People suffering from chronic fatigue syndrome are often told that their condition isn't real — that it's all in their head. It turns out this is true — but in a very literal sense. Researchers have learned that the brains of CFS patients have very specific brain abnormalities, a discovery that will lead to better diagnoses and a deeper understanding of the baffling condition.

Top image: Liao et al.

Chronic fatigue afflicts between one and four million people in the U.S. and millions more worldwide. But these are just estimates; a precise number is difficult to pinpoint because it's difficult to diagnose the disease. There are many symptoms in addition to overwhelming fatigue, including 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. These symptoms can persist for six months or longer, and vary from individual to individual.

Frustratingly, CFS patients often face a stigma. Some are even accused of hypochondria. Thankfully, a new study by Stanford Medicine radiologists may help to resolve these issues and ambiguities.

White Matter Matters

Using a series of imaging methodologies, Michael Zeineh and colleagues found that CFS patients' brains are different from those of healthy subjects in at least three distinct ways. Most notably, they discovered that they have diminished white matter and white matter abnormalities in the right hemisphere of their brains.


White matter, once thought to be useless, has been referred to as the subway of the brain. It connects different regions of grey matter in the cerebrum to one another. It's also fast, electrically stimulating myelin sheaths encasing each neuron's process transmitting signals to other neurons.

A Harvard release explains the findings:

[An] MRI showed that overall white-matter content of CFS patients' brains, compared with that of healthy subjects' brains, was reduced. The term "white matter" largely denotes the long, cablelike nerve tracts carrying signals among broadly dispersed concentrations of "gray matter." The latter areas specialize in processing information, and the former in conveying the information from one part of the brain to another.

That finding wasn't entirely unexpected, Zeineh said. CFS is thought to involve chronic inflammation, quite possibly as a protracted immunological response to an as-yet unspecified viral infection. Inflammation, meanwhile, is known to take a particular toll on white matter.

But a second finding was entirely unexpected. Using an advanced imaging technique — diffusion-tensor imaging, which is especially suited to assessing the integrity of white matter — Zeineh and his colleagues identified a consistent abnormality in a particular part of a nerve tract in the right hemisphere of CFS patients' brains. This tract, which connects two parts of the brain called the frontal lobe and temporal lobe, is called the right arcuate fasciculus, and in CFS patients it assumed an abnormal appearance.

Furthermore, there was a fairly strong correlation between the degree of abnormality in a CFS patient's right arcuate fasciculus and the severity of the patient's condition, as assessed by performance on a standard psychometric test used to evaluate fatigue.

The third finding was a thickening of the gray matter at the two areas of the brain connected by the right arcuate fasciculus.


Taken together, they serve as important biomarkers for the condition. What's more, they also point to an underlying mechanism in the disease process itself.

Read the entire study at Radiology: "Right Arcuate Fasciculus Abnormality in Chronic Fatigue Syndrome".