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

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. Nielsen et al. Acute Plasma NF-L Levels in Stroke 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.

Serum Neurofilament Light Chain Measurement in MS: Hurdles to Clinical Translation

“…Extensively reviewed elsewhere ( Khalil et al, 2018 ; Barro et al, 2020 ), higher sNfL is seen in many central and peripheral nervous system diseases that involve neuroaxonal injury including neurodegenerative conditions ( Forgrave et al, 2019 ), stroke ( Nielsen et al, 2020 - plasma concentrations), and peripheral neuropathies ( Altmann et al, 2020 ). Analogous to troponin in cardiac disease, clinical context is required.…”

Blood Neurofilament Light Chain: The Neurologist’s Troponin?

“…Meanwhile, for more acute neuronal injury, neurofilament may also have utility in stroke and traumatic brain injury prognostication. Following a stroke, blood NfL takes several hours to rise, limiting their utility in the hyperacute setting, however, the presence of elevated NfL may have utility in diagnosing subacute strokes as well as in the prognostication of outcomes [ 45 , 46 ]. Similarly, following traumatic brain injury, the extent of NfL increase acutely is predictive of the severity of injury, and while NfL decreases over time, it remains elevated relative to controls several years after the injury.…”

Characterization of the TNF and IL-1 systems in human brain and blood after ischemic stroke

“…Mixed organ tissue blocks were used as controls for immunohistochemical staining, as was brain tissue free of brain-specific disease (n = 3). Parallel tissue sections were used in previous studies [10,12,31,32,46].…”