The various “CFS” definitions are, *by definition*, not the same as M.E. ICD-10.

Dr Pall probably *does* know that M.E. has had a WHO classification (under G93.3) since 1969, precisely because of the significant body of evidence existing for it. Is he suggesting that the WHO adopted this classification of M.E. as a neurological disease but still thought it was undocumented?

The “CFS” definitions are fatigue-centred. M.E. (as studied by Drs Hyde, Ramsay, Richardson and Dowsett) ICD-10 is, by contrast, a neurological disease characterised by the inability of the body to maintain homeostasis. (That is its fundamental characteristic, not “post-exertional malaise”, as Dr Pall claims.) Fatigue is not a necessary symptom of it, let alone a central one. The “CFS” definitions state that the illness is ruled out upon discovery of physical pathology (I assume I don’t need to provide the Holmes and Fukuda definitions and that Mr Pall is aware of this). M.E. requires physical pathology.

Mr Pall writes: “All of the genetic, animal model and therapy study evidence that I cite were published under the name CFS.”
That’s fine, but it was unhelpful of him to respond to Aylwin Catchpole’s comments about M.E. as if Aylwin were writing about “CFS”, which she clearly was not.

Studying a particular group of patients (say “CFS” patients) and deciding to link that patient group to the very differently-defined M.E. (especially when you’ve said you don’t think much of the research on M.E.) is questionable, to say the least.

As is arguing that the Fukuda case definition *can* be made supportable by including “post-exertional malaise” as a criterion. Surely, a diagnosis by exclusion can only be a misdiagnosis. That is what Dr Byron Hyde has said – a doctor who has studied in M.E. in its various outbreaks, rather than studying patients with the very different “CFS” diagnosis.
[http://www.investinme.org/Documents/PDFdocuments/Byron%20Hyde%20Little%20Red%20Book%20for%20www.investinme.org.pdf]

The Fukuda case definition is not “inadequate” – it is simply not a definition of M.E.

As to Mr Pall’s complaint:
“That web site lists a whole series of citations but gives no clarification whatsoever about how any of those citations support any of the claims on the site. It fails, therefore, to provide any scientific support for any of the claims. In order to document claims scientifically, it is necessary to cite specific publications, giving specific information on what that specific publication shows and how it shows it.”

No, it is true the HFME doesn’t repeat the contents of those references documents word for word – the references were given so it would not need to. And it must be acknowledged that those unwilling to read the publications of the doctors who have studied actual M.E. most intimately (rather than patients selected using fatigue or sometimes immune-fatigue criteria) are unlikely to agree with much written on the HFME site anyway.

As I mentioned earlier, that fact that the M.E. and CFS definitions are mutually exclusive makes any claim about mixed M.E. and CFS research being scientifically rigorous quite dubious.

Usually, of course, “CFS/ME” research is in fact about “CFS” (although one usually needs to read the patient selection criteria in order to discover this). Sometimes, it is true, “CFS/ME” results in a mixed patient group, and unfortunately the Canadian criteria have added to this problem. Needless to say, it leads to results of dubious worth, since it’s hard to assess the meaning of research that contained an unknown quantity of actual M.E. patients.

As Mr Pall says at the end, he does not believe that “neurological dysfunction …is … at the core of the etiology” of M.E. In this, he contradicts not only the WHO’s classification, which has M.E. in the neurological section, due to M.E.’s damage to the brain stem (which is of course where the name comes from), but also the doctors who have studied M.E. most closely.

I would encourage Mr Pall to read Dr Hyde’s descriptions of the study of M.E. prior to the invention of the “Chronic Fatigue Syndrome” concept. Dr Hyde also describes how this new concept was so different from M.E., and the inventers of “CFS” had so little understanding of what M.E. was or contact with its patients or familiarity with research on it, that those researchers who *did* have familiarity with M.E. mainly withdrew from the committee devising this new disease construct.

And I do agree that fundamentally, we need to stick with the science. Simply by looking at the diagnostic and research criteria for “CFS” and “CFS/ME” work, we can see that it has nothing to do with M.E. When the criteria are fundamentally different and even mutually exclusive, that makes things fairly clear.

You will note that there is not one specific documented point that is made anywhere in Virginia Brown’s comments – simply a lot of undocumented claims.

As far as the issue of bureaucratic placement of CFS vs ME, it has nothing to do with the science. All of the genetic, animal model and therapy study evidence that I cite were published under the name CFS. There is little if any science that has been published on anything claimed to be ME but not CFS.

With regard to the documentation that Virginia Brown claims exists on the Hummingbird web site, what it states is the following:

All of the information concerning Myalgic Encephalomyelitis on this website is fully referenced and has been compiled using the highest quality resources available, produced by the world’s leading M.E. experts.

The problem is the following: That web site lists a whole series of citations but gives no clarification whatsoever about how any of those citations support any of the claims on the site. It fails, therefore, to provide any scientific support for any of the claims. In order to document claims scientifically, it is necessary to cite specific publications, giving specific information on what that specific publication shows and how it shows it. That is what I do in my publications and what every other reputable scientist does. Without that linkage of specific claims to specific documentation, there is no way to tell whether these publications that they list on the site support or fails to support any of the claims. A simple statement that they are supported does not even start to provide any scientific support.

I will make one more point. I agree with the point of view that the Fukuda case definition is inadequate. And the Oxford case definition is completely questionable. The Canadian case definition and also Jason and others argue that post-exertional malaise is THE most characteristic symptom of CFS/ME. My own view, that I have published, is that post-exertional malaise is produced by a failure to regulate cortisol properly in response to exercise. This, as a minimum, needs to be added to the Fukuda case definition to make it supportable, and this is what Jason has done. It can be argued from this deficiency to control cortisol in response to exercise, that therefore the core of CFS/ME is a specific neuroendocrine abnormality which is, of course, caused by a neurological dysfunction. So I agree that neurological dysfunction has a key role. But that does not mean that this is all that is at the core of the etiology. In fact, we know that that is NOT the case.

Martin L. Pall

If he had read Aylwin’s comment, he would have seen that she wrote about Myalgic Encephalomyelitis, not “CFS/ME”. Not only are these disease concepts very different, but they are also mutually exclusive. “CFS/ME” is another term for “CFS”, a concept invented in 1988 by the US Centre for Disease Control. Incorporated into that definition (and the subsequent “Fukuda” and “Oxford” definitions based on it), is the stipulation that (a) it is fatigue-centre, and (b) it is ruled out upon the discovery of measurable physical pathologies.

There are a few other possible findings for those diagnosed according to the Fukuda “CFS” criteria, but because they are pick-and-choose, it’s possible to be diagnosed with it without having the central characteristic of M.E. – neuro damage.

M.E.ICD-10 (which has had the G93.3 listing with the WHO since 1969, unlike “CFS”, which does not have a WHO listing), is an actual disease, not waste-basket definition like “CFS”. M.E. is testable for and the doctors who have studied its patients and outbreaks most closely (Ramsay, Hyde, Richardson and Dowsett) have stated that they believe it to be caused by an enterovirus, because of the pattern of outbreaks and other patterns and discoveries in their patients including the initiating factors possible given the incubation periods.

The false notion that M.E. and “CFS” are equivalent has meant that many studies on “CFS” patients have been attributed to M.E. – and given that “CFS” involves grouping together patients on the sole commonality of “fatigue” (a symptom which is not even necessary for an M.E. diagnosis, and by far the least severe symptom in those who have it) – of course, “CFS” studies will tend to find many catalysing factors for the patients’ problems.

Sadly, many doctors and patient advocate groups have fallen for the conflation of M.E. and “CFS”, and support names like “ME/CFS”, even though that legimitises the mixing in research of M.E. and general fatigue patients, and very frequently leaves out M.E. patients entirely, meaning some research results in recommendations which are positively harmful for M.E. patients. [Eg that M.E. patients should exercise. That might be a legitimate recommendation for some sick people with fatigue, but is dangerous, sometimes even fatal, for M.E. patients.]

It is also unfortunate that some researchers have taken the same tack.

Mixing together the disease concepts also removes the pressure on medical insurance companies and governments to provide support for M.E. patients – they can point to the research done on these “CFS” or mixed groupings and use the findings to claim that M.E. patients either don’t need, or would be undermined and rendered dependent by, real support being provided to them.

On Martin’s last point:
“the web site that he cites does not provide any evidence whatsoever supporting his view. It simply provides unsupported opinion, and unsupported opinion is never the basis of good science.”

Again, if Martin had read The Hummingbirds Foundation for M.E. website [www.hfme.org] as he indicated he has, he would have noticed the extensive footnotes (in addition to the in-text explanation) and pages of links to material by the researchers of actual M.E. patients and outbreaks. If Martin wishes to disagree with the research contained in the links (such as that performed by Drs Hyde, Ramsay, Dowsett and Richardson, those who studied M.E. in the early days and/or continued this work – were basically the parents of the research on this disease), that is of course his right, but it would be more respectful of him to do so directly rather than writing it off by dismissively characterising all commentary on this as “unsupported opinion”.

The following is my response to Aylwin Catchpole’s undocumented claims. There have been many attempts to argue that CFS/ME is simply a response to infection by a specific infectious agent, but none of them has ever been shown to fulfill Koch’s postulates or any modern version of Koch’s postulates. Consequently, his claim that enterovirus is THE cause is not supported by the literature. What is true is that we have substantial support that CFS/ME has a very good fit to the five principles underlying the NO/ONOO- cycle. These five principles are the rough equivalent of Koch’s postulates for NO/ONOO- cycle diseases. So here we do have substantial and I would argue overwhelming evidence that the NO/ONOO- cycle is causal.

There is specific substantial specific published evidence that contradicts Aylwin Catchpole’s claim – evidence from the pattern of stressors shown to be able to initiate cases of CFS/ME, evidence from genetic studies of susceptibility, implicating excessive superoxide levels, mitochondrial dysfunction and also inflammatory biochemistry as causal elements and also a various clinical trial studies of potential therapeutic agents also implicating these factors and other elements of the cycle as causal elements in CFS/ME. If Aylwin Catchpole wishes to argue with all of this evidence, he is free to publish his arguments but at this point, we must view the foundation of his comments as being based on quicksand.

One more point, the web site that he cites does not provide any evidence whatsoever supporting his view. It simply provides unsupported opinion, and unsupported opinion is never the basis of good science.

Martin L. Pall, PhD