Late-onset anti-NMDA receptor encephalitis

Objective: To describe the clinical features and outcome of anti-NMDA receptor (NMDAR) encephalitis in patients >= 45 years old. Method: Observational cohort study. Results: In a cohort of 661 patients with anti-NMDAR encephalitis, we identified 31 patients >= 45 years old. Compared with younger adults (18-44 years), older patients were more often male (45% vs 12%, p < 0.0001), had lower frequency of tumors (23% vs 51%, p = 0.002; rarely teratomas), had longer median time to diagnosis (8 vs 4 weeks, p = 0.009) and treatment (7 vs 4 weeks, p = 0.039), and had less favorable outcome (modified Rankin Scale score 0-2 at 2 years, 60% vs 80%, p < 0.026). In multivariable analysis, younger age (odds ratio [OR] 0.15, confidence interval [CI] 0.05-0.39, p = 0.0001), early treatment (OR 0.60, CI 0.47-0.78, p < 0.0001), no need for intensive care (OR 0.09, CI 0.04-0.22, p < 0.0001), and longer follow-up (p < 0.0001) were associated with good outcome. Rituximab and cyclophosphamide were effective when first-line immunotherapies failed (OR 2.93, CI 1.10-7.76, p = 0.031). Overall, 60% of patients older than 45 years had full or substantial recovery at 24 months follow-up. Conclusions: Anti-NMDAR encephalitis is less severe in patients >= 45 years old than in young adults, but the outcome is poorer in older patients. In this age group, delays in diagnosis and treatment are more frequent than in younger patients. The frequency of underlying tumors is low, but if present they are usually carcinomas instead of teratomas in younger patients. Early and aggressive immunotherapy will likely improve the clinical outcome.