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A neuro-immune model of ME/CFS.

Marco

Grrrrrrr!
Messages
2,386
Location
Near Cognac, France
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.


I'm happy to see I'm not the only one bothered by the alleged relapsing/remitting nature.

A little remitting wouldn't go amiss from time to time.
 

Snow Leopard

Hibernating
Messages
5,902
Location
South Australia
Who is Gerwyn Morris, never heard of a scientist by the name of Gerwyn Morris? What are his scientific credentials and education?

I'm sorry, but argumentum ad hominem is also invalid in science.

Reviews, no matter the method (qualitative or systematic) can be useful in scientific practise so long as they shine light in (testable) directions we had not previously considered. If you take a wider view of science as a social phenomena, then such reviews can serve a larger purpose, such as by creating more awareness. Given that CFS and ME are among the most neglected diseases in terms of research funding (by a magnitude of order) vs burden of disease, such awareness is sorely lacking.
 

Ecoclimber

Senior Member
Messages
1,011
Critical critique of the author's background is both necessary and justified, to establish if the author of the research article, has both the proper scientific background and education on the subject matter contained within the article. Otherwise, the article can be misleading to members within the ME/CFS patient community.

Notwithstanding, numerous allegations have been made against the credentials or lack thereof, of scientists who DO have the scientific background on the subject matter contained within research articles which they just published.



The legitimacy of Lipkin's credentials and background have been called into question many times on this forum with regard to the ongoing Lipkin research study concerning XMRV as well as other XMRV research from other top scientists across the field of retrovirology research. I don't feel it is necessary to cite those posts or threads.

In addition, my response also addressed issues and concerns within the article authored by Gerwyn Morris.

Eco
 

alex3619

Senior Member
Messages
13,810
Location
Logan, Queensland, Australia
I'm happy to see I'm not the only one bothered by the alleged relapsing/remitting nature.

A little remitting wouldn't go amiss from time to time.

I have wondered about the relapsing/remitting nature for a long time. I suspect they are talking about how symptoms wax and wane for the most part. Sure a good percentage go into recovery and then relapse later - but its hardly the norm. Waxing and waning symptoms, particularly if a PWME has a well managed condition, may give rise to the notion that the illness has retreated. For example, after more than a decade of pacing I am frequently not exhausted - it only happens if I push over my limit (though other symptoms are not so forgiving). I wonder if this is not the source of much of the confusion?

Bye, Alex
 

Mula

Senior Member
Messages
131
No, there's still no gun. Although the analogy might not be exact, and what we really need is a way to extract the bullet. Either way, the paper coalesces some of the existing data in a particular way, but doesn't really provide anything new. We already know everything the paper is stating, and it hasn't led to a treatment. I doubt this paper will lead to that, either, but go on believing it will if it helps you get through your day. I'll go back to waiting for a legitimate breakthrough.

If it was known then why were you unfamiliar with the model? It is not derived from MECFS studies alone. A line taking the known abnormalities has been marked to take others from MECFS through branches of research which have not been applied to MECFS.

"Figure 1 shows the effects of pathogens on the immune system leading to immuno-inflammatory cascades."
 

Mula

Senior Member
Messages
131
I have wondered about the relapsing/remitting nature for a long time. I suspect they are talking about how symptoms wax and wane for the most part. Sure a good percentage go into recovery and then relapse later - but its hardly the norm. Waxing and waning symptoms, particularly if a PWME has a well managed condition, may give rise to the notion that the illness has retreated. For example, after more than a decade of pacing I am frequently not exhausted - it only happens if I push over my limit (though other symptoms are not so forgiving). I wonder if this is not the source of much of the confusion?

Bye, Alex

That would be one explanation I could agree with.

Has anyone heard of Srinivasa Ramanujan?
 

Ecoclimber

Senior Member
Messages
1,011
If it was known then why were you unfamiliar with the model? It is not derived from MECFS studies alone. A line taking the known abnormalities has been marked to take others from MECFS through branches of research which have not been applied to MECFS.

"Figure 1 shows the effects of pathogens on the immune system leading to immuno-inflammatory cascades."

It negates the mutual exclusivity of a retroviral etiological cause since initial infections are never cleared in association with a retrovirus or HGRV infections especially when other viral or bacterial pathogens are considered.

Eco
 

Mula

Senior Member
Messages
131
It negates the mutual exclusivity of a retroviral etiological cause since initial infections are never cleared in association with a retrovirus or HGRV infections especially when other viral or bacterial pathogens are considered.

Eco

There is no necessity that an infection be cleared and the authors are saying there are multiple pathogens.

"Our model proposes that initial infection and immune activation caused by a number of possible pathogens leads to a state of chronic peripheral immune activation driven by activated O&NS pathways that lead to progressive damage of self epitopes even when the initial infection has been cleared."
 

Ecoclimber

Senior Member
Messages
1,011
There is no necessity that an infection be cleared and the authors are saying there are multiple pathogens.

"Our model proposes that initial infection and immune activation caused by a number of possible pathogens leads to a state of chronic peripheral immune activation driven by activated O&NS pathways that lead to progressive damage of self epitopes even when the initial infection has been cleared."

"even when the initial infection has been cleared." Maybe, I am missing your point or you're missing mine. If there is a retroviral etiological cause, then the conclusion on the premise is false. Infections are not cleared. In addition, there is no scientific proof or validation to support the hypotheses made in this article even though copious references are made.

We agree to disagree but if you find the article helpful then go for it. I don't prefer the channeling while the jury is still out with regards to the cause of ME/CFS nor the diagnostic of biomarkers concerning this illness when there has been absolutely no conclusive proof for such a claim. Research is still ongoing as to reliable bio-markers for this disease which have not been definitively stated to date.

Eco
 

adreno

PR activist
Messages
4,841
"Our model proposes that initial infection and immune activation caused by a number of possible pathogens leads to a state of chronic peripheral immune activation driven by activated O&NS pathways that lead to progressive damage of self epitopes even when the initial infection has been cleared."
Is this news? Basically that is what has been termed "post viral/infectious syndrome" for decades.
 

Mula

Senior Member
Messages
131
"even when the initial infection has been cleared." Maybe, I am missing your point or you're missing mine. If there is a retroviral etiological cause, then the conclusion on the premise is false. Infections are not cleared. In addition, there is no scientific proof or validation to support the hypotheses made in this article even though copious references are made.

We agree to disagree but if you find the article helpful then go for it. I don't prefer the channeling while the jury is still out with regards to the cause of ME/CFS nor the diagnostic of biomarkers concerning this illness when there has been absolutely no conclusive proof for such a claim. Research is still ongoing as to reliable bio-markers for this disease which have not been definitively stated to date.

Eco
The quote begins with "even when" as an alternative to your view which would be only when. The model is for multiple pathogens taking from work that is validated in MECFS and separate branches of medicine. The next stage is to subject the model to testing, which you do with all studies. If anyone comes up with another model we can test that too. It took more than fifty years for this one to be built.

Post viral fatigue is a fatigue following an infection which the model does not resemble.
 

WillowJ

คภภเє ɠรค๓թєl
Messages
4,940
Location
WA, USA
There is a rather dismaying (to me) repetition of the word "may" that runs right through the argument.

This is standard science speak. Many good scientists phrase even things they are more confident about in tentative language, because science is a dynamic knowledge base. Everything is subject to being challenged with new evidence (theoretically; some things have become dogma and are not subject to scrutiny even when scrutiny is due).

Also it is a model. Requires testing, and it's right that they should be tentative about this, at this point in time.
 

WillowJ

คภภเє ɠรค๓թєl
Messages
4,940
Location
WA, USA
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3166239/?tool=pubmed
Neurosci Med. Author manuscript; available in PMC 2011 September 2.
Published in final edited form as:
Neurosci Med. 2011 March 1; 2(1): 14–27.
doi: 10.4236/nm.2011.21003
PMCID: PMC3166239
NIHMSID: NIHMS267944
An Etiological Model for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Leonard A. Jason,* Matthew Sorenson, Nicole Porter, and Natalie Belkairous
Abstract

Kindling might represent a heuristic model for understanding the etiology of Myalgic Encephalomyelitis/chronic fatigue syndrome (ME/CFS). Kindling occurs when an organism is exposed repeatedly to an initially sub-threshold stimulus resulting in hypersensitivity and spontaneous seizure-like activity.

Among patients with ME/CFS, chronically repeated low-intensity stimulation due to an infectious illness might cause kindling of the limbic-hypothalamic-pituitary axis.

Kindling might also occur by high-intensity stimulation (e.g., brain trauma) of the limbic-hypothalamic-pituitary axis. Once this system is charged or kindled, it can sustain a high level of arousal with little or no external stimulus and eventually this could lead to hypocortisolism.

Seizure activity may spread to adjacent structures of the limbic-hypothalamic-pituitary axis in the brain, which might be responsible for the varied symptoms that occur among patients with ME/CFS.

In addition, kindling may also be responsible for high levels of oxidative stress, which has been found in patients with ME/CFS.

Johnson and DeLuca (2005) concluded that functional neuroimaging studies among patients with ME/CFS generally show hypometabolism in the frontal lobes and ganglia [22].

Neary et al. (2008) tested whether patients with ME/CFS have reduced oxygen delivery to the brain during and exercise challenge. They found that in addition to significant exercise intolerance, patients in comparison to controls evidenced reduced prefrontal oxygenation, suggesting altered cerebral oxygenation and blood volume in the brain [68].

Clearly, both kindling and oxidative stress could be implicated in these findings. Abnormal findings in different regions of the brain may be due to kindling that occurs in a secondary manner, separate from the initial kindling. These secondary sites could then affect different parts of the brain.
 

barbc56

Senior Member
Messages
3,657
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.

Thanks. this is spot on and sums up many of the problems/issues of the last three years. People are going with the scientiest not the science.

Barb C. :>)
 

Enid

Senior Member
Messages
3,309
Location
UK
Who is forcing any theory - all this (and always has been bringing together scientific findings into understanding ME). OK - models - part of it all. I assume we all here have dispensed with psycho mumbo jumbos who have tried their best to keep in their creepy ignorance - let's celebrate this. To all who been through the very worst - this is clearly neuro-immune.

This isn't who is in or out (much science in Maes papers building on previous researches) - takes brains/theorists too. Though I suspect Prof Maes (a scientist) would prefer to stick with science - he is a Doc but thinks too.
 

Sing

Senior Member
Messages
1,782
Location
New England
Thanks, Enid. Yeah, I think appreciating this concise model as a device to approach further thinking and research makes a lot of sense. It is a summary, a hypothesis about possible interrelationships among findings which have been already established, is my view. Science seems like a creative improvisation using facts already established in search of other facts not yet established. To bash it or its proponents on the head for lack of finished perfection with all details neatly accounted for and stowed away is not helpful. Let's review with the goal of moving research forward rather than knocking down everyone who doesn't have all the answers in place yet.
 

George

waitin' fer rabbits
Messages
853
Location
South Texas
I'm happy to see I'm not the only one bothered by the alleged relapsing/remitting nature.

A little remitting wouldn't go amiss from time to time.

I wonder what the percentage of "Relapsing/Remitting" patients are in the overall ME/CFS population? Do we have a thread on that somewhere? Or a poll? Because I think it's a very good question.

I'm with you other than the odd day that I can manage to do my laundry AND take a bath my illness is chronic rather than relapsing/remitting and I would love to have a whole week that I could do two whole things in a day instead of one. I'm thinking anybody who has to "smell me" would be happy for a little "remitting" for as well. (big grins)