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Associations of viral infections and antiviral vaccinations with anti-NMDAR and other forms of autoimmune encephalitis

Bamberg S, Schulte-Frankenfeld PM, Kreye J

Brain, behavior, & immunity - health, 2026

Abstract

Background: Autoimmune encephalitis (AIE) comprises a diverse group of neurological disorders characterized by autoantibodies targeting specific antigens of the central nervous system (CNS). While the pathophysiological effects of these autoantibodies have been extensively studied, the principles and immunological triggers underlying their generation remain less well understood. Viral infections and antiviral vaccinations have been reported as potential immunological triggers. However, a systematic overview of their specific associations and frequencies across AIE subtypes is lacking.

Methods: Here, we performed a systematic literature review in PubMed to identify published cases of AIE linked to viral infections or antiviral vaccinations, and to test whether herpes simplex virus (HSV)-associated anti-N-methyl-D-aspartate receptor encephalitis (NMDAR-E) represents a disproportionately strong association. We quantified the frequencies of viral infection- or vaccine-related AIE across ten common antibody-defined subtypes, and characterized their epidemiological and clinical features, complemented by data from 23 population-based viral encephalitis cohorts.

Results: We identified 556 cases, of which 488 were infection-associated and 68 followed vaccination. The most frequent combination was HSV infection in association with NMDAR-E, which outnumbered all other reported virus-AIE associations combined and was almost exclusively attributable to preceding HSV encephalitis (HSE).…

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