Modern infectious and immune-mediated causes of acute encephalitis in children

Acute encephalitis in children is a heterogeneous clinical syndrome with diverse infectious and immune-mediated causes. Despite the availability of diagnostic criteria proposed by the International Encephalitis Consortium, establishing the etiology remains challenging in many cases, as clinical manifestations often overlap across different etiological groups. Recent epidemiological changes, including the emergence of SARS-CoV-2 and the rise in recognized autoimmune encephalitides, have further expanded the spectrum of potential triggers in pediatric populations. Aim - to summarize current evidence on the etiological structure of acute encephalitis in children and analyze the contribution of infectious, autoimmune, and post-infectious mechanisms over the past decade. A structured literature review was conducted using publications from 2015-2025, focusing on epidemiology, pathogen distribution, diagnostic approaches, and the evolving role of advanced molecular technologies in etiology determination. Despite comprehensive diagnostic work-up, the etiological agent can be identified in only about half of pediatric encephalitis cases. Viral pathogens, particularly HSV-1, enteroviruses, HHV-6, influenza, and emerging infections such as SARS-CoV-2, remain the leading causes. However, autoimmune encephalitides, including anti-NMDAR, MOG-associated disease, and AQP4-IgG-positive neuromyelitis optica spectrum disorders, are increasingly recognized, accounting for a substantial proportion of previously unexplained cases. Novel diagnostic tools such as metagenomic next-generation sequencing, phage immunoprecipitation sequencing (PhIP-Seq), and rapid multiplex PCR panels significantly improve detection rates. The growing number of reported co-infections and virus-triggered immune dysregulation highlights the importance of considering both infectious and immune-mediated etiologies in every child with acute encephalitis. Conclusions. The etiological landscape of pediatric acute encephalitis is dynamic and continues to evolve in response to emerging pathogens and expanding diagnostic capabilities. Integrating modern molecular methods with standardized clinical and immunologic assessment is essential to increase the proportion of etiologically confirmed cases. The development and implementation of a unified, stepwise diagnostic algorithm will facilitate the earlier identification of the underlying cause, the timely initiation of targeted therapy, and improved outcomes in affected children. The authors declare no conflict of interest.