Identifying Key Prognostic Indicators for Relapse and Chronic Epilepsy in Autoimmune Encephalitis: Insights from a Multicenter Retrospective Study

Abstract

Objective: The aims of this study were to investigate clinical factors associated with encephalitis relapse and chronic epilepsy development, and to evaluate the effectiveness of immunotherapy on encephalitis relapse.

Methods: Patients with autoimmune encephalitis diagnosed as positive for neuronal surface antibodies in five general hospitals were included. A minimum 12-month follow-up period was conducted, and binary logistic regression analysis was used to identify predictors of encephalitis relapse and chronic epilepsy development. Additionally, decision curve analysis (DCA) was employed to assess the clinical net benefit of predicting encephalitis relapse and chronic epilepsy.

Results: The study encompassed 65 patients with autoimmune encephalitis. The one-year relapse rate for encephalitis was 13.9%. The CASE score (P=0.045) was associated with encephalitis relapse, with subsequent immunotherapy proving beneficial in enhancing outcomes. Chronic epilepsy prevalence at one year was 26.2%, particularly higher among patients with positive LGI1 antibodies. Although adjustments in antiseizure medications were partially effective, 41.2% of patients developed drug-resistant epilepsy (DRE). DCA confirmed that the predictive models provided significant net clinical benefit in assessing the risk of encephalitis relapse and chronic epilepsy. Notably, the presence of diffuse cortical atrophy, medial temporal lobe atrophy, or cerebellar hemisphere atrophy was linked to relapsing encephalitis and chronic epilepsy.

Conclusion: Most cases of autoimmune encephalitis are effectively managed, however, a minority of patients experience relapse or chronic epilepsy. The CASE score and LGI1 antibodies are independent risk factors for encephalitis relapse and chronic epilepsy development, respectively. Immunotherapy remains beneficial for relapsing patients, yet a portion may progress to DRE. Individuals with relapses and chronic epilepsy are predisposed to the development of cortical, temporal lobe, and cerebellar atrophy.

Keywords: autoimmune encephalitis; chronic epilepsy; immunotherapy; prognosis; relapse.

Figure 1

Elevated CASE scores represent independent predictors of patients’ higher risk for encephalitis relapse. (A) Forest plots of the multivariate logistic regression analysis for the prediction of encephalitis relapse. A multivariate model was adjusted for age at onset, diffuse slow wave, multiple seizures daily/daily, FBDS, and CASE scores. (B) Decision curve analysis highlighted the clinical net benefit in the prediction of encephalitis relapse.

Figure 2

Positive LGI1 antibodies were independent predictors of patients’ higher risk for chronic epilepsy. (A) Forest plots of the multivariate logistic regression analysis for the prediction of chronic epilepsy. A multivariate model was adjusted for age at onset, multiple seizures daily/daily, interictal epileptiform discharge, FBDS, CASE scores, SE, and LGI1 antibody. (B) Decision curve analysis highlighted the clinical net benefit in the prediction of chronic epilepsy.

Figure 3

Further immunotherapy provided beneficial for encephalitis relapsing patients. (A) The evaluation of CASE scores at 3, 6 and 12 months post-encephalitis relapse. (B) The evaluation of mRS scores at 3, 6 and 12 months post-encephalitis relapse.

Figure 4

Patients with relapsing encephalitis are prone to encephalatrophy. (A) Proportion of DCA, mTA or CHA in patients with relapsing versus non-relapsing encephalitis. (B) Proportion of DCA, mTA or CHA in patients with relapsing versus non-relapsing encephalitis. (C) mRS scores for encephalatrophy (DCA, mTA or CHA) and without encephalatrophy.

Figure 5

Patients with chronic epilepsy after encephalitis are prone to encephalatrophy. (A) Proportion of DCA, mTA or CHA in patients with and without chronic epilepsy. (B) Proportion of chronic epilepsy versus no chronic epilepsy in DCA, mTA or CHA.