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Meta-Analysis
7 October 2025

Blood neurofilament light chain as a predictive biomarker for functional outcome of acute ischemic stroke: a systematic review and meta-analysis

Abstract

Aim: Ischemic stroke continues to be a significant contributor to mortality and disability on a global scale. The blood neurofilament light chain (bNfL) as a prognostic indicator for stroke functional outcomes is a topic of ongoing debate. Thus, the objective of this systematic review is to assess the efficacy of bNfL as a predictor of stroke functional outcomes. Materials & methods: A systematic search was conducted in Pubmed, Cochrane and Embase databases from their inception to 21 October 2023. Two reviewers independently screened the search results to identify studies reporting on the association between bNfL and acute ischemic stroke outcomes. The quality of the studies was assessed using the Newcastle–Ottawa scale. Meta-analysis was conducted using the Comprehensive Meta-Analysis software Stata 12.0, utilizing a random effects model to estimate the pooled effect. Results: Nine studies involving 2302 patients were included in the analysis. A pooled analysis of adjusted odds ratios (ORs) from multivariate regression models in the meta-analysis revealed a pooled adjusted OR of 1.929 [95% CI:1.459, 2.550], suggesting that the patients with higher bNfL levels are at a greater risk of experiencing unfavorable functional outcomes compared with those with lower bNfL levels. Subgroup analysis indicated that factors such as sampling time, study region, participant age, blood specimen and sample size, may contributed to high heterogeneity in the results. After conducting a thorough analysis using funnel plot and Egger’s test, no significant evidence of publication bias was found in our study. Conclusion: In summary, bNfL demonstrates potential as a predictive biomarker for functional outcomes in acute ischemic stroke patients, albeit subject to influence from confounding variables. Additional rigorously designed and meticulously executed prospective studies on a larger scale are warranted to validate these findings.

Plain language summary

What is this article about?

Ischemic stroke, also known as ‘stroke’, is a condition with a high incidence and disability rate. Rapid and correct diagnosis is critical for the proper treatment of patients with stroke. Despite the use of many prognostic scales and methodologies, reliably predicting stroke outcomes remains a challenge. In this case, biomarkers have the potential to provide more efficient tailored strategies for prioritizing therapeutic interventions and predicting short- and long-term outcomes. The neurofilament light chain (NfL) is a neurofilament subunit that can be used as a biomarker for neurological illnesses with tissue damage. It is regarded as a direct indicator of the severity of the disease. However, the use of blood neurofilament light chain (bNfL) as a predictive indicator for stroke functional outcomes is still being debated. Thus, the goal of this study is to determine the effectiveness of bNfL as a predictor of stroke functional outcomes.

What were the results?

The analysis includes nine studies with a total of 2302 subjects. The findings revealed that patients with higher bNfL levels are more likely to experience poor functional outcomes than those with lower bNfL levels. Subgroup analysis revealed that a number of variables, including sample size, blood specimen, participant age, study region, and sampling time, may have contributed to the results’ high heterogeneity.

What do the results of the study mean?

Although it is susceptible to the influence of confounding variables, bNfL shows promise as a predictive biomarker for functional outcomes in patients who have suffered an acute ischemic stroke. It might aid medical professionals in determining a stroke patient’s prognosis.

Supplementary Material

File (supplementary data.docx)

References

Papers of special note have been highlighted as: • of interest; •• of considerable interest
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