Neutrophil-to-Lymphocyte Ratio Predicts Cerebral Edema and Clinical Worsening Early After Reperfusion Therapy in Stroke

Abstract

Background and purpose: The mechanisms linking systemic inflammation to poor outcome in ischemic stroke are not fully understood. The authors investigated if peripheral inflammation following reperfusion therapy leads to an increase in cerebral edema (CED), thus hindering the clinical recovery.

Methods: We designed a single-center study conducted at Centro Hospitalar Universitário São João between 2017 and 2019. Inclusion criteria were being adult, having an anterior circulation acute ischemic stroke, and receiving reperfusion therapy. Neutrophil-to-lymphocyte, platelet-to-lymphocyte ratios, and the systemic inflammatory response syndrome criteria were determined. The presence and grade of CED were evaluated on the computed tomography performed 24 hours following event. The clinical outcomes included early neurological deterioration and functional dependence at 90 days. Adjusted odds ratio and 95% CI were obtained by ordinal and logistic regression models. Optimal cutoff values were defined using receiver operating characteristic analysis in the training cohort and validated in an independent data set.

Results: Five hundred fifty-three patients were included. Neutrophil-to-lymphocyte increased with higher degrees of CED at 24 hours (adjusted odds ratio, 1.34 [1.09-1.68], P<0.01) and was associated with early neurological deterioration (adjusted odds ratio, 1.30 [1.04-1.63], P<0.05) and poor functional status at 90 days (adjusted odds ratio, 1.79 [1.28-2.48], P<0.01). Platelet-to-lymphocyte was not associated with the outcomes. Systemic inflammatory response syndrome was related to CED due to altered white blood cell counts. Neutrophil-to-lymphocyte was the best predictor with an area under the curve around 0.7. Neutrophil-to-lymphocyte ≥7 had and accuracy, sensitivity, and specificity around 60%.

Conclusions: Increased systemic inflammation is linked to the severity of CED early after reperfusion therapy in stroke. Easily obtained inflammatory markers convey early warning alerts for patients at risk of severe neurological complications with an impact on long-term functional outcome. CED quantification should be included as an end point in proof-of-concept trials in immunomodulation in stroke.

Keywords: brain edema; cerebral infarction; inflammation; ischemic stroke; thrombectomy.