Brain Dysfunction May Be at Root of Chronic Fatigue Syndrome

Brain Dysfunction May Be at Root of Chronic Fatigue Syndrome
26.02.2024

Until now, research about a debilitating condition that has become more common during the pandemic offered little hope for patients and the doctors who treat them that the patients could eventually resume normal daily activities. 

That’s because scientists didn’t know much about what caused the illness, called myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). It affects multiple body systems, with its hallmark symptom being extreme fatigue that leaves many people bedridden. There’s little understanding of what causes ME/CFS, and there are no treatments.

Now, a multimillion-dollar government study has revealed several key understandings about ME/CFS. The scientific findings were published Wednesday in Nature Communications.

One important new finding was that the people in the study had low activity in a brain region called the temporal-parietal junction, “which may cause fatigue by disrupting the way the brain decides how to exert effort,” according to a National Institutes of Health summary of the study’s major takeaways.

The researchers also found that people in the study had changes in spinal fluid that may have made them less able to move. And the abnormal spinal fluid may also explain changes in mental skills and the body’s response to effort. 

One of the most difficult aspects of ME/CFS is that fatigue worsens after activity. About 1 in 100 adults in the U.S. have ME/CFS, according to the National Center for Health Statistics, based on responses from a national survey done in 2021 and 2022. The odds of being diagnosed with ME/CFS increase as people get older but plateaus between ages 60 and 69. Fewer and fewer people are newly diagnosed with the condition after reaching age 70.

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A new analysis published last week by the CDC estimated that people are four times more likely to get chronic fatigue after having COVID-19, compared to people who didn’t have COVID. Scientists had previously found that ME/CFS is most often diagnosed after a person has an infection that the body struggles to overcome, and instead continues its immune response.

This latest investigation of ME/CFS was an enormous project. More than 70 authors are listed on the 70-page Nature Communications manuscript, and the study spanned 8 years and cost more than $8 million, STAT News reported.

“People with ME/CFS have very real and disabling symptoms, but uncovering their biological basis has been extremely difficult,” Walter Koroshetz, MD, director of the NIH’s National Institute of Neurological Disorders and Stroke (NINDS), said in a statement. “This in-depth study of a small group of people found a number of factors that likely contribute to their ME/CFS. Now researchers can test whether these findings apply to a larger patient group and move towards identifying treatments that target core drivers of the disease.”

Another key finding may bring a better understanding of why women are more likely to be diagnosed with ME/CFS than men. Researchers found there were gender-based differences in immune systems and patterns of inflammation among people in the study.

“Men and women were quite divergent in their data, and that tells you that ME/CFS is not one-size-fits-all,” senior study author Avindra Nath, MD, clinical director at NINDS, said in a statement. “Considering male and female immune differences in ME/CFS, the results may open up new avenues of research that could provide insight into other infection-associated chronic diseases.”

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The study was very small and included 17 people with ME/CFS who had been sick for less than 5 years, as well as 21 healthy people who served as a comparison group. Another key finding was that the brains of those with ME/CFS stayed unusually active in the area that controls movement. The unusual brain activity in the motor cortex occurred during fatiguing tasks, but there was no simultaneous muscle fatigue in other parts of the body. The mismatch suggests brain dysfunction.

“We may have identified a physiological focal point for fatigue in this population,” researcher Brian Walitt, MD, MPH, an associate research physician at NINDS, said in a statement. “Rather than physical exhaustion or a lack of motivation, fatigue may arise from a mismatch between what someone thinks they can achieve and what their bodies perform.”

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