Metagenomic analysis for central nervous system infections: clinical utility and future directions

Encephalitis and meningitis are neurological emergencies in which delayed diagnosis may lead to severe neurological sequelae, necessitating accurate and rapid etiological identification. In recent years, metagenomic next-generation sequencing (mNGS), which enables comprehensive analysis of microbial genomes without prespecified hypotheses, has attracted increasing attention. Its clinical application in neuroinfectious diseases has contributed to improved diagnostic yield and the detection of rare pathogens. In particular, mNGS has been shown to be useful in clinically challenging situations such as culture-negative cases, anaerobic infections, mixed infections, and immunocompromised hosts. However, the technology also has inherent limitations, including enormous data volume, challenges in interpreting pathogenic relevance, limited turnaround time, high cost, and a lack of standardized analytical pipelines. Thus, although mNGS represents a valuable complementary tool to conventional diagnostic methods, it is not universally applicable, and its results must be carefully interpreted within appropriate clinical contexts.