Acute Neurofilament Light Chain Plasma Levels Correlate With Stroke Severity and Clinical Outcome in Ischemic Stroke Patients
Helle Hvilsted Nielsen, Catarina B. Soares, Sofie S. Høgedal, Jonna Skov Madsen, Rikke B. Hansen, Alex Alban Christensen, Charlotte Madsen, Bettina Hjelm Clausen, Lars Henrik Frich, Matilda Degn, Christian Sibbersen, Kate Lykke Lambertsen
Abstract
Background: Ischemic stroke causes increased blood-brain barrier permeability and release of markers of axonal damage and inflammation. To investigate diagnostic and prognostic roles of neurofilament light chain (NF-L), we assessed levels of NF-L, S100B, interleukin-6 (IL-6), E-selectin, vascular endothelial growth factor-A (VEGF-A), vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1) in patients with acute ischemic stroke or transient ischemic attack (TIA) and healthy controls. Methods: We studied neurofilament (NF) expression in 2 cases of human post-mortem ischemic stroke, representing infarcts aged 3 to >7 days. In a prospective study, we measured plasma NF-L and inflammatory markers <8 hours of symptom onset and at 72 hours in acute ischemic stroke (n=31), TIA (n=9), and healthy controls (n=29). We assessed whether NF-L, S100B, and IL-6 were associated with clinical severity on admission (Scandinavian Stroke Scale, SSS), diagnosis of ischemic stroke versus TIA, and functional outcome at 3 months (modified Rankin Scale, mRS). Results: NF expression increased in ischemic neurons and in the infarcted brain parenchyma after stroke. Plasma NF-L levels were higher in stroke patients than TIA patients and healthy controls, but IL-6 levels were similar. Higher acute NF-L levels were associated with lower SSS scores at admission and higher mRS scores at 3 months. No correlation was observed between NF-L and S100B, NF-L and IL-6, nor between S100B or IL-6 and SSS or mRS. Compared to controls, stroke patients had significantly higher VEGF-A and VCAM-1 at <8 hours that remained elevated at 72 hours, with significantly higher VEGF-A at <8 hours; ICAM-1 was significantly increased at <8 hours, while S100B and E-selectin were unchanged. Conclusions: Plasma NF-L levels, but not IL-6 and S100B, were significant predictors of clinical severity on admission and functional outcome at 3 months. Plasma NF-L is a promising biomarker of functional outcome after ischemic stroke.