Exhaustion in ME/CFS, what is it and what causes it - discussion thread

interesting, this is exactly opposite to me - in that eating usually improves things for me (as long as i not in PEM, when in PEM its more variable, nausea issues etc) especially sugar.

 

I got ill at puberty and had worked out the sugar thing within the first two years, but the trouble is that even more complex carbs such as the ones in vegetables have an effect. It's not as bad as a slice of cake, but it's bad enough.

The only thing I can eat that doesn't make my limbs go numb (it is only my limbs and the area under my chin) is a bacon, sausage and egg fry-up. As long as there's no toast, tomatoes, beans or whatever, I can eat it and fully maintain the energy I had before I ate.

Shame it's a bit of a disaster health-wise, because I quite like it. I have to save it for when I really need to be able to keep going.

 

I still think there is some central reason (i.e. in the brain) for ME and PEM, and the often tantalising, research into the metabolome and mitochondrial function, which gives rise to my theory, that this intracellular problem is happening in every organ in the body, blood vessels, peripheral and central nerve pathways including in the brain. Whether one would call this inflammation, I am not sure about, maybe it comes and go with PEM but I don't think we have enough research to confirm this. Perhaps it is faulty wiring, who knows, not enough research but none of this is due to our behaviour trying to manage the illness and any other whacko theory the BPS brigade have thought up. It could be blood flow, it could be autonomic, it could be X and Y, who knows? but I do believe the brain is heavily involved in this via feedback loops, hormonal, neural, something yet unknown in the blood etc.

I recently had a head cold, something I have not had for many years. Interestingly, probably while I was incubating it, my heart metrics started to change, basal heart rate started to go up, as would be inspected from central mechanisms, and suddenly my HRV metrics started rapidly going down hill. I felt fine but there were the first signs of ME symptoms were deteriorating, especially sleep and cognitive function. But generally able to do most things. I definitely then developed an URTI but no systemic symptoms other than the worsening of my ME symptoms. I had some mild stress as my partner developed viral pneumonia and had to look after himself, away from me, this altered my pacing regime and I was concerned I might get it but not overly, as we had taken precautions.

Now most normal folk recovered from their URTI, even bad ones, and go back to work/normal duties etc. Not for me, my URTI cleared up but I had crashed and after being functional in my limited world of house-boundedness, I was bed bound for several weeks The only way to recover was to rest, pace but make sure I ate and drank well, which included the extra salt and electrolytes and putting on my compression stockings for the day and while resting (but off at night). They have made a notable difference to my OI especially cognition and feeling dizzy all the time (without verifiable orthostatic hypotension and a negative NASA lean test and despite normal fluid intake). So much so that I have gone from severe to moderate. I, personally call that a clinical response.

Now some here may see this as alternative medicine (on another thread)... and Johnathan, I do not think I would like you as an expert witness for physicians who can't problem solve and need an exact scientific explanation and that is a reason to not grasp the enormity of a situation and the potential risks (of starvation etc). I know you are trying to change physician's thinking from within the system and have to be rigorous but there is not a scientific explanation for everything, at this moment. I also take two types of antihistamines for some obvious mast cell activation. They work and the different types of reactions have not recurred. Clinical response. I am not sure I buy into all of the MCAS stuff but having treatment trials of different mast cell stabilisers seems quite practical to me, even a few other things, as long as they don't have significant harmful side effects. It is what helps the individual patient.

I think I have quite different thoughts on how to treat ME compared to some physicians. In psychiatry, we often don't know how things work in the brain and often rely on expert consensus, and this is a reasonable medico-legal defence, but we are willing to give things a go, with proper informed consent, as long as we can closely follow up the client, to manage any risk and follow their progress. It is hardly blue sky thinking and I can't understand why some clinicians are so fixated on their policies, which often have no relevance to ME because they can't be bothered seeing it as a medical problem.

Perhaps we don't know why increasing intravascular volume works but it does for some. In my books, that is formation of clinical practice. It is not clearly harmful once you have had a medical work up as I have described elsewhere and protocols exist and are being used quite happily by GP's. In NZ, increasing intravascular volume is standard practice for GP's and for the few ME experts we have. This is called symptomatic relief. In the absence of exact knowing, the aim is to reduce symptoms with medications that help particular symptoms. eg pain, dizziness etc. They do want evidence of other doctors using it and that is easy to find. There are plenty of anecdotal evidence and expert consensus. If it doesn't work, well, that is a failed treatment for that person but not a failed treatment for all.

I don't know why the big centres for ME in the USA haven't run trials on it. I can only presume, they are happy to treat people with their current level of knowledge for ME (and are pragmatic like most doctors have to be) and run off the feet with referrals. It takes time and energy to run clinical trials. Better funding and support to do this would be helpful. They are not hard to do but take some organising and needs all the usual stuff like ethics approval, consent, monitoring, good study design, etc . We don't have ME centres/clinics here and the the few people doing ME research are only funded through universities and it is pretty limited (and likely to stop soon as universities are going broke and the government is struggling to balance it's books so all things are uncertain.).

Actually most of the time, I don't really care what causes my ME, it doesn't affect how I manage my ME and also because I don't believe we will come up with a reason in my lifetime. So I don't bother getting hopeful at every new thing on the block. I am though, very interested in the literature and the increasing output of research studies (non psychiatric, yeah!) that are appearing because it will make a difference to someone and every little bit or research helps to prove or disprove things.

And if I had to say what I think causes ME, it is in our genes, we are born with it, there is nothing we can really do to prevent it and is triggered somehow by various things but mostly infection.

 

In considering what is happening when a PwME is experiencing PEM & exhaustion, please factor in that swollen lymph nodes are a significant symptom in sufficient numbers of people for it to be included in most guidelines.

 

This may seem pedantic but I don’t think “prevents voluntary effort” is quite the right wording. I can’t think of the right wording but it would be wrong to imply that the sense of intolerability prevents a normal amount of effort being expended – the point is that it massively increases the effort required to do things which would ordinarily require little or no effort.

Not short in general but possibly short in places where it is needed (ie cells)?

 

@Jonathan Edwards I’m still not sure I fully understand what you mean by a signalling problem. Are the symptoms of most illnesses not caused by signalling in some way, whether or not those signalling processes are understood? Is the question whether ME/CFS is fundamentally a problem with the signalling itself or whether there is something that is interfering with the signalling?

 

Time-varying fuel starvation? Alternative metabolic pathways with finite, short-term capacity - ultimately futile - and with bad effects?

Isn't this like the Olympic 100m or 200m sprinter? They go all out, reliant near-exclusively on anaerobic metabolism, up to hard limits of even an exquisitely highly trained physiology. At the end of the race they couldn't run it competitively again, but they could walk it and then they recover and can run again some hours later.

If pwME are using various rescue metabolic pathways in daily activity recruited at an abnormally low threshold compared to healthy people, overexertion would lead to deleterious buildup, eg ROS. I've seen it described that a pwME in daily life metabolically looks like someone who's run a race (can't find that quote just now).

The problem might be signalling, but it also may be getting oxygen/metabolic substrates where they're needed and/or being able to use them.

 

Or a signalling problem which is preventing oxygen/metabolic substrates from getting to where they're needed etc?

 

@hibiscuswahine

Just a quick question...

For people with problems associated with low blood volume, giving them saline helps them because it (temporarily) increases blood volume by dilution. Why don't doctors use real blood to boost blood volume? Giving saline repeatedly isn't actually making anyone better, is it? It's just a temporary fix.

 

One of the metabolic pathways we use, right at the start of actvity, is Phosphocreatine. It's used before the body can get normal metabolic pathways up and running, in the first 10 seconds or so. Isometimes wonder if we might rely on that for longer than other people and end up forcing levels lower than the body considers healthy, triggering homeostatic responses?

i also wonder if some energy-depletion states might trigger innate immune system responses? Are there times the body gets so depleted in energy it assumes something is very wrong and starts an immune response??

Just an idea, but I know that if I want to do something hard, starting off very very slow is helpful. Perhaps that's an approach that preserves phosphocreatine levels.

 

But in a way this is the exact opposite of my position. I would like a scientific explanation in the long run but when considering treatment I am saying that a scientific explanation is irrelevant. The only thing that matters is reliable evidence of effectiveness. Clinical effectiveness evidence and scientific causal evidence are completely separate issues.

It is Dr Weir who is focussing on scientific explanations, it seems to me, and even yourself @hibiscuswahine. You talk of expanding blood volume yet I am not sure we have evidence that salt and water intake even does that.

And there is another problem. Salt intake may in the long term aggravate things. It may further sensitise the signalling mechanisms. We have no idea. For fludrocortisone it is understood that its effect is compensated out by adrenal atrophy fairly quickly unless the dose is high enough to be supra physiologic and then you soon get nasty unwanted effects like hypertension.

In the heyday of anti-inflammatory drugs like indomethacin and naproxen and diclofenac everyone was sure that they were doing a great job helping pain. But now we know that doctors were killing tens of thousands of people with these drugs. We need the reliable evidence and we need it in all sorts of ways.

Setting up trials is hard work but it can be done. And the argument about money I think is a red herring. When I was a professor the other professors who had the biggest departments and most cash were the ones who were happy to do whatever drug trials the companies wanted. Trials were the main source of income for academics, not the other way around.

 

Yes, and that would fit with a signalling error along the lines of something like 'sickness behaviour' without necessary needing inflammation as such.

 

I need to emphasise the point that there are several parallel components to the process, but one of them I think is exactly this. As I get old, and having quite a lot of worn out joints, I meet this all the time. The knowledge that I will get pain severe enough to stop me being able to put my next step in the right place prevents me from making the voluntary effort of trying. The implicit knowledge that I will simply fall and end up with a bleeding face is enough to prevent the effort. The process is both unconscious and conscious.

That does not mean that I am not expending as much effort as I possibly can to achieve my task and in fact much more than I ever used to need to but there is still this aspect of a block to action.

If one tries to analyse the explanation in terms of one or other component it doesn't work well, I agree, but I think in order to understand why the patient's abilities seem to vary inexplicably one needs to build in all these facets. One of which I think is best described this way.

I don't honestly see any good evidence for that and I don't find it a very productive concept to build a working explanation on. There are no structural blocks as far as we know so presumably this would be some sort of regulatory shutting off of supply. The body does not do starve its organs of blood in any other situation I can think of. (Except when an artery is cut and goes into spasm in major trauma.)

 

There are lots of examples where disease symptoms are not signalling effects. If you are diabetic and your leg goes black with ischaemia going to the doctor and telling him that symptom is a matter of signalling. If osteoarthritic bone spurs prevent you from bending a hip enough to cut your toenails that isn't signalling. If you have myasthenia and cannot keep your eyes open or breath that isn't due to signalling, or at least not sensory signalling.

But when arthritis prevents movement through pain that is signalling.

 

I don't think it is about the amount of red blood cells and oxygen carriage. But the plasma volume of blood. It is nearing my bed time so major apologies if this comes out wrong. I am sure the physicians in the group could pick holes in it....but I did a lot of reading on that before committing to up my salt intake, use electrolyte drinks and compression wear. I have had a cardiology consult and all clear to try this. He didn't have any warnings for me, as Jonathan has suggested, and I keep an eye on my blood pressure and GP oversees monitoring my bloods.

The increase in intravascular volume may actually help the autonomic issues of ME and OI and increase cerebral blood flow. This is based on my understanding on the work by Van Campen et al. (Netherlands) His eletrophysiology work and his wife who is a cardiologist seem quite sure this is important and so it seems reasonable even though more research is planned.

I don't really fully understand the "cortisol's" Dr Strain talked about during the current corner's enquiry, but I am presuming he is talking about mineralocorticoids and corticosteroids and the renin angiotensin aldosterone hormone feedback pathway for electrolyte and fluid balance, so perhaps he could be clearer on that.

It is about maximising the intravascular fluid volume via retaining fluid in the blood stream. It has been posited that we have problems with blood pooling and venous return into the left side of the heart and this causes preload problems but I don't believe that applies to all people. (Systrom et al) and thus heart rate needs to pick up (increased sympathetic drive) to compensate. I have also read quite abit on baroreceptors not working correctly in the carotid sinus causing feedback problems throughout the cardiovascular system, problems with HRV etc. (ours are often lower than the general population). Compression wear helps with venous return in the lower extremities.

edit. I should also point out I have lowish blood pressure for most of my adult life but only had OH symptoms until a few years ago. I did have reduction in the Mean Arterial Pressure gap which improved with increased salt and electrolytes and BP is now in normal range. Correcting that has helped my ME functioning and OI but I still have to pace and rest like we all do and avoid PEM if possible. It has meant I could do more cognitively challenging activities that I would have not been able to achieve otherwise.

 

The athlete example works for these but one key point is that the time course in ME/CFS makes no sense in these terms through any mechanism that anyone has so far dreamt up. By what mechanism would organs by starved of energy supply two days after exertion?

As indicated to Robert, I simply see no scientific reason to think a lack of supply is plausible. I am pretty sure that people have researched metabolism and energy supply because they have translated the subjective sense of lack of energy into a story about metabolic energy without being aware of just how indirect our perceptions are. Most of this research is done by people without a medical training. As you know, in medicine, being sat in front of patients taking histories for hours and listening to accounts of all sorts of aspects of neurology in departmental meetings one gets an understanding of how bodily sensations have to be interpreted with care. We are aware of referred pain and stuff like that.

But yes, not being able to use substrates, or shunting into different pathways does seem a bit more plausible. The problem is the time course. And for the sort of problems we have been discussing in relation to very severe patients it looks very much as if the variability can be quite rapid and make even a shunting theory unworkable.

I guess a motivation here is that I think the medical world needs to understand that the problems of very severe ME/CFS can be explained entirely on signalling of a sort we are very familiar with in other illness without resorting to speculative theories about metabolism that nobody can yet provide convincing evidence for.

 

We don't actually know that saline helps through volume expansion. The amounts given are unlikely to make much difference even short term.

There are lots of reasons for not giving blood. It is very expensive. It can carry things like AIDS and mad cow disease. If given repeatedly it incites an immune transfusion reaction every time because it can never be perfectly matched. The blood will be degraded because the body thinks it is excess to use and so will put a nitrogen strain on the kidneys. It might act as food but that is a different question.

 

Perhaps another point is that this discussion arose in the context of very severe patients not being able to feed. I think it may be very misleading to focus on energy supply in that situation.

We all remember Stephen Hawking, whose muscles completely stopped doing anything. That wasn't shortage of energy, it was motor neurone failure, but it had the same effect. Hawking lived for years in a wheelchair writing scientific papers and going to meetings. I am not sure how he was fed. But as I understand it the problems for people with very severe ME/CFS are not like that. Doing and thinking is intolerable in a complicated way but a way that parallels what most people are quite familiar with in flu or acute vertigo or even with a tooth abscess.

In simple terms, if the intolerability of outside stimuli is mirrored by intolerability of inside stimuli it seems to me the illness begins to make sense.

 

It seems as though you are looking especially for an explanation regarding the variability in ability in severe and very severe ME-patients? And the explanation you find most relevant is to compare it with the sense of pain or dizziness or nausea, and the conscious and unconscious effort to avoid that? Is this a correct assumption or interpretation of your words?

Every person has experienced what you are describing, regardless of illness. That’s a part of being human. But every person has not experienced having severe ME where you have the strength to open the mouth, chew a bite of food and swallow it. Once, twice, maybe three times, but then it stops. You need a break to muster up new energy before you can do it again. I would say that those who probably know the best what this is like are very old, bed bound persons. How the exertion needs several breaks regardless of what kind of exertion it is. The less energy you have (or access to energy), the more you realize how everything is consuming energy. If you want to eat a full meal it might take hours. Not because you are avoiding unpleasant sensations, but because you can’t do it faster. The muscles simply don’t respond faster and they need rest in between.

So, if you would talk to me while I was at my worst I would sometimes answer you in a whisper, sometimes answer you with a thumbs up or sometimes answer you with silence in order to get enough strength to answer you later on. Consider me a hundred years old and you would probably understand how to best take care of me and also have the patience to wait for me to catch my breath. I wish compassionate patience was the approach the doctors and nurses would have when they meet a severe ME-patient.