Webinar: Massachusetts ME/CFS & FM research update - 23 October 2021

[Hutan]

fogged but i would like to see the misdiagnosis thing clarified.

incidentally, last time i checked, comorbidity could mean many things. an unrelated disease, a partly related disease, a disease related only by something that caused both, a coincidental relation like a common gene defect. thus, i'd find it useful if the word, if used, always be accompanied by a definition in these cases. i hope this was clarified?

Thanks Samuel. I think we really need a detailed report from them on misdiagnoses, and anything that they think clinicians can learn from it. I very much hope that the NIH will make such a report as they much surely know how interested people diagnosed with ME/CFS are in that issue.

Nath made a clear statement that he regarded OI and cognitive issues as part of the illness, rather than comorbidities. I'm pretty sure he wrote that in the 'chat facility' in answer to a question, so there wasn't detail.

it might be good to do formal studies on which symptom variations correlate /within/ individuals. e.g., if your oi and cognitive issues are bad on bad days then they correlate and thus are more likely to be part of the disease.

I have done an informal (but careful) tracking of my symptoms and activity, and OI and cognitive issues are definitely correlated, and I do think they are part of the disease, and not some downstream consequence (e.g. as OI due to long periods spent horizontal would be). But other things, like coldsore flares and ear infections, are also correlated with PEM and I think they are just a consequence of not having enough energy to deal with pathogens efficiently. So, who knows, and yes, the definition of what is and isn't the disease is a bit fuzzy. I agree, we could really use some careful longitudinal studies.

 

[Forbin]

Thanks for your great summary, @Hutan!

 

[Andy]

Michiel has blogged and tweeted a summary of the conference

 

[ME/CFS Skeptic]

We've made a summary of the conference here:
https://mecfsskeptic.com/a-summary-of-the-massachusetts-me-cfs-conference/

 

[Denise]

Here's some of the points that I thought were key, or interesting:

NIH funding for ME/CFS


She made the point a number of times that not many diseases or health conditions have dedicated funding. Mostly, funding depends on NIH receiving good quality research proposals. So, if the NIH received a whole lot of very good proposals for ME/CFS research next year, they could potentially all be funded. She really stressed that more good proposals are needed.

.

Question (to anyone) - would the research being done by the CRCs have been funded by NIH had they been submitted as part of the SEP grant review process (and not been part of the CRCs)?

 

[Denise]

@Hutan said "The selection of patients was very restrictive - they needed to fit CCC, Fukuda and IOM criteria. The requirements including being sick less than 5 years, aged less than 60, and to have an infectious cause documented in medical notes were restrictive."
Just to clarify - not only did study participants meet the CCC, Fukuda and IOM criteria, their inclusion in the study was only okayed after they were adjudicated by a panel of ME experts.

 

[DokaGirl]

The misdiagnosis issue is an absolute must to deal with.

These goof ups show up some medical practitioners as very slack indeed.

They need more than just education about ME!

ETA: I wonder if the misdiagnoses problem will be written up by Dr. Nath et al.

 

[Denise]

The misdiagnosis issue is an absolute must to deal with.


ETA: I wonder if the misdiagnoses problem will be written up by Dr. Nath et al.

I think you should urge Nath to do so! (Please tell him to!)

 

[Andy]

 

[Hutan]

The misdiagnosis issue is an absolute must to deal with.
These goof ups show up some medical practitioners as very slack indeed.
They need more than just education about ME!

I agree about the importance of the misdiagnosis issue, but without the details from the intramural study, we can't really know if the misdiagnoses were 'goof ups'. Given that @Denise said above that people only made it to the study after 'adjudication by a panel of ME experts', it almost certainly wasn't because they were slack. Perhaps people had ME/CFS and something else. Perhaps the doctors who diagnosed ME/CFS don't routinely have access to the kind of investigations that the NIH did. Probably the ME/CFS criteria are not yet specific enough. Whatever, surely there will be things that can be learned that might help some people diagnosed with ME/CFS.

 

[darrellpf]

Also she thinks that long covid has made clear that you can have a postviral illness without realizing it because the onset of symptoms can be delayed. I thought the same: this could explain the apparently non-infectious onset ME/CFS cases.

My suspicion is that most cases are non-infectious (being handled by adaptations) and that infection pushes things over the edge. I would expect to see more long COVID cases over a longer term as people's initial adaptations fail.

When I look back at my history I see a lot of signs of the problems

- tired after eating (high school, nothing found)
- inability to concentrate when sitting (university, diagnosed with "atypical narcolepsy", ritalin)
- uncomfortable standing in a lineup
- constant desire to move to get some exercise ("let me put that glass in the dishwasher for you")
- high blood pressure from mid-twenties (brain perfusion adaptation?)
- jobs that allowed an opportunity to get up from the desk. Any job that was mostly sitting didn't turn out well
- 3 pots of coffee a day for over 10 years (self medication and could still fall asleep...eg, exhaustion)
- spending the entire weekend in recovery and still not having energy on Monday morning.

My mother speaks of my father's love of Sunday shopping, and how she had such trouble with the slow walking and standing (also a huge coffee drinker) She constantly complains about soreness. However, the way she expresses her symptoms probably wouldn't lead a doctor to ME/CFS, though she has dermatomyositis.

With gradual onset, many of the initial symptoms have workarounds ("don't stand in a lineup", "get up and move for a bit"). This tends to delay and hide the problem until it become severe.

 

[DokaGirl]

I agree about the importance of the misdiagnosis issue, but without the details from the intramural study, we can't really know if the misdiagnoses were 'goof ups'. Given that @Denise said above that people only made it to the study after 'adjudication by a panel of ME experts', it almost certainly wasn't because they were slack. Perhaps people had ME/CFS and something else. Perhaps the doctors who diagnosed ME/CFS don't routinely have access to the kind of investigations that the NIH did. Probably the ME/CFS criteria are not yet specific enough. Whatever, surely there will be things that can be learned that might help some people diagnosed with ME/CFS.

Yes, thanks @Hutan. I think I had forgotten, or wasn't originally aware ME experts were diagnosing these people. It does makes sense specialists would do the diagnosing. I was thinking it was their own regular doctors. However, back deep in the recesses of what's left of my memory, I think there may have been something about ME experts....

 

[Denise]

Yes, thanks @Hutan. I think I had forgotten, or wasn't originally aware ME experts were diagnosing these people. It does makes sense specialists would do the diagnosing. I was thinking it was their own regular doctors. However, back deep in the recesses of what's left of my memory, I think there may have been something about ME experts....

The careful adjudication that ID'd PwME further emphasizes the need for education of healthcare professionals at every level and every stage of learning/practice.

 

[Amw66]

The careful adjudication that ID'd PwME further emphasizes the need for education of healthcare professionals at every level and every stage of learning/practice.

So much this

 

[Simon M]

Sorry, for going on and on.

3,500 words, when I copied into Word so I could print and read more easily! Clearly, all of us here are very grateful to you for sharing your notes and thoughts. Thank you too to @Michiel Tack (and Evelien?)

I have taken the liberty of summarising here what struck me as the most important findings/issues from the Webinar, based on your notes. Please shout if I have got things wrong.

1. Intramural study
Maybe the selection was too restrictive, given how difficut recruitment proved to be and the resulting small sample made it hard to hit statistical significance. . As well as requiring documented infectious cause (the biggest excluder), those with uncontrolled depression those inactive were excluded. Of 484 interested in the study, only 27 (6%)s completed visit 1 and just 17 (63%) of these were found to have ME/CFS. (Though only 21/25 healthy controls (84%) were found to be truly healthy.)

Findings (and my comments).

1. Decreased mitochondria function after exercise. A Seahorse study on lymphocytes found decreased maximal respiration and decreased respirator. Separately, Ian Lipkin reported that mitochondria were slow to recover ?? after exercise. Though nothing unusual was found in muscle biopsies. * were the mitochondria tested the same way or was it just looking at tissue samples?
2. Decreases in single CPET performance: decreased work rate, oxygen consumption and heart reserve (not always seen is all 2-day max exercise test studies on day 1).
3. Handgrip fatigability (but no maximum force) was lower in patients; greater fatigability was also seen in a recent study - including for cancer fatigue controls so may not be specific to ME/CFS.
4. No reduced Natural Killer cell cytotoxicity. This ties in with a large CureME study and contradicts the original NK findings. Although Nath said subgroups might differ in a larger sample, the original findings were not based on subgroups.
5. Nath said the stand-out finding was the big differences between men and women. Other researchers found sex-specific differences. If this is important then perhaps researchers should always analyse results from men and women separately. This would presumably mean that smaller studies should be women only because including a few men would only going to confuse the results.

More when migraines permit.

 

[Andy]

Do we know how many ME/CFS patients they were orintending

Brian Vastag stated here, USA: National Institutes of Health (NIH) intramural ME/CFS study, that they originally planned to recruit 40 patients.

 

[ME/CFS Skeptic]

nothing unusual was found in muscle biopsies

I think I heard Nath say this during the Q&A but at that point his audio was not very clear. Are there others who heard it too?

 

[Robert 1973]

Thanks, Simon.

My questions below quote Simon’s text but the questions are intended for anyone to answer.

1. Intramural study
Maybe the selection was too restrictive, given how difficut recruitment proved to be and the resulting small sample made it hard to hit statistical significance. . As well as requiring documented infectious cause (the biggest excluder), those with uncontrolled depression those inactive were excluded. Of 484 interested in the study, only 27 (6%)s completed visit 1 and just 17 (63%) of these were found to have ME/CFS. (Though only 21/25 healthy controls (84%) were found to be truly healthy.)

Apologies if I’ve not kept up but I’m puzzled by this. Do we know how many ME/CFS patients they were originally intending to include? I’m not saying it was necessarily wrong, and I realise that you have to start somewhere, but do we know what the rationale was for making the inclusion criteria so restrictive?

On the one hand the IOM report estimated 836,000 to 2.5 million people with ME/CFS in the US (with most undiagnosed) and yet this study seems to imply that using very strict criteria the prevalence might be lower (notwithstanding the fact that many were excluded from this study because of age, co-morbitities etc. and not because they were considered not to have ME/CFS). If that is the case, is the assumption that the other people have a different illness (in which case why isn’t that being studied too?) or is it just that they are assumed to be likely to give a weaker signal in this type of study? In which case, what is the rationale for that assumption?

NB I am not criticising the study, I’m just trying to understand.

Nath said the stand out finding was the big differences between men and women. Other researchers found sex-specific differences. If this is important then perhaps researchers should always analyse results from men and women separately. This would presumably mean that smaller studies should be women only because including a few men would only going to confuse the results.

Is this common to other illnesses which affect more women than men? For example, if these tests were run on people with MS or Lupus, would they expect to see these sort of differences between men and women, or do the differences between men and women in ME/CFS suggest that most men with ME/CFS may have a different illness, or a different form of the same illness, than most women with ME/CFS? If the latter were the case it would concern me if men were routinely excluded from studies.

More when migraines permit.

Yes please, Simon. Your summaries are always really helpful to me. I hope your migraine subsides soon.

 

[Paddler]

3,500 words, when I copied into Word so I could print and read more easily! Clearly, all of us here are very grateful to you for sharing your notes and thoughts. Thank you too to @Michiel Tack (and Evelien?)

1. Decreased mitochondria function after exercise. A Seahorse study on lymphocytes found decreased maximal respiration and decreased respirator. Separately, Ian Lipkin reported that mitochondria were slow to recover ?? after exercise. Though nothing unusual was found in muscle biopsies. * were the mitochondria tested the same way or was it just looking at tissue samples?

I asked the NIH specifically about whether muscle biopsies where going to be tested like the immune cells on Seahorse machine. Due to limitations of the Seahorse analyzer, individual muscle cells could not be separated and analyzed like free floating immune cells. So we do not know whether the metabolism of muscle cells are similarly affected. My assumption if that they looked at gross histology of muscle cells (including special staining) and also used electron microscopy. I am not sure if they looked at such variables such as muscle glycogen levels. They were able to pick up a study participant with myositis. They froze some muscle samples in case they want to go back reanalyze using a "new" technique.

I am interested to see the results of the metabolic chamber. My understanding is that the metabolic chamber should be sensitive enough to detect metabolic changes at the macro level.

 

[Milo]

I asked the NIH specifically about whether muscle biopsies where going to be tested like the immune cells on Seahorse machine. Due to limitations of the Seahorse analyzer, individual muscle cells could not be separated and analyzed like free floating immune cells. So we do not know whether the metabolism of muscle cells are similarly affected. My assumption if that they looked at gross histology of muscle cells (including special staining) and also used electron microscopy. I am not sure if they looked at such variables such as muscle glycogen levels. They were able to pick up a study participant with myositis. They froze some muscle samples in case they want to go back reanalyze using a "new" technique.

I am interested to see the results of the metabolic chamber. My understanding is that the metabolic chamber should be sensitive enough to detect metabolic changes at the macro level.

I had a muscle biopsy within the first 5 years of onset. Part of it was sent for mitochondrial DNA (which was normal). Respiratory chain analysis had abnormalities in it but was not considered serious. microscopy of the muscle fibers showed atrophy of the slow twitch fibers. And that was when the metabolic clinic said there was nothing they could do.

I hope the NIH looks deeply with what they have.