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

[Ash]

You're misinterpreting my argument @Creekside

I'm not saying PEM is the only phenomenon that needs looking at and I'm certainly not saying curing PEM is the same as curing ME. I'm not even claiming the current diagnostic criteria requiring PEM are necessarily right. However, for now, PEM is the one thing every pwME diagnosed according to current criteria has in common and which at the same time is uncommon in other diseases. Even if it eventually turns out that there's a variant of ME without PEM, there will still be a very large number of pwME who do get PEM. Therefore any serious ME-hypothesis has to be able to provide a credible explanation, backed by empirical data, for a mechanism that can at least enable downstream delayed PEM in susceptible people.

My key argument is nothing more than that shifting the research focus from fatigue and/or general lack of energy to investigating the delayed aspect of PEM serves to a) focus the mind and b) narrow the field of investigation. The usual focus on fatigue and/or general lack of energy has given us decades of muddled thinking including confusion about the nature of PEM. Importantly, fatigue and/or general lack of energy can be caused or impacted by about a trillion things. The potential causes for delayed PEM are, probably, still rather numerous but there'll be fewer than a trillion. So searching in this narrowed field increases the chances of finding that crucial thread on which to pull to hopefully unravel (some of) the rest of the ME mystery

And now that I've spent almost an entire day trying to write a single post that's precise enough to not also be misunderstood I realise there's another mystery: why is it that the more brainfog I have the longer and more complicated my sentences become (trust me, the draft versions were a lot more convoluted than what you've just read)? This is almost as weird as the delayed PEM thing. Anyway, back to bed for me, again. Sigh

Excellent point well made though thank you for sharing.

I feel this one.
Can’t hit the point with letters. In my case I’d add can’t speak the point with sounds, can’t quite recall the research details or other information, can’t locate this to check it. If I finally find it, can’t read about the subject to complete the crystallisation of the point. Just staring at the words.

 

[Kitty]

why is it that the more brainfog I have the longer and more complicated my sentences become

If you're anything like me, you lose the ability to approach from the garden gate. You start on the wrong side of next door's hedge, dodge round the back of the garage, trip over the bins, do a meandering circuit of the garden, eventually spot the gate, and then stumble up the path.

You then have to move blocks of text around, delete two and a half paragraphs, reorder the syntax, post it on the forum, realise it uses the same word three times in one sentence and contains at least one autocorrect that makes you sound like a fascist or a halfwit, and then go in and edit it. You've still started from three bus stops away instead of the garden gate, but it makes some kind of sense.

The following day, you realise you completely edited out the point you meant to make.

I feel this one.

Oh, yes.

 

[Ash]

Yes indeed.

A while back I realised that auto correct was really doing me dirty. I couldn’t work out why it had gotten worse. Then I remembered I had privacy settings turned on after a period of them having reset themselves. So now I wasn’t allowing it to “learn” from me instead of giving me the common regular word basics as I’d been used to it was vindictively inserting the most random little used words. But because I can’t see properly due to visual disturbances if the word looks similar in length and has some common letters to the one I wanted I can’t see the difference until it’s too late.

Also yeah don’t know exactly what ME is but I do know that it scrambles the syntax….

So I’d really like someone to study ME brains of the living.*

* Biomedically and with healthy controls and low risk for participation.

 

[cassava7]

One of the issues that has been consistently replicated by ME/CFS biomedical research groups is orthostatic intolerance (including the CDC), although it seems peculiar or unconventional in the sense that many people with ME/CFS experience OI without heart rate or blood pressure issues. I would like to see this finding investigated further, as have done the Bateman Horne Center and Cardiozorg (Prof Visser and Dr van den Campen), especially since it has been clinically shown to be tied to cognitive impairment (and, if I’m not mistaken, further supported by some neuroimaging data from Zack Shan and Michael VanElzakker’s groups).

I suspect there is something (micro)vascular that is at play and that, like Fluge and Scheibenbogen’s groups have hypothesized, it could lead to reduced tissue perfusion / hypoxia especially during recovery after exertion. There is limited, albeit recent, evidence for this hypothesis.

 

[Creekside]

One of the issues that has been consistently replicated by ME/CFS biomedical research groups is orthostatic intolerance

I challenge the "consistently" part. I did experience what may have been OI, but only for a few months of my 20+ years of ME. If I did exertion, such as lifting something heavy or running even a few steps, when I stopped, I'd start to feel faint, maybe get tunnel vision. However, that was only a few times, and it hasn't happened since. So, for me, it's anything but a consistent symptom. My guess is that ME affects brain cell function, and in my case it temporarily affected the cells involved in maintaining the proper functioning of other cells. It could be microvascular, or it could be signalling molecules or extracellular vesicles, or even some signalling mechanism that's still undiscovered.

especially since it has been clinically shown to be tied to cognitive impairment

I couldn't tell whether my cognition was impaired during those episodes. I was too focused on wondering whether I was having a heart attack. I was a bit shocked when the doctor I went to for that " I keep starting to black out" dismissed it as nothing to worry about.

 

[Trish]

I challenge the "consistently" part.

I think we need to be careful about challenging symptoms that are included either as frequent or defining symptoms in most definitions of a syndrome. PEM is a required symptom/phenomenon in all current definitions of ME/CFS, and all defintions list OI and cognitive problems as very commonly occuring or required.

Using one individual's symptom variations, especially in unusual cases that may not fit a recognised pattern of the syndrome, is not a good basis for challenging general points made about key symptoms.

 

[Creekside]

PEM is a required symptom/phenomenon in all current definitions of ME/CFS,

Isn't that a circular argument? PEM is a required symptom because all people who fit the criteria including PEM have PEM. There might be a considerable number of people who have the same core dysfunction of ME but get a negative diagnosis for ME because their ME doesn't result in PEM. If PEM is downstream of the core dysfunction, its mechanism may not be manadatory. It's part of the criteria now because there's too little known about ME and PEM, and someone (or some group) made a personal judgement that PEM is mandatory. There is no proof that it is mandatory.

I think it's healthy for science to challenge unproven assumptions. "Everybody knows" that PEM is mandatory ... until someone discovers that it isn't.

 

[Trish]

Isn't that a circular argument?

No. PEM is mandatory because ME/CFS is a syndrome defined by a set of symptoms, not by a pathology. Therefore, by definition, someone who doesn't get PEM at all when they exert beyond a limit, and who doesn't have functionally limiting fatigue and either OI or cognitive dysfunction, does not have ME/CFS. They may have had it in the past, they may be in remission, they may get it again in the future, they may still have some of the symptoms they had when they had ME/CFS, but they don't currently have ME/CFS.

If the pathology of ME/CFS is discovered and testable, then those people who test positive may then come to be defined as having a disease with a new name, like xyz-deficiency disease, or abc-opathy. But at the moment we are stuck with a syndrome defined by symptoms.

 

[duncan]

No. PEM is mandatory because ME/CFS is a syndrome defined by a set of symptoms, not by a pathology. Th

History has taught us - as have medical politics - that this is fluid. Very little is concrete here because, as you allude to, we don't yet know the pathology.

 

[Kitty]

There is no proof that it is mandatory.

Equally there's no proof that some people with ME don't have it.

Yes, of course it could be possible for the underlying dysfunction to produce few or no recognisable symptoms. But the fact that a theoretical possibility could lead to some people being excluded incorrectly still doesn't make it useful to change the defining symptom to optional. All that would achieve is making a lot of research impossible until the dysfunction is known, because it leaves no reliable way to identify pwME.

If it's eventually shown that a form of ME may not exhibit PEM, it'll be added to the definition then—the same process has happened in other conditions.

 

[Sean]

I don't know if ME can exist without PEM.

I do know that it is such a common feature of ME, and a distinct phenomenon in its own right, that it must be controlled for in any studies and assessments.

 

[Andy]

Not only is PEM a common feature of ME/CFS, but it is arguably the most disabling. For both of those reasons, PEM should be a priority for investigation. I'm delighted that some individuals might be fortunate enough to have found some way that appears to resolve their PEM but that is not a good reason to remove investigating PEM as a priority from the majority of the patient population.

 

[duncan]

I am embarrassed to feel a need to qualify this, but I'm going to anyway: I strongly believe PEM is a core feature of ME/CFS, maybe the core feature. As @Andy pointed out, for many of us it is arguably the most disabling.

But I'm torn about this mandatory/definitional thing because both present with problems - mandatory because it in my experience can be used more as a guideline or decree (and so allows for exceptions), and definitional because it's a math of sorts that permits no exceptions.

I think anything definitional has to be based on pathology, e.g positive culture or a genetic defect. I could be wrong here, and I would gladly defer to anyone more knowledgeable.

So putting definitional aside, even as pervasive as PEM is within the ME/CFS community, there are bound to be exceptions where someone appears not to exhibit that symptom - even though they have ME/CFS. Maybe it's only 1 in a 100, but that 1 percent is going to emerge.

I think.

Unless PEM proves definitional, but I don't believe we're there yet.

Sorry for the sidebar. I'd hoped to write with more clarity today, but it is what it is.

 

[Kitty]

I'm torn about this mandatory/definitional thing because both present with problems - mandatory because it in my experience can be used more as a guideline or decree (and so allows for exceptions), and definitional because it's a math of sorts that permits no exceptions.

I wonder if we might be slightly at cross purposes?

It seems to me that making PEM mandatory isn't so much about defining ME as researching what causes it. You can't study a disease unless you're as sure as possible your sample has it, and for the time being that makes PEM essential. Nothing else has been identified that's present in the vast majority and can separate them from people with other fatiguing conditions.

It doesn't automatically follow that PEM must define ME. It just identifies it better than anything else we've got.

 

[Trish]

There's also the perspective of why it's useful from a patient's point of view to have an accurate diagnosis and therefore what advice the clinician should give on how to manage it.

I think PEM is an essential feature for ME/CFS diagnosis, because the whole management by careful pacing, staying within your energy limits is èntirely about avoiding crashes and long term worsening.

For patients with some of the symptoms of ME/CFS, such as fatigue and cognitive problems but without PEM, there does not seem to be any reason to encourage them to find their energy limits and stay within them, because they are not in danger of crashing and worsening as a result of activity.

If a clinician is unaware of this difference, they will give bad advice, and when their patients without PEM are able to increase their activity and fitness without detriment, the clinician gets the idea that GET is harmless.

Similarly if people without PEM are wrongly diagnosed as having ME/CFS, and then recover while doing some quack therapy, they sometimes then mislead people with PEM with recovery stories and sales pitches for quackery.

So I think it really matters a lot that only people with PEM are diagnosed with ME/CFS.

 

[duncan]

So I think it really matters a lot that only people with PEM are diagnosed with ME/CFS.

Do we know that all people with ME/CFS have PEM?

This is where I worry a bit about the definition thing. That the wrong or flawed definition informs studies the wrong way, at least potentially. And by extension, diagnoses. Studies should not emerge from disease definitions; it should work the exact opposite

Like I said. I agree that PEM is integral to ME/CFS - I just don't know that we can wield that as confidently as we might like. Moreover, because it's still a symptom, we have to be ready to acknowledge and embrace exceptions.

Having said that, if I were spearheading a study or a diagnostic template, I'd want to include PEM, I'd just maybe do it with a caveat..

 

[Peter T]

Do we know that all people with ME/CFS have PEM?

There is no simple answer until we have a diagnostic biomarker. Under current definitions by symptom a diagnosis of ME is contingent on PEM. I think we should be very cautious of an ME diagnosis in individuals who have never displayed PEM, though given the variability within individuals experiencing ME, I think it would be less problematic allowing a diagnosis of ME if the individual previously or intermittently experienced PEM though not currently experiencing it.

If someone has never experienced PEM, but otherwise has a large symptom overlap and currently is presented with no other potential diagnoses there is the option of a provisional diagnosis of atypical ME, until such time as an alternative presents or a diagnostic biomarker is identified. With our current knowledge some fuzzy boundaries are inevitable and that worries me less than finding a diagnostic biomarker that leaves a subsection of people currently diagnosed with ME out in the cold. People with ME suffer enough at present from attitudes to this diagnosis, and if it turns out to involve more than one disorder, how will a subgroup who don’t meet the hypothesised emergent biomarker be treated. We see that at times in some proponents of an ME CFS split where CFS is devalued as a lesser diagnosis.

[added - as others have said research into ME, unless looking at subgroupings, should require PEM and not include people with my provisional atypical ME diagnosis.]

 

[Creekside]

I think PEM as a mandatory criteria is important for study subject selection. It might even be wise to limit selection for a given study to certain criteria for PEM, such as "reliable 24 hr delay". Adding in non-standard subjects could blur the data enough to hide a correlation.

Using that strict--but unproven--criteria for ME diagnosis could be harmful. "Okay, you meet the criteria, here's your $100k/yr of medical insurance. Oh, wait, your PEM delay is 19.5 hrs? That's below the (arbitrarily set) 20 hr criteria, no money for you."

 

[Trish]

Do we know that all people with ME/CFS have PEM?

I'm really struggling to understand this question. I've been trying to think of a way to illustrate what I mean.

Try this one:
A teapot is defined as:
a pot with a handle, spout, and lid, in which tea is brewed and from which it is poured.

The question I've quoted seems to me a bit like asking, how do you know all teapots have a pot and a spout? The answer is simple, because if they didn't have a pot/spout combination, they wouldn't be a teapot by definition.

There are some things about this definition which we can argue are optional and it is still a teapot, for example it may be used as an ornament and never used to make tea. But it's still a teapot. You may lose the lid, but it can still function as and be called a teapot. The handle might break off, and you can still make and pour tea. But without the pot and spout, it can no longer function as a teapot, nor does it look like one, so by definition it's not a teapot.

I'd say the combination of pot and spout are like chronic disabling fatigue and PEM. in the deciding whether someone has ME/CFS. Without those two, they may be sick, they may share lots of the symptoms of ME/CFS, but they can't, by definition have ME/CFS. They are not a teapot. They may be a saucepan, or a mug, or a bottle, sharing lots of the characteristics with a teapot, but they are not a teapot.

Of course the coffee pots among you will find ways to break down the analogy, but I hope you understand my point.

 

[duncan]

Of course the coffee pots among you will find ways to break down the analogy, but I hope you understand my point.

No worries. When all is said and done, I agree with you.

I'm just a worry wort who more often than not creates his own tempest.