Ep 137 ME/CFS: What’s in a name? (A lot, actually)

00:00:00
Speaker 1: Hi. My name is December. I'm twenty nine and I was diagnosed with my algic and cephalomyelitis product fatigue syndrome or MACFS, a week before I turned twenty six. I was always kind of a sick kid. I never had quater in school where I didn't need to take a day or more off due to illness. At the time. That was strucked out to a poor immune system. As I got older, I think professors and classmates thought I was being lazy and skipping class rather than being sick. If I had any illness, it would take me out for a lot longer than the average person. I would just stay in bed and barely be able to do homework. Missing a few days here and there was enough to make me look for a doctor or think that there was something wrong. Looking back, these six days were likely the result of having undiagnosed MACFS. In March of twenty twenty, I got invected with COVID nineteen and that triggered MIMECFS. I wasn't able to clear the COVID, so I had a fever on and off for about a month. It would go down with tylanol and then come right back up. Even after the fever stopped, the pain in my neck of my back was unbearable that I couldn't stand up more than several minutes unaided. I couldn't leave the house for very long. I kept thinking, well, you've been in bed for months, so you're unconditioned. You have to build your strength back up. And I would try to push myself a little bit, and every time I did, I would have a massive backlash. I would just be exhausted. The next day it would feel like I ran a marathon and all I did was go to the grocery store. I would have all this pain in my back and my hips, like I had been beaten up. I had a lot of brain fog. I would lose words or walk into rooms and forget what I was looking for. I couldn't remember simple instructions without writing them down. I couldn't have conversations because I would lose the startuper cents by the time I got to the end. At my absolute lowest, I couldn't wash my hair by myself. I was in too much pain to raise my arms for that long. The worst part was that I couldn't get better with sleep. Some days I would sleep for ten or twelve hours and wake up and still feel exhausted. I saw roomtologists who ordered X rays, mri CT scans, and none of them showed anything abnormal. It's pretty scary to know that something is wrong and have no way to prove it. She was very terse and diagnosed me with fibromyalgab, which is largely untreatable. The doctor didn't have any advice for making the pain better. I got the feeling she thought I was malingering, so I went to a different doctor. Thankfully, I saw a second rheumatologist at John Hopkins Hospital who specializes in chronic fatigue. He diagnosed me with my algic and cephalomyelitis chronic fatigue syndrome, and because rheumatological diseases are buy one get too free, he also diagnosed me with postero orthostatic techcardio syndrome or POTS and Eller Danlos syndrome. That seems like a lot, but they all interact with each other. Having EDS means that my collagen isn't formed correctly, so the valves in my veins aren't strong enough to keep the blood in my upper body when I stand up. When I stand up, I get incredibly weak and dizzy, which is the pots. Because I have pots. Standing up makes my heart rate go through the roof. Stand up, get what blood pressure and my heart rate hits one hundred and forty bpm just from standing. Means my body's working harder, which triggers post exertional malaise from the chronic fatigue, and the fiber malga is just the icing on the top that makes all the pain a whole lot worse. So these disorderfully fit together and feed off each other, and I have to treat all of them together. I took a long time to suss out my body's new limits and what will set off the post exertional malays. I used to be able to go on hikes, and now I have to sit down and rest every quarter mile or use a kne I've had to figure this out by trial and error. Oh Can I go to the grocery store and go out to dinner for my family? Can I do laundry and go to work? If I guess wrong, I get knocked out for a day or more. The thing with macfs is that it's not just physical labor that causes fatigue. It can be going out to the movies or just hanging out with friends. It can be completely mental and not at all physical. I took the Jerry and that took about as much out of me as walking a mile. I took it and immediately went to sleep. Anything that take the energy can leave me with this post exertional malaise. Took really long time to figure out where that limit was and how not to cross it. I will have to cancel plans because I'm too tired, and I know if I exceed my limit, I'll be a mess the next day. Try explaining to your boss, well, I can't come in because I overworked myself, so I have to prioritize my work and be strategic about how I use my energy. If I know I have work the next day, I can't hang out with friends or do anything the night before. It's difficult to come to terms with having the energy of a ninety year old in your twenties. I think the hardest thing about having MACFS is the number of people who don't believe it exists. You can't point to a lesion or tumor and say this is the cause of my problem. A lot of people think it's an excuse for laziness. When you hear chronic fatigue, you assume just being tired, But it's so much more than that. It's really and truly a bone deep exhaustion that prevents you from doing much of anything, including thinking. It's not as simple as just going to bed at a regular time. I can't push myself through it the way that someone with a sprain can still walk on a spring. It's a condition that impacts everything about how I live my life. I've been really fortunate with my doctors. I now have a medication regime that helps I take a tenolol and mitodron for my blood pressure. The mitodron helps me to stand and walk unaided for longer. I go to physical therapy once a week to strengthen my muscles. The muscles keep my ligaments in place so my droids aren't slipping as much from DS. Now I can go to physical therapy, lunch with friends, and work in the same day. I'm able to walk longer, even if I still need my cane sometimes. Right now, most of my symptoms are managed, and I'm finally at a point where I can start looking at my future.

00:05:40
Speaker 2: My algic and cephalomyelitis took my bones. When I was sleeping crept in well, I was arrested in breathing deep against my pillow or the paper of the books that I could no longer read. It grew inside me, drank my mitochondria like wine, took an angle grinder to my spine, and wore me away like twilight. I got sick at Uni, in a small room where nobody could hear me cry or permit me to my nervous system quit while I was working in the library, while my legs were burning, like the oven door against my forearms and the stovetop where I made myself curry for the first time independence embryonic hours. Nineteen November was called that year, and January was cold, as fresh and new as ours, and as stark and clean and painful as my fading or autoleomy. I tried to crystallize it in an essay or a poem, in biro, in an off brand toothpaste, like if I wrote it right, I could write myself well. And when the rain fell in February, I fell at the supermarket and at the train station and on the stairs, swallowed the stones in my throat, chose not to dare question why it was that I kept falling and got back up. Because strong people don't get sick. You stick it out, you do not quit, And when the elevator is out of service, you use the stairs. I never knew how high the curb was until I could not climb it. We searched for my bones, in decomposing diagnoses, degrading medication on my tongue, took blood tests and my blood lines, and on the coastline tried to calcify my insights. Strong again, put our hands in the wet sand to build a tibia shape my sternham like a castle, clavical and mandible and cranium, starlight and seafoam and gone. My bones are in the road Hunda Museum, under the skin of the gristorp man. We walk where he walked, and our walks no longer pressed behind glass, my skin tight as leather. My bones are in the limbstone cliff's edge, grown from sediment, calcium carbonate, cycling infinite.

00:08:26
Speaker 3: Ground down to shale.

00:08:29
Speaker 2: My bones are food for minky whales. And I am lying in bed and ugly like a princess, limp and formless and rolled out to sea. I am blue badge on double yellows, Pepsi Max and heavy metal, flat on the back seat, looking through the windscreen, whether Starlings will dance until nightfall. My bones are a murmur of starling, dark and undulating, the shapeless shape of nature, inexplice, poor, impermanent and strong. And it will not be another bleeding tragedy, another d wup dispensability.

00:09:09
Speaker 3: Too many of.

00:09:10
Speaker 2: Us have already died. Build on their body defiant. I am driven by duty and fury, and I want you to know that I am broken because they could not contain me whole. Chronic fatigue took my bones and they grew fragmented, transcendent and new. I am fragile, grounded, bound by dropped curbs and sick insides. But my bone, oh my bones are the sky.

00:10:34
Speaker 3: Thank you so much, December and Katie for sharing your first hand account and your incredible poem with us. I'll also post a link on our website to a video recording of another of Katie Walter's poems, which is also accompanied by just lovely music. Thank you again, Yeah, thank you so much.

00:10:55
Speaker 2: Hi.

00:10:56
Speaker 4: I'm erin Welsh and I'm erin Oman Updike.

00:10:59
Speaker 3: And this is this podcast will kill you.

00:11:02
Speaker 4: Welcome to this episode.

00:11:05
Speaker 3: As promised, we are taking on my algic and cephalomyelitis slash Chronic fatigue syndrome this week. I hope we don't have to keep saying we're just gonna say MECFS, right.

00:11:17
Speaker 4: Yeah, mecs, and we can talk about the issues with the name. Are you going to get into that controversy about the name a little bit?

00:11:24
Speaker 3: Like I'm gonna mention it. I think it's like a longer conversation than probably we're going to have here, but definitely it's something that I want to get into.

00:11:34
Speaker 4: Yeah. So it's going to be, as we always say, a big episode, but it's I am glad that we are covering it. I was very nervous to cover this episode too, but we are going to do our best and I learned a lot in researching for it, so hopefully people get a lot out of it.

00:11:53
Speaker 3: Yeah, I agree. I think this, both this one and the long COVID episode from last week, really have made me think a lot about diseases and how we classify disease versus health, and what is illness versus condition versus all of these different things that are like very fluid.

00:12:15
Speaker 4: Yeah, before we can get into all of that, though, yes, it's quarantiny time.

00:12:21
Speaker 3: It is. It is. What are we drinking this week?

00:12:24
Speaker 4: We're drinking the understatement. Yeah, yeah, it'll make a lot of sense, I think when we talk about the name chronic fatigue syndrome, especially.

00:12:35
Speaker 3: For sure, and in the understatement it's based on an existing cocktail. I have to pull up my text to you here because I have forgotten already everything about it and it's ten in the morning for me, so we're not drinking. It's based on a real cocktail called the Hugo Sprits, and it has prosecco, elderflower liquore, soda, water, fresh mint. Sounds delicious, and to be honest, I love a non alcoholic prosecco. I think it's wonderful.

00:13:07
Speaker 4: I don't think I knew that non alcoholic prosecco actually existed. Yeah, I was just excited about how many non alcoholic like elderflower syrups exist, because I've had some that are really good.

00:13:18
Speaker 3: So many. Yeah. I bought non alcoholic prosecco last year for to make a quarantine, because I was like, I don't want to open a bottle of prosecco and then just have it be you know. Also, I take pictures at like ten in the morning anyway, lighting, Yeah, exactly. We will post the full recipe for our quarantini and our non alcoholic the suber Rita for the understatement on our website This podcast will Kill You dot Com, as well as on all of our social media channels.

00:13:50
Speaker 4: So check us out there. On our website, you can also find so many goodies. You can find transcripts from all of our episodes. You can find link store good to our bookshop dot org affiliated account to Bloodmobile, who does our music. You can find merch you can find our Patreon. You can find sources from all of our episodes. Wow, I think I got most things.

00:14:10
Speaker 3: That's pretty good. First hand account form did we talk account.

00:14:13
Speaker 4: Form didn't say that one. There you go, so check it out. This podcast will kill You dot Com?

00:14:20
Speaker 3: Yes, Aaron, is there anything else that we need to business not that we know of? Awesome Rate review subscribe.

00:14:28
Speaker 4: Rate review subscribe. Oh we need to start saying that more we do.

00:14:32
Speaker 3: We've been told it really does help us out though, So please if you enjoy the podcast, please let us know. Rate review, subscribe, et cetera. Yeah, let's get started, Okay, get started right after this.

00:14:46
Speaker 4: Break myalgic encephalomyelitis or chronic fatigue syndrome. To even begin, we have to define what MECFS actually is, and to do that is difficult. The definitions of mecfs have changed over time, and I'm sure, Aaron, you'll kind of get into some of this, a lot of this, and honestly, it's probably not without controversy, like what the true quote unquote definition is even at this point. But what I'm going to do right now is go over one specific set of criteria that we're the result of, kind of like a big analysis I guess of all of the various criteria, and this is from a twenty fifteen Institute of Medicine report, and these are the kind of diagnostic criteria that we use to define CFS or ME when someone presents to the clinic. What I will say is that this specific set of criteria is mostly used, it seems, in clinical research, and so that's why it's the one that's most often cited in all of the papers that I'm reading. There are a lot of other diagnostic criteria out there that have different symptoms that will take into account and we'll get into all of that in a little bit, But like, what the heck For someone who's never even heard of MECFS, they're like, literally, what are you talking about? Aaron's let me tell you. So these criteria the diagnosis for a person to meet criteria for MECFS includes quote this is all a quote, a substantial reduction or impairment in the ability to engage in pre illness levels of occupational, educational, social, or personal activities that persist for more than six months and is accompanied by fatigue, which is often profound, is of new you or definite onset, has not been lifelong, and is not the result of ongoing excessive exertion, and is not substantially alleviated by rest, along with post exertional malaise will get there and unrefreshing sleep, and then at least one of cognitive impairment or orthostatic intolerance.

00:17:23
Speaker 3: At least one of those two.

00:17:25
Speaker 4: Okay, Yeah, So either cognitive impairment or orthostatic intolerance, sometimes both. Okay, So what does any of that actually MEANMYCFS is a chronic sometimes lifelong, but certainly months, years, years long. Neurologic disorder that results in significant fatigue and a lot of other symptoms, many of which we don't have a good handle on. That's kind of like what it means. I guess it's really hard to define because of how many different symptoms can be associated with it. And one of the things that this list of criteria tell us whenever we have a list of criteria like this, is that there's no test for ME or CFS. There's no thing that we can do to say definitively, Ah, what you are suffering from, person who came to the doctor's office is ME CFS. This is what's called a clinical diagnosis, which is something that's not weird or novel for a lot of listeners of this podcast, a lot of things that we've covered, there's not a single test for. There's like a collection of criteria. Think about migraines. There's a number of criteria that you have to meet to have a migraine disorder. So MECFS is a neurologic disorder which someone has if they're meeting all of these criteria. But while these criteria highlights some of the symptoms like profound fatigue, like unreferrasshing sleep, so someone even if they're able to sleep, they're not getting good rest from that, and they wake up not feeling like they've actually rested. Oftentimes there's big disruptions in the sleep cycle and post exertional malaise, which we talked a little bit about in our long COVID episode, because we see that sometimes with long COVID, which means if someone does try to exert themselves despite feeling fatigued, if they go beyond whatever their functional ability is within twelve to twenty four hours, they will feel significantly worse. That fatigue will be substantially worse, and it sometimes takes a really long time to then get back to feeling better, and then cognitive impairment or that brain fog that again we also talked about in long COVID. Or Orthostatic intolerance, which we also mentioned, is this thing that happens when your autonomic nervous system is not able to regulate itself well. Means people might have heart rates that jump twenty or thirty beats per minute when they stand up. They might have blood pressures that tank when they stand up or when they sit down, and so that can lead to a lot of things like dizzyness, lightheadedness, even loss of consciousness. This is a lot of different symptoms and it's not even all of the symptoms that are associated with MECFS. Pain is another really common symptom that's associated with MECFS. And this can be muscle pain, it can be joint pain. Sometimes it can be swollen or tender lymph nodes. We can also see issues with temperature dysregulation, the feeling of palpitations or chest pain. People could have nausea or diarrhea or constipation. You could even have sensory changes like new sensory sensitivities that never existed before. It's a really long list. And one of the biggest critiques even of the name CFS, and I know that you'll get into this, is that the name chronic fatigue makes it sound like it's just being tired.

00:21:11
Speaker 3: Right, I'm tired, Oh, chronic fit, you chronic fatigue? Ugh, tell me about it. I know what it's like to be tired. I got a toddler at home or whatever.

00:21:19
Speaker 4: It's like exactly, And oh, sorry, you're tired me too. Who isn't right?

00:21:25
Speaker 1: Right?

00:21:25
Speaker 3: Right? Right?

00:21:26
Speaker 4: And so for this, what I want to do is highlight another quote from this Institute of Medicine report from twenty fifteen, because I think it kind of sums up one of the issues with just this, the idea of fatigue and what it means in the context of MECFS, So I'm going to read another quote from this quote. Unfortunately, the word fatigue does not convey information about the cause, severity, or chronicity of fatigue or its impact on functionality. Although fatigue is a common experience, it has no unique physiological explanations or objective markers. MECFS patients often have a level of fatigue that is more profound, more devastating, and longer lasting than that observed in patients with other fatiguing disorders. In addition, fatigue in MECFS is not the result of ongoing exertion, not life long, and not particularly responsive to rest end quote.

00:22:32
Speaker 3: I think the other objection, or like fair point that I've seen made about the name chronic fatigue is that it reduces this incredibly diverse constellation of symptoms down to one thing. And there are some people who would say, actually, my pain is much worse than the fatigue that I experience, or on a given day, fatigue could be the biggest thing, or pain could be the biggest thing, or the sensory changes could be the biggest thing. And so it just kind of like oversimplifies this condition that's incredibly complex and incredibly poorly misunderstood and says extreme tiredness, and that's great, not it exactly exactly.

00:23:14
Speaker 4: It's it's a whole range of neurologic and other symptoms that we don't really understand but are all very real. And so to boil it down to just fatigue just tired, like it's it is not accurate nor is it helpful. Right, So there's also the critique of, like, we don't name most diseases after a symptom, right, and so that's kind of interesting as well.

00:23:40
Speaker 3: That's true.

00:23:41
Speaker 4: Yeah, So that's why some people prefer the term myolgic incephalomyelitis, right. There are other people who object to that because incephalomyelitis means that you have inflammation, specifically in the brain and the myelin, which is the sheaths that cover our nerves. And we see some evidence of inflammation, will get into it, but perhaps not in everyone. Is it truly the inflammation. So it's just a little bit like some people say that it's not perfectly accurate, right, but others argue that it sounds a lot more medical, which makes it sound more quote unquote legit, So maybe people take it more seriously rather than just being tired.

00:24:19
Speaker 3: But then that's really frustrating because we should take things seriously whether or not they's on medical. Shouldn't we shouldn't we hear the DLDR is that we don't have a good name or umbrella term for this, so we're just gonna say MECFS, MECFS. We can do better, and well, we did our best to define it, which is still probably inadequate, so that is like how we define and kind of what the main symptoms of MECFS are. So what I want to try and get into, even though just fair warning, we don't have a lot of information about what is going on in MECFS. So what I want for everyone to get out of this, to like understand from this, is that MECFS is a neurologic disorder. It is a disorder that has biologic underpinnings that just because we don't understand does not.

00:25:17
Speaker 4: Make them not real. And I think that that's the most important thing that I could possibly highlight from everything that I read about MECFS. Just because we don't yet know what is going on does not mean that nothing is going on, or that this is a psychosomatic disorder, or that this is a somatization disorder. And that has been a huge issue. I know you're going to talk about it, Arin. Oh, yeah, yeah, this is a real thing. I hate that I even have to say that, but I think I do. It is a real thing. There is a lot going on biologically that we're still trying to understand. So let's get into it to see what we know so far about how MECFS happens and what's going on in the body when it's happening. Yeah.

00:26:03
Speaker 3: I already have so many questions and I want to know so many things. I'll just avoid asking you all the questions right now and wait for my moment.

00:26:12
Speaker 4: You can ask me so that I can answer them one at a time with ooh, great question. I don't know.

00:26:17
Speaker 3: There we go, There we go.

00:26:19
Speaker 4: So the first question is kind of how does this happen? MECFS is not something that someone has for their entire life from birth till death. Though it is a chronic disorder. A lot of studies point to the links between infectious diseases, especially viral diseases, and the development or the onset of mecfs. The problem is we don't have a single identified viral or other infectious disease that we can point to that say this is the cause of macfs. Epstein bar virus has been implicated. HHV six human herpes virus six, the causative agent of rosiola, has also been implicated. We now know from our long COVID episode that stars covy two can cause a long COVID which many people meet criteria these diagnostic criteria for mecfs during their long covid illness, and overall up to eighty percent of cases of mecfs are associated with a known or like pinpointable prior infection of some kind and usually a non specific kind of like fluky illness, but not all of them.

00:27:33
Speaker 3: I also came across brucellosis.

00:27:35
Speaker 4: Brucellosis, sure, ross river virus q fever. A lot of these different viruses and bacterial illnesses that we know are associated with post acute infectious syndromes of one kind or another. A lot of those post acute infectious syndromes people would meet criteria for MECFS.

00:27:56
Speaker 3: Okay, so I can't I can't stop myself. Please, Is it thought that the mechanism is the same for all of these infections and how it triggers MACFS.

00:28:12
Speaker 4: It's it's really good question, Aaron. I don't think that there is a consensus at this point. One of the papers that I read, and I'll link to it argues that we can't say that MECFS is caused by all of these multiple different disorders. In fact, their argument is that it is enteroviruses, specifically enteroviruses that are the most likely culprit and so things that result post acute infectio syndromes that result from other viruses or bacteria should not be conflated with MECFS. That is their argument.

00:28:46
Speaker 3: Interesting, and that is because it can sort of muddy the waters of clinical trials.

00:28:52
Speaker 4: You know, it's a it's a it's really interesting because at this point, because all we have are these kind of still rather nonspecific diagnostic criteria, right, I mean, they are fairly specific, like you have to meet XYZ criteria for six months with post exertional malaise, et cetera. But I think it gets at the question of what you're asking Aaron, which is what is the underlying mechanism? Because if it is different, if it is different mechanisms that are causing similar symptomatology in these different infections, then it really matters to classify them differently because our treatment options are going to be different. If the underlying mechanisms are the same, then having one big umbrella term helps us because we can get a lot more data from larger groups if we're looking across all of these different infections. I didn't get a sense from all the literature that I read that we have an answer to that underlying question yet. Okay, maybe with all the more data that we have now on long COVID, we'll get closer to that, but at this point we don't have it. And I think there's people that argue kind of both ways, that people who meet criteria for mecfs due to long COVID should be called mecfs, and there are other people who say, no, this is something different and we should treat it as something different.

00:30:19
Speaker 3: So yeah, I think it's a really interesting sort of conundrum, and it's like, maybe we just do all these clinical trials and then include that as a as a factor.

00:30:29
Speaker 4: Right, I mean, you know, it's I think what it's important is trying to not forget about it right, right, because at some point can we have enough data to like really get down into the nitty gritty and disentangle those hopefully well.

00:30:42
Speaker 3: And that's I think really interesting. And where long covid comes into play is because if we can figure out the mechanism for long COVID, that could then sort of open the door to be like, Okay, is this the same mechanism for enteroviruses that seem to trigger MACFS or epstein bar virus or whatever, whichever virus or pathogen.

00:31:02
Speaker 4: Exactly will we someday not have the diagnosis of MACFS at all? Will we have long covid and long BBV and long HHV six and long enterovirus I don't know, Maybe who knows, But it gets even a little bit more complicated, And that sometimes cases are reported to not be associated with infection at all, and sometimes are associated with things like significant trauma, either physical trauma, psychological trauma, major surgeries, or even other like immune system changes that someone undergoes. Now, the paper that I read that argues that enteroviruses are the most likely. Culprit argues that enteroviruses are often asymptomatic, and so could it be that there is in fact an enterovirus infection and then a trauma that ends up triggering the presentation of MACFS. Again, we don't know. Right now, We don't know, but what we do know is that to meet the criteria for MECFS, there is kind of a time point at which and it might be gradual, but there is a timeframe in which someone is more well and then less well, right, And that I think is part of the important criteria for how MECFS is defined and why when there is an infection that we can pinpoint to, it makes that time point a little bit more identifiable. And so sometimes people might point to a trauma. Was that trauma the trigger? We don't know, but it's something that's identifiable where things are different thereafter.

00:32:43
Speaker 3: Okay, another question for you. When we do have a clear infection that we believe is responsible for a particular person being diagnosed with MACFS, what's the time frame there or is there a general time frame? How does it differ across these different pathogens? You know, Part one, two, three, four of my question.

00:33:20
Speaker 4: Great question, I don't know. Okay, Yeah, I don't know, and I think because a lot of times there isn't an identified infection. It's not like, oh I got flu and then I got this. It's like, oh, I was sick with something, I never went to the doctor, et cetera, whatever it was, and then I never got better. Or I was sick and then within a month I was significantly worse something like that. Okay, interesting, and we definitely don't know in terms of like the different infections. We don't know. Okay, So what do we know about, like what is going on? What's going on immunologically? I said that there's inflammation happening, Like what is the underlying path of physiology? Of course I could give you the short answer, which is we don't know, but of course I will give you more context than that, because again, this is something that has a lot of known biological changes. We just don't understand what the unifying factor is or like what the pinpointable path of physiology that underpins it all is. And maybe that's because we're dealing with multiple syndromes. I don't know. But let's go over what we know about all of the various biologic changes that we see in people living with macfs that we know are happening broad strokes, We see large scale changes in the immune system, so we know that this is at least in part an immune mediated disorder. And we talked about this a little bit in our long COVID episode, because that's most of the data for long COVID as well, is that this immune dysfunction plays a big role. One big paper that I looked at that came out in twenty twenty three really tried to drill down into these immune markers, and what was really interesting about what they found is that if they looked just at people living with mecfs as a huge cohort compared to healthy controls, what they found overall was a huge reduction in immune markers, both pro inflammatory and anti inflammatory cytokines and things like that. But when they drilled down even further and separated out people who had MECFS for a shorter time less than three years, compared to people who had had it for more than three years, it was almost the opposite. People who had me for three years or less had significantly higher pro inflammatory cytokines and lower anti inflammatory cytokines compared to healthy controls and compared to those who had emy of longer duration who had lower levels of everything right.

00:36:10
Speaker 5: Like sensitization response exactly exactly, And so what we see from this is like, that's major immune dysregulation, right, that's like pro inflammatory ramping up and anti inflammatory ramping down, which is consistent with some studies that have looked at like imaging studies that sometimes not like a typical MRI or something like that, but kind of very specific and nuanced imaging studies that can see things like neuroinflammation happening in people with ME.

00:36:42
Speaker 4: There's some kind of immune ysregulation going on. There's also evidence of things like dysfunction in some of our immune cells and not just cytokines, so things like natural killer cell dysfunction. Natural killer cells are a type of T cell that are mostly responsible for killer infected or cancerous cells, so they're really good at fighting off viruses specifically, and we can see disruptions in those like they're not functioning as well, and reductions in our activated T cells high again T cell exhaustion. There's a lot of potential in terms of what immune logic changes we see in people with MACFS, but we also see other things. We see things like a lower than typical cortisol level in people with macfs compared to healthy controls quote unquote healthy controls. Now here's where it gets really interesting. A lot of these immune markers, like these cytokines and things they don't test for at the regular doctor's office. You can't ask your doctor to order you like an ilight test or a natural killer cell function test. That's not something that is easily orderable for most physicians. Cortisol is. But we can't diagnose mecfs with cortisol numbers because while they are often and not always low, they're not necessarily outside the normal range on lab values. They're just at the lower end of what is typical or what is normal on those lab values that you see in your like my chart or whatever. And so the suggestion here, the thought is that cortisol. We think of cortisol as a stress hormone. Right, it's a steroid that we fight or flight, we release cortisol, right, But cortisol is released in times of stress in order to help lower inflammation and reduce our immune activation.

00:38:38
Speaker 3: Right.

00:38:38
Speaker 4: It's in response to stress. To be like ooh, back it off a little bit. Okay, So low levels of cortisol means that one of two things. Either it's causing a disruption to our axis, our hypothalamic pituitary axis that produces and like controls these hormones, or it is the result of a dysfunction in this axis, so our brain to adrenal axis is somehow not working. Is it the cause or the consequence? We don't know. But the end result is an increase in inflammation and an increase in immune activation because the cortisol levels are not enough to suppress it, but not low enough that we can like diagnose it based on cortisol levels.

00:39:24
Speaker 3: Okay, So I have a question. Okay, so if if this is a because I've I've come across this to this the sensitization sort of pro inflammatory of your immune system, if we if we suspect that that is a strong contender for a mechanism that's causing all of these symptoms, is there anything we can do about that? Like, are there you know what I mean, like to suppress this immune response or to raise cortisol levels or you know, how do we how do we approach that?

00:39:57
Speaker 4: Yeah, we can talk more about it in a little bit I'm gonna talk about all of the different options that we have for treatment. The short answer is both yes and no. Like, yes, it means that if we can identify what these specific immune things are, can we target those specifically potentially? So far, there isn't like one medicine that we know of that can like raise your cortisol just enough to be able to treat it. And like treating people with steroids doesn't generally help, so like just giving them more doesn't generally help in studies that have tried that.

00:40:34
Speaker 3: Okay, So yeah, okay, So that's the whole answer.

00:40:39
Speaker 4: It's not theoretically yes, and that is why these kinds of studies to investigate, like what is going on, Like what is the underpinning? Why is this cortisol just a little low? What is driving it? Is that the main Like is that just an indicator of dysfunction or is that the dysfunction itself?

00:40:56
Speaker 3: Right?

00:40:57
Speaker 4: We don't know? Does that make sense?

00:41:00
Speaker 3: Yes?

00:41:01
Speaker 4: Okay, There's more though, because there always is. There's also evidence in macfs of like dysfunction in the production of energy our body has to produce atp right to do anything, like for our cells to be able to function we have to produce energy in the form of ATP. In people with mecfs, we see increases in things like reactive oxygen formation and reductions in things like biological antioxidants, and it gets two too nitty gritty. The list goes on, but the bottom line is that these disruptions make it so that our production of ATP and our actual like metabolism, intracellular metabolism is a little screwy, and the end result is again a pro inflammatory state.

00:41:53
Speaker 3: Yeah why why is it pro inflammatory? If you you know, break down some mitochondria.

00:42:01
Speaker 4: So reactive oxygen species are pro inflammatory. Our immune system is going to react to those because a lot of bacteria make reactive oxygen, etcetera, blah blah blah, and oxidants are going to reduce inflammation. So okay, Yeah, that that's that part of it. Okay, So that is what we know so far about mecfs, and like what the biologic underpinnings are. One thing that I wanted to point out, Oh do you have a question?

00:42:28
Speaker 3: First, I do have a question, Okay, So to me, my question is about this these blood pressure changes? Yeah, what why? How like maybe we should do an episode on blood pressure period. But like, I guess, like we've talked a lot so far, or you've explained a lot about like a couple of the different mechanistic possibilities for why we see the symptoms that we see, but what about like how those symptoms actually work? So like why would mitochondrial dysfunction or why would of this pro inflammatory state lead to changes in blood pressure as we change our posture or like our you know, sitting up, standing down or whatever, standing up, standing up, sitting down. I can't.

00:43:14
Speaker 4: Yeah, Aaron, what a great question. Do you want to guess on.

00:43:20
Speaker 3: My answerest Oh no, we don't know.

00:43:24
Speaker 4: So one thing, one thought or one hypothesis that we have evidence for, is that some of this inflammation is happening. A lot of this inflammation is happening in our nervous system, and your nervous system, specifically, your autonomic nervous system is what is controlling your blood pressure and your heart nate. And so if you have inflammation, and I think I mentioned this in our long COVID episode, but if you have inflammation in that vegus nerve, and that vegus nerve is not able to function appropriately, then you can have dysautonomia where you're not controlling your heart rate appropriately, you're not compensating appropriately, so you're having these wild fluctuations in either heart rate or blood pressure or both. But to get more, like more than that, like why is it the vegus nerve? Is it also other nerves? I mean, yes, probably because we can also see things like sensory stimulation differences. We see things like generalized cognitive impairment, which is not probably specific to the vagus nerve, but is more about neuroinflammation in other parts of the brain and the brain stem. But it's really this brain stem and vagus nerve inflammation perhaps and dysfunction, Like why is it having so much dysfunction? How? I think if we knew that, then we could better treat POTS or postural orthostatic tachycardia syndrome and MECFS and the orthostatic changes that we see with MECFS, but we we still don't know exactly what it is.

00:44:59
Speaker 3: Okay, yeah, And gut.

00:45:02
Speaker 4: Stuff, gut stuff, Aaron, great question. There's a huge amount. So MECFS is if you meet the criteria that we talked about, then you have this diagnosis of MECFS. It does not also mean that you can't have other things. And there are a few other disorders that are also very what we call comorbid, so they often occur at higher than typical rates in people who also have mecfs, and that is things like IBS and fibromyalgia, and so the gut stuff we can see both if someone also has IBS or if someone doesn't have IBS, and that we really don't understand except that, I mean, the vegus nerve also innervates your guts, and your guts have their whole own essentially nervous system, like all of their own they're producing their own neuroendocrine hormones and everything, so it is also being affected. We just we don't understand exactly how. Okay, when it comes to fibermyalgia, I want to spend just a minute on this. There is a substantial amount of overlap in the symptoms of MECFS and fibermyalgia, and some of the kind of ways in the literature that it's often been kind of distinguished are these macfs is more fatigue predominant or like the hallmark symptoms, especially that post exertional malaise and pain. Widespread pain is the kind of hallmark of fibermyalgia. That being said, the symptoms, pain, fatigue, all of these symptoms can overlap substantially, and so that has led some people in the research communities to say, oh, well, these are actually the same thing, and it's true that some people end up diagnosed with both things. But from everything that I have read and the way that I understand it, the only drive that I saw in the literature to classify these as the same disease is to say that they result in similar dysfunction like in society, like not being able to live your life the way that you would want to. Kind of a thing. Okay, But whenever people have tried to actually look at what we need to look at the underlying pathophysiological differences that are happening in the bodies of people with MECFS or with fibermyalgia, or with both of them, they're not the same thing. Like there are different biologic changes, immiologic changes that are happening in mecfs, both with and without fibermiolgia and in fibermolgra like separate from mecfs. They're not the same.

00:47:54
Speaker 3: Just means that we'll be doing an episode on fibermiolgia that's talk about.

00:47:59
Speaker 4: We don't know, but so what it seemed to me in reading through the literature is that the people who are arguing that it should be classified as all the same thing are trying to argue that in both cases these are symptoms without an underlying biology, and so for that we should then treat them the same because the symptoms overlap so much, and that does not seem to hold water based on my understanding of the literature when you actually try and look at the differences in biologic markers that are happening in these two different disorders. Just because they overlap and sometimes at significantly higher rates than in someone without EMY or fibro, that does not mean that they're the same thing. And at the same time, people who have mecfs are more likely to also have fibermyalgia and vice versa. So these are two syndromes that while they have have similar symptoms, they are not the same thing, and they can both be happening simultaneously.

00:49:07
Speaker 3: That makes sense.

00:49:09
Speaker 4: Yeah, that's all I've got aaron for the biology.

00:49:13
Speaker 3: Does that mean tell me it's time for me? Okay, Yeah, let's take a quick break and then I'll get right into it.

00:49:24
Speaker 4: I cannot wait.

00:49:59
Speaker 3: Tracing the history of an illness when the definitions of said illness seem to be under constant revision. It's not the most straightforward thing in the world.

00:50:10
Speaker 4: Really, I'm sure.

00:50:12
Speaker 3: When it's been known by so many different names, and depending on which name you pick, you could be starting your history back in the seventeen hundreds, the mid eighteen hundreds, the nineteen thirties, or maybe as recently as the nineteen fifties, when enormous and really seemingly quite contentious arguments have broken out over the potential cause or causes of this illness. It's you know, there's a lot going on, when even right now, in February twenty twenty four, it seems like this is still very much a story that's being written, and I want to do the best that I can, especially after reading some absolutely infuriating papers that either explicitly dismiss the lived experiences of people with MACFS or just talk about how medicine has done that for quite some time. So last week I started off my bit talking about how patients are rarely centered in stories of science and medicine. In how long COVID was a rare and wonderful exception to that. And while it's still absolutely the case that the history of MACFS has been shaped, especially within the past few decades, by patient advocates who rightfully demanded a seat at the table, most of the story that I'm going to tell today has to do with what medicine and the rapidly dividing branches of medicine saw in their patients and how that influenced their definitions of disease. For this telling, I'm going to use names as sort of my guideposts, because there's a lot that we can tell from a name. Like we've already talked about chronic fatigue syndrome and some of the issues with that particular name. Over the course of about two hundred and fifty years or so, what we know today as MACFS, this can has been known by many other names. If we start back at the earliest, that name would be fibricula yep. Described I had not either. This is described in seventeen fifty by Sir Richard Manningham as quote little low continued fever, little transient chilliness, listlessness, with great lassitude and weariness all over the body, little flying pains. Sometimes the patient is a little delirious and forgetful end quote.

00:52:33
Speaker 4: Why is everything a little like a little.

00:52:36
Speaker 3: Just a little bit of this and a little bit of that, a sprinkling of fatigue, a sprinkling of fever spread.

00:52:42
Speaker 4: I have to say, I like the word lassitude.

00:52:46
Speaker 3: Yeah, interesting, and that's called what five bradica fibricula. Don't worry, We're not gonna We're not going to visit it. I felt like I had to include it just for posterity's sake or something.

00:52:59
Speaker 4: Okay.

00:53:00
Speaker 3: I also have no idea how widely this term was used. It doesn't really seem clear. But the author did make a note. The author of this like from seventeen fifty, did make a note that he had seen something similar described in hippocratic texts. So you know, it doesn't seem to be a new illness, not at not in seventeen fifty, nor does it seem to be a new illness in the eighteen hundreds, nor does it seem to be a new illness in the twentieth century, which is the opposite of what some physicians will have you believe when they describe it as quote unquote yuppie flu or twentieth century illness.

00:53:41
Speaker 4: Okay, it's good stuff, spicy already.

00:53:44
Speaker 3: Oh yeah, yeah, every well, I mean when I say every I mean, like, at least in the eighteen hundreds and the nineteen hundreds, these groups of physicians seem to think that, like, this is an illness unique to our time and society's place in our time. So the next name along our journey is no exception to this, neurasthenia. Okay, So I want to spend some time, like a good deal of time with neurasthenia, because I think that we'll see some parallels with mecfs in the second half of the twentieth century, especially as it relates to this divide of like mind body or physical psychiatric and you know, just like the medical gas lighting that's so prominent all of that stuff. Okay, So what was neurasthenia in short, exhaustion of the nervous system nervous exhaustion or if Greek translation is really more your thing, want of strength in the nerve?

00:54:48
Speaker 4: Okay.

00:54:49
Speaker 3: This term had been around since around the eighteen twenties or so, but it really took off in popularity in eighteen sixty nine, when the physician George Beard published an article about it. He listed many symptoms associated with neurosenia, like nerve pain, indigestion, headaches, insomnia, depression, and fatigue, especially fatigue after slight exertion, and which prevents someone from living the life the way they had before. Okay, okay, that's pretty in alignment. Being as he was the personal physician to much of the upper and middle class in the New York neighborhoods where he lived, Beard of course saw social class and gender patterns and who was prone to neurothenia. Essentially wealthy, successful businessmen who became overwhelmed by the fast paced and competitive city living that was a result of the Industrial Revolution and this like growth of capitalism, I guess, or women of the quote unquote better class, whose already sensitive nervous systems were pushed to the brink with a difficulty of maintaining a household or going out and about in high society. So it was it was a sensitivity of the upper classes, primarily wise.

00:56:10
Speaker 4: I have feelings about that, Aaron.

00:56:13
Speaker 3: Oh. It was also when a woman got an education and then developed neurasthenia.

00:56:22
Speaker 4: It was thy education.

00:56:24
Speaker 3: There's always ruining women, right It was Oh, you studied too much, you learned too much, your body can't handle that, gave.

00:56:31
Speaker 4: Yourself a migraine, And then there is sa.

00:56:33
Speaker 3: Yep, yep. But yeah, this this sort of reflects a lot of the other diseases that we've talked about on the podcast, and I can't remember any specifically, but it's just sort of like the cost of progress, right right, this new society, the way that we're living, you know, the cities, everything, the growth, it's all leading to disease.

00:56:54
Speaker 4: I also have to say it gives the same vibes of like, you know how every couple of years there's headlines like.

00:57:00
Speaker 3: The video games are destroying our youth.

00:57:02
Speaker 4: And like if you look back, there's been headlines about TV doing the same thing, then newspaper doing the same thing, the printing press, like it's the same thing, guys, over and over, Like it's not anything new, right, but Aaron.

00:57:17
Speaker 3: Social media is destroying TikTok.

00:57:23
Speaker 4: We're on TikTok by the way we are.

00:57:29
Speaker 3: But yeah, so Beard also, I think is really fascinating counted himself among those with nursenia. As a younger professional. He had been stricken down but recovered through resilience, and possibly electrotherapy. It's not really clear, great job Beard be resilient, but Beard's reports forred others, primarily in the US to compile their own case reports on nursenia, which tended to confirm what Beard said depending on their patient population. So if you if your primary patient population was the upper middle class of New York City, that's who you thought was going to get neurisenia. If you were a rural doctor, then it was people who worked on the farm for very long hours. Like basically, everyone is susceptible, exactly exactly. And also I will say too that it seemed like the distribution or the likelihood of getting neursenia was similarly distributed among the sexes across sects, So it was like equal rates males females. Yeah, but of course, also like who you said was likely to get neursenia and their reasons for getting neurisenia very much played into like maintaining these hierarchies of class and gender structures of the day. Neurasenia was seen as the quote unquote half sister of hysteria. It was the more respectable diagnosis of the two. So let me just read you a quote from a nineteen fifteen paper by Edward Angel. He puts it like this quote. The neurasthenic would but cannot, the hysteric could but will not.

00:59:15
Speaker 4: Stop its Wow.

00:59:23
Speaker 3: Okay, no, I know, isn't that wonderful? So it's so nice?

00:59:31
Speaker 4: Oh my god? Okay. Interesting, yea, interesting, I mean hysteria side interesting that it is sort of a it does seem like they're saying, this is a real thing. People can't can't not like they they are not well, and it's not because they are faking it or their head.

00:59:54
Speaker 3: To be sick. Yeah, exactly. And so that is that is something that really stuck out me in researching the history of neurosenia, because you know what Beard thought was causing neurosenia was I mean, he did, of course say that the ills of modern society played a role in this, but there was a biological mechanism. Beard was a neurologist, and around this time neurologists saw anything related to do with the nervous system and as well as psychiatry. So it was sort of this like blended unspecialized focus or like not as specialized as it is. And it became in later decades, and so he saw neurosthenia as having a neurological physical basis. He was inspired by the laws of thermodynamics, which really were only formalized in the nineteenth century, which I think is really interesting to kind of like take other knowledge developments that are happening around this time and how that influenced medicine. Really cool. He applied this these notions to the nervous system and nervous force in particular, and so if the problem was nervous exhaustion, then the obvious solution would be to get more rest The quote unquote rest cure interesting is exactly what it sounds like. So a bunch of retreats popped up across the US, Central Europe, and the UK. These retreats were where people could go to restore their stores of energy in theory. And I want to just side note. I can't. I like, was like, should I cut this? Is this interesting enough? I find it interesting? So I'm going to make you all listen to that. Okay, But here's my little fun fact.

01:01:47
Speaker 1: Arin.

01:01:47
Speaker 3: Does the name Charlotte Perkins Gilman sound familiar to you at all?

01:01:52
Speaker 2: No?

01:01:52
Speaker 3: Okay, what about the short story The Yellow Wallpaper.

01:01:57
Speaker 4: Nope, okay, sorry, I.

01:02:00
Speaker 3: Think I read this in like high school English or something like that. I can't remember where I came across it. But The Yellow Wallpaper, written by Charlotte Perkins Gilman, is an amazing piece of early feminist literature, published in I think eighteen ninety two, and it tells the story of a woman whose husband, a doctor, forces her to rest in a room in a rented mansion after the birth of her baby. She's not allowed to write, she's not allowed to read, she's not allowed to see anyone. Just complete and total rest. This is the rest cure. You should definitely read it if you haven't, and you can find it for free on the internet. I'm going to post a link, okay, but I can't resist reading you a quote from this quote. John, the narrator's husband, is a physician, and perhaps I would not say it to a living soul, of course, but this is dead paper and a great relief to my mind. Perhaps that is one reason I do not get well faster. You see, he does not believe I am sick. And what can one do if a physician of high standing and one's own husband assures friends and relatives that there is really nothing the matter with one but temporary nervous depression, a slight hysterical tendency. What is one to do? End quote good, it's so good. Go read it, Go read it. It's great. Okay. So back to neurasthenia. What was becoming apparent at the turn of the twentieth century was that no matter how much rest someone was getting, no matter how much electrotherapy they were receiving, because that was popular for a time, no matter how many quote unquote americanitis tonics they drank. That was a real thing. It was also called americanitis.

01:03:44
Speaker 4: Wait wasn't there something else that was called americanitis?

01:03:47
Speaker 3: Oh, I'm sure I can't remember.

01:03:49
Speaker 4: Probablysh that sounds so familiar. Maybe you just told me that about this while we were researching. I don't know.

01:03:56
Speaker 3: No, it sounds familiar to me too. I don't know it. Later we google it. But people didn't seem to be getting any better, and so this then cast doubt on Beard's hypothesis that the root cause of neursenia was a nervous system issue. Along with the fact that people weren't finding consistent results in like dissected nerves, they couldn't find out where the problem was, like there was, they couldn't distinguish someone who had neursenia from someone who had who did not have neurosenia based on dissections. Okay, So this led to by the early twentieth century in neursenia rapidly falling out of style as a neurological diagnosis. And this was not just because of this like the rest cure not working, not finding a a nervous or like a nerve basis for this disease, but it was also because of medical specialization, especially sort of the division of this field of neurology that kind of went to neurology and then psychiatry. And so this led to this mind body divide in medicine that hadn't really been there as much before. And what I mean by this is that conditions tended to be described as all physical where the signs and symptoms were from a physical quote unquote organic cause, or psychological where everything was arising in the mind. And to get better it was either if you didn't get better, it's because you didn't want to get better. Before this divide, patients tended to be treated more holistically and all of their symptoms were taken into account, whether objective or subjective, like something like pain. The message became, if we can't tell that you're experiencing something real, then it must be all in your head, and your physical problems are the result of your mental issues. So it like this causal arrow only went in one direction. You're the one to blame because you want to be this way, or for children, the mother was to blame.

01:06:07
Speaker 4: Oh always, so always blame the mother.

01:06:09
Speaker 3: This is that same guy who said the hysteric can but will not. So you know it's going to be good.

01:06:17
Speaker 4: Yeah.

01:06:18
Speaker 3: Quote Timidity so often inculcated by an over zealous mother, also is one of the early influences which later contributes its share to a neurasthenic diaesthesis. The forcing process of ambitious mothers is very reprehensible and at times a later cause of disastrous breakdowns and quote. So it's like, and if you read more of this, it's like, you know, either too strict, not strict enough, too much education, not enough education. Basically, you can't do anything right moms.

01:06:54
Speaker 4: Moms cannot do anything right and are responsible for one of their children's if.

01:07:00
Speaker 3: Always, always, but neurrosenia also faded from sort of public consciousness, or at least like popular diagnosis, because it was never well defined to begin with. And you know, I think that there is something to that, but I also think that it was sort of overused and eventually became broken down into other more specific diagnoses, largely psychiatric. And you know, it did make me wonder how many people with who were diagnosed with neurosenia in the late nineteenth century would be diagnosed with MACFS today. I have no idea, but I do think that at least probably a subset did have symptoms that would fit into that category that would lead to a diagnosis of MACFS. It's not so like neurosenia is not a perfect it's not the originator. It's not the thing like.

01:07:53
Speaker 4: A perfect parallel or anything.

01:07:55
Speaker 3: Right, it's a but it is a likely precursor, all right. So now I'm going to skip ahead the nineteen thirties, where we meet our next name. This decade, a series of epidemics of what was initially thought to be polio took place around the world. Yep, you know this, But people realized that this illness was milder than polio. It was more commonly seen in adults, and it resulted in fewer cases of paralysis and death, and so it was designated as quote unquote epidemic neuromyasthenia. Several of these outbreaks happened in hospitals among staff, like the Los Angeles and Switzerland epidemics in the nineteen thirties, or among military in close contact, also in Switzerland, and I won't list all of the symptoms, but among them were initial systemic and meningial symptoms similar that were similar to polio temperature fluctuations resulting in fever, localized muscular weakness, extreme fatigue, sensory changes, pain, recurrence of symptoms, and along sometimes years long period of recovery. The cause of these epidemics was still a mystery when another larger scale outbreak of something similar happened in Iceland between nineteen forty eight and nineteen forty nine. So this is eight hundred and forty one cases out of a population of fifteen thousand, pretty high attack rate, and this gave rise to the name Icelandic disease. Again, extreme pain and fatigue was a feature, and recovery was long, so one researcher went back like seven years after this epidemic happened, and found that only twenty five percent of those who were most severely affected had recovered completely and most still had pain, neurological symptoms, and fatigue. And interestingly, this is where the enteroviruses come in.

01:09:55
Speaker 4: Yes, well virus is an interrovirus.

01:09:58
Speaker 3: Exactly exactly so an outbreak of polio in Iceland several years after this sort of mysterious outbreak failed to take hold in the affected region, and children in that affected region who were laved or given the polio vaccine had really high antibody tighters, which led people to suggest that what was causing quote unquote epidemic neuromiothnia was some kind of enterovirus related to poliovirus. Yeah, I mean, and it's entirely possible. Like yeah. In the early nineteen fifties, a few more outbreaks of epidemic neuromiocenia cropped up in Australia, Florida, South Africa, Denmark and elsewhere, But the one that would give us our next name took place in London, England, at the Royal Free Hospital in nineteen fifty five, between July thirteenth and November twenty fourth of that year, two hundred and ninety two members of the medical, nursing and administrative staff of the hospital came down with an unknown disease, and two hundred and fifty five were admitted. So throwback to last week. In the whole, medical practitioner patients lending credence to a poorly understood disease definitely had a role to play, and a role that would soon be undermined. Oh dear foreshadowing. Yeah, The acute phase of this illness included malaise, headache, swollen lymph nodes, depression, mild sore throat, nausea, GI symptoms, and later dizziness, extreme pain in the back, neck and limbs, and fatigue. It was clearly contagious, but no one could track down the cause, and royal free disease, which is what it was initially termed, became quote benign myalgic and cephalomyelitis to reflect quote the absent mortality, the severe uscile pains, the evidence of parental damage to the nervous system, and the presumed inflammatory nature of the disorder end quote. Yep, And maybe you're thinking benign like that is not does not reflect accurately this disease at all, and yes I would agree with you, and many other people would also agree with you, including doctor Melvin Ramsay, which I'll tell you later about in a second. But for now, the benign thing is the least of our problems. Because in nineteen seventy, fifteen years after this Royal Free Hospital outbreak which people were still not fully recovered from, two papers came out in the British Medical Journal by psychiatrist mcvedy and Beard a different Beard by the way, that said.

01:12:57
Speaker 4: He wasn't the least for one hundred years, I know.

01:13:01
Speaker 3: And these papers said essentially they're making it all up. From the abstract of one of these papers, Oh my god.

01:13:10
Speaker 4: I'm sorry. I just need to take a breath because I know I'm about to get so frustrated.

01:13:15
Speaker 3: Okay, don't quote. It is concluded that there is little evidence of an organic disease affecting the central nervous system, and that epidemic hysteria is a much more likely explanation. The data which support this hypothesis are the high attack rate in females compared with males, the intensity of the malaise compared with the slight pyrexia, the presence of subjective features similar to those seen in previous epidemics of hysteria, over breathing, et cetera. End quote, There's more, there's more to it.

01:13:52
Speaker 4: It's just like we didn't think that you looked that sick, and therefore you're making it up right, that's what they're saying, your female.

01:14:01
Speaker 3: Uh huh oh yeah. They they absolutely did not attend the statistics class where they learned that an absence of evidence is not evidence of absence. It's not the same thing. The end of the article by saying, Okay, yeah, I know, we know mass hysteria doesn't have the greatest connotations, but quote, the occurrence of a mass hysterical reaction shows not that the population is psychologically abnormal, but merely that it is socially segregated and consists predominantly of young females. The quote can you believe that I made it so much worse?

01:14:42
Speaker 4: How do you make it worse?

01:14:44
Speaker 5: How do you do that?

01:14:46
Speaker 3: I know, I know, I know. This is a British medical nineteen seventies, nineteen seventy Yes, yep, wow, yep, And I just to un your line how egregious these papers are. I want to read you something from a nineteen fifty six paper about that Royal Free Hospital outbreak, speculating on the cause. And so this was by Ramsey, that Melvin Ramsey, the doctor that I mentioned, who did a lot of work on this particular outbreak. This is nineteen fifty six, fourteen years before quote. It remains to identify the syndrome more precisely, but we believe that its characteristics are now sufficiently clear to differentiate it from poliomyelitis, epidemic myalgia, glandular fever, the forms of epidemic encephalitis already described, and need it be said, hysteria end quote. Apparently it did need to be said, and I guess it wasn't said loudly enough because you choose to ignore it. They choose to ignore it. And those mcavedy and Beard papers became an absolute hit, and they led to a decades long battle to get the medical community to recognize that this is a disabling medical condition in need of treatment and care, and not just like psychotherapy. Nicknames like yuppie flu or twentieth century illness popped up to reflect this disturbingly popular feeling that this was just an imagined disease by people who felt disconnected to their community or who were bored and wanted attention from a doctor just stressed out. By discrediting the physical basis for this condition, mckevidy and Beard and subsequent doctors set back the field tremendously, making it more difficult to get funding for research, discouraging medical interest in the condition, and breaking the trust that patients have for their healthcare providers. Not to mention what never being believed does to a person. There was still a strong contingent of physicians and researchers who fought against this mass hysteria diagnosis, including doctor Melvin Ramsey, who also got the word benign dropped from benign myalgic encephalomyelitis and the nineteen eighties to reflect that like, no, this may not kill you, but it is severe, it can be severely disabling, certainly not benign. Ramsey also published the first diagnostic criteria for EMMY in nineteen eighty six, and it was like one of the first clear ones that people could finally use to be like, this is a diagnosis. And around this same time, in the nineteen eighties and mid nineteen eighties, a couple more outbreaks of what seemed to be mononucleosis happened in the US, specifically in Nevada and New York, and these cases were linked to epstein bar virus, leading to the name epstein bar virus syndrome, and research later cast doubt on that connection or at least like ebv being the universal call. I think at this point people were still seeking a universal.

01:18:03
Speaker 4: Cause, which which one makes sense.

01:18:06
Speaker 3: Yeah, And so the CDC then once that, once that connection was kind of on shakier ground, the CDC came up with the name chronic fatigue syndrome in nineteen eighty eight to be more quote neutral and inclusive. And like we've talked, we've talked about the issues with this name, largely with being stigmatizing and trivializing. And so hopefully we'll be getting another name change in the future and hopefully that will take you know, patient opinions into account, like not be nice, maybe have people with macfs be part of the conversation. Anyway, So mecfs finally began to gain some broader medical support in the twenty tens. The twenty tens not long ago, Yeah, as studies came out showing immunological differences in people with me E CFS compared to those without the condition. And this was a really important development because it meant finding new avenues for treatments, conducting clinical trials, and developing treatment plans which up to this point had pretty much focused solely on mental health strategies as opposed to a biological approach. Of course, like I really want to emphasize that addressing the mental health aspect of this and other chronic diseases, and just like life in general, is a critical part of treatment. But the labeling of this disease as solely of psychological origin as a result of too much stress, it shuts down other avenues of research or treatment which could bring much needed relief to someone. And I understand the argument that this tendency of medicine to declare a disease quote unquote legitimate only if it has a detectable biological as opposed to mental origin just further stigmatizes mental illness. But I think the point is bigger than that that maybe by fixating so much on this mind body divide and the need to categorize things as psychological or biological, does a disservice to everyone. Patient, physician, researcher alike. We know that our mental health can affect our physical sense of well being, and we likewise know that our physical health can very much affect our mental sense of well being. The road can go both ways and it can be entirely parallel, as in, our physical health may have nothing to do with our mental health at any given moment, and vice versa. MECFS has shown over the centuries, really if we go back to neurothenia, that we miss the big picture, if we're obsessed with the individual parts. Categorizing MACFS solely within psychiatry has invited victim blaming and gaslighting, where a healthcare provider can say, your test came back normal, there's nothing wrong with you. You just lack the resilience to deal with the modern world. Oh, the CBT I've prescribed for you isn't working. It's because you're not trying hard enough. And to persist with that approach, solely with that approach, when we have evidence to the contrary evidence, which you thoroughly explained to Aaron, it's regressive. It takes us back to at least the mass hysteria of the nineteen seventies, if not straight up back to Freud. Do we really want to be with Freud at this point? Please? Let's not. And similarly, medicine as a field I think has really underappreciated, at least until recently, the mental health impacts of diseases, chronic diseases in particular. The bottom line that I'm trying to make with all of this is that I am once again asking you to believe people, to listen to people, and to remember that we don't know everything. And so with that, Aarin, I'm handing it over to you.

01:22:00
Speaker 4: Oh what a place to take over from I. Oh, I agree entirely. Let's take a quick break and get into more, honestly of the same and some numbers of what's what we're dealing with right after this break. You're not going to be surprised to know that we don't have great numbers, But let's talk about what we have in the US public health agencies and the CDC estimate that between eight hundred and thirty six thousand and two and a half million people just a pretty huge range there in the US are living with MECFS. Okay, a significant number of people who likely meet these criteria have never gotten a diagnosis.

01:23:25
Speaker 3: So can you tell me more about that?

01:23:27
Speaker 4: Yeah, I can also tell you more because there is also a difference in severity. It cannot be stressed enough I think how debilitating MECFS can be, and at the same time, there can be a wide range. So it's estimated that only about five percent of people recover to their pre existing like pre illness baseline, So almost everyone who has a diagnosis or who meets criteria for MECFS will not fully recover. About twenty five percent of people with MECFS are estimated to have severe or very severe CFS or me meaning that they are housebound or bedbound. They are so ill that they can't leave their house, They cannot do things like go to the grocery store. Sometimes they don't have the strength to get out of bed, like we talked about in long COVID. This can be a severely debilitating disease for about twenty five percent of people with MACFS, which means that seventy five percent of people are struggling with very similar symptoms and somehow still functioning, which is like, it's just so depressing, I think. Because the other thing is that when we look at the statistics in terms of who gets diagnosed with MECFS across the board significantly. It's a significantly higher risk factor to be assigned female at birth. People assigned female at birth are like one and a half to two times more likely to have MECFS then people assigned male at birth. What are the biological underpinnings of that? We still don't know, right, And we've talked a lot about these kind of like sex differences in disease, things like migraines, things like long COVID And then exactly, yeah, we don't know necessarily what these biologic underpinnings are lupus, but it exists, right, People assign female at birth significantly more likely to have MECFS. But also, you are significantly more likely to be diagnosed with MECFS if you're white than if you're a person of color. Is that a biological basis or is that lack of access? Is that lack of recognizing, is that lack of like b being able to get a diagnosis because nobody believes you in the healthcare system. Right, So there's a lot, there's a lot. It's also suggested and I think that this is, like we've talked a lot on this podcast about how we don't like to just look at like the economy or like the numbers of like dollars lost. At the same time, what I think is astounding is that a lot of studies suggest that only about half of people with mecfs are able to work at all, and about nineteen percent of people with mecfs are able to work full time. And like, I do not think that we should base someone's worth on their ability to work full time, especially in America, where our work culture is ridiculous. Your worth is not tied to your productivity. At the same time, for an economy that is hugely important, how are we ignored up to two million people, half of whom can't work because of how debilitating their real illness is. Like, how are we ignoring this to the extent that we're ignoring it? How is this still not taught in most medical schools, because, by the way, it's not it's not on the curriculum for most medical schools. I didn't learn about mecfs until I was in residency.

01:27:25
Speaker 3: I'm sorry, what yep. I had a.

01:27:26
Speaker 4: Patient who has MECFS, and that was the first time that I had heard the term myalgic encephalomiolitis because it was not taught at my medical school.

01:27:36
Speaker 3: I am speechless.

01:27:40
Speaker 4: Yeah, you should be. And that's not just me saying that. That is straight from the CDC website, that it is not on the curriculum for a lot of medical schools, not just fine.

01:27:51
Speaker 3: Two million people up to like over two million people in the US, and we.

01:27:55
Speaker 4: Wonder why people can't get a diagnosis. Okay, you never heard of it, You can't diagnose it, right, if it's not on your differential, then it doesn't exist. And that's just the US. Globally, the estimates are all over the place. They are not great. Most studies cite anywhere between seventeen and twenty four million people likely live with MACFS. A lot of prevalence studies try and estimate like global prevalence at around one percent, but again it's who knows. We just don't. We don't have good data on this. But what we know is that we are talking about millions of people who are living with a debilitating illness. And at this point we do not have any specific treatments for MACFS. We have nothing that approximate a cure, We have nothing that targets the underlying dysfunction because we still don't know what that underlying dysfunction is or how many different disorders there might be that we are calling MECFS. So that doesn't mean we have nothing. Hope is not all lost right now. Treatment largely focuses on symptoms and getting back to functionality.

01:29:18
Speaker 3: Okay.

01:29:19
Speaker 4: An important thing that I want to mention at the top is that it used to be the case that something called graded exercise therapy or GET and CBT cognitive behavioral therapy, which I love for indications like anxiety or depression or panic disorder that have really good evidence, are not effective for MACFS period They used to be recommended mainstay of treatment. No longer, that is not the thing. One thing that is often recommended as treatment and most of the data suggests that it is helpful is something called pacing. And this is kind of like I think of it as like the opposite of a graded ex exercise therapy. It's not trying to increase your activity. It is trying to do only the amount of activity that you can without exerting yourself to the point that you end up with post exertional malaise. Because with someone with MACFS, if they exert themselves to that point, the recovery can be immense, and it can take significantly longer to then get back to just where you were before you exerted yourself.

01:30:27
Speaker 3: I just I was thinking about this pacing and how difficult, Like how do you know yep, that you pushed yourself too far until you know?

01:30:39
Speaker 4: Like, yeah, it's so hard. I think one of the things that's so hard is that it relies so much on someone having to be so hyper aware of their abilities in a way that most of us are not, Like I don't think that hard about what I could or couldn't do, And so someone living with MACFS they have to do that for themselves all the time. Like that alone, that cognitive load is exhausting, right, So yeah, that's that is really difficult. But pacing can be really helpful in alleviating that fatigue and in avoiding that post exertional malaise. Things like CBT could still be helpful in combination with other treatments if there is comorbid anxiety or depression, because, like you mentioned Aaron, mental health in living with chronic disease like can severely be affected just by living with chronic disease right, and then we get into kind of more medicine I guess based treatments of like, how are we trying to target some of these underlying biologic changes that we know are happening. And here there's a whole range of things that have been tried, some of which have evidence that there are benefit, a lot of which are still under investigation, but that doesn't mean that people might not be using them already. And so this includes even things like using anti virals to try and target herpes viruses in people who have high viral loads that has been shown to maybe be beneficial for some people with MACFS. A really interesting one that has a lot of good data again for some people with MACFS, is using low dose nowtrexone. Now trexone is a medicine that we also use for treatment of alcohol use disorder or opioid use disorder and things like that. It's a I don't need to get into the mechanism, but using it at really low doses helps target inflammation and bring inflammation down overall because while it targets opioid receptors, it also targets like other receptors that help reduce inflammation. There's also been other like immune modulators that people have tried to target. If there's auto to bodies that are going on for some people, perhaps you kind of asked, are there immune system things that we can do? People have tried. But the other big category that I think is really promising and needs a lot more research because at this point, most of these treatments are in the stage where they're kind of supplements that are non FDA regulated and they're not treated as pharmaceuticals yet. But that is using things like antioxidants and metabolic precursors, So that means things like ubiquinol, which is reduced co Q ten. Anyone who shops at Costco might see that you can buy coq ten on the shelves.

01:33:39
Speaker 3: Right, Oh, the only place for you now, it's just.

01:33:44
Speaker 4: Where I see. Costco has such a huge supplements area, like, oh, yeah, you can't ignore it, and we have feelings about supplements. We're going to do an episode on it.

01:33:55
Speaker 3: Later, we are, yeah, we are.

01:33:57
Speaker 4: But in this case there is evidence that things like ubiquinyl and selenium or even using NADH which again, these are all precursors in those energy metabolisms that our cells are doing in a lot of cases these are helpful in reducing the symptoms of ME and CFS. But again we'll get into the issues with supplements and the fact that they're not necessarily FDA regulated, So how do you know that you're getting a good one. That's part of the issue here is like these things need to be researched so that they're FDA regulated, so that we know that people are getting things that are actually going to help them based on the data. So there's a lot of work I think being done. And the other huge area of research that will help us eventually develop better therapeutics is trying to identify biomarkers, because that will help us with the diagnostics, right being able to more definitively diagnose someone with MACFS or distinguish maybe between these different variants perhaps of MEC, but also eventually then develop therapeutics to target if there are biomarkers that are targetable, like can we reduce this specific inflammatory cytokine, can we increase these T cell functions? I don't know. We don't have that yet, but that is where I think the research is going and needs to go to be able to actually help people the most. Yeah, that is what I know about MACFS.

01:35:32
Speaker 3: There's a whole lot we know and a whole lot we don't know, as surprised, and speaking of stuff we do know, sources, sources, Okay, So I have so many sources, Aaron, it is overwhelming, and I just want to before I want to preface this by saying that there are a lot of sources that you will find on our sources table on our post for this episode. And not all of those sources are like for information that is useful or helpful or accurate, but it's more about like showing how far we've come. So, for instance, I have cited those papers from nineteen seventy that said that MACFS is mass hysteria, so just keep that in mind. But I will say that one of the best sources for sort of tracing the history of MACFS is called Beyond Myologic Encephalomyelitis slash Chronic Fatigue Syndrome Redefining an Illness, and this was published by the Institute of Medicine in twenty fifteen.

01:36:35
Speaker 4: I can also vouch for that it was a really great source for some of the biology as well. If you want more details on the immunology of MECFS, there's a paper from Horning at All in twenty fifteen called Distinct Plasma immune signatures in macfs are present early in the course of illness, as well as a paper from twenty twenty three by mass Code at All that was Biomarkers from Myologic intef myelitis and Chronic Fatigue Syndrome a systematic review. But we will post the sources from this episode and all of our episodes because there's so many more on our website This podcast will kill You dot com under the episode step.

01:37:15
Speaker 3: Thank you again so much to the providers of our first hand accounts. I it just it really does mean so much to us and to our listeners.

01:37:25
Speaker 4: Yeah, thank you so much for being willing to share something so personal in your stories. We really appreciate it.

01:37:32
Speaker 3: Thank you to Bloodmobile for preventing the music for this episode and all of our episodes.

01:37:37
Speaker 4: Thank you to Tom and Leanna for the wonderful audio mixing.

01:37:42
Speaker 3: Thank you to Exactly Right, and thank you to you listeners.

01:37:47
Speaker 4: We hope that you liked this episode. These two this kind of series, a little bit kind of.

01:37:51
Speaker 3: If MAB series. Let us know what you think, yea, and a big thank you as always so much. Thank you to our wonderful patrons. We appreciate your support so so very much, so much. Well, uh yeah, I guess. Until next time, wash your hands you

01:38:10
Speaker 4: Feel the animals.