How do we stop charities and influencers spreading bio-babble about ME/CFS?'

[Evergreen]

@MinIreland, this is by no means comprehensive, but will give you an idea.

The quote below is one of two that Jonathan referred to as misinformation above. The fragility of the evidence linked to in the International Consensus Criteria is dealt with elsewhere on S4ME. Jonathan and Kitty have covered some of the big picture issues with the Facebook post. I'm going into the nitty gritty.

I've highlighted some problematic parts of the Facebook post quoted above, and explained some of the issues I see:

People often use the term “post-exertional malaise” or PEM when talking about what happens after exertion in Chronic Fatigue Syndrome (CFS). But what defines Myalgic Encephalomyelitis (ME) is not just malaise or tiredness — it is Post-Exertional Neuroimmune Exhaustion (PENE). The two terms sound similar, but they describe very different experiences and biological processes. [No, they don't. The ICC coined the term PENE to replace PEM, not as something to be distinguished from it, because they were trying to propose specific pathophysiology underlying PEM.]

Post-Exertional Malaise (PEM) — in CFS [This author is trying to create a distinction between CFS and ME, where CFS is trifling and ME is serious. They're trying to bolster this by saying that PEM is trifling but PENE is serious, so CFS only has PEM but ME has PENE. These distinctions are simply made up.]

In CFS, PEM generally means feeling worse after doing too much. A person might feel more fatigued, achy, or mentally foggy for a while. It’s unpleasant, but it’s often viewed as a temporary increase in symptoms, similar to what healthy people feel after overexertion — only stronger and longer-lasting. It usually improves with extra rest.
Post-Exertional Neuroimmune Exhaustion (PENE) -ME
In ME, the reaction is far more severe and far more dangerous. PENE means that the nervous system and immune system become pathologically overactivated [very shaky evidence] and then fail to recover after even very small amounts of activity; physical, mental, or emotional. This is not just feeling more tired. It is a full neurological and immunological crash [no evidence]. The exhaustion of PENE is not ordinary fatigue. It feels like the body’s energy system has been “shut down.” People may feel paralyzed, poisoned, or flu-like, and can become bedbound or unable to speak, move, or think clearly.
It can take 24 to 72 hours or more after the activity for the crash to appear, and recovery can take days, weeks, or months. During PENE, there is measurable evidence of biological change [all either shaky or not true]:
* The nervous system shows reduced brain blood flow and poor communication between brain regions.
* The immune system shows abnormal cytokine responses as if the body is fighting an infection that isn’t there.
* The cellular energy system (mitochondria) cannot produce energy normally, and lactic acid builds up in the muscles.
* The autonomic nervous system loses control of heart rate, blood pressure, and temperature, leading to dizziness, chills, or flushing.

Even very small activities — like brushing teeth, talking for too long, or sitting upright — can trigger this crash. The worsening is disproportionate to the effort and is not relieved by rest or sleep.
This distinguishes ME from CFS. {No, it does not. People who are given the label CFS are not less sick than people given the label ME. They have just seen a different doctor. ]

Summary in Simple Words
*Post-Exertional Malaise in CFS means “I feel worse after I do things.” *Post-Exertional Neuroimmune Exhaustion in ME means “My body crashes after even tiny efforts because my brain, nerves, and immune system can’t recover.”
*PEM is a symptom. *PENE is a systemic breakdown. [Fabrication and deeply unhelpful when the whole international research community is using the term PEM. The grain of truth is that PEM has been defined by some in a way that makes it simply mean pathological fatigue after activity, and it would be a good idea to do research to figure out how post-exertional phenomena differ in ME/CFS and other diseases.]
...
In Myalgic Encephalomyelitis (ME), Post-Exertional Neuroimmune Exhaustion (PENE) is not just feeling tired after activity. It is a biological crash [we've little or no idea what is happening biologically during PEM] in which the nervous system, immune system, and energy metabolism are all overwhelmed.
...
International Consensus Criteria for ME (2011)
* Carruthers, B. et al. Myalgic Encephalomyelitis: International Consensus Criteria.
* Key point: This paper explicitly distinguishes PENE from fatigue or PEM, describing it as the hallmark symptom of ME and warning that overexertion can cause severe, long-lasting crashes
https://pubmed.ncbi.nlm.nih.gov/21777306/ [The author has misunderstood the paper. The authors replaced the term CFS with ME and replaced the term PEM with PENE, both with the intention of underlining their seriousness. The authors of the ICC overstated the evidence.]
National Institute for Health and Care Excellence (NICE) – 2021 Guideline for ME/CFS
* NICE recognizes post-exertional symptom exacerbation (PESE) as a key symptom. [No, they recognise PEM as a key feature, and say PEM can also be called PESE (note not PENE). This is at least understandable, as the draft guideline did use PESE instead of PEM.]
* They caution that overexertion can worsen illness severity and cause long-term decline, aligning with the concept of PENE.
https://www.nice.org.uk/guidance/ng206
Educational Articles / Reviews
* Newton JL, et al. Management of ME: recognizing post-exertional neuroimmune exhaustion. [I cannot find an article by Newton with this title online. The article linked to two lines below is called "PENE is Post Exertional Neuroimmune Exhaustion". It does not list any authors. It does not read like something written by Newton. At one point "we" is used, and then a study by Chu et al. is linked, which is a study of PEM in ME/CFS using Fukuda criteria.]
* Explains why PENE is different from fatigue and why pacing and rest are essential for preventing long-term harm. https://25megroup.org/.../PENE-is-Post-Exertional... [See above.]
* Fluge Ø, et al. Evidence of metabolic dysfunction and post-exertional crash in ME. [Fluge et al. do not have a study with that title. The study linked is actually entitled "Metabolic profiling indicates impaired pyruvate dehydrogenase function in myalgic encephalopathy/chronic fatigue syndrome". See the switch between ME and ME/CFS?]
* Discusses biological mechanisms behind PENE, showing it’s not psychological or voluntary. [The study does not mention PENE. It mentions PEM. In ME/CFS.] https://pubmed.ncbi.nlm.nih.gov/28018972/

Here's what the International Consensus Criteria actually say:

The label ‘chronic fatigue syndrome’ (CFS) has persisted for many years because of the lack of knowledge of the aetiological agents and the disease process. In view of more recent research and clinical experience that strongly point to widespread inflammation
and multisystemic neuropathology, it is more appropriate and correct to use the term ‘myalgic encephalomyelitis’ (ME) because it indicates an underlying pathophysiology.

Here's what the NICE guideline actually says:

Post-exertional malaise
The worsening of symptoms that can follow minimal cognitive, physical, emotional or social activity, or activity that could previously be tolerated. Symptoms can typically worsen 12 to 48 hours after activity and last for days or even weeks, sometimes leading to a relapse. Post-exertional malaise may also be referred to as post-exertional symptom exacerbation.

Here's what Fluge et al. actually say:

The main symptoms of ME/CFS are fatigue, postexertional malaise, and lack of adequate restitution after rest or sleep, accompanied by cognitive disturbances and sensory hypersensitivity, including pain.

In conclusion, this study suggests that ME/CFS is associated with PDH impairment, leading to increased consumption of amino acids that fuel alternative pathways for ATP production. ME/CFS patient serum was found to increase mitochondrial respiration in cultured muscle cells, possibly as a compensation or adaptation to an inhibition of metabolic energy pathways. The physiological consequences of such defects are likely to include energy (ATP) deficiency and excessive lactate production, in agreement with the debilitating exertion intolerance seen in ME/CFS patients.

So if someone reads the Facebook post and takes it at face value, they're being misled.

Hope this helps.

 

[duncan]

I appreciate wanting to get it right, wanting others to get it right.

Playing the role of spoiler, however, comes with risk. If we want to be naysayers, I suggest we'd best be in a position to replace what we're undercutting.

What do we actually know about the biologics of ME/CFS? Not much. Maybe enough to make claims about what it ain't, but I'm not even sure about that - so much about what we chat cavalierly is rooted in theory and patient experience. So many of the studies are crap or not reproducible.

It's one thing to denigrate other theories, to expose weaknesses or even errors, to ostensibly fact-check them, but without replacing them with facts that extend beyond demographics and definitions, I worry that the vacuum left in their wake will be eagerly filled by the likes of the BPS cult.

 

[Braganca]

@MinIreland Since you’re in Ireland you may have come across a loosely organized group called MEAI — ME Advocates Ireland which I think is really one or two people. Most of what they put out is inaccurate, unhelpful and harping on about ICC ME. They are as far as I know the main advocates dealing with the HSE.

 

[MinIreland]

@MinIreland, this is by no means comprehensive, but will give you an idea.

The quote below is one of two that Jonathan referred to as misinformation above. The fragility of the evidence linked to in the International Consensus Criteria is dealt with elsewhere on S4ME. Jonathan and Kitty have covered some of the big picture issues with the Facebook post. I'm going into the nitty gritty.

I've highlighted some problematic parts of the Facebook post quoted above, and explained some of the issues I see:









Here's what the International Consensus Criteria actually say:


Here's what the NICE guideline actually says:


Here's what Fluge et al. actually say:



So if someone reads the Facebook post and takes it at face value, they're being misled.

Hope this helps.

That helps big time, and also @Jonathan Edwards . This is absolutely shocking. I think it's horrific that someone pretends to be 'the' expert by bringing a lot of 'nuance', which is then bollocks. Also for @Jonathan Edwards patients because I can imagine that to them it should like someone It sounds like the author and org are known for this?

@MinIreland, this is by no means comprehensive, but will give you an idea.

The quote below is one of two that Jonathan referred to as misinformation above. The fragility of the evidence linked to in the International Consensus Criteria is dealt with elsewhere on S4ME. Jonathan and Kitty have covered some of the big picture issues with the Facebook post. I'm going into the nitty gritty.

I've highlighted some problematic parts of the Facebook post quoted above, and explained some of the issues I see:









Here's what the International Consensus Criteria actually say:


Here's what the NICE guideline actually says:


Here's what Fluge et al. actually say:



So if someone reads the Facebook post and takes it at face value, they're being misled.

Hope this helps.

This helps big time, and also what @Jonathan Edwards and @Kitty explained. Thank you.

I feel it's absolutely terrible if someone presents themselves as 'the' expert and doing so under the 'nuance' umbrella. Is this something the author is known for and if so, are there others pointing out to her how harmful this is?

 

[MinIreland]

I appreciate wanting to get it right, wanting others to get it right.

Playing the role of spoiler, however, comes with risk. If we want to be naysayers, I suggest we'd best be in a position to replace what we're undercutting.

What do we actually know about the biologics of ME/CFS? Not much. Maybe enough to make claims about what it ain't, but I'm not even sure about that - so much about what we chat cavalierly is rooted in theory and patient experience. So many of the studies are crap or not reproducible.

It's one thing to denigrate other theories, to expose weaknesses or even errors, to ostensibly fact-check them, but without replacing them with facts that extend beyond demographics and definitions, I worry that the vacuum left in their wake will be eagerly filled by the likes of the BPS cult.

I don't necessarily agree. It's fine to have a theory, but then you should be absolutely transparent how the theory is or isn't (yet) backed up by evidence. It's not up to others to come up with a 'better' theory. It's up to the 'theory advocate' to demonstrate the evidence and show how they're polishing the theory based on evidence.

 

[MinIreland]

@MinIreland Since you’re in Ireland you may have come across a loosely organized group called MEAI — ME Advocates Ireland which I think is really one or two people. Most of what they put out is inaccurate, unhelpful and harping on about ICC ME. They are as far as I know the main advocates dealing with the HSE.

I've seen them, yeah. Normally, I would step up and speak up. I just don't have the energy. It's really a problem.

 

[duncan]

It's fine to have a theory, but then you should be absolutely transparent how the theory is or isn't (yet) backed up by evidence. It's not up to others to come up with a 'better' theory. It's up to the 'theory advocate' to demonstrate the evidence and show how they're polishing the theory based on evidence.

Agreed.

But I don't think that is what is being bantered around here. I may be wrong, but it seems to me the crux of the thread is to clarify what steps can be taken to correct what are perceived as other patient groups' errors.

 

[Jonathan Edwards]

I worry that the vacuum left in their wake will be eagerly filled by the likes of the BPS cult.

The idea that the advocacy groups and charities will want to replace ICC ME with BPS seems to me somewhat comical!!

 

[duncan]

Not remotely what I was trying to convey. Sorry for the poor wording. I was suggesting the likes of the BPS folk will probably be happy to replace the remnants of the denigrated theory with their own, and trumpet it - but not on the patient advocates' website or whatever.

You tear something down and often someone is going to replace it, and it may not be anyone or anything that is good for you. If we want to assume that role, I'd rather we have facts to replace those factual errors we've called out, as opposed to simply exposing others' mistakes.

 

[Jonathan Edwards]

I suggest we'd best be in a position to replace what we're undercutting.

What do we actually know about the biologics of ME/CFS? Not much. Maybe enough to make claims about what it ain't, but I'm not even sure about that - so much about what we chat cavalierly is rooted in theory and patient experience. So many of the studies are crap or not reproducible.

We are in that place. We know a good deal about the biology. We have rather precise replicated data on demographics with about 0.8% prevalence and two age peaks. We have replicated data relating to association with EBV and several other infections. We have what looks like a reliable estimate of genetic causation (~10%), with replication other than in one or two outlying studies. We have some gene loci, one of which is also found in chronic pain cohorts. We have data from several sources indicating that it is the same illness in men and women.

None of that is rooted in theory. As for patient experience, I keep getting told how important this is, and indeed it is, as long as it is not overinterpreted in terms of cause and effect. And the studies I am referring to are not crap and have proven to be remarkably reproducible.

We don't know what the precise pathways involved are but we don't know that for psoriasis or type I diabetes either. We may not yet have any clues from treatment but I don't think we should dismiss the daratumumab data - there are aspects to that which are pretty hard to explain on the basis of chance or confounders.

At the DecodeME showcase someone talked about ME/CFS always being treated as an exception. We don't need to any more. It is an ordinary disease like lots of others about which we know some things and not others. It needs to be taken out of the arena of social media-driven 'special diseases'. If we can stop arguing about theories of causation and just treat it as a well-delineated medical catastrophe for millions of people we might get somewhere.

 

[Jonathan Edwards]

Not remotely what I was trying to convey. Sorry for the poor wording. I was suggesting the likes of the BPS folk will probably be happy to replace the remnants of the denigrated theory with their own, and trumpet it - but not on the patient advocates' website or whatever.

But Simon Wessely did precisely that 40 years ago. And the theories put in place after he had scarpered fell apart with PACE. This is ancient history.

 

[duncan]

It is an ordinary disease like lots of others about which we know some things and not others. It needs to be taken out of the arena of social media-driven 'special diseases'.

First, I'm happy to see you writing that ME/CFS is a disease.

More importantly, it is NOT an ordinary disease. It is a contested disease, and as such is riddled with perils for its sufferers that ordinary diseases to not impart.

 

[duncan]

But Simon Wessely did precisely that 40 years ago. And the theories put in place after he had scarpered fell apart with PACE. This is ancient history.

It is a far cry from ancient history in the eyes of 99% of clinicians. It is a far cry from what is taught to this day in medical schools. And it's a far cry as far as insurance agencies are concerned.

 

[Jonathan Edwards]

what is taught to this day in medical schools.

Ancient history often continues to be taught for decades.

 

[Kitty]

I feel it's absolutely terrible if someone presents themselves as 'the' expert and doing so under the 'nuance' umbrella. Is this something the author is known for and if so, are there others pointing out to her how harmful this is?

I don't know anything about this particular author, but there seems to be someone like this in quite a few of the ME/CFS and long Covid social media groups. People who put forward other points of view tend to be sidelined, and anyone who tries to challenge them strongly risks being thrown out.

The groups are often led by one or two particularly vocal people who 'educate' the others on the 'right' way of understanding ME/CFS. Some of the members will be recently ill people who lack the knowledge and perspective to see what's going on. They start parroting the same guff, including to their GPs, and so the cycle goes on.


ETA: Most of these group leaders probably believe they're helping. They commit quite a bit of their time and energy to what they think is a social good. It's one of the things that makes it tricky to challenge them.

 

[Sasha]

We have what looks like a reliable estimate of genetic causation (~10%),

I don't want to derail the thread but where does this 10% come from? Is the idea that 10% of cases are genetic and the others are stochastic? Is that from DecodeME?

 

[Kitty]

Is the idea that 10% of cases are genetic and the others are stochastic?

I think it's more that genetics might be responsible for about 10% of risk.

 

[Sasha]

I think it's more that genetics might be responsible for about 10% of risk.

Thanks - but how do we know that? I don't remember it from the paper.

 

[hotblack]

Thanks - but how do we know that? I don't remember it from the paper.

It was either in the paper or brought up in one of the interviews Chris did IIRC

 

[Jonathan Edwards]

Is the idea that 10% of cases are genetic and the others are stochastic? Is that from DecodeME?

The 10% comes from various sources, including DecodeME. As Kitty says it is not about individual cases. At least 70% of cases are a bit genetic because they are women and two X chromosomes is genetic and confers risk. But for two any two identical female twins if one gets ME/CFS the chance of the other getting it may be only 10%. The percentage figure used here is a bit phoney. It is a mathematical value between 0 and 100% that indicates how important genes are overall to the risk but it isn't strictly what one might think of intuitively as 'proportion of cause'.

Things are further complicated byt the fact that there may be rare genes that give so much risk that the matching rate for identical twins might be 95% but so fr it looks as if the genetic risk is mostly carried by a scattering of genes that just nudge your risk up or down. There may still be some rare genes with high risk and these would be hugely useful to know about from a whole genome sequence study - which is at least one of the reasons for Sequence ME.