Evaluation of Plasma Neurofilament Light Chain Levels as a Biomarker of Neuronal Injury in the Active and Chronic Phases of Autoimmune Neurologic Disorders

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.

Multi-Omic Blood Biomarkers as Dynamic Risk Predictors in Late-Onset Alzheimer’s Disease

“…Elevated plasma NfL levels are detected in a wide range of neurodegenerative diseases [66] including AD [67,68], frontotemporal dementia (FTD) [69], amyotrophic lateral sclerosis [70] and HIV-associated dementia [71]. However, NfL can also be elevated in acute non-neurodegenerative causes of brain injury including stroke [72] and encephalitis [73], highlighting that clinical context is important for biomarker interpretation. The role of NfL may be in discriminating between neurological disorders and psychiatric disorders, both of which can present with cognitive and memory dysfunction, a common clinical dilemma [74,75].…”

Psychiatrische Autoimmunenzephalitis – Diagnose und therapeutische Ansätze

“…Wichtig sind in diesem Zusammenhang auch Hinweise auf eine stattfindende Neurodegeneration, die bei Autoimmunenzephalitiden reversibel oder irreversibel auftreten kann [17]. Insbesondere die Neurofilamentleichtketten (Nfl) im Blutplasma können als Biomarker einer neuronalen Schädigung im Akutstadium und weniger ausgeprägt auch im chronischen Stadium einer Autoimmunenzephalitis verstanden werden [18]. Dies ist insbesondere daher relevant, da im Serum und Liquor die Nfl hoch miteinander korrelieren.…”

Neural Surface Antibodies and Neurodegeneration: Clinical Commonalities and Pathophysiological Relationships

“…NFL has also been evaluated in serum, where its levels moderately correlate with those in the CSF [ 145 ]. Increased levels of NFL in both serum and plasma have been reported in AEs, including NSA-AEs and specifically NMDAR encephalitis compared to HC [ 138 , 145 , 146 ]. Serum NFL levels in NMDAR encephalitis, however, are lower compared to herpes simplex encephalitis (HSE) [ 138 ].…”

“…Moreover, in NSA-AEs the evolution of serum NFL levels seems to mirror the clinical course, with stable levels in clinically stable patients, increasing levels in cases with clinical worsening, and decreasing levels in patients with clinical improvement [ 145 ]. Another small study on AEs, not limited to NSA-AEs, reported longitudinally decreasing plasma levels of NFL; accordingly, patients with chronic AE (i.e., evaluated at least 6 months after symptom onset or last clinical deterioration) had lower plasma NFL levels, albeit non-significantly, compared to those with active AE [ 146 ]. Although in a study on LGI1 encephalitis no significant difference was observed between levels of T-tau, P-tau181 and NFL from CSF samples taken before or after initiation of immunosuppressive treatment [ 140 ], in NSA-AEs reduced CSF levels of T-tau have been reported following immunosuppressive treatment, while the normalization of CSF NFL levels paralleled the resolution of MRI abnormalities [ 139 ].…”