Question re: the ICC Criteria and Ion Transport issues

Inara

Senior Member
Messages
251
Likes
598
Is that how everyone understood the ICC Criteria? I am finding all of this very confusing :confused:
In another discussion, I said that I don't agree that the ICC/CCC don't require muscle fatiguability. In my view it is required. I think disagreement will remain on this point.

Foxglove explained what I think, too.

I am not sure, though, if muscle fatiguability is the same as muscle weakness. When reading peripheral neuropathy papers, muscle fatiguability was defined as part of muscle weakness.

From a mathematical point of view, and from an intellectual property viewpoint, the formulation in the ICC could be clearer. As Foxglove correctly said, in point 1 there is "and/or" meaning an option: physical fatiguability OR cognitive fatiguability. (And is muscle fatiguability part of physical fatiguability??) Point 5 contains "and": physical AND mental fatiguability. From an intellectual property view, due to point 5, in point 1 only "and" holds (because point 5 does not include the scope of "or" and ALL points 1-5 have to hold).

From a mathematical viewpoint: OR includes "and", so in point 1 "or" would suffice (in intellectual property this does NOT hold). But point 5 doesn't include "or". I would view it as ill-defined, because there is "and/or" and "and"; on the other hand, the denominator is "and". So "and" would hold. But honestly, I would have to discuss this with a mathematician.

In intellectual property, the entire text defines the invention, not just the claims. And the ICC text details a bit if muscle fatiguablity is required. Throughout the entire text, muscles are a topic.

All in all I need to conclude that muscle fatiguability/muscle issues are mandatory for an ME diagnosis.
 
Last edited:

duncan

Senior Member
Messages
2,188
Likes
4,729
I was shocked that the ICC included ion transport issues (which is why I started this thread to learn more about that) and now I am shocked again that it does not include muscle fatiguability (which was an absolute core issue for me prior to treatment).
Faitguability and fatigue are crap words. Weakness has limitations, too. We are constrained by our vocabulary. This dilemma is compounded in that everyone is different in how each disease manifests. This holds true for ME/CFS and for channelopathies.

Sometimes it is too complicated and I hang my head.
 

Gingergrrl

Senior Member
Messages
14,690
Likes
43,829
So we have in point 1, physical and/OR cognitive fatiguability in response to exertion but in point 5, low threshold of physical AND mental fatiguability.
That was part of what I found confusing (and I assume what JenB was referring to) when she said that the ICC does not include muscle fatiguability. It is not just the "and/or" that makes it confusing but also whether "physical fatiguability" is the same as "muscle fatiguability"? (meaning did the writers of the ICC criteria mean them as one and the same or as two different things)?

This is probably why some people prefer the very old definitions, or obscure definitions modified from those, as they explained the muscle weakness more clearly.
Do you know (Foxglove or anyone reading this) if the ICC Criteria is meant to be the most current, up-to-date diagnostic criteria that is meant to supersede all prior diagnostic criteria? Or is this not the case? I am trying to figure out if most ME/CFS specialists would be using the ICC Criteria and if so, would they be assessing for muscle weakness/ fatiguability and ion channelopathies (or would those two issues not be included)?

Fukuda, I think it was, specifically said "not asthenia" and "not somnolence" (not weakness and not sleepiness) which I think is straight-up wrong in the first instance, and wrong at least at some times or for some patients in the second instance. The field has been struggling to recover ever since, IMO.
I have to admit that I am not clear on which criteria is which at this point?! So Fukuda states that if you had actual muscle weakness (asthenia) that you would be excluded and probably have a different diagnosis?

In another discussion, I said that I don't agree that the ICC/CCC don't require muscle fatiguability. In my view it is required. I think disagreement will remain on this point.
I had thought it was required as well BUT I also had no idea that ANY of the criteria mentioned ion channelopathies so I am realizing that I don't understand the criteria or how they are being used (or not being used)?

I am not sure, though, if muscle fatiguability is the same as muscle weakness.
I am not sure either but I would have to assume that if someone had muscle weakness, then their muscle would also fatigue easier than someone who did not. Prior to my treatments, my arms and breathing (lungs and diaphragm) were so weak that if I had crossed the "invisible line" that I described a few posts above, if you offered me a million dollars to stand up and open my glass patio door, I could not have done it and would have had to decline the money vs. now I open this door multiple times per day with ease to let my dog onto the patio.

In intellectual property, the entire text defines the invention, not just the claims. And the ICC text details a bit if muscle fatiguablity is required. Throughout the entire text, muscles are a topic.
So, if I understand correctly, than muscle fatiguability is required as part of the ICC Criteria?

All in all I need to conclude that muscle fatiguability/muscle issues are mandatory for an ME diagnosis.
I had assumed so (but also that muscle issues could be part of many other diagnoses as well).

For me, this is about the ICC criteria and not so much about whether they mirror ME correctly. This would be another discussion.
I agree and I am interested in the criteria as well b/c I am starting to think they could lead to a high level of misdiagnosis.
 
Messages
51
Likes
101
Throughout the entire text, muscles are a topic.

All in all I need to conclude that muscle fatiguability/muscle issues are mandatory for an ME diagnosis.
I would tend to agree with that.

Because of context, I would think that it would be the best interpretation to understand the physical fatiguability as incorporating muscle fatiguability.
 
Messages
51
Likes
101
Do you know (Foxglove or anyone reading this) if the ICC Criteria is meant to be the most current, up-to-date diagnostic criteria that is meant to supersede all prior diagnostic criteria? Or is this not the case?
This is my understanding. I am not sure how things were before 1988 Holmes definition. I get the idea there was a consortium of mostly polio doctors, including someone named Parrish and that they may have had a consensus definiton possibly based on Ramsay, or possibly different regional definitions (such as atypical polio or epidemic neuromyasthenia in the US). But that these polio docs were originally the ones who cared for ME patients.

And that after Tahoe (but not before), the early ME/CFS docs we know of: such as Komaroff, Hyde, Peterson, Bell, Cheney, and so on, knew and worked with these polio docs. (Obviously, Cheney and Peterson did not know to refer their patients to the polio docs during the Tahoe outbreak; they called CDC.)

In 1988 an international group led by the US CDC wrote a new definition and coined the CFS name. Komaroff was part of this, but according to Hyde, Parrish and the other polio doctors left the meeting in frustration. I think Hyde followed them, if I recall correctly.

Also in 1991, the Oxford definition was published by psychiatrists in UK. It was (and is) used almost exclusively by psychiatrists and psychologists who appear to blame the condition on some fault of the patients (which fault changes, but it's always a fault).

CDC or someone thought there was something wrong with the 1988 definition (I can't recall what just at the moment--it might have been "too many symtpoms gets somatoform disorder patients included"--although it didn't have all that many symptoms, IMO, and redness in the throat was required, so I think it could have been an operalizational error combined with not liking to work with sick people when the illness is not well understood, or getting patients with various other diseases and not being good at differential diagnosis but recognizing that it might not be just ME/CFS ppl).

So in 1994 they wrote a new one with fewer required symptoms. Known as Fukuda or sometimes "International" (despite that many definitions have been international).

But none of the required symptoms of 1994 were specific, and none were physical. And still the confusing name. Not sure it solved any of the problems they wanted to solve, as papers continued to be published that other people could get diagnosed unintentially (if differential diagnosis was not good enough).

So in 2003, an international consortium supported by Canada but led by people who actually liked working with this population made a new definition that explained the illness more fully. This is called the Canadian Consensus definition. They used both names in order to not be confusing and because people are diagnosed with CFS, but as far as I could tell they really only thought ME was the correct usage.

In 2005, CDC published a way to operationalize Fukuda by not actually using the symptoms and adding others. This is known as the Reeves criteria or "Empirical" critieria (from the title) although it technically isn't a separate criteria. Hardly anyone besided CDC has used it, and it let to such results as publishing a paper saying people with CFS didn't have dysautonomia (but that hardly anyone in the study fulfilled the original Fukuda criteria for CFS). Plus a bunch of insulting junk papers.

In 2011, the International Consensus Criteria were made by some of the same people who wrote CCC and some new ones. They are basically updated CCC with what was known or thought at the time. This was when XMRV was thought to be a real thing, however.

In 2015, IOM/National Academy of Sciences made a literature review and definition. They included some experts that weren't previously working in the field, and some that previously were.

The late A. Martin Lerner was an author on both CCC and IOM.
Cindy Bateman and Nancy Klimas were authors on both ICC and IOM.

Other authors of IOM that we would previously know include Lily Chu, Ben Natleson, Betsey Keller, and Peter Rowe. (They didn't work on previous definitions.)

Reviewers of IOM include:
Dan Peterson, who worked on Fukuda and CCC

And also include:
Susan Levine, Chris Snell, Charles Lapp (retired), Jose Montoya (dismissed). (They didn't work on previous definitons).

So to answer your question about what updates what, Fukuda updates and replaces Holmes.

CCC to some people (some of the better experts, and many/most patients) updated Fukuda. To those people ICC may update CCC, or they may still like CCC.

We can safely ignore Oxford, Empirical/Reeves, and definitions that are not much used (there are more!).

If there's any one definition that would be meant to update all the others, it would be IOM, as it was a consensus between both government (the Holmes/Fukuda camp) and specialists (including those who used CCC/ICC).

But there was some bad publicity before the IOM report due to poor communication (of course), and no one understood what was going on.

When the report turned out actually good (none of us expect good in any case, I think), it's been really hard for the community to put aside all that energy against it. (My personal view).

Plus most people didn't like the name, or at least didn't like randoms and doctors making fun of the name (which was occurring in newspaper and Medscape comments). I think I remember a shift from "how would you pronounce that" to "it's just as terrible as the previous name" after the news articles started coming out.

But no matter which definition there are still papers saying it's not good enough.

I am trying to figure out if most ME/CFS specialists would be using the ICC Criteria and if so, would they be assessing for muscle weakness/ fatiguability and ion channelopathies (or would those two issues not be included)?
That I couldn't tell you. Neither of the ones I saw did anything besides take history and check that I'd had some tests to rule out major other diseases, test for viruses, and check out my heart.

I was a bit disappointed, especially since one of them told me I was "atypical," and I was hoping to get some immunological testing even though Klimas' clinic is too far for me. I thought they might refer me to some specialists who might be more knowledgeable to follow up on my random wierd tests. But no.
 
Messages
51
Likes
101
If there's any one definition that would be meant to update all the others, it would be IOM, as it was a consensus between both government (the Holmes/Fukuda camp) and specialists (including those who used CCC/ICC).
Maybe this is a bit misleading because CDC wasn't involved (afaik) nor happy with the result, but eventually they had to follow suit and publish the IOM criteria on their website.

NIH commissioned the report.
 

Gingergrrl

Senior Member
Messages
14,690
Likes
43,829
First, that was an incredible summary @Foxglove and the most comprehensive I have seen! I know that I won't retain it all but it was very helpful to read. It sounds like the ICC is the most current criteria until the IOM report came out (if I understood it correctly) but at the same time, no matter how many criteria are out there, doctors don't necessarily use them (and they are more for research)?

There are still two articles from earlier in this thread that I want to read and comment on when I get a chance. I am hoping they give the background re: how the doctors who created the ICC came to include "ion transport issues" and why they did not specifically include "muscle fatiguability" or "muscle weakness"?

In 2011, the International Consensus Criteria were made by some of the same people who wrote CCC and some new ones. They are basically updated CCC with what was known or thought at the time. This was when XMRV was thought to be a real thing, however.
I did not get Mono/EBV until 2012, and the final virus & POTS until Jan 2013, and I was not part of the community during the XMRV stuff. Was the ICC criteria based (in part?) on a theory that was later proven to be false (XMRV) or is that not what you meant?

In 2015, IOM/National Academy of Sciences made a literature review and definition. They included some experts that weren't previously working in the field, and some that previously were.
I do remember this very clearly and had joined PR in June 2014 before the IOM report was released. I was not sure though if at this point (2019) the IOM Criteria are what is used to diagnose vs. the ICC (meaning that ion transport issue and muscle fatiguability would no longer be included whatsoever)?

That I couldn't tell you. Neither of the ones I saw did anything besides take history and check that I'd had some tests to rule out major other diseases, test for viruses, and check out my heart.
I never had a doctor run through one of the criteria with me either (unless they used it as part of their assessment but did not explicitly mention it).

I was a bit disappointed, especially since one of them told me I was "atypical," and I was hoping to get some immunological testing even though Klimas' clinic is too far for me. I thought they might refer me to some specialists who might be more knowledgeable to follow up on my random wierd tests. But no.
Do you know why you were considered "atypical" or which tests you did which showed weird results? No worries if you do not remember or are not comfortable discussing and I totally understand!
 

percyval577

basal and ganglia
Messages
803
Likes
1,081
Location
Ik waak up
I would not necessarily see it as not including muscle fatiguability, although it could be a bit wooly. ICC says this regarding PEM:
...
So we have in point 1, physical and/OR cognitive fatiguability in response to exertion
but in point 5, low threshold of physical AND mental fatiguability.
...

This is probably why some people prefer the very old definitions, or obscure definitions modified from those, as they explained the muscle weakness more clearly.
Also the CCC (so a kind of precursor of the ICC, as the tread clarified, I think) are not very clear here.
They give the option to fullfill:

1. and 2. or
1. and 3-4.
and some additional points

so 2.
There is an inappropriate loss of physical and mental stamina, rapid muscular and cognitive fatigability, post-exertional malaise and/or post-exertional fatigue and a tendency for other associated symptoms within the patient’s cluster of symptoms to worsen. ...
or 4.
There is a significant degree of myalgia. Pain can be experienced in the muscles, and/or joints, and is often widespread and migratory in nature. Often there are significant headaches of new type ...
Via 4. instead of 2. muscle issues are not necessarily included ("can ...and/or"),

but it seems that already 2. rather means
"physical and/or mental stamina", and​
"muscular and/or cognitive" in accordance to​
"post-exertional malaise and/or post-exertional fatique".​

Maybe they mixed (in some hurry) the mathematical "or" up with "and", and should have written "or" instead of "and".
Or they should have written "and/or", as anyone could understand in an everyday´s manner that "or" would include "not both" which though is mathematically a more complicate case, and not a basic one.
 
Last edited:

Gingergrrl

Senior Member
Messages
14,690
Likes
43,829
Also the CCC (so a kind of precursor of the ICC, as the tread clarified, I think) are not very clear here. They give the option to fullfill:
I didn't realize until right now how confusing these criteria are and can understand why the average doctor (who spends only a few minutes with a patient) would not use these criteria.

My purpose for starting this thread was to understand the connection in the ICC criteria (if any) between ion transport issues and ME/CFS. Then I learned (from another thread) that muscle fatiguability was not required in the criteria (which surprised me) so I added it to this thread as part of the discussion of the ICC.

Whatever illness title I ultimately end up with, it definitely includes ion transport issues and muscle fatiguability in the core criteria.
 

percyval577

basal and ganglia
Messages
803
Likes
1,081
Location
Ik waak up
I didn't realize until right now how confusing these criteria are and can understand why the average doctor (who spends only a few minutes with a patient) would not use these criteria.
I think, they all are tries to conceptualize an illness that has intuitively an own right (so to say). The ICC then tend to be a bit bold in their classifications, when there may be commonly symptoms which involve a channelopathy, or when there seems to be a neuro-immune exhaustion (which is by far not proven).
Maybe they made it up to put a weight into the discussion not to end up in such loose samples like presumably in the pace trial.
Also the papers by Morris and Maes tend to sound very optimistic, BTW. I think the task for the ones who make critieria is, neither to be too wide nor too narrow in their conceptualization (both can be bad for the patients which presumably suffer from this illness), therefore it might even have been their intention to be not all that precise in their words(?).

Whatever illness title I ultimately end up with, it definitely includes ion transport issues and muscle fatiguability in the core criteria.
Please no, you might exclude me!: Some of the ion transport symptoms I meet only occasionally (so, what could it say in respect of a cause?), but I would certainly disagree with the muscles issue (I only can induce them by certain combinations of foods; when I detoriated movements were restricted mainly in certain directions, and only for one weak):mad:.

Taken together I would say, this is such a complex illness that it is no surprise that there isn´t already a clue.
We might need to wait for the GCC (Galactic Consensus Criteria);).
 

Inara

Senior Member
Messages
251
Likes
598
@percyval577, how do you conclude muscle issues are optional in CCC? I don't see this.

For a diagnosis, all points 1-7 must be fulfilled (some points have several subitems of which not all need to hold). The points that refer to muscles in any way are:

Point 1: "physical and mental fatigue"
AND
Point 2: "rapid muscular and cognitive fatigability" (the "and/or" here refers to post-(exertional malaise and/or fatigue and /or pain), and is not connected to the commas in the list - the commas here mean "and" because: "[There is an inappropriate loss of physical and mental stamina, rapid muscular and cognitive fatigability,
(post exertional malaise and/or fatigue and/or pain) and a tendency for other associated symptoms ... to worsen]."
AND
Point 4: "myalgia". This means muscle pain. (The following is funny: "Pain can be experienced in the muscles, and/or joints...", because it makes pain in muscles optional which directly contradicts myalgia as mandatory in point 4. Therefore I think what they meant was pain in joints is optional.) Still, even if muscle pain was optional, rapid muscular fatigability is not.

Therefore, the CCC are clearer than the ICC on the point of muscle issues: They are mandatory.
 

Inara

Senior Member
Messages
251
Likes
598
Returning to ion channels: I read in "Ion channels and disease" that Mg ions can block a voltage-gated ion channel (I don't know how it is with ligand-gated channels). That's maybe, @Gingergrrl, why you had bad experiences with it and were told not to use it?
 

percyval577

basal and ganglia
Messages
803
Likes
1,081
Location
Ik waak up
@Inara, you are somwhat right, I misread the key from page roman two of the CCC like so (my brackets, paragraphs and underlines)
A patient with ME/CFS will meet the criteria

for fatigue [1], post-exertional malaise [2]
and/or fatigue [1], sleep dysfunction [3], and pain [4];

[semicolon] have two or more neurological/cognitive manifestations [5]

and one or more symptoms from two of the categories of autonomic, neuroendocrine, and immune manifestations [6].
Instead it´s:
... for fatique [1],
post-exertional malaise and/or fatique [2] ...
But as far as "fatigue" in 2. shouldn´t be the same fatigue as in 1, the reader must feel tempted to read it differently, so rather as"(post-exertional) fatigue" - thereby giving the reference for the following dichotomies. And these dichotomies are now put together with "and" but not with "and/or".
On the other hand, the thing which is to be explained (=post-exertional malaise and/or fatigue") is part of the explanation (exactly the same words!), this rather not acceptable (it´s a fault in logic). Also the usage of the semicolon makes the whole thing pretty confusing.

I would say, the confusion particular in 2. ("and/or" vs "and") might have been made with intention, to suggest that it´s not only being a bit tired or unwilling when suffering with ME/CFS, so potentially a trick to try in an unclear situation to rule out rather inhuman science like pace, but in fact, is there good evidence that muscle issues are required?
If there is a hallmark, then it´s a huge (potentially delayed) exertional intolerance, PENE if you want, or PEM and/or in this number 2. PEF, if I am allowed to shorten "(post-exertional) fatique" (again, ruling out two logical mistakes, a repeating and an explanandum-explanans confusing).
___​

Also I would be surprised if there is a serious rationale why ion transport issues - literally ones - must be part of this difficult to grasp illness. Probably they just have written it because some heart diseases - as I guess or mean to remember - display an ion transport malfunction, and now some heart issues can also appear in these strange patients who presumably suffer from ME/CFS.
I had a very strange heart beat for three months, the cardiologist said "This is an announcement, my god!", three months later it was completely gone. And the ion transport findings n ME/CFS @Foxglove linked are of course very interesting, but this is nothing conclusive, the best one is probably the finding in NK cells (2016), so this should remain completely unclear so far.

Please correct me if I am wrong in the last major paragraph, I just won´t take it by word. They made a friendly guess, hopefully/probably driven by human insight.
___
Taken together, both criteria can not claim to have already successfully defined the illness.
 

percyval577

basal and ganglia
Messages
803
Likes
1,081
Location
Ik waak up
Interesting study, Whistler et al 2005 (Suzanne Vernon).

They looked at differences in gene expression in mononuclear cells, and found differences between
  • HC and CFS pre-exercise
  • HC and CFS post-exercise
  • pre- and post-exercise in HC
  • pre- and post-exercise in CFS
The differences may show up only when put together by "gene ontology" (with fields of genes where gene expressions will reinforce each other).

Sadly they don´t say in detail if the different genes are up- or downregulated.

Most significant then were the potassium and voltage gated ion channels (including VG-potassium-C´s),
which show up in the field "cellular component" with 20 genes,
and in the field "molecular function" with 43+44+22 genes,
(there is only one more filed "biological process").
 
Last edited:

Gingergrrl

Senior Member
Messages
14,690
Likes
43,829
Maybe they made it up to put a weight into the discussion not to end up in such loose samples like presumably in the pace trial.
Do you mean that the ICC Committee made up the "ion transport issues" as part of the criteria so it would have more weight (but there was nothing to back it up)? What would be the purpose of doing that?

Some of the ion transport symptoms I meet only occasionally (so, what could it say in respect of a cause?), but I would certainly disagree with the muscles issue (I only can induce them by certain combinations of foods; when I detoriated movements were restricted mainly in certain directions, and only for one weak):mad:.
How do you know that you occasionally meet criteria for an ion transport issue? Do you mean an autoantibody or a genetic issue (or something else)? Also, you did not have muscle weakness or fatiguability unless it was triggered by certain combinations of foods?

We might need to wait for the GCC (Galactic Consensus Criteria);).
LOL :rofl:

Returning to ion channels: I read in "Ion channels and disease" that Mg ions can block a voltage-gated ion channel (I don't know how it is with ligand-gated channels). That's maybe, @Gingergrrl, why you had bad experiences with it and were told not to use it?
That is my understanding @Inara (that Mg ions can block the voltage gated calcium channels which are already blocked for me by an autoantibody). This is as deep as my understanding goes though and I cannot tell you anything more! I would love to understand (for real life) if Propofol (anesthesia) is safe for me since it technically is a calcium channel blocker but have yet to find an answer. Hopefully I will never need it so it will not matter.