Is PEM cumulative? - public thread

Exactly - or some cell connections in a regulatory organ that are supposed to be switched on and then off, like in a telephone exchange, but get left switched on for too long so all lines are busy.

 

fatiguability rather than fatigue as a function of activity

 

It may be different with different people (maybe only different severity levels or maybe people have different diseases), but I really feel that it's not so much the exertion that is the problem, but more that there is something wrong with the recuperation. The exertion itself was the biggest problem when I was more severe, so I get that it doesn't feel that way to a lot of people. My remaining problem now (I'm more mild again) seems to be with the reaction after exertion. I can have a normal active day, but as soon as I sit down a the end of it, the symptoms start and there is a whole cascade of problems in a very specific order as well.

When I was a mild patient a few years back and still working, I was doing one hour consults and I did just two or three on a day, three days a week. Everyone kept telling me to spread these consults out in the day, take long breaks in between etc., but I did better when I just did three in a row, went home, lied down and rested properly for a day and a half. When I did one hour consult and sat down for a long tea break, the exhaustion would hit me and I would have a lot of trouble getting up again and doing another consult. So I have the feeling, as soon as the recuperation-process starts, I can't go back. So I always felt that as soon as the parasympathetic system takes over, a recuperation proces begins and it's hard to get out of that.

 

I also see this pattern of feeling not so bad or even OK while exerting, but being hit with exhaustion as soon as the body shifts into a resting state.

I'm also seeing the pattern of waking up and feeling awful because the day before I did too much. But during the day I probably felt good because I was doing something, and when going to bed, I was still feeling OK, with only very subtle changes to heart rate and feeling a little wired. I suspect this wired feeling is the sympathetic nervous system. And I suspect that this causes nonrestorative sleep. As Lately as it seems that there is less delay between exertion and PEM (the body caves in sooner), but maybe I'm just paying more attention to these things.

 

It's a long time since I really seriously overdid it but when I did, I noticed that the timing of the PEM was different - but I can't remember whether it was a longer or shorter post-exertion delay. Curious about others' experience.

I've also found that if I go out and then come back I know intellectually that I should rest but I'm so wired that I can't. The physical activity seems to rev me up somehow, and the effect carries me too far.

 

Definitely matches my experience.

Too wired to rest and I don't know of anything that settles that down. Not relaxation or breathing exercises, nor meditation. You just have to let your system work through it while trying limit the damage.

It's a bit like accidentally having a double shot coffee when you actually thought you were getting a decaff. There's no ready antidote, you just have to let your system try to process it.

A combination of both physical and mental exertion is most likely to trigger this, but it can be triggered by cognitive effort alone. Physical effort alone is least likely to trigger it.

The knock on effects are harsh - very poor sleep that night, reduced cognitive and physical function over the following days and it's so much easier to accidentally tip back into the phase again with the smallest exertion.

 

This describes my experience exactly. The other thing that happens is that if you keep trying to vacuum things up with a full bag, despite it's feebleness, it overheats & will start to smell burning/cut out/become otherwise unusable, until it not only cools down & cleaned out but gets a full machine service. And you can only run it to breaking point so many times before it starts to affect function even when newly serviced.

Also with the computer analogy, i have often described my cognitive difficulties/sensory sensitivity (the 2 things are inextricably linked for me) as being like an old pc - where you cannot do too many things at once or it just freezes up. eg on a windows95 pc it was ok to be surfing, & possibly have a doc open as well, but if you tried to have several programs all running at once, it would just freeze & nothing could be done until it rebooted....

So for example i might be able to read for 20mins when well rested & lying down in a quiet room & understand every word, inc dense/heavy content... but if there's sensory input (eg pleasant soft music in background) i can only read for 10mins before symptoms overwhelm.

But trying to read while also having the effort of holding myself upright in dining chair, while soft music on and someone talking and a flickering light will cause complete incapacitation within just a few minutes - & i'll become too weak to hold myself up in the chair & will fall off it, probably vomit, be unable to speak coherently or understand even simple statements/questions from other people. I dont know where i am, my proprioception goes haywire so i have to look at my arms & legs to know where they are, coordination non existent so struggle to get drink to mouth/dress self etc.

No doctor i have ever told has ever taken this in. They all think it's an emotional thing not being able to 'cope' & getting psych related sensory overload, but it's not like others i've seen who get anxiety related sensory overload & it happens just the same in enjoyable circumstances as in unpleasant ones. In fact if the circumstances that are emotionally difficult - eg the person talking is making me angry or something about it all is making me very anxious, or i'm in some way 'adrenalined up' beforehand - the stress hormones will allow me to do a huge amount MORE - tolerating all that input for at least 5 times longer before the total incapacitation/crash('freeze' in the computer analogy) will occur. Of course the crash/freeze experience will be so much worse then - commensurate with how much longer it all went on for.

I've often thought that was important to figuring out whats causing it all, but no Dr i've ever told takes the slightest bit of notice, so convinced are they that it's a psychological thing.

Yes exactly.
Especially for me, if the activity was done while stress hormones elevated for whatever reason.

ETA apologies for contribution to thread drift.

 

I found this on the other place in a post by @Hip on the McLaren-Howard, Myhill , Booth papers. It did seem to make a lot of sense. It dosn't explain what instigates the issues with energy demand and supply mismatch ( which could be signalling etc ), but it does give a mechanism to explain the dealy in PEM.
Note AMP can be recycled, but slowly.


In other words, Dr Myhill is saying that because of the poor energy metabolism and mitochondrial inefficiencies found in ME/CFS patients, during physical exercise, there is an acute shortage of energy and the mitochondria cannot recycle ADP back to ATP fast enough, so there is a build up of ADP molecules.

In a desperate attempt to harvest more energy, some of the ADP molecules, which are normally recycled back to ATP, instead get converted to AMP (this conversion to AMP occurs by what is known as the adenylate kinase reaction, in which two molecules of ADP combine to make one of ATP and one of AMP).

However, because AMP is not easily recycled, this AMP is flushed right out of the body, thereby causing a permanent loss of the ADP molecules that the AMP was derived from.

(The exact way AMP is flushed from the body is this: AMP is first changed into inosine monophosphate plus ammonia, the inosine monophosphate is then degraded to inosine, and then to hypoxanthine, then to xanthine, and finally eliminated in the urine as uric acid. Ref: Myhill 2012).

So you get a temporary acute shortage of ATP and ADP molecules, which is major problem, because ATP/ADP recycling is the main basis of the body's energy distributing system, responsible for carrying more than 90% of our cellular energy. So now your body is short of energy, simply because you do not have the means to transport it: the ATP and ADP molecules. The theory states that this temporary shortage of ATP and ADP molecules, which are needed to transport the energy from the mitochondria into the cell, causes PEM.

As a consequence of this temporary shortage, more of these ATP/ADP molecules have to be manufactured by the body from scratch, to replace the lost molecules. And efficient energy distribution can only be resumed once these lost molecules are manufactured.

But it takes 1 to 4 days for the body to rebuild its stock of ATP/ADP molecules, as it takes a lot longer to manufacture the ATP molecule from scratch (this called de novo synthesis), rather than the more usual and easier process of creating ATP by recycling ADP.

Myhill, Booth and McLaren-Howard think this 1 to 4 days of novo synthesis of ATP may explain the PEM period: you get PEM for several days after physical exertion due to the acute shortage of ATP/ADP molecules; and you remain in PEM until your body finishes rebuilding its stock of ATP and ADP molecules

Note: to be clear, when Myhill, Booth and McLaren-Howard are referring to a shortage of ATP/ADP molecules during the PEM period, this not so much a shortage of energy in the mitochondria (although mitochondrial energy supply may be poor as well), but rather an acute temporary shortage of ATP/ADP molecules with which convey the energy generated in the mitochondria to where it is needed in the cell. In other words, PEM is an acute problem of transport of energy, where you temporarily do not have enough ATP/ADP energy transportation molecules

Edit. Changed paper authors' names

 

Me too. Cortisol and adrenaline probably.

 

I find this explanation very unconvincing because PWME should the say 'every time I do a lot it takes me four days to get back to normal'. But my impression is that when a crash occurs it can last for ages. I also do not see why you would feel worse later than the point at which you use up the ATP - during the activity. You would expect recovery to be slow but not to hit symptoms some time after exertion.

 

Maybe we feel worse not because of the accumulation or depletion of molecule or signal X, but because the body senses that now it really needs to rest so that it can take care of this imbalance, and it can achieve prolonged rest by making us feel like crap.

A bit like most symptoms during a viral infection being not due to the virus but due to the immune system.

Maybe to achieve rest the body even uses the same tools it uses during a viral infection, and therefore patients often think that they keep getting viruses.

 

Yes, but to sense it needs rest it has to signal that to itself. Or perhaps more accurately one part of the body has to signal it to another. In viral infection the signal is usually thought to be interferon of some sort but that may be wrong.

 

If my daughter overdoes it the impact does not fully hit til 48 hrs after. It' s a bit like 2 day after gym feeling but worse- with swollen glands, brain fog, muscle ache, sore joints etc. The day after there is less energy and typically sore and joints,head and dizzy feeling, but second day she is floored. That' s why it made sense to me.

 

Interesting. In my earlier years what you described worked better for me too, but after awhile the 'wired tired' feelings set in and negatively affected my sleep.
So now I find spreading out my tasks throughout the day and getting adequate rest in between works better for me and I can accomplish more in the long run without PEM.

 

I wonder if what is usually described as swollen gland may be something this person describes as vascular neck pain and according to him due to autonomic dysfunction?

https://mdedge-files-live.s3.us-eas...ssues/articles/media_9014c8c_ccq27_1-0005.pdf

 

I don't quite follow which way you think it fits. According to Myhill's theory you should be poleaxed right at the time of exercise and gradually recover over about four days. But an impact hitting at 48hrs would not fit that - it would be a late deterioration rather than a gradual improvement.

 

I have had a lot of changes over the years, I've read somewhere that there is a lot of experience that the illness changes a lot and is different during the first years and later on in the disease.

I found that my problems start as soon as I sit down, with a specific chain of events. Half an hour after sitting down, my muscle weakness starts. 4-5 hours after exertion, the real PEM (flu-feeling, shivering) starts. I only have the wired feeling with a lot of cognitive exertion and I especially notice it in my sleep if that cognitive effort was late in the evening, so an evening with friends for example. With physical exertion, I don't have the wired feeling, but I still have the crappy sleep

After physical exertion I have almost all the signs of drinking too much (hangover). My sleep is distorted, I wake up all the time with a completely dried up mouth, having to pee five times a night. The next day I wake up with full on hangover feeling, whole body stiff and aching, nauseous and exhausted.

Yes, that is the same for me now. It depends if I want to do small aerobic tasks (like working on a computer and doing dishes) during the day, it works best for me to take breaks. Because if I do it well and pace good enough, that doesn't cause me PEM. My work was pretty physical, so it gave me PEM anyway, with or without breaks. With breaks the PEM started during work-time and without break, I could get home before it hit me.

 

This looks like nonsense to me. The carotid artery is a bit like a tough butyl rubber hose that probably varies in calibre hardly at all and if it does it is likely to be all the way up and there is no reason at all why it should be tender if dilated. Things may be different in the elderly with tortuous vessels but that is not what is described. The author also talks of the typical patient being sensitive and highly strung and all that garbage. I could not see a trace of objective evidence for his claim.

Almost everyone gets neck tenderness suggestive of lymph nodes at some time and it probably is lymph nodes - the tenderness is usually superficial to the sternomastoid. (The carotid is much deeper and pretty hard to palpate directly. It would be extraordinarily difficult to identify a dilatation of the carotid.) The trouble is that neck lymph node tenderness is very subjective and not a terribly useful clinical sign. The real value of feeling nodes in situations like ME is to exclude things like lymphoma where nodes feel completely different - like a whole unshelled almond nut or anything bigger - not easy to miss. Nodes swollen with infections are more like the flat bits of apricot in apricot jam. In young people one or two can be swollen most of the time but get tender with a virus infection so people are more aware of them.

I suspect the neck soreness in ME is lymph node soreness - which again makes it seem unlikely that there is just a shortage of ATP. Some regulatory system is switching on the flashing lights on the front of the hoover.

 

Yes indeed. It seemed like nonense to me also (published in 1961 but no uptake afterwards) but did raise a doubt in my mind that what are usually considered signs on some sort of infection might be something else completely which has implications for a CFS/ME model.

 

I probably picked it up wrongly then. I had read it as doing things is ok up to a threshold ( like pacing) as long as the usage ties to supply then you are ok. Doing things for too long or something intensely is like the energy currency being uncoupled - the recycling rate does not rise to meet demand. PEM in my mind was the real low when all the energy gone and de novo synthesis over a few days kicks in. The low for us is 48 hrs onwards - you are into overdraft territory. The initial downturn though can be within a few hours
Perhaps this is another substrate problem.