Long-term Outcomes in Leucine-Rich Glioma Inactivated-1 (LGI1) Autoimmune Encephalitis and Associated Biomarkers of Inflammation, Neuronal and Glial Injury

Tyler L Borko^1,2Phillip Winters³Kelli M Money^1,4Stefan Sillau¹Sadie Eggmann¹Sean Selva¹Alanna Richie¹Ryan Kammeyer^1,5Gregory P Owens¹Jeffrey L Bennett^1,6,7Amanda L Piquet^1*

• ¹Department of Neurology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States
• ²Midwestern University Arizona College of Osteopathic Medicine, Glendale, United States
• ³School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States
• ⁴UCHealth Memorial Hospital Central, Colorado Springs, Colorado, United States
• ⁵University of Colorado Children's Hospital, Aurora, Colorado, United States
• ⁶Department of Ophthalmology, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States
• ⁷Programs in Neuroscience and Immunology, University of Colorado Anschutz Medical Campus, Aurora, United States

Introduction: Leucine-rich glioma inactivated 1 (LGI1) autoimmune encephalitis (AE) is characterized by seizures and cognitive, memory, and behavioral disturbances. Blood-based biomarkers of inflammation and neuronal and glial injury have been evaluated as potential markers of disease severity and prognosis in AE. Methods: Patients diagnosed with LGI1 AE, confirmed by cell-based assay, were enrolled and followed prospectively to gather plasma samples for biomarker testing. Biomarkers of neuronal and glial injury included plasma neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), ubiquitin c-terminal hydrolase L1 (UCHL-1), tau, and cytokine markers of inflammation. Biomarker data was logarithmically transformed and analyzed using longitudinal regression with the ratio of means between LGI1 AE and non-inflammatory controls. Clinical data were collected correlated to the blood-based biomarkers to assess their relationship to disease severity and long-term outcomes. Results: Twenty-one LGI1 AE patients were enrolled from October 2018 to April 2024 and 16 migraine headache patients (56.3% male, average age 58.0 years old) served as non-inflammatory controls. One LGI1 AE patient in our cohort had a clinical relapse. Both modified Rankin Score (mRS) and Montreal Cognitive Assessment (MoCA) improved over time. The mRS at symptom onset was 3.34 and dropped to 0.56 in 5-year follow up. Mean MoCA scores were 18.45 at the onset and increased to 29.40 in 6-year follow up. The model estimated geometric mean plasma NfL values at disease diagnosis to be 11.86 pg/mL, compared to non-inflammatory controls 6.07 pg/mL, and plasma GFAP values were 77.70 pg/mL, compared to non-inflammatory controls at 36.26 pg/mL. The trend of clinical improvement is paralleled with a slow decline in NfL and GFAP levels, returning to levels like our control population after 6 and 3 years, respectively. In patients presenting with lower Nfl scores at symptom onset, MoCA scores tended to recover more quickly. Conclusion: Improved clinical symptoms were correlated with improvements in initially high NfL and GFAP levels. In one patient with a clinical relapse, NfL and GFAP levels increased. NfL and GFAP may be useful biomarkers of disease progression in patients with LGI1 AE, however additional studies are needed to better understand the effects of immunotherapy.