The Concept of ME/CFS

[Haveyoutriedyoga]

The problem is that the processes of muscle use involve chemical changes that will re-equilibrate within five minutes at most. A purely energy metabolic account just doesn't fit the time course of PEM. Delayed signals preventing re-use, in whatever way, could.

Could a part of whatever happens in the hours to days after any kind of exertion be the trigger for the reflex?

 

[Peter T]

I have a relevant anecdote to share on this.

After a 12 month period of bedbound with severe ME/CFS immediately on completing the NHS management course, I began to slowly increase activity (using 50% of energy envelope to the point where in the spring of 2013 I could spend 20 mins a day on a perching stool in the kitchen helping my late husband prepare the evening meal.

This particular day we were having a pasta dish and I was in charge of the easy bit; cooking the pasta. We were busy chatting about our day and my husband noted that I'd forgotten the pasta so he prompted me to give it stir. I stirred the pasta in the boiling water - with my hand.

My husband glanced across at me and leapt into action to withdraw my hand and shove it under a running cold water tap.

I hadn't noticed, and and still didn't realise what the panic was about, and no pain signals.

My brain seems to skip a signal or two when I am in PEM, rather like listening to someone talk on the phone when they have a bad signal. Whole sections of the conversation are missed completely such as "pick up the spoon to actually stir the pasta."

This, though very dramatic and very dangerous, is an example of ideomotor dyspraxia, where the executing and sequencing complex motor activities brakes down. I think most of us experience at some point, be it pouring the hot water for a cup of tea into the sugar bowl or putting the finished tea into the fridge and raising the milk bottle to your mouth to drink. A recent experience I posted was carefully pouring a line of mouth wash onto my tooth brush and staring incredulously as it ran away, I had mixed components of brushing my teeth and rising with mouth wash, and repeated the action before I could compute what had gone wrong. This brake-down in sequences of every day motor activity could be an aspect of our brain fog.

Perhaps what is unusual about this was that you didn’t register the pain.

 

[rvallee]

That said, my guess is that PEM is more likely similar to what we call reflex inhibition. If you by mistake touch a hot stove with a finger you will find that your arm jumps back from the stove before you feel any pain.

That analogy works, but backwards. 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. Many times we touch the stove, it doesn't hurt, then 1-2 days later our hands are scalded even though they were fine right after.

Which is exactly the opposite of the fear-avoidance model. If anything, we are driven to touch it almost compulsively, because life demands movement and exertion. There is no reflex or conditioning involved at all, this is the entire difficulty with how PEM is often delayed. So many times we feel fine, even a bit better, until it hits. Conditioning requires certainty, to know that doing x will result in y. With PEM that feedback is completely broken, it would be like trying to train an animal through feedback conditioning with totally confusing and chaotic feedback. Which doesn't work.

Personally I have touched the very hot stove hundreds of times. Every time expecting no pain, no heat. Most of the time simply forgetting what happened before, in large part because the reaction is usually delayed and disproportional, making it even harder to reasonably attribute its cause. But also because brain fog adds a huge layer of confusion, memory loss and turns off the executive functions that do the learning.

Which really all makes a complete mockery of the expertise in clinical psychology over the models they made up for us. They actually managed to invent models that are completely backwards, that reverse causality, attributing the cause to what followed, despite the cause-and-effect relationship being madly inconsistent, disproportionate and unpredictable, and especially in completely misunderstanding our behavior and motivations, which is their actual claim to expertise, that they understand our behavior and motivations better than we do. Which is laughable given that it's fully subjective experience and that they dismiss everything we tell them about that subjective experience, but that's the problem with social sciences: there are no right answers, you never actually know when you are right, even after the fact. Which makes it all so much harder than the 'hard' sciences, where you can have not just certainty after-the-fact but accurate predictions.

 

[rvallee]

'Mostly identical' doesn't cut it in useful diagnostic categories I think. Rheumatoid arthritis and seronegative inflammatory arthritis can be genuinely identical in clinical presentation but we have two syndromes because we had reason to think there were two different mechanisms and that turned out right.

Which is really the main problem in every illness that medicine doesn't understand: what to do while we have this lack of knowledge about how to tell illnesses apart based on observed pathophysiology? Of course when it comes to treatments, drugs and such, this is critical, but we don't have that here, all we have is clinical presentation and here they are definitely mostly identical. You rely on your own experience but I have read thousands of testimonies of LC that feature all the typical POTS and PEM presentation and resolved before hitting the magical 3-month mark, where others nearly identical did not. There is just a wild variation out there.

From the perspective of a patient facing this limbo period before the magical threshold, it's rational to apply the same approach, especially as it involves no specific treatment. We are not talking about deciding about which medication to use, each with their own problems and possible disaster scenarios, this is more about nursing, about being able to provide the best circumstances for full recovery while being aware of the potential for severe deterioration, including the long-term kind leading to a need for palliative care.

Which has been a regular discussion here, but frankly if there's one medical specialty that is most appropriate here, it's nurses. And it just happens to be cheaper than almost all other specialties, so there's an additional angle to convince those who don't see the lives, only the costs of pretending to care for us.

 

[rvallee]

Well most others in the discussion seem to think systems do shut down - i.e. that using muscles becomes impossible. If it was just feeling pain then nobody would talk about lack of energy surely? My impression is that the mechanism is going to be multilayered - much as it is for my knees and most of these things.

A common description of severe states is that it feels like the entire nervous system is on fire, and that the whole body is poisoned, leading to a kind of shock paralysis. I have experienced this state once, and that was enough to have it seared into my memory, and it is apt. This looks far more like a dynamic state, like being hooked on to continuous low-power electric shocks, than a passive coma-like state.

We have to keep in mind that even in the most severe states, the patients are fully lucid and aware. That awareness is fleeting and tenuous, the same way experiencing severe pain we are fully aware of it but lose track of the passage of time, but it is there. This is not a sedated/knocked out condition, it's more like being so overwhelmed by internal senses that external reality becomes too much to endure, and every external stimulus just adds to it, like salted sandpaper on a wound that keeps being sandpapered again and again.

 

[Maat]

This, though very dramatic and very dangerous, is an example of ideomotor dyspraxia, where the executing and sequencing complex motor activities brakes down. I think most of us experience at some point, be it pouring the hot water for a cup of tea into the sugar bowl or putting the finished tea into the fridge and raising the milk bottle to your mouth to drink. A recent experience I posted was carefully pouring a line of mouth wash onto my tooth brush and staring incredulously as it ran away, I had mixed components of brushing my teeth and rising with mouth wash, and repeated the action before I could compute what had gone wrong. This brake-down in sequences of every day motor activity could be an aspect of our brain fog.

Perhaps what is unusual about this was that you didn’t register the pain.

Yes, exactly that, and thanks for putting a name to it. I do that kind of thing everyday in little ways, like you say, as we all do.

The pasta incident was at my worst. Although the submerged hand and wrist were immediately bright red, absolutely no pain for at least 24 hours, boy did I feel it then and it seemed to take much longer than one would expect to heal.

 

[Maat]

A common description of severe states is that it feels like the entire nervous system is on fire, and that the whole body is poisoned, leading to a kind of shock paralysis. I have experienced this state once, and that was enough to have it seared into my memory, and it is apt. This looks far more like a dynamic state, like being hooked on to continuous low-power electric shocks, than a passive coma-like state.

We have to keep in mind that even in the most severe states, the patients are fully lucid and aware. That awareness is fleeting and tenuous, the same way experiencing severe pain we are fully aware of it but lose track of the passage of time, but it is there. This is not a sedated/knocked out condition, it's more like being so overwhelmed by internal senses that external reality becomes too much to endure, and every external stimulus just adds to it, like salted sandpaper on a wound that keeps being sandpapered again and again.

This.

 

[hotblack]

I’m through the document but not the thread so apologies. But a few notes I made this week:

I like this.

It starts making it clear we don’t know much. This is good.

I never got to the thread on the meed to lie down as it was quite long and daunting, but it’s very much a key symptom which showed up early in my ME and the correlation between lying down and severity for me is strong. The need is ever present, even when good it’s not long before I have to. And standing is out, even if my HR is ok. I’m on meds for my HR so some docs think/say I should be able to stand now but still can’t for long even when at my best.

The ups and downs are well described as snakes and ladders too. I’m doing a bit better at the moment. Why? Partly because there’s less making me worse (none of the big triggers of recent years) but also just because. If nothing happens to make me worse I will have ups and downs which are completely unrelated to what I do and inconsistent. Which is why a lot of the ‘tracking’ stuff some like us to do annoys me.

The distinction with PVFS is I think very important as we seem to be treated as if we have this but just an ongoing version. I think this is a mistake and leads into misconceptions. I would say we have something else and that these symptoms are clear quite early on. At least this has been the case for me, I obviously cannot speak for others.

And all the stuff about approaches from medics is great. We can’t yet make things better but they can and do make things worse. Not deliberately usually. But definitely due to a disinterest of dismissal of ME/CFS and not listening to patients.

Is there a way we can emphasise this? That patients want to work together with medics to not make things worse until we know how to make things better?

Thanks again @Jonathan Edwards and everyone else pitching in feedback now and over the years.

 

[Jonathan Edwards]

Compound that weirdness with the fact that it isn't necessarily a muscle thing that thrusts you into PEM. For many of us it can be just cognition, just too much focusing. I'm not sure your model accommodates all that.

Cognition fits fine because my analogy does not include specifically suggesting that PEM is a spinal reflex. Not at all. That may not have been transparent. I am using the spinal reflex as an analogy for things that go on in the nervous system over which we have no control whatever. Even in the spinal reflex situation visual inputs and inferences about hardness of surfaces that may be conscious or unconscious all feed in from different directions.

There is a mystery as to where the pain comes from if the muscles and joints are all normal. Which is why people talk of 'central sensitisation'. But what I am suggesting might involve something better thought of as 'peripheral sensitisation' which seems to be what we have with flu. Peripheral inhibitors of neural sensitivity like ibuprofen can help in flu. They may not help in ME/CFS but they wouldn't if the sensitisation was not through prostaglandins.

 

[Jonathan Edwards]

That analogy works, but backwards. We keep touching the stove.

I think we are wandering off what the original analogy was about. The idea was to explain why there appears to be no energy or ability to use muscles. That clearly comes with pain and for some people the pain is the main thing and for others it is the sense of paralysis that I was giving an account of. The hot stove analogy is just making the point that our bodies have responses that we have no control of. And yes, it is the backwards of the situation in ME/CFS, which is more like the situation in with my knees where I find myself paralysed, completely unable to undertake an action, if my body either is in pain or has been conditioned to expect pain. The latter comes with the former so it is difficult to disentangle exactly what creates the paralysis.

 

[Jonathan Edwards]

Is there a way we can emphasise this? That patients want to work together with medics to not make things worse until we know how to make things better?

Thanks for the helpful feedback @hotblack . I am glad the snakes and ladders is not completely off target. The description of OI, regardless of heart rate, is interesting. I like these two sentences. Maybe I could include them somehow.

 

[Kitty]

There is a mystery as to where the pain comes from if the muscles and joints are all normal. Which is why people talk of 'central sensitisation'. But what I am suggesting might involve something better thought of as 'peripheral sensitisation' which seems to be what we have with flu. Peripheral inhibitors of neural sensitivity like ibuprofen can help in flu. They may not help in ME/CFS but they wouldn't if the sensitisation was not through prostaglandins.

We're all a bit different, but the various kinds of pain I have aren't like "normal" pain. It's not like a bone, tendon or muscle injury, it's not like inflammatory processes in bruised soft tissue or arthritic joints, it's not the soreness and heaviness of having been on your feet too many hours.

The muscle pain is a burning I've never had from anything else, even though I managed a good range of interesting ways to knacker body parts doing contemporary dance. There are also distracting pins and needles, zaps, twitches and buzzing, and the worst pain of all feels as if it's just above the surface of your skin, so you can't even touch it.

As in viral infections, some of the pain is difficult to separate from fatigue and overall malaise. If a usually healthy person is unwell with a bug but needs to take part in an hour-long online work thing, a dose of painkillers will often get them through it. They might manage to come across normally and make cogent contributions, but flop over afterwards. Moderate ME pain-and-fatigue can work like that. The peripheral sensitisation idea does make sense from that point of view.

 

[JemPD]

This, though very dramatic and very dangerous, is an example of ideomotor dyspraxia, where the executing and sequencing complex motor activities brakes down. I think most of us experience at some point, be it pouring the hot water for a cup of tea into the sugar bowl or putting the finished tea into the fridge and raising the milk bottle to your mouth to drink. A recent experience I posted was carefully pouring a line of mouth wash onto my tooth brush and staring incredulously as it ran away, I had mixed components of brushing my teeth and rising with mouth wash, and repeated the action before I could compute what had gone wrong.

OMG this describes my ME experience exactly, I mean things are just jumbled so completely that I do the most absurd things. And what gets me about it is the incredulity, the repeated attempts at doing something incorrectly, but not being able to work out whats wrong with the picture.... it's the pure puzzlement as to why, when I attempted to make a jelly and a cup of the this morning, why the jelly in the jug was so dark, and getting darker by the minute, and why the mug full of water was still clear.
I stirred both and looked at them for some time, thinking why isnt the tea brewing...I threw away the 'tea' and poured it again thinking in exasperation 'what the f*ck's up with it?' before i worked out that i'd put the tea bag in with the jelly and the tea wasnt brewing in the mug because there was no ruddy tea bag in it! (FIW i recommend blackcurrant & tea flavoured jelly, its an unusual but pleasant flavour!)

its the incredulity... the sheer puzzlement as to what has gone wrong, that is so very bizarre.

Which is exactly the opposite of the fear-avoidance model. If anything, we are driven to touch it almost compulsively, because life demands movement and exertion. There is no reflex or conditioning involved at all, this is the entire difficulty with how PEM is often delayed. So many times we feel fine, even a bit better, until it hits. Conditioning requires certainty, to know that doing x will result in y. With PEM that feedback is completely broken, it would be like trying to train an animal through feedback conditioning with totally confusing and chaotic feedback. Which doesn't work.

this

We have to keep in mind that even in the most severe states, the patients are fully lucid and aware. That awareness is fleeting and tenuous, the same way experiencing severe pain we are fully aware of it but lose track of the passage of time, but it is there. This is not a sedated/knocked out condition, it's more like being so overwhelmed by internal senses that external reality becomes too much to endure, and every external stimulus just adds to it, like salted sandpaper on a wound that keeps being sandpapered again and again.

rvallee can i copy that & use it? its such a good explanation of what it's like when i'm at my absolute worst.

The distinction with PVFS is I think very important as we seem to be treated as if we have this but just an ongoing version. I think this is a mistake and leads into misconceptions. I would say we have something else and that these symptoms are clear quite early on. At least this has been the case for me, I obviously cannot speak for others.

Yes i completely agree. If anyone else tells me that they know what it's like to have ME because they 'had ME for 6mnths after glandular fever'... ! it's very annoying

Peripheral inhibitors of neural sensitivity like ibuprofen can help in flu. They may not help in ME/CFS but they wouldn't if the sensitisation was not through prostaglandins.

Interestingly and i think unusually, ibuprofen does help me a bit, I cant use it often because it makes me feel like i'm better than i am leading to PEM - which is then so bad that the ibuprofen doesn't touch it. But for the flu like stuff - painful glands etc it does help a little bit.

 

[duncan]

I am using the spinal reflex as an analogy for things that go on in the nervous system over which we have no control whatever. Even in the spinal reflex situation visual inputs and inferences about hardness of surfaces that may be conscious or unconscious all feed in from different directions.

There is a mystery as to where the pain comes from if the muscles and joints are all normal. Which is why people talk of 'central sensitisation'. But what I am suggesting might involve something better thought of as 'peripheral sensitisation' which seems to be what we have with flu. Peripheral inhibitors of neural sensitivity like ibuprofen can help in flu.

I am thinking you're not suggesting this 'peripheral sensitisation' is a thing in and of itself - it doesn't just happen, we don't grow into it. It is downstream. Something brings it along, and something maintains it? If so, what? Or am I misunderstanding?

There is a mystery as to where the pain comes from if the muscles and joints are all normal.

I'm not clear that we know they are all normal. Moreover, there are many other body parts/tissues - even down to the cellular level. Indeed, this is why an acquired channelopathy could work in theory (I'm not in favor of that theory, but it works, too).

 

[Jonathan Edwards]

If so, what?

Suggestions welcome.

 

[duncan]

Would't peripheral sensitisation make ME/CFS an interoceptive disorder? Does this align with Baraniuk's theories at all, or was it informed by them?

Baraniuk:
"Our magnetic resonance imaging studies of exercise-induced changes in brain blood flow are a model for postexertional malaise/symptom exacerbation that is the essential feature of ME/CFS. We found dysfunction in the dorsal midbrain, periaqueductal grey matter and reticular activating nuclei of the ascending arousal network. These nuclei are critical for threat assessment and respond to pain by activating descending antinociceptive pathways that shut off pain messages. We propose that dysfunction of these systems in the midbrain and brainstem may provide a unifying pathogenic mechanism to explain the heightened experiences of interoception in ME/CFS and allied conditions."

ETA: Is something akin to this what you meant by problems with signaling in pwME?

 

[Sean]

We need to bring back a conversation around convalescing.

This.

At this point in time early diagnosis and being able to enter convalescence mode is the only tool we have to maximise the chances of substantial sustained improvement, let alone actual full recovery.

The reason many of us end up so sick and disabled is precisely because our socio-economic structure does not allow that.

We have to keep in mind that even in the most severe states, the patients are fully lucid and aware.

This. I have never had any sense of being unaware of my surroundings, even at my sickest.

We're all a bit different, but the various kinds of pain I have aren't like "normal" pain. It's not like a bone, tendon or muscle injury, it's not like inflammatory processes in bruised soft tissue or arthritic joints, it's not the soreness and heaviness of having been on your feet too many hours.

The muscle pain is a burning I've never had from anything else, even though I managed a good range of interesting ways to knacker body parts doing contemporary dance. There are also distracting pins and needles, zaps, twitches and buzzing, and the worst pain of all feels as if it's just above the surface of your skin, so you can't even touch it.

This.

Baraniuk:

We found dysfunction in the dorsal midbrain, periaqueductal grey matter and reticular activating nuclei of the ascending arousal network.

How does he know it is 'dysfunction', instead of those brain systems functioning normally in response to some non-normal input?

–––––––

I think there is something to be said for investigating the possibility that PEM is, at least in part, a protective mechanism to stop us being active, in an analogous way to pain. Or possibly even a broken protective system.

 

[Tilly]

I think energy is unlikely to be the problem. There is no evidence for a problem with energy severe enough to explain the symptoms of ME/CFS. In general I think it is best not to try and mange people with ME/CFS on the basis of theories - of any sort. So far we don't seem to have a theory that makes much sense.

It is not severe, just takes a lot of time to adjust to demand until your reach a certain point of no return. Then there is the issue of getting back to the energy you had before, now how does that happen? Like you say makes no sense.

Or are we missing something?

That said, my guess is that PEM is more likely similar to what we call reflex inhibition. If you by mistake touch a hot stove with a finger you will find that your arm jumps back from the stove before you feel any pain. The reason is well understood. The spinothalamic sensory nerves in the finger link directly to motor nerves that make muscles contract, within the spinal cord, and the reflex response takes less time than the passage of a signal up to the brain where it has to be integrated in several steps before it is actually felt.

The point being that unpleasant inputs prevent our bodies from using energy in a way that we have no control over. Moreover, learnt unpleasant outcomes like previous episodes of PEM get fed into the reflex programming. I cannot stand from squatting because the muscles refuse to contract. That is at one level driven by pain if they do contract but it is also driven by having learnt that if the contraction does manage to lift me up, on past occasions it has failed me half way through and thrown me onto a concrete path, resulting in lacerations taking weeks to heal. Our reflex nervous system takes good care of us in ways we know nothing about.

That would not explain why reading a book makes legs ache or go chilly from the inside? and in the middle of the muscle or would it? As you say we know almost nothing about our bodies or it feels that way.

The problem I see for people with ME/CFS is that the reflex block is in response to something the nervous system cannot make any sense of, at any of many levels. The natural response of a system in that situation is to shut down more and more.

I don't see that, not in many cases unless pushed too hard and then there is a cascade of events and I wonder if someone took the time with all those that have fallen into very severe, would we see a distinct pattern of events and not just PEM?

What we get is a crash and a slow bounce (not a good word but the only one I could think of) back?

We forget that the way the nervous system protects itself isn't even necessarily in the brain.

I agree 100% we never look at how a body mends do we? Is that where we go wrong? If we looked more at how a body responds to threats and then fights back, would we find the area where the body fails? Those that do get normal or most normal function back how does their body look like inside?

I go back to when ME patients have a crash, what is the 1 thing that stops them falling further and does this change the longer you have ME? But what enables them to regain activity?

It is said that headless chicken can still run. The spinal cord can organise how we use our arms and legs to a great extent on its own.

Phantom limbs, we still can not determine why or how to avoid them and is there research?

In fact if you damage the brain, as in the typical corticospinal tract damage that gives you a typical stroke gait, the problem is that the spinal cord contracts the muscles too much. They go in to spasm. The brain actually controls the puppet that is the body by letting go of individual strings rather than pulling on them. It is all very upside down from how we think we work.

There is a lot to think about that

In stroke care, around the 1970s it became understood that stimulating the paralysed side was counterproductive because it just increased spasm. Strength had to be taught not through exercises kneading tennis balls but exercises in letting loose, encouraging postures that eased the overstimulation. I wonder whether what is needed in ME/CFS is something rather similar.

Worth thinking about and looking at for research.

The immune system plays a heavy role in repairing after stroke and I know there are images of this process happening. Just thinking this through not meaning anything by it then we have research into Small fibre neuropathy


Pacing seems to be the right idea. But maybe we need to understand more about the specifics. Musicians spend hours retraining their hands to achieve perfect control by eradicating the bad habits that come from trying too hard.

The visible app might give some good data on pacing and perhaps this can be adapted to factor in "not trying too hard"

Pacing is complex and individual and we have a lot to learn from listening intently to those individuals doing it and looking at the data. There are days when Angus has to move and he may not look or feel his best but something kicks off inside him and he HAS to move, striding up and down the house mostly. Now why is that!
His been using the visible free version, we are both intrigued to find out when this happens and if there is any changes that we can see, not for any particular reason because if he could replicate or sustain he would have but it is bizarre.

 

[hotblack]

On snakes and ladders, another way I’ve sometimes described it is this…

It’s like trying to cross a road while wearing a blindfold and ear muffs. You may make it across but you may well get hit by a car.

I think it describes both the potential impact but also the lack of reliable information we have from our senses on how to avoid that impact. And the way in which doing the same thing one day to the next may produce different results. A lot is down to external forces or at least factors outside of our control.

I think snakes and ladders may be a more useful and less brutal analogy for the purposes of this paper. But thought I’d share with people here anyway.

 

[Yann04]

systems don't shut down. They scream bloody murder! PEM isn't a reflex learnt to avoid being burned, it's being burned and feeling that pain.

Yep. When I’m in denial and pretend PEM doesn’t exist, it still happens. There’s no reflex forcing it to happen. The only reflex is resting when you know it’s going to happen so it lasts less long. But that is separate from the PEM itself.