Entire issue of Post Graduate Medical Journal (11/1978) devoted to ME

I read everything here with keen interest. What's especially interesting to me is the implication that there's a form with a greater number of neurological symptoms (hence the myalgic encephalomyelitis label), and one with fewer (hence epidemic neuromyasthenia), and that was why they couldn't agree on one name (to do so would misrepresent the other group).

Even then there was discussion of a 'spectrum' of illness (though it wasn't yet used as a wastebasket diagnosis), though everyone was pretty clear it was biological.

 

Those people who have read the articles, do any of them describe polio-like illnesses on onset, eg acute flacid paralysis or other severe weakness syndromes?

 

Actually predates this by 8 years ... McEvedy, and Beard.

 

It is certainly interesting to look at the way the CDC document was worded in 1988. It looks as if it reflects US parochialism and quite deep ignorance. The presence of Parish and Shelokov may not have been that much help because they were also very focused on the viral aspect of the problem.

What is missing from the CDC document is not just the early work reported in the 1978 volume but all the subsequent work done in the early 1980s, much of it by Richard Edwards's (no relation) unit, then at UCL. From 1982-6 I shared a lab with people working on muscle metabolism in a range of conditions including ME - David Jones, Joan Round, Mike Rennie etc.

To be fair, even Simon Wessely was aware of this work and reviewed it in his 1990 'Old Wine in New Bottles'. The key point was that despite the very best quality technology, including MR spectroscopy, as far as I am aware none of the original suggested findings from Ramsay or Behan were confirmed. If there really was a metabolic defect detectable by Ramsay it would have been nailed and embedded in the literature by 1986. I am not familiar with all the papers produced but I suspect part of the problem may be that negative findings did not necessarily get published.

 

There is an interesting discussion in 1993 Chronic Fatigue Syndrome, Wiley, Chichester, Ciba Foundation Symposium 173 @ p234 following Wesselys presentation on The neuropsychiatry of chronic fatigue syndrome.

Komaroff. In discussing your prospective study, Dr Wessely, you say that patients who develop a fatigue syndrome after a viral infection are not like CFS patients. Could you amplify on that?

Wessely. The difference is that these patients are not very ill. They are not well either, but they are not badly disabled, or polysymptomatic, and their social class is different. The whole feel of these postinfectious patients is different from the patients I see in the CFS hospital.

White. To follow up on that, I have been studying the people with acute postinfectious fatigue, whereas SW has been looking at chronically fatigued people and we are both aware of the contrast. It suggests that what we are seeing in patients who feel tired six months after having influenza is possibly the start of a long process, where the perpetuating factors then produce more symptoms and give the chronicity and disability.

Wessely. I doubt it. I think these are totally different people.


If they are different people, why lump them for research?

 

The conversation sounds about as evidence-based as the nineteenth century comments Wessely liked to quote.

 

I wonder if that is so, simply because it was, is so difficult for researchers to get funding.

 

Richard Edwards had no problem with funding. He was in charge of the entire Department of Medicine budget and had the sort of funding stream other people can only dream of. Muscle fatigue was studied very intensively and very competently by his group.

 

I thought that the problem with Edwards did not relate to his work on muscle but on the conclusions which he drew from not finding abnormality.

 

I have no idea what conclusion he drew. All I can assume is that his group could not confirm metabolic abnormalities, which seems to be the important part.

 

From the abstract of his paper at page102 of the same publication.

On physiological and pathological grounds it is clear thatCFS is not a myopathy.Psychological,psychiatric factors appear to be of greater importance in this condition.

 

Am I right in thinking that the big problem here is technique?
Some techniques appear to show the metabolic problems and others don’t.
It’s like - everyone is looking for a horse - but some look for it in the field and some in the stable.... just because one group can’t find it doesn’t mean there isn’t a horse... but everyone assumes that when the group says ‘there’s no horse in that field’, it’s just accepted at face value that the horse doesn’t exist.

If researchers don’t want to replicate exactly, then they shouldn’t assume that failure to achieve the same results means that the original results were wrong.

 

What amazes me is that in the early 90’s Behan did a muscle biopsy study that found that 39 of 50 patients had Type II muscle atrophy.

Reasonably recent papers state that Disuse tends to more Type I atrophy whereas Type II atrophy can be caused by inflammatory/metabolic factors, e.g., https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4327989/#!po=24.0385

I wrote to Behan and asked why as far as I could find the Type II muscle fiber atrophy findings seemed to have never become a key target but I didn’t hear back...

I also agree with @Trish regarding having never seen a better descriptor for the disease I have than severe muscle fatigeability (+ add in post exertion shutdowns)- I am very glad to hear that the NIH study is including muscle biopsies in their study and so wish more would do so

 

Richard was basically a physiologist interested in myopathies. His job was to see if ME was a myopathy. If there was no evidence it was outside his area. Maybe he should not have mentioned psychological factors but I don't think that is relevant to the issue of whether or not there is something wrong with the muscle metabolism, or the quality of his biochemical work.

 

I actually doubt it. If there is a metabolic problem with muscle that is causing symptoms directly then MR spectroscopy of basic metabolites should pick it up. It is a bit like saying if someone is tired because of anaemia a full blood count should pick it up - it should.

I read through one of Behan's papers yesterday and I am not that surprised the findings were not replicated. They are very preliminary and in many cases not very well described. I think in this case failure to get comparable results is pretty good evidence that the original findings were by chance or weak methodology.

That does not mean that it may not be worth looking yet again but I am doubtful anything will be found just in terms of metabolism that is enough to explain symptoms. What might be the case is that there are subtle change in metabolic pathways in mitochondria that lead to powerful signalling mechanisms. This was the suggestion that Mike Murphy made at IiME. The symptoms would not be due to metabolic deficit as such, which would not really seem to fit with the type of symptoms anyway, but to stimulation of nerve endings by by-products that are used as danger messages.

 

My memory from reading his stuff yesterday was that he reported an increase in number and size of type II fibres.

 

@Jonathon Edwards Behan found mild to severe type II muscle fiber atrophy in 39 of 50 cases - abstract attached.

Weird that no more research seems to focus on this finding— no chance to replicate if no one focuses on it again...

I guess as you say someone has done so and not reported negative finding?

I have talked to a couple of people in NIH study who have this finding from biopsy. Initially NIH study was not going to include muscle biopsy but now is...

 

That is from the 1991 paper.

But in his 1985 paper he says:
'Histochemical stains showed moderately increased size and numbers of Type II fibres in all.' (my bold)

I assume the 1991 paper includes the samples reported in the 1985 paper. There is a rabbit loose here. And reading the rest of the 1985 paper I am not that surprised.

I am pretty sure Edwards reported negative findings.
Edit: He reports 'There was no consistent correlation between symptoms and changes in fibre type prevalence, fibre size, degenerative or regenerative features, glycogen depletion, or mitochondrial abnormalities.'

 

That would not suprise me.

 

The biggest problem with muscle biopsy is that there is huge potential for sampling error. It is also pretty unpleasant. The sorts of changes that cause obvious symptoms are usually apparent on closed imaging techniques now, which can be done on any or all muscles as a whole and serially.