Retrovirus XMRV may not be associated with Chronic Fatigue Syndrome in the central nervous system

There has been substantial mystery surrounding the origins of Chronic Fatigue Syndrome (CFS), a condition affecting as many as four million Americans and marked by symptoms that include a sense of weariness that sleep does not improve and difficulty with memory and concentration. A study published in 2009 suggested that a retrovirus known as XMRV (xenotropic murine leukemia-related virus) was present in the blood of CFS patients, and that XMRV might be the cause. However, new research led by Steven E. Schutzer, MD, of the University of Medicine and Dentistry of New Jersey-New Jersey Medical School, and his colleagues, may be the first to examine the body compartment most involved for neurologic symptoms -- the central nervous system and its liquid spinal fluid.

This study did not find XMRV in the spinal fluid and is the latest of several studies that call the 2009 finding into question as a cause. However the other studies only focused on blood -- not the central nervous system.

Schutzer and colleagues, in an article published online by Annals of Neurology, examined the cerebrospinal fluid of 43 individuals with a generally accepted definition of CFS. The team targeted spinal fluid based on the belief that if there is a neurological component to CFS as the symptoms suggest, then spinal fluid might contain a relevant pathogen such as a virus that is associated with the syndrome.

"Spinal fluid is a liquid window to the brain," said Schutzer. "It is an important area of the body to examine when there is abnormal central nervous system function and an infectious or immunologic cause is suspected."

The relative separation of the central nervous system from the circulatory system was also an important consideration, because the sheer complexity of blood makes cause and effect far harder to decipher when substances are found there.

Schutzer and his team analyzed spinal fluid using specialized Polymerase Chain Reaction (PCR) techniques that amplified nucleic acid present in the fluid, and found no evidence of XMRV. Other common viruses also appeared to be absent.

This latest finding that XMRV does not appear to be in the spinal fluid of patients with Chronic Fatigue Syndrome comes within weeks of another study published by Schutzer and colleagues [PLoS ONE 6(2): e17287. doi:10.1371/journal.pone.0017287] that analyzed the spinal fluid of the same 43 CFS patients and found 738 proteins in those patients' fluid that appear to be specific to CFS. The earlier paper compared that group of patients with others who either were healthy controls or had been diagnosed with Lyme disease. The two studies, taken in tandem, strongly suggest that while XMRV does not appear to be directly associated with CFS in the central nervous system, other substances found in spinal fluid do have an association.

"This latest study was not designed to address the ongoing controversy over possible XMRV in the blood," said Schutzer. "It was specifically designed to survey the central nervous system for XMRV and, if found, other viruses. Here, and in general, the detection of a microbe is only a first step. Additional research would be necessary to prove that it is a cause of a condition," Schutzer emphasized.

The authors urge investigators to search prospectively for microbes and other possible mechanisms of the syndrome, paying particular attention to the central nervous system.