Clinical significance of human herpesvirus 6 detected in cerebrospinal fluid: a 10-year retrospective study in children

Abstract

Background. Human herpesvirus 6 (HHV-6) is occasionally detected in the cerebrospinal fluid (CSF) of young children, but its clinical significance remains uncertain. This study aimed to describe HHV-6-positive cases and to explore features that may help distinguish presumed infection from bystander detection. Methods. We retrospectively reviewed pediatric patients with CSF HHV-6 detected by multiplex polymerase chain reaction or the FilmArray Meningitis/Encephalitis (FA-ME) panel between January 2015 and March 2025 at a single tertiary hospital. Cases were categorized as presumed HHV-6 infection or bystander detection based on clinical features and the presence of alternative pathogens or diagnoses. Clinical and laboratory findings were compared between the two groups. Results. Among 1,865 children tested, HHV-6 was detected in 25 (1.3%; median age, 6 months), all of whom presented with fever. Seizures occurred in seven (28%) and ataxia in one (4%). Two patients developed encephalitis; one had abnormal imaging and later developed epilepsy. Seventeen patients were classified as presumed infection. In this group, rash was more prevalent (59% vs. 13%, p = 0.04), neutrophil and platelet counts were lower at admission and declined further at follow-up (p < 0.05), and aspartate aminotransferase (AST) levels were higher (p < 0.01) than those in the bystander infection group. CSF pleocytosis did not differ significantly between groups. Two patients received ganciclovir; both had HHV-6 detected early by the FA-ME panel, and one was subsequently diagnosed with bacterial sepsis. Conclusions. HHV-6 encephalitis was uncommon. Rash, changes in neutrophil and platelet counts, along with elevated AST levels may help interpret CSF HHV-6 detection, but these findings require validation in larger studies incorporating virologic confirmation.