Serostatus-Specific Prognostic Profiles and Phenotype-Dependent Therapeutic Windows in Autoimmune Encephalitis: A Multicenter Cohort Study

While autoimmune encephalitis (AE) outcomes vary, serostatus-specific prognostic determinants and institutional clustering effects remain poorly characterized. We aimed to delineate the distinct prognostic architecture of AE, identifying serostatus-specific risk factors and potential therapeutic windows.

This multicenter, retrospective cohort study (2016-2024) included 498 patients (382 antibody-positive [Ab+], 116 antibody-negative [Ab-]) across 11 tertiary centers. The primary endpoint was 1-year poor functional outcome (mRS > 2). We utilized Least Absolute Shrinkage and Selection Operator (LASSO) regression and generalized linear mixed models (GLMM) to adjust for institutional clustering, alongside phenotype-treatment interaction analyses.

Poor outcomes occurred in 12.9% of patients. GLMM analysis demonstrated negligible institutional heterogeneity. Prognostic architectures diverged by serostatus: Ab+ outcomes were dictated by failure to achieve early functional remission (discharge mRS: OR = 3.74; CASE: OR = 1.56; both p < 0.01) and age ≥ 65 years (OR = 5.78, p = 0.040). Conversely, Ab- outcomes were independent of discharge severity metrics, driven by baseline demographic and phenotypic features: age ≥ 65 and atypical presentation. Crucially, clinical phenotype modified the therapeutic response (p_interaction = 0.025). Delayed immunotherapy (≥ 30 days) significantly increased poor outcome risk in atypical presentations (OR = 9.16, p = 0.025) but not in canonical phenotypes. A derived prognostic nomogram yielded excellent discrimination (AUC = 0.909).

Long-term AE outcomes are dictated by patient-level clinical severity and phenotype, with negligible influence from institutional variations. These findings advocate for a serostatus- and phenotype-stratified management strategy. Crucially, atypical presentations exhibit a highly time-dependent therapeutic window requiring rapid immunotherapy, while elderly patients warrant prioritized intervention to mitigate inherent baseline risks.