April 19, 2011 There appears to be no link between chronic fatigue syndrome (CFS) and xenotropic murine leukemiarelated virus (XMRV), a gammaretrovirus, in the spinal fluid of patients with CFS, a new study suggests.
The study may be the first to examine cerebrospinal fluid directly regarding this issue and adds to the evidence against a controversial link between XMRV and CFS.
Steven E. Schutzer, MD, with the University of Medicine and Dentistry of New Jersey, Newark, and colleagues reported their findings online April 5, 2011, in the Annals of Neurology.
According to the researchers, "Spinal fluid is a liquid window to the brain. It is an important area of the body to examine when there is abnormal central nervous system (CNS) function and an infectious or immunologic cause is suspected."
The origins of CFS remain inconclusive, the researchers note. The condition affects around 4 million people in the United States, with symptoms that include cognitive dysfunction and fatigue that is not improved by sleep. It has previously been suggested, in a 2009 study, that XMRV may be a cause of CFS because it was detected in the blood of patients with CFS.
XMRV Absent in Spinal Fluid
The current study, however, found no evidence of XMRV in cerebrospinal fluid. It is the latest of multiple studies to question the 2009 findings and the cause of CFS.
A total of 43 individuals with a generally accepted definition of CFS underwent examination of their spinal fluid. Spinal fluid was analyzed using polymerase chain reaction techniques that amplified nucleic acid present in the fluid. The researchers found no evidence of XMRV or other common viruses.
Spinal fluid was assessed because CFS symptoms may include a neurologic component and spinal fluid may contain relevant pathogens associated with the syndrome. Another consideration was the relative separation of the CNS from the circulatory system when elements are found in the blood, cause and effect are difficult to interpret because of blood's complexity.
The current results are supported by an earlier study by Schutzer and colleagues in which the same 43 individuals underwent spinal fluid examination. The article compared the CFS group with either healthy controls or patients with Lyme disease. The results from both studies suggest that although XMRV does not appear to be associated with CFS, other substances found in cerebrospinal fluid are associated.
According to Dr. Schutzer, "This latest study was not designed to address the ongoing controversy over possible XMRV in the blood. It was specifically designed to survey the central nervous system for XMRV and, if found, other viruses." He suggests that microbe detection is only the first step and recommends further research to validate it as the cause of CFS.
The researchers encourage a prospective search for microbes and other possible causes of the syndrome, paying particular attention to the CNS.
Unanswered Questions
John Coffin, PhD, a research professor with Tufts University in Boston, Massachusetts, reported on the controversy on whether XMRV contributes to CFS in Medscape Medical News. "Even if other institutions find an association between XMRV and CFS, it does not prove that the virus causes CFS or that it is the only cause."
However, some patients with CFS reportedly are using antiretroviral drugs intended to treat HIV infection, according to a June 8, 2010, article in the Chicago Tribune.
Professor Greg Towers, with University College London in the United Kingdom, and colleagues reported no evidence of XMRV in CFS in their genomic study, according to Medscape Medical News.
"XMRV is not the cause of chronic fatigue syndrome," Dr. Towers said at the time. However, his research did not rule out a viral cause for CFS. "But we know it is not this virus causing it," he added.
Association Not Discounted
CFS researcher Athe Tsibris, MD, from the Division of Infectious Diseases at Massachusetts General Hospital, Boston, and colleagues suggested that "geographical clustering of XMRV infection" could explain why some researchers discovered XMRV in patients with CFS.
"[Our finding] suggests that differences in PCR [polymerase chain reaction] techniques from study to study do not explain the disparate results seen in XMRV studies of chronic fatigue syndrome," Dr. Tsibris noted in a written release from the Infectious Diseases Society of America.
Dr. Tsibris's research was previously reported on by Medscape Medical News. The peripheral blood mononuclear cells of 293 patients from academic hospitals were tested. Of the participants, 23 met the Centers for Disease Control and Prevention definition of CFS, and 95 were from a general cohort of patients who received medical care, which could have included healthy individuals seeking routine care. The study authors reported that they did not detect XMRV DNA in any samples.
Despite the number of studies that have been unable to find an association between XMRV and CFS, Dr. Tsibris suggests that it is too early to discount an association.
"Additional next steps that would be helpful would be a standardized, cross-validated assay for XMRV detection in clinical samples," he said. This would lead to agreement on what a positive XMRV test result is "and a blinded multilaboratory comparison of XMRV testing from CFS and control samples," Dr. Tsibiris adds.
Funding for Schutzer's study was provided by the National Institutes of Health through the National Institute of Allergy and Infectious Diseases. The study authors have disclosed no relevant financial relationships.
Ann Neurol. Published online April 5, 2011.
