Clinical significance of Epstein-Barr virus polymerase chain reaction in cerebrospinal fluid

Purpose Epstein-Barr virus (EBV) is implicated in various neurological conditions. However, the relationship between EBV DNA in cerebrospinal fluid (CSF) and central nervous system (CNS) infection is unclear. We evaluated the clinical manifestation of patients with EBV DNA detected in CSF. Methods We reviewed the medical records of patients admitted to Seoul National University Hospital from January 2000 to March 2021 who underwent EBV polymerase chain reaction (PCR) tests in CSF. The subjects were divided into positive and negative groups depending on the presence of EBV DNA, and further clinical information was obtained from positive patients. Results CSF EBV PCR tests were performed in 807 patients, and 57 (7.1%) tested positive. Pleocytosis was common (81.1%) in CSF samples with EBV DNA detected, and the proportion was significantly higher than that in samples that were EBV PCR negative (44.5%, p < 0.0001). Among 57 patients with EBV DNA detected in CSF, 51 (89.5%) were diagnosed with CNS infection or inflammatory disorders. Of the 51 patients, 31 (60.8%) had possible etiologies other than EBV. Follow-up evaluation was conducted in 19 of 20 patients, and 63.2% showed a favorable outcome. Conclusion Positive EBV PCR in CSF is mostly nonspecific and should be interpreted with caution. A comprehensive workup is needed to identify other etiologies before considering EBV as the sole culprit.