Some patients with CFS may have an encephalopathy

In earlier work, we have shown that CFS patients with no history of psychiatric comorbidity comprise the group that has the most cognitive impairment and the most brain MRI abnormalities relative to healthy sedentary controls. These findings appeared to be meaningful in view of the fact that this group of patients had poorer physical function than patients with psychiatric comorbidity. Our inference was that patients in the "no-psych" group had an underlying encephalopathy. To further test this hypothesis, we did spinal taps in patients and healthy controls. Approximately 30% of the patients had slight elevations in either protein concentration and/or in white cell count in comparison to 0% of controls. The group with abnormal spinal fluid had a significantly lower rate of current depression than those with normal fluid. This result supported in part our use of psychiatric comorbidity (or its lack thereof) as a stratification strategy. We assayed for multiple cytokines in spinal fluid and explored various stratification strategies. While psychiatric comorbidity was not useful, we did find elevations in IL-10 in those patients with abnormal spinal fluid; the increased IL-10 could be a direct consequence of whatever process caused the abnormalities. Additionally, we found increased IL-8 in patients with a sudden, influenza-like illness onset. We also review studies on cerebral blood flow and symptom endorsement. The results of all these studies support the hypothesis that central neuro-immunological dysregulation could be involved in the pathophysiology of chronic fatigue.