Rituximab Improves Recovery Trajectories in Pediatric N-Methyl-D-Aspartate Receptor Encephalitis

ObjectiveEarly first-line immunotherapy improves outcomes in pediatric N-methyl-D-aspartate receptor encephalitis (pNMDARE), while consensus guidelines reserve second-line therapies (e.g., rituximab) for refractory cases. Design/MethodsRetrospective pNMDARE cohort study across 18 institutions from the CONNECT (CONquering Neuroinflammation and Epilepsies ConsorTium) registry. Modified Rankin Scale (mRS) was evaluated at presentation, 3, 6, 12, and 24 months. Exact matching (2:1 without replacement) accounted for corticosteroids, intravenous immunoglobulin, plasmapheresis, cyclophosphamide, and presenting mRS. Generalized linear mixed models were used; adjusted models incorporated time and nested random effects. ResultsAmong 219 patients, 103 were matched (65 rituximab-treated, 38 no-rituximab). Baseline characteristics and unadjusted comparisons of mRS at each timepoint were similar. Severe disability (mRS 5) at 24 months occurred only in the no-rituximab group (n=2). In adjusted analyses across follow-ups (n=335 observations), rituximab-treated patients improved more over time (β=-1.47, 95% CI [-2.71, -0.22], p=.022). Rituximab effect varied by corticosteroid use (β=1.81, 95% CI [0.53, 3.08], p=0.006) and over time (β=-.23 per month, 95% CI [-0.45, -0.01], p=0.044). In post-hoc contrasts versus neither treatment, rituximab-alone showed the greatest mRS improvement (-2.30; 95% CI [-3.30, -1.30], p<0.001), followed by rituximab + corticosteroids (-2.16; 95% CI [-3.14, -1.18], p<0.001), and corticosteroids-alone (-1.66; 95% CI [-2.90, -0.43], p=0.009). mRS did not differ between rituximab + corticosteroids versus rituximab-alone (0.14; 95% CI [-0.20, 0.48], p=0.413) or corticosteroids-alone (-0.50; 95% CI [-1.44, 0.45], p=0.297). ConclusionsRituximab treatment in pNMDARE improves recovery trajectory, although benefits may be modulated by other treatment effects. Prospective large-scale studies are needed to validate findings and examine effects of individual immunotherapies, timing of treatments, and relapse rates.