From The New York Times, 24 November 2014. Words by David Tuller.
Patients with chronic fatigue syndrome are accustomed to disappointment. The cause of the disorder remains unknown; it can be difficult to diagnose, and treatment options are few. Research suggesting that an infection from a mouse virus may cause it raised hopes among patients a few years ago, but the evidence fell apart under closer scrutiny.
Many patients are still told to seek psychiatric help. But two recent studies — one from investigators at Stanford a few weeks ago and another from a Japanese research team published earlier this year — have found that the brains of people with chronic fatigue syndrome differ from those of healthy people, strengthening the argument that serious physiological dysfunctions are at the root of the condition.
“You’ve got two different groups that have independently said, ‘There’s something going on in the brain that is aberrant,’ ” said Leonard Jason, a psychologist at DePaul University in Chicago who studies the condition, also called myalgic encephalomyelitis and widely known as M.E./C.F.S. “I think you have a growing sense that this illness should be taken seriously.”
Both studies were small, however, and their results must be replicated before firm conclusions can be drawn. Still, other studies presented at scientific conferences this year also have demonstrated physiological dysfunctions in these patients.
In the most recent study, published by the journal Radiology, researchers at Stanford University compared brain images of 15 patients with the condition to those of 14 healthy people. The scientists found differences in both the white matter, the long, cablelike nerve structures that transmit signals between parts of the brain, and the gray matter, the regions where these signals are processed and interpreted.
The most striking finding was that in people with the disorder, one neural tract in the white matter of the right hemisphere appeared to be abnormally shaped, as if the cablelike nerve structures had crisscrossed or changed in some other way. Furthermore, the most seriously ill patients exhibited the greatest levels of this abnormality.
The researchers also found in M.E./C.F.S. patients a thickening of the gray matter at the two points of the right hemisphere connected by this particular neural tract. And the overall volume of white matter in the brains of patients was reduced, compared with the brains of people without the disorder.
The relationship between the symptoms experienced by patients and the findings is unclear. The two parts of the brain connected by the abnormally shaped white matter are believed to be important for language use, said Dr. Michael Zeineh, a radiologist at Stanford and the lead author of the more recent study.
Still, Dr. Zeineh said these differences and others, if borne out by further studies, could eventually serve as biological and diagnostic markers for the illness. “This opens the door to more detailed investigations because now we have targets for future research,” he said.
Dr. Zeineh and his colleagues are seeking funding to follow a greater number of patients over time. That would allow them to understand better the links between the brain changes they observe and the fluctuations of symptoms and severity in the illness itself.
In the other brain study, published in March by The Journal of Nuclear Medicine, a team led by researchers from Osaka City University compared PET scans of nine people with M.E./C.F.S. to those of 10 healthy controls. They reported widespread cerebral inflammation in the patients, and found that those with the most severe illness had more inflammation.
Dr. Zeineh said reduced white matter in patients was consistent with the hypothesis that brain inflammation plays a role in the illness.
“If there is widespread inflammation going on, that could explain many of the symptoms,” he said.
In the United States, about a million people are believed to have M.E./C.F.S., although there are no reliable diagnostic tests. Many patients report that doctors and other health care providers have dismissed or ignored their complaints. Extended bouts often disrupt relationships with employers, colleagues, friends and family members.
For many patients, the primary symptom is not just fatigue but more specifically postexertional malaise, the total depletion of energy after even minimal amounts of activity. Sleep disorders, lapses in cognitive function, and muscle pain are also common. Some patients remain virtually bedbound for long periods.
Many experts now believe that in people with M.E./C.F.S., 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. Next month, a panel convened by the National Institutes of Health will hold a two-day workshop charged with “advancing the research” on the illness of the disorder. The Institute of Medicine is conducting a separate, government-sponsored initiative to assess and evaluate the many sets of diagnostic criteria for M.E./C.F.S., with the results expected next year.
Advocacy groups have questioned the rationale for two separate efforts. They have also criticized the initiatives because in both cases many people with little or no expertise in M.E./C.F.S. will be voting on recommendations that could have a significant impact on the government’s future efforts.