Chronic Fatigue Syndrome Patients Have Reduced Activity in Basal Ganglia; the Brain’s 'Reward Center'

Chronic fatigue syndrome, a medical disorder characterized by extreme and ongoing fatigue with no other diagnosed cause, remains poorly understood despite decades of scientific study.

Although researchers estimate that more than 1 million Americans are affected by this condition, the cause for chronic fatigue syndrome, a definitive way to diagnose it, and even its very existence remain in question.

In a new study, researchers have found differing brain responses in people with this condition compared to healthy controls, suggesting an association between a biologic functional response and chronic fatigue syndrome.

The findings show that patients with chronic fatigue syndrome have decreased activation of an area of the brain known as the basal ganglia in response to reward.

Additionally, the extent of this lowered activation was associated with each patient's measured level of fatigue.

The basal ganglia are at the base of the brain and are associated with a variety of functions, including motor activity and motivation.

Diseases affecting basal ganglia are often associated with fatigue. These results shed more light on this mysterious condition, information that researchers hope may eventually lead to better treatments for chronic fatigue syndrome.

The study was conducted by Elizabeth R. Unger, James F. Jones, and Hao Tian of the Centers for Disease Control and Prevention (CDC).

More Fatigue, Less Activation
Dr. Unger, says that she and her colleagues became curious about the role of the basal ganglia after previous studies by collaborators at Emory University showed that patients treated with interferon alpha, a common treatment for chronic hepatitis C and several other conditions, often experienced extreme fatigue.

Further investigation into this phenomenon showed that basal ganglia activity decreased in patients who received this immune therapy.

Since the fatigue induced by interferon alpha shares many characteristics with chronic fatigue syndrome, Unger and her colleagues decided to investigate whether the basal ganglia were also affected in this disorder.

The researchers recruited 18 patients with chronic fatigue syndrome, as well as 41 healthy volunteers with no symptoms of CFS.

Each study participant underwent functional magnetic resonance imaging, a brain scan technique that measures activity in various parts of the brain by blood flow, while they played a simple card game meant to stimulate feelings of reward.

The participants were each told that they'd win a small amount of money if they correctly guessed whether a preselected card was red or black.

After making their choice, they were presented with the card while researchers measured blood flow to the basal ganglia during winning and losing hands.

The researchers showed that patients with chronic fatigue syndrome experienced significantly less change in basal ganglia blood flow between winning and losing than the healthy volunteers.

When the researchers looked at scores for the Multidimensional Fatigue Inventory, a survey often used to document fatigue for chronic fatigue syndrome and various other conditions, they also found that the extent of a patient's fatigue was tightly tied with the change in brain activity between winning and losing. Those with the most fatigue had the smallest change.

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The study was conducted by Elizabeth R. Unger, James F. Jones, and Hao Tian of the Centers for Disease Control and Prevention (CDC), Andrew H. Miller and Daniel F. Drake of Emory University School of Medicine, and Giuseppe Pagnoni of the University of Modena and Reggio Emilia. An abstract of their study entitled, "Decreased Basal Ganglia Activation in Chronic Fatigue Syndrome Subjects is Associated with Increased Fatigue," will be discussed at the meeting Experimental Biology 2012, being held April 21-25 at the San Diego Convention Center.

The abstract is sponsored by the American Society for Investigative Pathology (ASIP), one of six scientific societies sponsoring the conference which last year attracted some 14,000 attendees.

The above story is reprinted from materials provided by Federation of American Societies for Experimental Biology (FASEB).

Ampligen: Treatment for Chronic Fatigue Syndrome and ME rejected by FDA

Ampligen, the first drug ever seeking approval to treat chronic fatigue syndrome /myalgic encephalomyelitis (CFS/ME), recently hit another roadblock with the U.S. Food and Drug Administration (FDA).

In its long quest to treat 1 million Americans suffering from this debilitating illness, the FDA advisory panel did not recommend the drug to be sold on the market, largely because CFS/ME doesn't have clear biomarkers such as blood tests to define patients who most likely to respond to the drug.

Data from clinical trials of Ampligen has not convinced the FDA so far.

Nancy Klimas, M.D., one of the world’s leading researchers and clinicians in chronic fatigue syndrome/myalgic encepahalomyelitis (CFS/ME), is the director the NSU Institute for Neuro Immune Medicine.

"The real loser is not Ampligen, but CFS/ME patients whose daily suffering continues to be unabated," she says. "CFS/ME feels like you've been run over by a truck -- pain, inflammation, utter exhaustion and trouble concentrating."

Klimas has been caring for patients with CFS/ME for 26 years now. "It's heartbreaking seeing them struggle and suffer from this serious illness that has been trivialized by science and society. One of the early controversies quickly disproven suggested that CFS/ME is a form of depression. This led to enduring public policies that allowed insurance companies to limit coverage to CFS/ME to either mental health or exercise therapy, neither get to the root cause of CFS/ME," she explains.

"CFS/ME researchers, including myself, have seen major advances in our understanding of the biology of CFS/ME. It seems to resemble an illness we know how to treat like multiple sclerosis (MS), chronic viral diseases and autoimmune diseases."

Around since the late 1980s, this drug is not new to science and medicine. Two phase 3 clinical studies have been completed. The data shows that a subgroup of CFS/ME patients showed marked improvement, even recovery on the drug.

"Yet, that's not enough evidence for the FDA advisory committee to approve because they would like to see a conclusive biomarker," notes Klimas. "As a physician, I could live with this decision if I had other effective therapies to treat my CFS/ME patients. But I do not. Moreover, it defies common logic in used in drug approval for other complex immune mediated diseases."

The above story is reprinted from materials provided by Nova Southeastern University, via Newswise.