Circadian skin temperature rhythm and dysautonomia in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: the role of endothelin-1 in the vascular dysregulation

Abstract

Purpose There is accumulating evidence of autonomic dysfunction in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS); however, little is known about its association with circadian rhythms and endothelial dysfunction. This study aimed to explore the relationship between autonomic responses using an orthostatic test, skin temperature circadian variations, and circulating endothelial biomarkers in ME/CFS. Methods Sixty-seven adult female ME/CFS patients and 48 matched healthy controls were enrolled. Demographic and clinical characteristics suggestive of autonomic disturbances were assessed using validated self-reported outcome measures. Postural changes in blood pressure [BP], heart rate [HR], and wrist temperature (WT) were recorded during the orthostatic test. Actigraphy during one week was used to determine the 24-hour profile of peripheral temperature and motor activity. Circulating endothelial biomarkers were also measured as indicators of endothelial functioning. Results ME/CFS patients showed higher BP and HR values than healthy controls at rest (p < 0.05 for both), and also higher amplitude of the circadian activity rhythm (p < 0.01). Circulating levels of endothelin-1 (ET-1) and vascular cell adhesion molecule-1 (VCAM-1) were significantly higher in ME/CFS (p < 0.05). In ME/CFS, ET-1 levels were associated with the stability and amplitude of the temperature rhythm, (p < 0.01), and also with the self-reported questionnaires (p < 0.001). Conclusions ME/CFS patients exhibited alterations in circadian rhythms and hemodynamic measures that are associated with endothelial dysfunction, supporting previous evidence of dysautonomia in ME/CFS. Future investigation in this area is needed to assess vascular tone abnormalities and dysautonomia which may provide therapeutic targets for ME/CFS.

Association of circulating biomarkers with illness severity measures differentiates myalgic encephalomyelitis/chronic fatigue syndrome and post-COVID-19 condition: a prospective cohort study

“…Post-infection, excessive production of in ammatory mediators such as IL-1β, IL-6, IL-8, TNF-α, MCP-1, and IP-10, as well as the presence of endothelial in ammation markers (IL-6, TNF-α, ICAM-1) in lung tissues, have also been reported [49,50]. This chronic endothelial dysfunction could potentially contribute to the observed higher BP levels in ME/CFS patients, as reported previously [22]. In our study, however, it remains uncertain whether a similar pattern exists in long COVID patients.…”

“…Participants were asked to ll out a set of validated self-administered screening questionnaires regarding their current health status one week after the rst clinical assessment. Changes in perceived fatigue ), who oversaw compliance as described in our previous study [22].…”

“…All participants were of Caucasian descent, from the same geographical area, and had a sedentary lifestyle at the time of the study. They were subject to stringent exclusion criteria, as previously described by our group [21,22]. The major exclusion criteria were a relevant previous or current diagnosis of an autoimmune disorder, multiple sclerosis, psychosis, major depression disorder, heart disease, hematological disorders, infectious diseases, sleep apnea or metabolic disorders; pregnancy or breast-feeding; smoking habit; strong hormone-related drugs; and preexisting fatigue-associated symptoms or evidence of multi-organ failure that did not meet the case criteria for ME/CFS and long COVID used in this study.…”

Herpesvirus Infection as a Systemic Pathological Axis in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

“…Endothelial dysfunction is another prominent characteristic of ME/CFS pathology, and has been repeatedly demonstrated in older and more recent studies [16][17][18][19][20][21][22][23][24]. Blood flow, especially cerebral 2 blood flow is perturbed and reduced in ME/CFS patients (van Campen et al, 2020b, van Campen et al, 2020a, van Campen et al, 2021b, Staud et al, 2018, Biswal et al, 2011, Boissoneault et al, 2019, as well as the perfusion of various brain regions (COSTA et al, 1995, Yoshiuchi et al, 2006, Shungu et al, 2012, Li et al, 2021.…”