Clinical features of varicella-zoster virus meningitis diagnosed by polymerase chain reaction without abnormal routine cerebrospinal fluid analysis

This study aimed to investigate the clinical features of varicella-zoster virus (VZV) meningitis cases diagnosed by polymerase chain reaction (PCR) despite normal routine cerebrospinal fluid (CSF) testing. A retrospective review was performed on hospitalized central nervous system (CNS) infection cases at our institution from 2013 to 2024. VZV meningitis cases were analyzed and divided into two groups: those diagnosed by positive PCR without routine CSF abnormalities (PCR Group) and those with routine CSF abnormalities (Usual Group). PCR methods included conventional techniques and a rapid detection system (FilmArray^®). Among 75 CNS infection cases (49 viral, 13 bacterial, 6 tuberculosis, 2 fungal, and 1 amoebic), 29 VZV meningitis cases were identified. Compared to the Usual Group (n = 25), the PCR Group (n = 4) had significantly lower CSF cell counts (median 1.0 vs. 99.0/µl, p < 0.001) and protein levels (44.0 vs. 70.0 mg/dl, p < 0.001) but similar glucose levels (58.0 vs. 54.0 mg/dl, p = 0.17). All PCR Group cases were female (vs. 52% in the Usual Group), had a trigeminal skin rash (vs. 52%), and presented with headache without meningeal irritation signs (vs. 44.0%) or fever. 50% of cases in the PCR Group were immunocompromised (vs.24%). Other clinical and epidemiological features were similar in both groups. Routine CSF analysis may fail to reveal abnormalities in VZV meningitis, particularly in both immunocompromised and immunocompetent female patients presenting with trigeminal skin rash and headache in the absence of meningeal irritation signs or fever. PCR is recommended to facilitate prompt and accurate diagnosis in such cases.