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Scientists have discovered compelling evidence of abnormalities in the brain and immune system of patients with chronic fatigue syndrome (CFS), also known as myalgic encephalomyelitis (ME).
The findings, in some of the most rigorous research to date, begin to illuminate the biological basis of the disease that can cause disabling fatigue. The study is the first to demonstrate a link between imbalances in brain activity and feelings of fatigue, and suggests that these changes could be caused by abnormalities in the immune system.
“People with ME/CFS have very real and disabling symptoms, but uncovering their biological basis has been extremely difficult,” said Walter Koroshetz, director of the National Institute of Neurological Disorders and Stroke (NINDS) at the NIH in the United States. “This in-depth study of a small group of people found a number of factors that likely contribute to their ME/CFS.”
Only 17 patients participated in the study and the findings must be confirmed in a larger group before they can be considered a roadmap to new treatments. It is also unclear to what extent the findings apply to long Covid, as patients were recruited and tested before the pandemic. But scientists have described the work as a long-overdue deep dive into the biology of the disease.
“This is a very important paper and I am very pleased to see it published,” said Professor Karl Morten, who researches ME/CFS at Oxford University’s John Radcliffe Hospital, and who was not involved in the latest work. “We’ve done a lot of small studies that show there might be a problem with this or that cell, but no one had really looked at everything in a patient before.”
The patients in the study, carefully selected from an initial group of 300, had experienced an infection before becoming ill. During the study, they stayed in an NIH clinic for a week and underwent a wide range of physiological evaluations.
Results from functional magnetic resonance imaging (fMRI) brain scans showed that people with ME/CFS had lower activity in a region of the brain called the temporal-parietal junction (TPJ), which can cause fatigue by altering the way you think. that the brain decides how to exert effort. . The motor cortex, a region of the brain that directs body movements, also remained abnormally active during the strenuous tasks. However, there were no signs of muscle fatigue.
This suggests that fatigue in ME/CFS could be caused by dysfunction of the brain regions that drive the motor cortex and that changes in the brain may alter patients’ tolerance for effort and their perception of fatigue.
“We may have identified a physiological focal point for fatigue in this population,” said Brian Walitt, a research associate at NINDS and first author of the study, published in Nature Communications. “More than physical exhaustion or lack of motivation, fatigue can arise from a mismatch between what someone believes they can achieve and what their body performs.”
Morten said the discovery of abnormalities in brain function does not suggest that patients are psychologically driving their own illness or have any control over it. “The brain can respond to stimuli and impacts on the body,” he said. “The brain does not function physically and biochemically properly and it is the disease that does this, not the patient.”
The patients also had elevated heart rates and their blood pressure took longer to normalize after exertion. There were also changes in the patients’ T cells, taken from samples of the cerebrospinal fluid, suggesting that these immune cells were trying to fight something. This could indicate that the immune system has failed to stop after an infection has cleared or that there is a chronic, undetected infection present in the body.
The authors map out a possible cascade of events, starting with a persistent immune response, that could cause changes in the central nervous system, lead to alterations in brain chemistry, and ultimately affect the function of specific brain structures that control brain function. motor and the perception of fatigue.
“We believe that immune activation is affecting the brain in several ways, causing biochemical changes and downstream effects such as motor, autonomic and cardiorespiratory dysfunction,” said Avindra Nath, clinical director of NINDS and lead author of the study.
Scientists have welcomed the findings as an important step towards discovering the underlying biological causes of the disease. Until now, the lack of a clear biological basis for the disease has led to patients being dismissed, stigmatized, and having to navigate ineffective treatment options.