Association of Encephalitis With Viruses in Cerebrospinal Fluid in Children: A Case Series

Introduction The application of polymerase chain reaction (PCR) to cerebrospinal fluid (CSF) analysis has enabled the direct detection of neuropathogenic viruses in patients with meningitis or encephalitis. However, the presence of a virus in the CSF does not necessarily confirm a diagnosis of encephalitis. Clinical judgment is required to determine whether neurological follow-up is warranted. This study aimed to investigate the incidence of encephalitis among patients with viral detection in CSF and to evaluate the relationship between viral load and disease occurrence. Methods Patients under 16 years of age with a virus detected in CSF by PCR between April 2012 and March 2023 at the Tokyo Metropolitan Children's Medical Center were included in this study. Lumbar puncture and viral PCR testing were performed in patients with a clinical suspicion of meningitis or encephalitis. Encephalitis was diagnosed according to the criteria established by the International Encephalitis Consortium. Data on patient demographics, PCR results, viral load, and final diagnosis were extracted from electronic medical records. Viral species and viral loads were compared between patients diagnosed with and without encephalitis. Results A total of 64 patients had a virus detected in CSF between April 2012 and March 2023. Of these, 32 patients (50%) were diagnosed with encephalitis. The median age of patients with encephalitis was 13.5 months (interquartile range {IQR}: 1.75-33 months), compared to nine months (IQR: 0-22.5 months) in those without encephalitis. Among patients with encephalitis, the most frequently detected viruses were human herpesvirus 6 (HHV-6) in 13 patients, enterovirus (EV) in eight, and human parechovirus (HPeV) in one. In patients without encephalitis, HHV-6 was detected in eight cases, enterovirus in four, and HPeV in 13. Patients with encephalitis due to HHV-6 showed a higher viral load (median: 4,800 copies/mL) compared to those without encephalitis (median: 1,070 copies/mL; p = 0.019). Conclusion Encephalitis was diagnosed in 50% of patients with viral detection in CSF. HHV-6 and enterovirus were the most commonly identified pathogens. Elevated HHV-6 viral load may be associated with the presence of encephalitis.