The biological challenge of myalgic encephalomyelitis/chronic fatigue syndrome: a solvable problem (2016), Edwards, JC et al

[Mithriel]

I'd argue that this is just what we need. At the moment we have no way of reliably separating the people with TB from those with asthma or lung cancer, and as you say, we need to do this in order to make progress. Perceptive physicians could tease out some of the differences between the groups, IF they were given the time and resources to do so. It's hard when there's no pathology to observe or measure, but progress could be made.

The point is that we do not need a randomised controlled trial to do an initial sort of TB, lung cancer and asthma. A careful history of each patient showed they had different diseases so they were accepted as different.

The emphasis on fatigue in ME was done for ideological reasons. The doctors wanted to study fatigue and were able to claim ME because they acted unethically (ignoring previous work and experts) and were political with no care for patients.

It is the weirder symptoms of ME that are most important. Vision studies are sorely neglected for instance. Becoming exhausted by making small movements may be an important symptom to look at to distinguish it from other fatiguing illnesses.

I am talking about small well defined groups, maybe many separate groups, for research that can then be widened out.

I do not have high hopes of Jason's work, he does not seem to understand ME, just chronic fatigue.

 

[FMMM1]

Genes. Yep. That's important and might prove to be the mechanism. I was thinking more in lines of infectious or specific immune dysfunction. But really infectious. Who's looking these days, and for what, with what? Aren't most focusing soley on symptoms? I hope I am wrong.

If you hunt around this forum then you'll find some discussion re EBV in MS [large US Army study] - how that could be replicated for ME/CFS.

Just thought I should highlight that although the hunt for infections (e.g. the potential link to EBV) could be investigated by e.g. looking at the US Army data - I'm not aware of any proposal to do that. So although there are potential research areas, lack of funding etc. mean that these may not be pursued.

 

[alex3619]

The broader the definition the more larger the trial will have to be to make statistical sense of the answers.

I have been saying this for a decade now. We probably have issues with subgroups because when you find a potential subgroup in a small study its not guaranteed to be of sufficient power to say anything. A broad study works if its large, and if you massively increase the range of tests, and subgroups are identified and analysed in the cohort, each of which cause major increases in study cost.

 

[duncan]

Just thought I should highlight that although the hunt for infections (e.g. the potential link to EBV) could be investigated by e.g. looking at the US Army data - I'm not aware of any proposal to do that. So although there are potential research areas, lack of funding etc. mean that these may not be pursued.

Oh sure, I know and I appreciate your insight. I know what lots of key people have suggested over the years, e.g. Peterson and Chia and the New York guy (Cheney's friend) and several other researchers, and the links to EBV and enteroviruses and Herpes etc. I also know how MS started with a psych label then went to an unknown infectious disease as the putative agent, then to an immune dysfunction of some sort, and most recently back to infectious disease in some circles.

We share a lot of political history with MS. Alzheimers and ALS, too. The latter two also have infectious diseases which some have speculated either potentially cause them, or mimic them.

A recurring problem that seems cross-elastic among disparate diseases is inadequate diagnostics, or an unwillingness to rework the algorithms that define viral persistence. Setting aside our culture's disdain for chronicity in disease, I am torn whether greed or incompetence or laziness or politics or something worse is behind the catastrophic indifference that seems to characterize our diagnostics industry as a whole.

 

[Adrian]

Leonard Jason went in the other direction. He cast a wide loop. Healthy in coming freshmen was included in his loop. He found an abnormality. Jason is now trying to predict who will develop ME after an EBV infection. By casting a wide loop Jason found something, and best of all Jason is now working to replicate his findings. By Jason focusing on healthy people and watching what happens when the healthy become sick he has moved the ball forward.

I suspect that an approach that looks at variation over time will be one of the ways that ME may become understood. Its interesting that Jason is taking this approach. I suspect there is also value in looking at patient changes over time and seeing what corrolates with severity (I think there was a recent Newzealand study doing this). I think somewhere I heard this described as using someone as their own control.

 

[FMMM1]

A recurring problem that seems cross-elastic among disparate diseases is inadequate diagnostics, or an unwillingness to rework the algorithms that define viral persistence. Setting aside our culture's disdain of chronicity in disease, I am torn whether greed or incompetence or laziness or politics or something worse is behind the catastrophic indifference that seems to characterize our diagnostics industry as a whole.

Check out the comments here* if TPPP1 is implicated then there may not be a clear biomarker in blood or even cerebro spinal fluid (not that accessible). I think Angela Vincent mentioned to me once that there'd need to be a technological discovery to understand ME/CFS - check out comments in this thread*, which are along the same lines.

Industry is about making money. If you check out Jonathan's experience, re rituximab in rheumatoid arthritis, then you'll see that the proof of concept came from his group (not funded by industry) --- industry only came on board when the effectiveness of the drug had been demonstrated. Fairly typical.

*https://www.s4me.info/threads/genet...loci-2022-hajdarevic-et-al.25070/#post-411268

 

[Adrian]

The emphasis on fatigue in ME was done for ideological reasons. The doctors wanted to study fatigue and were able to claim ME because they acted unethically (ignoring previous work and experts) and were political with no care for patients.

I suspect there is something in fatigue but that fatigue is not fatigue but a range of different symptoms that are harder to express including PEM, brain fog etc (and also the energy use it requires to cause these symptoms. I wonder if comparing 'fatigue' in more detail across multiple diseases could help pick out what is common and what is different. But maybe this is along the same lines as when you say:

Becoming exhausted by making small movements may be an important symptom to look at to distinguish it from other fatiguing illnesses.

The problem can be that an outside obverser sees fatigue as fatigue rather than a range of symptoms that are different for different diseases and caused by different amounts of energy use,

 

[Kitty]

I suspect there is something in fatigue but that fatigue is not fatigue but a range of different symptoms

Yes, I've always found it interesting that when I have pain and fatigue and take painkillers, the fatigue fades out along with the pain. It's not due to a stimulant effect from opiate-type drugs—the same thing will happen with paracetamol taken for a headache, ibuprofen taken for an inflamed joint, and antihistamines taken for hay fever.

If I was describing how I felt at a time when I had fatigue but no other symptoms, I'd say things like "really tired" or "no oomph"—I'd never say "fatigued". Fatigue's always seemed more complicated than simply lacking energy.

(Sorry if that's not expressed very clearly, I'm having a really foggy day.)

 

[Mithriel]

I suspect there is something in fatigue but that fatigue is not fatigue but a range of different symptoms that are harder to express including PEM, brain fog etc (and also the energy use it requires to cause these symptoms. I wonder if comparing 'fatigue' in more detail across multiple diseases could help pick out what is common and what is different. But maybe this is along the same lines as when you say:


The problem can be that an outside obverser sees fatigue as fatigue rather than a range of symptoms that are different for different diseases and caused by different amounts of energy use,

I read an article in the MS society magazine that was originally published in the RA society magazine (with me!) It was about fatigue and was very interesting. They were definitely talking about fatigue as lay people think about it. Basically they felt that it was just so difficult to do anything with a damaged body that you get tired quicker than normal.

It felt like more effort because it was more effort. My friend with cerebral palsy saw this as a good description of why she had to go to bed if she did too much. I suspect a lot of the "PEM" that they find in so many diseases is actually this.

I never mentioned fatigue to a doctor in the first 17 years of my illness. It happened in ME but it was like talking about fatigue when you had a cold, there but not very important.

After CFS was invented new patients began to use the word fatigue to cover a lot of things that I would not have considered under that name. This happened especially in the US where the researchers never acknowledged the problem with exercise which had been seen as the most important thing by the ME medical people previously in the UK.

We have a circular problem in that fatigue is the only symptom considered for CFS so we think it covers everything but outsiders only see tiredness.

 

[Sean]

Turning ME into mere 'fatigue' was a massive propaganda coup for the psychs et al, for which we have paid a terrible price, and continue doing so.

 

[Sasha]

Wow, just realised that this paper is nearly nine years old!

@Jonathan Edwards, looking back, what sort of impact do you think it had on colleagues? Do you think there have been any substantive advances in our knowledge since then, or avenues of inquiry that can now be ruled out, or new ones that look promising?