Circulating Levels of Neurofilament Light Chain as a Biomarker of Infarct and White Matter Hyperintensity Volumes After Ischemic Stroke

Abstract

Abstract Serum neurofilament light chain protein (sNfL) shows promise as a biomarker for infarct size in acute ischemic stroke and monitoring diffuse cerebral small vessel disease (cSVD). However, distinguishing the cSVD contribution after stroke may not be possible due to post-stroke sNfL increase. Furthermore, it remains unclear if etiologic subtype differences exist. We measured infarct and white matter hyperintensity (WMH) volumes using MRI at the index stroke and 7-year follow-up in 316 ischemic stroke patients (mean age 53 years, 65% males). Serum NfL concentration was measured in the acute and convalescent phases, and at 7-year follow-up. In multivariable regression, acute and convalescent sNfL concentration was associated with infarct volume and time since stroke, but not with stroke etiology or infarct location. In long-term follow-up, sNfL was associated with WMHs and age, but not with stroke etiology. Nonlinear regression estimated that sNfL peaks around 1 month, and declines by 50% at 3 months and 99% at 9 months. We conclude that sNfL can serve as an indicator of infarct volume and elapsed time since brain injury in the acute and convalescent phases after stroke. Due to the significant post-stroke sNfL increase, several months are needed for reliable assessment of diffuse cSVD activity.