2024: NIH National Institutes of Health - ME/CFS Symposium on Intramural study - 2 May

Microbiome - another paper to come on the functional aspects of the various organisms. So, not about the specific taxa, but instead about what the organisms do e.g. produce butyrate

 

They are now on a break.

Some key points from memory were:

* inability to convert from IgG to IgM - B cells. Reliance on innate immune system. Suggestion that this could be indicative of a persistent infection

* cerebral spinal fluid - they were able to separate the ME/CFS and control groups on CSF contents (Walitt of course jumped on this with glee, suggesting the brain is where things are happening). However there were differences in other tissues, notably muscles I think, although most but not all individual differences were sex specific.

* lower butyrate production in the gut, lower butyrate in the brain. Suggestion that lower butyrate might increase gut permeability

 

Just on the set up of the event - there are very few people in the audience. I haven't had a good look, but maybe 20? It's a very empty auditorium. Must only be a fraction of the scientists who worked on the project. Lipkin asked a question, as did a couple of patients. 139 participants online.

There is no online chat function. The only way to submit a question is by email.

 

I thought the sex specific omics differences were interesting. Some of the omics data didn't appear to differentiate ME/CFS from HC until they did the analysis by sex, then within each sex there were clear differences between ME/CFS and HC. I think those omics were from blood (cells/plasma?).

The CSF data didn't show the sex differences in the same way, with the ME/CFS and HC differentiating and they said likely to be useful for biomarkers. As Hutan says, Walitt says that shows the problem is in the brain. I'm not convinced either.

Edit: Of course the sample sizes are so tiny, it could all be chance variations. I'm disappointed that they don't seem to have tried to replicate any of this in larger samples. They have had the data for ages.

 

I missed the beginning. Is it worth elaborating on what was said?

 

No difference between groups in maximum voluntary contraction, but ME/CFS couldn't sustain a grip force at half max voluntary contraction.
There was a very brief discussion on the suggested finding that the muscles still had the potential to perform, but they weren't.

Suggestion that the brain is not signalling for motor activity

Tilt test - no difference in heart rate, difference in epinephrine (lower in ME/CFS but variable, some patients had a big response)
no statistical difference in POTS incidence (although there was a definite trend) or symptoms.
Possibly increased vasoconstriction or reduced venous return in ME/CFS

24-hour ECG - decreased parasympathetic activity, trend to higher heart rate

Cognitive function - ME/CFS people report more cognitive problems, and more symptoms of depression and anxiety (although they are not very elevated)
No differences in neurocognitive tests ('tests are well validated and have been used for decades' subtext is 'our tests are great'
The problem is in ME/CFS patients' perceptions of poor performance and fatigue, not in actual cognitive performance reduction

 

Effort preference - an extremely junior presenter and he just read the presentation out, looking at the notes the whole time. Virtually no eye contact. He didn't even look up at the end!

There was a picture of a woman holding multiple shopping bags to illustrate effort
Effort preference isn't under voluntary control - people are just wired differently

Effort task - well validated (our test is great)
Reduced effort preference in ME/CFS, no evidence of fatigue over time

Findings are similar to people in Parkinsons. When the Parkinsons people were given dopamine, they engaged in the hard tasks more. Emphasised that people with ME/CFS aren't choosing this

 

Hallett is making it sound very definitive that there is no peripheral fatigue - although there was some evidence of 'disuse atrophy' (and yet the maximal voluntary contraction was the same?)
I don't think the Dimitriv slope index, the peripheral testing is that definitive. Although I don't understand all that very well.

He concludes the fatigue arises as a result of signals to the motor cortex

Norepinephrine leads to reduced control of blood pressure, and might affect brain metabolism directly. Affects supply of energy to neurons (supply of lactate).
A reduced supply of energy could produce central fatigue
Mentioned serotonin (I reckon the evidence for that is very weak)

Patient question from the floor - I think it was essentially 'did you take into account the patients' reduced ability to perform'? - presumably in the EFFrT task I think the response was a bit of a mess. The respondents didn't seem to understand the question.
Another patient question sent in by email - "the EFFrt is not supposed to be used where there are differences in the groups' abilities to complete the task'.
They have a prepared answer. Basically a dismissal of the assertion - it doesn't matter that some patients couldn't complete the task, some could. Walitt also delivered a prepared answer that really said nothing.

Question about POTS prevalence. Suggestion that it is a referral bias results in the over-estimation of POTS. Nath did note that there is autonomic dysfunction. Walitt noted that the lack of statistical difference wasn't that many of the ME/CFS group didn't have POTS, it was that a substantial number of the healthy volunteers did.

They all gave themselves a round of applause at the end of the session.

Overall - I reckon this idea of norepinephrine playing a role in fatigue is interesting. The defence of the EFFrT test was incredibly weak.

Lunch break

 

I wish I could have manage to write down the effort preference section and the answers to questions about it.

It was notable that even when answering questions about it, they were reading out prepared answers.

Dis I hear correctly that Walitt attributed the preference partly to unconscious brain activity, and partly to voluntary control?

 

I agree the defence of EEFRT was very weak. Do we know why they included it in the study?

 

The example he gave of Parkinson's disease and EEFRT he said gave similar results to ME/CFS, but when given dopamine the positions were reversed, with the PD group choosing more of the hard tasks than HC. Surely that indicates increases ability to perform a fine motor task with dopamine in PD, nothing to do with preference.

 

The participants were asked how fatigued they were, on a visual scale, presumably from 1 to 10. ME/CFS groups had higher fatigue at baseline, but didn't report tiring faster. The change in the reported fatigue was the same in both groups. Which is hardly surprising under those circumstances. It's a factor of where you start. If you start at 6, you can really only go to around a 9 and still be communicating. If you start at 0, you will probably only go to a 3 after cognitive tests.

 

Or, if it relates to preference, it's because the hard task has been made easier. Which is exactly what we are going on about - you can't accurately measure effort preference if one group has to, on average, work a lot harder than the other to physically complete the hard task. Their Parkinsons example pretty much illustrates exactly the point the people with ME/CFS are making.