AUTHOR=Nielsen Helle H. , Soares Catarina B. , Høgedal Sofie S. , Madsen Jonna S. , Hansen Rikke B. , Christensen Alex A. , Madsen Charlotte , Clausen Bettina H. , Frich Lars Henrik , Degn Matilda , Sibbersen Christian , Lambertsen Kate L. 

TITLE=Acute Neurofilament Light Chain Plasma Levels Correlate With Stroke Severity and Clinical Outcome in Ischemic Stroke Patients

JOURNAL=Frontiers in Neurology

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2020.00448

DOI=10.3389/fneur.2020.00448

ISSN=1664-2295

ABSTRACT=<p><bold>Background:</bold> 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.</p><p><bold>Methods:</bold> We studied neurofilament (NF) expression in 2 cases of human postmortem ischemic stroke, representing infarcts aged 3- to &gt;7-days. In a prospective study, we measured plasma NF-L and inflammatory markers &lt;8 h of symptom onset and at 72 h in acute ischemic stroke (<italic>n</italic> = 31), TIA (<italic>n</italic> = 9), and healthy controls (<italic>n</italic> = 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 vs. TIA, and functional outcome at 3 months (modified Rankin Scale, mRS).</p><p><bold>Results:</bold> NF expression increased in ischemic neurons and in the infarcted brain parenchyma after stroke. Plasma NF-L levels were higher in stroke patients than in 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 &lt;8 h that remained elevated at 72 h, with significantly higher VEGF-A at &lt;8 h; ICAM-1 was significantly increased at &lt;8 h, while S100B and E-selectin were unchanged.</p><p><bold>Conclusions:</bold> 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.</p>