Chronic fatigue: Brain matters

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  • Published: Nov 1, 2014
  • Author: David Bradley
  • Channels: MRI Spectroscopy
thumbnail image: Chronic fatigue: Brain matters

Chronic differences

US researchers have discovered, using magnetic resonance imaging, that the brains of patients with chronic fatigue syndrome have diminished white matter and white matter abnormalities in the right hemisphere. Credit: Stanford, Norbert von der Groeben

US researchers have discovered, using magnetic resonance imaging, that the brains of patients with chronic fatigue syndrome have diminished white matter and white matter abnormalities in the right hemisphere.

Chronic fatigue syndrome (CFS) is the term used to refer to a group of debilitating medical conditions characterized by persistent fatigue that is not caused by exertion nor is it alleviated by rest and has no obvious cause. CFS has variously been referred to as myalgic encephalomyelitis (ME), post-viral fatigue syndrome (PVFS), chronic fatigue immune dysfunction syndrome (CFIDS). There is no obvious, single biological, genetic, infectious or psychological aetiology for CFS and it may have multiple causes. It is thought to affect between 1 million and 4 million people in the USA and millions more worldwide. Unfortunately, precise numbers are elusive because diagnosis is difficult and misdiagnosis easy. All CFS patients do, however, have one thing in common they all suffer unremitting symptoms of fatigue that last for six months or longer with several other symptoms varying from patient to patient.

A new clue to the biology of CFS now emerges from MRI studies where radiology researchers at Stanford University School of Medicine have discovered that the brains of patients with CFS have diminished white matter and white matter abnormalities in the right hemisphere. Michael Zeineh and his colleagues studied the brains of patients with CFS and compared the scans with the brains of healthy people; they found distinct differences between the two groups. The findings may lead to a more definitive diagnosis of the syndrome, which is often ambiguous and perhaps also point to an underlying mechanism in the disease process. It is not uncommon for CFS patients to face several mischaracterizations of their condition, or even suspicions of hypochondria, before receiving a diagnosis of CFS.


"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," Zeineh explains. "CFS is one of the greatest scientific and medical challenges of our time," adds Jose Montoya. "Its symptoms often include not only overwhelming fatigue but also joint and muscle pain, incapacitating headaches, food intolerance, sore throat, enlargement of the lymph nodes, gastrointestinal problems, abnormal blood-pressure and heart-rate events, and hypersensitivity to light, noise or other sensations."

Such a combination of symptoms can easily be misconstrued as having other causes, leading to repeated, failed diagnostic tests and even treatments for many patients and in the mean time, they can suffer for decades without relief from their symptoms. Montoya has been tracking 200 CFS patients for several years in an effort to identify the syndrome's underlying mechanisms. He hopes to accelerate the development of new and more effective treatments than are currently available.

"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," Montoya explains. Zeineh adds that, "If you don’t understand the disease, you're throwing darts blindfolded. We asked ourselves whether brain imaging could turn up something concrete that differs between CFS patients' and healthy people's brains. And, interestingly, it did."

Inflammatory issues

The MRI study compared scans of 15 CFS patients that were being followed by Montoya and compared to 14 age- and sex-matched healthy volunteers with no history of fatigue or other conditions causing symptoms similar to those of CFS. The comparison revealed three main differences. Firstly, MRI showed that overall there was a reduction in white matter content of the CFS patients' brains, compared with that of healthy subjects. "White matter" refers to the long nerve tracts that carry signals among broadly dispersed concentrations of "grey matter", the information-processing tissue of the brain. Zeineh points out that finding this difference was not entirely unexpected given that CFS is suspected of causing chronic inflammation, perhaps due to a protracted immunological response to a viral pathogen, and inflammation is commonly detrimental to white matter.

The second finding, however, was not expected. The team had used diffusion-tensor imaging to look at the white matter in detail and this showed a consistent abnormality in a particular part of a nerve tract in the right hemisphere of CFS patients' brains that was not present in the healthy subjects. This tract, known as the right arcuate fasciculus, connects the frontal lobe and the temporal lobe in the brain. Moreover, the degree of abnormality in the right arcuate fasciculus correlated with the severity of the condition in the patient, as assessed by performance on a standard psychometric test used to evaluate fatigue.

The role of the right arcuate fasciculus is not entirely clear although its counterpart in the left hemisphere is well studied and is known to connect two critical language areas of the left side of the brain, Wernicke's and Broca's areas, two grey matter structures separated by a distance of several centimetres. These two structures are important to understanding and generating speech, respectively.

The third finding was a thickening of the grey matter at the two areas of the brain connected by the right arcuate fasciculus in CFS patients, compared with the healthy subjects. Zeineh suggests that it is no coincidence that this abnormality is seen in those with the abnormality in the white matter joining them. "This study was a start," Zeineh says. "It shows us where to look." A much larger study is now needed to confirm the findings and to provide evidence for substantial differences in the brains of people with CFS and healthy individuals.

Related Links

Radiol, 2014, online: "Right Arcuate Fasciculus Abnormality in Chronic Fatigue Syndrome"

Article by David Bradley

The views represented in this article are solely those of the author and do not necessarily represent those of John Wiley and Sons, Ltd.

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