# Long-term outcomes in leucine-rich glioma inactivated-1 autoimmune encephalitis and associated biomarkers of inflammation and neuronal and glial injury

## TL;DR

This study examines long-term outcomes and blood-based biomarkers in patients with LGI1 autoimmune encephalitis, finding that NfL and GFAP levels correlate with disease progression and recovery.

## Contribution

The study identifies NfL and GFAP as potential biomarkers for disease severity and prognosis in LGI1 autoimmune encephalitis.

## Key findings

- LGI1 AE patients showed significant improvement in clinical scores over 5-6 years.
- Plasma NfL and GFAP levels declined over time, aligning with clinical recovery.
- Higher initial NfL and GFAP levels correlated with slower cognitive recovery.

## Abstract

Leucine-rich glioma inactivated 1 (LGI1) autoimmune encephalitis (AE) is characterized by seizures, as well as cognitive, memory, and behavioral disturbances. Blood-based biomarkers for inflammation and neuronal and glial injury have been evaluated as potential markers of disease severity and prognosis in AE.

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 were logarithmically transformed and analyzed using longitudinal regression with the ratio of means between LGI1 AE and non-inflammatory controls. Clinical data were collected and correlated with blood-based biomarkers to assess their relationship to disease severity and long-term outcomes.

Twenty-one LGI1 AE patients were enrolled from October 2018 to April 2024, and 16 migraine headache patients (56.3% male; average age: 58 years) served as non-inflammatory controls. One LGI1 AE patient in our cohort had a clinical relapse. 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 a 5-year follow-up. Mean MoCA scores were 18.45 at the onset and increased to 29.40 in the 6-year follow-up. The model estimated geometric mean plasma NfL values at disease diagnosis to be 11.86 pg/mL; it was estimated to be 6.07 pg/mL when compared to non-inflammatory controls. The model also estimated the plasma GFAP values to be 77.70 pg/mL; it was estimated to be 36.26 pg/mL when compared to non-inflammatory controls. 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. MoCA scores tended to recover more quickly in patients presenting with lower Nfl scores at symptom onset.

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.