Anti-N-methyl-d-aspartate receptor encephalitis: insights and future treatment directions

Two decades after the first recognition of anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis, advances have led to consensus-based diagnostic criteria and treatment recommendations, yet no FDA-approved therapies exist. Recent studies highlight limitations of serum-only antibody testing, importance of tailored tumor surveillance, and epidemiologic variation across racial and ethnic groups. Prognostic indicators, exemplified by the anti-NMDAR encephalitis 1-year functional status (NEOS) score, have refined outcome prediction. Although nearly 80% of patients achieve favorable functional outcomes, persistent neuropsychiatric and cognitive deficits may impact quality of life, highlighting the need for improved therapeutic strategies. Accordingly, randomized clinical trials are underway, including studies evaluating B cell- and interleukin-6 (IL-6)-targeted therapies, for anti-NMDAR encephalitis. This review synthesizes these developments and discusses current treatment approaches with a focus on emerging investigational therapies.