Brain differences linked to chronic fatigue syndrome

Behind the Headlines

Friday October 31 2014

Chronic fatigue syndrome causes persistent fatigue that affects everyday life

Around 250,000 people in the UK have CFS

"Scientists find three differences in the brain [of people with chronic fatigue syndrome]," the Mail Online reports.

Chronic fatigue syndrome (CFS) affects around a quarter of a million people in the UK and causes persistent symptoms, such as fatigue, that can have a significant adverse impact on people's quality of life. The cause of CFS is unknown and the condition continues to be researched. 

The study behind this headline used a specialised type of MRI scan to examine whether there were any differences in the brain volume and structure of 15 people with CFS, compared with 14 people without.

The researchers found the volume of white matter (brain cell nerve fibres) was lower in the group with CFS. There were also some differences on the right side of the brain in the nerve fibres that connect the temporal to the frontal brain regions.

These are interesting developments in furthering our understanding of CFS. However, the study only involved a very small sample of 15 people, and we don't know how representative they are of all people with the condition.

The design of the study is able to demonstrate brain features that may be associated with the condition, but it cannot show cause and effect. We also don't know the order in which events happened.

It's not known whether these differences could have led to the development of CFS (and if so, whether they were always present, or whether some other unknown factors caused them to occur), or whether these are new changes that have occurred since the people developed CFS.

The next step would be to try to understand how these differences are associated with the condition's development.


CFS or ME?

There is some debate over whether the term chronic fatigue syndrome (CFS) or myalgic encephalomyelitis (ME) should be used.


Chronic fatigue syndrome (CFS) is the term often used and preferred by doctors because there is little evidence of brain and spinal cord inflammation, as the term ME suggests. ME is also thought to be too specific to cover all the symptoms.


Myalgic encephalomyelitis (ME) is the term preferred by some people who feel that CFS is too general and does not reflect the severity and different types of fatigue. It also highlights the fact that fatigue is not the only symptom.

Where did the story come from?

The study was carried out by researchers from Stanford University School of Medicine in California.

Financial support was provided by the Division of Infectious Disease Chronic Fatigue Syndrome Fund, and one of the authors received support from GE Healthcare.

The study was published in the peer-reviewed medical journal, Radiology.

The Mail Online's headline, "Is this proof chronic fatigue DOES exist?", casts doubt upon whether CFS actually exists. It's known CFS affects many thousands of people, with often severely debilitating consequences, so its existence is not in doubt.

However, the causes of CFS remain poorly understood. This study has tried to further understanding of the condition by examining brain features that may be associated with it. This study provides a starting point, but not the whole picture.


What kind of research was this?

This was a cross-sectional study that took brain scans of 15 people with CFS and a comparison group of age and sex-matched people without CFS. It aimed to research differences in the brain structure.

As the researchers explain, CFS is a debilitating condition characterised by six or more months of persistent or relapsing fatigue without any associated medical or mental health disorder.

The researchers consider that brain imaging may help inform diagnosis and prognosis, though conventional scan findings to date have been inconsistent and of limited help in any further understanding of the condition.

This study used a special MRI technique called diffusion tensor imaging (DTI). DTI measures the diffusion (movement or spread) of water through the brain tissues, which provides 3D images of the size, shape and microscopic structure of tissues.


What did the research involve?

The researchers scanned the brains of 15 people with CFS and compared them with 14 age- and gender-matched people without CFS. They were looking for any brain volume and structure differences between the two groups that may be linked to the condition.

People with CFS had to meet two inclusion criteria:

  • a clinical diagnosis of CFS made up of fatigue for six months or longer, with at least four other symptoms from: impaired memory or concentration, sore throat, tender lymph nodes, headaches, muscle pain, joint pain, unrefreshing sleep and malaise after exertion
  • ongoing memory or concentration problems causing severe enough impairment that a doctor thought brain imaging was necessary to confirm no other disease process was occurring

The group with CFS had an average age of 46 years. Eight people in the group were female (55%) and the average duration of their CFS symptoms was 12 years.

The age- and sex-matched comparison group were people without CFS, depression or substance use in the past year. Of 28 recruited, 14 chose to participate.

All participants completed a 20-item Multidimensional Fatigue Inventory (MFI-20), which assesses general, physical and mental fatigue, reduced motivation and activity. It is said to be a well-validated tool for assessing CFS, with higher MFI-20 scores indicating increased severity.

They also assessed whether each person was right- or left-handed or ambidextrous, as this is linked to differences in structure and volume in some brain areas.

The main analysis compared differences in brain volume and structure between the two groups using MRI (DTI) brain scans. This took into account variations in age, handedness and total brain volume.


What were the basic results?

The researchers found, on average, people with CFS had a lower total volume of white matter (nerve cell fibres) in their brain than people without.

They took a measure known as fractional anisotropy (FA), which gives a value between zero and one indicating the degree of diffusion of water, and whether there are any restrictions in any direction. A value of zero would mean that diffusion is the same in all directions.

They found significant differences in the FA of people with and without CFS in one particular region of the brain on the right side, called the right arcuate fasciculus. This is a nerve fibre tract that links the temporal region on the right side of the brain with the frontal region.

Most right-handed people with CFS had a maximum FA in the right arcuate fasciculus above 0.6, while those without CFS had a FA value below 0.6. They noticed that in people with CFS, FA of the right arcuate fasciculus tended to increase with disease severity.

The researchers also observed that people with CFS had areas of thickening in parts of the grey matter connected by the right arcuate fasciculus.


How did the researchers interpret the results?

The researchers concluded there is a loss of white matter in people with CFS. They also suggest the fractional anisotropy of the right arcuate fasciculus might be a biological indicator for CFS.



This study used a specialised type of MRI to examine whether there were any differences in the brain volume and structure of 15 people with CFS, compared with 14 people without.

They found the volume of white matter (nerve fibres) appeared to be lower, on average, in the people with CFS. There were also differences in the magnitude of water diffusion (a measure known as fractional anisotropy) in one particular white matter tract on the right side of the brain, which connects the temporal with the frontal brain regions.

These are interesting developments in furthering our understanding of CFS. But there are points to bear in mind when considering the meaning of these findings.

It must be remembered this research only used a very small sample of 15 people with CFS from the US, who may not be representative of the many thousands of people affected by this condition in the UK or elsewhere.

For example, these were people who had severe and persisting memory or concentration problems, such that their doctor thought brain imaging was required to make sure no other disease process was going on. The differences seen between these 15 people with CFS and 14 without may not be identical to differences that may be seen in a different sample.

Also, as this is a cross-sectional study, it cannot prove cause and effect: it can't tell us the order in which events happened. For example, it can't tell us whether these are structural features that occurred before people developed CFS, which may have been involved in the development of the condition, or whether these are changes that happened after the people developed CFS.

Further imaging studies in larger samples of people with this condition may reveal whether these results are consistent observations in the brain structure of people with CFS. The next step would then be to try to understand how these differences are associated with the condition's development.

These findings have no immediate treatment or preventative implications for CFS.

Analysis by Bazian. Edited by NHS Choices

Follow Behind the Headlines on TwitterJoin the Healthy Evidence forum.

Analysis by Bazian

Edited by NHS Choices

Links to the headlines

Is this proof chronic fatigue DOES exist? Scientists find three differences in the brain that suggest condition may not just be 'in the mind'. Mail Online, October 30 2014

Chronic fatigue syndrome is real, researchers say. CNN, October 30 2014

Links to the science

Zeineh MM, Kang J, Atlas SW, et al. Right Arcuate Fasciculus Abnormality in Chronic Fatigue Syndrome. Radiology. Published online October 30 2014


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Media last reviewed: 21/04/2017

Next review due: 21/04/2020

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