JAMA -"Advances in understanding the Pathophysiology of Chronic Fatigue Syndrome" by Anthony Komaroff

Tell us what you know about that. The forbidding, that is. We keep learning new things. Everything has a cause.

 

Hope is better than optimism.

 

I was just referencing what other people on the board have said about the NEJM. I was surprised when I read it. I don't know if it's an official stance of the NEJM or just a de facto policy.

 

I too have had the experience of bringing research to health professionals who roll their eyes. Maybe at first they're interested, but only at first. How disappointing and sad for physicians to see patients' research on their own disease as evidence they have a somatization disorder. But, I can definitely see this happening. Some physicians might see this as perseveration, and not getting on with life, the treatment they offer, or whatever. Governments give us the message - pay attention to your health - follow government food guides, exercise etc. However, we also get the opposite message - don't focus on your health, that is an psychological abnormality. What a fine balance we have to tread.

As regards the down regulation of the HPA axis, I recall info of this nature in vintage CDC and NIH booklets from the early 1990s. I can't recall anything further on this.

Thank you for links to these interesting articles. I will have a read through.

As for one article that gave me hope until I could see no great change in funding, or indeed much of any funding coming down the track, was the 2016 statement by the Canadian Institutes of Health Research (the research-funding branch of Health Canada):

"With regards to Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), CIHR – IMHA is committed to supporting high-calibre research that will contribute to the evidence base and develop capacity in this field. ME/CFS is a chronic, complex, multisystem illness. Preliminary research has linked it with disturbances in energy metabolism, immunology, brain and nervous system functioning, cardiovascular functioning, epigenetics, and the microbiome. More research is needed to determine the underlying pathology of ME/CFS, advance understandings of its relationship with overlapping conditions such as Fibromyalgia, and establish effective treatments. An estimated 800,000 Canadians are affected by ME/CFS, Fibromyalgia, or both. The National Institutes of Health (NIH) in the United States and the Stafford Fox Medical Research Foundation in Australia are ramping up investment in biomarker discovery, diagnostic testing, and patient subgrouping for ME/CFS. You will see in this newsletter that CIHR-IMHA recently launched a series of Catalyst Grants, with two dedicated to ME/CFS. These grants are intended to serve as seed money to support research activities that represent a first step towards the pursuit of more comprehensive funding opportunities. We are also seeking to engage in partnerships with other funding agencies to advance the ME/CFS research agenda. This is a fascinating area of research in which investigators from many disciplines have the potential to make groundbreaking contributions."http://www.cihr-irsc.gc.ca/e/50100.html

Thanks again for the links.

 

Komaroff is editor for UpToDate's ME/CFS section, which as recently as 2018 conflated ME/CFS with fatigue, failed to recognize the methodological flaws of PACE, and recommended GET/CBT.

UpToDate has improved somewhat, but still had not completely rejected PACE as of my subscription expiration in Dec 2018.

Someone should ask Komaroff directly his views on PACE. Komaroff never replied to my emails (only the UpToDate deputy editor did).

Clinical features and diagnosis of myalgic encephalomyelitis/chronic fatigue syndrome
https://www.uptodate.com/contents/c...ic-encephalomyelitis-chronic-fatigue-syndrome

Treatment of myalgic encephalomyelitis/chronic fatigue syndrome
https://www.uptodate.com/contents/treatment-of-myalgic-encephalomyelitis-chronic-fatigue-syndrome

 

Well said! Thank you for being my voice here too.

 

After reading this thread, am I to conclude that ME research is still rather paltry? Still in real infancy? Still really floundering? Still without substance? still without real hope?

what are we to tell those lying in dark rooms as quietly as statues, praying for relief?

There was recently another suicide, in Scandinavia, a former athlete.

Is there really nothing promising from the researchers? Are they just trying to validate and to continue obtaining their grants?

Does this mean another half century will go by with nothing much?

 

http://www.meaction.net/wp-content/uploads/2019/06/19_MEA_Revised_2019_Research_Summary_190610.pdf

are all these studies also not worth much?

how utterly devastating all this is.

 

I personally meant that the JAMA article was overstating what we know about ME/CFS, that very little has been demonstrated yet. That doesn't mean that there's nothing promising in the pipeline. I think there's some progress over the years in the quality of research, with big names such as Ronald Davis and Ian Lipkin involved, the ME/CFS centres in the US and the biobank in the UK etc. I certainly hope that the quality and quantity of ME/CFS research will keep improving until one day we'll reach a breakthrough and the medical world (including pharmaceutical companies) will wake up to fight this illness.

 

for clarity, i want to confirm whether you mean 1 or 2 here.

1) initial *infection* -- i.e. the individual cases' disease progression from the profile found in the description of an epidemic (which i said does not feel like meicc) into meicc?

vs.

2) early historical *epidemics* do not look like meicc (probably not even after disease progression) but later epidemics and sporadic cases look like meicc.

if you mean 1, that is what intrigues me the most! i'd be interested to know if we have good evidence that specified epidemics' victims become meicc victims over time.

this is also why i raised the topic of ltfu. for a serious disease that knocks victims down for lifetimes, i want lots and lots of ltfu.

lots of victims from royal free and incilne village and many more outbreaks were still sick for many many years after their respective epidemics. aside from bell, are there sheaves and sheaves of good work on this?

is it standard practice to have seemingly so little ltfu on epidemics? or am i missing the mountains of good work?

 

You get what you pay for. Chronic underfunding and absence of leadership guarantee this slow crawl.

It's simply advancing at a pace comparable to what current funding allows. Current funding is on the order of 1-2% of what it should be so to make one year's worth of fully-funded research requires 50-100 years. Fortunately thanks to technological progress this is more on the order of 10-15 but nonetheless the pace we are seeing is exactly what is expected by deliberately rejecting adequate funding and urgency.

Technological progress and advances in relevant areas are the X-factor when funding isn't there so the only thing that matters is that expertise is building up slowly and will be able to catch on when it happens.

Failure is a choice; it just isn't ours, but as patients we don't matter in the process so the best we can do is continue doing what we're doing. If we could affect the outcome any more than this we would would already have.

 

Thanks for that! I knew about that article but had missed it was in NEJM

 

I believe Byron Hyde said he has interviewed survivors of every epidemic in the 20th century.

Also didn't @dave30th interview survivors of the Royal Free outbreak?

 

I seem to recall a paper by Wessely on the subject possibly from the 1990s but cannot find it.

 

I think an important message in this article is there is something biologically amiss for pwME.

And, that "most abnormalities are not detected by standard laboratory tests."

I had another rinse and repeat experience of this a few months ago, when a physician, having read my basic lab test results said I"m actually quite healthy.

I kept in my figurative pocket the interesting and revealing results from tests I have done that reflect some of Dr. Lily Chu's, and other ME experts' recommended tests.

I chose not to tell this doctor, as the results would probably be dismissed, and I would be seen as someone much too focused on my health.

However, when very few around you believe you, including authority figures, proof is often sought for confirmation, and a comeback to these naysayers.

 

Hi @MSEsperanza - re HPA axis down regulation - under Point 4 in the article link below: "Basal hypocortisolism was first reported in CFS in 1981.":

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4045534/

Interesting, this discovery goes that far back. I would have said a few years later.

1981 is even before the Lake Tahoe outbreak.

 

Yes, you get what you pay for. During the aids crisis Hollywood was even on board to help. The whole world as on alert. And with this, and the utterly stupid ‘fatigue’ name it’s hard to get attention. Plus, the majority are ill women, another negative. In aids it was men. At this rate, I guess all that is left is to pray that one of the researchers cracks it. But they are all over the place, all over the body, and they are not zeroing in. I’m sorry folks, I’m left speechless for the rest of the night once again!

 

Hi @Perrier - if it helps here's a hug.

At least I think it's a hug.

Take care.

 

Just wanted to say quickly that I believe that this article is a part of the effort to grow the research field here in the US. As such, it probably is a bit optimistic to catch the attention of potential researchers. NIH is sticking to its usual funding mechanisms where researchers compete for funding within the various Institutes. Most advocates here think that they should provide more set-aside funding like the RFAs that funded the cooperative research centers, but Dr Collins & his crew want to hold off on additional set-asides to see whether the Centers grow the field and, in my opinion, to see whether breakthrough research indicates a good direction to follow.

Efforts like the NIH young investigators conference and this summary are, in my opinion, small efforts to excite new researchers and grow the field. Dr Komaroff is respected enough in the medical community to attract attention in a journal like JAMA. Respect for him at JAMA is probably why he was allowed to publish this summary in the Viewpoints section.

I agree that unfortunately we are still playing at the edges with this disease. And in my opinion, NIH needs to do much more to move research efforts more quickly. The sad state of the research community is their fault and they need to repair it.

Also I do want to remind you that those of you in the UK were being diagnosed with ME in the early ‘80s and earlier. We over here were being diagnosed with nothing until the Tahoe and Lyndonville outbreaks caught the interest of the medical community. (I became ill in 1983 and have never improved significantly, I was diagnosed with CFS in 1988 shortly after the CDC 1988 definition meeting.)

I think that conflating the histories of the disease in the two countries can become confusing. Dr Komaroff is speaking about our timeline; yours is quite different.

 

I do not want to destroy hope and I don't think it would be right to say there has been no progress and no reason for hope that there will be much more. But I think the reality of the situation is rather different from what many PWME assume.

Those who support the BPS model dismiss biomedical studies not because they are small and not replicated so much as because they really don't look likely ever to amount to much and are consistently hyped. Moreover, nobody admits they were wrong when they find the results are not repeatable. And you do not have to be a BPS enthusiast to think that. I have a lot of very reasonable colleagues with no special commitment to what ME is about who will look at the list of studies flagged up by Komaroff and say to themselves - 'well that looks like going nowhere much'. Science isn't about how many studies you have done. It is about fitting things into a single solid, plausible story.

The way to bring physicians and researchers on board, to my mind, would be to write something very different. It would start with admitting that nothing substantive has yet been identified that indicates what the causal mechanism of ME really is. But it would go on to list the real achievements of the last ten years. Those for me would be things like:

1. Epidemiological studies have shown that there is a consistent cohort of people, independent of geography, who suffer from a well defined clinical syndrome that deserves to be distinguished by the name ME/CFS.
2. Re-analysis of trials of therapist-delivered treatments has established that a psychological model of disease perpetuation is not supported and made very implausible.
3. A population based ME Biobank has been set up and is distributing samples worldwide.
4. Well executed trials have shown that B cell depletion is not a useful treatment.
5. Immunological and microbiological studies have indicated that it is very unlikely that ME causation relates to an NK defect allowing reactivation of, or repeated infection with, viruses.
6. A number of studies indicate that mitochondrial metabolic pathways may be diverted, perhaps involving amino acids, although the exact nature of any shift has not yet been identified.
7. Preliminary genetic screening and epidemiological studies have suggested that there may be a significant heritable aspect to ME. Plans are being developed to set up more powerful genetic screening studies.
8. A number of studies are focusing on the key feature of post exertion malaise and beginning to clarify the physiological changes that can be documented.

That is just off the top of my head. If I was attending a general physician education meeting and someone flagged up that sort of list in 2010 (before I ever thought about ME) I might think 'maybe this is important and interesting after all'. If the speaker had gone through a list saying there is lots of evidence blah blah I would have thought the opposite.