A Retrospective, Cross-sectional Study Evaluating Plasma Neurofilament Light Levels in Autoimmune Encephalitis (2553)

Objective: To evaluate plasma neurofilament light (NfL) levels in autoimmune encephalitis (AE). Background: Despite an incidence rate of 0.8/100,000 person-years in AE, individual antibody syndromes are rare. Each particular antibody syndrome has a different clinical phenotype, making one unifying clinical outcome measure difficult to assess as a group. However, the final common pathway is neuronal damage, suggesting that NfL may be a unifying biomarker of central nervous system injury that is easily obtainable through blood and may demonstrate a quantitative treatment response. NfL is a promising biomarker for neuronal injury that may predicting disease activity in other inflammatory diseases such as relapsing-remitting multiple sclerosis, but this has not been well studied in AE. Design/Methods: Patients were retrospectively identified who were enrolled in the biorepository at the Rocky Mountain MS Center at the University of Colorado. Patients had a well-defined autoimmune neurological disease and followed between 2014 and 2019. NfL was tested using the Single Molecule Array (SIMOA) technology (Quanterix). Levels >10 pg/ml were considered positive values based on normative control data. Results: Twenty plasma and 8 CSF samples stored in the biorepository were evaluated. Elevated plasma levels of NfL were seen in patients with the various types of AE: glial fibrillary acidic protein (GFAP), glutamic acid decarboxylase (GAD)-65, leucine-rich glioma-inactivated (LGI1), glycine receptor, and N-methyl-D-aspartate (NMDA) receptor antibodies. Higher NfL levels in the blood were found in untreated, acute presentations and subjects with active symptoms. Six of seven patients with levels >10pg/ml presented acutely. Patients within 6 months of presentation had plasma NfL that were higher (17.6+/−22.4pg/ml) than those who were farther out from presentation (5.8+/−7.3pg/ml)(p=0.025) There is a positive correlation between plasma and CSF (r=0.74) with mean levels 39pg/ml higher in CSF. Conclusions: Our findings support the use of plasma NfL as a potential non-invasive biomarker in patients with antibody-mediated AE. Disclosure: Dr. Piquet has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Sanofi Genzyme and honorarium from MedLink. Dr. Piquet has received research support from Drake Family through the Children’s Hospital Colorado Foundation and research funding from the Rocky Mountain MS Center.. Dr. Alvarez has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with consulting fees from Actelion, Bayer, Biogen, Celgene, EMD Serono, Genentech, Genzyme, Novartis, and TG Therapeutics. Dr. Alvarez has received research support from Biogen, Genentech, Novartis, TG Therapeutics, and Rocky Mountain MS Center.Dr. Bennett has received personal compensation from Alexion, Chugai, Clene Nanomedicine, Equillium, Frequency Therapeutics, Genentech, Roche, MedImmune/Viela Bio, Novartis. Dr. Bennett has received royalty, license fees, or contractual rights payments from Aquaporumab. Dr. Bennett has received research support from EMD Serono, Novartis.Dr. Knapp has nothing to disclose. Dr. Sillau has nothing to disclose. Dr. Nair has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Celgene, Genentech, Novartis, Gilead. Dr. Nair has received research support from Genentech, Biogen.Dr. Vollmer has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen Idec, Genentech-Roche, Siranax, Celgene, EMD Serono, Novartis. Dr. Vollmer has received research support from Rocky Mountain MS Center, Biogen, Actelion, F. Hoffman -La Roche, TG Therapeutics.