Deep phenotyping of post-infectious myalgic encephalomyelitis/chronic fatigue syndrome, 2024, Walitt et al

Actually, I think it is likely that people making conscious decisions just IS neurons making decisions based on their chemical/electrical environment. That is what the biological, rather than the BPS account, would say. But I think your intended meaning is quite right - if conscious meaning implies drawing on some belief that may be misguided, or a 'deliberative choice' rather than just 'heck I can't do this'. This is where the topsy-turvy BOS approach to dualism shows through. They don't even understand what 'psychological' means.

I don't think anyone will find more substantive new positive findings. But a detailed analysis may reveal some useful negatives. The real problem is that with such small numbers those negatives will be very uncertain.

 

That goes a good way to explaining why so many recovered.

 

Together these findings suggest that effort preference, not fatigue, is the defining motor behavior of this illness.

This comment is meaningless. Fatigue is not motor behaviour, it is sensory. They don't even know how to construct a coherent argument.

 

The vast majority of the people were not picked because they had an onset greater than 5 years ago, had no record of infection or had other diagnoses. I don't think they weren't picked because of CCC criteria. 9 of the study participants fulfilled the CCC and for those that did not, 3 were because they had no pain and 4 were because they had neither one immune or neuroendocrine symptom. However, the CCC states "There is a small number of patients who have no pain or sleep dysfunction, but no other diagnosis fits except ME/CFS. A diagnosis of ME/CFS can be entertained when this group has an infectious illness type onset." so I guess 12 of the participants actually did fulfill CCC.

 

I was also wandering about this. Especially as they mention "Two PI-ME/CFS participants had detectable antibody secreting B-cells in cerebrospinal fluid; these participants did not have oligoclonal bands or autoantibodies." Is that something that can be quite common and as such isn't too relevant at these sample sizes? Is there anything interesting in the supplementary material in regards to this?

Is suppose there could also be a discrepancy between what the authors via as ME/CFS and what the Adjudicators think. I have no reason to believe that Lucinda Bateman, Andy Kogelnik, Anthony Komaroff, Benjamin Natelson and Daniel Peterson would give a less suitable selection than the selection used in any other study that I've read (especially since many of those studies are theirs), independently of whether the authors understand or have tried to understand what PEM entails.

 

Good point.

 

I was confused because eg in the Daily Mail article in the above comment is the following related to this:

So I'm slightly trying to unpick what they do specifically mean when they say it isn't a 'lack of motivation' but 'a mismatch between what someone thinks they can achieve and what their bodies perform'

It isn't my experience either because my issue is the payback from having forced (or just being stupid or over-eager) my way through things before-hand, or not even forced. I'm likely to be ham-fisted with my words here, but appreciated the Workwell paper that said pwme weren't 'unfit'. An awkward feature of having ME/CFS for many years before the science came out was being more capable than most physically on eg individual tasks or activities (even if this was a shadow of my former self), of course I wasn't trying to do them on a bad day generally because I was knocked out fast asleep. eg The connection with having helped pick up that fridge wasn't as obvious because I was doing other things too. But boy did people pick up on my 'bad behaviour'/illness/strange sleep patterns - all of which are just plain ME but back then..

anyway, the point here is the gap from good day-bad day differences on this particular finding I'm struggling to explain.

I also get fatiguability now for many years and e.g. my arm shakes as I lift if I've done too much and eventually just can't lift it at all in that context. Muscles twitching and doing very specific 'the tugs' type jerks are another part of that. It is normally immediate so perhaps closer to this example. But I still haven't worked out in that context how it all fits with this.


I'm also wary when someone is taking evidence from scans to understand whether the scan was only of the brain (the task was a hand strength/exertion test), on the basis that the brain is in effect part of a system. But also what within that system is and isn't 'mapped' from the method but has to be assumed (like cellular level).

And so to understand the following more precisely:

I'm now trying to think around what they would have seen should there be an issue 'elsewhere in the system' between the hand gripping and if you want to think of it that way the part of the brain saying 'keep up the gripping'. ie if it were 'something else' causing the ability to keep gripping to decrease, would the feedback loop look similar in that part of the brain?

Although even that is something that has been labelled as the function based on mapping healthy individuals or other conditions I guess - in whom exertion = exerting effort (I'm not just being pedantic as theoretically exertion could be 'done to' e.g. very loud noise)

 

@dave30th you really must get up to speed on your metaphors. We did it in year 5, along with the siege of Pondicherry. You shut the stable door after the horse has bolted.

 

Agreed. It seems they could be picked if they fulfilled Fukuda, IOM or CCC and in reality they most consistently met IOM. But the point about immune and neuroendocrine features is what I regard as 'over-imaginative' about CCC. A sensible physician would ignore those, since they are interpretations relating to putative mechanisms that are not core to the ME/CFS concept.

The study may be an interesting illustration of CCC being too fussy for research purposes. I suspect ICC is even worse. The consistent meeting of IOM suggests that this may in reality be what most physicians think of as ME/CFS.

 

Don't know. It is a bit surprising to me but may be within normal expectations.

 

Thank you.

I think what Walitt is trying to do is to find a new spin on BPS, quite similar to what the new FND brigade is doing.

At the very bottom of the discussion lingers the question and uncertainty of/around 'free will' (not really a question actually, cells behavior, and therefore our behavior, is determined). I guess the 'new spin' consists more or less of:

'yes, these people/patients have no choice, it is their brain telling them to not exert effort, but, there is certainly no damage or real danger in trying to modulate these choices and behavior, because it is a false alarm anyways'.

And this, is 100% wrong (and indeed very dangerous), at the very least in in my very own case of ME, but, I must assume also in many other people/cases.

I can not exclude that there are people with ME that have some kind of subconsciously programmed fear or mismatch that leads to 'less effort', though (but wouldn't that be equivalent to anhedonia?). Nobody can, and that is the heart of the issue: Yes, ME is a central disease, and/but we know very little about this center, the brain.

I can also explain why I am so sure about my own case. Every single deterioration I had was triggered by over-exertion or an infection. The loss of function appeared almost instantaneously with every baseline worsening crash. What this means is that there was no room/not enough time for a significant deconditioning to happen that could explain it. There is deconditioning, obviously, but it it's a side effect.

How does Walitt's concept explain deterioration in patients? It can't. It tries to explain the end result in a very awkward kind of manner. Either there are immunological effects that cause the deterioration or there aren't. That's it. The rest is just assumptions about people's 'trained behavior' and mumblejumble about 'preferences'.

 

Mine weren't instantaneous but sustained periods of time doing increased exertion (for me) and daily and cumulative exertion probably well above what normal people would have been doing (exempting those who were gym bunnies), I think also important to not the exertion-rest equation too as I suspect that as you get more ill then having more and more rest to recover from exertion is vital otherwise cutting that short to 'just enough rest to carrying on pushing through/perform' which was often my classic situation really seemed to manage to do the trick in long-term worsening eg. 6months on.

The deconditioning makes little sense to me as it is preceded by 'more' and not 'less' - in fact the presumptions behind 'wastage' don't make sense because increased walking on calves when I'd been ill for a long time and car parks moved a long way away led to it rather than other way around.

I haven't read as far as the free will bit .. interesting

 

Just to clarify, with 'at the bottom of the discussion' I meant that there is a deeper almost philosophial layer to the discussion. I was not talking about the discussion part of the paper. Bad coice of wording. Sorry!

 

makes complete sense - one of those quirks of language that amuses me that I read it as that (functionedly-focused on trying to keep track, I'm finding it hard with a paper that has so many bits all at once in it as one thread)!

 

Rob Wüst pointed out on Twitter earlier (with regards to his much appreciated publication in January) that he had been testing several former athletes with long-covid in his lab. He wrote something along the lines of that they showed the same abnormalities post exercise, even though their exercise capacity at day0 was “relatively good”. I can only add that I am very much looking forward to his ME trial. What he finds in long covid does not align well with Wallits (ill conceived) ponderings.

https://twitter.com/user/status/1743330438360272965

 

Good to see this from Wust:

"The pathology of reduced exercise capacity is different from PEM"

I get the impression that he is someone who listens and learns and looks for the complexities.

 

Someone who does his job, in short.

 

According to this email from Walitt posted on social media, all participants had PEM.

https://x.com/sharonc97936831/status/1760457561768067322

 

https://www.s4me.info/threads/usa-national-institutes-of-health-nih-intramural-me-cfs-study.2980/


We have been expressing disappointment and confusion at the lack of consideration of PEM in the new Walitt paper.

On rereading some of the initial thread on here (above), I came across Brian Vastag posting in March 2018 a reference to a paper on PEM from the focus groups .


"The first paper out will probably be from the researcher who led the focus groups on PEM. Twenty patients participated in a total of four phone calls, and those discussions helped guide the design of the second visit of the study (which is explicitly studying PEM after an exercise challenge). She said she's finishing up that paper. As for most of the results, they won't come until all of the volunteers finish their visits."

(Also was a second exercise challenge ever done? I have a vague memory that it wasn't but may have misremembered.)

 

https://twitter.com/user/status/1760457561768067322
( link posted by @Sid)

( link posted by @Sid)


edit: I'm personally very confused about this PEM issue.1) Did the participants have to have PEM and 2)did the study research PEM?

It's hard to distinguish between comments on the study and the study itself, and I've no more capacity to dig into this. I have a headache on top of my usual brain fog. Not a state to make sense of things. I hope it becomes clearer.

edit2: thank you to @Medfeb for unpicking this issue somewhat in #206. I understand more of the issues now.