If you had to guess ME/CFS cause, what'd you say?

[Woozy]

if you had to guess or say what you think causes ME/CFS from your experience, what would you say it is? I would guess it is a metabolic/hormonal cause somewhere. Now you. what do you guess/say?

 

[Trish]

I don't think one or another person's experience can possibly give any answers to the cause of their ME/CFS. For that we need high quality scientific studies on many patients. If you explore this forum you will see many papers are published with all sorts of hypotheses.

There is also the question of what you mean by cause.
There are predisposing factors, genetic and environmental, precipitating factors including infectious diseases and possibly other assaults on the body's equilibrium like vaccines, surgery etc. Then there are perpetuating factors, hypotheses range from mitochondrial dysfunction, to inflammation, autoimmunity, persistiing virus, and many others.

As a lay person without the detailed knowledge of biochemistry, cell biology and all the other specialisms that study the human body, I cannot possibly make any sort of sensible guess as to what it might turn out to be.

But it's fascinating learning a bit more each time I read a scientific paper and get glimpses of just how incredibly complex the human body is.

 

[Barry]

As @Trish says, it's not for laypeople to presume any causes of ME/CFS. We are Science for ME/CFS after all. But if you were instead asking what reported correlations might fit with our own experiences, post viral issues would be one. My wife had an operation and went down with a nasty bout of flu immediately after. What seemed to us to just be a very slow post-op recovery, proved in fact to be the onset of her ME.

 

[oldtimer]

Welcome to the forum @Woozy .
I've driven myself crazy over many years trying to sort it out. Now I'm just waiting it out and alternately guffawing and fuming at all the money wasting psych stuff that keeps coming like a never-ending sewage overflow.

 

[RedFox]

Low grade neuroinflammation. In interesting paper is Broken Connections: The Evidence for Neuroglial Failure in ME/CFS (S4ME thread)

An infection, another event, or an seemingly spontaneous change causes glial cells in the brain to become hyperreactive to changes in the body (including the brain) that come with physical or mental activity. I liked this hypothesis paper because it attempts to explain both the existence of PEM and its delayed nature, which most ME/CFS hypotheses just handwave away. Many people talk about impaired energy production, but not why that causes PEM in ME/CFS as opposed to weakness, immediate exercise intolerance, and fatigue.

 

[EndME]

Personally my guess on what ME/CFS is change throughout time depending on my personal bias of my own lived experiences and is even more so driven by the bias of which research has recently been published. The only thing I know for sure is that there isn't a simple explanation and studies looking to oversimplify things by reducing it to some phenonmenon we would have long since discovered are useless from the start.

Similarly the currently dominating hypotheses for Long Covid are:

• Viral Persistence
• Immune Dysregulation
• Latent virus reactivation
• Autoimmunity
• Dysfunctional Neurological Signaling and/or Neuroinflammation
• Coagulation problems
• Disruption of the Microbiome

I expect the list for ME/CFS would be extremely similar. Every item on the list itself contains various different theories. For example viral persistence can mean a viral reservoir or no reservoir but viral antigens. Furthermore different theories can be taking place in different people at the same time and can be heavily interacting with each other.

Today my personal belief is that the answer lies somewhere amongst autoimmunity, immune dysregulation and Dysfunctional Neurological Signaling and/or Neuroinflammation. If they once again find more and better evidence for viral persistence my beliefs are once again shifted into that direction.

Hypotheses are typically a reflection of the evidence and studies of that time. For example before the RCT with Rituximab CD-20 B-cell mediated autoimmunity was probably the most popular hypothesis. Now it is clear that if ME/CFS is an autoimmune disease that it won't just be driven by CD-20 B-cells and it also won't just be driven by those type of autoantibodies which have been searched for or looked at over and over again.

Most importantly Long Covid and to a slightly lesser degree, but still very much so ME/CFS, are extremely heterogeneous conditions. For Long Covid it is clear that there will be different driving causes in different people, I don't always expect ME/CFS to be one homogeneous condition with one root cause, I expect the answer will be far more complex and that there are different things that today are all considered to be ME/CFS. I think the complexity can be compared to MS and even though they know a million times more there, one still can't pinpoint one cause. This reflects the complexity of the disease and also the human body in which these theories are embedded in.

As a layman without any deeper biological, chemical or medical knowledge I can only asses the quality of current research on the basis of pretty basic faults or flaws in the methodology or reasoning. All to often these are unfortunately present.

I currently think we can get closer to an or one of the root causes, by doing well controlled studies of things that might only be happening downstream or are a reflection of certain symptoms. To me assessing mircocirulatory problems in vivo using modern measurement techniques seems like one of the most hopeful avenues to do this.

 

[Kitty]

I have some long-standing thoughts, but none of them are explanations:

• When it is worked out it sounds obvious, and people wonder why it took so long.

or/and

• It was elusive because it couldn't have been measured before the introduction of a new technology, or an unexpected way of combining old ones.

or/and

• Something needed to be understood or accepted more widely, though it might not be a new concept. (It wouldn't surprise me if someone at a less well-known university who didn't publish in English suggested it in 1953.)

 

[CRG]

A question I've been concerned with for close on 40 years. Only honest answer = "I don't know".

Specualtion is always fun, and having a favoured answer can give comfort by adding a false certainty to a confusing world, but getting overly attached to an explanation that has no fundamental science to support it only ends up getting in the way of real understanding. The one thing that I do now think is indicated by what data there is, is that what we call ME/CFS is not a single homogenous 'disease' but a set of conditions that in varying degrees share impairments of function; the what, why and how of those impairments remain to be established.

 

[Trish]

I could of course add the obvious conclusion from my own and countless others' experience: ME/CFS is NOT caused or perpetuated by fear of exercise, avoidance of exercise or deconditioning.

These hypotheses are so clearly contradicted by my own and others' experience that it would be laughable if it were not a tragedy that these hypotheses still gain traction in so much of the medical world, and have enabled careers and national guidelines to be built on them.

 

[Sean]

*shrugs*

Let us know if you ever find out.

 

[Mij]

I'm more interested in the physiological processes of delayed PEM associated with M.E and other post-infectious syndromes. I hate PEM but find it fascinating.

 

[Mij]

To add, symptoms related to autonomic dysfunction arising in para infectious or post infectious period is interesting too and still hasn't been studied very much. It is so disabling for many.

 

[Creekside]

My preferred hypothesis is a feedback loop in a fairly small number of brain cells, probably glial cells, that locks those cells in an abnormal state, with various symptoms resulting from that. Unfortunately, it's a hypothesis that would be hard to verify (can't just dig around in live brains). I do think it's treatable, but needs just the right chemical that crosses the BBB and doesn't have unwanted effects. I also think we'd find a treatment more quickly by testing lots of different chemicals and seeing what effects they have on ME symptoms; basically a black box approach. I think there'd be plenty of volunteers, since even a small chance of success is better than what the present "search for abnormalities" offers.

 

[Hutan]

Several posts on CFS and ME as distinct diseases have been moved to Diagnosis of ME and the use of the labels ME and CFS.

 

[SNT Gatchaman]

Agree with others that personal experience of symptoms probably doesn't inform much of biological mechanisms. If it did and given that pwME are probably some of the most invested and committed patients, we'd have published the answer a while ago.

I could of course add the obvious conclusion from my own and countless others' experience: ME/CFS is NOT caused or perpetuated by fear of exercise, avoidance of exercise or deconditioning.

100%. Things we can definitely rule out.

I have some long-standing thoughts, but none of them are explanations:

• When it is worked out it sounds obvious, and people wonder why it took so long.

or/and

• It was elusive because it couldn't have been measured before the introduction of a new technology, or an unexpected way of combining old ones.

or/and

• Something needed to be understood or accepted more widely, though it might not be a new concept. (It wouldn't surprise me if someone at a less well-known university who didn't publish in English suggested it in 1953.)

I think Kitty's point 2 will be the relevant one here. For point 1, I don't think it will be obvious in hindsight, but I do think understanding our disease mechanism will revolutionise medical understanding of (very) many other diseases, so there will be a "why you take so long?" response.

if you had to guess or say what you think causes ME/CFS

To answer the original question, and in the spirit of fun and speculation as we track the direction of ME and LC publications —

Spoiler: I think the core dysfunction underlying ME/CFS is

Lipids.

 

[LarsSG]

To be flip, I think ME is caused by infection, most commonly, but not exclusively, viral (and maybe other immunological events). Beyond that, who knows? It probably has something to do with the immune system.

 

[Creekside]

• It was elusive because it couldn't have been measured before the introduction of a new technology, or an unexpected way of combining old ones.

or/and

• Something needed to be understood or accepted more widely, though it might not be a new concept. (It wouldn't surprise me if someone at a less well-known university who didn't publish in English suggested it in 1953.)

I was quite surprised at some of the new discoveries in the past few years: whole organs, such as the brain's glymphatic system, which was a rediscovery, since it had been published and denounced and forgotten I think in the early 1900's. A more recent paper was on some microfilaments on glial cells, which people knew existed, but a new imaging technology allowed researchers to actually image them. A few days ago was a story about a new microscopy technique that combined two technologies to allow better imaging of the interior of cells and tagged molecules, so you could measure ATP concentration in or near a specific mitochondria, for example.

Technology progresses, but a weak link is the humans who don't bother to actually look and pay attention, preferring to blind themselves with past beliefs, or limit their studies to some self-serving goal.

 

[Kitty]

For point 1, I don't think it will be obvious in hindsight, but I do think understanding our disease mechanism will revolutionise medical understanding of (very) many other diseases, so there will be a "why you take so long?" response.

I didn't mean that it necessarily is obvious, but you know how things are sometimes so logical that it appears they ought to have been? Like the discovery of air, when we'd all been breathing it for millennia and knew it was a bit problematic if we suddenly couldn't.

There's a chance it could be one of those, but equally, it could be "Well, it's not surprising nobody unpicked that!".

 

[Hubris]

In my opinion, looking at all the features, ME is obviously some kind of immune illness.

I think it is obvious doctors have no clue how the immune system really works. We rely on fever to tell us if a person has an infection, we have otherwise no way to know. We can try to detect pathogens or specific antibodies but no way to know if a person just has an infection, generally speaking. I think that tells us everything about our lack of knowledge.

If you have a rash, a lot of the time doctors can't even tell if it's viral, bacterial, autoimmune or allergic. And that's exposed skin!

I think the main problem is the absolute hubristic nature of medicine that they can deduce there is no immune issue from some blood tests and half assed tissue studies. We are still in the stone age.

 

[Ravn]

I liked this hypothesis paper because it attempts to explain both the existence of PEM and its delayed nature, which most ME/CFS hypotheses just handwave away. Many people talk about impaired energy production, but not why that causes PEM in ME/CFS as opposed to weakness, immediate exercise intolerance, and fatigue.

This!

I've no opinion on this or any other particular hypothesis but it's absolutely the case that most hypothesis papers - actually, most ME papers, full stop - don't go beyond a vague "xyz may explain some PEM symptoms". I blame it on the f-word. Even researchers who have grasped PEM on an intellectual level still get pulled off track by the deeply ingrained easy familiarity of the concept of fatigue and/or the related lack of energy - so much easier to think about than the highly unintuitive nature of delayed PEM. Heck, this even happens to patients! (Just to be clear, I'm not saying people don't experience fatigue or lack of energy, just that it's time to shift the research focus.)

I've no idea what causes or perpetuates ME but I'm pretty certain there's a crucial clue hiding in the delay aspect of PEM. Once someone figures that one out we can hopefully reverse-engineer our way back upstream, if not all the way to the original cause then at least to a point where effective treatment is possible.

I didn't mean that it necessarily is obvious, but you know how things are sometimes so logical that it appears they ought to have been? Like the discovery of air, when we'd all been breathing it for millennia and knew it was a bit problematic if we suddenly couldn't.

That's my sense, too, something very very basic (not the same as simple). Though it may take new technology to be able to identify and measure whatever it is. As others have pointed out, we still know almost nothing about most processes in the body