Relapse Burden and Long-term Recovery in LGI1-IgG Autoimmune Encephalitis: Predictors and Treatment Responses
Naveen Paramasivan1, Soo Hyoo Ahn2, Andreu Vilaseca-Jolonch1, Felipe Jones1, Andrea Stabile1, Surendra Dasari1, Kelsey Smith1, Jeffrey Britton1, Eoin Flanagan1, Andrew McKeon1, Anastasia Zekeridou1, Sean Pittock1, Stephen Yates3, Panayotes Demakakos3, Soon-Tae Lee2, Divyanshu Dubey1
1Mayo Clinic, 2Seoul National University Hospital, 3UCB
Objective:
To characterize long-term outcomes, relapse burden, and treatment responses in Leucine-rich glioma inactivated 1 (LGI1)-IgG Autoimmune Encephalitis (AE).
Background:
Factors that influence relapses and long-term outcomes in LGI1–IgG AE are poorly defined.
Design/Methods:
Retrospective longitudinal study of 171 adults with LGI1-IgG AE evaluated at Mayo Clinic (January 1, 2000–December 31, 2023), with external validation in 64 adults from Seoul National University Hospital. Poor functional (modified Rankin Scale >2), cognitive (Clinical Dementia Rating >0.5), and relapse outcomes were assessed at short-term (3–6 months) and last follow-up. Associations were examined using multivariable logistic regression, Cox proportional hazards models with time-varying covariates, and mixed-effects ordinal regression.
Results:
Among 171 Mayo Clinic patients (65% male; median age 66 years), 145 completed 6‑month follow‑up; 53 (37%) experienced 69 relapses. Corticosteroid use at presentation was associated with favorable short‑term functional, cognitive, and seizure outcomes. Poor baseline CDR, treatment delay, and cumulative relapses predicted poor long‑term functional and cognitive outcomes. Male sex (OR 3.71; 95% CI, 1.29–10.72; p=0.015) and persistent LGI1‑IgG seropositivity (OR 2.94; 95% CI, 1.10–7.86; p=0.032) were associated with relapse. Chronic immunotherapy reduced relapse risk, particularly rituximab (HR 0.19; 95% CI, 0.05–0.76) and chronic corticosteroids (HR 0.32; 95% CI, 0.14–0.73). Higher cumulative relapse burden limited long‑term functional recovery (OR 2.94; 95% CI, 1.44–6.01; p=0.003).
Validation in the SNUH cohort (64 patients; 18 relapses) confirmed these associations, including relapse risk with persistent LGI1‑IgG seropositivity (OR 6.90; 95% CI, 1.40–33.92), poor cognition with baseline CDR, treatment delay, and relapses; and reduced relapse hazard with rituximab (HR 0.06; 95% CI, 0.00–0.89).
Conclusions:
In LGI1-IgG AE, baseline cognitive deficits, treatment delay and cumulative relapses are strongly associated with poor long-term functional and cognitive outcomes. Persistent LGI1-IgG seropositivity identifies patients at increased risk of relapse. Strategies that prevent relapses, particularly rituximab and chronic corticosteroid therapy appear to be essential for optimizing sustained recovery.
Generative AI Usage
No, did not use generative AI in the drafting or editing in this abstract.
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