Circulating neurofilament light in ischemic stroke: temporal profile and outcome prediction

Pedersén, Annie; Stanne, Tara M.; Nilsson, Staffan; Klasson, Sofia; Rosengren, Lars; Holmegaard, Lukas; Jood, Katarina; Blennow, Kaj; Zetterberg, Henrik; Jern, Christina

doi:10.1007/s00415-019-09477-9

Cited by 52 publications

(68 citation statements)

References 27 publications

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“…The stroke group had higher serum NfL levels than the stroke-free group, which is consistent with previous findings. 14,23 Since NfL is a major component of axonal proteins, neuronal damage and death caused by acute ischemic stroke induces its release into the cerebrospinal fluid (CSF) and entry into the bloodstream through the blood-brain barrier. 7 Serum NfL levels are lower than CSF NfL levels 24,25 though strongly correlated.…”

Section: Discussionmentioning

confidence: 99%

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Combination of Serum Neurofilament Light Chain Levels and MRI Markers to Predict Cognitive Function in Ischemic Stroke

Peng

Qin

et al. 2021

Neurorehabil Neural Repair

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Background: It is important to predict poststroke cognitive outcome to guide individualized treatment and prevention strategy. We aimed to evaluate the predictive value of the combination of a serum biomarker for axonal damage (neurofilament light chain [NfL]) and neuroimaging markers (volume of infarction and white matter hyperintensities [WMH]) for neuronal abnormality in poststroke cognitive outcome. Methods: A total of 1028 patients were screened; among them, 144 patients with acute ischemic stroke (stroke group) and 30 patients without stroke (control group) were enrolled. Serum NfL levels of samples obtained from both groups were measured through single molecule array assay. Neuroimaging markers of neuroaxonal injury, including infarct volume and WMH in the stroke group were quantified on magnetic resonance images using an in-house MATLAB code (MATLAB 2017; MathWorks). The primary outcome was the functional independence measure (FIM) cognitive subscores on discharge. We assessed the association of serum NfL levels and neuroimaging markers with cognitive outcome. The prognosis value of the combination of serum NfL levels and imaging markers for predicting FIM cognitive subscores on discharge was calculated using the area under curve (AUC) of the receiver operating characteristic. Results: Serum NfL levels of the stroke group were 9-fold higher than those of the control group (1449.7 vs 157.2 pg/mL, n = 144/30, P < .001). There was a correlation of serum NfL levels with infarct volume ( r = 0.530, P < .001) and functional outcome, including FIM cognitive subscores ( r = −0.387, P < .001) and FIM motor subscores on admission ( r = −0.306, P < .001), but not with WMH volume after adjusting for infarct volume ( r = −0.196, P = .245). Serum NfL levels on admission independently predicted poststroke FIM cognitive subscores on discharge (AUC = 0.672, P < .001). The predictive value for poststroke cognitive outcome was improved by combining serum NfL levels with infarct and WMH volume (AUC = 0.760, P < .001). Conclusion: The combination of serum NfL levels with volume of infarct and WMH shows an improved predictive value for cognitive function during acute rehabilitation phase after stroke, providing a promising panel of biomarkers for prognosis and guidance of treatment.

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Section: Discussionmentioning

confidence: 99%

“…27,28 Additionally, our findings are consistent with previous reports that NfL is stable within 3 poststroke months. 23…”

Section: Discussionmentioning

confidence: 99%

Combination of Serum Neurofilament Light Chain Levels and MRI Markers to Predict Cognitive Function in Ischemic Stroke

Peng

Qin

et al. 2021

Neurorehabil Neural Repair

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“…22 Furthermore, cerebrovascular events are accompanied by a rise in blood NfL proportional to the lesion burden 17,21,22,[117][118][119] and clinical scores. 17,22,[117][118][119][120][121] In addition blood NfL is prognostic for disability at 3 months 17,22,121 and at 3-7 years, 17,118,121 as well as survival at 17 years, 118 though not all studies have found a prognostic association. 119,120 Following an acute stroke, prophylaxis to prevent or reduce further events is initiated.…”

Section: Strokementioning

confidence: 99%

Blood neurofilament light: a critical review of its application to neurologic disease

Barro

Chitnis

Weiner

2020

Ann Clin Transl Neurol

145

163

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Neuronal injury is a universal event that occurs in disease processes that affect both the central and peripheral nervous systems. A blood biomarker linked to neuronal injury would provide a critical measure to understand and treat neurologic diseases. Neurofilament light chain (NfL), a cytoskeletal protein expressed only in neurons, has emerged as such a biomarker. With the ability to quantify neuronal damage in blood, NfL is being applied to a wide range of neurologic conditions to investigate and monitor disease including assessment of treatment efficacy. Blood NfL is not specific for one disease and its release can also be induced by physiological processes. Longitudinal studies in multiple sclerosis, traumatic brain injury, and stroke show accumulation of NfL over days followed by elevated levels over months. Therefore, it may be hard to determine with a single measurement when the peak of NfL is reached and when the levels are normalized. Nonetheless, measurement of blood NfL provides a new blood biomarker for neurologic diseases overcoming the invasiveness of CSF sampling that restricted NfL clinical application. In this review, we examine the use of blood NfL as a biologic test for neurologic disease.

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“…NFs are highly specific structural, neuronal cytoskeletal proteins that consist of four NF subunits: NF light (NF-L), NF medium (NF-M), and NF heavy (NF-H) chains, and alpha-internexin. NF-L has been studied as a potential CSF and circulation biomarker for a wide range of neurological disorders (4-7), including cerebral small vessel disease (8) and subacute ischemic stroke (9,10).…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2020

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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.

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Circulating neurofilament light in ischemic stroke: temporal profile and outcome prediction

Cited by 52 publications

References 27 publications

Combination of Serum Neurofilament Light Chain Levels and MRI Markers to Predict Cognitive Function in Ischemic Stroke

Combination of Serum Neurofilament Light Chain Levels and MRI Markers to Predict Cognitive Function in Ischemic Stroke

Blood neurofilament light: a critical review of its application to neurologic disease

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

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