Objective: Management of autoimmune encephalitis (AE) is challenging due to a lack of reliable biomarkers. We here assess the combination of glial fibrillary acid protein (GFAP) and neurofilament (NfL) as biomarkers for diagnosis and disease monitoring of AE.

Methods: GFAP and NfL CSF levels (cGFAP, cNfL) of 42 AE patients were correlated with CSF markers of neuroinflammation. NfL/GFAP ratios were compared between patients with stable and active AE, stable and active multiple sclerosis (MS), and patients undergoing diagnostic lumbar puncture without evident pathological alterations (controls).

Results: In patients with AE, cGFAP levels showed strong correlations with albumin and IgG quotients and moderate correlations with CSF cell count; cNfL levels showed weak correlations with albumin quotients. cGFAP and cNfL levels showed no significant differences between patients with and without epileptic activity or inflammatory MRI lesions. Both sNfL and sGFAP correlated with the Clinical Assessment Scale in Autoimmune Encephalitis. Compared to NfL or GFAP alone, the NfL/GFAP ratio from CSF or serum led to a clearer separation of AE from MS patients and controls. Furthermore, serum NfL/GFAP ratios better discriminated active from stable AE.

Conclusions: cGFAP levels indicate intrathecal inflammatory processes in patients with active AE to a stronger degree than cNfL levels. Serum NfL/GFAP ratios recognize active AE, suggesting this ratio identifies AE patients with CNS-compartmentalized neuronal injury (autoantibody-mediated or cytotoxic) behind a relatively intact blood-brain barrier. Our findings indicate that the NfL/GFAP ratio can function as a blood-based biomarker, aiding clinicians with diagnosis and disease management of AE.