Dr. David M. Systrom of Brigham and Women’s Hospital (Boston) is confident that his team has objective evidence of small-fiber polyneuropathy (SFPN) in 40-50% of ME patients. Dr Systrom was interviewed by Llewelyn King in this video: . I put the timestamp at the part involved with SFPN but the whole video is highly informative and worth watching. His specialty is exercise intolerance of any kind and his work lead him to try to differentiate ME patients. About 40% of fibromyalgia and POTS patients are also suspected to have SFPN and it is a relatively simple test involving a skin biopsy. The doctor is also confident to have evidence of preload failure, which if I understood and remember half correctly is caused by poor constriction of the lower-body vascular system, leading to decreased ability of the blood to reach the heart. This is tested using an invasive CPET session, with radial and heart catheters. His team has funding for a double-blind RCT for a drug used to treat myasthenia gravis, pyridostigmine, targeting acetylcholine receptors but possibly also reduces inflammation. Some patients seem to have shown objective benefits from smaller trials. The drug has been approved for decades so it is well-known.