# Associations of Neutrophil-to-Lymphocyte Ratio with Cerebral Small Vessel Disease and Functional Outcome in Acute Ischaemic Stroke Patients

## TL;DR

This study explores how the neutrophil-to-lymphocyte ratio relates to brain imaging signs and recovery in stroke patients, finding limited reliable associations.

## Contribution

The study provides new insights into the potential but inconsistent role of NLR as a marker for cerebral small vessel disease and stroke outcomes.

## Key findings

- Higher NLR was linked to more lobar cerebral microbleeds in unadjusted models but not after adjusting for confounders.
- Middle NLR tertile showed a higher chance of better 90-day functional outcomes, but this may be a chance finding.
- NLR showed no consistent associations with other neuroimaging markers of cerebral small vessel disease.

## Abstract

Background: The relationship between inflammatory markers and cerebral small vessel disease (CSVD) in patients with acute ischaemic stroke (AIS) remains unclear. This study aimed to investigate the association between simplified inflammatory biomarkers and neuroimaging markers of CSVD. Methods: This retrospective cohort study included patients with AIS who had symptom onset within 72 h and underwent MRI brain between January 2019 and December 2023. The associations between tertiles (T) of the neutrophil-to-lymphocyte ratio (NLR) and CSVD markers were studied using multinomial logistic regression. Functional outcomes at discharge and 90 days, as measured by the modified Rankin Scale (mRS), were also evaluated. Results: A total of 299 eligible patients were included, with a mean age of 65.7 ± 13.8 years and 55.5% (166/299) were male, and categorised into three tertiles of NLR (T1: 101, T2: 101, T3: 97). Patients with a higher NLR tertile had more admission NIHSS (T3 vs. T1: 3 (2, 5) vs. 2 (1, 3), p = 0.005). NLR was associated with an increased risk of ≥5 lobar cerebral microbleeds (CMBs) in an unadjusted model (T3 vs. T1: relative risk ratio (RRR), 5.69 (95% confidence interval (CI) 1.21–26.68); p = 0.03); however, this was not significant when adjusted for potential confounders (RRR 3.86; 95% CI 0.79–18.89; p = 0.10). No significant associations were observed in the remaining neuroimaging markers of CSVD. Patients in the T2 of NLR had a higher likelihood of achieving an mRS of 0–1 at 90 days (RRR 2.16; 95% CI 1.05–4.44; p = 0.04) compared to those in T1. Conclusions: In AIS, admission NLR showed a possible association with higher lobar CMB burden in unadjusted analyses, but this was not robust after adjustment, and no consistent relationships were observed with other CSVD markers. Associations with functional outcomes were not uniform across tertiles, and the apparent benefit in the middle NLR tertile should be interpreted cautiously as a potentially non-linear or chance finding, indicating that NLR is not a reliable independent imaging or prognostic marker in this cohort.