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J Stroke. 2018 May;20(2):228-238. English. Original Article.
Duering M , Konieczny MJ , Tiedt S , Baykara E , Tuladhar AM , van Leijsen E , Lyrer P , Engelter ST , Gesierich B , Achmüller M , Barro C , Adam R , Ewers M , Dichgans M , Kuhle J , de Leeuw FE , Peters N .
Institute for Stroke and Dementia Research (ISD), University Hospital, Ludwig-Maximilians-University Munich, Munich, Germany.
Department of Neurology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands.
Stroke Center and Department of Neurology, University Hospital Basel, Basel, Switzerland.
Neurorehabilitation Unit, University of Basel and University Center for Medicine of Aging, Felix Platter Hospital, Basel, Switzerland.
Neurologic Clinic and Policlinic, Departments of Medicine, Biomedicine and Clinical Research, University Hospital of Basel, Basel, Switzerland.
Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.

Background and Purpose

Neurofilament light chain (NfL) is a blood marker for neuroaxonal damage. We assessed the association between serum NfL and cerebral small vessel disease (SVD), which is highly prevalent in elderly individuals and a major cause of stroke and vascular cognitive impairment.


Using a cross-sectional design, we studied 53 and 439 patients with genetically defined SVD (Cerebral Autosomal-Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy [CADASIL]) and sporadic SVD, respectively, as well as 93 healthy controls. Serum NfL was measured by an ultrasensitive single-molecule array assay. We quantified magnetic resonance imaging (MRI) markers of SVD, i.e., white matter hyperintensity volume, lacune volume, brain volume, microbleed count, and mean diffusivity obtained from diffusion tensor imaging. Clinical characterization included neuropsychological testing in both SVD samples. CADASIL patients were further characterized for focal neurological deficits (National Institutes of Health stroke scale [NIHSS]) and disability (modified Rankin scale [mRS]).


Serum NfL levels were elevated in both SVD samples (P < 1e-05 compared with controls) and associated with all SVD MRI markers. The strongest association was found for mean diffusivity (CADASIL, R²=0.52, P=1.2e-09; sporadic SVD, R²=0.21, P < 1e-15). Serum NfL levels were independently related to processing speed performance (CADASIL, R²=0.27, P=7.6e-05; sporadic SVD, R²=0.06, P=4.8e-08), focal neurological symptoms (CADASIL, NIHSS, P=4.2e-05) and disability (CADASIL, mRS, P=3.0e-06).


We found serum NfL levels to be associated with both imaging and clinical features of SVD. Serum NfL might complement MRI markers in assessing SVD burden. Importantly, SVD needs to be considered when interpreting serum NfL levels in the context of other age-related diseases.

Copyright © 2019. Korean Association of Medical Journal Editors.