perhaps organic acids testing could show something?
I don't think that's true, at least not in my experience anyway. People (myself included) are too quick to conflate "all in your head" with "making it up".
Things "in your head" can and do have real, physical, life-limiting, effects.
If it turns out that ME/CFS doesn't has a physical marker, then what? There may never be a way to verifiably test for it other than symptomatically. It's no less real for the people living with the effects, but there may be no pill to take, or injection to administer.
The problem is that ME/CFS is similar in presentation to other conditions such as for example certain kinds of depression. The difference is that exercise is thought to help with those conditions and exacerbates ME/CFS. Thus there are two different groups of people, one who you are helping by encouraging them to exercise and one who you are harming. If you can't tell them apart the system is bound to hurt someone.
Cochrane systemic review, "exercise therapy for chronic fatigue syndrome", 8 studies, 1518 participants
"Investigators compared exercise therapy with 'passive' control in eight trials, which enrolled 971 participants. Seven studies consistently showed a reduction in fatigue following exercise therapy at end of treatment, even though the fatigue scales used different scoring systems ... Serious adverse reactions were rare in both groups (RR 0.99, 95% CI 0.14 to 6.97; one study, 319 participants; moderate‐quality evidence)"
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6419524/
Fairly plausible, mitchondrial biogensis is an adaption to exercise, it may be impaired in ME/CFS patients, but not totally inhibited, and more mitochondria may lessen the severity of the pathogenesis of ME/CFS.
Hence it is important to make a distinction between the two, so you give proper treatment.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7988339/
First problem, I do not have ME/CFS, let's use the Maes et al (2012) scale. 0-5 scale, 5 being the worst.
"1 means mild exacerbations of fatigue/pain/neurocognitive symptoms following exercise (either cognitive or physical)" Yep, after a longer, harder than normal bike ride I'm quite fatigued, in quite a bit of pain (bad back, knee, shoulder), and can't think particularly well.
"2 means moderate exacerbations of symptoms following exercise; 3 means severe, incapacitating exacerbations lasting less than 24 hours;" Accurately describes what happens when I do HIIT style intervals that exceed my work capacity, or what it's extremely hot outside. Dreadfully exhausted, usually have to nap, or lay on the couch, every muscle hurts, extremely sore, difficult & painful to move for 24-72 hours.
I'm not saying ME/CFS does not exist, this is just a terrible indicator.
The worst part is making it so specific obscures the large body of existing research that would provide tools for treatment protocols here, eg work capacity in athletes.
I know you said you don't have CFS, but trust me - the fatigue we suffer after PEM is nothing like "normal" body fatigue after exercise.
I think we'll find a diagnostic test eventually. At least, I hope we do.
My experience (in California) is that a large fraction of doctors are willing to assume the patient is being truthful and another large fraction are willing to spend their time and energy only on patients who can prove they are sick.
It's proven to be the case. A repeat cardiopulmonary exercise (2-day CPET) is currently the only widely replicated biomarker for ME/CFS. Only ME/CFS shows a reduction in performance and a lowering of ventilatory threshold on the second day. Anyone else (sedentary, cancer, heart or lung disease, MS, depression) will show an improvement. [1]
A study this year showed a striking effect looking at the metabolites in urine after exercising female ME patients vs sedentary healthy controls. The ME patients just did not excrete metabolites as the healthy controls did. [2]
"This indicates that ME/CFS patients have a general metabolic dysregulation that is part of their exercise intolerance and PEM in which altered metabolic excretion is a contributing factor."
There's also a very simple clinical discriminator between ME/CFS and depression. If you ask a depressed person what they would do if they were suddenly cured, their answer will be "Not sure, I don't know, I can't think of anything, nothing really." If you ask someone with ME/CFS the same question, the response would be "Go to the shops, drive my car, walk on the beach, see my friends... etc".
To me, this argument does not make sense. Consider the example of Physics Girl (I linked the video in another comment). The video shows her before COVID, and after COVID. It's obvious that her COVID infection did something to cause her to go from being an amateur astronaut to being bed-bound. There is clearly some kind of imbalance, somewhere. We use biomarkers like CRP levels to determine whether someone has an infection, others for cancer, or any other disease. Why would it be different for this?
If we can identify some kind of biomarker... be it a protein, something in the blood, etc, and link it to COVID, then we can start testing treatments to see how they impact the biomarker.
I didn't really make an argument to "not make sense". Right now, ME/CFS may just be a collection of symptoms rather than a specific _thing_ that can be tracked, measures and cured. Or it may be a specific infection. We don't know.
Sure, it's compelling. But the plural of anecdote isn't data. It may seem obvious, but so far we haven't found the biomarker yet and must surely keep an open mind that one may not exist.
I'm not saying we should stop looking, but that the thing we're looking for may not appear.
I think a more logical approach (for me) would be to say that there might be multiple biomarkers which could present ME/CFS type symptoms in different ways.
Dr. Bhupesh Prusty has recently given some lectures on his discoveries related to Fibernectin, for example. That could be a massive breakthrough, but we need more studies on it.
One other data point that might interest you: apparently a large percentage of ME/CFS patients are finding relief through valtrex. Apparently there is some relation to the herpes virus, although nobody understands how or why.
_Are they though?_ This needs a citation. What constitutes large? A majority? That's unlikely, especially in the UK where medications aren't prescribed unless there's measured clinical value in it. I'm sure some are finding relief, but until we know how many and how much relief it could just be a placebo effect, right?
I hope that anyone affected by ME finds relief, but the discourse online about it always confuses me. There's always a slight undercurrent of "those mean doctors" and a breakthrough _just_ on the horizon:
"That could be a massive breakthrough, but..."
"apparently a large percentage of ME/CFS patients are finding relief..."
"Apparently there is some relation to the herpes virus, although nobody understands how or why."
In reality, nobody actually knows. Some scientists have got some ideas, some of which stand up to some form of scientific scrutiny. But that's basically it.
It's also why I opened my initial post with "There needs to be more research into this horrible disease."
https://iv.iiarjournals.org/content/invivo/21/5/707.full.pdf
Other trials into antivirals have been negative.
This study screened for active vs latent on number of viruses in patients vs assumed health controls, bottom chart here is what you would evaluate Valtrex effectiveness against.
https://translational-medicine.biomedcentral.com/articles/10...
EBV, HHV6 and HHV6 tend to reactivate during stress, but don't typically cause symptoms. I think what we're seeing in ME/CFS is this reactivation, but it's not necessarily what is causing the problem (if it was, antivirals would help, but they don't).
I was suggesting to crossreference Valtrex effectiveness against the activated virii in the study I linked. If Valtrex is not effective against the reactivated cohorts, we need more falsification around antivirals <-> ME/CFS.
From the article:
>Viruses can trigger ER [endoplasmic reticulum] stress, perhaps explaining why ME/CFS and related conditions often arise after infection.
Since you mention herpes, I'll bring up what I've read about Epstein-Barr (EBV) (which belongs to the herpes family of viruses). It's estimated that 90% of the global population will contract EBV in their lifetime. In most people, EBV goes dormant for after the initial infection is cleared and more or less stays that way for life. But in some people, for unknown reasons, it can chronically reactivate, triggered by stress, other illnesses, immune dysfunction episodes, etc. Apparently it loves to hang out in the spleen, although I believe it has been found to reside in other organs as well in these cases of chronic reactivation.
I would be shocked if this were the only virus to do so, but at present it seems to be the most studied, perhaps because EBV is fairly strongly correlated with a bunch of cancers, auto-immune disorders, and chronic conditions (including MS as recently demonstrated in a huge study by the VA, n=10,000,000). Very interesting and important stuff. I look forward to further research into these mysterious long-term effects of viral infection.
We know that infections cause sickness behaviour (fatigue, depression, etc.) due to the effect of the cytokines on the brain. The interesting thing is that the brain itself releases similar cytokines in response to mental stress, and mental stress also activates the glial immune cells in the brain.
Infections also activate the HPA axis (the body's stress system) in the same way as mental stress does. This is to give the immune system energy to fight the infection, and also to prevent a fatal over-reaction by the immune system. Chronic long-term stress can result in a blunted HPA axis response, and this is commonly seen in ME/CFS.
Patients who have been bedbound with ME/CFS report that they were trapped by fear that there was something wrong with their bodies, and they felt fear when going outside or doing anything, and this caused further symptoms. Reducing that fear, and experimenting with activities again in a calm manner seems to be key to recovery. Looking at some of the tweets from physics girl, it looks like she may be stuck in this state.
Doctors, generally, want the best outcome for their patients. I find it hard to believe that they're doing something actively harmful that's against accepted best practices, informed by scientific literature, because... they hate their patients?
If there truely were thousands of papers showing a specific biology for the disease that could be targeted and treated why would any doctor ignore that?
Any illness with primarily neurological symptoms have a history of medical malpractice and gaslighting.
As early as 1944, an author in the Journal of Nervous and Mental Disease remarked: "The history of prefrontal lobotomy has been brief and stormy. Its course has been dotted with both violent opposition and with slavish, unquestioning acceptance."
The last recorded lobotomy in the United States was performed by Dr. Walter Freeman in 1967 and ended in the death of the person on whom it was performed.
Let's assume that all doctors fit your description. (I don't agree, but let's go with it.)
What's the alternative? I just can't accept that the vast majority of medical professionals are ignoring a potential cure or refusing to accept that one for ME may exist because it might hurt their egos.
Being medical professionals doesn't educate them away from having the same human flaws and cognitive biases that we all are capable of.
I remember learning about a physician who helped his sister with child birth and she died. He was aware of the washing hands but ignored it. I believe he ended up committing suicide as he wasn’t able to cope with basically killing his sister due to his ignorance.
> "He didn't discover it, he was told by midwives over and over and over until he looked into it. Midwives at the hospital observed that when doctors delivered babies, mothers were at a higher risk. Any housewife knew that food would spoil faster if handled with dirty hands and they always used vinegar solutions to clean their hands, tools, and surfaces. Any housewife would do this and midwives did it because mothers and their babies are more important than pumpkin preserves. Only doctors never washed their grubby hands while it was a deeply ingrained habit in most midwives. Semmelweis listened to women. No wonder they locked him away."
Which is uncited/unsupported, but back in the Black Death time of the 1660s: "The villagers established a system of boundary stones around the village’s periphery, boring holes into the rocks and leaving coins soaked in vinegar – they believed it acted as a disinfectant – in the holes. Merchants from surrounding villages would collect the money and leave bundles of meat, grains and trinkets in return." - https://www.bbc.com/travel/article/20151026-the-sleepy-villa...
And from the same Reddit thread:
> "Oh again with this "before Germ Theory no one knew anything about disease!" bullshit. We always knew dead and dirty things caused disease. Dead animals for artillery ammo, dead animals buried by wells, leaving your swords in latrines. We also knew how copper and silver could help heal and prevent disease."
So, it's not like Semmelweiss proposed Germ Theory, or was the first to observe a connection between death and disease, or between 'disinfectant' of some kind and reduced disease. And https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1299347/ says:
> "(notably Alexander Gordon of Aberdeen) had shown that puerperal fever was contagious some 40 years before Semmelweis. The mortality rate in lying-in hospitals did not fall but rose after Semmelweis' treatise was published, and his ‘much-cited but seldom-read’ thesis is immensely long (over 500 pages) and so badly written that it is almost unreadable. [...] Semmelweis deserves to be remembered for his observation in 1847 that making medical students wash their hands in a disinfectant solution before going from the post-mortem room to the lying-in wards of the Vienna lying-in hospital, led to a fall in mortality due to puerperal fever from a very high level to a moderate level. [...] After his death in 1865, Semmelweis was totally forgotten, not only in Vienna but also in Hungary where he was born and to which he returned in 1850. It was not until the late nineteenth century that the introduction of Listerian antisepsis applied to obstetrics led to a steep fall in deaths from puerperal fever. Only then was Semmelweis' work recalled and his faults forgotten."
Which is fine, he shouldn't be knocked, but how did it take 200 years for humans to decide to use the tools that were already internationally known (vinegar) to a large number of people (housewives, midwives) to avoid some kind of death-related contamination, on childbirth and hospital and post mortem scenarios? And why did it take a guy writing a 500 page near-psychosis rant?
Was that low hanging fruit and if so, how much more of that is still in the world today?
If 90% of your patients come in sneezing and it's a flu for 30 years, then you generally give them advice for handling a flu and it works most of the time. But that also means you have a tenth of the experience handling the edge cases, at best.
Confounding variables make this a lot worse, like people having multiple symptoms, or not telling the doctor things because they felt dismissed before, or that they stopped seeing them because they gave actively harmful advice.
Having a lot of experience with doctors is what has convinced me medical training needs reform. Doctors actively ignore patients telling them objective factual reasons their advice is incorrect or harmful, and treat you as a hypochondriac for arguing.
I have stopped seeing a number of doctors over the years after they looked at my medical history and said "let's try X again", and when asked why, "just to see", when I have already tried X and two or three other medications in the same family as X, in the history (often from their own larger department, not something I provided), in the last 2 years.
I have stopped seeing doctors over me telling them that raising the dose of a medication made me much worse and having them then cut the visit short by leaving the office, saying they were late for something else, and telling me they were writing a script for double the dose as they left (and no, the drug in question did not have strange dose-response relationships like, say, Seroquel).
I have stopped seeing doctors over them insisting I just had a cold when I told them I was too exhausted to reliably walk two blocks to their office without an escort, every day for a week, not sleeping, and unable to keep any food down, without changing their mind, when I turned out to have pneumonia.
None of them were trying to be harmful.
This is a baseless claim, there's a Cochrane review showing exercise is beneficial. Pacing appears to be a common strategy, and it's exercise in of itself.
>In the 1980s they found numerous immune and metabolic dysfunctions in sufferers as well and the list of physiological things wrong has steady increased since
None replicated as yet.
??? The Royal Free is in Hampstead, and still exists. St Thomas’ is on the south bank of the Thames at Westminster bridge.
How did politicians fuck up?
That is all a political failure that has led to no progress on the disease and widespread abuse of patients.
https://www.ninds.nih.gov/about-ninds/who-we-are/advisory-co...
To me it sounds like trying to do rocket research in the hope of reaching the moon back in 1900.
Doing it once the time is ripe is a completely different matter. I hope it is ripe now.
Yes, but what part of “a gentleman’s hands are always clean” do you not understand?
Another: 19 September 2022, US President Biden declares COVID to be "over" https://www.youtube.com/watch?v=tHT1enFH2sI
Meanwhile, it is easy to get Pfizer and Moderna vaccines (mRNA based), and hard to get Novavax (protein based). By hard I mean impossible. mRNA are not well understood, have nasty side effects for some people (including me), and lose their efficacy after a few months, thus the need for boosters. You can verify this with blood tests that show antibody levels. With Novavax, which is based on technology that's been around for 20 years, it appears (based on studies) that it keeps its efficacy for at least a year after multiple doses, and it has minimal side effects (including my own shot).
That said, many governments have relationships with Pfizer and Moderna, and so these vaccines are easily attainable, while no such relationship exists with Novavax, and it is impossible to get it. I say impossible after asking about 50 doctors, contacting pharmacies, and finally contacting Novavax themselves, who told me that it is not possible to get until the new mix comes out.
So why would a vaccine that seems to actually work be unavailable, while ones that do not work are easy to get?
I realize that this is more a commentary on COVID than ME/CFS, but I'm arguing that they are very similar. Just consider Physics Girl, who contracted COVID a year ago, and is now bed bound: https://www.youtube.com/watch?v=vydgkCCXbTA
It's very easy to frame what doctors say like this, but in my experience at least that's not really what they're doing. A doctor is a classification machine - they take your symptoms as inputs and output a disease or a syndrome, hopefully with mitigation measures associated with it.
When my wife had long covid for 3 years and doctors couldn't find anything wrong with her a neurologist diagnosed her with a "functional neurological disorder" and suggested psychiatry. My wife felt dismissed and was really mad about it, but the reality is that some sets of symptoms are psychosomatic, and psychiatry can help, so if the neurologist saw 100 people with my wife's symptoms and made the same recommendation to them all, some of them would benefit (as opposed to her making no diagnosis and none of them benefiting)
I think it's unlikely, however, that symptoms are never psychosomatic. If what we think had no effect on how we feel then the placebo effect wouldn't exist
Being told you're crazy is a net nocebo.
I was 32 at the time. Never had a panic attack before. Sometimes felt something was wrong but clear thinking and a few deep breaths and I was okay. Not this time.
In the subsequent couple of months I had a few more random panic attacks - once on a highway; I had to pull over.
So I went and saw a therapist. I don't think they actually helped reduce the attacks - the frequency dropped with time, together with the fatigue. Now, two years later, I only have the mildest of attacks (and I'm at around 60-70% of energy). But they did help me calm down, gave me tools to deal with an attack when it happens and reduced my stress around the entire experience.
It was definitely money well spent, and as much as I can tell from being my own carer, clinically relevant.
After getting COVID, I went from being an avid coffee connoisseur to getting extreme anxiety from a cup (I've never had anxiety either). I switched to decaf for 2 years before finally incrementally building my tolerance back up. Several colleagues and random people I've met have had similar issues. It goes away over time, but is very real.
I went to a cardiologist and did a stress test. Nothing showed up and eventually it also went away. Note, I was a little stressed from work, but nothing unreasonable. Home situation wasn't too bad either.
however, about ten years ago my general feeling of anxiety suddenly got much worse. I was able to cope with it using all of my usual anxiety coping skills but it seemed kind of off that everything had shifted. I went onto Lexapro, which helped. But then in 2019 or so things really started getting nutty again, where I'd be up all night with panic, often waking me up in the middle of the night, would be up until 5 am, finally fall asleep, then would have another during-sleep panic attack that would last all day.
Turns out I have a node in my thyroid producing thyroid hormone. I now take a very low dose of medication for hyperthyroidism and my panic-esque anxiety levels are kind of lower than they've been for like my entire life (still need the lexapro though, I am sure that my anxiety issues are not strictly the thyroid node).
Basically it sucks to have psychiatric illnesses that are standalone, but also compounded by other non-psychiatric pathologies.
We really need proper diagnostics for this condition, so that people can be diagnosed and not dismissed or even denied benefits and support.
Therapy didn't help but sertraline helped me a lot. I still have no idea what the root cause is, and I've never quite been the same since, especially my energy levels.
However, I am at least functional and can hold down a job!
No, because the only replicated findings are that stress (and infections) are triggers, believing in a physical cause is a perpetuating factor, and multi-disciplinary rehabilitation leads to improvement in about 2/3rds and recovery in about 1/3rd of patients.
https://my.clevelandclinic.org/health/diseases/9833-munchaus...
Using "chance of occurrence" is a major logical fallacy for diagnosis identification and can ruin the whole practice.
Also, when a patient succeeds in getting a correct diagnosis after trying multiple doctors, the previous doctors generally will not find out about their mistake, so there's a bias against them actually learning the right probabilities: you can expect them to be overconfident on this score.
You know, doctors told me for years that the pain in my chest and back was all because of my mental illness, even though my brother and mother both needed spinal surgery for Anklysoing Spondylitis by the time they were 60.
They dismissed me till I told them I wanted an MRI of my spine and chest and there it was, Non-radiographic axial spondyloarthritis, the precursor to AS. So not I can treat it so it does not process into AS. They all told me there was " physiological cause to symptoms".
There is a HUGE stigma in medicine against any pain in people with mental illness, it is their best excuse to not even look. That is why there is no progress.
Most diseases have a psychological component, but patients are seldom referred to a psychiatrist for treating their heart ache when they get an infarction.
I just mentioned these findings (and others about autoimmunity against the satellite cells in dorsal root ganglia) to my mum, a doctor specialized in physical therapy and rehab. She went into retirement this year and many patients with ME/CFS.
Her reaction: "So fibromyalgia is real now. I have a hard time believing it… I spent my career fighting it."
That being said, when in doubt, I thin that doctors should trust patients (defendants are presumed innocent, patients should be presumed to be sick).
Stiffing the ill to spite possible asshats is a bad societal bargain.
By all accounts, there is no way to test for or to treat CFS. Assuming it is real, and OPs wife did have it, what is to be done? The doctor ruled everything else out, and now there is nothing more they can do.
Much better to say "I don't know" than to give a confident diagnosis just because you've run out of things to test for.
For diagnosis, there are clear diagnostic criteria, including the presence of post-exertional malaise, which is very easy to recognize simply by talking to the patient. (“I went grocery shopping last week, and I didn’t think I’d overdone it, because I felt okay that afternoon, and I had a full night’s sleep, but I woke up the next day feeling terrible and I could hardly get out of bed all day.”) There is a lab test that can be done for it, but it essentially consists of making the patient “crash” by exercising two days in a row and observing how much worse they are the second day. It’s not recommended for diagnosis because it’s harmful (it can take months to recover from a bad crash) and, again, not necessary.
For treatment, there are a few supplements and prescription drugs that can help each of the symptoms. Many patients experience dysautonomia (it’s in the diagnostic criteria) and there are several treatment options for that (beta blockers, drugs to raise blood pressure, drugs to encourage sodium retention, and others, in addition to non-pharmaceutical options like increasing salt and water intake). The fatigue itself is harder to treat, but a few supplements have been found to help. Cognitive dysfunction is a major problem that is definitely treatable (with ADHD and dementia drugs); that alone is enough reason to get diagnosed and treated.
My wife had an emergency department refuse to treat her because they disagreed with an unrelated diagnosis that was in her medical record. Until she admitted that she was "making it up" and didn't have it, so they could "correct" the record, they would not treat her. She ended up having to leave and go to another hospital.
Depression is a comorbidity of chronic illness. It's hard not to become depressed when dealing with an unexplained illness.
Psychiatric treatment can reduce the contribution of the comorbid depression, which can create a net improvement for these patients.
Too many patients with chronic illness will refuse any psychiatric treatment because they are resistant to the idea, but they end up suffering more than necessary.
When doctors can't identify or treat the core illness, they can at least address comorbidities and work on increasing quality of life. Psychiatric care is at the top of the list for helping people's quality of life in these situations.
Fun fact, the drug Xywav which has been FDA-approved for narcolepsy (and ideopathic hypersomnia) has also been shown in studies to help with fibromyalgia. They even sought FDA approval for that but the FDA rejected it on the grounds that there are too many fibromyalgia patients and therefore the risk of abuse is too high (the drug is related to GHB).
It's heavily published on and widely accepted as valid by neurologists, but that does not make it true.
The concept with FND is that there is no identifiable structural pathology, but that the neural circuits are dysfunctional, and that this can be fixed with things like cognitive behavioural therapy. This is typically framed to the patient as "the hardware is completely OK, there's just a problem with the software." (As most of this audience would recognise there is very little overlap between how brains work and how computers work.)
However, more advanced imaging techniques, such as 7T MRI are now showing structural abnormalities in these patients, which is a pretty fundamental problem for the above hypothesis. An attempt to rationalise this by FND proponents is made here.[2]
A recent example involves a 10yo child who developed a movement disorder following Covid.[3] Typically these would be diagnosed as functional movement disorder [4][5][6] and psychological therapy advised. However this group showed that in fact it was due to a neuroimmune pathology, with auto-antibodies forming that targeted some portion of the basal ganglia. The patient recovered completely with immunosuppression.
[1] https://www.bmj.com/content/325/7378/1449
[2] https://neurosymptoms.org/en/faq-2/can-people-with-fnd-have-...
[3] https://link.springer.com/article/10.1007/s00415-023-11853-5
[4] https://movementdisorders.onlinelibrary.wiley.com/doi/10.100...
And that's ignoring that there is a mechanism normally preventing this. And what happens when you become allergic to your own hormones is called a cytokine storm ... and it's serious enough that you can say comfortably that no doctor will miss it.
Autoimmune reactions may be the longest covid; cell/organ damage is another; it is also possible that people may have less-than clinically detectable viral activity, or viral activity in some "pocket".
I'm not a medical professional, this is not medical advice.
https://www.nih.gov/news-events/nih-research-matters/blood-t...
The scary thing is that there seems to be a vicious path, of COVID->long COVID->ME/CFS. We're not sure what makes COVID evolve into long COVID, which also means we have no idea how many people who catch COVID eventually wind up with long COVID or ME/CFS. And there is a total media blackout on the topic, seemingly because politicians don't want to admit they fucked up.
Hopefully once there is a way to verifiably test for it, a lot of things will change for the better.