one puzzles me, vexes me the most. I mean many of these symptoms we see. So tinnitus we see in a lot of patients. Again, there's a high incidence of it in POTS, but numbness, tingling, balance problem. That vibration, I never encountered patients telling me that until I got into seeing POTS and hypermobility and MCAS. So, the short answer unfortunately is I don't know. So, you know, some people will say, “oh you know, vibration sensation is very common with bartonella infection which is a tick-borne infection.” And so, there's a lot of controversy about. It's a hard subject 'cause like if you just do a test for some of these infections, those tests will come back negative and then if you speak to people who work with this, they'll say, well, they're not sensitive enough and people are saying, hey, I'm seeing this pattern, so obviously I can't... I don't want to dismiss the pattern idea, I was just saying it's an important part. But somebody else has recognized it as a pattern, but then some people will say that toxic exposure, so like mold, is a common thing that can cause that by buzzing. So, then I learned more that people who deal with infections have these questionnaires. You know, you get so many points and one of them buzzing, tinnitus is probably on there, and if you get enough points it's like this suggests you have Lyme or Bartonella or some sort of vector borne infection. But then the people who say that mold toxicity, they have very similar questions. And then you back up and you go to mast cell activation syndrome, and you'll get their questionnaire and the three questionnaires are almost the same questionnaire. So maybe there are many things and I do think that patients who develop POTSs by and large are somehow genetically or other reasons susceptible to certain problems are susceptible to reacting poorly, and that gets back to why viruses might trigger, it why COVID might trigger it. And so that’s a long way to say I don't know the answer. I definitely look deeply and consider those things and consult with other colleagues.

32:45 Jill (Host): OK, I just have one more mystery symptom left. It seems like a lot of POTS patients get migraines. Is there any reason you know of that that would be related to POTS?

32:56 Dr. Saperstein (Guest): No, I don't know the reason other than it's definitely common. Most patients do have it. But one interesting thing is that there you know, there's a high inherited character to them, and so I just wonder if there's certain factors... this tendency towards migraine, tendency towards mast cell dysfunction. Maybe they're all traveling together. Again, is it mast cell activation that... that triggers migraines? If you're not getting appropriate blood flow to your brain all the time in POTS that make your brain unhappy. We know that migraine, to some degree, there's a role for blood vessels either constricting too much or dilating too much, so there's an autonomic nervous system component to why people get migraines to begin with. It's not a stretch to say if your autonomic nervous system is messed up in some way that that will make it more likely to get migraines. A lot of times, again, when you're talking about your list, when you're talking to somebody who developed POTS in their 20s or in their 30s, they had migraines when they were eight, so there’s a history... and so more often you find there's a history of it. It may have been trivial, and then, like a lot of things, when the POTS came on, the migraines got worse, the GI symptoms got worse. So, it it's hard to untangle cause and effect. Was already something not right about the autonomic nervous system that caused them to get an occasional migraine, and then something happened and really just threw things into chaos? But we... we don't know.

34:29 Jill (Host): OK, interesting. Well, I appreciate you being willing to dig into these things and really carefully consider them, even though nobody knows. So, you are located in sunny oven-like Phoenix, right? Last time I was in Phoenix the temperature was 117 and actually the other day I was researching hot tubs and I saw that there's a brand made in Phoenix that cools down the water because just sitting outside all day makes the water too hot. [Laughs] So I was thinking that you and your patients might be experts in dealing with the heat. Do you guys have any favorite ways to stay cool, like especially your patients who have to wear compression stockings or anything?

35:08 Dr. Saperstein (Guest): You’d think we would. It is hard, I must confess that a lot of my patients don't wear compression stockings 'cause it's just too hot, so they have to forfeit a potentially helpful tool. It is hard, and this time of year, you know where it's just hot, hot, hot - scorching hot for several months, you really need to be careful about your activities. I mean, it's still hot at the end of the day, but like doing things earlier in the day. Patients use it, not a huge amount, but these cooling vests that put ice packs into these higher tech things that are cooling or there's cooling hats and scarves. So, we're sort of doubly screwed in Phoenix or in Arizona, because it's very dry. And so, some of these devices like you can just wet a scarf and slowly evaporates and cools you. The problem when there's no humidity is that [makes swish noise] it evaporates super quick, and so then it's over and done with, so we can't exploit some of those things as well.

36:07 Jill (Host): I think I read a story last year about hikers going hiking at like 2:00 AM in Phoenix to beat the heat, and I guess that's one way to do it.

36:15 Dr. Saperstein (Guest): Yeah.

36:16 Jill (Host): OK. So, I just wanted to pick your brain about one more thing. Since you have seen thousands of POTS patients and some of the most complex ones, I was wondering if there's any characteristics you've noticed in the patients who tend to see more improvement or less improvement. Is there anything that you've noticed where like, oh, patients who do this tend to get better faster or anything at all like that, just to to kind of search through all your amazing experience?

36:45 Dr. Saperstein (Guest): So, in POTS there's a lot of emphasis on lifestyle interventions and certainly hydration and salt intake, electrolyte intake, using compression stockings, exercising... all those things are important. I almost feel that there's like bit of puritanism in POTS, where this idea that the people who aren't doing well, it's like if only they were more meticulous about hydration, more meticulous about salt intake, or they're not being active enough. And it's hard and part of it, obviously, a bias 'cause I see the people who have POTS that's responds well to initial treatments or recovers, I see some of those patients, but mostly I see the more difficult cases. And so, I always tell them you when your POTS is bad enough, you can't drink and sallt your way out of it. And again, those you got to attend to the basics. To answer the second part more easily, you know, the ones who don't do as well, when there is comorbidities. So, when there's clearly mast cell activation syndrome going on, not only that but if the mast cells are particularly riled up, and that gets back into that multiple factors and if there is a role of infections and exposures or maybe that's because that's flaring up the mast cells. I find that, and again these are the patients I see more often, you know, when you have POTS in the setting of hypermobility or EDS, that seems harder to treat than POTS in isolation. And so unfortunately, the textbook picture that gets quoted to patients when they first get diagnosed is more applicable to a young adolescent girl who had a virus and she developed POTSs and then, you know, they'll say a lot of kids grow out of it and certainly data from Mayo Clinic and other places that a lot of people do, but that's not everyone. And does that mean that just because you have hypermobility, you won't or grow out of it? No, you can. But again, the... the more comorbidities there I think POTS can be a trickier animal to treat and then we just... the ones who aren't doing well we need to look at, do we have all the comorbidities identified? So, I... I find that we all have our bag of tricks for POTS and beta blockers, and midodrine and fludrocortisone. And then you often need to treat the other parts, too. So, things for mast cells or again certainly if there is some sort of infection or again being open to autoimmune or trying to figure out who should be or who shouldn't be treated. And you spoke of IVIG helping you and we certainly see patients helped by it. Yeah, I... I can figure out things that would make me concerned they're going to have a rockier Road, but even some of those do really well.

39:46 Jill (Host): Great. And I know that you have a lot of good videos online, and some of them mention the intersection of Ehlers Danlos Syndrome and POTS and some of these trickier, tougher things. So, I know that you've gone way beyond just being a neurologist for POTS. I think, like you say, you address the mast cell activation syndrome and maybe the autoimmunity and maybe the infections. And so, I can see where this definitely kind of takes you into the much wider area than just neurology. So speaking of your videos online, where can people find you online?

40:22 Dr. Saperstein (Guest): Our website is a starting point – complexneurology.com, but we're on Facebook, Instagram, YouTube, which are all variants of Center for Complex Neurology.

40:33 Jill (Host): Well, Dr. Saperstein, thank you so much for sharing all of your knowledge and your insights with us today. I feel like we saved up all of our hardest questions for you, and I really appreciate you just digging in and sharing all of your thoughts on everything. And thanks for the work that you do. I know on your research and the presentations that you give, I know you spend a lot of time outside of patients’ time trying to help our community. So we just really appreciate your work and your compassion for all of us.

41:03 Dr. Saperstein (Guest): You're welcome. Thank you. Thank you for what you do. That was an enjoyable podcast to do.

41:09 Jill (Host): Oh, good. OK, listeners, that's all for today, but we hope you enjoyed this conversation. We'll be back next week. So, until then, thank you for listening. Remember, you're not alone and please join us again soon.

41:23 Announcer: As a reminder, anything you hear on this podcast is not medical advice. Consult your healthcare team about what's right for you. This show is a production of standing up to pots which is a 501(c)(3) nonprofit organ. You can send us feedback or make a tax-deductible donation at www.standinguptopots.org. You can also engage with us on social media at the handle @standinguptopots. If you like what you heard today, please consider subscribing to our podcast and sharing it with your friends and family. You can find us wherever you get your podcasts or at www.thepotscastcom. Thanks for listening. © 2022 Standing Up to POTS. All rights reserved. [Transcriber’s note: If you would like a copy of this transcript or the transcript for any other episode of the POTScast, please send an email to volunteer@standinguptopots.org]