Does Very Severe ME/CFS involve a extra process: ME/CFS + X?

Jonathan Edwards

Jonathan Edwards

Senior Member (Voting Rights)
Trish suggested starting a thread based on this post from me:

But I think we my have to consider the possibility that people who are so ill they cannot feed themselves do not just have the process we think will be the basis of ME/CFS, but have another process as well. Which means that treating their immobility as 'a feature of ME/CFS' may not be helpful.

This is not so easy to explain but there are other situations where one disease can be associated with an extra form of pathology if there is another causal factor involved. One example is Kaplan's syndrome - lung nodulosis - which occurs only in people with RA who also have pneumosilicosis. For very severe ME/CFS there might be a separate risk gene involved. Where ME/CFS has risk genes CA10, OLFM4 and BTN2A1, maybe if you also have a variant of XYZ456 your ME/CS may be complicated by immobility. There are subsets of Parkinson's that are familial and have different features, I believe.

So rather than either sort of shaman's folklore that at present people argue over we need some serious clinical science.
 
Thanks for starting the thread.

I find this idea really interesting and I hope potentially productive. I'm not sure how much we can discuss it until there is more research, but perhaps the starting point would be what sort of research is needed to try to find out why some people diagnosed with ME/CFS get so much sicker, often in their teens or twenties, and what tips them from 'ordinary' severe ME/CFS, to being so sick they can't eat or move.

I think it would be useful to look at it from the perspective of the course of the illness in a sample of people whose ME/CFS became very severe, and another sample of people who stayed at severe or the upper end of very severe (bedbound but able to move and eat) and then improved or stabilised. Does it always go with extreme sensory sensitivity - would that give a clue to the biology?

And genetic study comparing very severe/extreme cases with moderate/severe who are stable or impoving could help clarify if there is a genetic difference.

Are there other studies that could help find out whether there's a difference in biology? Or a difference in lifestyle factors such as whether people did GET or some variation of over exertion? Or maybe catching another infection.
 
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Jonathan Edwards said:
Trish suggested starting a thread based on this post from me:

But I think we my have to consider the possibility that people who are so ill they cannot feed themselves do not just have the process we think will be the basis of ME/CFS, but have another process as well. Which means that treating their immobility as 'a feature of ME/CFS' may not be helpful.

This is not so easy to explain but there are other situations where one disease can be associated with an extra form of pathology if there is another causal factor involved. One example is Kaplan's syndrome - lung nodulosis - which occurs only in people with RA who also have pneumosilicosis. For very severe ME/CFS there might be a separate risk gene involved. Where ME/CFS has risk genes CA10, OLFM4 and BTN2A1, maybe if you also have a variant of XYZ456 your ME/CS may be complicated by immobility. There are subsets of Parkinson's that are familial and have different features, I believe.

So rather than either sort of shaman's folklore that at present people argue over we need some serious clinical science.
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My experience of MECFS is that episodes of immobility and getting PEM from very basic tasks gets more severe the worse you get. I first got episodes of temporary paralysis when in a crash while mild, and they got longer and more frequent the worse I was doing. When my condition has dipped towards very severe in the past those episodes of paralysis and that weakness and PEM doing very basic things increased massively.

It feels like an exponential worsening of the same process on one hand. But the sicker you get the more things like extreme sensory sensitivity are 'added in' and if you improve they go away.

I would guess very severe ME is the extreme end of that process, but that there are additional complications or loops of erroneous signalling turned on the further down you go. But it could be something else on top of it. People do seem to improve from very severe back to severe or even better fairly often though.
 
My experience was that forced to hospital, forced way beyond my limits took me from severe to a very bad place with extreme sensory sensitivity and problems feeding myself after I was discharged, I managed to get back to a more manageable severe with family support, but am always treading a tightrope and have been close to the edge on other occasions. And tbh fear I will end up there again given how we’re treated and my experiences.

The X is the health and social care systems. The lack of appropriate support. There may be a biological factor Y too ofc but if those systems changed to be safe for us less people with that would end up in these dire situations.
 
When I was at my worst, I considered myself at the edge of very severe. Maybe not quite there yet, because I was still able to do 200 steps a day. But zero screen time and not able to speak more than a few sentences without crashing.

What I remember is that every movement needed extreme willpower and using my muscles felt extremely "wrong". Sometimes I laid for hours without any movement. It may be a bit comparable to the feeling of "can't move" that marijuana can produce (though far less pleasant). But at the same time, it never felt like moving was fundamentally impossible, if I really wanted to.

So for me it was very much a "continuum", on the way down and on the way up.

I would be interested to hear from people that went through worse, if something felt fundamentally different?
 
I’m not sure if this relevant to the discussion, but in a recent series of articles / podcasts on Radio NZ, “All in Her Head”, genetic testing of one of the young women found Visceral Myopathy 2.
https://www.malacards.org/card/visceral_myopathy_2
The series is based on the difficulties faced by young women with “hEDS” and severe eating/digestive issues getting treatment in the public health system. I do not intend to derail this into a discussion about hEDS - but am curious if there is any merit in looking at the genetics in Visceral Myopathy 2 as a cofactor in why some people with very severe MECFS often have similar eating/digestive issues.
 
Be interesting to know whether the DecodeME analyses looked at (or are looking at) this. If I remember right, the second questionnaire asked about being housebound; it might not identify very severely ill people with 100% accuracy, but it would be a useful indicator.

As Trish says, another possible factor is age. Many of the people we've lost were very young when they became ill.
 
At my worst, I wouldn't have described it as paralysis, but I was so extremely weak that I couldn't sit up for more than a couple of minutes, if that. I couldn't hold utensils or a pen in my hand to write, couldn't hold a cup of tea, it was too heavy. Using my jaws to eat was so exhausting, I couldn't eat a full meal in one go despite being hungry and wanting to. I had to take a few bites, while lying down, collapse in weakness and exhaustion and rest for ages, then take a few more bites and so on.

It coincided with severe sensory symptoms, difficulty tolerating movement of objects or people visually, intolerance to light, severe sound intolerance, couldn't bear more than one person's voice talking, definitely no background radio or noise. It was about this time I had the surreal experience of a work dr berating me down the phone to get back to work. If I spoke / listened on the phone for 3 mins I couldn't speak the rest of the day, not because I couldn't physically but because the concentration and listening was so hard that I felt unbearably ill and couldn't do it again till the next day.

I didn't get to the stage of not being able to move at all, but I could imagine a more severe scenario as part of whatever that process was, where someone would be too weak to move at all or to chew food. Maybe that's what some people mean when they describe a paralysis?
 
fst said:
So for me it was very much a "continuum", on the way down and on the way up.
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Was very much a continuum for me as well especially on the improvement side which was very slow and got to see it progress. Just as endurance is lost in muscles on a set of weight lifting to the point where they hurt and fail and can no longer lift the weight they did moment before I had the same thing chewing food and digesting it, every stage of it was beyond my muscles abilities and hurt and they couldn't then do it. I never reached full paralysis but there was no doubt I was worsening my condition and injuring myself to do anything. Had the building been on fire I would not have been able to leave as my leg and body muscles would not have been able to cope with that level of exertion and would fail.

The continuum to full loss of that movement from the slight movements I could do seems completely reasonable to me based on how severe I got. I can absolutely see how someone would call that paralysis because in its final stages you can't move the muscles, they don't respond to your will just as they wont lift a weight they did moments before in the gym, it feels the same only at a substantially lower exertion. No new understanding of mechanism is required beyond that basic understanding, its extreme muscular exhaustion.

This is not just happening in young women.
 
It is always difficult to draw a precise line and clearly define what “very severe” ME/CFS actually means. Does it necessarily imply near-total paralysis, being unable to feed oneself, or complete intolerance to any kind of stimulation ?

But what about someone who falls somewhere between severe and very severe, who can still manage around 300 steps a day, but is bedbound for the vast majority of the time and cannot normally tolerate noise, light, or screens ? At that point, are we not already dealing with a qualitatively different form of the illness ?

At a certain stage, you can very clearly feel that the body simply cannot go beyond a few minutes of walking. It is not just a general feeling of tiredness: it becomes something you can physically feel in the muscles, as if the body no longer has the resources needed to continue.
Most patients are thought to be mild or moderate. They do not necessarily seem to experience this same extreme physical limit all the time. In severe illness, it can be present even outside an obvious PEM episode.

I have often wondered whether severe and very severe patients really have exactly the same illness as mild and moderate patients, or whether, beyond a certain threshold, additional mechanisms come into play.

The difference seems striking to me : major hypersensitivity to noise and light — watching television is impossible for me, for example — extreme muscular fatigability, and often much more significant digestive problems.

In my case, this muscular weakness was already present before I became bedbound. Then came a final crash, after which my body simply never regained its previous level of activity.
I went through an extremely severe phase where I was paralysed, could only consume liquids, and had to stay in complete darkness for a month.
LDA somehow pulled me out of that state, strangely enough. And I have remained out of it ever since, even after taking a two-month break from LDA.

This raises a real question : are severe and very severe forms simply the far end of the same continuum, or does the pathophysiology change in a more fundamental way once a certain threshold is crossed ?
 
For context I haven’t left this room or managed more than a few steps in many years. I manage with the right support but that is fragile.

For those particular bad times It definitely felt like my body or parts of it were shutting down. But not like the way you see with old people who sleep for hours. In some ways a continuum but in other ways a trap you can’t get out of. I get why people use some of the terms they do which some here find unhelpful because there’s little adequate way to describe the experience and we need a way to try to get others to understand and accept so try anything to do so.

There’s obviously something going on biologically as this doesn’t happen to everyone. But we don’t know what that is. We do seem to have pretty good idea I think that there are things which can make the situation worse and yet the services do not avoid them. Sometimes quite the opposite.

So I think the biological question is really interesting and something we should spend time on. At the same time, while we’re trying to understand that there should be far more focus on what we already understand which is there are things which could be done now to if not completely avoid then to reduce the chances of making peoples lives significantly worse.
 
My best friend died of ME complications, he was considered severe, and gradually worsened over 18 years-slow death. Severe insomnia from day one, feeling "poisoned', severe gut/ emptying issues, BP slowly dropping and feeling dizzy. He was more mobile than I am, and I consider myself moderate.
I feel it really depends on what body systems are affected.
 
From Google

"In practical terms, this means the brain is still refining its wiring in the teens and 20s, with synaptic pruning slowing down compared with adolescence and often leveling off in adulthood."

I have no idea if this is relevant, but are the natural physiological changes in brain maturation being impacted in some way.
 
BrightCandle said:
Was very much a continuum for me as well especially on the improvement side which was very slow and got to see it progress. Just as endurance is lost in muscles on a set of weight lifting to the point where they hurt and fail and can no longer lift the weight they did moment before I had the same thing chewing food and digesting it, every stage of it was beyond my muscles abilities and hurt and they couldn't then do it. I never reached full paralysis but there was no doubt I was worsening my condition and injuring myself to do anything. Had the building been on fire I would not have been able to leave as my leg and body muscles would not have been able to cope with that level of exertion and would fail.

The continuum to full loss of that movement from the slight movements I could do seems completely reasonable to me based on how severe I got. I can absolutely see how someone would call that paralysis because in its final stages you can't move the muscles, they don't respond to your will just as they wont lift a weight they did moments before in the gym, it feels the same only at a substantially lower exertion. No new understanding of mechanism is required beyond that basic understanding, its extreme muscular exhaustion.

This is not just happening in young women.
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Very fitting description, much better than my attempt!

For me the weakness was also very paradoxical — having my phone slide out of my hand, unable to hold it for more than 60 seconds, but at the same time, able to pull above average grip strength on a hand dynamometer. In such moments, I can understand why some people find it hard to believe.
 
V.R.T. said:
When my condition has dipped towards very severe in the past those episodes of paralysis and that weakness and PEM doing very basic things increased massively.
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What does the paralysis feel like for you? I’ve experienced something like paralysis only once, in a crash. Normally I’m somewhat mobile but bedridden. I woke up being unable to move my legs except for toes. Attempts to move them only caused myoclonus. They hurt a lot more than usual. There was also something wrong with my proprioception. I couldn’t tell which position my legs were in, though they weren’t numb. The “paralysis” went away along with the pain when a caregiver bent each leg at the knee and moved it around (though I also took Mestinon a few minutes earlier). He said they were unusually hot to the touch but idk if I trust that assessment. I was covered with a blanket and it was summer. I thought it could’ve been a blood clot or something though in that case it would be weird that it affected both my legs. Or maybe it was like when your leg falls asleep but 10x worse and without anything obviously constricting the blood flow. That was years ago and it never happened again.

Normally the thing that can make me immobile for hours is that any movement exacerbates symptoms and moving too much can cause additional PEM. Also, in severe crashes, I feel as though I have muscle weakness in the sense that objects whose weight I know really well suddenly feel much heavier
 
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I feel as though my condition could have worsened further in terms of cognitive, sensory, perceptual and autonomic functions (and I was severely affected in those areas), but not in terms of muscle function, which were, admittedly, very heavy and difficult to manoeuvre but never weaks. And I was thinking more along the lines of protective factors. (I had a ready-made explanation: the thalassaemic trait - - Salmon mousse! In *The Meaning of Life* by Monty Python).
It’s a bit irrational. But given my ignorance and carelessness for ten years, my condition should have worsened, and that didn’t happen. So it’s possible that the very severe forms have something extra or something missing.
 
I get the point about it being a continuum in terms of symptoms and functional capacity. The descriptions of members' exeriences are a very valuable contribution to this discussion.

My question then would be why, biologically, for some pwME the continuum takes them to such extreme incapacity, and for others it never goes that far.
 
lelelemonade said:
Normally I’m somewhat mobile but bedridden. I woke up being unable to move my legs except for toes.
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I recall two moments in my very severe period where I woke up but was locked in, I couldn't open my eyes or move at all, was complete paralysis. They both lasted a while, an hour or two. They ended after I fell asleep and awoke again able to move. Potentially this is something that these very severe people who are being mistreated are getting into more frequently and trying to explain. Could be that is what they are describing. I don't think I have heard other ME patients talk about this type of experience but it could be most very severe that suffer it are still very much in the depths of it being very hard to communicate clearly or didn't survive it.
 
neophyte32 said:
It is not just a general feeling of tiredness: it becomes something you can physically feel in the muscles, as if the body no longer has the resources needed to continue.
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That doesn't mean that the limitation is in the muscles. There doesn't seem to be any evidence of failure in the muscles themselves; no lack of ATP or other such factors. I'd like someone to do a proper study of the signalling to/from muscles in people who are feeling that inability to use muscles (maybe compared to PWME who aren't feeling that inability?). Maybe the severe PWME have stronger or weaker signals than mild PWME. I don't know how deep into the brain signals they'd have to look. I suppose they could measure the easiest ones first.
 
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