Friday, April 3, 2015

Cerebrospinal Fluid, Autoimmunity, and Cognitive Dysfunction in ME/CFS

The hippocampus, a small organ located in the limbic
system, is associated with short-term memory, learning
 and spatial navigation. 
Columbia University has published the second of two significant studies examining immune system markers in ME/CFS. The study, "Cytokine network analysis of cerebrospinal fluid in myalgic encephalomyelitis/chronic fatigue syndrome," was published in Molecular Psychiatry, a top-ranked journal in the field of neuroscience.

The first study, "Distinct plasma immune signatures in ME/CFS are present early in the course of illness" (February 27, 2015), showed that pro-inflammatory cytokines were elevated in the early phase of the disease, but depressed in later stages. After examining cerebrospinal fluid in long-term patients, the Columbia research team found a similar decrease in pro-inflammatory cytokine IL-1 signaling.

What is interesting about the cerebrospinal fluid study is that patients showed an increase in a chemokine called CCL11 (eotaxin).

Eotaxin is a chemical involved in stimulating eosinophils, immune molecules that are implicated in allergic responses. Studies have shown that increased eotaxin reduces cognitive performance. Particularly affected are spatial navigation and the processing of short into long-term memory (learning). These are both functions of the hippocampus, a small organ in the limbic system.

In his book, The Limbic Hypothesis (1993), Dr. Jay Goldstein proposed the damage to the limbic system was the driving force behind ME/CFS. Research conducted since then has repeatedly confirmed Dr. Goldstein's theory. Now, evidence is mounting that the damage is caused by an autoimmune response.

The Columbia researchers concluded that their results:
"...indicate a markedly disturbed immune signature in the cerebrospinal fluid of cases that is consistent with immune activation in the central nervous system, and a shift toward an allergic or T helper type-2 pattern associated with autoimmunity."

Scientists find clues into cognitive dysfunction in chronic fatigue syndrome

Press Release: Columbia University's Mailman School of Public Health, March 31, 2015. Scientists at Columbia University's Mailman School of Public Health have identified a unique pattern of immune molecules in the cerebrospinal fluid of people with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) that provides insights into the basis for cognitive dysfunction - frequently described by patients as "brain fog" - as well as new hope for improvements in diagnosis and treatment.

In the study published in Molecular Psychiatry, Mady Hornig, MD, and colleagues used immunoassay testing methods to measure the levels of 51 immune biomarkers called cytokines in the cerebrospinal fluid of 32 people with ME/CFS for an average of seven years, 40 with multiple sclerosis, and 19 non-diseased controls. The researchers found that levels of most cytokines, including the inflammatory immune molecule, interleukin 1, were depressed in individuals with ME/CFS compared with the other two groups, matching what was seen in the blood study in patients who had the disease for more than three years. One cytokine - eotaxin - was elevated in the ME/CFS and MS groups, but not in the control group.

"We now know that the same changes to the immune system that we recently reported in the blood of people with ME/CFS with long-standing disease are also present in the central nervous system," says Dr. Hornig, professor of Epidemiology and director of translational research at the Center for Infection and Immunity at the Mailman School. "These immune findings may contribute to symptoms in both the peripheral parts of the body and the brain, from muscle weakness to brain fog."

Implications for Diagnosis and Treatment

"Diagnosis of ME/CFS is now based on clinical criteria. Our findings offer the hope of objective diagnostic tests for disease as well as the potential for therapies that correct the imbalance in cytokine levels seen in people with ME/CFS at different stages of their disease," adds W. Ian Lipkin, MD, John Snow Professor of Epidemiology and director of the Center for Infection and Immunity. There is precedent for use of human monoclonal antibodies that regulate the immune response in a wide range of disorders from rheumatoid arthritis to multiple sclerosis. However, the researchers note, additional work will be needed to assess the safety and efficacy of this approach.

Journal Reference: M Hornig, G Gottschalk, D L Peterson, K K Knox, A F Schultz, M L Eddy, X Che, W I Lipkin. Cytokine network analysis of cerebrospinal fluid in myalgic encephalomyelitis/chronic fatigue syndrome. Molecular Psychiatry, 2015; DOI:10.1038/mp.2015.29
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