Top

Published in:

01-04-2017 | CLINICAL RESEARCH REPORT

Neutrophil-To-Lymphocyte Ratio Predicts 3-Month Outcome of Acute Ischemic Stroke

Authors: Sen Qun, Yan Tang, Jing Sun, Zhaoxia Liu, Juncang Wu, Ji Zhang, Jidong Guo, Zhiqiang Xu, Dan Zhang, Zhengxu Chen, Fuyong Hu, Xingshun Xu, Wei Ge

Published in: Neurotoxicity Research | Issue 3/2017

Abstract

Increasing evidences have demonstrated that inflammation is involved in the mechanisms of acute ischemic stroke (AIS). As an important and easy-to-measure inflammatory marker, neutrophil-to-lymphocyte ratio (NLR) shows a high association with mortality in patients with stroke in recent studies. In this study, we evaluated the prognostic role of NLR in patients with AIS. One hundred forty-three patients with AIS were enrolled. Clinical data were collected and the NLR was calculated from the admission blood work. The patients were followed up for 3 months after stroke onset. The occurrence of death and the major disability at 3 months after onset were end points in this study. Modified Rankin Scale score ≥3 was considered as poor outcome. In this study, 75 patients (52%) had poor outcome. We used binary logistic regression model to evaluate risk factor for poor outcome of AIS and found that the NLR was independently associated with the poor outcome of 3 months (P < 0.001). The optimal cutoff value for NLR as a predictor for 3-month outcome was 2.995. Therefore, in our study, high NLRs inversely predicted 3-month outcome in patients with AIS.

Azab B et al (2010) Usefulness of neutrophil to lymphocyte ratio in predicting short- and long-term mortality after non-ST-elevation myocardial infarction. Am J Cardiol 106:470–476. doi:10.1016/j.amjcard.2010.03.062 CrossRefPubMed

Banks JL, Marotta CA (2007) Outcomes validity and reliability of the modified Rankin scale: implications for stroke clinical trials: a literature review and synthesis. Stroke: a journal of cerebral circulation 38:1091–1096. doi:10.1161/01.STR.0000258355.23810.c6 CrossRef

Barone FC et al (1991) Polymorphonuclear leukocyte infiltration into cerebral focal ischemic tissue: myeloperoxidase activity assay and histologic verification. J Neurosci Res 29:336–345. doi:10.1002/jnr.490290309 CrossRefPubMed

Bowes MP, Rothlein R, Fagan SC, Zivin JA (1995) Monoclonal antibodies preventing leukocyte activation reduce experimental neurologic injury and enhance efficacy of thrombolytic therapy. Neurology 45:815–819CrossRefPubMed

Brooks SD et al (2014) Admission neutrophil-lymphocyte ratio predicts 90 day outcome after endovascular stroke therapy. J Neurointerv Surg 6:578–583. doi:10.1136/neurintsurg-2013-010780 CrossRefPubMed

Buck BH et al (2008) Early neutrophilia is associated with volume of ischemic tissue in acute stroke. Stroke; a journal of cerebral circulation 39:355–360. doi:10.1161/STROKEAHA.107.490128 CrossRef

Buratti L et al (2014) Blood pressure variability and stroke outcome in patients with internal carotid artery occlusion. J Neurol Sci 339:164–168. doi:10.1016/j.jns.2014.02.007 CrossRefPubMed

Castellanos M, Leira R, Serena J, Pumar JM, Lizasoain I, Castillo J, Davalos A (2003) Plasma metalloproteinase-9 concentration predicts hemorrhagic transformation in acute ischemic stroke. Stroke; a journal of cerebral circulation 34:40–46CrossRef

Celikbilek A, Ismailogullari S, Zararsiz G (2014) Neutrophil to lymphocyte ratio predicts poor prognosis in ischemic cerebrovascular disease. J Clin Lab Anal 28:27–31. doi:10.1002/jcla.21639 CrossRefPubMed

Chopp M, Li Y, Jiang N, Zhang RL, Prostak J (1996) Antibodies against adhesion molecules reduce apoptosis after transient middle cerebral artery occlusion in rat brain. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 16:578–584. doi:10.1097/00004647-199607000-00007 CrossRef

Clark WM, Lauten JD, Lessov N, Woodward W, Coull BM (1995) The influence of antiadhesion therapies on leukocyte subset accumulation in central nervous system ischemia in rats. Journal of molecular neuroscience : MN 6:43–50. doi:10.1007/bf02736758 CrossRefPubMed

Connolly ES Jr et al (1996) Cerebral protection in homozygous null ICAM-1 mice after middle cerebral artery occlusion. Role of neutrophil adhesion in the pathogenesis of stroke. J Clin Invest 97:209–216. doi:10.1172/jci118392 CrossRefPubMedPubMedCentral

Davies CA, Loddick SA, Stroemer RP, Hunt J, Rothwell NJ (1998) An integrated analysis of the progression of cell responses induced by permanent focal middle cerebral artery occlusion in the rat. Exp Neurol 154:199–212. doi:10.1006/exnr.1998.6891 CrossRefPubMed

Demir R, Ulvi H, Ozel L, Ozdemir G, Guzelcik M, Aygul R (2012) Relationship between plasma metalloproteinase-9 levels and volume and severity of infarct in patients with acute ischemic stroke. Acta Neurol Belg 112:351–356. doi:10.1007/s13760-012-0067-4 CrossRefPubMed

Duffy BK, Gurm HS, Rajagopal V, Gupta R, Ellis SG, Bhatt DL (2006) Usefulness of an elevated neutrophil to lymphocyte ratio in predicting long-term mortality after percutaneous coronary intervention. Am J Cardiol 97:993–996. doi:10.1016/j.amjcard.2005.10.034 CrossRefPubMed

Fiorelli M et al (1999) Hemorrhagic transformation within 36 hours of a cerebral infarct: relationships with early clinical deterioration and 3-month outcome in the European cooperative acute stroke study I (ECASS I) cohort. Stroke; a journal of cerebral circulation 30:2280–2284CrossRef

Fu Y, Liu Q, Anrather J, Shi FD (2015) Immune interventions in stroke. Nat Rev Neurol 11:524–535. doi:10.1038/nrneurol.2015.144 CrossRefPubMedPubMedCentral

Garau A et al (2005) Neuroprotection with the CXCL8 inhibitor repertaxin in transient brain ischemia. Cytokine 30:125–131. doi:10.1016/j.cyto.2004.12.014 CrossRefPubMed

Gary T et al (2013) Neutrophil-to-lymphocyte ratio and its association with critical limb ischemia in PAOD patients. PLoS One 8:e56745. doi:10.1371/journal.pone.0056745 CrossRefPubMedPubMedCentral

Gautier S, Ouk T, Petrault O, Caron J, Bordet R (2009) Neutrophils contribute to intracerebral haemorrhages after treatment with recombinant tissue plasminogen activator following cerebral ischaemia. Br J Pharmacol 156:673–679. doi:10.1111/j.1476-5381.2009.00068.x CrossRefPubMedPubMedCentral

Gibson PH et al (2007) Preoperative neutrophil-lymphocyte ratio and outcome from coronary artery bypass grafting. Am Heart J 154:995–1002. doi:10.1016/j.ahj.2007.06.043 CrossRefPubMed

Gibson PH et al (2010) Usefulness of neutrophil/lymphocyte ratio as predictor of new-onset atrial fibrillation after coronary artery bypass grafting. Am J Cardiol 105:186–191. doi:10.1016/j.amjcard.2009.09.007 CrossRefPubMed

Gokhan S, Ozhasenekler A, Mansur Durgun H, Akil E, Ustundag M, Orak M (2013) Neutrophil lymphocyte ratios in stroke subtypes and transient ischemic attack. Eur Rev Med Pharmacol Sci 17:653–657PubMed

Herz J, Sabellek P, Lane TE, Gunzer M, Hermann DM, Doeppner TR (2015) Role of neutrophils in exacerbation of brain injury after focal cerebral ischemia in hyperlipidemic mice. Stroke; a journal of cerebral circulation 46:2916–2925. doi:10.1161/STROKEAHA.115.010620 CrossRefPubMedCentral

Horne BD et al (2005) Which white blood cell subtypes predict increased cardiovascular risk? J Am Coll Cardiol 45:1638–1643. doi:10.1016/j.jacc.2005.02.054 CrossRefPubMed

Huang J, Upadhyay UM, Tamargo RJ (2006) Inflammation in stroke and focal cerebral ischemia. Surg Neurol 66:232–245. doi:10.1016/j.surneu.2005.12.028 CrossRefPubMed

Jickling GC, Liu D, Ander BP, Stamova B, Zhan X, Sharp FR (2015) Targeting neutrophils in ischemic stroke: translational insights from experimental studies. Journal of cerebral blood flow and metabolism: official journal of the International Society of Cerebral Blood Flow and Metabolism 35:888–901. doi:10.1038/jcbfm.2015.45 CrossRef

Kim JY, Park J, Chang JY, Kim SH, Lee JE (2016) Inflammation after ischemic stroke: the role of leukocytes and glial cells. Exp Neurobiol 25:241–251. doi:10.5607/en.2016.25.5.241 CrossRefPubMedPubMedCentral

Klehmet J et al (2009) Stroke-induced immunodepression and post-stroke infections: lessons from the preventive antibacterial therapy in stroke trial. Neuroscience 158:1184–1193. doi:10.1016/j.neuroscience.2008.07.044 CrossRefPubMed

Lakhan SE, Kirchgessner A, Hofer M (2009) Inflammatory mechanisms in ischemic stroke: therapeutic approaches. J Transl Med 7:97. doi:10.1186/1479-5876-7-97 CrossRefPubMedPubMedCentral

Lattanzi S, Cagnetti C, Provinciali L, Silvestrini M (2015) Blood pressure variability and clinical outcome in patients with acute intracerebral hemorrhage. J Stroke Cerebrovasc Dis 24:1493–1499. doi:10.1016/j.jstrokecerebrovasdis.2015.03.014 CrossRefPubMed

Lattanzi S, Cagnetti C, Provinciali L, Silvestrini M (2016) Neutrophil-to-lymphocyte ratio predicts the outcome of acute intracerebral hemorrhage. Stroke; a journal of cerebral circulation 47:1654–1657. doi:10.1161/STROKEAHA.116.013627 CrossRef

Liesz A et al (2009) Regulatory T cells are key cerebroprotective immunomodulators in acute experimental stroke. Nat Med 15:192–199. doi:10.1038/nm.1927 CrossRefPubMed

Liesz A et al (2013) Boosting regulatory T cells limits neuroinflammation in permanent cortical stroke. The Journal of neuroscience : the official journal of the Society for Neuroscience 33:17350–17362. doi:10.1523/JNEUROSCI.4901-12.2013 CrossRef

Lyden P et al (1994) Improved reliability of the NIH Stroke Scale using video training. NINDS TPA Stroke Study Group. Stroke 25:2220--2226

Matsuo Y, Kihara T, Ikeda M, Ninomiya M, Onodera H, Kogure K (1995) Role of neutrophils in radical production during ischemia and reperfusion of the rat brain: effect of neutrophil depletion on extracellular ascorbyl radical formation. Journal of cerebral blood flow and metabolism: official journal of the International Society of Cerebral Blood Flow and Metabolism 15:941–947. doi:10.1038/jcbfm.1995.119 CrossRef

Montaner J et al (2001) Matrix metalloproteinase expression after human cardioembolic stroke: temporal profile and relation to neurological impairment. Stroke; a journal of cerebral circulation 32:1759–1766CrossRef

Montaner J et al (2003) Matrix metalloproteinase-9 pretreatment level predicts intracranial hemorrhagic complications after thrombolysis in human stroke. Circulation 107:598–603CrossRefPubMed

Muhmmed Suliman MA, Bahnacy Juma AA, Ali Almadhani AA, Pathare AV, Alkindi SS, Uwe Werner F (2010) Predictive value of neutrophil to lymphocyte ratio in outcomes of patients with acute coronary syndrome. Arch Med Res 41:618–622. doi:10.1016/j.arcmed.2010.11.006 CrossRefPubMed

Papa A, Emdin M, Passino C, Michelassi C, Battaglia D, Cocci F (2008) Predictive value of elevated neutrophil-lymphocyte ratio on cardiac mortality in patients with stable coronary artery disease. Clinica chimica acta; international journal of clinical chemistry 395:27–31. doi:10.1016/j.cca.2008.04.019 CrossRefPubMed

Petrault O, Ouk T, Gautier S, Laprais M, Gele P, Bastide M, Bordet R (2005) Pharmacological neutropenia prevents endothelial dysfunction but not smooth muscle functions impairment induced by middle cerebral artery occlusion. Br J Pharmacol 144:1051–1058. doi:10.1038/sj.bjp.0706124 CrossRefPubMedPubMedCentral

Posada-Duque RA, Barreto GE, Cardona-Gomez GP (2014) Protection after stroke: cellular effectors of neurovascular unit integrity. Front Cell Neurosci 8:231. doi:10.3389/fncel.2014.00231 CrossRefPubMedPubMedCentral

Ren X, Akiyoshi K, Dziennis S, Vandenbark AA, Herson PS, Hurn PD, Offner H (2011) Regulatory B cells limit CNS inflammation and neurologic deficits in murine experimental stroke. The Journal of neuroscience: the official journal of the Society for Neuroscience 31:8556–8563. doi:10.1523/JNEUROSCI.1623-11.2011 CrossRef

Satoh S et al (1999) Inhibition of neutrophil migration by a protein kinase inhibitor for the treatment of ischemic brain infarction. Jpn J Pharmacol 80:41–48CrossRefPubMed

Schroeter M, Jander S, Witte OW, Stoll G (1994) Local immune responses in the rat cerebral cortex after middle cerebral artery occlusion. J Neuroimmunol 55:195–203CrossRefPubMed

Tokgoz S, Kayrak M, Akpinar Z, Seyithanoglu A, Guney F, Yuruten B (2013) Neutrophil lymphocyte ratio as a predictor of stroke. Journal of stroke and cerebrovascular diseases: the official journal of National Stroke Association 22:1169–1174. doi:10.1016/j.jstrokecerebrovasdis.2013.01.011 CrossRef

Tokgoz S, Keskin S, Kayrak M, Seyithanoglu A, Ogmegul A (2014) Is neutrophil/lymphocyte ratio predict to short-term mortality in acute cerebral infarct independently from infarct volume? J Stroke Cerebrovasc Dis 23:2163–2168. doi:10.1016/j.jstrokecerebrovasdis.2014.04.007 CrossRefPubMed

Yenari MA et al (1998) Hu23F2G, an antibody recognizing the leukocyte CD11/CD18 integrin, reduces injury in a rabbit model of transient focal cerebral ischemia. Exp Neurol 153:223–233. doi:10.1006/exnr.1998.6876 CrossRefPubMed

Zahorec R (2001) Ratio of neutrophil to lymphocyte counts—rapid and simple parameter of systemic inflammation and stress in critically ill. Bratislavske lekarske listy 102:5–14PubMed

Zhang RL, Chopp M, Chen H, Garcia JH (1994) Temporal profile of ischemic tissue damage, neutrophil response, and vascular plugging following permanent and transient (2H) middle cerebral artery occlusion in the rat. J Neurol Sci 125:3–10CrossRefPubMed

Title: Neutrophil-To-Lymphocyte Ratio Predicts 3-Month Outcome of Acute Ischemic Stroke
Authors: Sen Qun
Yan Tang
Jing Sun
Zhaoxia Liu
Juncang Wu
Ji Zhang
Jidong Guo
Zhiqiang Xu
Dan Zhang
Zhengxu Chen
Fuyong Hu
Xingshun Xu
Wei Ge
Publication date: 01-04-2017
Publisher: Springer US
Published in: Neurotoxicity Research / Issue 3/2017
Print ISSN: 1029-8428
Electronic ISSN: 1476-3524
DOI: https://doi.org/10.1007/s12640-017-9707-z

At a glance: The STEP trials

Springer Medicine

Neutrophil-To-Lymphocyte Ratio Predicts 3-Month Outcome of Acute Ischemic Stroke

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 3/2017

Intracerebroventricular Streptozotocin as a Model of Alzheimer’s Disease: Neurochemical and Behavioral Characterization in Mice

The Impact of CB2 Receptor Ligands on the MK-801-Induced Hyperactivity in Mice

Topiramate Confers Neuroprotection Against Methylphenidate-Induced Neurodegeneration in Dentate Gyrus and CA1 Regions of Hippocampus via CREB/BDNF Pathway in Rats

Human Umbilical Cord Blood-Derived Neural Stem Cell Line as a Screening Model for Toxicity

Aminoglycoside Increases Permeability of Osseous Spiral Laminae of Cochlea by Interrupting MMP-2 and MMP-9 Balance

Nitric Oxide Production in the Striatum and Cerebellum of a Rat Model of Preterm Global Perinatal Asphyxia