The neutrophil-to-lymphocyte ratio is associated with functional outcome among single small subcortical infarction: Mediating effects of white matter hyperintensities

J Stroke Cerebrovasc Dis. 2025 Jul;34(7):108341. doi: 10.1016/j.jstrokecerebrovasdis.2025.108341. Epub 2025 May 8.

Abstract

Background: Increasing evidence indicated that neutrophil-to-lymphocyte ratio (NLR) was correlated with unfavorable functional outcome in ischemic stroke. However, limited studies have explored the relationship between NLR and single small subcortical infarction (SSSI). This study aims to investigate the link between NLR and functional outcome in patients with SSSI and assess whether white matter hyperintensities (WMH) mediates the relationship between NLR and unfavorable functional prognosis.

Methods: This research analyzed data from patients with SSSI in a Chinese cohort study. The primary outcome was unfavorable functional outcome (modified Rankin Scale score of 2-6) at 90 days after ischemic stroke onset, and the secondary outcome was unfavorable functional outcome at discharge. The relationship between NLR and functional outcome was analyzed using restricted cubic spline (RCS) and multivariable logistic regression. A mediation analysis was conducted to examine the link between NLR and unfavorable functional outcome mediated by WMH.

Results: Among the 513 patients with SSSI included in the study, unfavorable functional outcome was seen in 145 (28.3 %) patients at the 90-day follow-up and 156 patients (30.4 %) at discharge. After controlling for confounding variables, elevated NLR levels were found to be linked with unfavorable functional outcome both at 90 days and at discharge. Mediation analyses indicated that overall WMH significantly mediated the relationship between NLR and unfavorable functional outcome at 90 days and discharge, with mediation proportions of 29.6 % and 24.2 %, respectively. Periventricular WMH accounted for 36.4 % and 32.1 % of the mediation effects, respectively.

Conclusion: Elevated NLR independently increased the risk of unfavorable functional outcome in individuals with SSSI. In patients with SSSI, WMH partially mediated the relationship between NLR and unfavorable functional outcome.

Keywords: Functional outcome; Neutrophil lymphocyte ratio; Single small subcortical infarction; White matter hyperintensities.

MeSH terms

  • Aged
  • Cerebral Infarction* / blood
  • Cerebral Infarction* / diagnostic imaging
  • Cerebral Infarction* / physiopathology
  • Cerebral Infarction* / therapy
  • China
  • Disability Evaluation
  • Female
  • Functional Status
  • Humans
  • Leukoencephalopathies* / diagnostic imaging
  • Leukoencephalopathies* / physiopathology
  • Lymphocyte Count
  • Lymphocytes*
  • Magnetic Resonance Imaging*
  • Male
  • Middle Aged
  • Neutrophils*
  • Predictive Value of Tests
  • Prognosis
  • Recovery of Function
  • Retrospective Studies
  • Risk Assessment
  • Risk Factors
  • Time Factors
  • White Matter* / diagnostic imaging