Serum neurofilament light A biomarker of neuroaxonal injury after ischemic stroke

Tiedt, Steffen; Duering, Marco; Barro, Christian; Kaya, Asli Gizem; Böck, Julia; Bode, Felix J.; Klein, Matthias; Dorn, Franziska; Gesierich, Benno; Kellert, Lars; Ertl-Wagner, Birgit; Goertler, Michael W.; Petzold, Gabor C.; Kuhle, Jens; Wollenweber, Frank A.; Peters, Nils and Dichgans, Martin (2018): Serum neurofilament light A biomarker of neuroaxonal injury after ischemic stroke. In: Neurology, Vol. 91, No. 14, E1338-E1347

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 x 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 x 10(-05)). Conclusion Serum NfL holds promise as a biomarker for monitoring primary and secondary neuroaxonal injury after IS and for predicting functional outcome.

• Item Type: Journal article
• EU Funded Grant Agreement Number: info:eu-repo/grantAgreement/EC/H2020/666881
• EU Projects: Horizon 2020 > RIA - Research and Innovation action > SVDs-at-target - Small Vessel Diseases from a therapeutic perspective: Targets for intervention. Affected pathways and mechanistic exploitation for prevention of stroke dementia; Horizon 2020 > RIA - Research and Innovation action > CoSTREAM - Common mechanisms and pathways in stroke and Alzheimer's disease
• Faculties: Medicine > Institute for Stroke and Dementia Research (ISD)
• Research Centers: Graduate School of Systemic Neurosciences (GSN)
• Subjects: 600 Technology > 610 Medicine and health; 500 Science > 500 Science
• ISSN: 0028-3878
• Language: English