What are the necessary conditions and criteria for a theoretical model of ME/CFS?

[JemPD]

Is it because the sound forces you to shift attention to it, and you can't deprioritise it?

sort of. I do have sensory gating issues, but they are there when i am at my best & were there before i was ill (there is some debate among my non blood relative family who are all autistic about whether i am autistic myself, but thats another story).

so the difficulty with sensory gating has always been a low level issue, but this is different. I fall over if there is loud noise & trying to walk to the bathroom while the window is open & birds singing becomes impossible when in PEM even when i still have the juice to stand upright for a minute. Its like there isnt enough 'juice' or bandwidth to manage everything so it all just stops functioning properly. It feels like someone took a whisk to my brain & mixed all the signals up. Sound also interferes with my proprioception. (once in PEM) it doesnt have that effect when i well rested. But sound added to other forms of exertion reduces how long i can do it for before i crash by roughly 80%

I used 'birds singing' because its a sound i love and so many 'outsiders' think sensory sensitivity is an emotional thing & its not, at least for me, its the same with sound i love as sound i hate, although obviously i also get irritated by sound i hate, which adds a slightly higher burden of exertion, but only slightly.

 

[JemPD]

So, a few subjects who don't fit the model don't really negate it.

my bolding. i think thats really important. Until there is some kind of breakthrough in terms of aetiology we cant be sure that any of us have the same thing, so we need to be careful not to write off a model because it cant explain outliers.

My cognitive-induced PEM has a much shorter (<1 hr) and more variable delay,

Mine too, not the (,1hr) part but it does come quicker, & it seems a lot more unpredictable & variable too

 

[Kitty]

Its like there isnt enough 'juice' or bandwidth to manage everything so it all just stops functioning properly.

I put it badly, but that's what I meant. I have poor balance, and both music and light can make me fall or stumble when I'm in PEM or very tired. I need visual input to stand upright, and if there isn't the bandwidth for that, off I go. I think it's made worse by not having any filters to start with, though; before I got ME I never actually fell over, but it would confuse me.

 

[duncan]

The conventional model, e.g. CDC's, for ME/CFS is exclusionary: You cannot have any infection that can cause ME/CFS symptoms. So, does testing negative for all the usual suspects have to be part of the model?

I suspect there is a logical fallacy embedded in that question, but my point is that when you're qualifying a disease likely, in part at least, to be characterized by corrupted immune responses, how do you factor that into a diagnostic model?

 

[Peter T]

Why cant i control my gait when the birds are singing (a favourite sound of mine, that makes me happy)? it seems to scramble all the signals in my brain like a rotary wisk.

When at home and rested, even over rough ground, I can usually walk without a stick. However when on unfamiliar ground, even with level surfaces I need a stick, especially if there are any distractions including traffic. However any motor activities are noticeably harder in novel situations, when there is any distraction or when I am in PEM. I suspect my issues are not at the level of muscle function, but are rather ideomotor dyspraxia, a matter of organising the motor sequence.

 

[alex3619]

This rules out models that rely on long-term deterioration or processes that take a long time to show effects

I am very interested in explaining temporary remissions, including rapid declines and improvements. These took hours in my case. ME in at least some of us is an active process, or is modified by active processes. However we do not know if this applies to all ME patients or just a subgroup.

 

[alex3619]

However when on unfamiliar ground, even with level surfaces I need a stick

I have had this problem for the last several years. I am hoping my cataract surgery reverses this, but I think its unlikely. I need a stick for balance, an extra signal as to where the ground is.

 

[Peter T]

I have had this problem for the last several years. I am hoping my cataract surgery reverses this, but I think its unlikely. I need a stick for balance, an extra signal as to where the ground is.

I think for me in part using a stick serves to focus my attention, to remind me to concentrate on walking and not get distracted.

 

[Kitty]

I am very interested in explaining temporary remissions, including rapid declines and improvements. These took hours in my case.

Yes, this is puzzling, and also (at least the remissions) something I've experienced. But I suppose if an immune mediated switch can go the wrong way to trigger ME or cause PEM, it can presumably do the opposite.

I'd like the sleep dysfunction accounted for too. It's always seemed central to me, especially as occasionally I sleep normally and it greatly improves my physical and mental capacity.

 

[Ash]

Yes, this is puzzling, and also (at least the remissions) something I've experienced. But I suppose if an immune mediated switch can go the wrong way to trigger ME or cause PEM, it can presumably do the opposite.

I'd like the sleep dysfunction accounted for too. It's always seemed central to me, especially as occasionally I sleep normally and it greatly improves my physical and mental capacity.

Mmm me too sleep that absolutely refuses to accommodate “sleep hygiene” measures and only gets worse with the attempt to coach it back into line. But then apparently spontaneously resets itself into a perfect pattern leading to a massive reduction in symptom severity. Only to plummet back into disarray a few days or weeks later.

 

[JemPD]

I put it badly, but that's what I meant. I have poor balance, and both music and light can make me fall or stumble when I'm in PEM or very tired. I need visual input to stand upright, and if there isn't the bandwidth for that, off I go. I think it's made worse by not having any filters to start with, though; before I got ME I never actually fell over, but it would confuse me.

yes this reflects my experience also

When at home and rested, even over rough ground, I can usually walk without a stick. However when on unfamiliar ground, even with level surfaces I need a stick, especially if there are any distractions including traffic. However any motor activities are noticeably harder in novel situations, when there is any distraction or when I am in PEM. I suspect my issues are not at the level of muscle function, but are rather , a matter of organising the motor sequence.

that sounds very familiar, although i cant ever walk without a stick outside the home, indoors i can manage because its quite small so there isnt the space around me, as long as its silent. But when in deep PEM i have to crawl sometimes anyway, but even that is not a fluid movement if there is sound... its like it scrambles the series of actions that are needed so it all just doesnt work & i have to lie on the floor until its quiet again.

It was a nightmare when a neighbour started with a whacker unexpectedly, i couldnt even get to the toilet.

 

[Hutan]

Atleast in my personal illness experience, when completely bedridden, no sound or light input, only liquid food etc. No confounding factors. Sometimes simply thinking about a stressful thought, or thinking about something that takes a lotta energy (like solving a math problem in my head) could cause visible delayed PEM which presents in the exact same way physical PEM did. Since I did absolutely nothing all day except swallowing pills and nutritional drinks, I can’t think of a confounding factor that would explain that except that cognitive PEM must exist.

I'm trying to think what happens as a result of both physical and mental exertion (as well as immunological exertion). One thing seems to be lipid mobilisation.

Effects of mental stress on lipolysis in humans, 1992

Lipid mobilization was investigated in subcutaneous adipose tissue specimens obtained before and after a standardized mental-stress test in 14 non-obese healthy subjects. All participants responded with an increased heart rate and elevation of plasma glycerol levels.

I can imagine lipid mobilisation potentially having some negative downstream, delayed effects. Perhaps women, who have more fat stores or a particular hormonal response, might be more prone to higher levels of lipid mobilisation in response to a stressor?

I remember one investigator, was it Ron Davis, when looking at the pattern of metabolites or mRNA in people with ME/CFS commenting that the pattern looked like that of starvation, and there is lipid mobilisation in starvation. Maybe that fits with the indication that people with ME/CFS do better on a low carbohydrate diet,

However, serum lipids generally improve with the low-carbohydrate diet, especially the triglyceride and HDL measurements. In sharp contrast, high-carbohydrate diets, which reduce high-density lipoprotein (HDL) cholesterol and raise triglyceride levels

Just chucking this in, not sure if it all hangs together, not sure if the other evidence we have fits.

 

[Lidia Thompson]

I think this is an excellent idea and it should be possible to come up with some "basic checklist".

Would it include alcohol intolerance?

I literally went from being able to drink a fair amount with few adverse effects = pre ME/CFS
to going completely doolally (and very ill) after seemingly a mere thimble full of any alcoholic beverage = post ME/CFS

 

[SNT Gatchaman]

For things like alcohol intolerance (which was a sudden new feature for me too) I wonder if we might have 2 or even 3 levels. Level 1 would be the must-haves and level 2 could be "lesser" priority things that we'd like to explain and understand but aren't mandatory. Level 3 might be for outlier/atypical observations.

 

[EndME]

Would it include alcohol intolerance?

I literally went from being able to drink a fair amount with few adverse effects = pre ME/CFS
to going completely doolally (and very ill) after seemingly a mere thimble full of any alcoholic beverage = post ME/CFS

I would say no, since it isn't even clear to me what alcohol intolerance in ME/CFS specifically entails and also because it is a far from necessary criteria for someone to have ME/CFS. From what I've seen sensitivies to different substances are extremely heterogeneous in ME/CFS and given the gut and migraine problems commonly reported in ME/CFS I don't think alcohol sensitivities would be specific or upstream enough, as also discussed in this comment by @Ravn :

Both true. Plenty of reports, yes, but they're typically vague and poorly characterised

I don't think the term alcohol intolerance is helpful without further definition. Alcohol intolerance has been discussed here and elsewhere on and off for yonks but the only conclusion that can reasonably be drawn is that people mean very different things when they say alcohol intolerance. Anecdotal reports cluster into at least 5 groups, at least some of which have different mechanisms:

• histamine/anaphylactic type reactions
• normal reactions to alcohol - i.e. feeling drunk and/or hungover - occur more quickly and/or after only minimal alcohol intake
• abnormal reactions to alcohol that superficially look a little like Asian flushing (genetic) or Carcinoid syndrome (neuroendocrine)
• ME symptoms increase after alcohol consumption, either immediately or delayed
• people get the same symptoms from alcohol they always did but are no longer prepared to tolerate them because feeling alcohol-lousy on top of feeling ME-lousy is one level of lousy too much

It would be interesting to investigate these - but separately. And also separately from the settings in which we often consume alcohol because these often involve other exposures to potentially problematic substances and exertion, just the thing to mess up your observations

Then there's the issue of how to create a non-alcoholic control substance that people can't tell from real alcohol

I think it's an interesting enough phenomenon that it deserves proper studies, but before that I find it hard to say more.

 

[EndME]

For things like alcohol intolerance (which was a sudden new feature for me too) I wonder if we might have 2 or even 3 levels. Level 1 would be the must-haves and level 2 could be "lesser" priority things that we'd like to explain and understand but aren't mandatory. Level 3 might be for outlier/atypical observations.

I'm not too sure.

Level 2 and most definitely level 3 sound like they have nothing to do with necessary conditions?

Figuring out what belongs to which levels and what can be regarded as a "necessary condition" will probably be quite hard and maybe somewhat arbitrary but once that is done anything not belonging to level 1 would surely be discarded on such a list?

I'm not sure how much sense it makes to keep a list of 100s of different things that one would like to have explained, when in reality no one can even come up with a convincing argument to explain delayed PEM.

I could be wrong, but I don't think the point of this list would be that any theory/model/hypothesis would have to explain the full set of symptoms present in everyone but rather that it is used to check whether one explains at least a subset of core pathologies but more importantly that a hypothesis doesn't involve contradictions with things that are on such a list (and that seems less likely to apply to something like alcohol intolerances, since it seems unlikely to me that someone would come up with a hypothesis that includes something along the lines of "thus via my proposed mechanism it is impossible for pwME to develop alcohol intolerances").

 

[SNT Gatchaman]

Figuring out what belongs to which levels and what can be regarded as a "necessary condition" will probably be quite hard and maybe somewhat arbitrary but once that is done anything not belonging to level 1 would surely be discarded on such a list?

Yes, I think so. Tagging by levels, eg in a working summary post could help during the discussion as we refine what we think should be the necessary conditions. Maybe it will all become a bit clearer what truly belongs and what doesn't as we post ideas in-thread.

 

[Deanne NZ]

I don’t recall if it has been mentioned in this thread, but I’d like to have the inflammation of lymph nodes included. My son is in one of the most severe PEM crashes he has had in the past couple of years and has a ping pong ball and a few marbles on one side of his neck & under his jaw line. They have been there for more than 2 weeks now. Less severe PEM crashes result in only pea sized lymph nodes. Previous crashes have included shingles - with inflammation in neck, armpits & groin.

 

[rvallee]

Would it include alcohol intolerance?

I literally went from being able to drink a fair amount with few adverse effects = pre ME/CFS
to going completely doolally (and very ill) after seemingly a mere thimble full of any alcoholic beverage = post ME/CFS

What's more important about a good model isn't so much that it accounts for all things, but allows for them, makes sense of them.

A model accounting for every detail would probably be too complex, it has to be distilled into its most fundamental components. But as long as it makes sense of the data, certainly as long as it doesn't contradict the data, then it's probably good enough. At least as a starting point.

 

[bobbler]

For things like alcohol intolerance (which was a sudden new feature for me too) I wonder if we might have 2 or even 3 levels. Level 1 would be the must-haves and level 2 could be "lesser" priority things that we'd like to explain and understand but aren't mandatory. Level 3 might be for outlier/atypical observations.

Yep. That one seems to fluctuate for me significantly there is probably a term of like when the illness is ‘live’ I’m reaching for ie where I feel like my body is on a free fall/ downward situation and definitely if I’d had an illness exacerbate

I remember @Peter Trewhitt doing a good post about the types of alcohol mattering too - I’ve never been able to tolerate even tiny quantities of wine but sometimes other types I can in certain ways so I can see how what your normal tipple might be and other comorbidities could be part of that

it’s an interesting clue though as it back in the days would give me full on rheumatic aches everywhere the next day when I had a few which seems so much different to what others might have as a hang over