Chronic Fatigue Syndrome Is ‘Unambiguously Biological’

Similar to previous studies, people with ME/CFS had higher resting heart rates, markers of a drawn-out and overstimulated immune response that exhausts T cells, and less diverse gut bacteria than controls.

The ME/CFS group showed no signs of muscle fatigue, and performed normally on cognitive tests, despite reporting greater cognitive symptoms.

And yet the immune and gut microbiome changes clearly impacted the central nervous system in several ways. People with ME/CFS had lower levels of chemicals called catechols, which help regulate the nervous system, in their cerebrospinal fluid and less activity in a brain region called the temporal-parietal junction (TPJ) during motor tasks.

The TPJ drives the motor cortex, a brain region in charge of telling the body to move, so its dysfunction might disrupt how the brain decides to exert effort, the researchers think. In turn, these changes might alter patients’ tolerance for exertion and their perception of fatigue.

“We may have identified a physiological focal point for fatigue in this population,” says Brian Walitt, lead author and medical scientist studying ME/CFS at NINDS.

“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.

While welcoming the research effort, ME/CFS advocacy groups have questioned the use of some assessments of fatigue in the study, and the exclusion of other core features of the condition, namely post-exertional malaise.

Some might also query how the initial group of 217 patients who were screened for the study were whittled down to just 17 people who a panel of clinicians unanimously confirmed had post-infection ME/CFS.

In selecting a small group of patients, the study aimed to complete the most rigorous assessment practically possible to land the best chance of pulling out meaningful differences that researchers could then investigate in larger groups. Otherwise, as with long COVID and Alzheimer’s disease, it can be hard to get to the bottom of what causes these conditions, which in turn makes it difficult to find a treatment that works.

The researchers had wanted to recruit 40 patients with ME/CFS but the COVID-19 pandemic cut their efforts short. They also opted not to include people who had been sick for more than 5 years or were too unwell to travel; and avoided asking participants to complete days-long physical tests because they were concerned about harming patients through overwork.

Only with more research will it become clear whether the changes detected in these 17 patients translate to more people with ME/CFS, but this study lays the foundation for that future work.