Predictive value of persistent cerebrospinal fluid antibodies at 12 months for long-term clinical outcomes in pediatric anti-NMDAR encephalitis: a retrospective cohort study

Abstract

Persistent cerebrospinal fluid (CSF) antibodies against the N-methyl-D-aspartate receptor (NMDAR) are common in children recovering from anti-NMDAR encephalitis, but their association with long-term clinical outcomes remains unclear. This study aimed to assess whether persistent CSF NMDAR antibodies at 12 months after diagnosis predict long-term clinical outcomes. In this retrospective observational cohort study, we included patients diagnosed with pediatric anti-NMDAR encephalitis between November 2012 and January 2026. Participants were stratified into two groups according to their CSF NMDAR antibody status at the 12-month follow-up. Clinical characteristics were compared between the groups, and long-term seizure-free rates were assessed using Kaplan–Meier survival analysis. Among 162 initially identified patients, 41 (25.3%) met the inclusion criteria (mean age 8.7 ± 4.2 years; 78.0% female). At 12 months, CSF NMDAR antibodies remained detectable in 68.3% (28/41) of patients. Although the antibody-persistent group showed a trend toward a higher relapse rate than the antibody-negative group (42.9% vs. 0%), this difference did not reach statistical significance ( P  = 0.053). In contrast, the antibody-persistent group required significantly more frequent first-line (57.1% vs. 7.7%, P  = 0.003) and second-line (39.3% vs. 0%, P  = 0.024) immunotherapy. Survival analysis revealed no statistically significant difference in seizure-free rates between the two groups during long-term follow-up (median 26 months; log-rank P  = 0.601). In pediatric anti-NMDAR encephalitis, persistent CSF NMDAR antibodies at 12 months serve as a marker of incomplete remission and are associated with a trend toward a higher relapse rate and a significantly greater need for intensified immunotherapy, and may help identify patients who would benefit from more intensive immunomodulatory therapy.