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Created in 2008, Phoenix Rising is the largest and oldest forum dedicated to furthering the understanding of, and finding treatments for, complex chronic illnesses such as chronic fatigue syndrome (ME/CFS), fibromyalgia, long COVID, postural orthostatic tachycardia syndrome (POTS), mast cell activation syndrome (MCAS), and allied diseases.
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Doesn't sound like anything too new... and doesn't sound good! ;-)
These kinds of immune abnormalities, inflammatory cytokines, T & B cell reactivities, etc. seemingly would be SO easy to test for & differentiate from the normal population. How many years are researchers just going to repeat this stuff over and over without proposing all the immune dysfunction as at least some kind of biomarker?
I understand that some people are under the impression that the model portrays ME/cfs as an autoimmune disease. The model is best explained by referral to the diagram contained in the paper. Autoimmunity is a very small part of the model. I appreciate that it is difficult for those without a scientific background in this area to understand. I have tried to make it as patient friendly as possible and also attempted to explain the mechanisms to scientists who are not familiar with neuroimmunology.A cursory examination of the disease model will reveal that an interaction between PICs RN and OS coupled with mitochondrial dysfunction is the cause of the landmark symptom of ME/cfs, namely a global exacerbation of symptoms induced by even trivial increases of cognitive or physical activity. If people do not have this phenotype then the weight of scientific evidence would strongly suggest that they do not have ME/CFS but of course may have idiopathic chronic fatigue and four somatic symptoms and thus fulfill the Fukuda definition of chronic fatigue syndrome.You may reproduce this e-mail as long as you do so in full.
This model provides considerable
evidence that the pathophysiology of ME/CFS is associated
with immuno-inflammatory pathways, which lead to neuro-
logical aberrations, including behavioral responses, and
neuro-endocrine, autonomic and brain dysfunctions.
Thanks, JT--have now read the paper as best I could, though some of it is frankly beyond me. But I do have a couple of comments on it. There is a rather dismaying (to me) repetition of the word "may" that runs right through the argument. There is a need to make it clear that this is a hypothesis, a model, but.. And, to go back to the discussion of definitions, it begins with a very explicit discussion of CFS and ME, which concludes that "ME and CFS are therefore different diagnostic concepts" ( and according to the brief definitions offered here, I am clearly ME and not CFS.) The authors then note that most research has been on ME/CFS, and so use that term for the body of the essay, though I think it is implied (I cannot find an explicit statement) that they are really talking only about what they have just defined as ME. It does look like an interesting attempt to wrap up the disease processes, including the gradual emergence of autoimmunity as a response to gathering uncleared damage. Nothing here about possible therapies, though--I guess that will have to wait. Chris
Just a few observations:
The model actually doesn't provide evidence. The evidence already perhaps exists, and the model is incorporating that evidence into its schema. But the model itself does not provide new evidence. Just to clarify that point.
Altogether, I have to say that the paper looks kind of like a "kitchen sink" approach, where everything was thrown into the mix, and then random speculations were attached. If I presented this to any of my physicians, they would laugh at me. It might be useful for directing research, but I question even the utility of that - directly, at least.
For example, the authors attribute brain fog to changes in glucose metabolism: "The ensuing lack of glucose would potentially explain the brain fog that so many people with this illness complain of." "Potentially," hmmm. It's just a speculation that, again, my doctors would laugh at.
And specifically, there is really no lack of serum glucose - many ppl w/CFS have increased serum glucose, in fact. As the authors first stated, perhaps there are metabolic changes that reset glucose homeostasis, etc. However, brain fog could just as easily be attributed to: cytokine storms, excitatory neurotoxicity, lowered cortisol or corticosteroid receptor function, impaired alpha-adrenergic or other neurotransmitter/receptor function, NMDA receptor function, thyroid hormone imbalance, disturbances in oxygen uptake patterns and resulting hypoxia, chemical sensitivities, food allergy or autointoxication from dysbiosis, candida toxins, and many other factors that we could go on to list.
A lot of people experience temporary worsenings and then relative improvements in brain fog, in fact. And the brain itself, as we know, is extremely sensitive to changes in blood glucose, and keeps a tight rein on that. So the idea that the brain is "resetting" its glucose metabolism up and down in such short periods seems like one of the least plausible explanations.
Just one example where attempting to force some "theory" onto the phenomenon is not really helpful, imo. Let the researchers find out what exactly is going on, rather than just making up fairly implausible "explanations" that actually don't explain anything. Get the facts, not the fabrications.
Another point unrelated to the paper specifically, but one that I wanted to comment on, regarding the WHO definition of ME mentioned in the paper:
I think the WHO ME definition is flawed, as it refers to a "chronic relapsing-remitting course." But the vast majority of ME/CFS sufferers don't go into remission, from which they then again relapse. The vast majority stay chronically ill, from which there might be small or sometimes even signifcant *improvements,* but they are not "in remission." That's an important distinction, and the language of "remitting" is not accurate, imo.
Stating that there is remission when in the vast majority of cases there is no remission trivializes the disorder. Even if doctors know the WHO ME definition, they are likely to say having ME/CFS is really no big deal since you'll probably go into remission anyway - it's part of the definition! I think that criterion needs to be changed to reflect what is closer to the reality for the vast majority of patients: chronic unwellness, often with worsening symptoms, and occasionally with some minor or relative improvement. Sometimes even major improvement. But almost never remission. If there is remission, in fact, in most cases they DIDN'T have ME, but some other problem (jaw infection, mono, severe allergy, etc.) So imo the definition there is completely erroneous.
The model is new evidence. It is constructed on the foundation of all MECFS research and biomedical evidence of how the human body functions. A hypothetical model could not be so if the kitchen sick was not also in there. Patients and clinicians report improvement, remission and relapse. The model must mechanistically explain all.
Speculation is not the right use of terminology.
Jeffrez you are speculating on the model from your simplified understanding of pathophysiology.
New evidence would be like someone investigating a murder case finding the gun. Rearranging or presenting what we already know about the case isn't new evidence, only an interpretation of the existing evidence. The latter is what this paper does.
It then goes on to speculate about these things we already know - about the existing evidence - devising a theory to explain it, but there doesn't appear to be a gun anywhere in sight.
Where's the gun? That's what we need to find out.
The model includes the gun, the bullet and the anatomy of impact and subsequent damage. There has never been a paper which achieved a model of MECFS. Please do read the paper and see if you can find the relevant quote.
If people do not have this phenotype then the weight of scientific evidence would strongly suggest that they do not have ME/CFS but of course may have idiopathic chronic fatigue and four somatic symptoms and thus fulfill the Fukuda definition of chronic fatigue syndrome.