Skip to main content
Top
Published in: Journal of Neuroinflammation 1/2018

Open Access 01-12-2018 | Research

Neutrophil to lymphocyte ratio predicts intracranial hemorrhage after endovascular thrombectomy in acute ischemic stroke

Authors: Slaven Pikija, Laszlo K. Sztriha, Monika Killer-Oberpfalzer, Friedrich Weymayr, Constantin Hecker, Christian Ramesmayer, Larissa Hauer, Johann Sellner

Published in: Journal of Neuroinflammation | Issue 1/2018

Login to get access

Abstract

Background

The development of intracranial hemorrhage (ICH) in acute ischemic stroke is associated with a higher neutrophil to lymphocyte ratio (NLR) in peripheral blood. Here, we studied whether the predictive value of NLR at admission also translates into the occurrence of hemorrhagic complications and poor functional outcome after endovascular treatment (EVT).

Methods

We performed a retrospective analysis of consecutive patients with anterior circulation ischemic stroke who underwent EVT at a tertiary care center from 2012 to 2016. Follow-up scans were examined for non-procedural ICH and scored according to the Heidelberg Bleeding Classification. Demographic, clinical, and laboratory data were correlated with the occurrence of non-procedural ICH.

Results

We identified 187 patients with a median age of 74 years (interquartile range [IQR] 60–81) and a median baseline National Institutes of Health Stroke scale (NIHSS) score of 18 (IQR 13–22). A bridging therapy with recombinant tissue-plasminogen activator (rt-PA) was performed in 133 (71%). Of the 31 patients with non-procedural ICH (16.6%), 13 (41.9%) were symptomatic. Patients with ICH more commonly had a worse outcome at 3 months (p = 0.049), and were characterized by a lower body mass index, more frequent presence of tandem occlusions, higher NLR, larger intracranial thrombus, and prolonged rt-PA and groin puncture times. In a multivariate analysis, higher admission NLR was independently associated with ICH (OR 1.09 per unit increase, 95% CI (1.00–1.20, p = 0.040). The optimal cutoff value of NLR that best distinguished the development of ICH was 3.89.

Conclusions

NLR is an independent predictor for the development of ICH after EVT. Further studies are needed to investigate the role of the immune system in hemorrhagic complications following EVT, and confirm the value of NLR as a potential biomarker.
Literature
1.
go back to reference Broderick JP, Berkhemer OA, Palesch YY, Dippel DW, Foster LD, Roos YB, van der Lugt A, Tomsick TA, Majoie CB, van Zwam WH, et al. Endovascular therapy is effective and safe for patients with severe ischemic stroke: pooled analysis of interventional management of stroke III and multicenter randomized clinical trial of endovascular therapy for acute ischemic stroke in the Netherlands data. Stroke. 2015;46:3416–22.CrossRef Broderick JP, Berkhemer OA, Palesch YY, Dippel DW, Foster LD, Roos YB, van der Lugt A, Tomsick TA, Majoie CB, van Zwam WH, et al. Endovascular therapy is effective and safe for patients with severe ischemic stroke: pooled analysis of interventional management of stroke III and multicenter randomized clinical trial of endovascular therapy for acute ischemic stroke in the Netherlands data. Stroke. 2015;46:3416–22.CrossRef
2.
go back to reference Berkhemer OA, Majoie CB, Dippel DW, Investigators MC. Endovascular therapy for ischemic stroke. N Engl J Med. 2015;372:2363.CrossRef Berkhemer OA, Majoie CB, Dippel DW, Investigators MC. Endovascular therapy for ischemic stroke. N Engl J Med. 2015;372:2363.CrossRef
3.
go back to reference Badhiwala JH, Nassiri F, Alhazzani W, Selim MH, Farrokhyar F, Spears J, Kulkarni AV, Singh S, Alqahtani A, Rochwerg B, et al. Endovascular thrombectomy for acute ischemic stroke: a meta-analysis. JAMA. 2015;314:1832–43.CrossRef Badhiwala JH, Nassiri F, Alhazzani W, Selim MH, Farrokhyar F, Spears J, Kulkarni AV, Singh S, Alqahtani A, Rochwerg B, et al. Endovascular thrombectomy for acute ischemic stroke: a meta-analysis. JAMA. 2015;314:1832–43.CrossRef
4.
go back to reference Saver JL, Goyal M, van der Lugt A, Menon BK, Majoie CB, Dippel DW, Campbell BC, Nogueira RG, Demchuk AM, Tomasello A, et al. Time to treatment with endovascular thrombectomy and outcomes from ischemic stroke: a meta-analysis. JAMA. 2016;316:1279–88.CrossRef Saver JL, Goyal M, van der Lugt A, Menon BK, Majoie CB, Dippel DW, Campbell BC, Nogueira RG, Demchuk AM, Tomasello A, et al. Time to treatment with endovascular thrombectomy and outcomes from ischemic stroke: a meta-analysis. JAMA. 2016;316:1279–88.CrossRef
5.
go back to reference Bracard S, Ducrocq X, Mas JL, Soudant M, Oppenheim C, Moulin T, Guillemin F, Investigators T. Mechanical thrombectomy after intravenous alteplase versus alteplase alone after stroke (THRACE): a randomised controlled trial. Lancet Neurol. 2016;15:1138–47.CrossRef Bracard S, Ducrocq X, Mas JL, Soudant M, Oppenheim C, Moulin T, Guillemin F, Investigators T. Mechanical thrombectomy after intravenous alteplase versus alteplase alone after stroke (THRACE): a randomised controlled trial. Lancet Neurol. 2016;15:1138–47.CrossRef
6.
go back to reference Goyal M, Demchuk AM, Menon BK, Eesa M, Rempel JL, Thornton J, Roy D, Jovin TG, Willinsky RA, Sapkota BL, et al. Randomized assessment of rapid endovascular treatment of ischemic stroke. N Engl J Med. 2015;372:1019–30.CrossRef Goyal M, Demchuk AM, Menon BK, Eesa M, Rempel JL, Thornton J, Roy D, Jovin TG, Willinsky RA, Sapkota BL, et al. Randomized assessment of rapid endovascular treatment of ischemic stroke. N Engl J Med. 2015;372:1019–30.CrossRef
7.
go back to reference Hao Y, Yang D, Wang H, Zi W, Zhang M, Geng Y, Zhou Z, Wang W, Xu H, Tian X, et al. Predictors for symptomatic intracranial hemorrhage after endovascular treatment of acute ischemic stroke. Stroke. 2017;48:1203–9.CrossRef Hao Y, Yang D, Wang H, Zi W, Zhang M, Geng Y, Zhou Z, Wang W, Xu H, Tian X, et al. Predictors for symptomatic intracranial hemorrhage after endovascular treatment of acute ischemic stroke. Stroke. 2017;48:1203–9.CrossRef
8.
go back to reference Choi JH, Pile-Spellman J. Reperfusion changes after stroke and practical approaches for neuroprotection. Neuroimaging Clin N Am. 2018;28:663–82.CrossRef Choi JH, Pile-Spellman J. Reperfusion changes after stroke and practical approaches for neuroprotection. Neuroimaging Clin N Am. 2018;28:663–82.CrossRef
9.
go back to reference Suzuki Y, Nagai N, Umemura K. A review of the mechanisms of blood-brain barrier permeability by tissue-type plasminogen activator treatment for cerebral ischemia. Front Cell Neurosci. 2016;10:2.PubMedPubMedCentral Suzuki Y, Nagai N, Umemura K. A review of the mechanisms of blood-brain barrier permeability by tissue-type plasminogen activator treatment for cerebral ischemia. Front Cell Neurosci. 2016;10:2.PubMedPubMedCentral
10.
go back to reference Dentali F, Conte G, Guasti L. Neutrophil-to-lymphocyte ratio: a new prognostic factor even in patients with heart failure. Pol Arch Med Wewn. 2016;126:116–7.PubMed Dentali F, Conte G, Guasti L. Neutrophil-to-lymphocyte ratio: a new prognostic factor even in patients with heart failure. Pol Arch Med Wewn. 2016;126:116–7.PubMed
11.
go back to reference Xue J, Huang W, Chen X, Li Q, Cai Z, Yu T, Shao B. Neutrophil-to-lymphocyte ratio is a prognostic marker in acute ischemic stroke. J Stroke Cerebrovasc Dis. 2017;26:650–7.CrossRef Xue J, Huang W, Chen X, Li Q, Cai Z, Yu T, Shao B. Neutrophil-to-lymphocyte ratio is a prognostic marker in acute ischemic stroke. J Stroke Cerebrovasc Dis. 2017;26:650–7.CrossRef
12.
go back to reference Yu S, Arima H, Bertmar C, Clarke S, Herkes G, Krause M. Neutrophil to lymphocyte ratio and early clinical outcomes in patients with acute ischemic stroke. J Neurol Sci. 2018;387:115–8.CrossRef Yu S, Arima H, Bertmar C, Clarke S, Herkes G, Krause M. Neutrophil to lymphocyte ratio and early clinical outcomes in patients with acute ischemic stroke. J Neurol Sci. 2018;387:115–8.CrossRef
13.
go back to reference Qun S, Tang Y, Sun J, Liu Z, Wu J, Zhang J, Guo J, Xu Z, Zhang D, Chen Z, et al. Neutrophil-to-lymphocyte ratio predicts 3-month outcome of acute ischemic stroke. Neurotox Res. 2017;31:444–52.CrossRef Qun S, Tang Y, Sun J, Liu Z, Wu J, Zhang J, Guo J, Xu Z, Zhang D, Chen Z, et al. Neutrophil-to-lymphocyte ratio predicts 3-month outcome of acute ischemic stroke. Neurotox Res. 2017;31:444–52.CrossRef
14.
go back to reference Brooks SD, Spears C, Cummings C, VanGilder RL, Stinehart KR, Gutmann L, Domico J, Culp S, Carpenter J, Rai A, Barr TL. Admission neutrophil-lymphocyte ratio predicts 90 day outcome after endovascular stroke therapy. J Neurointerv Surg. 2014;6:578–83.CrossRef Brooks SD, Spears C, Cummings C, VanGilder RL, Stinehart KR, Gutmann L, Domico J, Culp S, Carpenter J, Rai A, Barr TL. Admission neutrophil-lymphocyte ratio predicts 90 day outcome after endovascular stroke therapy. J Neurointerv Surg. 2014;6:578–83.CrossRef
15.
go back to reference Maestrini I, Strbian D, Gautier S, Haapaniemi E, Moulin S, Sairanen T, Dequatre-Ponchelle N, Sibolt G, Cordonnier C, Melkas S, et al. Higher neutrophil counts before thrombolysis for cerebral ischemia predict worse outcomes. Neurology. 2015;85:1408–16.CrossRef Maestrini I, Strbian D, Gautier S, Haapaniemi E, Moulin S, Sairanen T, Dequatre-Ponchelle N, Sibolt G, Cordonnier C, Melkas S, et al. Higher neutrophil counts before thrombolysis for cerebral ischemia predict worse outcomes. Neurology. 2015;85:1408–16.CrossRef
16.
go back to reference Pikija S, Trkulja V, Mutzenbach JS, McCoy MR, Ganger P, Sellner J. Fibrinogen consumption is related to intracranial clot burden in acute ischemic stroke: a retrospective hyperdense artery study. J Transl Med. 2016;14:250.CrossRef Pikija S, Trkulja V, Mutzenbach JS, McCoy MR, Ganger P, Sellner J. Fibrinogen consumption is related to intracranial clot burden in acute ischemic stroke: a retrospective hyperdense artery study. J Transl Med. 2016;14:250.CrossRef
17.
go back to reference Pikija S, Sztriha LK, Killer-Oberpfalzer M, Weymayr F, Hecker C, Ramesmayer C, Hauer L, Sellner J. Contribution of serum lipid profiles to outcome after endovascular thrombectomy for anterior circulation ischemic stroke. Mol Neurobiol; 2018. https://doi.org/10.1007/s12035-018-1391-3. Pikija S, Sztriha LK, Killer-Oberpfalzer M, Weymayr F, Hecker C, Ramesmayer C, Hauer L, Sellner J. Contribution of serum lipid profiles to outcome after endovascular thrombectomy for anterior circulation ischemic stroke. Mol Neurobiol; 2018. https://​doi.​org/​10.​1007/​s12035-018-1391-3.
18.
go back to reference Higashida RT, Furlan AJ, Roberts H, Tomsick T, Connors B, Barr J, Dillon W, Warach S, Broderick J, Tilley B, et al. Trial design and reporting standards for intra-arterial cerebral thrombolysis for acute ischemic stroke. Stroke. 2003;34:e109–37.CrossRef Higashida RT, Furlan AJ, Roberts H, Tomsick T, Connors B, Barr J, Dillon W, Warach S, Broderick J, Tilley B, et al. Trial design and reporting standards for intra-arterial cerebral thrombolysis for acute ischemic stroke. Stroke. 2003;34:e109–37.CrossRef
19.
go back to reference von Kummer R, Broderick JP, Campbell BC, Demchuk A, Goyal M, Hill MD, Treurniet KM, Majoie CB, Marquering HA, Mazya MV, et al. The Heidelberg bleeding classification: classification of bleeding events after ischemic stroke and reperfusion therapy. Stroke. 2015;46:2981–6.CrossRef von Kummer R, Broderick JP, Campbell BC, Demchuk A, Goyal M, Hill MD, Treurniet KM, Majoie CB, Marquering HA, Mazya MV, et al. The Heidelberg bleeding classification: classification of bleeding events after ischemic stroke and reperfusion therapy. Stroke. 2015;46:2981–6.CrossRef
20.
go back to reference Adams HP Jr, Bendixen BH, Kappelle LJ, Biller J, Love BB, Gordon DL, Marsh EE 3rd. Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of org 10172 in acute stroke treatment. Stroke. 1993;24:35–41.CrossRef Adams HP Jr, Bendixen BH, Kappelle LJ, Biller J, Love BB, Gordon DL, Marsh EE 3rd. Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of org 10172 in acute stroke treatment. Stroke. 1993;24:35–41.CrossRef
22.
go back to reference Lee JS, Kim NY, Na SH, Youn YH, Shin CS. Reference values of neutrophil-lymphocyte ratio, lymphocyte-monocyte ratio, platelet-lymphocyte ratio, and mean platelet volume in healthy adults in South Korea. Medicine (Baltimore). 2018;97:e11138.CrossRef Lee JS, Kim NY, Na SH, Youn YH, Shin CS. Reference values of neutrophil-lymphocyte ratio, lymphocyte-monocyte ratio, platelet-lymphocyte ratio, and mean platelet volume in healthy adults in South Korea. Medicine (Baltimore). 2018;97:e11138.CrossRef
23.
go back to reference 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;10:12.CrossRef 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;10:12.CrossRef
24.
go back to reference Gokhan S, Ozhasenekler A, Mansur Durgun H, Akil E, Ustundag M, Orak M. Neutrophil lymphocyte ratios in stroke subtypes and transient ischemic attack. Eur Rev Med Pharmacol Sci. 2013;17:653–7.PubMed Gokhan S, Ozhasenekler A, Mansur Durgun H, Akil E, Ustundag M, Orak M. Neutrophil lymphocyte ratios in stroke subtypes and transient ischemic attack. Eur Rev Med Pharmacol Sci. 2013;17:653–7.PubMed
25.
go back to reference Hermann DM, Kleinschnitz C, Gunzer M. Implications of polymorphonuclear neutrophils for ischemic stroke and intracerebral hemorrhage: predictive value, pathophysiological consequences and utility as therapeutic target. J Neuroimmunol. 2018;321:138–43.CrossRef Hermann DM, Kleinschnitz C, Gunzer M. Implications of polymorphonuclear neutrophils for ischemic stroke and intracerebral hemorrhage: predictive value, pathophysiological consequences and utility as therapeutic target. J Neuroimmunol. 2018;321:138–43.CrossRef
26.
go back to reference Guo Z, Yu S, Xiao L, Chen X, Ye R, Zheng P, Dai Q, Sun W, Zhou C, Wang S, et al. Dynamic change of neutrophil to lymphocyte ratio and hemorrhagic transformation after thrombolysis in stroke. J Neuroinflammation. 2016;13:199.CrossRef Guo Z, Yu S, Xiao L, Chen X, Ye R, Zheng P, Dai Q, Sun W, Zhou C, Wang S, et al. Dynamic change of neutrophil to lymphocyte ratio and hemorrhagic transformation after thrombolysis in stroke. J Neuroinflammation. 2016;13:199.CrossRef
27.
go back to reference Fang YN, Tong MS, Sung PH, Chen YL, Chen CH, Tsai NW, Huang CJ, Chang YT, Chen SF, Chang WN, et al. Higher neutrophil counts and neutrophil-to-lymphocyte ratio predict prognostic outcomes in patients after non-atrial fibrillation-caused ischemic stroke. Biom J. 2017;40:154–62. Fang YN, Tong MS, Sung PH, Chen YL, Chen CH, Tsai NW, Huang CJ, Chang YT, Chen SF, Chang WN, et al. Higher neutrophil counts and neutrophil-to-lymphocyte ratio predict prognostic outcomes in patients after non-atrial fibrillation-caused ischemic stroke. Biom J. 2017;40:154–62.
28.
go back to reference Gensicke H, Wicht A, Bill O, Zini A, Costa P, Kagi G, Stark R, Seiffge DJ, Traenka C, Peters N, et al. Impact of body mass index on outcome in stroke patients treated with intravenous thrombolysis. Eur J Neurol. 2016;23:1705–12.CrossRef Gensicke H, Wicht A, Bill O, Zini A, Costa P, Kagi G, Stark R, Seiffge DJ, Traenka C, Peters N, et al. Impact of body mass index on outcome in stroke patients treated with intravenous thrombolysis. Eur J Neurol. 2016;23:1705–12.CrossRef
29.
go back to reference Sun W, Huang Y, Xian Y, Zhu S, Jia Z, Liu R, Li F, Wei JW, Wang JG, Liu M, Anderson CS. Association of body mass index with mortality and functional outcome after acute ischemic stroke. Sci Rep. 2017;7:2507.CrossRef Sun W, Huang Y, Xian Y, Zhu S, Jia Z, Liu R, Li F, Wei JW, Wang JG, Liu M, Anderson CS. Association of body mass index with mortality and functional outcome after acute ischemic stroke. Sci Rep. 2017;7:2507.CrossRef
30.
go back to reference Heck DV, Brown MD. Carotid stenting and intracranial thrombectomy for treatment of acute stroke due to tandem occlusions with aggressive antiplatelet therapy may be associated with a high incidence of intracranial hemorrhage. J Neurointerv Surg. 2015;7:170–5.CrossRef Heck DV, Brown MD. Carotid stenting and intracranial thrombectomy for treatment of acute stroke due to tandem occlusions with aggressive antiplatelet therapy may be associated with a high incidence of intracranial hemorrhage. J Neurointerv Surg. 2015;7:170–5.CrossRef
31.
go back to reference Puetz V, Dzialowski I, Hill MD, Subramaniam S, Sylaja PN, Krol A, O’Reilly C, Hudon ME, Hu WY, Coutts SB, et al. Intracranial thrombus extent predicts clinical outcome, final infarct size and hemorrhagic transformation in ischemic stroke: the clot burden score. Int J Stroke. 2008;3:230–6.CrossRef Puetz V, Dzialowski I, Hill MD, Subramaniam S, Sylaja PN, Krol A, O’Reilly C, Hudon ME, Hu WY, Coutts SB, et al. Intracranial thrombus extent predicts clinical outcome, final infarct size and hemorrhagic transformation in ischemic stroke: the clot burden score. Int J Stroke. 2008;3:230–6.CrossRef
32.
go back to reference Bang OY, Saver JL, Kim SJ, Kim GM, Chung CS, Ovbiagele B, Lee KH, Liebeskind DS, Collaborators UC-SS. Collateral flow averts hemorrhagic transformation after endovascular therapy for acute ischemic stroke. Stroke. 2011;42:2235–9.CrossRef Bang OY, Saver JL, Kim SJ, Kim GM, Chung CS, Ovbiagele B, Lee KH, Liebeskind DS, Collaborators UC-SS. Collateral flow averts hemorrhagic transformation after endovascular therapy for acute ischemic stroke. Stroke. 2011;42:2235–9.CrossRef
33.
go back to reference Balami JS, White PM, McMeekin PJ, Ford GA, Buchan AM. Complications of endovascular treatment for acute ischemic stroke: prevention and management. Int J Stroke. 2018;13:348–61.CrossRef Balami JS, White PM, McMeekin PJ, Ford GA, Buchan AM. Complications of endovascular treatment for acute ischemic stroke: prevention and management. Int J Stroke. 2018;13:348–61.CrossRef
Metadata
Title
Neutrophil to lymphocyte ratio predicts intracranial hemorrhage after endovascular thrombectomy in acute ischemic stroke
Authors
Slaven Pikija
Laszlo K. Sztriha
Monika Killer-Oberpfalzer
Friedrich Weymayr
Constantin Hecker
Christian Ramesmayer
Larissa Hauer
Johann Sellner
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Journal of Neuroinflammation / Issue 1/2018
Electronic ISSN: 1742-2094
DOI
https://doi.org/10.1186/s12974-018-1359-2

Other articles of this Issue 1/2018

Journal of Neuroinflammation 1/2018 Go to the issue