Brain abnormality, not muscle fatigue, found in ME/CFS


An in-depth study of 17 people with virally triggered ME/CFS has uncovered an imbalance in brain activity triggered by abnormalities in the immune system. They also found distinct differences between men and women with the disease.

Brain scans showed that people with ME/CFS had lower activity in a brain region called the temporal-parietal junction (TPJ), which may cause fatigue by disrupting the way the brain decides how to exert effort.

They also analysed spinal fluid and found abnormally low levels of catecholamines and other molecules that help regulate the nervous system in people with ME/CFS.

Deep phenotyping of post-infectious myalgic encephalomyelitis/ chronic fatigue syndrome, by Avindra Nath et al in Nature Communications vol 15, no. 907 (2024)

Research abstract:

Post-infectious myalgic encephalomyelitis/chronic fatigue syndrome (PI-ME/CFS) is a disabling disorder, yet the clinical phenotype is poorly defined, the pathophysiology is unknown, and no disease-modifying treatments are available.

We used rigorous criteria to recruit PI-ME/CFS participants with matched controls to conduct deep phenotyping. Among the many physical and cognitive complaints, one defining feature of PI-ME/CFS was an alteration of effort preference, rather than physical or central fatigue, due to dysfunction of integrative brain regions potentially associated with central catechol pathway dysregulation, with consequences on autonomic functioning and physical conditioning.

Immune profiling suggested chronic antigenic stimulation with increase in naïve and decrease in switched memory B-cells. Alterations in gene expression profiles of peripheral blood mononuclear cells and metabolic pathways were consistent with cellular phenotypic studies and demonstrated differences according to sex.

Together these clinical abnormalities and biomarker differences provide unique insight into the underlying pathophysiology of PI-ME/CFS, which may guide future intervention.

See also:

MERUK: NIH ME/CFS Deep Phenotyping Study: Part 1. Overview

MERUK: NIH ME/CFS Deep Phenotyping Study: Part 2. Methods

Health rising: The Nath ME/CFS Intramural Study Pt. I: “It’s a Brain Disease…”

Health rising: The Nath Intramural ME/CFS Study Pt. II: Missed Opportunities, Misreadings and… Success (?)

Guardian: Scientists find link between brain imbalance and chronic fatigue syndrome

“The brain can respond to stimuli and impact on the body,” says Prof Karl Morten from Oxford University. “The brain is physically, biochemically not functioning properly and it’s the illness that’s doing that, not the patient.”

NIH: NIH study offers new clues into the causes of post-infectious ME/CFS

“We think that the immune activation is affecting the brain in various ways, causing biochemical changes and downstream effects like motor, autonomic, and cardiorespiratory dysfunction,” said Avindra Nath, senior author of the study.

JAMA: NIH Study Provides Long-Awaited Insight Into Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

“Overall, what we show is that ME/CFS is unambiguously biological, with multiple organ systems affected,” researcher Nath said. “It’s a systemic disease, and the people living with it deserve to have their experiences taken seriously.”

Nath also noted that even if people who display ME/CFS-like symptoms don’t have ME/CFS, they may have another condition for which medical attention would be beneficial, it just hasn’t been diagnosed yet.

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