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

[Dolphin]

@Dolphin I think the "nothing we didn't know" comment could be interpreted in ways other than having swallowed Walitt's spin.

As a standalone comment in this piece, Walitt's quoted comment is ambiguous - it could mean people can do more than they think or less than they think. If the commenting GP has only read this piece, not the paper, then I suspect the GP is more likely to have interpreted Walitt's comment to mean "People think they can do more than they actually can". GPs would be constantly hearing people reporting things like "I went back to work and now I can't get out of bed."

It is possible I suppose. I checked and here is an earlier comment by the same account:
https://www.pulsetoday.co.uk/news/clinical-areas/neurology/poor-mental-health-increases-long-covid-risk-finds-study/


Poor mental health increases long Covid risk, finds study


Matt Hancock
9 September, 2022 9:53 pm
Dont think this is rocket science. Add it to the list with fibro , me etc

 

[Kitty]

Matt Hancock
9 September, 2022 9:53 pm
Dont think this is rocket science. Add it to the list with fibro , me etc

Don't think he'll be mistaken for someone who knows anything about anything, TBH.

 

[Hutan]

The low catechol levels were measured in the CSF, is that correct?

Let's assume low catechol levels are a real signal, the authors seem to indicate they might be, wouldn't it be a bit odd not to specifically mention that despite low central catechols the patients suffered from sympathetic overdrive according to HRV results?

Yes, catechols were measured in the CSF.

I get confused when sympathetic nerve function gets mentioned. But, just looking at Parkinsons patients who appear to tend to have lowish levels of some of the catechols, they also seem to have low heart rate variability*. So, it's not impossible to have both, and perhaps these things are even connected. People with ME/CFS seem to tend to have low heart rate variability.

Not that I'm trying to suggest there's a coherent story around the catechols, because mostly, an ME/CFS result in the Walitt et al study was not distinguishable from a healthy control result. Have I understood your question?

* Association Between Heart Rate Variability and Parkinson's Disease: A Meta-analysis

 

[Evergreen]

It is possible I suppose. I checked and here is an earlier comment by the same account:
https://www.pulsetoday.co.uk/news/clinical-areas/neurology/poor-mental-health-increases-long-covid-risk-finds-study/


Poor mental health increases long Covid risk, finds study


Matt Hancock
9 September, 2022 9:53 pm
Dont think this is rocket science. Add it to the list with fibro , me etc

Yep, he absolutely could be the kind of know-it-all-but-have-no-clue we all need to avoid, but since the same genuinely has been reported for both conditions he mentions, I wouldn't indict him just on these comments. I suspect that if he expanded on his comments, it would become abundantly clear that your interpretation is correct! But since he hasn't, I'd wait to see a third.

 

[Dolphin]

Yep, he absolutely could be the kind of know-it-all-but-have-no-clue we all need to avoid, but since the same genuinely has been reported for both conditions he mentions, I wouldn't indict him just on these comments. I suspect that if he expanded on his comments, it would become abundantly clear that your interpretation is correct! But since he hasn't, I'd wait to see a third.

I'm not convinced that there is good evidence that poor mental health increases the risk of ME/CFS, though as you say it has been reported.
I think a lot or all of the studies that found this had the flaw that people could have been ill with ME/CFS but undiagnosed at that stage rather than truly being preillness.

This would cause problems in 2 ways:
(i) if you're not diagnosed, symptoms could be misdiagnosed as mental health problems
(ii) if you're not diagnosed but you are ill with ME/CFS, it's very stressful. It's quite likely you will have to work or study full-time and you are probably unlikely to be able to access many disability accommodations.

I remember Peter White did a study but didn't mention these possibilities.

 

[Evergreen]

Oh you don't need to convince me of that!

 

[Creekside]

My own personal history completely rules out deconditioning having any primary causal role.

My ME doesn't involve a reduction in physical ability, so I'm basically as active as I was before ME, possibly more so, since I live in an area that encourages long hikes and bike rides, plus necessary chores (moving 100+ wheelbarrows of soil each year to patch my driveway, plus cutting and handling firewood). So, no deconditioning involved here.

 

[Mij]

My own personal history completely rules out deconditioning having any primary causal role. I was simply too active in the early stages for that to be true.

I've been able to keep some level of fitness during my 32 year M.E career as long as I stay within my energy limits. I even pass people walking on the side walk.

 

[Hoopoe]

I don't like is the focus on deconditioning. I often feel like I'm under the influence of a mildly toxic sedative. This has nothing to do with deconditioning. I suspect this is some low grade neuroinflammation. It is very hard to get any meaningful work done when affected this way, even when no muscles are involved. I'm significantly impaired before muscles even come into play. At the muscle level, if I'm affected, the muscles will tire quickly and be unable to perform as well, and this is a fluctuating effect which also seems inconsistent with deconditioning. There is without a doubt some loss of strength and endurance due to low activity but it's not something that should be emphasized when it's a lesser downstream effect (at least for me).

 

[Amw66]

Regarding CPET, they do say

That's relevant, right?

And in a blow to women, they found what they interpret as more evidence of deconditioning in females, if I've understood correctly:


I edited to add something and took it out again because it was a brain fog metabolite.

Mm.From some metabolic studies If females preferentially use amino acids as a base fuel if glycolysis is compromised would this down regulate fatty acids ( males seem to pop referentially use fats )
Or is this not a consequence

 

[Lidia Thompson]

I thought you might find this interesting:

 

[Lidia Thompson]

... and this:

 

[Dolphin]

"Study offers clues into chronic fatigue syndrome"
https://www.pulsetoday.co.uk/news/c...y-offers-clues-into-chronic-fatigue-syndrome/

Unfortunately Walitt gets quoted in this media outlet for UK GPs.
In the comments, two of the GPs pick up on his spin suggesting many other readers will do likewise

https://twitter.com/user/status/1761399900841931234

https://twitter.com/user/status/1761404659648848338

There were four comments, now there are two though one still focuses on the Walitt comments.

 

[Trish]

I thought you might find this interesting:

Copy of tweet:

The conclusion that 'The results suggest the impact of effort preference in ME/CFS patients,' based on a study with only 17 participants and centered around the hypothesis that the temporoparietal junction plays a role in coding mismatches, stands on very shaky ground. It is unjust to label a group of patients, who are immobilized by the severity of their condition, as having 'effort preferences' based on such a fragile scientific premise. As a neurologist with a special interest in the TPJ, I have identified numerous questionable aspects of this study. I am keen on writing a letter to Nature to express my concerns about this article, but my duties as a mother are my priority. Should I find the time to write this letter, I would value
@basarsarikayamd
, a neuroradiologist, perspective on the study's radiological methodology, which I also find to be flawed. #mecfs #longcovid #LongCovidKids https://nature.com/articles/s41467-024-45107-3

 

[Eddie]

We don't need to do CPET the second day, we'll start doing other tests to measure PEM.

Its not quite that, its more like we aren't going to try and objectively measure PEM (for the reasons given) but instead going to measure lots of things to see if we can find something that could be causing PEM. Of course they failed to make any real progress towards that goal.

1) if the 2 day CPET worsening is such an established truth that it doesn't even need replication, why did this paper conclude that the disability is caused by deconditioning? If your CPET performance gets worse on the second day, that's objective evidence going against the effort preference + deconditioning theory.

Because they had Walitt in charge of the paper and they didn't want to admit they spent 8 million and 7 years to fail to find an answer. Perhaps the 2 day CPET results are less established that I would have thought. However, there have been 15+ 2 day CPET studies run with around 500 people in total (from Me Action and adding the Hanson study). If these studies failed to establish the 2-day CPET as a fact, then a 17 person study at the NIH would have added almost nothing. I'm with you that a much larger 2 day CEPT study would be useful in confirming or refuting these results. However, there are so many results I want to see confirmed and its hard to fault Nath for not running a completely different study. Would a 300 person 2-day CPET have been more useful in hindsight? Probably. But I can only say that because they didn't get more interesting results.

2) are we even really sure the patients had PEM the second day? And deduce that it can't be objectively measured (with things other than CPET), despite all the red flags in the study? When I have PEM, my POTS gets objectively worse as well as other measurable things.

Until we have a good idea of what PEM actually is, it is going to be hard to objectively ensure that all the patients had PEM. Maybe for you and me our POTS gets objectively worse, but none of these participants had POTS (still unclear why) and I not sure what other measurable things you are talking about. As far as I'm concerned the people selecting the patients had a desire to appropriately select people with ME/CFS. Also if someone who has been diagnosed with ME/CFS says and acts like they have PEM, I'm inclined to take them at their word. Yes, it is a concern that the patients had less severe PEM than some, but that is always going to be the case for a study like this.

This was a missed opportunity to do a deep dive on PEM and see if any other marker or measurement would correlate with the CPET worsening. I don't see how their response can be considered acceptable given the stakes and how this study was hyped as the ultimate deep dive into ME.

My guess is that they thought they were doing a deep dive on the pathology of PEM (or at least why people say they feel worse after exertion) with the tests on the days after the CPET. They did run lots of tests, unfortunately in hindsight they weren't looking in the right places or with advanced enough tech because they didn't find much. I agree this study was hyped up far too much for what they found and that is obviously very disappointing to me.

 

[dave30th]

It took us several months, maybe a couple of years

I spent a year on and off reading and interviewing before finally publishing my initial 15,000-word investigation of PACE. Added: As @Dolphin might remember!

 

[siobhanfirestone]

My ME doesn't involve a reduction in physical ability, so I'm basically as active as I was before ME, possibly more so, since I live in an area that encourages long hikes and bike rides, plus necessary chores (moving 100+ wheelbarrows of soil each year to patch my driveway, plus cutting and handling firewood). So, no deconditioning involved here.

on medication im very much able to weight lift and ive become quite strong over the last year
tell someone who can lift 25kg+ as a smaller woman that they are deconditioned when most lift <20kg lol

 

[Sean]

If these studies failed to establish the 2-day CPET as a fact, then a 17 person study at the NIH would have added almost nothing....

Would a 300 person 2-day CPET have been more useful in hindsight? Probably.

Ideally you would want enough patients to split them into two groups, those who did a single CPET, and those who did the 2 test version.

Finding any differences, or lack of them, could have been useful. Most likely the main difference, if any, would have just been one of degree, with the 2 test group results being significantly worse.

 

[Sean]

I've been able to keep some level of fitness during my 32 year M.E career as long as I stay within my energy limits. I even pass people walking on the side walk.

I walk significantly faster now than before I got sick. Best I can tell it is because I had to instinctively recalibrate the optimal relationship between factors like energy reserve and expenditure, haemodynamics, balance and coordination, and momentum. With momentum being the main compensating variable under my control. An increase in momentum helping to reduce the amount of effort required to manage the other factors.

 

[Eddie]

Ideally you would want enough patients to split them into two groups, those who did a single CPET, and those who did the 2 test version.

Finding any differences, or lack of them, could have been useful. Most likely the main difference, if any, would have just been one of degree, with the 2 test group results being significantly worse.

What do you mean by finding any differences? What are you comparing between the people did 1 CPET vs 2? The people who did the 1 day would still have PEM you just wouldn't pick it up on the 2nd CPET assuming a difference really does occur.