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

[Jonathan Edwards]

"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 wish it were so. My more cynical view would be that it will not. Those who try to keep up with science will think 'nothing much nailed then'. Those who do not may well take the message as:

"Remember those ivory tower academic colleagues of yours that you thought were attention seeking or just plain nuts?"

"Well, they're still around."
!!

 

[Peter]

I wish it were so. My more cynical view would be that it will not. Those who try to keep up with science will think 'nothing much nailed then'. Those who do not may well take the message as:

"Remember those ivory tower academic colleagues of yours that you thought were attention seeking or just plain nuts?"

"Well, they're still around."
!!

Hehe. Like the frankness and your valuable sort of devils advocate perspective on different matters. Not referring to Komaroff in particular, but more in general, it clearly is a problem when overselling findings and results. To some extent that may also be a problem on the biomedical side also, but it’s surely a tenfold on the BPS-side. There are exceptions, but as a main rule, I find the researchers on the biomedical side to be somewhat more sober when presenting. But at this point in time it is counterproductive to say this is how it is, this is what pwme are.

I like that sort of sober list. Could probably add another few points to.

In hindsight of history, it is not at all strange that patients and researchers speak and presents like they do, as trying to weigh in on all the psycobabble. Knowing the history, it would be unwise not to understand and accept that patients and advocates do what they do, but if it is strategic is a different question. It is probably so muddled, patients and organizations so desperate that there are little room for strategy.

Except from a whole lot of more money, that from what we know from medical history and basic common sense, would increase the chance of substantial progress significantly, I guess we have to keep pushing on the science and non-science, the lack of methodology. Getting doctors and others outside to take a closer look at the “truth”.

Without money, little progress. We claim to hope, but it’s a bit frustrating hearing now it is happening, now it is happening, the next five years, next two years and so on. The fact is nothing or very little will happen before funding. And unfortunately, no one can say in a convincing way, that this is the pathology of ME, this is what we found and know.

Guess I’ll have to put this negative on the account of what Kyle McNease calls “Rat Bastard Monday”.

https://www.healthrising.org/blog/2...-of-all-part-iii-didnt-life-know-i-had-plans/

 

[Sunshine3]

Well one thing we haven't had in the past is the real potential of a proper diagnostic test.. The nanoneedle. This could be the game changer. I have big hopes for all the Collaborative work OMF are doing now...a long road but it's looking more promising than 10 years ago.

 

[Snow Leopard]

Well one thing we haven't had in the past is the real potential of a proper diagnostic test.. The nanoneedle. This could be the game changer. I have big hopes for all the Collaborative work OMF are doing now...a long road but it's looking more promising than 10 years ago.

The nanoneedle paper is only suggestive evidence - the samples were not blinded, we don't know what was causing the effect, the study has not been replicated. It's too little evidence to pin any hopes on at this point in time.

 

[Sunshine3]

The nanoneedle paper is only suggestive evidence - the samples were not blinded, we don't know what was causing the effect, the study has not been replicated. It's too little evidence to pin any hopes on at this point in time.

I don't get the need to constantly put down the positives. The testing on the nanoneedle has been 100 percent accurate so far. Ron Davis is optimistic.. I will join him.

 

[Mithriel]

I think you may mean "epidemic neuromyasthenia," not "epidemic neurasthenia."]

You're right, I was getting confused because SW and mates insisted the ME was actually neurasthenia as seen in Victorian times.

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.

I can only say that Ramsay was still seeing new patients and working to get better treatment for them in 1984 when I was diagnosed (16 years after I became ill!) he felt what he was seeing was ME as his patients had developed in 1955, and there were still many of them involved in the ME community at that time.

Those of us who are still here fit the ICC which share many of the same points as we felt were important in 1984. I have only felt a disconnect when they brought in CFS - I never felt fatigue, but fatiguability. I do not recognise myself in any of the BPS descriptions of the disease and I was very disappointed by the SEID definition as it is so wimpy and leaves out so many important things.

Survivors of the 1955 epidemic were still involved in the ME community until very recently and I have never heard that they felt they did not have ICC ME.

 

[Webdog]

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.

In the 1999, Komaroff delivered a presentation to the Medical Board of California, recommending GET and CBT for "CFS". It's still on their website.

I've asked both the Medical Board of California and Komaroff to update the "CFS" content on the website, or to remove it. Didn't get a reply.

http://www.mbc.ca.gov/Publications/Newsletters/action_report_1999_01.pdf

The report also says, "The Medical Board will continue to work with the Department of Health Services and will provide additional information in these pages as more becomes available."

However, the California Department of Health Services no longer exists, and its replacements, the California Department of Public Health and the California Department of Managed Healthcare expressed zero interest when I inquired about providing "additional information...as more becomes available" (specifically updating their information after the IOM report).

 

[DokaGirl]

I think you're right @Forbin, about the audience aimed at with the article. Physicians who know little about ME, have never heard of it, or have discounted their patients with this disease.

I recently met a 3rd year med student who had never heard of ME. Still! Still, med schools are not teaching about ME. Unless of course they are still using the derisive name "cfs".

I had gradual onset ME starting in 1985. By the time I was diagnosed, the term "cfs" was well established.

I am familiar with the attitude or practise of not naming an illness, nor painful condition, nor thoroughly testing it, as patients may become fixated with the health problem if they know more about it.
We are not in kindergarten!

And what if further testing might find a different result - something life threatening? Instead, some physicians make an educated guess based on symptoms, and/or cursory testing that the
patient doesn't need further investigation.
Examples I can cite where this gamble has not panned out are: 1 - liver failure; 1- stomach cancer; 1- leukemia. The first diagnosed with "cfs"; the other two told it was nothing or just stress. Treatment was significantly delayed, or not applied, and all died.

 

[Jacqz]

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.

So do you think the NCNED research findings at Griffith University (Queensland) in Oz are nothing to write home about?? I thought they were trying to find someone to trial drugs re calcium ion channels?
https://www.griffith.edu.au/__data/...y-and-Emerging-Diseases-Publications.doc.docx

 

[Hutan]

Welcome to the forum @Jacqz

Here's a recent thread on the work by the NCNED team. The studies are very small, so there's a feeling that statements are being made with more certainty than is warranted.

 

[Jonathan Edwards]

So do you think the NCNED research findings at Griffith University (Queensland) in Oz are nothing to write home about??

I am afraid I find it a bit like Komaroff - 'we found this, this, this and this'
But as yet I don't see how these findings are supposed to help us understand ME, and, as Hutan says, the studies are small and not replicated by other groups.

 

[Simon M]

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

That’s a good list and I’m sure that’s the right way to go to really interest people in the field. I think two other findings are worth adding to the list:

The fact that, consistently, around 80% of patients are women. This is pretty unusual, I think. And while more females receive a mental health diagnosis, I thought that typically this was around 2/3, rather than the 80% same for any CFS.

Also, the remarkable “two peaks“ age profile of the honours, with the first peak in adolescence/early adult hood (with the gender difference emerging during puberty) in the second pic starting in people‘s thirties. It’s hard to explain this finding, but it surely a sign that something unusual is going on here.

Moderator note: This post and two posts responding have been copied to create a new thread, and subsequent posts moved:
ME Epidemiology - prevalence, peak ages of onset and gender ratio

 

[Jonathan Edwards]

I think two other findings are worth adding to the list:

Yes, I agree. I guess the female predominance has been known for a while so is not so much 'progress'. The double peak would follow point 1. I am not sure that it has been replicated across geography but the emergence of gender predominance in adolescents certainly has.

 

[Perrier]

After reading and reflecting on this thread, the obvious unarticulated questions are: and how many more decades will it take to arrive at something meaningful, if these are the results in 20 or 30 years? will it even be in my lifetime? perhaps another 50 years? perhaps more? perhaps it is only in a distant future that the young people will get help? How many generations will be lost at the rate things are going?

John Keats' parents were dead by the time he was diagnosed, and fortunately were spared watching him die but they were not there to assist him either. I think about him non stop. Look how long it took-- (after his death in 1821) to come up with a TB vaccine (developed in the 1920s)--and the first vaccinations took place decades later in the post war period in the 1950s. This all adds up to 130 years between his death and treatment.

If we have, as it is indicated here, not much progress in 30 years, this means decades upon decades to go. Someone, please tell me that I have it all wrong.

PS: and please let us not say that this illness does not bring death: it brings a living death, for that is what lying in a bed for years is.

 

[Jonathan Edwards]

If we have, as it is indicated here, not much progress in 30 years, this means decades upon decades to go. Someone, please tell me that I have it all wrong.

Fortunately, it does not work like that. When I entered rheumatology in 1973 there were no treatments for rheumatoid arthritis really worth bothering with. By 2000 we had a range of powerful treatments that can keep almost everyone with RA well all the time, even if there are practical difficulties to negotiate. Most of the treatments had been developed already for something else. I does not necessarily take that long from working out what the treatment should be to getting it to work. For me with rituximab it was 3 years. Pretty much all the new treatments went from lightbulb moment to reality in a time frame of about ten years 1990-2000.

It is never possible to know when the lightbulb moment will occur. So how long it has taken so far tells us nothing about how long it will take from now.

And very often what slows things up is people thinking they know what the answer should be when they don't and making the entire research community follow blind alleys. Rather than have an article saying we know there are lots of abnormalities in ME I think it would be better to emphasise that the question is still wide open. If people think lots has been worked out they will be happy to sit back and watch further progress. If they understand that there is a serious illness that is still a complete mystery they may be more likely to have a crack at working out where to start.

Interestingly, the treatment for TB was already known and under way in 1821, although not put into effective practice until the early twentieth century, which is when TB started to disappear. Vaccination came along after the problem was sorted. Even anti-TB drugs like streptomycin mostly cleared up the few remaining cases. The treatment was isolation - sending people with open infectious TB to sanatoria. It did not cure their TB but it prevented ten more people getting it. The continuing infection of the majority of the population with TB was probably due to a rather small number of people with progressive open disease coughing in public.

The solution to ME may come completely from left field at any time.

 

[ME/CFS Skeptic]

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.

I think there have only been decent epidemiological studies in the US and the UK. A study on the European mainland, by Euromene for example, would be useful.

more females receive a mental health diagnosis, I thought that typically this was around 2/3, rather than the 80% same for any CFS.

I think there's only one study that reported 80% of ME/CFS patients being female; the Wichita, Kansas study (Reyes et al. 2003) which reported 83,2%. Jason et al. said it was more around 70% (23/32) and the study by Nacul in the UK found a much lower figure of around 50%. So I don't know if there's clear differences between the % being female in mental health diagnoses.

the remarkable “two peaks“ age profile of the honours, with the first peak in adolescence/early adult hood (with the gender difference emerging during puberty) in the second pic starting in people‘s thirties. It’s hard to explain this finding, but it surely a sign that something unusual is going on here.

I thought that was just one study (Bakken et al. 2014). Does it show in other publications as well?

I would add another finding that has been confirmed by multiple research teams: the prevalence of ME/CFS is increased following infections such as EBV-infection. I think Wessely and others initially thought this was a spurious finding and that ME/CFS patients just wanted to make sense of their symptoms by making that connection with infections. But Peter Whites study showed that the prevalence of ME/CFS increased following EBV-infection while this was not the case for mood disorders such as depression. That seems like an important finding to me.

 

[Medfeb]

I think there have only been decent epidemiological studies in the US and the UK. A study on the European mainland, by Euromene for example, would be useful.

Jason has done some good epi studies but the epi studies by the CDC have been awful. Their 2007 epi study reported a prevalence of 2.54% using the Reeves/Empiric criteria (10 fold over CDC's estimate in its 2003 epi study) that the IOM discredited for including an overrepresentation of patients with depression and PTSD. Unfortunately, a number of other papers have flowed out of that study that have inappropriately colored the narrative about the disease (e.g. childhood trauma causing 6 fold increase in risk, maladaptive coping skills, etc) and also reached conclusions such as premature telomere attrition that IMO need to be looked at more carefully because of the patient selection issues with the study.

 

[Perrier]

I am afraid I find it a bit like Komaroff - 'we found this, this, this and this'
But as yet I don't see how these findings are supposed to help us understand ME, and, as Hutan says, the studies are small and not replicated by other groups.

You are indeed correct: 'we found this, this, this, and this.' Then in three months at another conference, again: there is this and this and that.

Patients sit at the edge of their seats, and the real problem is never seized.

But worst of all: I do not see any time line. In other fields, folks work with time lines, or certainly try to. I guess, I will be told, research doesn't work that way.

 

[DokaGirl]

@Medfeb, interesting you note a CDC study in the same era as this one I recently came across, that includes one of the same authors:

"U.S. healthcare providers' knowledge, attitudes, beliefs, and perceptions concerning Chronic Fatigue Syndrome
Results
Healthcare providers in both samples were aware of CFS and exhibited a high level of knowledge. Overall, 96% of respondents in the DocStyles (probability) sample had heard about CFS. Healthcare providers in the conference (convenience) sample demonstrated good KAB scores; physicians' scores were highest on KAB scales and lowest in perception. Nurses' scores were lowest in knowledge. More than 40% of physicians reported ever giving a CFS diagnosis and in the DocStyles (probability) sample more than 80% of physicians correctly identified CFS symptoms. Physicians reported professional journals, the Internet, and continuing education programs as the top 3 sources from which they obtain CFS information."

https://bmcfampract.biomedcentral.com/articles/10.1186/1471-2296-11-28

 

[Perrier]

I wish I had a clue. Flinging a few things in



That lots of these issues impact liver and @ Mario vitali may be onto something

I don't think it is any one thing ( or else it should have been found) it is an enigma code of combinations

If that is the case, how can it be solved?. If it is some tragic combination of genetics, birth defects, hormones, environment, toxicity, stress, etc etc, all these variations will be different in each person.

This is all getting very dark.