Question re: the ICC Criteria and Ion Transport issues

Gingergrrl

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In the International Consensus Criteria (ICC), it lists in Section D:

at least ONE energy metabolism/ ion transport impairment symptom.
The bolding above is mine so it would be easier to see. I was wondering if anyone could explain to me what is meant by "ion transport impairment symptom" within the context of the ICC criteria. I do not see this symptom listed in the other criteria (although I could certainly be missing it).

I have an autoimmune calcium channelopathy and did not think it was relevant to the ME/CFS criteria until someone recently pointed this out to me. Is this listed in the criteria due to the research being conducted in Australia with calcium ion issues or is it unrelated?

I would love to understand this better if anyone happens to have any info! Thanks in advance.
 

Gingergrrl

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I'm just bumping this in case anyone missed it who might be familiar with the ICC criteria and know what they meant re: "ion transport impairment" or how that got included as a symptom? I was so surprised when someone pointed that out to me and I never knew there was any connection.
 

Mary

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Hi @Gingergrrl - I looked at MEpedia and the ICC: https://me-pedia.org/wiki/International_Consensus_Criteria
and I saw where you refer to ion/transport impairment system under Section D.

I clicked on "ion transport system" above, and it brought me to this page:
https://me-pedia.org/wiki/Ion_transportation#cite_note-:0-1
and found this sentence:
Evidence of ion transportation dysfunction has been found in ME/CFS.[1]
Clicking on footnote 1 led to this reference: https://books.google.co.uk/books?id...C-4Q6AEIRDAG#v=onepage&q=channelopathy&f=true
which is a book about channelopathies. So I'm guessing that the origin of "ion/transport impairment system" in the ICC might have its origins in this book. It look like the entire book may be on-line -
 
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Hi, the ICC lumps together cellular energy and ion transport in the introduction
dysfunction of cellular energy metabolism and ion transport [9-11]
I am not sure which of these would involve ion channels, but could look them up gradually:
altered immune and adrenergic signalling [29, 30] and altered oestrogen receptor expression [31].
modifications in serotonin transporter genes [32, 33], the glucocorticoid receptor gene [34],
Here again is cellular energy and ion transport:
Postexertional neuroimmune exhaustion is part of the body’s global protection response and is associated with dysfunction in the regulatory balance within and between the nervous, immune and endocrine systems, and cellular metabolism and ion transport [42-46].
Here's a bit with a some more details:
The consistent clinical picture of profound energy impairment suggests dysregulation of the mitochondria and cellular energy metabolism and ion transport and channelopathy [9-11, 100, 101]. A biochemical positive feedback cycle called the ‘NO/ONOO‐ cycle’ may play a role in maintaining the chronic nature of ME, the presence of oxidative stress [102-104], inflammatory cytokine elevation [94-96] and mitochondrial dysfunction [105-108] and result in reduced blood flow and vasculopathy [106, 107].
The papers are:

10.

  • 29 Light AR, White AT, Hughen RW, Light KC. Moderate exercise increases expression for sensory, adrenergic, and immune genes in chronic fatigue syndrome patients but not in normal subjects. J Pain 2009; 10: 1099– 112.
    Crossref CAS PubMed Web of Science®Google Scholar

  • 30 Light AR, Bateman L, Jo D et al. Gene expression alterations at baseline and following moderate exercise in patients with Chronic Fatigue Syndrome, and Fibromyalgia Syndrome. J Intern Med 2011; ???: ???. May 26. doi: 10.1111/j.1365‐2796.2011.02405.x. [Epub ahead of print].
    Google Scholar
  • 31 Gräns H, Nilsson M, Dahlman‐Wright K, Evengård B. Reduced levels of oestrogen receptor beta mRNA in Swedish patients with chronic fatigue syndrome. J Clin Pathol 2007; 60: 195– 8.
    Crossref CAS PubMed Web of Science®Google Scholar

  • 32 Narita M, Nishigami N, Narita N et al. Association between serotonin transporter gene polymorphism and chronic fatigue syndrome. Biochem Biophys Res Commun 2003; 311: 264– 6.
    Crossref CAS PubMed Web of Science®Google Scholar

  • 33 Falkenberg VR, Gurbaxani BM, Unger ER, Rajeevan MS. Functional genomics of serotonin receptor 2A (HTR2A): interaction of polymorphism, methylation, expression and disease association. Neuromolecular Med 2011; 13: 66– 76.
    Crossref CAS PubMed Web of Science®Google Scholar

  • 100 Nijs J, De Meirleir K, Meeus M, McGregor Nr, Englebienne P. Chronic fatigue syndrome: intracellular immune deregulations as a possible etiology for abnormal exercise response. Med Hypotheses 2004; 62: 759– 65.
    Crossref CAS PubMed Web of Science®Google Scholar


  • 101 Wong R, Lopaschuk G, Zhu G et al. Skeletal muscle metabolism in the chronic fatigue syndrome. In vivo assessment by 31P nuclear magnetic resonance spectroscopy. Chest 1992; 102: 1716– 22.
    Crossref CAS PubMed Web of Science®Google Scholar

Thanks to @Mary for posting a link to the ME-Pedia page. That made it really easy to find the paper.
 

Hip

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I'm just bumping this in case anyone missed it who might be familiar with the ICC criteria and know what they meant re: "ion transport impairment" or how that got included as a symptom?
"Energy Metabolism/Ion Transportation Impairments" is just the title of section D on page 8 of the ICC. But what is important is the symptoms and conditions listed within section D, which you have to have at least one of in order to satisfy the ICC.


I've not seen the ICC used much in studies; it's still the CCC and/or the Fukuda criteria that are usually used to select patient cohorts for ME/CFS studies.
 

Gingergrrl

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I just got a chance to read through everything and have a lot of questions as I suspected... :D

Hi @Gingergrrl - I looked at MEpedia and the ICC: https://me-pedia.org/wiki/International_Consensus_Criteria
and I saw where you refer to ion/transport impairment system under Section D.
Thank you for finding this @Mary and it is a great starting point. I literally never knew that ion channelopathies were listed as part of ANY of the ME/CFS criteria and am trying to understand the connection!

I clicked on "ion transport system" above, and it brought me to this page: https://me-pedia.org/wiki/Ion_transportation#cite_note-:0-1 and found this sentence:
The sentence you found from MEpedia said:

Evidence of ion transportation dysfunction has been found in ME/CFS.[1]
https://me-pedia.org/wiki/Ion_transportation#cite_note-:0-1

So I am now trying to figure out if there was a specific study that found evidence of ion transportation dysfunction in ME/CFS. There must be for it to be cited but I am just not very good at finding things.

Clicking on footnote 1 led to this reference: https://books.google.co.uk/books?id...C-4Q6AEIRDAG#v=onepage&q=channelopathy&f=true
which is a book about channelopathies. So I'm guessing that the origin of "ion/transport impairment system" in the ICC might have its origins in this book. It look like the entire book may be on-line -
I clicked on the book (where they got the citation from) and most of the book is listed on-line like you said. I was tempted to buy the book (if this is even possible?) but from the sections that I read, it is just too complex for me to understand. I was particularly interested in the section of the book that starts around page 361 on autoantibodies (vs. genetic mutations) that affect the ion channels and it talks about both of the autoantibodies that I have (N-type Calcium Channel Ab and GAD65 Ab). I could not find any mention in the book of a connection to ME/CFS but it is very possible that it is there and I just did not find it.
 

Gingergrrl

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Part 2:

Hi, the ICC lumps together cellular energy and ion transport in the introduction
Would this relate to muscle weakness or some other symptom?

I am not sure which of these would involve ion channels, but could look them up gradually:
Thank you for all of those links and I will look them up gradually. I am very interested in understanding this better.

"Energy Metabolism/Ion Transportation Impairments" is just the title of section D on page 8 of the ICC. But what is important is the symptoms and conditions listed within section D, which you have to have at least one of in order to satisfy the ICC.
I had ALL of the symptoms listed in "Section D" (in the box below) before remission from my treatments. I am not at pre-illness level, and probably never will be, but "remission" is the best word I can find, especially b/c my doctors do not know if my current state is temporary, if it will stay at this level, if it will improve further, or if it will completely deteriorate. But I had all of the issues listed below (plus muscle weakness and MCAS/allergic reactions).


I've not seen the ICC used much in studies; it's still the CCC and/or the Fukuda criteria that are usually used to select patient cohorts for ME/CFS studies.
Do you know what the ICC criteria is used for (if not for research studies)? I've never seen it used as a clinical diagnostic criteria by a doctor. When is it used (or is it not currently being used)? Do you know why the ICC is the only criteria to list ion transport/ channelopathy issues and link them to ME/CFS? (I don't know any of these answers myself but am very curious now)!
 
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I've not seen the ICC used much in studies; it's still the CCC and/or the Fukuda criteria that are usually used to select patient cohorts for ME/CFS studies.
The ICC is the evolution of the CCC, and the ICC Primer is the largest and most detailed document on ME. Therefore, it is still incomprehensible to me why it is not used. Even the most ME patient organization have been calling for the ICC for years.

but you can see for decades, as the health authorities to dilute the ME diagnosis. first with the euphemism "CFS" and most recently with SEID.

Sorry for the excursus. Everything has already been said about the actual topic.
 
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Do you know why the ICC is the only criteria to list ion transport/ channelopathy issues and link them to ME/CFS? (I don't know any of these answers myself but am very curious now)!
because the ICC (2011) are the latest criteria (the SEID 2015 criteria are absolute garbage).
fukuda is from 1993 (garbage) and CCC from 2003.
 

Moof

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I was wondering if anyone could explain to me what is meant by "ion transport impairment symptom" within the context of the ICC criteria.
It reads as if it isn't necessary to show evidence of an ion transport impairment; just at least one symptom of such (and the symptoms, of course, are common to a number of conditions and can have multiple causes.) I don't know whether it's deliberately vaguely worded or not, though.
 

Hip

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The ICC is the evolution of the CCC
The ICC makes some assumptions about the nature and pathophysiology of ME/CFS which are not supported by rigorous science. For example, the ICC call the post-exertional symptoms of ME/CFS "PENE" (post-exertional neuroimmune exhaustion), thereby making the assumption that the post-exertional symptoms are caused by neurological and immunological factors. But there is no solid evidence for this, and the cause of PEM remains a mystery.

Similarly regarding the topic of this thread: the ICC section entitled Energy Metabolism/Ion Transportation Impairments: I don't think there is any solid evidence to indicate that the symptoms and conditions listed in this section are caused by either energy metabolism or ion transport dysfunction.
 

Hip

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Do you know what the ICC criteria is used for (if not for research studies)?
The ICC were based on the CCC, with some very minor changes, such as the ICC dropping the requirement for the patient to be suffering from their symptoms for 6 months before an ME/CFS diagnosis is given.

I don't see what advantages adopting the ICC in place of the CCC would offer. In fact the CCC I think are better for research purposes, because it's actually a good idea to wait until a patient has suffered symptoms for 6 months before including them in a study, just to ensure that have not got some transient condition causing their symptoms.



Do you know why the ICC is the only criteria to list ion transport/ channelopathy issues and link them to ME/CFS?
See my above post (my reply to Peter Pain).

Incidentally, in the original ICC paper, that section is labelled not Energy Metabolism/Ion Transportation Impairments, but Energy Metabolism/Transportation Impairments.

So it may be an error that it was called ion transportation; what they may have meant was energy transportation impairments.
 
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duncan

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I don't think there is any solid evidence to indicate that the symptoms and conditions listed in this section are caused by either energy metabolism or ion transport dysfunction.
What symptoms and conditions, specifically, are we talking about? I have a copy of the ICC lurking about, but I'd rather not have to search for it, if someone doesn't mind supplying the specifics.

Generally speaking, many ME/CFS symptoms can be exhibited by patients of channelopathies. In fact, it can be devilishly hard sometimes to distinguish the two.
 
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Hip

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What symptoms and conditions, specifically, are we talking about?
Those listed in the section D of the ICC, namely:
D. Energy production/transportation impairments: At least one symptom
 1. Cardiovascular: e.g. inability to tolerate an upright position - orthostatic intolerance, neurally mediated hypotension, postural orthostatic tachycardia syndrome, palpitations with or without cardiac arrhythmias, light-headedness/dizziness
 2. Respiratory: e.g. air hunger, laboured breathing, fatigue of chest wall muscles
 3. Loss of thermostatic stability: e.g. subnormal body temperature, marked diurnal fluctuations; sweating episodes, recurrent feelings of feverishness with or without low grade fever, cold extremities
 4. Intolerance of extremes of temperature
 
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The ICC makes some assumptions about the nature and pathophysiology of ME/CFS which are not supported by rigorous science. For example, the ICC call the post-exertional symptoms of ME/CFS "PENE" (post-exertional neuroimmune exhaustion), thereby making the assumption that the post-exertional symptoms are caused by neurological and immunological factors.
PENE does not mean that neurological and immunological factors cause PENE, but that during PENE, neurological and immunological symptoms predominate. That's a big difference.

and by the way: in the most severe cases of ME, dorsal root ganglionitis were found in autopsies. Who is looking for it? nobody. The researchers prefer to invest millions in microbiome research. ridiculous.
 

Hip

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PENE does not mean that neurological and immunological factors cause PENE, but that during PENE, neurological and immunological symptoms predominate. That's a big difference.
The ICC say:
The underlying pathophysiology of PENE involves a profound dysfunction of the regulatory control network within and between the nervous systems. This interacts with the immune and endocrine systems affecting virtually all body systems, cellular metabolism and ion transport.
So here they are saying that PENE is caused by dysfunction of the nervous system, which then affects the immune and hormonal systems.

But this statement from the ICC goes beyond what we know for sure. It's more of a hypothesis than a fact.
 
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The ICC say:

So here they are saying that PENE is caused by dysfunction of the nervous system, which then affects the immune and hormonal systems.

But this statement from the ICC goes beyond what we know for sure. It's more of a hypothesis than a fact.
It says that the underlying pathophysiology involves disorders of the nervous system. And that's right, because the nervous system is inflamed in ME and therefore also belongs to pathophysiology. please also do not confuse pathophysiology with pathomechanism.


ICC are the evolution of the CCC and the CCC are from 2003. 16 years old. many studies are not included there. we would have been far more advanced in research if every researcher were to take on the ICC. instead, researchers use fukuda or SEID to recruit people with depression.
 
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Hip

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@Peter Pain, researchers do not use the IOM SEID criteria to recruit patients for studies, because the IOM criteria are not designed for research, they are designed only for clinical use in the doctor's office.

You have your own opinions on these various criteria, but they are just opinions. Some patients believe that the original Ramsey criteria for ME/CFS (which were created in the 1980s) are the only true criteria for ME, and that all the others, including the ICC and CCC, do not represent true ME. But again, that's just an opinion, not a fact.


One recent paper which examined the various ME/CFS diagnostic criteria concludes:
There is considerable ongoing discussion regarding the case criteria to use. With the release of the IOM’s clinical criteria, it was clear that these criteria would not be used as a research case definition.

Due to this, it is possible that many researchers will continue to use the Fukuda et al. case definition as a research criteria. However, it is also possible that some may now begin using the IOM clinical criteria for research purposes, or as in the present study, identify a smaller more impaired group of patients who are homebound.

Others might select other characteristics, such as research criteria that include those meeting IOM and also having Fibromyalgia or Multiple Chemical Sensitivities.

Alternatively, the research community might select one set of research criteria, either an empirically based one (though not the Reeves et al. criteria), the Myalgic Encephalomyalitis-International Consensus Criteria (ME-ICC), the Canadian Consensus Criteria (CCC), the Ramsay Criteria, or the IOM clinical criteria with more extensive and concretely specified exclusions.
 
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@Hip
The ICC is the latest consensus with 400 years of experience by the authors.
Anyone who has seen 50,000 ME patients knows what the symptoms are that are needed to diagnose.
Every ME patient knows that these criteria best describe the disease. everyone I've talked to and who certainly has ME says that and especially the most seriously ill.
why are you so against the ICC?

ICC:
"Accordingly An International Consensus Panel has been formed, the clinician, researcher, teacher
and an independent patient representative and whose goal is the development of
Criteria based on existing knowledge. 13 countries and a broad one
Spectrum of subjects were represented. Together, the members of the
Consensus Panel on more than 400 years of experience in the clinical and
Teaching, they have published hundreds of peer-reviewed publications, such as
50,000 ME patients were diagnosed and treated and several of the panel members were
already involved in the preparation of the earlier consensus criteria."
 
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