AUTHOR=Bai Lin , Geng Chang , Guan Hongzhi 

TITLE=Rediscovering parainfectious encephalopathy in the post-COVID-19 era

JOURNAL=Frontiers in Immunology

VOLUME=Volume 16 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1634383

DOI=10.3389/fimmu.2025.1634383

ISSN=1664-3224

ABSTRACT=The COVID-19 pandemic has unveiled the pivotal role of systemic inflammatory responses in neurological complications, particularly parainfectious encephalopathy. Accumulating evidence has established innate immune overreaction—distinct from direct viral neuro-invasion or autoantibody-mediated reaction—as the fundamental mechanism. The clinical manifestations of parainfectious encephalopathy are highly diverse, spanning from mild cases, such as mild encephalopathy with or without a reversible splenial lesion (MERS or ME), to catastrophic syndromes like acute necrotizing encephalopathy (ANE) and febrile infection-related epilepsy syndrome with or without a claustrum lesion (FIRES-C or FIRES). In this article, we summarize the phenotypes, diagnosis, and treatment strategies for parainfectious encephalopathy to enhance clinical recognition and understanding of this re-emerging disorder.