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

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

doi:10.3389/fneur.2020.00448

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

Front Neurol. 2020 Jun 11:11:448. doi: 10.3389/fneur.2020.00448. eCollection 2020.

Authors

Helle H Nielsen^{1

2

3}, Catarina B Soares^{1

2}, Sofie S Høgedal¹, Jonna S Madsen^{4

5}, Rikke B Hansen^{1

2}, Alex A Christensen¹, Charlotte Madsen¹, Bettina H Clausen^{1

3}, Lars Henrik Frich^{6

7}, Matilda Degn⁸, Christian Sibbersen^{3

9}, Kate L Lambertsen^{1

2

3

7}

Affiliations

¹ Department of Neurology, Odense University Hospital, Odense, Denmark.
² Department of Neurobiology Research, Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark.
³ BRIDGE - Brain Research - Inter Disciplinary Guided Excellence, Department of Clinical Research, Odense, Denmark.
⁴ Department of Biochemistry and Immunology, Lillebaelt Hospital, University Hospital of Southern Denmark, Vejle, Denmark.
⁵ Department of Regional Health Research, University of Southern Denmark, Odense, Denmark.
⁶ The Orthopaedic Research Unit, Department of Clinical Research, Odense, Denmark.
⁷ OPEN, Open Patient data Explorative Network, Odense University Hospital, Department of Clinical Research, University of Southern Denmark, Odense, Denmark.
⁸ Pediatric Oncology Laboratory, Department of Pediatrics and Adolescent Medicine, University Hospital Rigshospitalet, Copenhagen, Denmark.
⁹ Mental Health Services in the Region of Southern Denmark, Odense, Denmark.

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 postmortem ischemic stroke, representing infarcts aged 3- to >7-days. In a prospective study, we measured plasma NF-L and inflammatory markers <8 h of symptom onset and at 72 h 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 vs. 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 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 <8 h that remained elevated at 72 h, with significantly higher VEGF-A at <8 h; ICAM-1 was significantly increased at <8 h, 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.

Keywords: Scandinavian Stroke Scale; biomarkers; functional outcome; modified rankin scale; transient ischemic attack.