Would it have to also be in the muscle or could it be solely in the brain? DecodeME points strongly to the brain right? I guess that's harder to test?
As
@jnmaciuch says, this is a critical question worth trying to settle. Testing muscle isn't easy either because of sample variability and other practical problems but it may be worth pursuing.
I am less impressed by the data so far than jnmaciuch. We have about 50 years of negative findings both in dedicated muscle units and clinical practice and a few positive findings that are a bit hard to interpret. I am not sure what cultured myoblasts can tell us about an acquired regulatory disturbance in muscle if these are newborn cells dividing under artefactual conditions. A genetic difference could have shown up but then there is still a question of what switches disease on.
Nevertheless, I like the idea that the same sort of homeostatic (normally) signal circuits may be operating in some central control compartment and in peripheral target organs like muscle. The immune system can operate like a central control compartment, despite being distributed across many centres, because cells recirculate between these. The brain, via autonomic and neuroendocrine pathways, can operate as a central control. I have difficulty in seeing how muscles could be responsible on their own. (And of course muscle failure isn't the real problem for PWMECFS. Someone with burnt out muscles from myositis or progressive dystrophy may be able to hold down a job and lead a fairly normal life maybe with a motorised chair.)
The argument is something like this: We do have examples of muscles getting stuck in feedback loops but (a) these are local and (b) the loop tends not just to be in the muscle. Examples are overuse tendinitis or enthesopathy, as in tennis elbow, or things like Writer's Cramp Syndrome, which is primarily a neural loop. If ME/CFS involved signal loops in muscle flipping from homeostasis to an 'off-centre' stable disease mode, precipitated by an immune response perhaps, then it is hard to see why this should occur in all muscles, and even harder to see why it should wax and wane in some people over months and years, in all muscles together.
I am thinking that maybe we have to consider all sorts of under-recognised ways that CNS might control signal loops in muscles and other tissues. That might include autonomic signals to brown fat and leptin secretion, MAIT cells trafficking to meninges or subfornical organs, and so on.
, but it reminded me of Dutch researcher Marjan Versnel. She's new to the field and she's been studying Sjörgen and also IFN-I and she will be studying it in ME as well.
