Relapse risk and functional outcomes in anti-LGI1 encephalitis: A multicenter retrospective analysis.

BACKGROUND: Anti-leucine-rich glioma-inactivated protein 1 (LGI1) encephalitis presents relapse risk and potential functional impairment, with no established maintenance treatment guidelines. OBJECTIVES: The study aimed to uncover prognostic signatures, and identify predictors of relapse and poor outcome using real-world evidence. DESIGN: This multicenter retrospective study included anti-LGI1 encephalitis patients from five tertiary hospitals in Eastern China between January 2015 and January 2024, with ≥ 24-month follow-up. METHODS: Relapse was defined as the presence of new or worsening clinical features after at least 3 months of stability or improvement. Poor outcome was defined as a modified Rankin Scale score > 2 at last follow-up. RESULTS: A total of 104 patients were included (median age 56.5 years, 60.6% male). Following the acute phase, the majority (66.3%) received prolonged corticosteroid treatment (≥6 months) without steroid-sparing maintenance immunotherapy (SSMI), whereas 16.3% received SSMI. Twelve patients (11.5%) experienced relapse. Hyponatremia at diagnosis was more common in relapsing patients (p = 0.017), and was significantly associated with an increased risk of relapse in Cox regression (hazard ratio = 4.67, 95% confidence interval [CI] = 1.41-15.53, p = 0.012). Poor outcome was observed in 17 patients (16.3%), with male sex (odds ratio [OR] = 5.12, 95% CI = 1.27-34.48, p = 0.041) and hyponatremia (OR = 4.69, 95% CI = 1.54-15.47, p = 0.008) as potential risk factors. CONCLUSION: This study suggests that hyponatremia is associated with an increased risk of relapse and poor outcome in anti-LGI1 encephalitis. These findings may facilitate individualized risk stratification, but further validation in larger prospective cohorts is needed.