Serum Neurofilament Light Chain as a Predictive Biomarker for Ischemic Stroke Outcome: A Systematic Review and Meta-analysis

•The serum NfL was a promising predictive biomarker for ischemic stroke outcome.•The patients with higher sNfL, compared with lower sNfL patients, had a 1.71 times higher risk of poor functional outcome during follow-up.•Blood sampling time was of great importance to make sNfL a significant predictor.•The temporal change of sNfL after stroke deserves further exploration in large longitudinal studies. Background: Stroke is the leading cause of death and long-term disability worldwide. The purpose of the study is to examine the role of serum neurofilament light chain (sNfL) as a predictive biomarker for ischemic stroke outcome. Methods: We searched PubMed, Web of Science, and EMBASE for potential studies published in English previous to November 15, 2019. Two independent reviewers screened the search results for studies reporting the correlation between sNfL and stroke outcome in ischemic stroke or transient ischemic attack patients. The Newcastle-Ottawa Scale was adopted to evaluate the quality of the included studies. The pooled odds ratio (OR) of sNfL for stroke functional outcome was calculated with the Comprehensive Meta-Analysis software, version 2. Heterogeneity and publication bias were assessed with the I2 test and funnel plot, respectively. Results: Seven studies met the inclusion criteria. The qualities of the included studies ranged from moderate to high. Despite of the different methods used to measure infarct volume, 5 of the included studies reported similar results about the association between sNfL and infarct volume. Two studies investigating the relationship between sNfL and recurrent ischemic events both reported positive results. In pooled analysis with the adjusted odds ratios (Ors) from multivariate regression models, the meta-analysis reached a pooled adjusted OR = 1.71 [95% CI: 1.17-4.29], which represented that the patients with higher sNfL, compared with lower sNfL patients, had a 1.71 times higher risk of poor functional outcome during follow-up. Both meta-regression and subgroup analysis found that sampling time was an important source of heterogeneity. Based on funnel plot and Egger's test, we did not detect obvious publication bias in our study. Conclusions: The sNfL was a promising predictive biomarker for ischemic stroke outcome, and blood sampling time was of great importance in the correlation. The temporal change of sNfL after stroke deserves further exploration in large longitudinal studies and a standardized procedure is