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Neurology. 2018 Oct 2;91(14):e1338-e1347. doi: 10.1212/WNL.0000000000006282. Epub 2018 Sep 14.

Serum neurofilament light: A biomarker of neuroaxonal injury after ischemic stroke.

Author information

1
From the Institute for Stroke and Dementia Research, University Hospital (S.T., M. Duering, A.G.K., J.B., B.G., F.A.W., M. Dichgans), and Graduate School of Systemic Neurosciences (S.T.), LMU Munich; Munich Cluster for Systems Neurology (SyNergy) (S.T., M. Dichgans), Munich, Germany; Neurologic Clinic and Policlinic (C.B., J.K.), Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel, University of Basel, Switzerland; German Center for Neurodegenerative Diseases (DZNE) (F.J.B., G.C.P.), Bonn; Department of Neurology (F.J.B., G.C.P.), University Hospital Bonn; Departments of Neurology (M.K., L.K.), Neuroradiology (F.D.), and Radiology (B.E.-W.), University Hospital, LMU Munich; Department of Neurology (M.W.G.), University of Magdeburg, University Hospital; German Center for Neurodegenerative Diseases (DZNE) (M.W.G.), Magdeburg, Germany; Stroke Center and Department of Neurology (N.P.), University Hospital Basel, Switzerland; and German Center for Neurodegenerative Diseases (DZNE) (M. Dichgans), Munich, Germany.
2
From the Institute for Stroke and Dementia Research, University Hospital (S.T., M. Duering, A.G.K., J.B., B.G., F.A.W., M. Dichgans), and Graduate School of Systemic Neurosciences (S.T.), LMU Munich; Munich Cluster for Systems Neurology (SyNergy) (S.T., M. Dichgans), Munich, Germany; Neurologic Clinic and Policlinic (C.B., J.K.), Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel, University of Basel, Switzerland; German Center for Neurodegenerative Diseases (DZNE) (F.J.B., G.C.P.), Bonn; Department of Neurology (F.J.B., G.C.P.), University Hospital Bonn; Departments of Neurology (M.K., L.K.), Neuroradiology (F.D.), and Radiology (B.E.-W.), University Hospital, LMU Munich; Department of Neurology (M.W.G.), University of Magdeburg, University Hospital; German Center for Neurodegenerative Diseases (DZNE) (M.W.G.), Magdeburg, Germany; Stroke Center and Department of Neurology (N.P.), University Hospital Basel, Switzerland; and German Center for Neurodegenerative Diseases (DZNE) (M. Dichgans), Munich, Germany. martin.dichgans@med.uni-muenchen.de.

Abstract

OBJECTIVE:

To explore the utility of serum neurofilament light chain (NfL) as a biomarker for primary and secondary neuroaxonal injury after ischemic stroke (IS) and study its value for the prediction of clinical outcome.

METHODS:

We used an ultrasensitive single-molecule array assay to measure serum NfL levels in healthy controls (n = 30) and 2 independent cohorts of patients with IS: (1) with serial serum sampling at hospital arrival (n = 196), at days 2, 3, and 7 (n = 89), and up to 6 months post stroke; and (2) with standardized MRI at baseline and at 6 months post stroke, and with cross-sectional serum sampling at 6 months (n = 95). We determined the temporal profile of serum NfL levels, their association with imaging markers of neuroaxonal injury, and with clinical outcome.

RESULTS:

Patients with IS had higher serum NfL levels compared with healthy controls starting from admission until 6 months post stroke. Serum NfL levels peaked at day 7 (211.2 pg/mL [104.7-442.6], median [IQR]) and correlated with infarct volumes (day 7: partial r = 0.736, p = 1.5 × 10-15). Six months post stroke, patients with recurrent ischemic lesions on MRI (n = 19) had higher serum NfL levels compared to those without new lesions (n = 76, p = 0.002). Serum NfL levels 6 months post stroke further correlated with a quantitative measure of secondary neurodegeneration obtained from diffusion tensor imaging MRI (r = 0.361, p = 0.001). Serum NfL levels 7 days post stroke independently predicted modified Rankin Scale scores 3 months post stroke (cumulative odds ratio [95% confidence interval] = 2.35 [1.60-3.45]; p = 1.24 × 10-05).

CONCLUSION:

Serum NfL holds promise as a biomarker for monitoring primary and secondary neuroaxonal injury after IS and for predicting functional outcome.

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