The Concept of ME/CFS, 2024, Edwards

[Simon M]

PVF(S) & ME/CFS

from the paper @Jonathan Edwards
"The concept of ME/CFS is not focused on a specific agent...

What remains unclear is to what extent the majority of cases of post-viral fatigue resemble ME/CFS or are more like the fatigue associated with conditions like rheumatoid arthritis and heart failure.

Differences in temporal profile may also be critical. Active EBV infection can produce severe malaise for several weeks and post-EBV ‘fatigue’ may be seen simply as a failure of resolution of those symptoms with normalisation of the blood picture.

Long term ME/CFS is recognised after EBV infection, but it may not be merely a longer version of a ‘PVFS’ category (that need not include ‘crashes’ and sensitivity to light and sound). ...
Covid-19 has joined the group of infections with a high rate of post-infective problems, much like EBV.

Sifting out different clinical patterns may be crucial to useful explanatory research, and detailed time course may be as important as symptom categories. Very likely the situation is not simple, just as the relationship of ‘palindromic arthritis’ ..."

This is a very helpful way of looking at things, esp PVFS.

Are you saying that you think there are two groups of PVF (inc post-Covid):
1. Similar to more typical fatigue, delayed or non-resolution of the initial fatigue?
2. And ME/CFS or similar?

And are you also saying that some of the first category could wind up with an ME/CFS diagnosis?

Some relevant data: We know from initial DecodeME survey data (see Fig 1) that 17% of those with an ME/CFS diagnosis report a glandular fever onset. A further 2.5% are post Covid and another 44% report other infectious onset: about 2/3 in total. Over 90% of those with a diagnosis report PEM - it's probably much higher amongst the 83%+ that meet CCC/IOM criteria.

PS over 70% report variations in severity: fluctuating or relapsing remitting (also fig 1).

 

[JohnTheJack]

I am aware that the lying flat bit and the unpredictability are not 'in the books' but to me they point to aspects that have not been that well covered by the standard accounts and so I think they are worth stressing a bit.

I have now listened to about 500 people on forums describing their symptoms. I am pretty sure that not having an element of feeling forced to lie flat and not having an element of unpredictability are atypical. That isn't to say not having them must be outside the syndrome but time and time again I hear people talking about OI in the wider sense that being recumbent or partly recumbent is necessary some of the time. And I think this distinguishes ME/CFS symptoms quite clearly from 'secondary fatigue' seen with systemic illness like renal failure or RA. I also think it is not typical of depression. I have trained on, and visited, wards with people with severe depressive illness and encountered it in the family. In general the seriously depressed individual sits motionless looking out of a window or into the middle of a room. It also emphasises that the problem is not just deconditioning or lack of ability to move about, although that lack is there. It is a symptom complex that no way would one expect to benefit from doing exercises any more than you would tell someone with acute vertigo to go for a walk (ensuring that they vomit and call over).

But thanks for the comments.

Yes, I know and appreciate you have spent a lot of time listening to patients.

I feel quite strongly, though, that there is no source that can support these claims. I would not put it as strongly as the paper does. I think it would be better to say that from this experience of yours you think these are areas to investigate both as ways to differentiate the experience of ME/CFS from that of other illnesses and, possibly, as a way of differentiating different kinds of ME/CFS.

Also, as I say, I am concerned that a new criteria is implicitly being created: the Canadian, the international consensus, the NICE and now the ME/CFS 2024 criteria.

I'll leave it at that. I won't keep returning to these same points.

 

[Andy]

I wonder how many of us are significantly worse in the mornings? Outside of PEM/crashes I am, too; that seems to be fairly common and will not be shared by people with some other fatiguing conditions (some will worsen as the day progresses).

On average, my peak hours are normally between late morning and mid afternoon. Cognitively before that period I am typically at my worst, and afterwards is when my physical capacity starts to diminish as time passes.

 

[MeSci]

I feel worst from about 1100 to 1500, after which I start to 'recover'. It's largely driven by my gut, I think. When it's emptied (through defecation) I feel better.

 

[Yan]

I feel worst from about 1100 to 1500, after which I start to 'recover'. It's largely driven by my gut, I think. When it's emptied (through defecation) I feel better.

I've found a similar pattern to me. I've also noticed that if I don't eat at evening, and then I sleep/rest for about 12 hours, there's a good chance that I wake up feeling quite ok. Then after breakfast comes few hours worse times before I start to get better towards evening again. Usually.

 

[rvallee]

It does appear that BPS, but also health economics have taken away this crucial part of medicine - to relieve suffering

If only. I have only studied economics for a year, but I can assure you that serious health economics evaluations in chronic illness would yield very different recommendations than we see. Economics is a lot smarter than that. What we're seeing instead is pseudoeconomics applied to validate pseudoscience in an excessively biased culture dominated by politics, where what they evaluate makes exactly as much sense as having PACE's overlapping entry and recovered criteria.

You can find economists who will sign off on this BS. You can also find economists who will agree that slavery has its merits. Opinions can be interjected anywhere, even by people who otherwise know better. But it would be a misapplication of most of the basic principles and none of it would stand a serious neutral assessment.

One of the early concepts in intro economics classes is the notion of homo economicus. This model of a person that is central to the early pedagogic examples, one that is wholly artificial, having perfect information and always making rational decisions maximizing the utility of their money, time or resources. It's just a teaching model. For a while it was a bit overemphasized and misapplied onto real world economics but that went out the window quickly, because models are not reality. It's the math for physics equivalent of "imagine a cow as a spherical object of uniform density" when calculating ballistic trajectories.

In the biopsychosocial model, those are central. The models are the whole. In fact there is nothing else than the BS reductive bigoted stereotype of a dumb infantile person who is completely ruled by emotions. Economics isn't science, most of the concepts are social in nature, and still it's so much smarter than this biopsychosocial nonsense it's actually an absurdity that they are taught at the same level. One is a serious academic field of study. The other is kindergarten level eating paste at the back of the class. We would be far better served if economics played a more significant role.

 

[rvallee]

I think that's well worth doing.

I'e always assumed it's to do with severity, since the only times I've physically needed to lie down during the day were when I was very ill. I sometimes feel like lying down, but not enough to make it worth the discomfort—slouching will do instead.

In reality the pattern may be nothing like that at all. If that's the case, we ought to know about it.

It would probably yield conflicting data since adaptation to the illness is so difficult to master. Lots of people push through things, may follow recommendations to avoid naps and so on, then later improve a bit by integrating naps, and now you have data points where less severity is associated with more naps.

Problem is there is no data about the illness that can ignore the adaptation to the illness. They're mixed in together and are very hard to disentangle. I think it's possible but not humanly realistic. It would take AIs working with huge datasets to get anything useful here.

 

[Simon M]

I am concerned that a new criteria is implicitly being created: the Canadian, the international consensus, the NICE and now the ME/CFS 2024 criteria.

I think that is a fair point, given lack of hard evidence of high levels of OI.

Though I like the concept of orthostatic intolerance when it is treated solely as a symptom without the questionable haemodynamic claims.

I like the simplicity of the IOM criteria:
Substantial functional impairment, fatigue and PEM
+ cognitive impairment and/or OI
+ sleep disturbances.

(The inclusion of OI surprised many, and I had wondered if it was there because Peter Rowe was an author.)

What I'm uncomfortable with is prioritising OI over cognitive and sleep issues when we know these are extremely common (though not quite universal). DecodeME is a good data source again.

Sleep is more questionable, but when I looked it was only reported for around half of MS patients and is "hard to pin down for RA" according to one report, but appeared to be far from universal.

It would help to at least explain why OI is being elevated to effectively one of 2 core symptoms (alongside PEM), and others are being deprioritised compared with other criteria.

 

[Jonathan Edwards]

I can understand the concerns but I have no intention of creating diagnostic criteria. I have always thought they were pretty unhelpful in rheumatology. Each patient's problems are different and managed accordingly. For research purposes it is usually best to study very typical cases and extrapolate where it seems justified.

I could have added in sleep and cognitive difficulties but I am not sure that it would change the argument being made - that there is a concept of a symptom complex that is not simply fatigue of unknown origin. This is not an article trying to give an exhaustive account of ME/CFS or advising people on how to recognise it. It is intended to serve quite different purposes.

And when it comes to useful clinical discrimination whether or not a feature is common or universal isn't necessarily what matters. And as indicated, I am not sure that I would ever want to try to pin down a set of criteria. Most of the time in medicine one works with probabilities and incomplete information. And as we come to see that pathogenic mechanisms involve alternative overlapping interacting elements looking for neat diagnostic categories was never justified on a priori theoretical grounds.

 

[Robert 1973]

Some more comments:

Secondly, symptoms relapse or worsen with a time relation to exertion that is delayed and prolonged but also unpredictable, in a way not explained by immediate physiologic change, or local tissue effects (in contrast to post-exercise muscle soreness).

I'm not sure I fully understand this. Would it be better to say: "in a way not explained by identified immediate physiologic change, or local tissue effects"?

Certainly physicians, since the key skills required are the evaluation of ongoing symptoms for signs of alternative or additional diagnoses and early preventive measures for problems such as osteoporosis and, in rare cases, nutritional failure. But which? Neurologists? Rheumatologists? Infectious Disease Physicians? This may be the wrong question. We have so little theoretical base for ME/CFS care that it may not matter what specialty training carers have received, other than, crucially, a training in critical thinking that prevents them sliding into poorly grounded theory-driven practice.

They also need to know how to observe and to have the appropriate knowledge, skills, time and motivation to make use of their observations (as you have). I also think you could put more emphasis on the need for physician-led services as a gateway to advancing research.

The advantage of ME/CFS is that it is overtly a pragmatic compromise term that implies an illness with a reasonably well-established epidemiology that we understand nothing about and for precisely that reason need to turn our attention to.

I wonder if that is an overstatement, or perhaps not specific enough. Earlier you write: "Nevertheless, a huge amount of progress has been made in the last decade." Does that not contradict the notion that we know understand nothing about it? Might it be better to say something to the effect that we know nothing or very little about the aetiology or pathophysiology other than what it isn't?

It might turn out to be as simple as another error of acetyl choline metabolism, with complicated secondary effects.

Is that consistent with the assertion that "Metabolic deficits do not fit well either"?

 

[Simon M]

I have no intention of creating diagnostic criteria.

I appreciate that. At the same time, I had the impression you were were describing the concept of something by focusing on the symptoms that you feel Best capture it.

I’m not sure the PEM plus OI are the best way to capture what I feel I have. Of course, people with ME experience a vast range of symptoms, so we’re talking about the most distinctive ones here.

I’m not sure that these two symptoms are the best way to describe what most people experience, or indeed to experience describe it to a stranger.

I can understand that OI could be a better discriminator than cognitive difficulties. But without any data to support this, it feels like a big pivot.

Overall, though, I think this article helps move things forward with its clarity of thought. I was initially uncertain as to its purpose, but now I’ve understood what you mean, I can see how it shows the problem more clearly and wI’ll, hopefully, make it easier for people to see how to make progress.

 

[Jonathan Edwards]

I’m not sure the PEM plus OI are the best way to capture what I feel I have.

But that isn't really the issue, Simon. I have highlighted certain things to make certain strategic points relating to how we can justify a concept of ME/CFS. I emphasised a relation to lying flat (not actually OI per se) because it seemed to me a bit different from the usual story and maybe more likely to make people think.

If I trotted out the usual stuff I suspect it would appear that I am just trotting out the usual stuff because I have the usual axe to grind (whatever that might be).

I am also quite interested in the fact that these concerns are all coming from men! Maybe the male illness is a bit different. What you feel you have may not be what others feel they have. What matters to me is that this is neither an encephalitis, nor an exaggerated form of what follows exertion ('fatigue') but something with completely unrelated features - some of which I mention, some not.

 

[Trish]

I think the prominence given to OI in the article is justified because it seems to be a major factor in problems very severe pwME face with enteral feeding, and not coping with lying at the angle recommended by guidelines.

For me, OI is a significant problem and is more disabling than cognitive problems.

 

[Kitty]

I can understand that OI could be a better discriminator than cognitive difficulties. But without any data to support this, it feels like a big pivot.

I guess it might depend what you mean by OI? I use it as a shorthand for feeling unwell after a brief period of standing still—in a way that healthy people almost never do—which drives me to sit down. More severely affected people get the same thing when sitting upright, and have to lie down.

So it's a very common and rather distinctive symptom of ME/CFS, for which we have no explanation. PEM is in the same category; we don't understand it and can't test for it, so the only data we have are that a very large proportion of people report experiencing it. That doesn't automatically make it questionable, though.

ETA: I missed the posts by Jonathan and Trish whilst writing this, so it's probably superfluous!

 

[SNT Gatchaman]

For me, OI is a significant problem and is more disabling than cognitive problems.

Same here. Although I certainly have neurological problems in terms of sound >> light hypersensitivity and maybe chronic daily headaches also falls under that umbrella, maybe not. I was struck when one of the few specialists I have seen (I've been quite discriminating, especially after one of the first was hopeless!) reported that my case was quite atypical due to the lack of cognitive impairment.

I suspect this is more common than realised, so I quite like the IOM criteria as a result. One possibility I've commented on previously is the idea that OI is a protective mechanism driven by the brain to save itself (and thereby cognitive function on the way). If that's true perhaps this compensation is simply not possible in many or beyond a certain level of severity. Perhaps part of that also relates to the cardiovascular differences between the sexes. I might be biased but I like the way Jonathan has emphasised this feature, which like PEM seems distinctive. Even though I'm significantly improved to moderate from being unable to raise my head from the pillow, I still walk only a little around the house, sit most of the day, and at least a few hours of that is with my legs elevated.

 

[Sean]

OI has been a major feature for me since day one, it was one of the first obvious symptoms (though I did not recognise it as OI to start with, having no previous experience with it or medical knowledge about it, all I knew then was that lying down helped, and sometimes was necessary to avoid fainting).

Not just the immediate sensations from standing for too long, but other things, such as: feet that were cold (not merely cool) to the touch in the middle of a tropical summer (so could not possibly be due to weather/environment), and not just my touch but other people's, who were shocked at how cold they were; and purpling of the lower legs and feet (i.e. pooling, the failure to get blood adequately recirculated back to the heart and lungs for re-oxygenation, and this was in somebody in their early 20s who was by all conventional standards fit and healthy – it simply should not have been happening, but it was).

Also, I wonder how many of us experience periods of complete remission? (I never have, not in 20 years.)

Never experienced anything remotely resembling remission. I have shifted between levels of severity (though broadly always on the worse half of the spectrum), but never felt in any way healthy. Not even close.

What we're seeing instead is pseudoeconomics

aka Justifications for cost cutting (for governments on health and welfare budgets) and profiteering (for private businesses – looking straight at you health and income insurance companies).

It would probably yield conflicting data since adaptation to the illness is so difficult to master....

Problem is there is no data about the illness that can ignore the adaptation to the illness.

This.

 

[Nightsong]

Strange that this paper has been assigned to the subfield of "Psychiatry and Mental Health". Perhaps some automated categorisation by Qeios? Looking back at the nutrition paper it was Medicine > Rheumatology. The categorisation is on the left, under the Altmetric score.

(Speaking of Altmetric scores, they're highly correlated with shares/citations/mentions on social media. Just saying.)

 

[obeat]

OI is a hugely significant symptom from the point of view of getting good clinical care.

 

[Jonathan Edwards]

Strange that this paper has been assigned to the subfield of "Psychiatry and Mental Health".

Oops. I will ask Qeios to change that.

 

[Simon M]

@Jonathan Edwards, it's up to you if you reply, but I wanted to check you had seen this post (quoting the most relevant bit). Thanks

This is a very helpful way of looking at things, esp PVFS.

Are you saying that you think there are two groups of PVF (inc post-Covid):
1. Similar to more typical fatigue, delayed or non-resolution of the initial fatigue?
2. And ME/CFS or similar?

And are you also saying that some of the first category could wind up with an ME/CFS diagnosis?

Some relevant data: We know from initial DecodeME survey data (see Fig 1) that 17% of those with an ME/CFS diagnosis report a glandular fever onset. A further 2.5% are post Covid and another 44% report other infectious onset: about 2/3 in total. Over 90% of those with a diagnosis report PEM - it's probably much higher amongst the 83%+ that meet CCC/IOM criteria.