Longitudinal dynamics of serum neurofilament light chain and prognostic value for functional outcome after acute stroke: a prospective cohort study

Background Serum neurofilament light chain (sNfL) is a blood biomarker of neuroaxonal injury, but its early longitudinal dynamics and prognostic value in clinically heterogeneous acute stroke populations remain insufficiently defined. This study characterized early sNfL changes and examined their association with functional outcome after acute stroke. Methods This prospective cohort study consecutively enrolled 104 patients with acute stroke and 86 healthy controls (HCs) between January 2023 and December 2024. Patients were grouped as intracerebral hemorrhage (ICH, n = 28), ischemic stroke treated with intravenous thrombolysis (IS+IVT, n = 33), and ischemic stroke without intravenous thrombolysis (IS−IVT, n = 43). sNfL was measured within 24 h after onset (D1) and on day 7 (D7). Functional outcome was assessed by modified Rankin Scale (mRS) at 3 and 6 months. Linear mixed-effects models assessed longitudinal sNfL trajectories. Multivariable logistic regression assessed prognostic associations, with the 3-month outcome as the primary endpoint and the 6-month outcome as the secondary endpoint. Restricted cubic spline (RCS) and interaction analyses were exploratory. Results sNfL increased significantly from D1 to D7 ( p < 0.001) and was higher in patients with stroke than in HCs at D1 ( p < 0.001). In the linear mixed-effects model adjusted for age and admission National Institutes of Health Stroke Scale (NIHSS) score, longitudinal sNfL trajectories did not differ significantly among the clinical stroke groups (time × group interaction, p = 0.225). The predominantly mild-to-moderate severity profile may have limited the detection of trajectory differences. In multivariable logistic regression, each 10-pg/mL increase in D1 sNfL was associated with 5% higher odds of poor functional outcome at 3 months (OR = 1.05; 95% CI, 1.00–1.12; p = 0.047) and 7% higher odds at 6 months (OR = 1.07; 95% CI, 1.01–1.14; p = 0.025). D7 sNfL was not independently associated with poor functional outcome after adjustment. Exploratory RCS analyses found no statistical evidence of nonlinearity for D1 sNfL and suggested a nonlinear association between D7 sNfL and 3-month poor functional outcome. Conclusion sNfL levels increased during the first week after acute stroke. Higher D1 sNfL was associated with poor functional outcome at 3 and 6 months, suggesting potential value for early prognostic assessment.