Steffen Tiedt1, Marco Duering1, Christian Barro1, Asli Gizem Kaya1, Julia Boeck1, Felix J Bode1, Matthias Klein1, Franziska Dorn1, Benno Gesierich1, Lars Kellert1, Birgit Ertl-Wagner1, Michael W Goertler1, Gabor C Petzold1, Jens Kuhle1, Frank A Wollenweber1, Nils Peters1, Martin Dichgans2. 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.
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.
Authors: Frederick K Korley; Jason Goldstick; Mitra Mastali; Jennifer E Van Eyk; William Barsan; William J Meurer; Jeremy Sussman; Hayley Falk; Deborah Levine Journal: Stroke Date: 2019-05-29 Impact factor: 7.914
Authors: Vladimir Hachinski; Karl Einhäupl; Detlev Ganten; Suvarna Alladi; Carol Brayne; Blossom C M Stephan; Melanie D Sweeney; Berislav Zlokovic; Yasser Iturria-Medina; Costantino Iadecola; Nozomi Nishimura; Chris B Schaffer; Shawn N Whitehead; Sandra E Black; Leif Østergaard; Joanna Wardlaw; Steven Greenberg; Leif Friberg; Bo Norrving; Brian Rowe; Yves Joanette; Werner Hacke; Lewis Kuller; Martin Dichgans; Matthias Endres; Zaven S Khachaturian Journal: Alzheimers Dement Date: 2019-07 Impact factor: 21.566