I think glial improper function is the most likely candidate for ME's core mechanism. That fits the observations (triggered by immune activation), and the complexity of the glial/neural/blood vessel interaction makes it reasonable for a feedback loop to lock it in an abnormal state. The extreme difficulty of measuring all the properties involved in those interactions, especially if the problem is in a few cells in the hindbrain, explains why no one has found the cause yet, and also the difficulty (BBB) in finding chemicals that affect the symptoms. Also, if it's a few brain cells, that fits the rapidity of temporary remission. Overall, it's my best fit for explaining ME.
Muscle weakness could be cause by neural dysfunction. The signals going to the muscles could be weaker, or the feedback could make it feel like weakness, or it could affect whatever hormones or other supporting signals are important for optimum muscle use. I still think someone should do a test for muscle response to electrical stimulation (bypassing the neural system). With electrical stimulation, do the muscles of PWME contract less strongly? Are they less efficient metabolically than those of healthy people? It seems a simple enough test, and more economically efficient than funding countless studies on grip strength or exercise biking when the problem isn't proven to involve the muscles themselves?
I've posted a number of links recently about the complexity of the brain and the interaction between neurons and glial cells. It just seems so reasonable that a disturbance in the body's immune system would disturb the brain's immune system, which in turn would disturb neural function, leading to such symptoms as brainfog, lethargy, pain, and general malaise, and it would also disturb the various parts of the brain that autonomously control body functions, such as the gut, the muscles, lungs, eyes, etc. Different parts of the brain have subtly different glial cells (and maybe neurons too?) and these probably vary with the individual too. Throw in the variations in blood and glymph vessels, and it's quite reasonable to expect a disease to produce widely varied symptoms and responses to various factors. I think the really amazing thing is that humans don't have more of these "screws up the brain and everything else" diseases. Actually, there are probably more such diseases that we don't think fit, because they've been dismissed as somatic, or the result of some body dysfunction (muscles, liver, whatever) despite a lack of solid evidence.
