This is a call for research help, not a definitive statement. Some time ago member SnowLeopard asked a question about possible rhabdomyolysis following exercise. Several of us told him this was a serious condition amounting to a medical emergency which could destroy his kidneys. He needed quick testing to tell if his colored urine showed actual breakdown of muscle fibers. Pogoman has since posted saying that a result of his own medical odyssey was a diagnosis of necrotizing autoimmune myopathy. Reading some papers on that illness raised questions in my mind about patients with the corresponding autoantibody who self-limit exercise to avoid the horrible effects of rhabdomyolysis bad enough to produce colored urine. (A patient I know with a different disorder producing rhabdomyolysis describes the feeling of "having muscles shredded", so it would not surprise me if he avoided exercise.) One distinctive feature I noticed was special weakness in large proximal muscles, which some patients I've talked to have reported without prompting. The autoantibody in question attacks the enzyme 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). From a biochemical standpoint this is a particularly interesting enzyme. Treatments for this autoimmune illness are fairly new, but are possible. (Aside: pogoman's test for HMGCR antibodies was negative, but this is a new test and it is quite possible all relevant antibodies have not been covered. Consider how long it took to find antibodies to MuSK in patients with myasthenia gravis who met the clinical definition, but did not have the antibodies to nicotinic acetylcholine receptors.) Anyone who has recently reviewed citric acid cycle/Krebbs cycle/TCA cycle biochemistry will notice the central importance of acetyl-co A. The mevalonate pathway gets into a wide range of regulatory processes for metabolism, fatty acids and endocrine function. In terms of products affected we find cholesterol, steroids, heme and ubiquinones. This is suspiciously close to a number of pathways with anomalies found in many patients. One problem here is that we don't know which differences cause the pathology itself and which are attempts at compensation. Bad responses to statins are fairly common in the general population, but like many things these are more common among ME/CFS patients. I also note that doctors who have treated many such patients over a long period of time have remarked on the low incidence of atherosclerosis among them, which is surprising when you consider low levels of exercise. Impairment of the metabolic pathway producing cholesterol would explain both this finding and diffuse damage to nerves. (Cholesterol, including the "bad" form, is needed to build cell walls, and nerves have more cell surface area than most other types of cells.) Another aspect related to rhabdomyolysis is that, in those few extreme cases where ME/CFS patients die, kidney failure is often blamed, though this is usually considered the result of dehydration. If I were designing a chip with an array of tests for autoantibodies, a test for antibodies to HMGCR would be on the list. Declaring a problem psychosomatic without running such tests is irresponsible. A big problem with present-day medicine is that such a test is expensive, and is not run unless there are clear clinical signs suggesting such a problem. Waiting for a patient to produce colored urine indicating rhabdomyolysis before testing is not sound medical practice. Several other tests I would include are now done in paraneoplastic panels. Unfortunately, there are many doctors who feel you can't have a "real" paraneoplastic disorder unless you have cancer. Research publications show nearly half of those with the antibodies do not have detectable neoplasms. The devastating effects of such problems as an autoimmune response to NMDA receptors, N-type calcium channels or Ma2 make such illnesses worthy of treatment in their own right.