Predictive Value of Neuronal Apoptotic Bodies in Cerebrospinal Fluid for the Differential Diagnosis of Bacterial from Viral Meningitis

Introduction: Rapid and accurate differentiation of bacterial and viral meningitis is critical for effective treatment but remains challenging. To address this, our study investigated the frequency of apoptotic bodies in cerebrospinal fluid (CSF) as a potential diagnostic biomarker to distinguish the cause of infection. Materials and Methods The study was conducted on 1115 CSF samples collected from patients clinically suspicious of meningitis. CSF was directly analyzed to evaluate leukocyte count, protein, and sugar concentration, and to determine bacterial causative agents using direct smear, Gram staining, and culture on blood and chocolate agar. Furthermore, to determine viral meningitis, PCR was used to detect the presence of viral agents such as Herpes simplex virus type 1 (HSV-1) and Enterovirus (EV). Given the leukocyte count, the samples were divided into CSF with less or more than 5 leukocytes per ml as negative and positive CSF, respectively. Then CSF was assessed for the frequency of small particles as neuronal apoptotic bodies stained with fluorochrome-labeled anti-CD24 and CD54 antibodies and intracellular staining of Choline acetyltransferase (ChAT) and Tyrosine hydroxylase (TH) using flow cytometry. Results Out of 1,115 analyzed CSF samples, 77 were positive (WBC ≥ 5/mm³), and 77 negative samples (WBC < 5/mm³) were randomly selected as controls. Within the positive group, the causes of infection were identified as bacterial for 10 samples, viral for 12, and the cause remained unknown for 55 samples. No significant differences were observed in the levels of CD24+, CD54+, or CD24/CD54 + apoptotic bodies—which express the neuronal markers ChAT and TH—across the bacterial, viral, and unknown cause (UC) infection groups. Despite this, their frequencies were substantially elevated in all positive CSF samples compared to negative controls. Conclusions While the levels of apoptotic bodies in CSF can differentiate between samples with pleocytosis (WBC ≥ 5/mm³) and those without, they cannot distinguish bacterial from viral meningitis. This suggests that the elevation in neuronal particles is likely a nonspecific consequence of leukocyte recruitment into the CNS and subsequent neuronal apoptosis, rather than a pathogen-specific response or a marker of patient survival. Furthermore, the low incidence of confirmed bacterial and viral meningitis in our study may have influenced these results.