Role of Neutrophil-Lymphocyte Ratio in the Prognosis of Acute Ischaemic Stroke After Reperfusion Therapy: A Systematic Review and Meta-analysis

Abstract

Background: Inflammation may mediate response to acute reperfusion therapy (RT) in acute cerebral ischaemia. Neutrophil-lymphocyte ratio (NLR), an inflammatory biomarker, may play an important role in acute ischaemic stroke (AIS) prognostication.

Objective: This meta-analysis sought to examine the effect of NLR on functional outcomes, mortality and adverse outcomes in AIS patients receiving RT.

Methods: Individual studies were retrieved from PubMed/Medline, EMBASE and Cochrane databases. Data were extracted using a standardised data sheet and meta-analysis on association of admission (pre-RT) or delayed (post-RT) NLR with clinical/safety outcomes after RT was conducted.

Results: Thirty-five studies (n = 10 308) were identified for the systematic review with 27 (n = 8537) included in the meta-analyses. Lower admission NLR was associated with good functional outcomes (GFOs), defined as 3-month modified Rankin scale (mRS) 0-2 (SMD = -.46; 95% CI = -.62 to -.29; P < .0001), mRS 0-1 (SMD = -.44; 95% CI = -.66 to -.22; P < .0001) and early neurological improvement (ENI) (SMD = -.55; 95 %CI = -.84 to -.25; P < .0001). Lower delayed admission NLR was also associated with GFOs (SMD = -.80; 95%CI = -.91 to -.68; P < .0001). Higher admission NLR was significantly associated with mortality (SMD = .49; 95%CI = .12 to .85; P = .009), intracerebral haemorrhage (ICH) (SMD = .34; 95% CI = .09 to .59; P = .007), symptomatic ICH (sICH) (SMD = .48; 95% CI = .07 to .90; P = .022) and stroke-associated infection or pneumonia (SMD = .85; 95% CI = .50, 1.19; P < .0001). Higher delayed NLR was significantly associated with sICH (SMD = 1.40; 95% CI = .60 to 2.19; P = .001), ICH (SMD = .94; 95% CI = .41 to 1.46; P < .0001) and mortality (SMD = 1.12; 95% CI = .57 to 1.67; P < .0001). There were variations in outcomes across RT groups.

Conclusion: Higher admission or delayed NLR is significantly associated with worse morbidity, mortality and safety outcomes in AIS patients receiving RT.

Keywords: Stroke; endovascular therapy; intravenous thrombolysis; meta-analysis; neutrophil-to-lymphocyte ratio; overall survival; prognosis; reperfusion therapy; systematic review.

Figure 1.

Flow chart of study selection according to the PRISMA diagram. The PRISMA flowchart shows the main characteristics of the included studies. Outcomes for which a meta-analysis could successfully be carried out also have the number of patients shown. Abbreviations: N = Number of Included Studies; n = number of patients; GFOs = Good Functional Outcomes; mRS = Modified Rankin Scale; sICH = Symptomatic intracerebral haemorrhage; SR = Successful Recanalization; ICH = Intracerebral haemorrhage; ENI = Early Neurological Improvement; DENI = Dramatic Early Neurological Improvement; END = Early Neurological Deterioration; SAI = Stroke Associated Infection; SAP = Stroke Associated Pneumonia.

Figure 2.

Forest plot of meta-analysis on the association of neutrophil-lymphocyte ratio (NLR) with functional outcomes and mortality at 90 days in acute ischaemic stroke patients receiving reperfusion therapy. Abbreviations: mRS = Modified Rankin Scale; NLR = Neutrophil-Lymphocyte Ratio; IVT = Intravenous Thrombolysis; EVT = Endovascular Thrombectomy. Note: Studies, where only IVT was used with no EVT adjunct, are denoted with an asterisk (*) unless these have been already split up into TPA and IVT ± EVT.

Figure 3.

Forest plot of meta-analysis on the association of neutrophil-lymphocyte ratio (NLR) with bleeding complication outcomes in acute ischaemic stroke patients receiving reperfusion therapy. Abbreviations: ICH = Intracerebral Hemorrhage; sICH = Symptomatic Intracerebral Hemorrhage; NLR = Neutrophil-Lymphocyte Ratio; IVT = Intravenous Thrombolysis; EVT = Endovascular Thrombectomy. Note: Studies, where only IVT was used with no EVT adjunct, are denoted with an asterisk (*) unless these have been already split up into IVT and IVT ± EVT.

Figure 4.

Forest plot of meta-analysis on the association of neutrophil-lymphocyte ratio (NLR) with early neurological improvement and stroke-associated infection outcomes in acute ischaemic stroke patients receiving reperfusion therapy. Abbreviations: ENI = Early Neurological Improvement; SAI = Stroke-Associated Infection; SAP = Stroke-Associated Pneumonia; NLR = Neutrophil-Lymphocyte Ratio; IVT = Intravenous Thrombolysis; EVT = Endovascular Thrombectomy. Note: Studies, where only IVT was used with no EVT adjunct, are denoted with an asterisk (*), unless these have been already split up into IVT and IVT ± EVT.

Figure 5.

Funnel plots of meta-analyses studies on effect of neutrophil-lymphocyte ratio (NLR) on clinical and safety outcomes in acute ischemic stroke patients receiving reperfusion therapy. A: Admission NLR association with Good Functional Outcomes; B: Delayed NLR association with Good Functional Outcomes; C: Admission NLR association with mRS 0–1; D: Admission NLR association with Mortality; E: Delayed NLR association with Mortality; F: Admission NLR association with sICH; G: Delayed NLR association with sICH; H: Admission NLR association with ICH; I: Delayed NLR association with ICH; J: Admission NLR association with ENI; K: Admission NLR association with stroke-associated infection/pneumonia (SAI)/(SAP). Note: Funnel plots for each meta-analysis.