The Concept of ME/CFS

[Mij]

Cold sores, mouth ulcers, swollen glands crop up at the beginning of Spring every year in my case. I also experience immediate PEM from overexertion during the Spring/allergy season. The delayed PEM lingers longer during the Spring, around 1-2 days. This has been occurring like clockwork for many years in my case.

It feels like my immune system is more overwhelmed during the Spring months which lowers my energy levels on top of PEM.

Immediate PEM does not negatively affect my cognition.

 

[Jonathan Edwards]

Oversimplifying what?

Voluntary action.

 

[duncan]

Our perception of voluntary action is known to be very illusory. You can trick it in bizarre ways. All our experiences of not just the world but our own bodies are narrated in artificial stories in our brain cells. This is where Nath and Walitt end up oversimplifying and coming up with 'effort preference'.

I'm sorry, I find this "perception of voluntary action" reference combined with "our own bodies are narrated in artificial stories in our brain" - both in close proximity to ME/CFS - a little disconcerting. I'd greatly appreciate you explaining how this fits your ME/CFS understanding, preferably without analogies.

I apologize if I am being dense.

 

[Jonathan Edwards]

how this fits your ME/CFS understanding

Nath and Walitt claim that if it is shown that your muscles work OK and you claim not to be able to use them this must be due to a faulty 'effort preference'. At least I think they say that, they seem to say different things at different times.

We know that is nonsense because there are lots of situations where the muscles are fine but you cannot use them - because there is some more subtle blockage to the signals to and from muscles. Myasthenia is the easiest one; we now the precise mechanism. Not being able to run away during REM sleep is a well known one but not at all understood. Pain inhibition is. well known one that is reasonably well understood.

The point being that the sense that 'my muscles simply don't contract' is perfectly consistent with normal muscles and normal volition.

 

[duncan]

Nath and Walitt claim that if it is shown that your muscles work OK and you claim not to be able to use them this must be due to a faulty 'effort preference'. At least I think they say that, they seem to say different things at different times.

We know that is nonsense because there are lots of situations where the muscles are fine but you cannot use them - because there is some more subtle blockage to the signals to and from muscles. Myasthenia is the easiest one; we now the precise mechanism. Not being able to run away during REM sleep is a well known one but not at all understood. Pain inhibition is. well known one that is reasonably well understood.

The point being that the sense that 'my muscles simply don't contract' is perfectly consistent with normal muscles and normal volition.

Thank you, and sure, but how does that relate to ME/CFS, and how do perception and artificial stories in our brain cells and faulty neural signaling fit?

If I say "persistence" is at the root of ME/CFS, or a corrupted immune response, or an autoimmune issue - any of these could qualify as an explanation of ME/CFS as far as I'm concerned. Something outside those three I need help with.

 

[Jonathan Edwards]

Thank you, and sure, but how does that relate to ME/CFS, and how do perception and artificial stories in our brain cells and faulty neural signaling fit?

When I try to stand up from near the floor my brain tells itself that my muscle cannot contract. It just won't. But I know that if you put an electric current through it it contracts fine - I have had it done as part of electrophysiological tests. And of course the muscle works fine in other positions. The same happens when you have flu. Your brain tells itself that it cannot stand up. Neural circuits are blocked by cytokine effects it seems. It seems to me likely that something similar is going on in ME/CFS.

Autoimmunity occurs when perfectly normal negative signalling feedback loops flip into an abnormal positive loop for reasons that are reasonably well understood, at least for some conditions. The central nervous system has at least complicated feedback systems. Nothing needs to persist other than the continuing signalling and some sort of self-perpetuating 'set' to switches to the wrong position. The big question for ME/CFS is whether the wrong set is in the immune system, the central nervous system or both. I think any of those could be true but the more I see of the literature on ME/CFS and the more I listen to personal experience accounts the more I tend to think that a long term re-setting of the immune system is relatively unlikely, other than perhaps in terms of local adhesion of complement regulatory proteins that can affect peripheral nerve responsiveness.

 

[poetinsf]

I don't quite understand what this paper is trying to accomplish. Aren't we well past the concept stage with ME/CFS? ME/CFS is not a concept; it is a concrete manifestation with well-understood symptomology and well-defined diagnosis criteria: disabling fatigue not refreshed by rest or sleep + PEM (though I'd argue PEM alone is enough). As for "ME/CFS", it is just an identifier as far as I'm concerned that is uniquely attached to ME/CFS. It could well be MC19jxt-2 or something for all I care. I don't quite see a need to rehash what ME/CFS is or isn't.

As for Walitts of the world, they wouldn't have made a mistake of applying the concept of effort preference or FND if they understood that the essence of ME/CFS is PEM, not fatigue.

 

[duncan]

Thank you very much. I hate to ask questions when everyone else gets it.

When I try to stand up from near the floor my brain tells itself that my muscle cannot contract. It just won't. But I know that if you put an electric current through it it contracts fine - I have had it done as part of electrophysiological tests. And of course the muscle works fine in other positions. The same happens when you have flu. Your brain tells itself that it cannot stand up. Neural circuits are blocked by cytokine effects it seems. It seems to me likely that something similar is going on in ME/CFS.

I think this may be wrong on a couple of levels. I think you may be oversimplifying the ME/CFS experience. More worrisome to me personally is this again seems to suggest issues with perception e.g., we think we cannot do something when we can. That is not what most pwME are saying. We are saying we are too sick to do many things we used to do comfortably or without risking major consequences. BTW. same is true with the flu.

Nothing needs to persist other than the continuing signalling and some sort of self-perpetuating 'set' to switches to the wrong position. T

Maybe. But unless we can cite a cause for that, we've potential political issues to deal with from the likes of Walitt.

Regardless, thank you for taking time for my questions. I disagree with you on some things, but I enjoy embracing differing possibilities given how frequently I can be wrong these days.

Edited for clarity.

 

[MeSci]

I hate to ask questions when everyone else gets it.

Don't assume that. I at least often don't have the time or brainpower to comment or even read things thoroughly!

 

[poetinsf]

When I try to stand up from near the floor my brain tells itself that my muscle cannot contract. It just won't. But I know that if you put an electric current through it it contracts fine - I have had it done as part of electrophysiological tests. And of course the muscle works fine in other positions. The same happens when you have flu. Your brain tells itself that it cannot stand up. Neural circuits are blocked by cytokine effects it seems. It seems to me likely that something similar is going on in ME/CFS.

That's not what Walitt paper says though. It used 1-day CPET test as evidence that patients are capable of exerting, but patients are choosing, consciously or unconsciously, not to exert. I agree, however, that something similar happens when you have flu. ME/CFS, after all, feels like a flu, sans fever.

 

[AliceLily]

Immediate PEM does not negatively affect my cognition.

I see I missed adding 'Immediate PEM' to my list of PEM types. Cognition is always affected with my ME, which I think made my earlier years of ME very hard to work out what was happening to me.

 

[Jonathan Edwards]

That's not what Walitt paper says though.

I am not quite sure what the paper really says, if it is indeed consistent. I am not sure anywhere it says what you are suggesting the data showed.

but Nath has specifically said that patients 'can' do things but don't.

 

[Jonathan Edwards]

Aren't we well past the concept stage with ME/CFS?

I don't see that we ever past a concept stage. After fifty years I have a clearer concept of rheumatoid arthritis but I still have a concept.

And I think we are very much at a concept stage in the sense that a syndrome concept is actually more than just a group of people with similar clinical problems. It entails the assumption that putting these people in a group is likely to be justified by some common process that will have a common implication for prognosis and response to treatment. In fact a pretty complex concept. But a pragmatic one.

In fact you have reminded me that I think there is a poorly constructed argument in the paper as it is - that ME/CFS is a fact of reality in that these people are known to exist. Things are more subtle because we do not know if this is the best way to group people's illness. The difference from 'ME' is that that was based on a presumption of a particular sort of unifying process. ME/CFS simply entails that we think there is a commonality of process that will prove clinically useful. At present we do not have much information on the prognostic value of ME/CFS rather than broader or narrower groupings. We certainly have very little information on response to treatment.

 

[Jonathan Edwards]

As for "ME/CFS", it is just an identifier as far as I'm concerned that is uniquely attached to ME/CFS.

isn't that so for all words and acronyms attached to concepts. I don't follow Davison's suggestion that you need language to have concepts. Words are just a set of indices. But by convention they are what we use when we refer to concepts. It would seem a bit silly to make the title 'The Concept Pointed to by the Acronym ME/CFS'

 

[SNT Gatchaman]

The point being that the sense that 'my muscles simply don't contract' is perfectly consistent with normal muscles and normal volition.

It's also consistent with muscles whose mitochondria are defective, which produce abnormal amounts of reactive oxygen species due to an uncoupled electron transport chain, whose fibre type has shifted to rapidly fatiguable glycolytic predominant as a compensation, and which results in increased muscle cell necrosis/repair when over-challenged.

In the scenario where pwME say their muscles can't perform, but that if absolutely necessary they can push through at cost of much worse PEM, I think what's happening might be relying on two things: the muscle fibres that are still relatively uncompromised but that will now be further added to the damaged quota; using inefficient (rescue?) metabolic pathways that will produce more and more ROS.

If those things are true, then a pwME won't know that's the case (and indeed we don't know this mechanism is correct scientifically) but the pwME will learn the symptoms, including the associated lag and will try and judge what they can and can't do in order to live their life to the fullest with the least symptoms. And it's only a best-guess with inherent variability. Eg I got it wrong on Saturday and paid for it that night and Sunday.

 

[duncan]

And I think we are very much at a concept stage in the sense that a syndrome concept is actually more than just a group of people with similar clinical problems. It entails the assumption that putting these people in a group is likely to be justified by some common process that will have a common implication for prognosis and response to treatment. In fact a pretty complex concept. But a pragmatic one.

Seems like a "diagnosis" to me. "Diagnosis" would be safer than a concept. Everything is a concept, and concepts carry unintended ambiguities when we've enough of those already..

 

[Louie41]

TATT

???

We keep touching the stove. Again and again and again, no matter how many times we get burned. Even through increasingly severe burns that take longer to heal, we look longingly at the stove for the next time we get to touch it.

This captures my experience well. I know I should rest much more than I do, but I seem unable to most of the time.

Do your symptoms vary over periods of days or weeks @Louie41 ? Does your illness play Snakes and Ladders? If not at all then maybe there is something different in your case?

Thank you so much, Jonathan, for asking these questions and for listening to us! I've found this whole discussion provocative and enlightening.

I seem to get PEM, but I question whether it is the cardinal symptom of ME/CFS. The sense of exhaustion is so complete for me that it obliterates my ability to understand how PEM could be so important. I do have periodic symptoms of sore throat, sleep reversal, and light, sound, and visual commotion intolerance. And cognitive issues that are hard to separate out because of age.

But to be honest, I have no sense that these occur after too much other activity of whatever sort. I suspect I haven't been paying enough attention to figure this out. I was 48 when first ill, was involved in many different activities, and I continue to be interested in a great many things. Because of my age of onset, I suspect I saw myself with a closing frame on my life--without much time for convalescence. I'm also a fighter, with a somewhat belligerent attitude about limitation in general. My efforts at pacing have been limited to a day or two in bed following a big event like the opera or going to the theater, and to putting quite stringent time boundaries around visits whenever possible. My dear husband and I continue to struggle with conversation. I'm so exhausted by leaving the house that I resist doing so. Thus many of my interests have fallen by the wayside.

It is possible that you are managing to keep at this particular level all these years. Are you resting lots each day? It wasn't until I reached very severe ME that PEM was without a doubt shouting its existence to me over and over. Its impact is forever imprinted.

See my comments on pacing above.

Just to add to this @Louie41 It wasn't until I hit very severe ME that I was able to look back and recognize PEM in my earlier years. In my earlier years I was describing symptoms as unusual and ' something very wrong'.

And I thank you for your input, @AliceLily. It has prompted me to think along some new lines.

 

[Jonathan Edwards]

Seems like a "diagnosis" to me. "Diagnosis" would be safer than a concept. Everything is a concept, and concepts carry unintended ambiguities when we've enough of those already..

You can call it a diagnostic concept but most people's idea of diagnoses is that they constitute mutually exclusive 'diseases' and that is a very unhelpful view because different cross-cutting categories with different prognostic and treatment0response implications are more useful.

And a diagnosis is surely a concept - the idea that there is a disease here - so you cannot get away from having a concept.

Concepts can certainly carry ambiguities but the point of the paper is to try to identify and minimise those.

A diagnosis like rheumatoid arthritis carries a multitude of ambiguities, I can assure you.

 

[JemPD]

Sorry @Louie41
TATT is short for Tired All The Time - a ubiquitous cause for GP consults. ie being tired all the time but little else in the way of symptomatology.

 

[Jonathan Edwards]

But to be honest, I have no sense that these occur after too much other activity of whatever sort.

Yes, I often wonder whether this is more the picture for many people with ME/CFS. Maybe the relation to exertion is not the cardinal thing that makes it look as if this is a unified process. That makes sense to me. My attempt to grasp a central feature ends up with something like:

Disablingly severe and persistent over months bleurrgh (substitute with your favoured word - fatigue, exhaustion, ghastliness....) with periods of worsening, and or diversifying, usually of rapid onset and only gradual fading away that may or may not follow a while after exertion and with a protracted time scale different from the immediate worsening seen in most metabolic or structural neuromuscular disorders.