Aseptic central nervous system infections: age-related and etiological differences in a ten-year cohort from eastern hungary

Abstract Background Aseptic central nervous system (CNS) infections remain diagnostically challenging, with the causative pathogen unidentified in a substantial proportion of cases and clinical presentation varying by age and etiology. Regional epidemiological data are important for understanding local disease patterns and supporting routine diagnostic decision-making. This study evaluated the clinical, laboratory, microbiological, and outcome characteristics of suspected or confirmed viral CNS infections in a ten-year tertiary-center cohort from Eastern Hungary. Methods We retrospectively analyzed patients hospitalized between January 2014 and November 2024 with clinically suspected or microbiologically confirmed viral CNS infection at a tertiary referral center in Eastern Hungary. Patients were stratified by age group (17–49 vs. ≥50 years) and etiological subgroup: West Nile virus (WNV) infection, other confirmed viral infections, and unidentified etiology. Age-stratified analyses were repeated using a 60-year cutoff as a sensitivity analysis. Demographic characteristics, presenting clinical symptoms, cerebrospinal fluid findings, microbiological test results, neuroimaging data, hospital stay, and short- and long-term clinical outcomes were evaluated. Results Among 120 patients, younger individuals more frequently presented with headache, whereas older patients more often had impaired consciousness, neuropsychiatric manifestations, cranial nerve symptoms, lower Glasgow Coma Scale scores, higher serum C-reactive protein levels, and longer hospital stays. These age-related findings were largely consistent in sensitivity analyses using a 60-year cutoff. In the overall cohort, increasing age correlated with longer hospitalization and lower CSF white blood cell counts. WNV infection accounted for half of the cohort and was associated with older age, higher CSF protein levels, polymorphonuclear CSF predominance, and less frequent headache. In multivariable analysis, older age (OR 1.040/year, 95% CI 1.015–1.065; p = 0.002) and higher CSF protein concentration (OR 1.003/mg/L, 95% CI 1.001–1.004; p = 0.001) were independently associated with WNV infection. Other confirmed viral infections were more often associated with seizures and skin manifestations, whereas cases with unidentified etiology showed milder CSF abnormalities and shorter hospitalization. Conclusion Viral CNS infections showed marked age- and etiology-related differences in clinical presentation and CSF profiles. In this endemic region, WNV was a leading etiology, and was independently associated with older age and higher CSF protein concentration. The substantial proportion of unidentified cases highlights persistent diagnostic limitations and supports the need for etiology- and region-specific diagnostic strategies in routine clinical practice.