A hypothesis involving maintenance and restorative processes in ME/CFS

[Hoopoe]

PEM is generally the main cause of disability in ME/CFS and it is typically delayed with respect to the activity that triggered it.

It seems possible that PEM is closely related to maintenance and restorative processes that occur in the body. More activity during the day would lead to more maintenance and restoration work later on. Much of this work is performed at night and the brain coordinates these processes, which include removal of metabolic waste, synaptic homeostasis, memory consolidation, reset of the ANS. Unrefreshing sleep seems like it would fit well with this idea.

PEM may be a form of sickness response that is triggered when brain senses that the repair and maintenance is going badly, and that more activity would dangerously exceed the repair and maintenance capacity. The symptoms of PEM would then force the person to reduce activities to the minimum necessary and to learn how to better stay within their limits. That the recovery from PEM is prolonged seems consistent with the general idea.

We don't know what exactly could be going wrong in the maintenance and restorative processes. As DecodeME suggests it may involve the brain and the immune system. This idea doesn't seem incompatible with a "faulty signal" hypothesis either.

Unfortunately much of ME/CFS research has not studied the biology of patients before, during and after PEM.

I remember there were two papers that did, and which found a post-exercise non-response pattern in ME/CFS patients compared to controls, one in the protein signature, the other I can't remember. I have focused on other things than ME/CFS science in the mean time and can't remember enough to locate these papers. The interpretation was that the usual processes triggered by exercise were blunted in patients.

If this idea lacks detail, it is because I'm an amateur that struggles to come up with something more detailed. I think the idea may have some merit because it focuses on, arguably, the biggest problem and attempts to explain the unusual and characteristic delay of PEM in the simplest way. It's not an attempt to explain everything.

 

[Kitty]

PEM may be a form of sickness response that is triggered when brain senses that the repair and maintenance is going badly, and that more activity would dangerously exceed the repair and maintenance capacity.

Either that, or signals that sign off those processes don't get sent? So there is no damage, no risk of harm, but the production manager can't allow the lighting crew on the scaffolding without a scaff tag.

 

[Hoopoe]

Either that, or signals that sign off those processes don't get sent? So there is no damage, no risk of harm, but the production manager can't allow the lighting crew on the scaffolding without a scaff tag.

The idea is roughly that the brain senses that the maintenance isn't proceeding at the rate that is sustainable with current activity levels and that the only option is to limit further activity and dedicate more time to rest. It achieves this via PEM.

 

[EndME]

In which part of the body do you postulate that repair and maintenance are not happening? Is it something happening in the muscles (say related to T-cells) or something happening directly in the brain (say synaptic homeostasis)? In the first case, is the repair and maintenance system really not working locally or is it perhaps that it's working as it should but some signal is sent that it's not (T-cells are doing their thing inside muscles but the T-cell management team has told the higher ups that they are off duty for the day).

(Edit: I just saw that the last question is what @Kitty already asked, but the answer doesn't quite make sense to me. Why does the body have to produce symptoms of pain, malaise etc if things are not sustainable with current activity levels? This to me sounds like a "lack of ATP theory" but that doesn't make much sense to me, why not just tell the person "have a snickers and I'll keep busy repairing and maintaining"?)

 

[Creekside]

More activity during the day would lead to more maintenance and restoration work later on.

My experience is contrary to this theory. A 40 km bike ride did not trigger PEM, but climbing a few rungs of a ladder did. The difference seems to be straining (causing microtears) muscles in unusual ways rather than usual. The former would trigger a different immune response.

Resting extra-long or having an unusually deep sleep never seemed to reduce my ME or PEM symptoms, nor did shorter or disrupted sleep make those symptoms worse. I don't feel that sleep, or even rest, is closely connected to ME's mechanism.

 

[Hoopoe]

In which part of the body do you postulate that repair and maintenance are not happening?

Maybe it's happening at a limited rate and PEM is effective at keeping the person's activity within sustainable limits.

There may be no permanent damage precisely because of PEM.

For some reason I can tolerate riding a bike much better than walking. I suspect the reason is that walking is fully upright activity.

 

[EndME]

I suspect it's happening at a limited rate and that PEM is effective at keeping the person's activity within sustainable limits.

There may be no permanent damage precisely because of PEM.

For some reason I can tolerate riding a bike much better than walking. I suspect the reason is that walking is fully upright activity.

I still don't understand. Why do you need to reduce global functioning for local repair processes? Why would they benefit? What are you depriving of the repair processes if you continue life like normal, that is why are the repair and maintenance processes related to keeping the person in limits? If the repair processes are happening in my arms why do I need to rest my whole body, that is why get PEM rather than DOMS?

I suspect that there may be some neurological "refreshment periods" of maybe something like 10 hours that all humans require for neurological functioning, sort of like a screensaver, but why induce global PEM for repair processes occuring in the muscle tissue elsewhere?

 

[Hoopoe]

Why do you need to reduce global functioning for local repair processes?

DecodeME seems to be telling us that the problem is in the brain. Maybe as result ordinary wear & tear in the whole body appears to the brain as extreme so that a disproportionate response occurs in the form of PEM. Maybe the wear and tear is in the brain in certain areas, without leading to neurodegeneration, and we just can't detect it yet.

It's not progressive damage to muscles.

 

[Kitty]

(Edit: I just saw that the last question is what @Kitty already asked, but the answer doesn't quite make sense to me. Why does the body have to produce symptoms of pain, malaise etc if things are not sustainable with current activity levels? This to me sounds like a "lack of ATP theory" but that doesn't make much sense to me, why not just tell the person "have a snickers and I'll keep busy repairing and maintaining"?)

Because the pain and malaise would be the sickness response that @Hoopoe describes, which is thought to be protective. I wondered if it could be triggered and maintained if "all's well" signals are absent, infrequent, or at too low a level.

 

[EndME]

Because the pain and malaise would be the sickness response that @Hoopoe describes, which is thought to be protective. I wondered if it could be triggered and maintained if "all's well" signals are absent, infrequent, or at too low a level.

Yes, but there's something I don't understand about that analogy: If the sickness response is the body telling us to keep quiet because the immune system (or here repair processes) needs extra energy, why doesn't it just tell us to eat more energy gels? (I can understand the genetic and behavioural reasoning in terms of evolutionary pressure, but the "energy reasoning" I can't make sense of).

 

[Kitty]

Yes, but there's something I don't understand about that analogy: If the sickness response is the body telling us to keep quiet because the immune system (or here repair processes) needs extra energy, why doesn't it just tell us to eat more energy gels?

I don't see that energy comes into it. It's feeling crap, part of which is a sense of fatigue. Having fatigue doesn't necessarily mean I lack energy; it means I feel fatigued and if I try to push against it and do things, the dial for the rogue signal gets turned up so I feel even more crap.

I don't know if our brains even have a mechanism for telling us we're genuinely short of energy. It's possible they don't, they might just tell us we've used a lot of resources or we need to sleep. But that's not the same thing.

 

[Jonathan Edwards]

Yes, but there's something I don't understand about that analogy: If the sickness response is the body telling us to keep quiet because the immune system (or here repair processes) needs extra energy, why doesn't it just tell us to eat more energy gels?

I don't think this is about the immune system needing energy. It is more likely about needing time, perhaps to refresh interstitial structures.

Maybe there is an analogy with an orchestra stopping between pieces, or even between movements in a long piece, to re-tune instruments. The stringed instruments with playing may get a bit out of line and need re-setting. The oboe player may want to change a reed that is playing a bit soft and 'fluffy', and so on. In the interval the string players may rub a bit more rosin on their bows and trim off hairs on the bow that have frayed.

The interstitium in muscle may need to be constantly run over by macrophages to ensure that every fascicle moves smoothly over the next but is also tightly anchored so that it can respond with maximum force quickly. If this process is not carried out you may suddenly run into friction and tearing problems of the sort you see with tenosynovitis or tennis elbow.

I think it is reasonable to ask why this 'service intermission' has to be global rather than local but I don't think that is too surprising. When you sw a piece of wood, apparently doing the work with your pectorals and triceps, you are in fact making use of all the postural muscle sin your trunk, not to mention muscles in the other arm and in your legs. The innervation to every muscle is linked up through spinal reflexes to all sorts of others and completing an action successfully requires all the efferent and afferent pathways to be working in harmony. Which is why when you get tired you make mistakes and cut your fingers.

So the repair process is almost like a piano tuner comparing every note with several others to amke sure everything works together.

The other thing is that if the problem involves activation of a danger signal, which may come without information on exactly where the danger is, then general shut down makes sense.

 

[Hoopoe]

In more general terms, the way I experience PEM and its dynamics gives the impression of it being the result of an imbalance between decumulation and accumulation of something. We could use other words and analogies, it's not important.

Roughly:

Rest and sleep allow decumulation.
Non-demanding activities lead to low rate of accumulation.
More demanding activities lead to high rate of accumulation.
The activity of the previous days can contribute to the level of accumulation of today. That means the rate of accumulation can exceed the rate of decumulation.
If too much of something accumulates, it leads to symptoms. This tends to happen with a delay. There may be no awareness of having exceeded the threshold.
The symptoms force me to rest and eventually, balance is restored.

All of this is clear. There must be something in the body where this description fits well. The delay and the possibility of being unaware that anything is wrong is very important and shows that this is very different from fatigue occurring immediately in response to activity, even if fatigue is part of the illness.

One thing that I thought would maybe fit is something involving the maintenance & restorative processes. Initially I thought of these because PEM would often present on the next day, as if something had disturbed my ability to recover from the previous day.

 

[EndME]

Thanks for bearing with me, hopefully after my necessary repair period things will sit more naturally with me tomorrow.