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   Scientific American   
      
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   HEALTH   
   Baffling Chronic Fatigue Syndrome Set for Diagnostic Overhaul   
   Researchers might soon redefine the mysterious condition, while the latest   
   findings point to the role of brain inflammation   
   May 16, 2014 |By Katherine Harmon Courage   
   **   
   CFS   
   More than one million people in the U.S. suffer from a poorly understood,   
   difficult-to-diagnose condition that can leave them debilitated by unshakable   
   exhaustion, pain, depression and cognitive trouble. Researchers, however, are   
   still unsure what causes    
   chronic fatigue syndrome (CFS), how to treat it, how best to diagnose it and   
   even what to call it.   
   A new study is now providing hope for better understanding--and potentially   
   better diagnosing--the disease. It has revealed a striking pattern of brain   
   inflammation in CFS patients. Meanwhile, diagnosis and definition of the   
   disease could soon be getting    
   a major overhaul as a new $1-million Institute of Medicine (IOM) study gets   
   underway at the request of the U.S. Department of Health and Human Services   
   (HHS). Is the exhausting search for answers about CFS finally coming to an end?   
   In your head   
   Chronic fatigue syndrome was first formally described in the late 1980s. Soon   
   thereafter it was lumped in with another perplexing condition known as myalgic   
   encephalomyelitis (ME), which had been classified as a disease of the nervous   
   system in the 1960s.   
    A precise definition and diagnosis of CFS--sometimes called CFS/ME--has   
   largely eluded doctors and researchers, however. Its subjectively described   
   symptoms seem untestable: everyone is exhausted from time to time; many people   
   suffer from occasional    
   aches and pains; and, sure, we all have foggy days as well as down ones.   
   A large obstacle is that, unlike cancers or high blood pressure, researchers   
   have no particular biomarkers that would allow them to test for the condition.   
   Doctors rely exclusively on patient reports of the severity and duration of   
   the symptoms--usually    
   requiring the symptoms to be present for at least six consecutive   
   months--along with the presence of extreme post-physical or mental exertion,   
   fatigue and unrefreshing sleep, to diagnose the condition. Remissions and   
   relapses confound clinicians further.   
   A change might be on the distant horizon, however, thanks in part to a new   
   study of the brains of patients living with CFS.   
   Doctors have long suspected brain inflammation as a potential cause, but no   
   definite traces of it had been detected. New research, in the June issue of   
   the Journal of Nuclear Medicine, shows for the first time distinct increases   
   in inflammation in    
   particular regions of CFS patients' brains.   
   Yasuyoshi Watanabe, director of the RIKEN Center for Life Science Technologies   
   and professor of physiology at Osaka City University Graduate School of   
   Medicine, and his colleagues studied positron emission tomography (PET) scans   
   of the brains of 10    
   health controls and nine patients with CFS. "Many researchers and clinicians,   
   including our group, thought of this before, but apparently no one tried it   
   using PET," Watanabe says.   
   The research team found increases in inflammatory markers in regions including   
   the amygdala, thalamus and midbrain in CFS patients who had more severe   
   cognitive troubles. They found more of these markers in thalamus and cingulate   
   cortex in individuals    
   who reported worse pain. And they found higher traces of inflammation in the   
   hippocampus in patients with severe depression.   
   More than a decade ago, Watanabe's group found tantalizing suggestions that   
   certain neurotransmitters were not being synthesized as well in people with   
   CFS. These patients also had lower levels of serotonin transporters in   
   particular brain areas. Other    
   research had found higher levels of inflammatory cell-signaling proteins   
   called cytokines circulating in the blood. All of these results led Watanabe   
   to look closer for inflammation.   
   These PET-scan correlations do not precisely explain the symptoms, Watanabe   
   notes. And only a handful of patients were in the study. But the work opens a   
   new trail researchers can follow. Watanabe and his team are now looking into   
   the amount of    
   neuroinflammation in patients with CFS as well as the levels of circulating   
   cytokines, which could both lead to the development of tests for the   
   condition. Having a biologically based test could help those who do have the   
   disease as well as patients who    
   might have a different condition that has similar symptoms, such as   
   depression, fibromyalgia or late-stage Lyme disease, which would be managed   
   differently and potentially be cured with antidepressants, pain relievers or   
   antibiotics. "Most important,"    
   Watanabe says, is "how to treat [CFS] patients and how to prevent this   
   disorder." Currently, clinicians can only try to treat the symptoms--not the   
   disease--with medications or lifestyle recommendations. "We are now planning   
   to study therapeutics, such    
   as anti-inflammatory agents, including herbal medicine," which might treat the   
   underlying pathology, Watanabe says.   
   By any other name   
   Watanabe's study, and other new and forthcoming findings, however, may not be   
   included in the current IOM review of the disease. "It is possible that the   
   committee could examine new research that comes out during the study," says   
   Jennifer Walsh, a    
   spokesperson for the IOM. But, she notes, it depends on the study.   
   The study committee members will largely be assessing major research efforts   
   and definitions developed previously for the disorder. "There were a number of   
   case definitions that had come up over the years," says Nancy Lee, director of   
   the Office on Women'   
   s Health at HHS and the department's designated federal officer of the Chronic   
   Fatigue Syndrome Advisory Committee. Bringing so much of the work together to   
   come up with a unified definition would help researchers not only better   
   understand the illness,    
   as well as help to convey information to clinicians so they can make faster,   
   more definitive diagnoses. As Lee points out, "most U.S. physicians do not   
   have a good understanding of how to make the diagnosis of ME/CFS." The IOM   
   will try to develop new    
   evidence-based criteria for diagnosing CFS, decide whether the condition   
   should be renamed and come up with a way to best get the new recommendations   
   to health care providers. It will not, however, be making recommendations on   
   treatment, for now. The    
   report is due by spring 2015.   
      
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