MEA Summary Review: Grey and white matter differences in chronic fatigue syndrome | 19 October 2017

October 19, 2017


A recent study reported differences in brain structure in people with chronic fatigue syndrome (ME/CFS). This was not the first paper to report such aberrations, but it was the first to report increased Grey Matter volume compared to healthy controls.

Rather than attempt to place all of our review on this blog, we have made it available to view online or download as a pdf. file

The full review is a lay explanation of this study, of other research in this area, and it includes an overview of brain pathology and explains how these findings might affect functionality. Some extracts from the review are shown below, beginning with a summary from Dr Shepherd.


Comment from Dr Charles Shepherd, Hon Medical Adviser, ME Association:

This study was carried out in Newcastle by Professor Julia Newton and colleagues – a team who have not only achieved a long and distinguished record in ME/CFS research but also have access to patients who have been very carefully assessed from a clinical point of view. So, the results should be taken seriously.

As has been pointed out in this review, three of the main criticisms of previous neuroimaging studies involving people with ME/CFS is that the numbers involved have often been far too small; there has been a lack of information from other control groups that would be relevant in addition to the use of healthy controls; and that different imaging techniques have been used.  So, not surprisingly, the results are not always consistent.

Despite these caveats, these results clearly add weight to the findings from previous neuroimaging studies describing white matter abnormalities in ME/CFS but also raise the possibility of grey matter involvement in ME/CFS.

There are several possible explanations for these findings but no clear answer has emerged in the paper.  Are they a primary feature of ME/CFS?  Or are they secondary to other factors – e.g. duration of illness, decrease in activity, severity of fatigue – that are related to having ME/CFS?  The only way to find out is through further research into what is clearly an interesting aspect of neuropathology in ME/CFS.

A fully referenced summary of all the key findings from both functional and structural neuroimaging studies in ME/CFS can be found in the Research section of the ME Association ‘An Exploration of the Key Clinical Issues’ available from our online shop.

Overview of the study

42 patients with ME/CFS – who met the Fukuda diagnostic criteria and were pre-screened for comorbid psychological disorders – and 30 healthy controls, had their brains imaged by MRI scanner.

Comparisons of areas of the brain found that, on average, ME/CFS patients had lower white matter volume overall, consistent with previous findings.

However, this study also found several areas of increased grey matter volume, which was different to other studies in this area.

What made this study different?

  1. This study had a larger sample size than previous studies, with other studies having <30 patients.
  2. The paper stated that, ‘not all studies explicitly excluded patients with a psychiatric comorbidity, which may have affected findings,’ and so the patients in this study, were ‘meticulously screened for psychiatric comorbidities’.
  3. The VBM analysis followed a recently revised protocol which aimed to improve the quality of the results over previous implementations.

The Results

Whole-brain volume measurements

The study measured the overall brain segment volume in terms of:

  1. Total intracranial volume (TIV),
  2. Grey matter (GM) volume,
  3. White matter (WM) volume, and,
  4. Cerebrospinal Fluid (CSF) volume.

TIV is a measure of the total space within the skull and CSF is the liquid surrounding the structures of the brain and spinal cord.

These measurements were taken as absolute (on their own separately) and when adjusted to take account of the total intracranial volume (TIV) of each person.

This adjustment is important as people with smaller skull size could naturally have less volume, and vice-versa in people with larger skulls.

When looking at the absolute values on their own:

  • The average TIV of patients was ~5% lower than the healthy controls (1487ml vs 1560ml).
  • The average WM volume was ~8% lower in patients than healthy controls (517ml vs 559ml).
  • There was no significant difference in absolute GM volumes between the two groups (667ml vs 669ml).
  • There was a trend for lower absolute CSF volume in patients than in healthy controls, by ~9% (303ml vs 332ml). However, this trend is not significant as the p-value was 0.08 and the cut off for significance is <0.05.

After adjusting for total intracranial volume (TIV):

  • The average GM volume was ~3% higher in patients than the healthy controls (676ml vs 655ml).
  • The average WM volume was ~3% lower in patients than healthy controls (527ml vs 542ml).
  • There was no significant difference in the CSF volume (313ml vs 318ml) between the two groups.


Read the full review and explanation of brain pathology, online or as a download

Image copyright: lightwise/123RF Stock Photo

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