Why is it so often said that almost nothing is known about ME/CFS?

Why is it so often said that ME/CFS is the last major disease we know almost nothing about? I get that there is still lots left to discover. We haven't even isolated the primary disease mechanism, or if we have we dont recognize it as such yet. But aren't there already nearly ten thousand ME/CFS publications? What sort of threshold needs to be met before a reasonable scientifically-minded person could say that something meaningful is known about this disease?

 

Recognising that knowledge is a spectrum (e.g. despite a lot more funding, we know surprisingly little about ASD, IMHO) and so it's not a binary case of either knowing a lot or not, I would say the biggest gaps are:

• reliable, consistent, objective biomarkers
• pathological mechanism(s) <--- this is the biggie
• as a consequence, disease classification: is it immunological, metabolic, neurological, psychological, a mixture of two or more?
• are there subtypes? Does a more severe case indicate 'more of the same' or a different pathology?
• disease prognosis - surprisingly few longitudinal studies have been carried out and patients, frustrated, tend to drop out of the system

I don't think we'd need an effective treatment or cure to stop classifying ME/CFS as a disease 'we know almost nothing about'. But we would need to address at least some of the gaps above, in my view.

 

I do feel that the BPS cult, intentionally or otherwise, takes advantage of and deliberately exaggerates the gaps in our understanding of ME to push their preferred psychological interpretations and behavioural interventions.

Having said that they make no attempt to evaluate their own theories, be it the deconditioning myth or the central sensitisation fantasy.

We do know a lot about the abnormalities in various neurological and physiological systems, and though we lack a theoretical explanation drawing this all together is it that different from many other diseases that are still not properly understood? The current lack of an agreed clinically useful biomarker is a practical problem, but hopefully given there are a number of identified biological abnormalities this is not far away, or would not be far away if research was proportionately funded.

 

There were longitudinal studies of patterns of MS long before MRI scans etc. The trivialisation of this illness by the psychs meant this never happened.

 

Honestly I'm having trouble thinking of anything that we do know for sure, we don't even have agreement on what it is or what the symptoms are, even hallmark symptoms like PEM are not always mandatory (eg Fukuda and CCC criteria)

If ME/CFS was a 100 piece jigsaw puzzle we probably have 50 of the pieces but they don't all fit together and we're not even sure they all even belong to the same puzzle.

 

It always seemed clear that the policy of lumping everything that had similarities of a certain type was designed to cause obfuscation. They must have known what they were doing. If they did not, then they must be even dimmer than imagined. That possibility cannot be entirely ruled out.

 

Thinking about this sentence. Is it the last major disease we know almost nothing about? genuine question. I've heard or read Ron Davis say this, and I understand where he's coming from, but I don't know that it is.

I was surprised that for example migraine is in the WHO's list of top ten most disabling conditions. They know something about treating migraine (lots of types under that one name) though it is largely trial and error, but they know very little for a condition that affects so many people and can be so very disabling. I'm not touting migraine as the last major disease we know almost nothing about, of course, but I think that term is probably just a means to make people pay attention.

Psychosocialists don't go around calling 'cfs' the last major disease but their agenda is different, as other s are saying.

 

Wikipedia has a whole page of them.
https://en.wikipedia.org/wiki/Category:Ailments_of_unknown_cause

 

Brain fag syndrome? Shouldn't that be 'fog'?!

 

Thanks @wdb.

I think I've seen that wikipedia entry before and think there was a previous discussion. Vague memory. I probably took part in it too . I've got the brain of a fish.

(but fish do actually have functioning memories (+ feel pain and fear) according to some research, which I cna't remember.)

 

I think "the last major disease" is the key phrase. It is severely disabling where even so called mild cases have their lives altered in very profound ways. Even people with quite severe MS can do much more than us so it is a major disease by any criteria.

But the amount we know about it, after sixty years of neglect, is miniscule. So much so, that no one can believe we can be so ill and so neglected. I believe that is one reason ME is trivialised in people's minds. If it was as bad as we claim why has it not been seen as the threat that polio or AIDS were?

 

I am not scientifically trained but what struck me flicking through other guidance to compare to our own was how science and drug focused they were. Our illness not having a biomarker or established tests or any medical treatment is way behind. Other illness without effective medical treatment such as dementia and MND at least has some understanding of what’s gone wrong even if why is less known. That’s clearly a reflection on the research effort into ME, rather than the illness being too vague or not organic enough, contrary to what is implied by the BPS lot who also blatantly lie and say “despite exhaustive studies” nothing has shown up.

I think the CPET research is indicating we have genuine issues on exertion not caused by deconditioning, enough for the IOM to recognise PEM and suggest SEID but it’s not been replicated enough yet and isn’t enough on the radar in the UK and Europe where funnily enough there’s everLasting funding for simplistically exploring exercise as treatment but no interest in research on its harms.

I think in the next 3 years we will be in a clearer position on mitochondria, , the immune system brain inflammation and exertion.
I dislike the narrative of BPS people that CFS is MUS , MUS is illness not explained or explained sufficiently therefore psychological and social factors are likely very important. I think in ME we have enough suggestions of at least what could be going wrong in pathology to explain symptoms ( although the profundity of severe ME is still baffling to me with it) to not be needing to be focusing on the PS as the gap filler as th y do.

 

@Cinders66 I'm not sure what you mean in your reference to severe M.E

 

Maybe I’m being a bit dense in this and part of it is because most of the studies are on ambulant people.
What I mean is, whilst the research so far could be sufficient to suggest why we are ill, weaker, not functioning well, worse with exertion I am unsure we have demonstrated why severe ME can be utterly incapacitating like someone end stage terminal, where I’d have thought there would have to be pretty dramatic findings somewhere, especially on brain affects or function ? Maybe Ron Davis severe ME work has some data for this. So the studies on reduced energy production, do they explain how there can be zero energy, the studies suggesting brain inflammation, is that inflammation bad enough to explain why people have to lie alone in a dark Room...

 

PEM is mandatory in CCC... https://me-pedia.org/wiki/Canadian_Consensus_Criteria

PEM is included as a possibility in Fukuda but not required; it is not included in Oxford at all.

 

I may be interpreting it wrong but it is listed as "and/or"

 

Uh huh... sure it is.

 

I've started typing my answer a few times, now...

There are a few things that make people say this.

1) Studies are small.

Most studies in ME are low-powered and viewed by research scientists as "maybe interesting; maybe nothing". To clinicians, who seem to want meta-analyses of 200 double-blind, placebo-controlled studies before recommending a glass of water in the morning, it means zilch.

Low power means a high likelihood it's chance.

2) Poor methodology & execution...

So often it is chance, and Research Group B tries to replicate a study and it doesn't work out like Research Group A said it should. Or Research Group A tries to replicate its own results in a larger cohort, and it fails.

This can be because of poor initial methodology / execution from Group A, or poor methodology / execution from Group B... or it can be that Group A genuinely found that data using good methods, but see #1: could've easily been statistical chance.

In our field we have higher incidence of poor methodology and execution.

Why?

Because there's no money, so the median grant is small. That means poorer researchers and new/young researchers (both of whom may only be able to aim for smaller grants) are going to apply in our field. That isn't to say there aren't amazing people working on ME -- there are! -- but that this isn't the median.

[Edit: the best and the worst research & treat ME... what other patient population can say that?]

3) No replication at all.

Found a good theory? Seems to work out in your small group of patients? Awesome!

Spin the hell out of it in the press -- and never, ever replicate.

It's really tough to get funding for a medium-sized study in this field. And besides, what if your genius theory is proved wrong in a larger cohort? That could bring in less funding in the future...!

No, no... better to swing to some other, completely new idea and get funded for the next mini-study!

(Sorry, this is the modus operandi of at least one group...)

4) Fatigue conflated with ME

So far as I'm concerned, our real issue isn't so much that fatigue studies exist, or that studies on Fukuda or even Oxford exist, but that their results are conflated with results using any of the criteria that require PEM.

It's interesting to see what, if anything, all "chronically fatigued" people have in common. So long as you don't label your study as being about ME!

ME is an absolute minefield of weird assumptions, illogical conflations. How are you supposed to know all this as a researcher? It takes a year or two to get a handle on all the strangeness in research so far, and that's if your exclusive focus is ME.

One onus against the name chronic fatigue syndrome that I haven't often heard (but wish I heard more often): it invites newcomers to the field to conflate the symptom of chronic fatigue and the disease as a whole. It's usually one of the first things you have to explain if you say the name aloud. "...but it's much more than the symptom of chronic fatigue". Ugh.

5) Dogma

I'm not sure why, but there are a lot of ride-or-die theorists in ME. They'll come up with an idea and stick to it, come hell or high water. We need open-minded research: come up with a hypothesis but don't marry it and ask us to throw rose petals at the wedding. Hypothesize, test, and if you're wrong, move on.

I just came across a paper again from the Norwegian researchers who worked on adolescent CFS using clonidine.

Their first paper on this, several years ago, started from the assumption that CFS was linked to anxiety, and so if they blocked adrenaline/noradrenaline with clonidine, their patients would improve.

They didn't. They worsened on actimeter.

The researchers (rather sensibly) concluded that the increased adrenaline and noradrenaline was adaptive, and blocking it might be a poor idea. I thought at the time that it was refreshing they could admit they'd been wrong.

Now this month they came out with a paper showing that there are two groups of pwME: low adrenaline, and high adrenaline. It appears they're still using clonidine. And they've collected yet more evidence that they're wrong: pwME with higher adrenaline did better on two subjective fatigue surveys.

Your. Data. Says. You're. Wrong.

Stahp.

Oi, this raised my BP & HR.

[Edit: gotta say I haven't done a 'deep dive' on this study, yet, so my interpretation at a glance may well be incorrect. (Let's hope.) If I am correct, however, they're one example of MANY, not an 'isolated case'.]

6) A lot of the results we've found & replicated are NOT unique.

Hand grip. NKC activity. Metabolomics.

These all mimic things we've seen in other illnesses or conditions.

2-day CPET seems to produce a pretty standard pattern... in some pwME. There's a second group who, according to one clinician who's worked on this for decades, look more like very elderly people on day one & replicate that on day 2. I had a one-day CPET where the ANS specialist said I functioned "like an 80-year-old" so this checks out. So even PEM has its variance.

______________________________

Ok that was all a little dark and a bit negative, so.

Researchers & clinicians need to listen carefully to pwME in order to be successful.

If you're in science and you're reading this, there is so much you don't know that a pwME can tell you. The fact that you're here and listening speaks well for you. Get a pwME with a science background to help you design your study. It will go SO MUCH BETTER. You will avoid SO MANY MISTAKES.

Don't do it for brownie points. Don't do it because your grant says "you gotta".

Do it because you'll produce a crappier study without us.

It's true.

 

What an excellent summary. Are there even 100 papers that are high quality and replicated in a larger number?