Findings of brain anomalies may shed light on chronic fatigue | San Francisco Chronicle | 29 October 2014

October 29, 2014

From the San Francisco Chronicle, 29 October 2014 (story by Erin Allday).

Stanford researchers have found some striking abnormalities in the brains of people with chronic fatigue syndrome, a frustrating and debilitating condition for which there is no known cause and no treatment that’s widely effective.

The findings, published Wednesday in the journal Radiology, could improve diagnosis and spark new scientific understanding of the disease.

Perhaps even more noteworthy, the results — if they can be confirmed with larger studies — could provide some of the first objective evidence that chronic fatigue syndrome is a severe illness that causes real physiological damage. That would be a major step for patients and their advocates, who still suffer under the stigma of having a condition that for decades was ignored or not taken seriously.

“If this finding holds, it will be exciting because yes, we’ve found something that has never been found before. But there’s this additional layer of looking at a disease that was completely ostracized. So there’s also this component of validation,” said Dr. Jose Montoya, an infectious disease specialist who helped establish a chronic fatigue syndrome team at Stanford School of Medicine a decade ago. Montoya was the senior author of the Stanford study.

Study’s limitations

For patients, Montoya said, “It’s almost like we’re saying, ‘You were right all along. Hopefully this will put you where you deserve to be, in a real clinic with treatments.’”

There are limitations to the study, Montoya said. Most notably, the sample size is fairly small, with 15 chronic fatigue patients and 14 healthy control subjects.

Researchers also are leery of the fact that earlier brain imaging studies in chronic fatigue syndrome have produced results that couldn’t be replicated or were too vague to be useful.

But the Stanford researchers used new imaging technology that is largely untested in chronic fatigue subjects and may be suited to uncovering subtle differences in brain physiology, said Dr. Michael Zeineh, a Stanford radiologist who led the brain imaging study.

Chronic fatigue syndrome is thought to afflict up to a million people in the United States. Patients can have a broad range of symptoms, including muscle and joint pain, overall weakness, insomnia and cognitive impairments. But the most remarkable symptom is an intense, crippling fatigue that can last for weeks, months or even years.

Because the symptoms can be vague and often are mistaken for other conditions, doctors may be reluctant to diagnose chronic fatigue syndrome in a patient. In fact, until the 1990s many doctors refused to consider it a “real” condition, and that doubt persists among many health care professionals today.

Danville resident Susan Kreutzer, 58, was only diagnosed with chronic fatigue syndrome in 2010, after being symptomatic since 1991. She went on an experimental antiviral treatment shortly after being diagnosed, and that hugely improved her symptoms for a while, but early last spring the fatigue flared up again, and she’s been housebound, mostly bedridden, since April.

“Just the idea of going into the kitchen and making a meal, that’s a big deal. Even taking a shower is too taxing,” Kreutzer said.

“Can you imagine having something, feeling it in your body and knowing it’s real, but most of the functioning world is questioning you?” she said. “We know there’s an answer out there. But are we going to get an answer in our lifetime? I don’t know.”

Kreutzer said there’s a frustrating pattern of research into chronic fatigue, where scientists seem to make some progress toward new discovery or treatments, only to fall short when findings can’t be replicated or therapies don’t hold up under further scrutiny.

For a few years, scientists looked closely at a particular virus as a possible cause of chronic fatigue syndrome, but follow-up studies repeatedly failed to confirm any conclusions and the cause remains a mystery.

The Stanford paper released this week notes that earlier brain scan studies were “inconsistent.” No previous scanning techniques produced strong, reliable physiological results.

But authors of the new study, and others involved in chronic fatigue research, said the latest results are encouraging, in part because new technology allowed scientists to produce more detailed scans and nuanced measurements than in the past.

Significant abnormalities

The team found three significant types of abnormalities in the brains of chronic fatigue patients. The first, using magnetic resonance imaging that looked at overall size of certain types of brain matter, found that so-called white matter areas were smaller in the brains of chronic fatigue patients than in healthy subjects.

The white matter of the brain holds the synapses, or communication cables, that connect neurons and allow them to send messages to one another. White matter is thought to be highly susceptible to inflammation, and researchers previously have noted other areas of inflammation in patients with chronic disease, so this result wasn’t surprising, said Zeineh, the Stanford radiologist.

Unexpected, however, was the discovery of abnormalities in a tract of the brain called the arcuate fasciculus, which connects the frontal and temporal lobes. Zeineh’s team uncovered these abnormalities using a scanning technique that looks at water displacement in the brain.

In the brain’s left hemisphere, the arcuate fasciculus connects areas devoted to language production and comprehension. But the chronic fatigue study found abnormalities only in the right hemisphere, and scientists aren’t sure what that part of the brain does on the right side. The team also found that in areas of the brain that were connected by the arcuate fasciculus, the gray matter was thicker.

Both findings involving the arcuate fasciculus suggest that the tract may be hyperactive in chronic fatigue patients, Zeineh said. But he noted that he’s only able make guesses for now.

“This right-sided change in the brain, this arcuate fasciculus being strong, it may be some kind of pathological fatigue network that develops. Like the brain gets shuttled into some fatigue state rather than the normal state,” he said.

Dr. Jon Kaiser, a Mill Valley physician who treats chronic fatigue patients and has developed a therapy that is in clinical trials now, said he is intrigued by the new research though well aware that the results will need to be verified.

“From a research perspective,” Kaiser said in an e-mail, the Stanford study “adds to the growing body of evidence substantiating that people with CFS have real physical defects, especially in the central nervous system.”

And he’s not sure whether the results, even if they hold up under further study, will lead to new options for diagnosing chronic fatigue syndrome. Most doctors and clinics don’t have access to the refined equipment and techniques available to Stanford scientists, he said.

’I missed a lot’

Kreutzer said that while she’s encouraged by the ongoing research into better understanding and treating of chronic fatigue syndrome, she struggles daily with the condition and it’s hard to stay hopeful.

Last weekend, she stayed home in bed while her husband drove up to Chico to visit their son, who just turned 21. She knew she wasn’t up to the drive or a weekend of social activities.

“Sometimes you feel like you’re Rip Van Winkle, because time in the rest of the world is marching forward without you,” Kreutzer said. “The hard part is seeing how much you’ve missed. I have a 21-year-old — how did that happen? High school and middle school, I missed a lot of that. But you just think, ‘I’m thankful I’m still here. I’m still alive. I have hope.’”

Erin Allday is a San Francisco Chronicle staff writer. E-mail:

Stanford University's own press release on the subject.

Shopping Basket