If you had to guess ME/CFS cause, what'd you say?

There is the issue of ‘black swans’. For hundreds of years in Europe the definition of ‘swan’ included it being white, until the first [Europeans] visited Australian and were confronted with ‘black swans’.

edited to correct word selection error

 

Also to add what I've mentioned a good few times in the past. Although we speak of energy limitations, I'm pretty sure it is more accurately a power limitation. i.e. A limit of the rate at which energy can be processed (and subsequently recovered). Like a partial fuel blockage.

My wife is the person with mild'ish ME, and I cannot help seeing things from an engineering perspective. She can work in the garden for quite long periods, or on her quilting also for quite long periods. But only at a pace she has developed a natural instinct for keeping to, and does extremely well. She does herself in for a few hours and is then OK again (as much as a pwME can ever be 'OK'). But the other week we had a little holiday to ourselves, going out from home most days to just change the scenery. And my wife was then totally done in for two to three weeks after, only just getting back what is normal for her this week. She very much wanted to do it, but as everyone here knows, there is always a payback.

So I'm sure that once the illness mechanisms are better understood, the notion of power limitations will feature, at least for some patients. When my wife walks our dog on a lead, who is lovely but a bit "pully", my wife can walk quite fast. But without our dog on the lead, my wife walks a lot slower, and slows down much more quickly. But I very much suspect my wife's own power consumption is much the same in both cases, given our dog provides much much of the power when on the lead. I call her my wife's power-assistance dog .

 

IMO it's both an energy and a power limitation i.e. in the distant past, when I had more energy, I could feel that I had enough energy to, say, walk faster, I just couldn't utilise it, it was like my feet, ankles and lower legs were 'damaged' and were operating as well as they could, which was considerably below what I could have managed if that were not the case.

Of course...these days..I almost never have that sensation, but it used to be quite frequent.

 

Just to put a spanner in the works here . I do know of someone very prominent in a ME advocacy organisation who mentioned long time back they were worried because not sure if they experienced PEM. I've also gone through phases when I've thought my wife (the person with ME), may not be experiencing PEM any more. But I think the notion of pacing has to be accounted for.

I can only speak with regards to my wife, whose ME is mild'ish, and who seems to be very good at instinctively pacing. It may be the case if someone's ME is reasonably mild, and they are also very capable at pacing well, then maybe their PEM is kept in abeyance very well. But in my wife's case it is abundantly clear that if her pacing fails her at all, then she gets hit with PEM very clearly; so it's that her pacing can sometimes reduce the severity of her PEM. Maybe for some people if they manage their pacing very well, then it may seem like they are not prone to PEM, but it may just be they are staving it off with good pacing. But no idea if this is relevant to what was being asked though.

So maybe the question should not be a bald "Do you get PEM?", but "Do you normally get PEM, and if not do you get it if you don't pace so well?"

Obviously for many pwME they are going to get PEM no matter how well they pace. I'm only suggesting the above for a subset.

 

I'm a coffeepot short and stout.

 

Agreed, though I think it's a little more complex than that, it's a limitation on total power output over a certain threshold for a certain time. So maybe I can lift an object without causing PEM (a significant power output), but I can't lift the same object five times in a row (the same power output, but sustained over a longer time period). Maybe I can climb one flight of stairs, but I can't climb two in a row. Similarly, maybe I can work for some length of time if I'm in bed (a certain cognitive power output), but I can't work for the same length of time while standing (because now I have the cognitive power output plus the power output required to stand). It's not that exceeding a certain power output will immediately cause PEM, but that exceeding a certain power output for a certain period of time will cause PEM.

I can also feel this directly sometimes in terms of shortness of breath. One flight of stairs is fine, but two might cause shortness of breath. To my mind, this must be related to the anaerobic versus aerobic energy systems.

 

Yes, agree entirely, and in fact this ties in with what I was saying I think. Observing my wife, the longer she applies power to something (walking for instance), the more her power progressively declines, meaning in this case her walking speed slows. Or to put it another way, the longer and faster she consumes energy, the progressively slower her body is able to process energy, so she slows down - power is all about the rate of processing energy, so lower power equals slower doing stuff.

And I very much suspect that patterns of energy consumption may prove insightful to researchers.

 

Yes, and that weird thing about how capacity collapses in PEM.

When rested I can take steps across a room whilst speaking or laughing and it doesn't make me breathless. In PEM, I move six paces to pick up a book and I'm out of breath; when I sit down again, it takes several deep breaths to recover. I look like someone who's just dropped into a seat on a bus after sprinting 200 metres to catch it.

 

My PEM triggering was different. It seemed to be triggered by abnormal muscle use. If I worked up to a daily 40 km bike ride, that wouldn't trigger PEM. Climbing a few steps up a ladder (uncommon activity) would trigger PEM, because it strained those muscles (and connective tissue?) beyond their normal limits. Arms raised above my head in far less common than leg work, so washing a window or lifting something to a top shelf might trigger PEM. Triggering did not correlate with power output/time. My theory is that my PEM was triggered by muscle cell damage, which in turn activated immune cells, which in turn activated glial cells.

Of course, that's the coffeepot version of PEM.

 

I've often thought this would be a useful thing to investigate. My experience is similar, albeit on a more modest scale.

For me, the quickest route to PEM is using my abdominal muscles to lean forward and outwards, as you would if putting a new shrub into a garden planter. My abs are fairly strong from swimming, but they're not used to that specific movement. Mowing my little lawn uses a lot more energy, but it doesn't have the PEM potential of having to keep leaning forward for a few seconds whilst I firm compost around the roots of a plant.

 

There are 4 different types of MS.

• Clinically isolated syndrome
• Relapsing-remitting MS
• Secondary progressive MS
• Primary progressive MS

 

This is the case for me too, the delay is around 12-14 hrs fro me.

What is interesting is that over exerting my cognitive energy affects my calf muscles, I feel as though I climbed a mountain, my arms are also affected. The symptoms are immediate and the recovery period is much faster.

 

The brain has some cells that communicate over long ranges. Imagine ME altering a glial cell that reaches into several different parts of the brain. When that cell activates, it could affect calf muscles and maybe the "need to pee" signal and thymus gland function. In another person, that malfunctioning cell might affect tongue muscles and liver function and peristalsis.

 

I think it must be nonsense because individual glia do not extend beyond a millimetre. It is the neurons that have connections over metres.

 

I was going to check that vaguely-remembered fact, but ME made me not make the effort. Still, there is long-range interconnection between some brain cells. If it's a neuron affecting multiple areas, that neuron does depend on glia for support, so a glial malfunction could have long-range effects.

 

I think Creekside is suggesting that activated or dysfunctional glia would affect their local neuron, which could then have effects distant in the body. (ETA cross-posted, yes)

From Shaping Neuronal Fate: Functional Heterogeneity of Direct Microglia-Neuron Interactions (2020, Neuron) —

Although, I'm more in favour of a general failure of energy production having effects around the body, rather than it being a brain-derived problem. My subjective experience, for all that it's worth, is that my earliest sensations of early fatiguability or pathological at rest fatigue (or the "zinginess" of what feels like local lactate accumulation) was in my non-dominant forearm muscles. I surmise that that relates to variation in vasculature, but of course I have no idea if that's true.

 

So do I. However, I'm still waiting for the "sound science" explaining ME. This forum would be pretty empty if it was limited to known facts about ME.

Speculation by non-scientists isn't without value. Discussion, even about far-out ideas could trigger thoughts in the right direction. Even a wrong idea could trigger "No, it doesn't work that way. Instead it works ... hmmm, maybe it actually works this other way instead." Questioning a hypothesis--even by non-experts--could reveal flaws that no one else had thought of yet. For that matter, the "experts" could be blinded by well-known but actually false facts.