Causes and consequences of autonomic dysfunction in Chronic Fatigue Syndrome

PhD ThesisChronic Fatigue Syndrome (CFS) is an incapacitating condition characterised by extreme fatigue. In the absence of an objective diagnostic test CFS remains a clinical diagnosis based on a broad spectrum of symptoms, including autonomic dysfunction and cognitive impairment. This has given rise to significant challenges, not least the development of multiple sets of diagnostic criteria that may represent different disease phenotypes. This thesis examines autonomic and cognitive features between subgroups that meet different diagnostic criteria to better understand this possibility. It also examines the overlap between symptoms of CFS and depression, a potential confounder. Methods A subset of data from a larger Medical Research Council funded observational study Understanding the pathogenesis of autonomic dysfunction in CFS and its relationship with cognitive impairment was examined. Patients were screened using the SCID-I assessment tool to exclude major depression prior to the main study. Depressive symptoms were compared to CFS Fukuda criteria. The DePaul Symptom Questionnaire (DSQ) was used to differentiate between diagnostic criteria. COMPASS and COGFAIL questionnaires were administered for self-reported autonomic and cognitive features respectively. The Task Force® Monitor was used for autonomic assessment and a battery of neuropsychological tests administered for objective cognitive assessment. Results Subjective autonomic and cognitive symptoms were significantly greater in CFS subjects compared to controls. There were no statistically significant differences in objective autonomic measures between CFS and controls. There were clinically significant differences between DSQ subgroups on objective autonomic testing. Psychomotor speed was significantly slower in CFS compared to controls. Visuospatial memory, verbal memory and psychomotor speed were significantly different between DSQ subgroups. Conclusion The findings indicate phenotypic differences between DSQ subsets and suggest that elucidating the symptoms seen in CFS, or its disease spectrum, will support research into its underlying pathophysiology and enable more tailored treatment. The absence of significant differences in objective autonomic function between CFS and controls in this cohort contrasts to findings of some other studies and may reflect study exclusion for depression. Together with the overlap between CFS and depressive symptoms, this reinforces the need to better understand the underpinning causality to allow appropriate identification and management.Medical Research Counci