A review of the relationship between stroke and neutrophil-lymphocyte ratio

Mustaq Ahmed, Dhruvi Reddy, Siva Ranganathan Green


Neutrophil-lymphocyte ratio (NLR) has been a novel biomarker in the literature over decades to assess systemic inflammation. This easily available and cost-effective marker has shown clinical significance in various disease conditions such as infections, sepsis, malignancies, cardiovascular events and even in SARS-COVID-19 pneumonia. NLR has a major association in ischemic stroke patients. Inflammation is a crucial step in the development of ischemic stroke, with neutrophils and lymphocytes comprising the first line defence mechanism. It has a role in stroke initiation, progression of injury, and recovery. This article showed significant correlation between NLR and stroke patients in terms of days of hospital stay, severity and prognosis. High NLR values were found to be associated with higher risk of stroke, prolonged hospital stay and a worse 3 month mortality rate. NLR can thus be integrated into any clinical practice, having an impact on early diagnosis in many clinical scenarios.


Stroke, Ischemic stroke, NLR, Inflammation, Stroke prognosis

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Benjamin EJ, Virani SS, Callaway CW, Chamberlain AM, Chang AR, Cheng S et al. Heart disease and stroke statistics-2018 update: A report from the American Heart Association. Circulation. 2018;137(12):e67-e492.

Caplan LR. Basic pathology, anatomy, and pathophysiology of stroke. In: Caplan’s Stroke: A Clinical Approach, 4th ed, Saunders Elsevier, Philadelphia. 2009;22.

Pandian JD, Sudhan P. Stroke epidemiology and stroke care services in India. J Stroke. 2013;15:128-34.

Lozano R, Naghavi M, Foreman K, Lim S, Shibuya K, Aboyans V, et al. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012;380:2095.

Prasad K, Vibha D, Meenakshi. Cerebrovascular disease in South Asia-Part I: A burning problem. JRSM Cardiovasc Dis. 2012;1:20.

Xavier D, Pais P, Devereaux PJ. Treatment and outcomes of acute coronary syndromes in India (CREATE): a prospective analysis of registry data. Lancet. 2008;371(9622):1435-42.

Kirino T. Ischemic tolerance. J Cereb Blood Flow Metab. 2002;22:1283-96.

Feigin VL, Forouzanfar MH, Krishnamurthi R. Global and regional burden of stroke during 1990-2010: Findings from the Global Burden of Disease Study 2010. Lancet. 2014;383:245-55.

Hackett ML, Köhler S, O’Brien JT. Neuropsychiatric outcomes of stroke. Lancet Neurol. 2014;13:525-34.

Iadecola C, Anrather J. The immunology of stroke: from mechanisms to translation. Nat Med. 2011;17:796-808.

Tokgoz S, Kayrak M, Akpinar Z, Seyithanoglu A, Guney F, Yuruten B et al. Neutrophil lymphocyte ratio as a predictor of stroke. J Stroke Cerebrovasc Dis. 2013;22:1169-74.

Saver JL, Altman H. Relationship between neurologic deficit severity and final functional outcome shifts and strengthens during first hours after onset. Stroke. 2012;43:1537

Ethier JL, Desautels D, Templeton A, Shah PS, Amir E. Prognostic role of neutrophil-to-lymphocyte ratio in breast cancer: A systematic review and meta-analysis. Breast Cancer Res. 2017;19(1): 2.

Zhang J. Prognostic role of neutrophil-lymphocyte ratio in patients with acute ischemic stroke. Medicine. 2017;96(45): e8624.

Hyun S. Can the neutrophil-to-lymphocyte ratio appropriately predict carotid artery stenosis in patients with ischemic stroke? A retrospective study. J Stroke Cerebrovasc Dis. 2015;24(11):2646-51.

Qun S. Neutrophil-to-lymphocyte ratio predicts 3-month outcome of acute ischemic stroke. Neurotox Res. 2017;31(3):444-52.

Song Q. Increased neutrophil-to-lymphocyte ratios are associated with greater risk of hemorrhagic transformation in patients with acute ischemic stroke. Curr Neurovasc Res. 2018;15(4):326-35.

Wang L. Neutrophil to lymphocyte ratio predicts poor outcomes after acute ischemic stroke: A cohort study and systematic review. J Neurol Sci. 2019;406:116445.

Zhang R. Neutrophil-to-lymphocyte ratio predicts hemorrhagic transformation in ischemic stroke: A meta-analysis. Brain Behav. 2019;9(9):e01382.

Song SY. Clinical significance of baseline neutrophil-to-lymphocyte ratio in patients with ischemic stroke or hemorrhagic stroke: An updated meta-analysis. Front Neurol. 2019;10:1032.

Liu S, Liu X, Chen S, Xiao Y, Zhuang W. Neutrophil-lymphocyte ratio predicts the outcome of intracerebral hemorrhage: A meta- analysis. Medicine. 2019;98(26):e16211.

Seshadri S, Beiser A, Kelly-Hayes M, Kase CS, Au R, Kannel WB et al. The lifetime risk of stroke: Estimates from the Framinham Study. Stroke. 2006;37:345-50.

WHO. Stroke, Cerebrovascular accident. 2010. Available at: accident/en/. Accessed on 21 January, 2021.

Warlow C, Sudlow C, Wardlaw DJ, Sandercock P. Stroke. Lancet. 2003;362(9391):211-24.

Strong K, Mathers C, Bonita R. Preventing stroke: saving lives around the world. Lancet Neurol. 2007;6(2):182-7.

Das SK, Banerjee TK, Biswas A, Roy T, Raut DK, Mukherjee CS et al. A prospective community-based study of stroke in Kolkata, India. Stroke. 2007;38:906-10.

Musuka TD, Wilton SB, Traboulsi M, Hill MD. Diagnosis and management of acute ischemic stroke: Speed is critical. CMAJ. 2015;187:887-93.

Kaul S, Sunitha P, Suvarna A, Meena AK, Uma M, Reddy JM. Subtypes of ischemic stroke in a metropolitan city of south India (one year data from hospital-based stroke registry). Neurol India. 2002;50:S8-14.

Chopra JS, Prabhakar S, Sodhi JS. Stroke in young: A clinico-radiological study. Neurol India. 1979b;27:160-9.

Padma MV, Gaikwad S, Jain S, Maheswari MC, Misra NK. Distribution of vascular lesions in ischemic stroke: A magnetic resonance angiographic study. Natl Med J India. 1997;10:217-20.

Dalal PM. Burden of stroke: Indian perspective. Int J Stroke. 2006;1:164-6.

Broughton BR, Reutens DC, Sobey CG. Apoptotic mechanisms after cerebral ischemia. Stroke. 2009;40:e331-9.

Flaherty ML, Woo D, Haverbusch M, Sekar P, Khoury J, Sauerbeck L et al. Racial variations in location and risk of intracerebral hemorrhage. Stroke. 2005;36:934-7.

Aronowski J, Zhao X. Molecular pathophysiology of cerebral hemorrhage: Secondary brain injury. Stroke. 2011;42:1781-6.

Liu CC, Ko HJ, Liu WS, Hung CL, Hu KC, Yu LY et al. Neutrophil-to-lymphocyte ratio as a predictive marker of metabolic syndrome. Medicine. 2019;98(43).

Fest J, Ruiter TR, Koerkamp BG, Rizopoulos D, Ikram MA, Van Eijck CH et al. The neutrophil-to-lymphocyte ratio is associated with mortality in the general population: The Rotterdam Study. Eur J Epidemiol. 2019 May;34(5):463-70.

Forget P, Khalifa C, Defour JP, Latinne D, Van Pel MC, De Kock M. What is the normal value of the neutrophil-to-lymphocyte ratio? BMC Res Notes. 2017;10(1):1-4.

Liu X, Shen Y, Wang H, Ge Q, Fei A, Pan S. Prognostic significance of neutrophil-to-lymphocyte ratio in patients with sepsis: a prospective observational study. Mediators Inflammation. 2016;2016.

Imtiaz F, Shafique K, Mirza SS, Ayoob Z, Vart P, Rao S. Neutrophil lymphocyte ratio as a measure of systemic inflammation in prevalent chronic diseases in Asian population. Int Arch Med. 2012;5(1):1-6.

Watson J, Jones HE, Banks J, Whiting P, Salisbury C, Hamilton W. Use of multiple inflammatory marker tests in primary care: using Clinical Practice Research Datalink to evaluate accuracy. Bri J General Pract. 2019;69(684):e462-9.

Gabay C, Kushner I. Acute-phase proteins and other systemic responses to inflammation. N Eng J Med. 1999;340(6):448-54.

Meisner M. Update on procalcitonin measurements. Ann Lab Med. 2014;34(4):263-73.

Luo B, Sun M, Huo X, Wang Y. Two new inflammatory markers related to the CURB-65 score for disease severity in patients with community-acquired pneumonia: The hypersensitive C-reactive protein to albumin ratio and fibrinogen to albumin ratio. Open Life Sci. 2021;16(1):84-91.

Man MA, Rajnoveanu RM, Motoc NS, Bondor CI, Chis AF, Lesan A et al. Neutrophil-to-lymphocyte ratio, platelets-to-lymphocyte ratio, and eosinophils correlation with high-resolution computer tomography severity score in COVID-19 patients. Plos one. 2021;16(6):e0252599.

De Jager CP, Van Wijk PT, Mathoera RB, De Jongh-Leuvenink J, Van der Poll T, Wever PC. Lymphocytopenia and neutrophil-lymphocyte count ratio predict bacteremia better than conventional infection markers in an emergency care unit. Critical care. 2010;14(5):1-8.

Fest J, Ruiter TR, Koerkamp BG, Rizopoulos D, Ikram MA, van Eijck CH, Stricker BH. The neutrophil-to-lymphocyte ratio is associated with mortality in the general population: The Rotterdam Study. Eur J Epidemiol. 2019;34(5):463-70.

Zhang J, Ren Q, Song Y, He M, Zeng Y, Liu Z, Xu J. Prognostic role of neutrophil–lymphocyte ratio in patients with acute ischemic stroke. Medicine. 2017;96(45).

Man MA, Rajnoveanu RM, Motoc NS, Bondor CI, Chis AF, Lesan A et al. Neutrophil-to-lymphocyte ratio, platelets-to-lymphocyte ratio, and eosinophils correlation with high-resolution computer tomography severity score in COVID-19 patients. Plos One. 2021;16(6):e0252599.

Liu Y, Du X, Chen J, Jin Y, Peng L, Wang HH, Luo M, Chen L, Zhao Y. Neutrophil-to-lymphocyte ratio as an independent risk factor for mortality in hospitalized patients with COVID-19. J Infect. 2020;81(1):e6-12.

Haley EC Jr, Levy DE, Brott TG. Urgent therapy for stroke. Part II. Pilot study of tissue plasminogen activator administered 91-180 minutes from onset. Stroke. 1992;23:641-5.

Haley EC Jr, Brott TG, Sheppard GL. Pilot randomized trial of tissue plasminogen activator in acute ischemic stroke. The TPA Bridging Study Group. Stroke. 1993;24:1000-4.

The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. Tissue plasminogen activator for acute ischemic stroke. N Engl J Med. 1995;333:1581-7.

Adams HP Jr, Olinger CP, Barsan WG. A dose-escalation study of large doses of naloxone for treatment of patients with acute cerebral ischemia. Stroke. 1986;17:404-9.

Roach GW, Newman MF, Murkin JM. Ineffectiveness of burst suppression therapy in mitigating perioperative cerebrovascular dysfunction. Multicenter Study of Perioperative Ischemia (McSPI) Research Group. Anesthesiology 1999;90:1255-64.

Newman MF, Wolman R, Kanchuger M. Multicenter preoperative stroke risk index for patients undergoing coronary artery bypass graft surgery. Multicenter Study of Perioperative Ischemia (McSPI) Research Group. Circulation. 1996;94:II74-80.

Mathew JP, Fontes ML, Tudor IC. A multicenter risk index for atrial fibrillation after cardiac surgery. JAMA 2004;291:1720-9 .

Shernan SK, Fitch JC, Nussmeier NA. Impact of pexelizumab, an anti-C5 complement antibody, on total mortality and adverse cardiovascular outcomes in cardiac surgical patients undergoing cardiopulmonary bypass. Ann Thorac Surg. 2004;77:942-9.

Cook DJ, Huston J 3rd, Trenerry MR, Brown RD Jr, Zehr KJ, Sundt TM 3rd. Postcardiac surgical cognitive impairment in the aged using diffusion-weighted magnetic resonance imaging. Ann Thorac Surg. 2007;83:1389-95.

Gurm HS, Yadav JS, Fayad P. Long-term results of carotid stenting versus endarterectomy in high-risk patients. N Engl J Med. 2008;358:1572-9.

SPACE Collaborative Group. 30-day results from the SPACE trial of stent-protected angioplasty versus carotid endarterectomy in symptomatic patients: a randomised non-inferiority trial. Lancet. 2006;368:1239-47.

Brott TG, Hobson RW 2nd, Howard G. Stenting versus endarterectomy for treatment of carotid-artery stenosis. N Engl J Med. 2010;363:11-23.

Derdeyn CP, Chimowitz MI, Lynn MJ. Aggressive medical treatment with or without stenting in high-risk patients with intracranial artery stenosis (SAMMPRIS): the final results of a randomised trial. Lancet. 2014;383:333-41.

Grubb RL Jr, Powers WJ, Clarke WR. Surgical results of the Carotid Occlusion Surgery Study. J Neurosurg 2013;118:25-33.

Powers WJ, Clarke WR, Grubb RL Jr. Extracranial-intracranial bypass surgery for stroke prevention in hemodynamic cerebral ischemia: the Carotid Occlusion Surgery Study randomized trial. JAMA. 2011;306:1983-92.

Sato S, Toyoda K, Uehara T. Baseline NIH Stroke Scale Score predicting outcome in anterior and posterior circulation strokes. Neurology. 2008;70:2371-7.

Meyer BC, Hemmen TM, Jackson CM, Lyden PD. Modified National Institutes of Health Stroke Scale for use in stroke clinical trials: prospective reliability and validity. Stroke. 2002;33:1261-6.

Wojner-Alexandrov AW, Alexandrov AV, Rodriguez D, Persse D, Grotta JC. Houston paramedic and emergency stroke treatment and outcomes study (HoPSTO). Stroke. 2005;36:1512-8.

Bray JE, Martin J, Cooper G, Barger B, Bernard S, Bladin C. Paramedic identification of stroke: community validation of the melbourne ambulance stroke screen. Cerebrovasc Dis. 2005;20(1):28-33.

Nor AM, Davis J, Sen B. The Recognition of Stroke in the Emergency Room (ROSIER) scale: development and validation of a stroke recognition instrument. Lancet Neurol. 2005;4:727-34.

Fu Y, Liu Q, Anrather J, Shi FD. Immune interventions in stroke. Nat Rev Neurol. 2015;11(9):524-35.

Kim JY, Park J, Chang JY, Kim SH, Lee JE. Inflammation after ischemic stroke: The role of leukocytes and glial cells. Exp Neurobiol. 2016;25(5):241-51.

Grau AJ, Boddy AW, Dukovic DA. Leukocyte count as an independent predictor of recurrent ischemic events. Stroke. 2004;35(5):1147-52.