To qualify as an adjudicated case "have moderate to severe clinical symptom severity". Yet all the participants managed to complete a week of testing, including exertion, without dropping out due to PEM? That really seems unlikely, and puts the whole study in question.
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Deep phenotyping of post-infectious myalgic encephalomyelitis/chronic fatigue syndrome, 2024, Walitt et al
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And how was recovery assessed?
Also, were those who considered themselves recovered queried at later points in time to see if their "recovery" continued, ebbed and flowed, other?
Surely the recent Wust paper in long covid did find mitochondrial dysfunction and cell necrosis in people with ME type long covid post exercise (we can debate til the cows come home over whether this counts as PEM) and they have a paper on the way in pwME. If those findings are borne out in the upcoming study (and replicated eventually) would that not be evidence of something wrong in the muscles?
The other thing I got from the study is that there were findings of a fairly large number of factors being slightly abnormal. That fits my belief that ME involves a large number of components being slightly abnormal, rather than one component being blatantly dysfunctional. My analogy is two gears meshing. If one part is slightly worn, the system still functions properly. If one gear is work and the other is also worn and the bearing is worn, then you may get malfunctions. In ME, some immune cells may be operating slightly abnormally, and some other cells' mitochondria might be operating slightly abnormally, and ratios of specific lipids or nutrients might be slightly differing from average, and that all adds up to a positive feedback loop that keeps us locked in an abnormal state.
Hoopoe
Senior Member (Voting Rights)
How I actually experience effort, fatigue and PEM:
There is an initial mental barrier to initiating activities that might lead to increased symptoms. It's roughly proportional to how unpleasant things could get. I'm also willing to tolerate some degree of symptom worsening, especially if things are predictable and controllable.
If the activity or a project involves unpredictable and possibly high amounts of exertion, or social pressure to do things, deadlines, or similar, then it's very hard for me to get started at all. I'm risk averse when uncertainty or external pressure is involved.
None of these barriers are by disabling or something that I couldn't deal with on my own. I regularly exceed them, and do so in a selective manner. Sometimes doing more and ending up with cumulative PEM, sometimes doing less and recovering. It's a continuous balance.
It's correct to say that there is a "psychological" element and choice and learning involved, but that doesn't mean there is anything maladaptive going on, or some false perception of things. That's just dumb prejudice. The problem is that for some reason, activity is just too physically stressful and it has to be done in a measured manner and sparingly to avoid setting off PEM, which seems to be some kind of emergency response by the body to protect itself.
Learning to live with other illnesses also requires adaptation at the "psychological" level, and choices and learning. But we don't jump to the conclusion that these are the cause of symptoms because these illnesses are better understood and not as stigmatized as ME/CFS.
There is an initial mental barrier to initiating activities that might lead to increased symptoms. It's roughly proportional to how unpleasant things could get. I'm also willing to tolerate some degree of symptom worsening, especially if things are predictable and controllable.
If the activity or a project involves unpredictable and possibly high amounts of exertion, or social pressure to do things, deadlines, or similar, then it's very hard for me to get started at all. I'm risk averse when uncertainty or external pressure is involved.
None of these barriers are by disabling or something that I couldn't deal with on my own. I regularly exceed them, and do so in a selective manner. Sometimes doing more and ending up with cumulative PEM, sometimes doing less and recovering. It's a continuous balance.
It's correct to say that there is a "psychological" element and choice and learning involved, but that doesn't mean there is anything maladaptive going on, or some false perception of things. That's just dumb prejudice. The problem is that for some reason, activity is just too physically stressful and it has to be done in a measured manner and sparingly to avoid setting off PEM, which seems to be some kind of emergency response by the body to protect itself.
Learning to live with other illnesses also requires adaptation at the "psychological" level, and choices and learning. But we don't jump to the conclusion that these are the cause of symptoms because these illnesses are better understood and not as stigmatized as ME/CFS.
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From the NIH press release
“We think that the immune activation is affecting the brain in various ways, causing biochemical changes and downstream effects like motor, autonomic, and cardiorespiratory dysfunction,” said Avindra Nath, M.D., clinical director at NINDS and senior author of the study.
“We may have identified a physiological focal point for fatigue in this population,” said Brian Walitt, M.D., M.P.H., associate research physician at NINDS and first author of the study. “Rather than physical exhaustion or a lack of motivation, fatigue may arise from a mismatch between what someone thinks they can achieve and what their bodies perform.”
This is ludicrous, they are saying totally different things. Wallitt is just talking utter bps babble. It would be laughable if it wasn't our futures on the line...
We can never as a patient group accept someone like Wallitt's involvement in a biomedical ME study again.
“We think that the immune activation is affecting the brain in various ways, causing biochemical changes and downstream effects like motor, autonomic, and cardiorespiratory dysfunction,” said Avindra Nath, M.D., clinical director at NINDS and senior author of the study.
“We may have identified a physiological focal point for fatigue in this population,” said Brian Walitt, M.D., M.P.H., associate research physician at NINDS and first author of the study. “Rather than physical exhaustion or a lack of motivation, fatigue may arise from a mismatch between what someone thinks they can achieve and what their bodies perform.”
This is ludicrous, they are saying totally different things. Wallitt is just talking utter bps babble. It would be laughable if it wasn't our futures on the line...
We can never as a patient group accept someone like Wallitt's involvement in a biomedical ME study again.
Jonathan Edwards
Senior Member (Voting Rights)
I suspect that there are scores of known programmed defence responses with varying time scales. Some of them may come under 'sickness response' but that probably includes a whole range of different mechanisms with different times cases too.
Ones I can think of:
Tanning with sun exposure.
Cessation in bone growth in sick children - Harris lines.
Loss of bone density in immobile adults.
Callus formation on hands.
B and T cell immunity.
Osteophyte formation following articular cartilage change.
Changes in heart rate with training and detraining.
Fever.
The weeks long catabolic response after surgery and trauma.
Telogen effluvium.
Limb temperature regulation adaptation in Inuit.
...
Yes, but a bit more complicated. Maybe more like the messages on your desktop to change time zone when you do not need to, which you can get to disappear temporarily but then later keep coming back three times before they will disappear again.
With no less than the NIH imprimatur.
Years of progress against BPS trash potentially undone. If so, unforgivable.
Jonathan Edwards
Senior Member (Voting Rights)
That paper may change things but I have two caveats.
One is that many previous papers have claimed to find things that have not replicated.
The bigger concern for me is that it would be hard to see how necrosis after exercise could explain PEM - which is a generalised symptom. In years past I would have muscle pain after a 100 mile sea trip requiring repeated winching. After Covid I had nothing like that. I was just poleaxed. I doubt most PWME see PEM as relating to local muscle pain - what has by some been called delayed muscle soreness.
I am not qualified to comment on the mitochondrial studies but again it is unclear what they would explain. Most studies show single CPET to be pretty normal in ME. Most PWME find their activity is curtailed not by shortness of breath or failure of muscle contraction but inability to continue exertion or fear of later payback. Delayed payback does not really fit with a mitochondrial defect which would be expected to kick in at the time.
Jonathan Edwards
Senior Member (Voting Rights)
Which maybe is right. But of course it is then not telling us about what is wrong that makes people need to pace. Working in medicine one gets to realise that not many clinical investigators can think thoughts that complicated!
Kitty
Senior Member (Voting Rights)
Not in the slightest. I feel like I'm wearing a lead suit, have the 'flu, am wearing something I'm allergic to, am developing cystitis, and have just found out a favourite uncle's terminally ill.
I'd pay money to have sore muscles instead.
Hoopoe
Senior Member (Voting Rights)
Nausea discourages people from eating things.
Pain discourages people from doing things.
Fatigue also discourages people from doing things, in a different way.
PEM discourages people from doing things, but in a very different way, more in a "don't do anything too intense, or too much in a certain time span" way.
Since these are obviously different responses, and one can conclude that they must involve different signals and programmed responses at the cellular level. It's really this simple.
If we understood how PEM signalling occurs, we might understand why some people have such a low PEM threshold.
Pain discourages people from doing things.
Fatigue also discourages people from doing things, in a different way.
PEM discourages people from doing things, but in a very different way, more in a "don't do anything too intense, or too much in a certain time span" way.
Since these are obviously different responses, and one can conclude that they must involve different signals and programmed responses at the cellular level. It's really this simple.
If we understood how PEM signalling occurs, we might understand why some people have such a low PEM threshold.
Upon further thought: It would also be good to know which of the intramural patients were patients in the WASF3 study, which criteria did they meet and were they later considered to have recovered. Perhaps some interesting data could be found in this subset.
Agree..
30% of this patient group recovered
And 30% didn’t have WASF3 I think.
…overlap?
Is this the study: https://www.theguardian.com/society...-brain-imbalance-and-chronic-fatigue-syndrome ?
A family member just sent it to me.
A family member just sent it to me.
Andy
Retired committee member
Scientists find link between brain imbalance and chronic fatigue syndrome
https://www.theguardian.com/society...-brain-imbalance-and-chronic-fatigue-syndrome
https://www.theguardian.com/society...-brain-imbalance-and-chronic-fatigue-syndrome
Then maybe they should have studied severe patients that actually can't physically do things, instead of mild patients that choose not to do them in order to avoid PEM.
One of my pet peeves is that all MECFS papers use HV or similarly deconditioned subjects as the control. What about similarly sick people? Does flu patients have "effort preference" while they still can exert maximally? (Maybe hay fever patients since the subjects in this paper are moderate/mild patients). Michael Jordan played a full championship game while suffering from severe flu, so maybe flu patients have similar "effort preference" problem. If they do, surely nobody will call that psychological.