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CSF can show if central nervous system disease is infection-related

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November 6, 2018

Mark Curtis, MD, PhD
Mark T. Curtis

Cerebrospinal fluid cytokine levels may be clinically useful in determining if central nervous system disorders are infection-related and to distinguish between viral and non-viral infections, according to study findings published in PLoS One.

“Prompt diagnosis for central nervous system (CNS) disorders is very important because the brain is a critical structure and its response to both inflammations generated by infectious agents — viruses, bacteria, fungi or other organisms — or even autoimmune processes is very serious for the brain,” Mark T. Curtis, MD, PhD, associate professor of pathology, anatomy and cell biology at Jefferson (Philadelphia University + Thomas Jefferson University) in Philadelphia, told Infectious Disease News. “People are starting to look at the CNS and realize that, in addition to the cell count, the glucose and the protein, it has other information in it. This is not validated yet, but it’s an approach that is novel.”

The spread of known pathogens and emergence of new ones can make early diagnosis of certain infections difficult, and quickly distinguishing between CNS infections and other brain and spinal cord disorders is critical, according to the researchers.

“Importantly, therapy for these various diseases is drastically different. For example, immunosuppressive and immunomodulatory agents indicated in CNS autoimmune disease and demyelinating disorders (including multiple sclerosis) would be contraindicated and potentially detrimental in the setting of a CNS infection,” they wrote.

According to Curtis and colleagues, cerebrospinal fluid (CSF) “serves as a convenient conduit for inflammatory mediators and signaling proteins released during changes in the CNS environment.” For their study, rather than testing patients for a bacteria or virus, Curtis and colleagues investigated the different cytokine profiles of CNS diseases “and test their potential to differentiate distinct neuropathologic processes.”

They conducted a retrospective study of CSF samples obtained by lumbar puncture at Thomas Jefferson University Hospital in Philadelphia. The 43 patients with a CNS disease included in the study were aged 2 to 80 years. Curtis and colleagues assessed cytokine levels for seven control patients negative for neuro inflammatory processes, 15 patients with CNS infections, three patients with malignant glial (astrocytic) neoplasms, 11 patients with autoimmune and demyelinating disease and six patients with B-cell lymphoma involving the CNS, according to the study.

To determine patterns that could potentially differentiate infections from the other disease groups, Curtis and colleagues analyzed the CSF and tested for the presence of 41 different cytokines. According to the study, 100% of the cases were placed in the appropriate disease group — infection, autoimmune, demyelination, tumor, lymphoma and control — based on the immune response and determined by CSF cytokine level. This revealed an association between cytokine expression and grouping of disease types. They also observed a different cytokine fingerprint associated with a CNS infection when compared with a tumor or autoimmune disease. Furthermore, the CSF cytokine fingerprint differed between viral and non-viral pathogens, including bacteria and fungi.

“It’s the response of the body to the insult. It’s the here and now,” Curtis said. “It’s right now when the person comes into the emergency room, say they have an infection or it’s an autoimmune process, the immune system is actively responding to that insult right now and the proteins that are being released are a response to the state of the patient at that time. That’s pretty powerful.” – by Marley Ghizzone

Disclosures: The authors report no relevant financial disclosures.