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

[tuppence]

I recall writing on this forum multiple times about how my body, when not in PEM, appears to be unable to fully sense whatever problem it is that leads to PEM.

The brain feels as if it's capable of doing a thing, and motivation and interest surge, but then the actual ability to do things is vastly lower. It fails to predict the consequences and overestimates its abilities. We cannot trust that feeling good and motivated in the moment actually means being able to complete the task that we feel good and motivated about. This is a very consistent pattern.

The behaviour that we patients learn to compensate for this comes across as anxious, overly passive, lacking motivation, negativity, etc. Other people think the cure is to get us to enter into a more positive mental state but that doesn't help at all in the log term.

If anything the perception problem is that we think we can, but actually can do much less (especially in a sustained manner).

Exactly.

And my reading of this Study from a lay persons point of view is that some of the language used by the writers to discuss their findings obfuscates the issue by not clearly drawing out that their findings as reported completely validates Hoopoes and countless other ME patients description of their ‘effort intolerance’ and ‘behavioural response’ to the disconnect between what they often feel they can do, but find their body physiologically disagrees with them and they suffer physical symptoms as a result.

The reported findings in this study, to me, validate entirely the ‘Pacing’ response employed by patients and those medics who for years have understood the disconnect between what patients want to/try to do and what their bodies actually allow them to do.

The Researchers own stated outcome of this study is that it provides yet more proof of the biological basis of ME by identifying a range of biological anomalies not present in healthy controls and that it is unequivocally wrong to say or think that ME patients can think or change their behaviour in any way to cure themselves. In this they validate the 2021 NICE recommendation that the BPS approach and treatments of GET and CBT based on the idea that Patients can do more than they think they can, is an inappropriate response to this illness. This biological research in fact demonstrates the biology of why the reported outcomes of BPS behavioural trials in ME actually show their treatments are universally ineffective and potentially harmful to ME patients. The lack of ‘effort’ is ‘not motivational’ but ‘physiological’ as stated in this Studies biological findings.

These Researchers acknowledge they themselves are no nearer to explaining the why or what of ME other than to say it is Biological Science and much more of it that is required to find the answers.

I am pleased after being at this same place since my first involvement with ME over 40 years ago, that at last the Press is largely, finally reporting that a Study unequivocally shows ME to be biological and not a result of false illness belief on the patients part. I will be kind in my judgement of the obfuscation apparent in some of the researchers analysis and press comments, by putting it down to them getting used to a new paradigm.

I bow to and am grateful for the scientific knowledge shared by the members of this forum and thank you for your past efforts to advance the biological research on ME. I am sure that you will continue to comment on and push for good quality ME research as we move forward.

 

[Creekside]

Actually, I think it is likely that people making conscious decisions just IS neurons making decisions based on their chemical/electrical environment.

Yes, and some of those decisions are autonomic, bypassing conscious or even subconscious thought. We might want to pick up a 40 kg item, but that autonomic processing loop is not sending the signals needed to contract the muscles enough for that. The control system for a front-end loader, for example, limits how much hydraulic pressure can be applied to the cylinders, to prevent damage if you try to lift something too heavy. A flake or rust in the sensor might mean that the relief valve opens when trying to lift 100 kg rather than the expected 1000 kg capacity. I'd love to see a psychologist trying to convince a loader to lift more. "Just try harder and you'll succeed..."

 

[Creekside]

If PEM was called next-day malaise it would help.

No, my cognitively-induced PEM had a delay of < 1 hr, and was gone by the next day. The symptoms were indistinguishable from my 24-hr delayed physically-induced PEM. Other people reports shorter or longer delays for physically-induced PEM, so "next day" is too limiting.

 

[Mij]

Wouldn't an experience of lack of willingness be indicative of depression or asked differently what would be different to depression then?

Depression is a physical illness, some can't leave their beds or eat for 3-4 days.

Feeling depressed and depression are not the same.

 

[Hubris]

Depression is a physical illness, some can't leave their beds or eat for 3-4 days.

Feeling depressed and depression are not the same.

The difference is that, fundamentally, people with depression do not want to leave the bed. They have no POTS, PEM, and If they are forced to go out and exercise they will feel better almost immediately, and in the following days as well.

Doctors prefer to prescribe SSRIs because motivating someone 24/7 to do things is just not feasible (CBT is already a huge spend and you only do it 1h every week) but the fundamental thing is that people with depression can do things, even if they won't. There is no scenario where a depressed patient ends up being worse off because they were forced (or convinced, hence the CBT) to do things.

The doesn't mean depression is not organic, of course it is, but it's simply a very different kind of illness compared to ME.

If the researchers don't understand this crucial difference and think ME is like depression how will they ever find the cause of the illness?

The only reason they didn't recommend CBT in this paper is the political pressure. If you think unwillingness to put in effort is a core feature of the illness, CBT/psych drugs is the obvious treatment. I don't really see how it would be different from depression. Depression mouse models are quite literally this, mice that don't want to move or swim as much.

 

[rvallee]

Oddly, I see a lot of people talking about being able to push through, knowing there will be pushback, but in my experience, and I've seen it plenty of times, there is another limit beyond which physical movement becomes impossible, the leaded body feeling that is completely unique to this. To me it's not comparable to being weak with the flu, it's that poisoned feeling that feels like everything is rusty, as if the nerves are incapable of producing anymore activity.

At this point there is no amount of forgetting, or not knowing, about the wall. There is only the wall. It's the point that causes extended deterioration, past which there is often a permanent lowering of functioning. It feels like all energy being drained out of the body, it just ceases being able to exert anymore.

So really there are two thresholds: one we can push through with consequences, and one where no amount of threat, coercion or willpower can overcome. It's a near paralytic state at first. I'm quite sure it's the CNS driving most of it, but it could be as a feedback response from exhausted muscles, although that wouldn't account for instances where it happens without physical exertion, such as sensory or cognitive overload.

 

[duncan]

I cannot decide whether this study is a Fool or a Tool.

 

[Sid]

The reason they didn't pay attention to PEM and the 2 day CPET is that they don't think it's real

Of course. It was obvious from the start. Many of us were pointing out the huge red flags, like the 1-day CPET, the gruelling protocol which would prevent moderate and severe participants from taking part, the background of key investigators like Walitt (FM is psychosomatic) and Hallett (major FND guy). All of this was debated at length 7-8 years ago on the previous forum when the details first began to emerge. But all concerns were dismissed as paranoia. Trust the NIH, we were told. The NIH has changed. Etc.

 

[Mij]

The difference is that, fundamentally, people with depression do not want to leave the bed.

People suffering from depression are stigmatized in the same way as pwME. I am not comparing symptoms of depression to M.E.

Some with MDE are physically unable to leave their bed and have to be hospitalized.

I had a close friend who was bedbound for days, not because she didn't want to leave her bed, but because she was physically unable to leave her bed. She needed a caretaker.

 

[V.R.T.]

The difference is that, fundamentally, people with depression do not want to leave the bed. They have no POTS, PEM, and If they are forced to go out and exercise they will feel better almost immediately, and in the following days as well.

Doctors prefer to prescribe SSRIs because motivating someone 24/7 to do things is just not feasible (CBT is already a huge spend and you only do it 1h every week) but the fundamental thing is that people with depression can do things, even if they won't. There is no scenario where a depressed patient ends up being worse off because they were forced (or convinced, hence the CBT) to do things.

The doesn't mean depression is not organic, of course it is, but it's simply a very different kind of illness compared to ME.

If the researchers don't understand this crucial difference and think ME is like depression how will they ever find the cause of the illness?

The only reason they didn't recommend CBT in this paper is the political pressure. If you think unwillingness to put in effort is a core feature of the illness, CBT/psych drugs is the obvious treatment. I don't really see how it would be different from depression. Depression mouse models are quite literally this, mice that don't want to move or swim as much.

I mean when I had depression and not ME (as far as I know, it's all a bit up in the air looking back) I felt miserable when I was out in the world.

When I tried to do things that used to cause me joy or excitement I often felt nothing.

So I see your point but I don't think you understand depression.

 

[Trish]

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

A) MECFS patients are capable of exerting, and B) if they do, they keel over the next day.

A) MECFS patients are capable of exerting, and B) if they do, they keel over the next day. The only difference is the use of term "effort preference" to denote that the fatigue in non-PEM state is the product of pacing, not peripheral fatigue.

Oddly, I see a lot of people talking about being able to push through, knowing there will be pushback, but in my experience, and I've seen it plenty of times, there is another limit beyond which physical movement becomes impossible, the leaded body feeling that is completely unique to this. To me it's not comparable to being weak with the flu, it's that poisoned feeling that feels like everything is rusty, as if the nerves are incapable of producing anymore activity.

I'm with @rvallee on this. The stuff about effort preference makes no sense to me. I stop an activity because I can't keep doing it. I also try to pace by breaking up activities and resting between and avoiding activities I know from experience will be impossible or cause a crash, but the thing that stops me part way through an activity is becoming increasingly unable to do it.

It's happening now. I spent far too much time today thinking and typing my response to a questionnaire and submitting it. I pushed myself to keep going because I know from experience that if I don't submit I go on thinking and tinkering for ever. Now I'm trying to type this and am slowed right down, every word is an effort and full of typos that I have to correct. It's not effort preference that is slowing my typing, it's physical fatigue and cognitive fatigue that prevents me accurately touch typing so I'm doing it letter by letter and still making mistakes.

 

[Sid]

Oddly, I see a lot of people talking about being able to push through, knowing there will be pushback, but in my experience, and I've seen it plenty of times, there is another limit beyond which physical movement becomes impossible, the leaded body feeling that is completely unique to this. To me it's not comparable to being weak with the flu, it's that poisoned feeling that feels like everything is rusty, as if the nerves are incapable of producing anymore activity.

At this point there is no amount of forgetting, or not knowing, about the wall. There is only the wall. It's the point that causes extended deterioration, past which there is often a permanent lowering of functioning. It feels like all energy being drained out of the body, it just ceases being able to exert anymore.

So really there are two thresholds: one we can push through with consequences, and one where no amount of threat, coercion or willpower can overcome. It's a near paralytic state at first. I'm quite sure it's the CNS driving most of it, but it could be as a feedback response from exhausted muscles, although that wouldn't account for instances where it happens without physical exertion, such as sensory or cognitive overload.

Agreed. The description of the disease by the paper does not ring true to me. As someone who has POTS, I can only do so much. After a certain point, I can’t physically push through the shortness of breath, weak muscles and tachycardia. It’s sit/lie down or literally collapse on the floor.

 

[duncan]

It's not just fatigue or weakness. ME/CFS includes other feelings of sickness. Balance, poisoned sensation, pain, dizziness - this study seems to gloss over these. Others like cognitive decline, it seems to dismiss or discount. PEM appears MIA. Overall this study seems a gross mischaracterization of ME/CFS.

How do they get it this wrong?

 

[dave30th]

The EI in SEID I have assumed implied something like 'food intolerance' in the sense of adverse reaction with PEM.

yes, the exertion intolerance isn't the wish to stop. It's the fact that people have a physical, somatic reaction afterwards. You're not having PEM during the exertion itself, so you can't really have the exertion intolerance during the exertion, at least as I've been understanding the term.

 

[dave30th]

Additional (rhetorical) question, how do they know that the encouragement was an influence either way? Did they have the patients do a CPET with and without encouragement, in order to be able to compare?

Also, just because someone can push themselves to finish a task doesn't mean their bodies can actually handle that without subsequent damage. The logic seems off.

 

[Hutan]

Also, the IOM criteria require that core symptoms be present at least ½ the time and be at least moderately severe. But the study's source data for the CDC symptom Inventory responses show that 10 of 17 pwME experienced this "unusual fatigue after exertion" only "a little of the time.” The other options were a) Some of the time, b) A good bit of the time, c) Most of the time, or d) All of the time.

The IOM criteria are not straightforward to apply.

Do I have PEM half of the time? No, because I manage my activity levels to mostly avoid that. I don't have "unusual fatigue after exertion" most of the time because I often try not to exert in a way that produces that outcome. (I don't think I even have fatigue half of the time, although it's possibly a bit like fish not recognising water, perhaps some level of fatigue is my normal now.)

Am I likely to develop PEM if I do a strenuous physical activity that, when I was healthy caused no problems? Yes, most of the time.

The criteria are problematic. I think the NIH could quite easily have got a group of people who obviously have mild ME/CFS, but still have them saying that they have PEM only a little of the time. It comes down to how you interpret the question.

I believe that, given the involvement of clinicians who see a lot of people with ME/CFS, at least most of the 17 participants were appropriately selected. The study has a lot bigger problems than selection, in my view.

 

[Hubris]

It's not just fatigue or weakness. ME/CFS includes other feelings of sickness. Balance, poisoned sensation, pain, dizziness - this study seems to gloss over these. Others like cognitive decline, it seems to dismiss or discount. PEM appears MIA. Overall this study seems a gross mischaracterization of ME/CFS.

How do they get it this wrong?

Those symptoms are psychosomatic and thus not relevant. The only symptom that they considered "real" was this apparent unwillingness to do things, whether it is immune mediated or some brain process gone wrong. They are studying ME like a psych illness.

 

[dave30th]

But the study's source data for the CDC symptom Inventory responses show that 10 of 17 pwME experienced this "unusual fatigue after exertion" only "a little of the time.” The other options were a) Some of the time, b) A good bit of the time, c) Most of the time, or d) All of the time.

This question seems problematic. If folks are pacing effectively, maybe they're not experiencing PEM. Or maybe only a little. Is the question asking about what happens IF they have too much exertion or WHEN they have too much exertion? Those are different questions.

 

[duncan]

Those symptoms are psychosomatic and thus not relevant. The only symptom that they considered "real" was this apparent unwillingness to do things, whether it is immune mediated or some brain process gone wrong. They are studying ME like a psych illness.

Didn't they have ME/CFS researchers advising them? There should be a response from that group. There also should be a coordinated response from every ME advocacy organization condemning this Russian Doll "effort" drivel embedded within what was advertised to be a serious and dedicated ME/CFS study.

 

[dave30th]

The only reason they didn't recommend CBT in this paper is the political pressure. If you think unwillingness to put in effort is a core feature of the illness, CBT/psych drugs is the obvious treatment.

They state clearly, if I remember, that CBT and exercise are "downstream" treatments not likely to have any impact on the immune-related causal factors--so that's a positive message at least. I think the choice of the phrase and model of "effort preference" was spectacularly misguided and ripe for misinterpretation and over-interpretation, like the choice of "chronic fatigue syndrome"--and they've done very little if anything to make sure that it is not misinterpreted. But having said that, I'm trying to absorb or interpret the term in the more narrow scientific sense in which I think they seem to be using it and not in the way it obviously sounds to the average reader--as a purely psychological or conscious decision.