Post-Exertional Malaise - a discussion including defining and measuring PEM

[Eddie]

My thinking on this is that there is a group of symptoms that occurs from exertion in ME/CFS. There is also a group of symptoms that occurs when sick and particularly when exerting when sick. Mij you clearly think these two things are completely separate and because ME/CFS is likely not one thing, in some cases I am sure you are correct. However, there does seem to be considerable overlap at least in the types of symptoms between PEM and how people feel after exerting themselves when sick.

Lets say that you got sick and while the fever went away all the other "sickness" symptoms remained. In that situation while you would have fatigue, soreness, probably some brain fog. I would imagine that being too hot, being upright too long, lots of loud sounds and too much light, physical activity would make you feel much more terrible. I am not sure that this worsening would be delayed like PEM, but I really don't know, it could be depending on the method of exertion. It is also not something that people would typically experience because people who have a significant sickness response they typically lie in bed all day and do not exert.

In ME/CFS it would also be hard to differentiate the PEM from a sickness response. Any activity that would drive exertion related symptoms when sick would likely also cause PEM. It is also plausible that in ME/CFS the specific part that is malfunctioning is doing so in a way that is more severe than a typical sickness response and leads to worse exertional symptoms.

Does anyone know if there are any studies looking at what happens in healthy people when they exercise when really sick? I'd imagine that isn't the kind of study that would get ethics approval but you never know what they might have run in the past.

Also, if it PEM is caused by an exhausted immune system wouldn't we expect extremely evident changes given the level of symptoms. It seems like there are some immune changes in pwME/CFS but nothing that resembles severe immune exhaustion and certainly not to the level of causing someone to become bedbound. Perhaps there is some hard to find immune cell causing major issues. However, I find it hard to see how the immune system could produce PEM and why that wouldn't be producing a more detectable sign if that were really what was happening.

 

[Mij]

My thinking on this is that there is a group of symptoms that occurs from exertion in ME/CFS. There is also a group of symptoms that occurs when sick and particularly when exerting when sick. Mij you clearly think these two things are completely separate and because ME/CFS is likely not one thing, in some cases I am sure you are correct. However, there does seem to be considerable overlap at least in the types of symptoms between PEM and how people feel after exerting themselves when sick.

I agree. Our experiences with PEM will differ. During the first several years of illness I would get a sore throat after over exerting, but that was during the PVFS phase.

Symptoms change over time, and for those of us who have been ill for decades it's easily distinguishable.

 

[Kitty]

Also, if it PEM is caused by an exhausted immune system

I'm not sure what an exhausted immune system is. Even if it's a meaningful concept, it's probably not very useful in the context of PEM. Part of the PEM phenomenon does resemble some kind of immune response (sore throat, swollen glands, etc), but a common cold can do it a lot better.

[ETA: and if the immune system really was exhausted in PEM, it presumably wouldn't be able to produce this response?]

I find it hard to see how the immune system could produce PEM and why that wouldn't be producing a more detectable sign if that were really what was happening.

Yes, that seems about right.

I would imagine that being too hot, being upright too long, lots of loud sounds and too much light, physical activity would make you feel much more terrible. I am not sure that this worsening would be delayed like PEM

I suppose it'd be somewhat delayed if the virus was in one of the eight measures of whiskey they'd had.

But seriously ... people do sometimes have to work through illnesses, sometimes pretty unpleasant ones. My own experience is that it seems to prolong the recovery, but it's not like PEM. It's not delayed, and you're not 'wired' in the same way. You're fatigued, fed up, and you sleep a lot.

 

[Sean]

Symptoms change over time,

Not clear to me if the symptom profile has changed over time, or just the balance between the symptoms (mostly due to learning how to reduce PEM).

Similarly, I can't tell if going deep into PEM introduces new symptoms, or just alters the balance between pre-existing symptoms by exacerbating some more than others.

Some symptoms may be (relatively) mild and being masked when not in PEM, and only become dominant when in PEM.

 

[Mij]

Not clear to me if the symptom profile has changed over time, or just the balance between the symptoms (mostly due to learning how to reduce PEM).

Similarly, I can't tell if going deep into PEM introduces new symptoms, or just alters the balance between pre-existing symptoms by exacerbating some more than others.

I can understand that. I don't have many symptoms so it's easier for me to identify a change in fatigue state and know when it's time not to go over my baseline. It took many years of trial and error figuring this out though

 

[Jonathan Edwards]

I know little about biology but aren't there a tremendous amount of things where symptomology occurs delayed?

Yes, but by and large not simply depletion of metabolic pathways, usually where there is an innate or adaptive immune response. But also where there is cell damage and activation of repair. The odd thing is that pretty much all of these are associated with easily measured biochemical markers like c-reative protein or creatine kinase and in ME there is nothing.

 

[Jonathan Edwards]

I'm not sure what an exhausted immune system is. Even if it's a meaningful concept

Agreed. As an immunologist I have no idea what it means. There are technical terms for T cells that have gone through a maturation process to what has been called 'exhaustion' - associated with the winding down of a T cell response - but they are unlikely to be relevant here. One or two researchers have noted these 'exhaustion' markers but I don't think we have any idea how to interpret them and the differences were not very great anyway.

 

[poetinsf]

That would be the threshold for that iteration. But then repeat the entire process another five times over the next five weeks. Do you think you'd get the same threshold each time?

In my experience, yes, as long as you do the experiment at a similar baseline. But that's just me. It would be useful info if we can establish that generally for ME/CFS.

I used to describe the PEM threshold as bright red line. It was such that walking a loop in one direction would trigger PEM while the opposite direction didn't, probably because the how the loop descended gradually in three sides and then rise steeply on one. Then the experiment with walking speed in 2012-2013 established that walking 5% faster over the same distance was enough to trigger PEM. These days though, it is more like fuzzy grey line. When I'm on the road, I'm completely PEM-free. In springtime at home, I'm back to pacing. So, I can see the line becoming floaty in certain stages. For most patients, however, I think the experiment will show the same PEM threshold. We'll never know for sure though, till someone does the experiment with n > 1.

 

[Kitty]

For most patients, however, I think the experiment will show the same PEM threshold. We'll never know for sure though, till someone does the experiment with n > 1.

But we can't do the experiment unless we can start from a known point. Most pwME have no way of knowing what number on the scale they're at right now, so they don't know how much capacity they have left. Without that, they can't work out how far away they are from a threshold and what level of activity will push them over it.

Even if they could measure activity, they still couldn't account for all the other factors—noise, light, temperature, headache, IBS, hay fever, menstrual pain, traffic fumes, other people's behaviour—that on a day to day basis are often the difference between PEM/not PEM.

There might be an individual threshold, but it's not really a meaningful or practical notion when there are so many variables that it can only ever be known after the fact.

 

[poetinsf]

But we can't do the experiment unless we can start from a known point. Most pwME have no way of knowing what number on the scale they're at right now, so they don't know how much capacity they have left.

3-days of no more than baseline activities in non-PEM state probably is a good buffer as far as physical exertion is concerned.

Even if they could measure activity, they still couldn't account for all the other factors—noise, light, temperature, headache, IBS, hay fever, menstrual pain, traffic fumes, other people's behaviour—that on a day to day basis are often the difference between PEM/not PEM.

That's true, there are other non-physical variables. Not sure how much they contribute toward PEM threshold though. My guess is that physical exertion is the predominant factor for PEM for an average patient for most of the time. I think it would be meaningful enough if we can control at least one major variable even if we can't account for all variables. Some control is better than no control, after all.

 

[Kitty]

3-days of no more than baseline activities in non-PEM state probably is a good buffer as far as physical exertion is concerned.

Even so, I'm still not really clear how establishing a PEM threshold would be useful.

This is because we never normally have the opportunity to start from three days of minimal activity—we have to use up some capacity every day doing basic living activities like washing, dressing, getting and eating food, toileting, etc. That means we still wouldn't know whether we might incur PEM by adding a further activity, because we can't know how much capacity we have that day or how much of it we've already used.

I'm sorry if I'm being a bit dense and just not understanding what you're saying(!). Thing is, I've been muddling my way through this since the 1970s and I've never yet found a way to know how much I can do on any day without risking PEM.

It's partly because it doesn't work like a battery—at one point I can be unable to shower without becoming so exhausted I risk a fall, yet manage it fine eight hours later—but mostly it's because my scale is made of knicker elastic, it has no graduation markers on it, and the only thing I do know is it never resets to zero.

 

[poetinsf]

Even so, I'm still not really clear how establishing a PEM threshold would be useful.

Knowing is always more useful than guessing, right? Without knowing where your threshold is, you can only resort to something like 50% method. Or, stick to the routine only. If you know where the line is on the other hand, you could push it to, say, 80%, or venture outside of the routine.

This is because we never normally have the opportunity to start from three days of minimal activity—we have to use up some capacity every day doing basic living activities like washing, dressing, getting and eating food, toileting, etc. That means we still wouldn't know whether we might incur PEM by adding a further activity, because we can't know how much capacity we have that day or how much of it we've already used.

This is where the idea of measuring the exertion and rolling PEM come in handy. If you can measure the toll of washing and toileting somehow, and know where the threshold is, then you would have some idea how much capacity left in the tank. And you don't have to start from the empty/full tank as long as you roll-sum the costs that you've been incurring.

I'm sorry if I'm being a bit dense and just not understanding what you're saying(!). Thing is, I've been muddling my way through this since the 1970s and I've never yet found a way to know how much I can do on any day without risking PEM.

It's partly because it doesn't work like a battery—at one point I can be unable to shower without becoming so exhausted I risk a fall, yet manage it fine eight hours later—but mostly it's because my scale is made of knicker elastic, it has no graduation markers on it, and the only thing I do know is it never resets to zero.

No, you are not being dense. We only have our experiences to go with and you and I have slightly different experiences, that's all. And that is what I'd like to find out: how useful would the model be, and to how many people? They say every patient is different, but I'm frequently struck that how similar we are on average.