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

ABSOLUTELY NOTHING here will help survivors recover.  Biomarkers and predictions are just functions of the complete failure of the status quo in stroke recovery. CHANGE THAT FAILURE!

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

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 and Kate L. Lambertsen^1,2,3,7*

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

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.