The autonomic nervous system (ANS) is responsible for controlling processes in the body that occur without our conscious control – including energy production, and regulating heart rate, blood pressure and temperature – many of which are linked to ME/CFS.
When the nerves in the ANS do not communicate as they should, symptoms of autonomic dysfunction (dysautonomia) can develop. These include dizziness, feeling faint or fainting, and hot flushes.
Orthostatic intolerance is commonly experienced by people with ME/CFS, and occurs where the ANS responds abnormally to a change in posture – for example, when moving from lying down to an upright position.
When a person stands up, blood pools in the lower body. In a healthy person, the ANS is able to quickly redistribute blood throughout the body using a system that regulates blood pressure. In those with orthostatic intolerance, this does not happen effectively, and leads to either:
- A very quick increase in heart rate; i.e. postural orthostatic tachycardia syndrome (PoTS), or
- An abnormal drop in blood pressure (orthostatic hypotension).
Both orthostatic intolerance and PoTS lead to the exacerbation of symptoms of autonomic dysfunction which can only be relieved by reclining.
What are circadian rhythms, and how might they be involved?
Nearly all processes in the body – including those controlled by the ANS – are regulated by the 24-hour sleep-wakefulness cycle which responds to light and dark (circadian rhythm).
Disruptions in circadian rhythms have been found to result in problems with how the body uses and produces energy, leading to symptoms of fatigue, cognitive disturbance and autonomic dysfunction – all of which are observed in ME/CFS.
While it has been proposed that disrupted circadian rhythms may play a role in ME/CFS, the exact mechanisms involved remain unclear.
Skin temperature is a factor that changes with the sleep-wakefulness cycle, and has previously been associated with dysautonomia in people with ME/CFS.
Therefore, a recent study considered the relationship between 24-hour changes in skin temperature and autonomic dysfunction in those with ME/CFS.
As both skin temperature and blood pressure are partially regulated by contraction and expansion of blood vessels – vasoconstriction and vasodilation – the study also considered biomarkers related to these processes (biomarkers of endothelial function).
What did the study do?
Participants were recruited from an ME/CFS centre at Vall d’Hebron University Hospital, Barcelona, Spain, between October 2019 and March 2022.
There were 67 participants who the study referred to as having ME/CFS (having been diagnosed by a specialist using the International Consensus Criteria which identifies cases of ME) and 48 healthy controls. All participants were female.
Participants attended a clinic appointment in either the morning (32 people with ME/CFS and 29 controls) or the afternoon (35 people with ME/CFS and 19 controls). During this appointment, information on a number of different factors was collected:
- General characteristics such as age, body mass index (BMI), current medication use and duration of illness.
- Responses to questionnaires which related to fatigue, sleep quality, anxiety and depression, autonomic symptoms, symptoms of orthostatic intolerance, and quality of life in relation to health.
- A blood sample containing information on three biomarkers of endothelial function – this was only taken from participants who attended the morning clinic.
- 24 hour variations in movement, and skin temperature – both measured using a device attached to the wrist of each participant.
- Changes in blood pressure, heart rate and skin temperature during a test which asked participants to sit upright, lay down and stand up for a set period of time to assess orthostatic intolerance – the 10 minute NASA Lean Test (NLT). Changes in skin temperature could only be measured for 42 participants with ME/CFS and for 33 healthy controls.
The information collected was then compared between those with ME/CFS and healthy controls, and relationships between the different measures were also considered.
Finally, the researchers considered whether blood pressure, biomarkers related to endothelial function, and information on circadian rhythms could be used to accurately differentiate those with ME/CFS from healthy controls.
What did the study find?
The findings from the study were complex. In summary, compared with healthy controls, those with ME/CFS had:
Levels of anxiety and depression
Symptoms of autonomic dysfunction and orthostatic intolerance
Levels of two of the three markers of endothelial function measured which related specifically to vasoconstriction and inflammation
Quality of life
Levels of movement in a 24-hour period
|No difference in||Temperature over a 24-hour period|
Results from the NLT showed that those with ME/CFS had higher blood pressure and heart rate measurements when lying down and upon standing. Despite this, the number of people with orthostatic intolerance were similar in the two groups: 16% of people with ME/CFS and 13% of healthy controls. There were also no differences in skin temperature between the two groups during the NLT.
Interestingly, for those with ME/CFS, levels of one of the biomarkers of endothelial function – related specifically to vasoconstriction – was associated with the stability of skin temperature over a 24-hour period, and with symptoms of autonomic dysfunction reported in the questionnaire.
The findings also showed that, when considered together, blood pressure, biomarkers related to endothelial function, and information on circadian rhythms could be used to accurately differentiate those with ME/CFS from healthy controls.
What do the findings mean?
The authors state that the findings – particularly the link between the biomarker for vasoconstriction, stability of skin temperature over a 24-hour period, and symptoms of autonomic dysfunction – may indicate a possible role of impaired functioning of the lining of the blood vessels (endothelial dysfunction) in ME/CFS. This is in agreement with previous research, including that funded by ME Research UK.
While this study did not identify any specific mechanisms leading to symptoms of autonomic dysfunction in ME/CFS, the results support the need for research which reflects the complexity of the disease.
As with all research, the findings must be interpreted in light of the study limitations. These include:
- Small sample size: This decreases the ability to detect statistically significant differences between those with ME/CFS and healthy controls.
- Lack of diversity: Participants with ME/CFS were all female, and had all been recruited from the same clinic at one hospital in Spain. This means that the results may not be applicable to men with ME/CFS or to those living in other countries.
- The criteria used to diagnose ME/CFS: This study used the ICC which diagnoses cases of ME. Unlike other ME/CFS criteria such as the Canadian Consensus Criteria, and the NICE guidelines for a diagnosis of ME/CFS, the ICC does not require “post exertional malaise” (PEM) to be present for a diagnosis to be made – PEM is often referred to as the cardinal symptom of ME/CFS. While the criteria do use “post-exertional neuroimmune exhaustion” (PENE), and this does capture elements of PEM, the use of inconsistent definitions, and different terminology complicates the comparisons that can be made with those diagnosed using other ME/CFS criteria.
- Information was only collected at one point in time (a cross-sectional study): This means that the researchers were unable to distinguish the direction of the associations they investigated; for example, whether ME/CFS leads to endothelial dysfunction, or if endothelial dysfunction leads to ME/CFS.
- Lack of consideration of other factors which may affect results: Researchers did not consider other health conditions occurring alongside ME/CFS, the stage of menstrual cycle- which may affect blood pressure, or other lifestyle factors that may influence endothelial dysfunction such as physical activity.
More research is needed to assess whether these findings could be replicated in larger, more diverse groups of participants, using criteria for ME/CFS that require PEM for a diagnosis, and are consistent with the definitions used. There is also a need for research which aims to establish a better understanding of the mechanisms underlying autonomic dysfunction in ME/CFS.
- A recent study considered the relationship between skin temperature and autonomic dysfunction in people with ME/CFS.
- The results showed that those with ME/CFS were older and had a higher BMI; had questionnaire scores indicating higher levels of fatigue, more symptoms of autonomic dysfunction, and lower quality of life and sleep quality; and had higher levels of markers of constriction of the lining of the blood vessels.
- When considered together, blood pressure, markers relating to the function of blood vessels, and information on the 24-hour sleep-wakefulness cycle could be used to accurately differentiate those with ME/CFS from healthy controls.
- The authors state that the findings of the study may indicate a possible role of impaired functioning of the lining of blood vessels in ME/CFS.
- More research is needed to assess whether these findings could be replicated in larger, more diverse groups of participants using criteria for ME/CFS that require PEM for a diagnosis, and are consistent with the definitions used. There is also a need for research which aims to establish a better understanding of the mechanisms underlying autonomic dysfunction in ME/CFS.