Serum neurofilament light

Abstract

<h3>Objective</h3> To explore the utility of serum neurofilament light chain (NfL) as a biomarker for primary and secondary neuroaxonal injury after ischemic stroke (IS) and study its value for the prediction of clinical outcome. <h3>Methods</h3> We used an ultrasensitive single-molecule array assay to measure serum NfL levels in healthy controls (n = 30) and 2 independent cohorts of patients with IS: (1) with serial serum sampling at hospital arrival (n = 196), at days 2, 3, and 7 (n = 89), and up to 6 months post stroke; and (2) with standardized MRI at baseline and at 6 months post stroke, and with cross-sectional serum sampling at 6 months (n = 95). We determined the temporal profile of serum NfL levels, their association with imaging markers of neuroaxonal injury, and with clinical outcome. <h3>Results</h3> Patients with IS had higher serum NfL levels compared with healthy controls starting from admission until 6 months post stroke. Serum NfL levels peaked at day 7 (211.2 pg/mL [104.7–442.6], median [IQR]) and correlated with infarct volumes (day 7: partial <i>r</i> = 0.736, <i>p</i> = 1.5 × 10⁻¹⁵). Six months post stroke, patients with recurrent ischemic lesions on MRI (n = 19) had higher serum NfL levels compared to those without new lesions (n = 76, <i>p</i> = 0.002). Serum NfL levels 6 months post stroke further correlated with a quantitative measure of secondary neurodegeneration obtained from diffusion tensor imaging MRI (<i>r</i> = 0.361, <i>p</i> = 0.001). Serum NfL levels 7 days post stroke independently predicted modified Rankin Scale scores 3 months post stroke (cumulative odds ratio [95% confidence interval] = 2.35 [1.60–3.45]; <i>p</i> = 1.24 × 10⁻⁰⁵). <h3>Conclusion</h3> Serum NfL holds promise as a biomarker for monitoring primary and secondary neuroaxonal injury after IS and for predicting functional outcome.