Scientists have compelling evidence for abnormalities in the brain and immune systems of patients with chronic fatigue syndrome (CFS), also known as myalgic encephalomyelitis (I).
The findings, in one of the most rigorous investigations to date, begin to illuminate the biological basis for the disease that can cause debilitating fatigue. The study is the first to demonstrate a link between imbalances in brain activity and feelings of fatigue, and suggests that these changes may be caused by abnormalities in the immune system.
“People with ME/CFS have very real and disabling symptoms, but discovering their biological basis has been extremely difficult,” says Walter Koroshetz, director of NIH’s National Institute of Neurological Disorders and Stroke (NINDS) in the US. “This in-depth study of a small group of people found a number of factors likely to contribute to their ME/CFS.”
The study involved only 17 patients and the findings need to be confirmed in a larger group before they can be claimed as a road map to new treatments. It is also not clear to what extent the findings apply to long Covid, as the patients were recruited and assessed before the pandemic. But scientists described the work as a long overdue deep dive into the biology of the condition.
“This is such an important paper and one that I am so pleased to see come out,” said Prof Karl Morten, who researches ME/CFS at the John Radcliffe Hospital, University of Oxford, and was not involved in the latest work not. “We’ve had a lot of small studies showing that there might be a problem with this cell or that cell, but no one had really looked at everything in one patient before.”
Patients in the study, carefully selected from an initial pool of 300, all experienced an infection before becoming ill. During the study, they stayed at an NIH clinic for a week and were given a wide range of physiological assessments.
Results from functional magnetic resonance imaging (fMRI) brain scans showed that people with ME/CFS had lower activity in a brain region called the temporal-parietal junction (TPJ), which can cause fatigue through the way the brain decides how to exert effort. do, to disrupt. . The motor cortex, a brain region that directs the body’s movements, also remained abnormally active during fatiguing tasks. However, there were no signs of muscle fatigue.
This suggests that fatigue in ME/CFS may be caused by a malfunction of brain regions that drive the motor cortex and that changes in the brain may alter patients’ tolerance for exercise and their perception of fatigue.
“We may have identified a physiological focal point for fatigue in this population,” said Brian Walitt, associate research physician at NINDS and first author of the study, published in Nature communication. “Rather than physical exhaustion or a lack of motivation, fatigue may result from a mismatch between what someone thinks they can accomplish and what their bodies are performing.”
Morten said that the discovery of abnormalities in brain function does not indicate that patients psychologically manage their own illness or have any control over it. “The brain can respond to stimuli and impacts on the body,” he said. “The brain is not functioning properly physically, biochemically and it is the disease that does this, not the patient.”
The patients also had increased heart rates and their blood pressure took longer to normalize after exercise. There were also changes to patients’ T cells, sampled from cerebrospinal fluid, suggesting that these immune cells were trying to fight something. This may indicate that the immune system has failed to stand up after an infection has cleared or that a chronic infection is present, undetected, in the body.
The authors trace a possible cascade of events, starting with a persistent immune response, which can cause changes in the central nervous system, leading to changes in brain chemistry and ultimately the function of specific brain structures that control motor function and the perception of fatigue.
“We think that the immune activation affects the brain in multiple ways, causing biochemical changes and downstream effects such as motor, autonomic and cardiorespiratory dysfunction,” said Avindra Nath, clinical director at NINDS and senior author of the study.
The findings have been welcomed by scientists as an important step towards uncovering the underlying biological causes of the disease. Until now, the lack of any clear biological basis for the disease has led to patients being dismissed, stigmatized, and having to navigate ineffective treatment options.
