To correlate clinical outcomes measures including Modified Rankin Score (mRS) and Montreal Cognitive Assessment (MOCA) with blood-based biomarkers in anti-Leucine-Rich Glioma Inactivated-1 (LGI1) Autoimmune Encephalitis (AE) as possible biomarkers of disease severity and long-term outcomes.

LGI1 AE is characterized by seizures and cognitive, behavioral, and memory disturbances. Biomarkers of inflammation and neuronal and glial injury have been evaluated as potential markers of future disability and prognosis in AE.

We prospectively enrolled 21 LGI1 AE patients from October 2018 to April 2024. NfL, GFAP, UCHL-1, and tau were calculated by SIMOA using SR-X from Quanterix (67 blood and 6 CSF samples) and a cytokine panel (hIL12p70, hIL1B, hIL4, hIL5, hIFNg, hIL6, hIL8, hIL22, hTNFα, hIL10) using SP-X (46 serum samples). We include 16 migraine patients as non-inflammatory controls. Biomarker concentrations were logarithmically transformed and analyzed using longitudinal regression.

The LGI1 AE group was 76.2% male with an average (sd) age of 63.3 (11.2) years at the onset of symptoms; control group was 56.3% male with an average age of 58.0 years. The ratio of means between LGI1 AE and controls (ratio estimate) for NfL was 1.55 (p=0.0372) at symptom onset and approached controls at 6 years. The ratio estimate for GFAP was 1.73 (p=0.0018) at symptom onset and 1.50 (p=0.0218) at 3 years. The ratio estimates of cytokines hIL1b and hIL10 were 2.65 (p=0.0373) and 6.97 (p<0.0001) respectively at symptom onset. The mRS at symptom onset was 3.34 and dropped to 0.56 at 5 years. Mean MOCA scores were 18.45 at onset and increased to 29.40 at 6 years. This cohort remained seizure-free for up to 6 years post symptom onset.

This trend of improved clinical symptoms is paralleled with initially high NfL and GFAP levels, followed by a decline in these levels over time without clinical relapse over 6 years.