Why so little focus on Functional Disability and so much focus on “Symptoms”?

[MrMagoo]

The threshold isn’t totally fixed, though. If you said to me right now, go outside and walk 1 mile to x place and I will give you £1000, I’d do it. I could force myself. And I’d be destroyed, probably would miss my GP appointment later in the week. In real life -Am I going to hoover today? No, I’m resting after doing washing. I haven’t been outside for a few days.
If you said 5 miles for £5000, I wouldn’t even attempt it because I wouldn’t finish it, guaranteed.

 

[poetinsf]

It’s the fact that if you do more than you currently are doing not only will your symptoms worsen, but the threshold for your symptoms worsening will continue to lower.

Severe PEMs that last months feel like that in my experience. And it does take some time for me to get back to the baseline after the PEM is over. But there is no evidence that PEMs, at least the average ones, make you progressively worse. If it did, I'd be basket case by now. I was a slow learner and I used to suffer weekly PEMs for years.

PEM is nasty, no doubt about it. And it needs to be avoided best you can. But being overly afraid of it, like everything else, could be also detrimental.

 

[Mij]

Continuing to push myself into delayed PEM years ago from exercise took its toll and negatively affected my cognitive function when was normal for 10 years from ME onset. Some people may not realize that they are declining from pushing until it's too late.

 

[Keela Too]

I’m thinking there are 3 ME states linked to activity/exertion.

1. In the moment symptoms and associated fatiguability.

These symptoms can be mild to severe, and once a pwME knows how to interpret their own set of symptoms, they can try to use them to pace activities. (Other tools like Fitbits can also help).​

2. A delayed Post Exertional Malaise (PEM) response starting 12-48 hours after having been active.

This is different to a normal healthy person’s tiredness or achy-ness, and can feel like flu with other additional symptoms.

PEM symptoms can also range from mild to severe.

Weirdly, a severe level of PEM can be triggered by very mild in the moment symptoms, and severe in the moment symptoms might produce only relatively mild PEM.

The pwME is the best placed person to judge their likely PEM response.
​

3. The Long-term Aftermath.

This is where the pwME is left after passing through states 1&2. (Note This may be compounded by re-entering states 1 & 2, before stabilising enough to judge the aftermath)

The long term aftermath can range from no change, to a severe lowering of the pwME’s long-term ability to function.

The dilemma for the pwME is trying to judge what level of in the moment & PEM symptoms they can experience, without producing a long term down step in their functioning.
​

Pacing to prevent long term decline is the absolute priority.

*
When I was most ill, I needed to be attentive to very mild in the moment symptoms, in order to prevent PEM as much as possible, because each and every time I got PEM my functioning was ratchetted to a lower level.

Now that I am less ill, I can accept more symptoms both in the moment, and as PEM, because the aftermath is currently negligible. (Don’t worry, I continue to be very observant, and am constantly assessing my thresholds).

In short, it is the aftermath that pwME fear most.

This is particularly so for the individuals who can have a big detrimental aftermath from only very mild in-the-moment symptoms. These are also the people judged most harshly for being overly concerned about symptoms.

Ignoring in the moment symptoms is a risk.

The pwME is the person best placed to assess their own susceptibility.

 

[Yann04]

@Creekside I understand what you’re saying, but I never meant to say every PEM bout leads to permanent worsening. But a common theme in people’s experiences is that some severe or prolonged ones do.

The large majority of moderate and severe people seem not to have started out in that state, but an event or culmination of events lead them to spiral down into that severity. The common theme about these events seems to be major overexertion followed by a major PEM crash that never really got better.

The current status quo seems to be leaning more on the side of ignoring that PEM can lead to permanent worsening for some, and failing to take it into account, which is why I think it’s important I made this thread, even if it doesn’t encompass every single experience of everyone with ME.

 

[Kitty]

The current status quo seems to be leaning more on the side of ignoring that PEM can lead to permanent worsening for some

Yep. And they have no way of knowing they're in that subgroup until they find out through experience. For some, that'll be too late.

We could really do with some research on this. What proportion of people with ME/CFS only experience worsening, and what proportion tend to recover some of their previous function after a severe crash, even if it takes years? Do some of the 'recoverers' eventually convert to 'worseners'?

 

[Trish]

I also think this feature of ME/CFS where people decline after crashes and don't recover to their previous level is really important, and not taken into account enough in descriptions of ME/CFS.

Perhaps the only way of finding out is long term large scale longitudinal studies that use wearables and symptom apps to see whether there are discernable patterns.

 

[Peter T]

I also think this feature of ME/CFS where people decline after crashes and don't recover to their previous level is really important, and not taken into account enough in descriptions of ME/CFS.

Perhaps the only way of finding out is long term large scale longitudinal studies that use wearables and symptom apps to see whether there are discernable patterns.

I very much agree, we desperately need some basic but reliable descriptive data.

 

[Keela Too]

Yep. And they have no way of knowing they're in that subgroup until they find out through experience. For some, that'll be too late.

We could really do with some research on this. What proportion of people with ME/CFS only experience worsening, and what proportion tend to recover some of their previous function after a severe crash, even if it takes years? Do some of the 'recoverers' eventually convert to 'worseners'?

Definitely.
I changed from being a ‘worsener’ to being more steady state.

Why was I initially a ‘worsener’ (great word BTW) but now that I’m back to the functioning level I had in my first months of ME, am I no longer a ‘worsener’?

Why did being in a ‘worsener’ state seem to make me increasingly susceptible to worsening?

What has changed to mean I can now tolerate more symptoms without worsening?

What particular things might flip me back to being in a ‘worsener’ state again. I’d really like to know, because I am very aware that things can change after many years of apparently better stability.

Good thread @Yann04

 

[Sean]

Pacing to prevent long term decline is the absolute priority.

This.

 

[Creekside]

What causes PEM in your case then? Is it emotional or mental exertion, sensory?

I've had some incidents that might have been PEM induced by cognitive exertion (socializing (chatting briefly) and driving in stressful conditions) but I'm not absolutely sure. I've never had sensory-induced PEM or hypersensitivity.

 

[Creekside]

However, if I am understanding you correctly, your own theory briefly stated is "cumin cures a subportion of people that experience ME/CFS from PEM caused by physical exertion"

No, not a theory, just an observation that cumin had that effect on me. I don't consider N=1 to be a subportion; maybe an aberration. Maybe I have a mutant microbe that responds to cuminaldehyde, or that molecule interacts with protein folding in a unique way with a DNA sequence unique to me.

I agree that one person who doesn't get worse PEM due to a previous PEM episode doesn't discount any theory based on the rest of the population. It comes down to numbers: how many people do report that effect and how many don't. From these forums, I haven't gotten the impression that that pattern of PEM worsening is overwhelmingly common. For some, any PEM leads to serious worsening. For others, PEM is a short-term annoyance, and they're willing to accept it in return for doing something enjoyable. I went for bike rides knowing that I'd feel worse the next day, because I really felt like going for a nice ride that day. For me, pacing just wasn't an issue, because PEM didn't result in long term decline. That was true for cognitively-induced PEM too.

 

[Peter T]

I've never had sensory-induced PEM or hypersensitivity.

It is hard to separate hypersensitivity issues from other things as mostly they do not occur without other things also happening. Reviewing in retrospect the 30 years of my ME I have a couple of possible examples:

• A rock band played on a flat bed truck with speakers point straight at my windows during the village carnival. I had had a busy day photographing the various events during the day for the village website so was too tired to drive elsewhere. The sound levels were perhaps the most unpleasant experience of my life. I now understand how noise can trigger neighbour violence. The next day I had PEM but can’t be certain how much was the activity and how much sound levels.
• Gardening on a bright sunny day is more likely to trigger PEM than gardening on a cloudy day, especially if I forget to wear my sunglasses. Though again sensory issues are interacting with physical activity.
• On one occasion when it was exceptionally cold on the journey home from work (so a number of years ago) I was just nipping in and out of the car so I had not bothered to put my coat on. Getting out of the car I met someone I had not seen for a while so ended up talking for ten minutes. Getting very cold triggered two weeks in bed.

More generally I feel that sensory issues and orthostatic issues interact with physical and cognitive activity making PEM more likely.

 

[EndME]

No, not a theory, just an observation that cumin had that effect on me.

I was trying to say that, that in itself would still be a theory, because you'll unfortunately never be able to prove that it was in fact cumin that had that effect. A member of the international association for scuba-diving enthusiasts might argue that it was in fact entirely psychological, someone else might even go as far as saying that your childhood trauma relates to cumin in some magical way, whilst someone else will try to tell you that it had something to do with mold or xyz. I think the patients that reported improvement on Rituximab would have initially been equally convinced that it was Rituximab that had that effect and some possibly still remain convinced that it was the case.

But I do agree with your larger point. I think the evidence to suggest permanent worsening from repeated PEM is probably at the same level of the evidence that long-term avoidance of PEM leads to permanent improvements. Heterogeneity seems to be rather large and without a good study it's hard to discern any meaningful pattern.

 

[Jonathan Edwards]

Think of it as having to budget on a low income using a credit card, that if you overdrew at all, even just a tiny amount, you were are hit with high interest, AND a lowering of the next threshold for the big interest rates kicking in.

Yes I get all this stuff but I am trying to make the point that I think in unravelling the problem scientifically the biggest mistake is to disregard the actual symptoms and focus on thresholds. Understanding thresholds needs a quantitative model and we rarely ever get that good with our models. We tend to identify qualitative mechanisms and then see if a drug designed to reverse the model works. We then choose doses by trial and error rather than knowing enough about threshold levels to predict what is needed.

 

[Jonathan Edwards]

And judging by reading a bit more of the thread the thresholds seem pretty much all over the place both for different people and individuals across time so as a scientists I wouldn't;t even try to model that.

 

[Jonathan Edwards]

The current status quo seems to be leaning more on the side of ignoring that PEM can lead to permanent worsening for some, and failing to take it into account,

Yes, I agree that researchers seem not to be even trying to model that long term aspect. Theories about mitochondrial function or low blood volume or whatever never seem to provide any explanation for the long term time profile.

What is not clear to me is that we know that it is the PEM (exacerbation of symptoms) that causes decline. I thin more in terms of the exertion causing the decline and the long term nature of that decline as part of what we call the effect - PEM.

Which is why in recent articles I have suggested that not only do we not have any useful information on mechanisms yet, but it looks as if we need to look for an entirely new sort of mechanism, in the way that autoimmunity was once new, viruses were once new, prions were once new etc.

 

[Sasha]

What is not clear to me is that we know that it is the PEM (exacerbation of symptoms) that causes decline. I thin more in terms of the exertion causing the decline and the long term nature of that decline as part of what we call the effect - PEM.

I once gave myself a long-term setback by being upright for longer than my orthostatic intolerance could really stand, which might amount to exertion. I also see PEM as a symptom of over-exertion, not the driver of a decline. I think that driver is over-exertion, as you say.

Which is why in recent articles I have suggested that not only do we not have any useful information on mechanisms yet, but it looks as if we need to look for an entirely new sort of mechanism, in the way that autoimmunity was once new, viruses were once new, prions were once new etc.

Roll on, DecodeME...

 

[Sasha]

Which is why in recent articles I have suggested that not only do we not have any useful information on mechanisms yet, but it looks as if we need to look for an entirely new sort of mechanism, in the way that autoimmunity was once new, viruses were once new, prions were once new etc.

I'm wondering what sort of mechanism can have gone undiscovered at this point. Is it weird that the glymph system has only just been discovered?

 

[Jonathan Edwards]

I'm wondering what sort of mechanism can have gone undiscovered at this point. Is it weird that the glymph system has only just been discovered?

All sorts of mechanisms may well have gone under our radar. The mechanism I based treating RA on had gone under the radar of immunologists for decades despite being fairly easy to see if one thought clearly (which one can do with hindsight).

Prions were totally unexpected. Even germs were unexpected until Pasteur came along.

But these things are undiscovered precisely because we have not thought of anything like them.

The 'discovery of the lymphatic system' is to my mind pretty much hype. It is hardly surprising that brains have some glymphatic outflows. I doubt it is of any great relevance though. Most of the stuff I have seen talking about glymphatic function is based on simple errors of understanding of flux and compartmentalisation.