Revisiting the viral etiology of aseptic meningitis: A comparative evaluation of PCR and cell culture methods in cerebrospinal fluid specimens

Aim: Aseptic meningitis is caused by a wide range of infectious agents, and viruses are the leading etiology. Although molecular diagnostic tools have improved considerably, the causative pathogen cannot be identified in a large proportion of cases. In this study, we investigated the presence of Enterovirus, Herpes Simplex Virus (HSV), Varicella-zoster  Virus (VZV), and Cytomegalovirus (CMV) in cerebrospinal fluid (CSF) specimens from patients with suspected aseptic meningitis, using both polymerase chain reaction (PCR) and conventional cell culture.

Materials and Methods: We analyzed CSF specimens from 30 patients (15 pediatric, 15 adult; 20 female, 10 male) hospitalized with a prediagnosis of aseptic meningitis at Erciyes University Hospitals between March 2004 and June 2005. HSV-DNA, CMV-DNA, VZV-DNA, and Enterovirus-RNA were tested by real-time PCR. Twenty-three specimens with sufficient volume were also inoculated into Hep-2 and MRC-5 cell cultures for viral isolation. We calculated sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of cell culture using PCR as the reference method.

Results: HSV-DNA was positive in 15 of 30 specimens (50%). None of the specimens yielded CMV-DNA, VZV-DNA, or Enterovirus-RNA. Cytopathic effect (CPE) consistent with HSV appeared in 7 of 23 (30.4%) Hep-2 cultures and in only 1 of 23 (4.3%) MRC-5 cultures. Compared with PCR, Hep-2 culture had a sensitivity of 87.5% (95% CI: 52.9 to 97.8%), specificity of 100%, PPV of 100%, and NPV of 93.8%. Five patients (16.7%) died during hospitalization.

Conclusions: HSV was the only viral agent detected in this hospitalized cohort. PCR was faster and more sensitive than cell culture for identifying viral pathogens in CSF. We recommend using both methods together to maximize diagnostic accuracy. The persistent difficulty in identifying the etiology of viral meningitis, even with newer multiplex panels, confirms that comparative diagnostic studies on this topic are still needed.