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Brain abnormalities in ME/CFS

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Reprinted with the kind permission of ME Research UK. This article first appeared in Breakthrough Magazine, Spring 2015.
Nervous system symptoms are as characteristic of ME/CFS as post-exercise malaise or muscle pain (myalgia). In historical publications on ‘epidemics’ of ME, symptoms consistent with central nervous system pathology were regularly reported, as Sir Donald Acheson pointed out in a review more than 50 years ago. And today, fatigue, non-refreshing sleep, short term memory impairments, sensitivity to variable stimuli like bright light and chemicals, and widespread pain are all suggestive of central nervous system involvement.
In a previous issue (Breakthrough, Autumn 2014), we reported on research from Osaka City University, Japan, showing inflammation of nervous tissue in widespread brain areas in ME/CFS patients. Since then, Prof. Jose Montoya’s group at Stanford University School of Medicine has published a scientific report containing some striking results which complement the Japanese findings.
The US researchers’ aim was to see whether ME/CFS patients had differences in gross brain structure, microscopic structure or brain blood flow that could explain their symptoms, so they compared brain MRI images from 15 long-term ME/CFS patients with images obtained from 14 age and sex-matched healthy volunteers with no history of relevant symptoms.
They found abnormalities in a brain tract called the arcuate fasciculus, as well as reductions in the volume of white matter in the brain in patients compared with healthy controls. As lead author Dr Michael Zeineh, assistant Professor of Radiology, explains, “Using a trio of sophisticated imaging methodologies, we found that CFS patients’ brains diverge from those of healthy subjects in at least three distinct ways.”
Overall, the three key findings were, first, that white-matter content (which tends to carry information between different parts of the brain) was reduced by about 7% in the brains of ME/CFS patients compared with healthy people. Second, using an advanced imaging technique (diffusion-tensor imaging), a consistent abnormality in the right arcuate fasciculus was identified, and there was a thickening of the grey matter at the two areas of the brain connected by the right arcuate fasciculus. Lastly, the researchers reported a significant correlation between the severity of the patients’ condition (assessed by psychometric and other testing) and the degree of abnormality in the right arcuate fasciculus.
As Dr Michael Zeineh continues, “White matter is thought to be highly susceptible to inflammation, and researchers have previously noted other areas of inflammation in patients with chronic disease, so this result wasn’t surprising.” However, he was surprised by the discovery of abnormalities in the right arcuate fasciculus (‘curved bundle’ in Latin) which is a long bundle of nerve fibres (axons) connecting the frontal and temporal lobes. The function of this structure remains something of a mystery, but it is generally thought to connect two brain areas (Broca’s area and Wernicke’s area) that are important for the use of language.
This Stanford study adds to the growing body of evidence that people with ME/CFS have real physical defects, especially in the central nervous system, and may point to an underlying mechanism in the disease process. Unusually for a ‘forgotten illness’ such as ME/CFS, the results were widely reported across the world, including the New York Times blog which pointed out that “many experts now believe that, in people with ME/CFS, a viral infection or some other physiological insult or exposure, or perhaps a combination of exposures, has kicked the immune system into permanent overdrive, leading to the cascade of symptoms. The new brain research appears at a timely moment.”
Prof. Montoya is planning a substantially larger study to explore the findings: “In addition to potentially providing the CFS-specific diagnostic biomarker we’ve been desperately seeking for decades, these findings hold the promise of identifying the area or areas of the brain where the disease has hijacked the central nervous system.” He makes the point, however, that these results, though quite robust, need to be confirmed by others since replication is the backbone of science.

ME Research UK commissions high-quality biomedical investigation into the causes, consequences and treatment of ME/CFS. The charity’s mission is to “Energise ME Research.” Visit ME Research at

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2 thoughts on “Brain abnormalities in ME/CFS”

  1. DoreneB says:

    Are they looking for more test subjects? Who can I contact? I have been dealing with these problems for years.

  2. evan-emma says:

    I have had symptons since the eighties, not officially diagnoised

    My daughter diagnoised with Parkinson at age 35. No definitive test, she is on medicine for Parkinson but is worst instead of improvement.

    Is it possible misdiagnosed.

    sorry for misspelled words

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