Abstract
ObjectiveTo evaluate plasma neurofilament light (NfL) levels in autoimmune neurologic disorders (AINDs) and autoimmune encephalitis (AE).BackgroundEach particular neural autoantibody syndrome has a different clinical phenotype, making one unifying clinical outcome measure difficult to assess. While this is a heterogeneous group of disorders, the final common pathway is likely CNS damage and inflammation. Defining a biomarker of CNS injury that is easily obtainable through a blood sample and reflects a positive treatment response would be highly advantageous in future therapeutic trials. Measurement of blood concentration of neurofilament light (NfL) chain, however, may provide a biomarker of central nervous system (CNS) injury in AE and other AINDs. Here we provide an initial evaluation of plasma NfL levels in AE as well as other AINDs during active and chronic phases of disease and demonstrate its potential utility as a minimally-invasive biomarker for AE and AINDs.Design/MethodsPatients were retrospectively identified who were enrolled in the biorepository at the Rocky Mountain MS Center at the University of Colorado, or were prospectively enrolled after initial presentation. Patients had a well-defined AIND and were followed between 2014 and 2021. NfL was tested using the Single Molecule Array (SIMOA) technology. Patients with headaches but without other significant neurologic disease were included as controls.ResultsTwenty-six plasma and 14 CSF samples of patients with AINDs, and 20 plasma control samples stored in the biorepository were evaluated. A positive correlation was found between plasma and CSF NfL levels for patients with an AIND (R2 = 0.83, p < 0.001). Elevated plasma levels of NfL were seen in patients with active AE compared to controls [geometric mean (GM) 51.4 vs. 6.4 pg/ml, p = 0.002]. Patients with chronic symptoms (>6 months since new or worsening symptoms) of AE or cerebellar ataxia (CA) showed a trend toward lower plasma NfL levels (GM 15.1 pg/ml) compared to active AE or CA. Six patients with longitudinal, prospective sampling available demonstrated a trend in decreased plasma NfL levels over time.ConclusionsOur findings support the use of plasma NfL as a potential minimally-invasive biomarker of CNS injury.
Highlights
Over the past decade, multiple autoimmune neurologic disorders (AINDs) mediated by pathogenic neuronal cell surface antibodies have been identified
AINDs encompass all neurologic isolated inflammatory disease thought to be mediated by the adaptive immune system–including autoimmune encephalitis (AE), stiff person spectrum disorder (SPSD), autoimmune cerebellar syndromes, and demyelinating diseases like neuromyelitis optica spectrum disorder (NMOSD) or anti-myelin oligodendrocyte (MOG) antibody disease (MOGAD)
Plasma neurofilament light (NfL) levels in patients with chronic AE/Cerebellar Ataxia (CA) were obtained a median of 10 months after the last episode of symptom worsening
Summary
Multiple autoimmune neurologic disorders (AINDs) mediated by pathogenic neuronal cell surface antibodies (neuronal surface antibody syndromes, or NSAS) have been identified. AINDs encompass all neurologic isolated inflammatory disease thought to be mediated by the adaptive immune system–including autoimmune encephalitis (AE), stiff person spectrum disorder (SPSD), autoimmune cerebellar syndromes, and demyelinating diseases like neuromyelitis optica spectrum disorder (NMOSD) or anti-myelin oligodendrocyte (MOG) antibody disease (MOGAD) Both observational and retrospective studies have reported improved clinical outcomes with immunotherapy [1–5] in AINDs; there remains a strong need for randomized, controlled clinical trials to establish a standard of care for the treatment of AE and the nondemyelinating AINDs. While change in seizure frequency and cognitive functional status have been used as outcome measures for AE therapy, these measures are problematic end-points due to their poor specificity and sensitivity across the heterogenous presentations of even AEs caused by the same autoantibody [6].
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