Neurovascular Dysregulation in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome
Abstract
Topic Area: Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome (ME/CFS). Overview: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a common and clinically devastating disorder whose cause is poorly understood. ME/CFS is estimated to 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 a related condition, fibromyalgia (FM), compared to non-deployed 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 lost productivity due to ME/CFS results in an estimated direct and indirect cost approaching $23 billion per year to US society. There is a substantial clinical overlap among FM, postural orthostatic tachycardia syndrome (POTS), and ME/CFS. Both FM and POTS have a high prevalence of small fiber neuropathy (SFN), diagnosed by skin biopsy, which may be responsible for symptoms. The prevalence of SFN in ME/CFS is not known. A maximum invasive upright exercise test (iCPET) simultaneously and directly measures the blood flow, vascular pressures and ventilation, and gas exchange in the lungs and skeletal muscles during exercise. Using these techniques, we have found that abnormal vascular regulation and exercise intolerance are highly prevalent in patients with ME/CFS. The purpose of this project is to link vascular dysregulation during exercise to SFN and exercise intolerance in a large cohort of ME/CFS compared to normal controls. Critical Problem to Be Addressed: The current diagnosis of ME/CFS is entirely clinical and lacks insight into the underlying pathophysiology of exercise intolerance. The prevalence and relevance of blood vessel dysfunction to SFN and exercise intolerance, as well as its relationship with the blood flow and gas exchange throughout the lungs and the rest of the body in ME/CFS, are unknown. We hypothesize that exertional intolerance in ME/CFS is related to blood vessel dysfunction, which in turn is related to SFN. Innovation of the Idea: This will be the first study to investigate the link between vessel dysfunction, dysfunctional small fiber nerves, and exercise intolerance in ME/CFS during exercise using iCPET. The innovative approach of this study will be the simultaneous and direct measurements of blood flow, vascular pressures, ventilation and gas exchange in the lungs and skeletal muscles during an iCPET to investigate exertional intolerance in ME/CFS. These data will be combined with a unique skin biopsy, which will document small fiber density percentile. Furthermore, we aim to identify ME/CFS subgroups with specific and diagnostic vascular and neural characteristics. We will analyze more than 2000 clinically indicated iCPET’s performed at an academic medical center between 2011 and 2020 for unexplained exertional intolerance. Patients who meet the Institute of Medicine (IOM) criteria for ME/CFS and are free of comorbidities will be analyzed according to the exercise vascular dysregulation variables and nerve density to calculate the prevalence of vascular dysregulation and SFN. We predict that we will find a high prevalence of SFN in ME/CFS, associated with evidence of vascular dysregulation during exercise. We believe this unique marrying of abnormal neuroanatomy to abnormal vascular physiology during exercise will explain exertional intolerance in ME/CFS. Sophisticated statistical analyses will be performed to link symptoms, vascular dysregulation, and SFN. This will help establish specific diagnostic biomarkers for ME/CFS, understand mechanisms underlying exercise intolerance, and justify targeted therapy. Ultimate Applicability and Impact: We believe that our findings will, for the first time, explain exercise intolerance in ME/CFS and establish biologically based diagnostic criteria of the disease. This will
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 05, 2021
- Source ID
- W81XWH2110027
Entities
People
- David Systrom
Organizations
- United States Army