Abstract
OBJECTIVES: To investigate the value of cytokine, chemokine, and neurofilament light chain (NfL) concentrations in predicting relapse risk, chronic epilepsy, and functional impairment in LGI1 autoimmune encephalitis (AE). METHODS: Cytokines/chemokines (IL-1-beta, IL-2, IL-4, IL-5, IL-6, IL-8/CXCL8, IL-10, IL-12p70, IL-13, IL-17A, GM-CSF, TNF-alpha, IFN-gamma, CXCL9, CXCL10, CXCL13, BAFF) and NfL concentrations were measured in CSF and paired serum from LGI1-AE patients evaluated at Mayo Clinic (01/2015-02/2024), using a multiplex immunoassay system (ELLA, Bio-Techne) and correlated with clinical outcomes. A laboratory-based cohort of LGI1-IgG-positive patients and control cohorts, including patients with mixed non-inflammatory disorders (MNID), Alzheimer's disease (AD), and temporal lobe epilepsy (TLE) were analyzed. RESULTS: Forty-four patients with LGI1-AE were included; 29 (66%) were male, with a median age of 68.5 years (range, 8-85). Median time from symptom onset to CSF sampling was eight months (IQR, 3-17); 19/42 (45%) experienced a clinical relapse and 27% developed chronic epilepsy. Serum IL-6, serum and CSF IL-8/CXCL8, and IL-17A were higher in LGI1-IgG positive patients than MNID (p < 0.05). TLE cytokine/chemokine profiles were similar to LGI1 AE; AD patients had lower serum IL-6 and CSF IL-8/CXCL8 (p = 0.04; p = 0.01), and higher serum IL-17A and GM-CSF (p = 0.004; p = 0.01) than LGI1-AE. Higher CSF IL-6 and IL-8/CXCL8 in LGI1-AE associated with clinical relapse (p < 0.05) and higher CSF NfL associated with chronic epilepsy (p = 0.01). CONCLUSION: Elevations in IL-6, IL-8/CXCL8, and IL-17A were identified in this LGI1-AE cohort. CSF IL-6, IL-8/CXCL8, and NfL levels are potential prognostic biomarkers for risk of relapse and chronic epilepsy in LGI1-AE.