Neurovascular Dysregulation in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Rationale: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a common and clinically devastating disorder whose pathogenesis is poorly understood. ME/CFS may affect as many as 2.5 million people in the United States. Veterans who were deployed to the Persian Gulf during the Gulf War have a higher prevalence of ME/CFS and the related condition fibromyalgia (FM) compared to nondeployed Veterans. Furthermore, almost a quarter of the Veterans of the Gulf War developed chronic multisystem illness/Gulf War illness (CMI/GWI), which has many overlapping symptoms with ME/CFS. The underestimated direct and indirect cost of ME/CFS to society may approach $23 billion per year. There is substantial clinical overlap among FM, postural orthostatic tachycardia syndrome (POTS) and ME/CFS. Both FM and POTS have ahigh prevalence of small fiber neuropathy (SFN) diagnosed by epidermal biopsy, which may be responsible for symptoms. The prevalence of SFN in ME/CFS is not known. Using a maximum invasive upright exercise test (iCPET), which simultaneously measures ventilation, pulmonary and systemic gas exchange and hemodynamics, we have found that vascular dysregulation and exertional intolerance are highly prevalent in patients with ME/CFS. The purpose of this project is to link vascular dysregulation during exercise to small fiber autonomic neuropathy and exercise intolerance in a large cohort of ME/CFS compared to normal controls. Hypothesis: Exertional intolerance in ME/CFS is related to neurovascular dysregulation. Innovative aspects: This will be the first study of ME/CFS to link vascular dysregulation during exercise to SFN. Our innovative approach will attempt to link abnormal neuroanatomy (SFN by epidermal biopsy) to vascular dysregulation (by iCPET) as an underlying mechanism for exercise intolerance for ME/CFS. Furthermore, we aim to deep phenotype ME/CFS, with particular attention to diagnostic vascular and neural subgroups.