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Although autonomic nervous system (ANS) dysfunction in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) has been proposed, conflicting evidence makes it difficult to draw firm conclusions regarding ANS activity at rest in ME/CFS patients. Although severe exercise intolerance is one of the core features of ME/CFS, little attempts have been made to study ANS responses to physical exercise. Therefore, impairments in ANS activation at rest and following exercise were examined using a case-control study in 20 ME/CFS patients and 20 healthy people. Different autonomous variables, including cardiac, respiratory, and electrodermal responses were assessed at rest and following an acute exercise bout. At rest, parameters in the time-domain represented normal autonomic function in ME/CFS, while frequency-domain parameters indicated the possible presence of diminished (para)sympathetic activation. Reduced parasympathetic reactivation during recovery from exercise was observed in ME/CFS. This is the first study showing reduced parasympathetic reactivation during recovery from physical exercise in ME/CFS. Delayed HR recovery and/or a reduced HRV as seen in ME/CFS have been associated with poor disease prognosis, high risk for adverse cardiac events, and morbidity in other pathologies, implying that future studies should examine whether this is also the case in ME/CFS and how to safely improve HR recovery in this population.

Background: The diagnosis of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is problematic due to the lack of established objective measurements. Postexertional malaise (PEM) is a hallmark of ME/CFS, and the two-day cardiopulmonary exercise test (CPET) has been tested as a tool to assess functional impairment in ME/CFS patients. This study aimed to estimate the potential of the CPET. Methods: We reviewed studies of the two-day CPET and meta-analyzed the differences between ME/CFS patients and controls regarding four parameters: volume of oxygen consumption and level of workload at peak (VO2peak, Workloadpeak) and at ventilatory threshold (VO2@VT, Workload@VT). Results: The overall mean values of all parameters were lower on the 2nd day of the CPET than the 1st in ME/CFS patients, while it increased in the controls. From the meta-analysis, the difference between patients and controls was highly significant at Workload@VT (overall mean: −10.8 at Test 1 vs. −33.0 at Test 2, p < 0.05), which may reflect present the functional impairment associated with PEM. Conclusions: Our results show the potential of the two-day CPET to serve as an objective assessment of PEM in ME/CFS patients. Further clinical trials are required to validate this tool compared to other fatigue-inducing disorders, including depression, using well-designed large-scale studies.