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Maybe its also a different interpretation of the term 'relapse'? To me that suggests frequent oscillation between good and bad periods like in multiple sclerosis or in depression. When it comes to prognosis I've seen/heard multiple trajectories including people whose decline was gradually or...

I wrote to the editors in january 2025 raising similar issues. And they said they would look into it but nothing happened. Hope it will be different this time.

Can I ask why you would put so much emphasis on relapses? I know it was a prominent feature in old ME descriptions but not sure if they are an essential aspect of ME/CFS. Is there data showing that relapses are characteristic of ME/CFS compared to other diseases?

Just speculating but from an evolutionary perspective the advantage of experiencing symptoms such as fatigue and malaise was probably to keep the organism still and quiet - to conserve energy or avoid pathogens from spreading. So if the animal pushes against this signal and remains active, it...

Yes I think both might play a role. These studies weren't randomized so you have multiple factors that can influence the results such as placebo effects, response bias, regression to the mean, etc.

Except that we might now have a good indication of where the magic is happening and what we need to investigate to understand how it works.

Thanks, would be good to have more discussion about this and an overview of arguments pro and contra. I've tried to reply to your points below. BTN2A1 also featured prominently in GWAS on anxiety (see here and here) while OMFL4 was one of the pleiotropic genes associated with multiple...

Yes this is one of the ME/CFS Lines consortium funded by the Dutch research agency ZonMw. It's part of the Dutch research agenda on ME/CFS. More about this study here: https://projecten.zonmw.nl/en/project/post-exertional-malaise-starting-point-investigate-and-understand-mecfs

Couldn't it be as straightforward as PD and MS having a different pathology that activates the central fatigue pathway, while ME/CFS might not. So in the latter the pathology might be in the neural network itself?

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