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Thanks! I wonder what you make of the hypothesis by Chaudhuri and Behan about central fatigue being generated by a striatal-thalamic prefrontal cortex network. Made a thread about their papers here: https://s4me.info/threads/fatigue-and-basal-ganglia-2001-chaudhuri-behan.51412/

They also mention this hypothesis in a 2004 Lancet review that they wrote. Perhaps they can be discussed together on the same thread. Abhijit Chaudhuri, Peter O Behan, 2004. Fatigue in neurological disorders Abstract Chronic fatigue is a typical symptom of neurological diseases, and is most...

The reason for posting this is that there are some genetic links (potentially) pointing to striatal neurons in ME/CFS namely the (eccentric) medium spiny neurons. See: https://s4me.info/threads/eccentric-medium-spiny-neuron-emsn.50276/post-708197

Abstract Fatigue is a common symptom in neurology and occurs in the diseases of the central and peripheral nervous system. In order to understand the mechanism of fatigue, it is important to distinguish symptoms of peripheral neuromuscular fatigue from the symptoms of physical and mental fatigue...

Yes my guess would be that it points to a neuronal network involving the striatum and other brain regions. The results for fibromyalgia look similar so I suspect it's picking up on a more general signal rather than something specific to (a subgroup within) ME/CFS. Perhaps others have a more...

I've written a blog post that summarizes some of the findings on cell type and tissue enrichment that have been posted on the forum. It also zooms in on (eccentric) medium spiny neurons. Hope I've managed to do this with sufficient caveats...

I've written a blog post that summarizes some of the findings on cell type and tissue enrichment posted in this thread: https://mecfsscience.org/cell-and-tissue-enrichment-in-me-cfs/

Thanks. I suspect they are a bit too confident about this. The only way to be sure that there's a subgroup that responds is to do a new randomized trial in this subgroup only and compare the treatment versus a placebo. What they seem to be doing is, after a trial finished and produced null...

Yes, I think @wallfish explained it well. These are the BPS people from Belgium and they see ME/CFS like a sort of stress-related burnout. There are some biological measurements in this study that might be interesting like the PET scans but am afraid that most will be interpreted in light of...

I don't fully understand, though, because it is quite likely that inebilizumab will turn out to be ineffective. So then this follow-up study with tafasitimab would no longer be indicated?

Yes

Someone has looked into it on Twitter:

Not sure, but I suspect it would be bigger because the standardized effect size was a Cohen's d of 0.56. That is usually larger than the minimal clinically important difference. Think the biggest problems of this trial lie elsewhere: no control condition, no objective outcomes, no correction...

Anyone able to find the trial registration? Don't see it either and they mention 5 primary outcomes. With correction none would be statistically significant. Post-hoc usually means that it wasn't pre-specified and decided after seeing the results. Don't think the ANCOVA versus MMRM...

Positive news again, hope many people will apply.

In addition, the treatment effects were not clinically significant from what I can see. They defined the minimally clinically important difference (MCID) for the primary outcome (the FAS) as a change of 3 points. The FAS benefits compared to no treatment were : -1.49 points [95% CI –2·92 to...

Looks like a clear result. I think people will say it's in tissues like the gut, not in the blood, but I wonder if that theory holds.

Ah sorry, could be that I misunderstood this.

I suspect the daratumumab trial would be the quickest way to get a breakthrough, but it's very uncertain whether it will bring positive results. The underlying scientific evidence, in my (amateur) opinion, is not very strong. The genetic data from DecodeME looks more robust, but it probably has...

One caveat here is that if you look at the raw numbers in supplementary table 2, the rate with infectious onset was almost identical. An infectious onset was reported by 61.1% in the high symptom burden group compared to 61.2% in the low symptom burden group. So this doesn't separate them at...