Spinal fluid abnormalities in patients with chronic fatigue syndrome
Authors
Natelson BH, Weaver SA, Tseng CL, Ottenweller JE
Publication
Clinical and Diagnostic Laboratory Immunology 2005; 12(1): 52–5
Abstract
Arguments exist as to the cause of chronic fatigue syndrome (CFS). Some think that it is an example of symptom amplification indicative of functional or psychogenic illness, while our group thinks that some CFS patients may have brain dysfunction. To further pursue our encephalopathy hypothesis, we did spinal taps on 31 women and 13 men fulfilling the 1994 case definition for CFS and on 8 women and 5 men serving as healthy controls. Our outcome measures were white blood cell count, protein concentration in spinal fluid, and cytokines detectable in spinal fluid. We found that significantly more CFS patients had elevations in either protein levels or number of cells than healthy controls (30 versus 0%), and 13 CFS patients had protein levels and cell numbers that were higher than laboratory norms; patients with abnormal fluid had a lower rate of having co-morbid depression than those with normal fluid. In addition, of the 11 cytokines detectable in spinal fluid, (i) levels of granulocyte-macrophage colony-stimulating factor were lower in patients than controls, (ii) levels of interleukin-8 (IL-8) were higher in patients with sudden, influenza-like onset than in patients with gradual onset or in controls, and (iii) IL-10 levels were higher in the patients with abnormal spinal fluids than in those with normal fluid or controls. The results support two hypotheses: that some CFS patients have a neurological abnormality that may contribute to the clinical picture of the illness and that immune dysregulation within the central nervous system may be involved in this process.
Comment by ME Research UK
This paper provides interesting evidence for cytokine abnormalities within the cerebrospinal fluid of some, but not all, CFS patients. There is extensive evidence available in the literature of immunological abnormalities in patients with CFS usually represented as a decrease in NK cell activity, an increase in the percentage of T cells expressing activation markers, decreased lymphocyte stimulation by certain mitogens and soluble antigens, and increased production of certain pro-inflammatory cytokines such as transforming growth factor β1 (1). These abnormalities are usually presented as significant differences between the CFS patients and age and gender matched control subjects but this hides the fact that not all of the patients are different from the controls — that’s the problem with statistics — and for this reason none of these measurements can be afforded the status of a ‘marker’.
Natelson et al carried out a lumbar puncture on 44 CFS patients and 13 healthy controls and investigated the cerebrospinal fluid for white blood cells, protein concentration and cytokines. They found that thirty percent of CFS patients had elevations in protein levels and/or in white blood cell count relative to laboratory norms; in contrast, none of the control subject had such elevations. Just as important, the team of researchers stratified their patients in terms of symptom presentation and showed that the sub-group of patients without evidence of current depression had the highest rate of abnormalities in their spinal fluid. This adds further weight to the developing hypothesis that CFS is heterogeneous and that clinical examination, MRI imaging and neuropsychological testing can be used to delineate sub-groups of patients and that research studies need to address this problem by using adequate numbers of patients that are well characterized in terms of gender, age, type of onset (e.g., sudden vs gradual, viral vs stress), duration of symptoms, other concurrent clinical conditions and geographic occurrence (cluster vs isolated cases) (2).
Is it possible that the abnormalities expressed in this paper could explain some of the symptoms of ME/CFS? The answer is yes they can explain some ME/CFS aspects but there is a gap in our knowledge as to how alterations in cytokine levels lead to the severe symptoms that some ME/CFS patients experience. The finding of an immune dysfunction with the central nervous system of some patients is important but just as significant is the emergent view that the term CFS needs to be unpacked, urgently.
