Relapse predictors and brain atrophy in antibody-positive and antibody-negative autoimmune encephalitis: a...

Autoimmune encephalitis (AE) is clinically heterogeneous, but whether relapse predictors and structural correlates of disability differ by antibody status remains unclear. We aimed to identify serostatus-specific predictors of relapse and determine whether brain atrophy is associated with 12-month functional outcome across the AE spectrum.

In an 11-center retrospective cohort study conducted from 2016 to 2024, we included patients fulfilling 2016 AE diagnostic criteria with ≥12 months of follow-up. Serostatus, relapse, 12-month modified Rankin Scale (mRS), and MRI-defined diffuse cortical atrophy (DCA), medial temporal atrophy (mTA), and cerebellar atrophy were analyzed. Multivariable logistic regression was used to identify relapse predictors within serostatus strata. Functional outcomes and regional brain atrophy patterns were compared between antibody-positive and antibody-negative cohorts.

Among 467 patients (361 antibody-positive, 106 antibody-negative), 1-year relapse rates were 25.5% and 22.6%, respectively. In antibody-positive AE, faciobrachial dystonic seizures were independently associated with relapse (OR = 2.50, P = 0.022). Within LGI1-AE, older age at onset was associated with relapse (OR = 1.04, P = 0.042). In antibody-negative AE, frequent daily seizures independently predicted relapse (OR = 4.12, P = 0.023). Antibody-negative patients had more frequent DCA than antibody-positive patients (32.1% vs 16.6%, P < 0.001). Across serostatus groups, moderate-to-severe DCA and mTA was associated with worse 12-month functional outcome (all P < 0.05).

Relapse-associated factors differed between antibody-positive and antibody-negative AE. In both cohorts, moderate-to-severe DCA and mTA were associated with greater disability at 12 months. Structural MRI may therefore provide complementary information for prognostic assessment, pending prospective validation.