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

[richie]

I can appreciate where this may be coming from; none of us likes the cavalier hijacking of an acronym which for years has been considered unique to us, and therefore partially definitional. However, I do think there are a handful of conditions that share it with us. And yes, the other two as well. Channelopathies come to mind.

Fair point, I'm not excluding other conditions besides ME/CFS/PVFS/LC experiencing PEM. I don't have the medical knowledge or personal experience to do that. I'm just saying we have all 3 of PEM, PEF and exercise intolerance, , whereas some conditions only have one or two of that list.

Perhaps a category of "post activity malaise" needs to be added for conditions such as sarcoidosis. The experience there for many is beyond PEF and beyond exercise intolerance but thus far has not given 2 day CPET worsening. I think fibro and GWS would fit too and possibly Lyme and post Lyme also.

 

[richie]

In my opinion we need to define "post" - how long after, "exertion/al" remembering that in any illness much normal activity will be an exertion, and "malaise", because in normal usage fibro sufferers, sarcoid sufferers. GWS, Lyme, post Lyme can put a good argument that they get malaise. We must also be careful not to minimise their experience as sth not quite as bad as PEM without knopwledge of the degree of their post exertional distress.
IMO For pwME, the fact is that the diagnosed may represent a mixed bunch, few with actual encephalomyelitis and possibly in fact differing as to PEM. All will have significant "activity is exertion" with exertion/activity intolerance and not one will want to be basketed as "not ME CFS" with all that has implied.

 

[richie]

If I were attempting to define or measure something, I'd start by not assigning it a misleading label - or if that ship has sailed, making sure everyone knew that label was misleading.

Shouldn't be hard to shed "malaise" since so few of us live in antebellum Charleston.

If I were attempting to define or measure something, I'd start by not assigning it a misleading label - or if that ship has sailed, making sure everyone knew that label was misleading.

Shouldn't be hard to shed "malaise" since so few of us live in antebellum Charleston.

Suppose that was pre-exertional.

 

[FMMM1]

On a slightly different tack I wonder whether there is still a confusion between exertion and energy-consuming activity. For a fit young person running down to the sea and jumping into a wave involves no exertion, just activity. For someone with old eyes like me threading a needle requires huge exertion but zero activity.

I am thinking that the exertion is that is the problem in ME is a purely central nervous system property. The battery is the brain. Being run down is not actually an issue of ATP or lactate or aerobic thresholds or any of that. It is more like an increase in 'entropy' of an information processing system. The running down of a battery is also an increase in entropy but it is recognised that there are two sorts of 'entropy'.

Physics entropy relates directly to energy and thermodynamics - free energy rules.
Informational entropy is analogous but not does not actually involve the energy of physics. It can apply to a computation written on a napkin. Cognitive scientists have their own concept of informational 'free energy' (e.g. Karl Friston) which relates to order but not actual thermodynamics.

This may all sound airy fairy but take the travelling thing. It is often mentioned that PWME are exhausted by travelling. Travelling involves exertion. My wife and I have a rule that a day's travelling uses up an extra hour of brain time. Nine o clock at night becomes ten o clock. So jet lag is worse one way and than the other. And of course most travelling involves little or no activity - sitting in a train maybe. The worst thing is driving at night. There is no activity of note but exertion is maximum.

Maybe another analogy is cooking for guests. There comes a point when all the pans, and vegetable knives, and indeed spoons, are in a jumble covered in food debris on the worktop and you have to clear the sink to get enough things clean to move on.

What I see as different about ME is not that there s some unique phenomenon of relation of exertion to symptoms. Normal people encounter travelling fatigue. Normal people with flu get malaise (which I think is a good word because in medicine it spells the serious danger of things like septicaemia or typhoid rather than just fatigue) which is precipitated by exertion (although thinking about it it might in that case be more activity). The difference in ME is that the kinetics are distorted. Like the disturbance of circadian rhythm with jet lag something has put the metaphorical/informational free energy accounting out of line. Like the computer system at the Post Office, it doesn't make sense. It is an unstable kinetics a well as a 'dragged down' kinetics.

Thank you - I agree with what you have written. However, I wonder if the underlying cause/predisposition would be identifiable via GWAS [DecodeME] and/or is there some way to objectively measure this?

 

[Andy]

On a slightly different tack I wonder whether there is still a confusion between exertion and energy-consuming activity. For a fit young person running down to the sea and jumping into a wave involves no exertion, just activity. For someone with old eyes like me threading a needle requires huge exertion but zero activity.

Well, I for one don't understand the distinction being made between exertion and energy-consuming activity. Or at least I don't understand the importance of the difference within the context of this discussion. In your examples exertion seems to equate to what I would understand as "use of brain", which in my experience consumes energy, so would seem to be an "energy-consuming activity". I would argue that the difference between a fit young person and someone with old eyes is either larger energy reserves or the ability to replenish that energy, or both.

This may all sound airy fairy but take the travelling thing. It is often mentioned that PWME are exhausted by travelling. Travelling involves exertion. My wife and I have a rule that a day's travelling uses up an extra hour of brain time. Nine o clock at night becomes ten o clock. So jet lag is worse one way and than the other. And of course most travelling involves little or no activity - sitting in a train maybe. The worst thing is driving at night. There is no activity of note but exertion is maximum.

This example seems to confirm my understanding. Recently I was talking to my wife about how even short car trips are demanding not just because of the energy used to move myself from the flat, into the car, then out of the car and into the destination, but also because of all the additional processing my brain will have to do from the extra sights and sounds, even if I'm not actually driving. Now I am more than willing to concede that there might be a technical difference between a physical consumption of energy and a mental one, but ultimately they don't feel any different to me.

What I see as different about ME is not that there s some unique phenomenon of relation of exertion to symptoms. Normal people encounter travelling fatigue. Normal people with flu get malaise (which I think is a good word because in medicine it spells the serious danger of things like septicaemia or typhoid rather than just fatigue) which is precipitated by exertion (although thinking about it it might in that case be more activity). The difference in ME is that the kinetics are distorted. Like the disturbance of circadian rhythm with jet lag something has put the metaphorical/informational free energy accounting out of line. Like the computer system at the Post Office, it doesn't make sense. It is an unstable kinetics a well as a 'dragged down' kinetics.

Again, I'm not sure I understand you, but my best attempt to explain how I view things is that pwME have a reduced amount of energy as a baseline, this then makes any form of energy consumption proportionally more impactful when compared to someone who doesn't have that reduced baseline. So it might be that energy expenditure might be the same for a pwME and someone who is similarly sedentary, but the pwME will be affected more by it. On top of that, each pwME has an individual amount for energy consumption, which if they go beyond results in PEM.

 

[Jonathan Edwards]

@Andy,
I am not sure that we have much evidence for the brain using more energy when it is struggling hard to solve a problem or cope with discomfort or anything that requires mental exertion. I just don't think there is any biological reason to connect the two.
Yes, you can see increases in oxygen uptake in certain areas during thinking, but the changes are local and probably not that big. The brain needs a huge amount of energy just to stay alive and be capable being used. I suspect pretty much like a computer, that uses energy refreshing its screen and rather little more calculating Pi to 100 decimal places.

This is basically the argument Mike Murphy made at the IiME conference around 2015. A failure of actual energy availability as in ATP would give a very different picture from ME it seemed to him, and to me. If PWME ran out of brain energy they would black out lying down. They don't.

My wife swims a kilometre or two several days a week. After swimming she is bright and perky and even more ready to face dealing with water bills or cooking a dinner. On the other hand if we sit in a car with me driving and her watching out for things I might have missed for an hour we are completely drained.

I think exertion has to do with activities that require deliberate shifts in routine activity patterns. The greatest mental exertion is doing a difficult exam. I very much doubt that uses more physical energy than playing snap with a five year old.

 

[duncan]

Suppose that was pre-exertional.

My issue is with the word "malaise." It cheapens and sullies decades of accrued patients' experience. It reduces a definitional symptom cluster down to a quaintly idiosyncratic period piece.

I don't care if some doctors claim to understand it clinically different than the typical layperson; it cannot be extricated from its cultural knots. It should be deep-sixed.

 

[Jonathan Edwards]

Thank you - I agree with what you have written. However, I wonder if the underlying cause/predisposition would be identifiable via GWAS [DecodeME] and/or is there some way to objectively measure this?

What genetic studies might do is identify some neural regulatory protein that is involved in refreshing 'mental' metaphorical free energy stores. For instance it has been suggested that complement proteins may be involved in tidying up dendrites during sleep after a day's experiences, to ensure memory is laid down coherently and efficiently.

 

[Jonathan Edwards]

I would argue that the difference between a fit young person and someone with old eyes is either larger energy reserves or the ability to replenish that energy, or both.

It is not about age. A shortsighted teenager would have just as much trouble as I do.

 

[Andy]

@Andy,
I am not sure that we have much evidence for the brain using more energy when it is struggling hard to solve a problem or cope with discomfort or anything that requires mental exertion. I just don't think there is any biological reason to connect the two.
Yes, you can see increases in oxygen uptake in certain areas during thinking, but the changes are local and probably not that big. The brain needs a huge amount of energy just to stay alive and be capable being used. I suspect pretty much like a computer, that uses energy refreshing its screen and rather little more calculating Pi to 100 decimal places.

This is basically the argument Mike Murphy made at the IiME conference around 2015. A failure of actual energy availability as in ATP would give a very different picture from ME it seemed to him, and to me. If PWME ran out of brain energy they would black out lying down. They don't.

My wife swims a kilometre or two several days a week. After swimming she is bright and perky and even more ready to face dealing with water bills or cooking a dinner. On the other hand if we sit in a car with me driving and her watching out for things I might have missed for an hour we are completely drained.

I think exertion has to do with activities that require deliberate shifts in routine activity patterns. The greatest mental exertion is doing a difficult exam. I very much doubt that uses more physical energy than playing snap with a five year old.

Are we not talking about different things here? I make no claim to be able to define PEM or the other issues that pwME face in terms of what is actually going on biologically, but what I do claim is that I try to explain as clearly and as logically as I can my experience, and what I understand to be the experience of many other pwME. So I'm sorry if my explanation doesn't make sense biologically, but it doesn't change how true it is to me, or to those pwME who recognise their experience in my descriptions.

 

[Andy]

It is not about age. A shortsighted teenager would have just as much trouble as I do.

Then that shows I don't understand your analogy.

 

[Jonathan Edwards]

So I'm sorry if my explanation doesn't make sense biologically, but it doesn't change how true it is to me, or to those pwME who recognise their experience in my descriptions.

The problem comes when subjective experience is expressed in terms like 'energy' which has both a colloquial subjective meaning and a scientific meaning. The confusion is important because any number of people are researching into ME on the assumption that there is a problem with the scientific sort of energy. They do 2 day CPET studies, study mitochondria and lactate and so on. All these may be irrelevant.

There is also the concept of energy limiting chronic illness. Google says:
What is an 'energy-limiting condition'? An energy-limiting condition is not a medical diagnosis. Instead, it is a term that describes the symptoms of reduced physical and cognitive energy levels often experienced by people living with underlying health conditions and disabilities.

Which is pretty confused. If this is not a diagnosis what actually is it? A symptom pattern, maybe. But what are these 'energy levels'. Nobody feeling fatigued actually experienced a 'level' as far as I know. It is just a metaphor. So 'energy-limiting condition' just seems to be a way of making a popular turn of phrases sound as if it has some medical validity.

 

[Jonathan Edwards]

Then that shows I don't understand your analogy.

The analogy was contrasting an activity that could be done without thinking with one that needed great concentration. It was nothing to do with me being old and them being young.

 

[duncan]

I think exertion has to do with activities that require deliberate shifts in routine activity patterns.

Not always. In pwME, that is frequently not the case.

With pwME the "deliberate" aspect is learned and then relearned, and can remain a moving target. Same holds true with what you casually refer to as routine. This is why pacing has to be individually recalibrated every so often.

But what are these 'energy levels'. Nobody feeling fatigued actually experienced a 'level' as far as I know. It is just a metaphor. So 'energy-limiting condition' just seems to be a way of making a popular turn of phrases sound as if it has some medical validity.

Might not be "fatigue levels" because we don't speak that way. But there are certainly degrees. If depleted energy or reduced energy is merely a poor patient metaphor, it is nonetheless reflective of the patients' experience and I would argue carries more medical validity than any clinician saying we haven't a clue what's going on - or worse, the patients' experience carries little or no medical validity because researchers can't grasp hold of it empirically (or even conceptually) to measure it.

 

[Jonathan Edwards]

I don't have a lot of time for Friston's concept of informational free energy in the brain but there is no doubt that computational systems depend on a relationship between useful signals and noise that parallels the situation for free energy in a motor or battery and entropy.

In a battery what matters is not energy as such but usable energy. That turns out to depend on charges being lined up in order - having ducks in a row. Computers also depend on useful signal resources and having ducks in a row.

So maybe a useful analogy is the old computer that is full of software and files and as a result goes slower and slower. The energy level is the same. The apparent 'lack of energy' of the computer is in fact a measure not of a level but of the ducks being all over the place so that it takes five times as much activity to achieve the same thing.

 

[Jonathan Edwards]

With pwME the "deliberate" aspect is learned and then relearned, and can remain a moving target.

That would be my point. For someone with ME for whom brushing the teeth requires exertion all sight has been lost of an othe automatic routine, so the act of getting up and brushing the teeth is no longer a routine but something that requires exertion. The autopilot isn't operating.

If depleted energy or reduced energy is merely a poor patient metaphor, it is nonetheless reflective of the patients' experience and I would argue carries more medical validity than any clinician saying we haven't a clue what's going on

That seems to me an unhelpful non sequitur. Nobody here is denying that patients' accounts are not useful. We are totally dependent on them to get an insight into the problem. And talking of energy depletion is helpful if one realises it is used in the colloquial sense. But there is no comparison with the entirely accurate claim by physicians that we have no idea what is going on which means we have no mechanistic explanation.

What is needed is for those who talk in mechanistic explanations - the scientists - and those who talk in colloquial symptomatology to ensure that the two languages are not being confused. If we want to 'define and measure PEM' I think we want to find a language that can be applied to mechanistic theories. That is how medical science gets to useful results.

I would actually challenge the idea that anyone actually experiences 'energy depletion'. I suspect that they have an overwhelming sense of inability to initiate a task. Energy depletion draws on popularly supposed mechanisms that may not apply. I have total respect for human subjective experience but not for the folk interpretations that so often colour it and are mistaken for it. I spent my life asking patients not to describe their symptoms the way they thought they were supposed to describe them but as they actually felt. Was it really a 'shooting pain'? Or a 'nerve pain'? Or was it something often called those but actually better described as a short very strong and local pain in the front of the thigh - which would fit a hip joint pathology.

 

[Trish]

For someone with ME for whom brushing the teeth requires exertion all sight has been lost of an othe automatic routine, so the act of getting up and brushing the teeth is no longer a routine but something that requires exertion. The autopilot isn't operating.

That doesn't seem to me to describe my experience at all.

It's not about autopilot. I know very well the routine of, for example, having a shower, and do it on 'autopilot' but am completely exhausted by it. If I have a shower on the same day as one or two other activities of equal amount of physical activity, or try to shower every day for several consecutive days while doing my normal very limited routine of other lighter activities and rests, I'm likely to crash.

The idea of autopilot, if I understand it correctly, doesn't seem to take into account the cumulative effect of lots of individually manageable activities, especially if done without sufficient rest between them, that can lead to crashing.

I can walk about my house, that's on autopilot, I start walking without any feeling of effort requiring extra concentration, yet after about 10 steps it becomes less secure, and if I try to keep walking for more than about 20 metres, I feel my legs are going to collapse. Standing still is even worse than walking. Apart from feeling generally unwell at the start of my ME, that feeling of legs about to collapse and an urgent need to sit down was startling and seemed really odd.

 

[duncan]

Nobody here is denying that patients' accounts are not useful.

We are totally dependent on them to get an insight into the problem

And talking of energy depletion is helpful if one realises it is used in the colloquial sense.

But there is no comparison with the entirely accurate claim by physicians that we have no idea what is going on which means we have no mechanistic explanation.

What is needed is for those who talk in mechanistic explanations - the scientists - and those who talk in colloquial symptomatology to ensure that the two languages are not being confused.

I have total respect for human subjective experience but not for the folk interpretations that so often colour it and are mistaken for it.

Why do I feel like a waif in a Dickens' novel? I'm sure it's the time of year.

 

[Jonathan Edwards]

That doesn't seem to me to describe my experience at all.

Yes, I agree.
I was paraphrasing past posts from other people but I also recognise your account from past posts. It isn't a simple autopilot thing. And I recognise your account from my own recent post-Covid phases. But it seems quite complex.

When we first discussed these things five years ago I remember emphasis on it being post-exertion rather than post-activity/exercise - I think largely driven by the fact that mental exertion could cause PEM. Now I hear you saying, in effect, that showering, at least to start with, does not require exertion, just letting the body do its routine. So the problem is post-activity.

To me that leads back to the idea that there is some accounting system going on in the central nervous system that is likely sensitive to immune cytokines at nerve endings and maybe shifts in sugar hormones that is at a subliminal level and that operates over quite long time frames (more than minutes at least) which, like a trip switch on a fancy modern appliance, turns off the operating system despite all measurable molecules being normal. And when it trips it can take a long time to free up.

Maybe we are searching around for a simple account of what seem to be cause and effect relations when the process is going on at a control level that at present we cannot think of a good model for.

 

[richie]

My issue is with the word "malaise." It cheapens and sullie
decades of accrued patients' experience. It reduces a definitional symptom cluster down to a quaintly idiosyncratic period piece.

I don't care if some doctors claim to understand it clinically different than the typical layperson; it cannot be extricated from its cultural knots. It should be deep-sixed.

I think you have a fair point. I was amused by your reference to the antebellum. What word might be better is another matter.