Association between neutrophil-to-lymphocyte ratio and cerebral small vessel disease: a systematic review and meta-analysis.

BACKGROUND AND OBJECTIVES: Cerebral small vessel disease (CSVD) causes about 25% of ischemic strokes, most intracerebral hemorrhages, and is a major cause of vascular dementia. The neutrophil-to-lymphocyte ratio (NLR), an inflammatory marker, has shown inconsistent associations with CSVD. We performed a meta-analysis to quantify the association between NLR and CSVD imaging markers. METHODS: Pubmed, Embase, and Cochrane Library were searched through August 10, 2025 for studies of NLR and CSVD. Fifteen studies (n = 62,961) were included. Outcomes included CSVD presence, total CSVD burden, and imaging subtypes (white matter hyperintensities [WMH], lacunes, microbleeds [CMBs], enlarged perivascular spaces [EPVS]). RESULTS: Elevated NLR was associated with presence of CSVD (OR 1.43, 95% CI 1.07-1.93) and greater total CSVD burden (OR 1.55, 95% CI 1.11-2.18). NLR also had associations with WMH (severe WMH: OR 1.36, 95% CI 1.04-1.76; WMH volume: β=0.08, 95% CI 0.02-0.15) and lacunes (OR 1.26, 95% CI 1.16-1.36); it was not associated with CMBs (OR 0.94, 95% CI 0.82-1.09), and EPVS data were limited. Substantial heterogeneity was noted for CSVD and WMH but not for lacunes or CMBs. Removing one study resolved heterogeneity for total CSVD burden, and excluding a high-bias study eliminated the WMH severity association. CONCLUSION: Higher NLR showed a limited but consistent association with ischemic CSVD markers, particularly WMH and lacunes, whereas no association was observed with hemorrhagic markers such as CMBs. NLR may therefore reflect inflammatory pathways more closely related to ischemic small vessel injury, but larger longitudinal studies are needed to confirm its causal and clinical relevance. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/view/CRD420251125195, identifier: CRD420251125195.