Publications that show ME is biological

I don't know if this contributes to the discussion but thats never stopped me before....

@Hutan it sounds like you were away from home during your test. So, and I'm making wild assumptions here about what you did on the day in between the two CPETs, if you did much less than you normally do in the second day the rest may have dialled down the overt symptoms of PEM. No strain of cooking and washing up etc. So, potentially,you could have been in PEM all the while.

There are degrees of PEM in my experience. I can be in low level PEM and not really noticing it until I try to do something and discover my body won't work properly and if I persevere I will feel really ill really quickly. So in some ways my behaviour is masking PEM.

I'm thinking that, as a process, when we experience PEM we may just be seeing the tip of the iceberg.

 

@Jonathan Edwards

I was thinking about your faulty signalling hypothesis.

I think the symptoms might be analysed as:

1) symptoms that occur all the time eg parasthesiae or pain.

2) symptoms that occur upon intended to do something eg the feeling that the battery is almost flat and will not turn the starter motor, leading to a sort of inertia.

3) symptoms that occur during exercise, separate and other than normal sensations.

4) symptoms that occur sometime after exercise eg PEM in whatever form it takes for the individual.

Do you think that your hypothesis would be sufficient to cover the full range of these symptoms?

I tend to think of the encephalitis lethargica cases described by Sacks, bearing in mind that they may just have been the most extreme cases of a spectrum. It would be possible to see their symptoms of being caused by faulty signalling, but it could equally be argued that they were caused by some dopamine deficiency, or by whatever it was that caused the L-dopa treatment to become ineffective.

But as you well know, I might be making no sense.

 

That's the sort of thing I mean by faulty signalling. Faulty signalling covers a huge range of things including immune responses, brain responses, autonomic responses, muscle mitochondrial responses - whatever you like. What is does not cover is structural damage or sheer lack of ATP or oxygen.

 

Feel free to adopt the Gavin Williamson approach and tell me to shut up and go away, if you wish.

By "signalling"I had understood you to mean something much narrower than that. My misunderstanding.

When looking through the Wessely 1993 paper Neuropsychiatry of CFS I came across the remark "basal ganglial abnormalities were found in a small study (Costa et al 1992) confirmed by a larger Canadian sample (Ichise et al 1993)." This brought to mind the recent post mortem findings.

The report is Costa D, Brostoff J, Douli V, Ell P 1992 Post Viral Fatigue Syndrome Br Med J 304:1567 This was apparently merely a preliminary report and as such was criticised in the BMJ but there was a reference to it having been fully written up in a specialist Journal a little later after a further expert had been recruited, but I have not found that. It is hard to avoid the conclusion that this would have been a more productive area for research funding.

 

They do? I never had the impression. But I agree, if they do, this is difficult.

I understood it such that the 2-day CPET shows something is going on in ME - as does the pyruvate dehydrogenase paper - and that exercise is not beneficiary.

 

The 2 day CPET seems to show that one vigorous exercise is followed by a dip in function a day or two later. But there are situations where this occurs in normal people. After repeated exercise the effect goes away and the muscle gets more powerful.

 

I realised that my use of the term signalling might not be transparent. Nothing like dialogue to get on the same page.

In 1992 I was working with Durval Campos-Costa and Peter Ell on nuclear medicine projects. The ME project seemed interesting but I guess was not considered convincing enough to get them further funding. I agree that at least some follow up replication studies would have been justified. Jonathan Brostoff would have been the ME clinical involved.

 

I suspect the consequence of the first test is to reduce the anaerobic threshold for a while. The PEM symptoms are just the way that reduction manifests itself. If you rest and do nothing to test the limits of the lower threshold you may not experience the PEM symptoms if your resting energy requirements are below the lower threshold.

 

Relative to the CPET metric for attempting to demonstrate PEM, I have often wondered what happens if the subject is suffering from PEM during the initial CPET. Simply traveling for the test could trigger PEM, and depending in part on how long one has been sick with ME/CFS, PEM - according to some - might not kick in in a predictable time frame. The result may be that during the first CPET, prior to the kicker second CPET, the patient may be in the grips of PEM.

This could skew results.

They'd need to run a baseline, arguably well before the trial. As in weeks, possibly.

 

Re: reduced outcomes on the CPET even though you weren't experiencing overt symptoms of PEM, this reminds me of the Ramsay wording. He didn't focus on PEM at all but on 'muscle fatiguability'. It seems like your experience was measuring that more than an increase in certain symptoms, per se?

So maybe PEM is something separate but overlapping? Or a consequence of whatever is causing the reduction in outcomes on the CPET?

 

For me, how fast the muscles burn or how fast they feel "drained" is a measure of whether I have a good day or a bad one (PEM).

 

Is there any evidence of that? CPET with decrease in capacity? I think some trials compared sedentary people to ME and I believe every single one show same or better results on the second day.
But then if we add Light et al gene expression studies to those results, I think it becomes really hard to argue against some kind of biological/metabolic/immune problem, and even if that's not enough, what's the alternative explanation then? Some kind of magical psychiatric disease which affects the body so strongly and is so prevalent? I mean, I could understand the stress angle and the possibility that for some folks that could be a contributing factor, but I don't see how it could be THE thing.

 

This is interesting new research on post exercise and the immune system in healthy subjects

"In their study, the authors from the University of Bath explain that, for competitors taking part in endurance sports, exercise causes immune cells to change in two ways. Initially, during exercise, the number of some immune cells in the bloodstream can increase dramatically by up to 10 times, especially 'natural killer cells' which deal with infections. After exercise, some cells in the bloodstream decrease substantially -- sometimes falling to levels lower than before exercise started, and this can last for several hours".