Microbiological Diagnosis of Emerging and Re-Emerging Infections of the Central Nervous System—A Scoping Review

Emerging infectious diseases (EIDs) are an increasing global health concern, and central nervous system (CNS) involvement is particularly critical owing to its high morbidity and mortality. Despite advances in diagnostic technologies, timely and accurate microbiological diagnosis remains challenging. This scoping review maps the available evidence on microbiological diagnostic methods for emerging and re-emerging CNS infections and identifies key knowledge gaps. Articles published between January 2020 and December 2024 were reviewed, and 142 articles were included. Diagnostic approaches comprised polymerase chain reaction (PCR)-based molecular testing, metagenomic next-generation sequencing (mNGS), nanopore-targeted sequencing, cytokine profiling, and unbiased serology, among others. Viral pathogens were more frequently represented than bacterial, fungal and parasitic ones, for which evidence derived mainly from case reports, small case series and retrospective studies and requires validation in larger prospective studies. Although culture remains the reference standard for the diagnosis of many emerging and re-emerging CNS pathogens, molecular assays, particularly PCR-based methods, are currently the cornerstone of diagnosis. Overall, the findings highlight the central role of molecular diagnostics in the detection of emerging and re-emerging CNS infections, while underscoring the need for further validation of novel diagnostic approaches and more robust evidence across pathogen groups, particularly those underrepresented in the literature.