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

Thank you very much for your comments and list, of more promising findings, as well as noting negative results @Jonathan Edwards. It is helpful, and hopeful to see this list.

 

I am now a participant in a genetics study .

 

IIRC the ‘benign’ was only to distinguish it from the polio myelitis of the time, and signified it wasn’t associated with increased mortality.

 

Why then do they believe in the psychological findings that have similar flaws? Small sample sizes, weak effect sizes, poor sensitivity and specificity, (often) lack of correction for multiple outcomes and so on?

 

I think you be making a category error. There is in fact no requirement for consistency of approach.

 

Articles making these sorts of false and exaggerated claims are very unhelpful IMO. Nothing is known about the underlying biology of ME/CFS today, nothing whatsoever. The literature is a nuclear wasteland of one-off unreplicated results. If you had gone into a coma 35 years ago and woken up today you would have missed out on zero replicated findings and zero evidence-based treatments.

 

My balance is still not good, the hand-eye coordenation I trained with simple computer games.

 

@Sean, good idea - the effects of PEM on basic activities like coordination. If I over stretch myself, I get clumsy, and my thinking gets fuzzy. I can't figure out, or remember how to do things I can do when I'm not in PEM. Simple things.

We still need so much research done!

 

I understand that reaction. Unfortunately that was my reaction after the recent NIH conference. I had 2 reactions - joy at seeing all of those researchers together at last and the feeling that we have a very long way to go.

Dr Komaroff’s summary was taken from that meeting. He’s been doing summaries of most of the meetings since the ‘90s and will be on the next CDC call summarizing the work again.

My guess is that he focused on the research from that meeting in part to signal that NIH is open to individual research proposals concerning ME/CFS even in the absence of set-aside funding. Broadening the field is essential.

Your list is a very good one. We have come a long way, especially because all of the work presented at NIH was biomedical research - no psychobabble. It’s just a much longer struggle than I would have hoped. So much time has been wasted.

 

Interesting points @Wilhelmina Jenkins. Thank you.

I think this article may convey some basic concepts to clinicians and researchers. A couple of which are: there is something wrong biologically, and standard lab tests usually don't find anything wrong.

And, as you say, it may interest researchers in some of these areas.

Your comments about the differences in diagnoses, or lack thereof in North America until 1988, got me wondering what case definition was used in the UK prior to 1988. Ramsay? Oxford came about in 1990, or '91.

 

What do you think you/we could do that we are not already doing to try to attract more of the right sort of brains to take an interest in trying to crack this problem? Clearly all the ongoing efforts to expose the BPS falsehoods are helping, as are efforts to try to improve the accuracy and relevance of information disseminated by charities and organisations, but what more can we do? How, for instance, might we attract more retired physicians like you, with appropriate knowledge and no COIs, to get involved? Are you a unique species? Why have you taken it up when so few others have? Historically, hard problems have not deterred the best minds from trying to solve them – they have attracted them (as well as a lot of crackpots!) Is it all because of the false BPS narratives – the belief that the problem has been solved, that there is no real problem to be solved, or that ME research is fraught with danger?

Although I know you disagree – and I understand the arguments against it – but I think ring-fencing substantial public funds for high-quality research would help. But what more can we do?

 

Prior to the 1984 outbreaks in Tahoe and Lyndonville, people were just not being diagnosed here. Including me. Ramsey wasn’t used here, with a few possible exceptions.

After the outbreaks, information became fairly widespread. Initially most people called the disease Chronic Epstein Barr Virus, but since the relationship with EBV was not proven, the CDC went with CFS.

Patients and some doctors pushed for chronic fatigue & immune dysfunction syndrome (CFIDS), but it wasn’t accepted by the medical community.

Before the 1988 meeting, there wasn’t an official definition used here. What was happening in the UK was known, but there was debate initially about whether we were looking at the same disease.

I often wonder how the history might have been different had the 1984 outbreaks not occurred.

For historical comparison, the people who became ill in 1956 in the Punta Gorda outbreak never got a good explanation of their disease. They were interviewed in the film I Remember Me - it’s on YouTube if you haven’t seem it.

 

It's what they believe, therefore it must be right. It's no more complicated than that, an article of faith. This is a group that will deny and reject everything, including a cure, for the rest of their lives. They will simply move the goalposts to saying they were focused on a subset and that they will keep on working on that psychosomatic subset but nonetheless they were right all along and everyone else is wrong.

Ideology is one hell of a drug. The psychosocial alternative model of medicine is irrational, nothing rational will break it. It's no coincidence that the body of research on the psychosocial model of ME is nearly identical to the psychosocial research in peptic ulcers, it was simply recycled onto a different target. They will likely move on to the rest of the MUS list until it dwindles down and this failed model fades into obscurity, with no one to blame because it was all an honest mistake now move along nothing to see here no one's responsible.

 

Everything comes down to funding. It's the only important factor here. If the money had been there, we would already have significant results, centers of expertise, a professional certifying board, experts with decades of meaningful experience. That and partnership with the patient community to make sure the funds are properly used, but the money comes first.

Nothing else will have 1/100th the impact as guaranteed funding. Which is why the standard approach won't work, because it specifically avoids setting aside funding to kickstart a field. Decades of failure make that very clear.

If we can figure out how to bring money, most likely from wealthy donors with a personal stake in the outcome, we would solve half the problem. Funding to research is like water to crops. No amount of other efforts will make up for dry soil.

 

I think that helps to make the point that I made that small study size is not the issue.

Otherwise I would have thought the answer was obvious - personal kudos and £££.

 

I can understand the skepticism the article has generated. And I agree that we have lots of unreplicated studies and don't yet have a handle on the actual cause of the disease.

But I'd disagree that we don't know anything about the underlying biology - for instance, what about CPET studies replicated by multiple groups have demonstrated changes in aerobic metabolism associated with the symptom of PEM that are not seen in a number of other chronic diseases. (relates to #6 and #8 on Jonathan Edwards' list)

Admittedly, we don't know how that fits which reports of e.g. neurological and immunological changes/impairment. But in the US, this test is used not only in research but is also accepted by the Social Security Administration to demonstrate functional impairment and has also used in private disability cases.

 

I may be wrong, but the Journal of the American Medical Association (published weekly) seems to be mainly aimed at physicians, some of whom would be researchers, but many of whom would not.

I take Dr. Komaroff's article as intended primarily for physicians who see patients, and that its overall message is:

"Remember those chronically 'fatigued' patients of yours that you thought were depressed, deconditioned, attention seeking, malingering or just plain nuts?"

"Think again."


There are, no doubt, a great many physicians out there who have never questioned their preconceived notions of ME/CFS. An article like this may get them thinking that the landscape has changed.


I also think the article supports many of JAMA's stated key objectives, as outlined here.

 

Yeah - I fell ill in the US in 1983 and my doctors made no mention of "myalgic encephalomyelitis," even though my neurologist's summary contained the words "myalgia" and "possible encephalitis." I was left with the idea I had a poorly defined post-infectious condition which, hopefully, would improve over time.

I think it's quite likely that none of my doctors, including the neurologist, had ever heard of "myalgic encephalomyelitis."

The other possibility is that they did know about it, but thought that giving it a label (especially one they could do nothing about) might impede my chances to recover in the event that my condition was indeed psychological. It was not.

I had tested negative for EBV about 6 weeks after onset, so, even though the Lake Tahoe cases I first read about in 1986 sounded similar to mine, I couldn't be sure they were the the same (as they were being connected to "chronic EBV"). The case descriptions also lacked what was, for me, a key feature of my illness: a severe balance disorder.

A year later, in 1987, I practically fell out of my chair when Dr. Komaroff confirmed on ABC's Nightline that balance disorders were not uncommon in the disease. That's when I knew what I had.

 

That has pretty much been Dr. Komaroff’s message for the past 30 years. I remember back in the ‘90s when he delivered that message to 1/4 of the clinicians in California at once. Still hanging in to get the message out.