Study offers new clues to causes of post-infectious chronic fatigue syndrome

In a detailed clinical study, National Institutes of Health researchers discovered differences in the brains and immune systems of people with post-infectious myalgic encephalomyelitis/chronic fatigue syndrome (PI-ME/CFS). They also found clear differences between men and women with the disease. The results were published in Natural communications.

“People with ME/CFS experience very real and disabling symptoms, but uncovering their biological basis has been extremely difficult,” said Walter Koroshetz, MD, director of the National Institute of Neurological Disorders and Stroke ( NINDS) from the NIH.

“This in-depth study of a small group of people revealed a number of factors that may contribute to their ME/CFS. Researchers can now test whether these findings apply to a larger group of patients and move towards identifying treatments that target the key drivers of disease. disease.”

A team of multidisciplinary researchers has discovered how feelings of fatigue are processed in the brains of people with ME/CFS. Results of functional magnetic resonance imaging (fMRI) brain scans showed that people with ME/CFS had lower activity in a region of the brain called the temporoparietal junction (TPJ), which can cause fatigue by disrupting the way the brain decides how to exert effort. .

They also analyzed spinal fluid collected from participants and found abnormally low levels of catecholamines and other molecules that help regulate the nervous system in people with ME/CFS compared to healthy controls. Reduced levels of certain catecholamines were associated with poorer motor performance, exercise-related behaviors, and cognitive symptoms. These findings suggest, for the first time, a link between specific abnormalities or imbalances in the brain and ME/CFS.

“We believe that immune activation affects the brain in diverse ways, causing biochemical changes and downstream effects such as motor, autonomic, and cardiorespiratory dysfunction,” said Avindra Nath, MD, clinical director of NINDS and senior author of the study.

Immune testing revealed that the ME/CFS group had higher levels of naive B cells and lower levels of switched memory B cells (cells that help the immune system fight pathogens) in the blood compared to controls. healthy. Naive B cells are always present in the body and become activated when they encounter a given antigen, a foreign substance that triggers the immune system.

Memory B cells respond to a specific antigen and help maintain adaptive or acquired immunity. Further studies are needed to determine the link between these immune markers and brain dysfunction and fatigue in ME/CFS.

To study fatigue, Dr. Nath and his team asked participants to make risk-based decisions about physical exertion. This allowed them to assess the cognitive aspects of fatigue, or how an individual decides how much effort to exert when given a choice.

People with ME/CFS had difficulty with the effort choice task and with effort maintenance. The motor cortex, a region of the brain responsible for commanding the body to move, also remained abnormally active during strenuous tasks. There were no signs of muscle fatigue. This suggests that fatigue in ME/CFS may be caused by dysfunction in brain regions that drive the motor cortex, such as the TPJ.

“We may have identified a physiological focal point of fatigue in this population,” said Brian Walitt, MD, MPH, a research associate physician at NINDS and first author of the study. “Rather than physical exhaustion or lack of motivation, fatigue may result from a mismatch between what a person thinks they can accomplish and what their body accomplishes.”

Further analyzes revealed differences between men and women in gene expression patterns, immune cell populations and metabolic markers. Men showed impaired T cell activation, as well as markers of innate immunity, while women showed abnormal growth patterns of B cells and white blood cells. Men and women also had distinct markers of inflammation.

“The data from men and women were quite divergent, indicating that ME/CFS is not a one-size-fits-all solution,” Dr. Nath said. “Given the immune differences between men and women in ME/CFS, the findings could open new avenues of research that could provide insight into other chronic diseases associated with infections.”

The study, conducted at the NIH Clinical Center, comprehensively examined ME/CFS that developed after a viral or bacterial infection. The team used cutting-edge techniques to examine 17 people with PI-ME/CFS who had been ill for less than five years and 21 healthy controls.

Participants were screened and medically evaluated for ME/CFS over several days and underwent extensive testing, including clinical examinations, fMRI brain imaging, physical and cognitive performance tests, autonomic function tests, biopsies skin and muscle and advanced analyzes of blood and cerebrospinal fluid.

Participants also spent time in metabolic chambers where, under controlled conditions, their diet, energy consumption, metabolism, sleep patterns and gut microbiome were assessed. During a second visit, they performed a cardiopulmonary exercise test to measure the body’s response to exercise.

Many studies have identified immune, microbiological, and other abnormalities in ME/CFS, but results tend to be inconsistent and exactly how these markers relate to or cause fatigue and other symptoms is unknown.

Using a rigorous phenotyping approach to extract meaningful differences, this study helps validate previous findings and may identify new ways to therapeutically target the brain or immune system.

The highly collaborative project involved 75 researchers across 15 NIH Intramural Research Program institutes and centers and national and international institutions. Dr. Nath and his colleagues plan to publish additional results from the data collected during this study.