The association of neutrophil-to-lymphocyte ratio and delayed cerebral ischemia in patients with aneurysmal subarachnoid hemorrhage: possible involvement of cerebral blood perfusion

Aneurysmal subarachnoid hemorrhage (aSAH) is an important type of stroke with the highest rates of mortality and disability. Recent evidence indicates that neuroinflammation plays a critical role in both early brain injury and delayed neural deterioration after aSAH, contributing to unfavorable outcomes. The neutrophil-to-lymphocyte ratio (NLR) is a peripheral biomarker that conveys information about the inflammatory burden in terms of both innate and adaptive immunity. This review summarizes relevant studies that associate the NLR with aSAH to evaluate whether the NLR can predict outcomes and serve as an effective biomarker for clinical management. We found that increased NLR is valuable in predicting the clinical outcome of aSAH patients and is related to the risk of complications such as delayed cerebral ischemia (DCI) or rebleeding. Combined with other indicators, the NLR provides improved accuracy for predicting prognosis to stratify patients into different risk categories. The underlying pathophysiology is highlighted to identify new potential targets for neuroprotection and to develop novel therapeutic strategies.

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The Prognostic Value of Neutrophil-to-Lymphocyte Ratio in Patients With Aneurysmal Subarachnoid Hemorrhage: A Systematic Review and Meta-Analysis of Observational Studies

Frontiers in Neurology ◽

10.3389/fneur.2021.745560 ◽

2021 ◽

Vol 12 ◽

Author(s):

Min Shi ◽

Chao Yang ◽

Qing-wen Tang ◽

Ling-fei Xiao ◽

Zu-han Chen ◽

...

Keyword(s):

Systematic Review ◽

Subarachnoid Hemorrhage ◽

Malignant Tumors ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Meta Analysis ◽

Delayed Cerebral Ischemia ◽

Neutrophil To Lymphocyte Ratio ◽

Cochrane Library ◽

Lymphocyte Ratio ◽

Poor Outcome

The neutrophil–to-lymphocyte ratio (NLR), as an essential systemic inflammation factor, has been widely used as a prognostic indicator in various diseases, such as malignant tumors, cardiovascular disease, and intracranial hemorrhage. An increasing number of studies have believed that NLR is a valuable predictor of prognosis for patients with aneurysmal subarachnoid hemorrhage (aSAH). However, these results remain controversial. In the current study, we planned to carry out a systematic review and meta-analysis to investigate the association between NLR and poor outcome, and the occurrence of delayed cerebral ischemia (DCI). We carried out a comprehensive search for published literatures on PubMed, EMBASE, Cochrane Library, and Web of Science databases from inception to April 1, 2021. We conducted an assessment of all included studies based on the principles proposed in the Newcastle-Ottawa Quality Assessment Scale (NOS). Poor outcome and the occurrence of DCI were considered as the main outcome measure. We calculated the pooled odds ratio (OR) and corresponding 95% confidence interval (CI) to examine the strength of the association of NLR with poor outcome or the occurrence of DCI. We strictly selected a total of 10 studies comprising 4,989 patients. Nine studies reported the association between NLR and poor outcome, and five studies reported the association between NLR and the occurrence of DCI. The pooled results indicated higher NLR was significantly associated with both poorer outcomes (OR = 1.32, 95%CI 1.11–1.57; P = 0.002, I2 = 87%), and the occurrence of DCI (OR = 1.72, 95%CI 1.22–2.41; P = 0.002, I2 = 82%) in aSAH patients. The NLR is a valuable indicator of inflammation to independently predict poor outcome and occurrence of DCI after aSAH, where a higher NLR is significantly associated with poor outcomes and occurrence of DCI. These findings suggest that the NLR can help clinicians evaluate the prognosis and identify potentially severe patients early, which may contribute to better management and improve poor prognosis of aSAH patients.

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Admission neutrophil–lymphocyte ratio predicts delayed cerebral ischemia following aneurysmal subarachnoid hemorrhage

Journal of NeuroInterventional Surgery ◽

10.1136/neurintsurg-2019-014759 ◽

2019 ◽

Vol 11 (11) ◽

pp. 1135-1140 ◽

Cited By ~ 11

Author(s):

Fawaz Al-Mufti ◽

Krishna Amuluru ◽

Nitesh Damodara ◽

Vincent Dodson ◽

David Roh ◽

...

Keyword(s):

Subarachnoid Hemorrhage ◽

Cerebral Ischemia ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Delayed Cerebral Ischemia ◽

Neurological Impairment ◽

Logistic Regression Models ◽

Neutrophil Lymphocyte Ratio ◽

Lymphocyte Ratio ◽

Fisher Grade ◽

Grade 3

BackgroundDelayed cerebral ischemia (DCI) following aneurysmal subarachnoid hemorrhage (aSAH) has a multifactorial pathophysiology, with immune dysregulation being an important component. The neutrophil–lymphocyte ratio (NLR) is an established prognostic marker in patients with cancer, cardiac disease, and sepsis.ObjectiveTo determine whether there is a relationship between NLR and DCI in patients with aSAH.MethodsWe evaluated 1067 patients with aSAH between 2006 and 2015 enrolled in a single-center, prospective, observational cohort study. Admission white blood cell differentials (NLR) were analyzed using a cut-off point of ≥5.9. DCI from cerebral vasospasm was defined as the occurrence of focal neurological impairment, or a decrease in at least two points on the Glasgow Coma Scale, which was not apparent immediately after aneurysm occlusion, and could not be attributed to other causes. Cerebral infarct was defined as a new infarct on CT that was not visible on the admission or immediate postoperative scan, when the cause was thought to be vasospasm by the research team. Logistic regression models were generated.ResultsWe found that 768 (72%) patients had an admission NLR ≥5.9. In a multivariable model, elevated NLR was associated with poor admission Hunt-Hess grade (OR=1.6, 95% CI 1.2 to 2.6, p=0.005), Caucasian ethnicity (OR=2.6, 95% CI 1.9 to 3.7, p<0.001), anterior aneurysm location (OR=1.7, 95% CI 1.2 to 2.4, p=0.004), loss of consciousness at ictus (OR=1.4, 95% CI 1.0 to 2.0, p=0.055), and thick SAH (modified Fisher grade ≥3) (OR=1.8, 95% CI 1.3 to 2.4, p<0.001). Admission NLR predicted development of delayed cerebral ischemia (DCI) (OR=1.7; 95% CI 1.1 to 2.5, p=0.008) after controlling for known predictors such as age, poor admission clinical grade, thick SAH blood, and elevated admission mean arterial pressure.ConclusionsThis study provides further evidence of the association between inflammation and DCI. Admission NLR is a readily available and convenient biomarker that may be a clinically useful tool for prognostication when evaluating aSAH.

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Abstract TP421: Admission Neutrophil-Lymphocyte Ratio Predicts Delayed Cerebral Ischemia Following Aneurysmal Subarachnoid Hemorrhage

Stroke ◽

10.1161/str.48.suppl_1.tp421 ◽

2017 ◽

Vol 48 (suppl_1) ◽

Author(s):

Vincent Dodson ◽

Ethan Wasjwol ◽

Fawaz Al-Mufti ◽

Krishna Amuluru ◽

Mohammad Elghanem ◽

...

Keyword(s):

Subarachnoid Hemorrhage ◽

Cerebral Ischemia ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Delayed Cerebral Ischemia ◽

Logistic Regression Models ◽

Neutrophil Lymphocyte Ratio ◽

Lymphocyte Ratio ◽

Patients With Cancer ◽

Level Of Consciousness ◽

Observational Cohort

Introduction: Immune dysregulation has long been implicated in the development of delayed cerebral ischemia (DCI) following aneurysmal subarachnoid hemorrhage (aSAH). The neutrophil-lymphocyte ratio (NLR) is an established prognostic marker in patients with cancer, cardiac disease, or sepsis. This study sought to determine whether there is a relationship between NLR and DCI in SAH patients. Methods: We evaluated 340 aneurysmal SAH patients between 2002 and 2015 enrolled into a single center, retrospective, observational cohort study. Admission NLR was analyzed using a ≥10 cutoff. DCI from cerebral vasospasm was defined as (1) clinical deterioration (i.e., a new focal deficit, decrease in level of consciousness, or both), and/or (2) a new infarct on CT that was not visible on the admission or immediate postoperative scan, when the cause was thought by the research team to be vasospasm. Logistic regression models were generated. Results: We found that 132 (39%) patients had an admission NLR ≥ 10. Admission NLR predicted development of DCI (OR: 1.7; 95% CI: 1.1- 2.5, p=0.008) after controlling known predictors including age and incidence of rebleed. Conclusions: This study shows that the admission NLR provides further evidence to the association between inflammation and DCI. Admission NLR is a readily available biomarker that may be a clinically useful tool for prognostication when evaluating SAH.

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Faculty Opinions recommendation of Effect of pharmaceutical treatment on vasospasm, delayed cerebral ischemia, and clinical outcome in patients with aneurysmal subarachnoid hemorrhage: a systematic review and meta-analysis.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.722313796.793510609 ◽

2015 ◽

Author(s):

Peter Andrews

Keyword(s):

Systematic Review ◽

Subarachnoid Hemorrhage ◽

Cerebral Ischemia ◽

Clinical Outcome ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Meta Analysis ◽

Delayed Cerebral Ischemia ◽

Pharmaceutical Treatment

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Faculty Opinions recommendation of Cerebral Autoregulation in the Prediction of Delayed Cerebral Ischemia and Clinical Outcome in Poor-Grade Aneurysmal Subarachnoid Hemorrhage Patients.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.732595998.793542399 ◽

2018 ◽

Author(s):

Stephan Mayer

Keyword(s):

Subarachnoid Hemorrhage ◽

Cerebral Ischemia ◽

Clinical Outcome ◽

Cerebral Autoregulation ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Delayed Cerebral Ischemia ◽

Poor Grade

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Neutrophil-to-Albumin Ratio As a Biomarker of Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage

World Neurosurgery ◽

10.1016/j.wneu.2020.12.084 ◽

2020 ◽

Author(s):

Xin Zhang ◽

Yumeng Liu ◽

Sheng Zhang ◽

Congkai Wang ◽

Changsheng Zou ◽

...

Keyword(s):

Subarachnoid Hemorrhage ◽

Cerebral Ischemia ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Delayed Cerebral Ischemia ◽

Albumin Ratio

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Sevoflurane and Desflurane Exposures Following Aneurysmal Subarachnoid Hemorrhage Confer Multifaceted Protection against Delayed Cerebral Ischemia

Biomedicines ◽

10.3390/biomedicines9070820 ◽

2021 ◽

Vol 9 (7) ◽

pp. 820

Author(s):

Keshav Jayaraman ◽

Meizi Liu ◽

Gregory J. Zipfel ◽

Umeshkumar Athiraman

Keyword(s):

Subarachnoid Hemorrhage ◽

Cerebral Ischemia ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Delayed Cerebral Ischemia ◽

Preclinical Studies ◽

Large Artery ◽

Sham Surgery ◽

Neurological Patients ◽

Neurologic Function ◽

Preclinical And Clinical Studies

Numerous studies have demonstrated the ability of isoflurane conditioning to provide multifaceted protection against aneurysmal subarachnoid hemorrhage (SAH)-associated delayed cerebral ischemia (DCI); however, preclinical studies have not yet examined whether other commonly used inhalational anesthetics in neurological patients such as sevoflurane or desflurane are also protective against SAH-induced neurovascular deficits. We therefore sought to identify the potential for sevoflurane and desflurane conditioning to protect against DCI in an endovascular perforation mouse model of SAH. Neurological function was assessed daily via neuroscore. Large artery vasospasm and microvessel thrombosis were assessed three days after SAH or sham surgery. Four groups were examined: Sham, SAH + room air, SAH + 2% Sevoflurane, and SAH + 6% Desflurane. For the SAH groups, one hour after surgery, mice received 2% sevoflurane, 6% desflurane, or room air for one hour. We found that conditioning with sevoflurane or desflurane attenuated large artery vasospasm, reduced microvessel thrombosis, and improved neurologic function. Given their frequent clinical use and strong safety profile in patients (including those with SAH), these data strongly support further studies to validate these findings in preclinical and clinical studies and to elucidate the mechanisms by which these agents might be acting.

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Effects of post-interventional antiplatelet therapy on angiographic vasospasm, delayed cerebral ischemia, and clinical outcome after aneurysmal subarachnoid hemorrhage: a single-center experience

Neurosurgical Review ◽

10.1007/s10143-021-01477-6 ◽

2021 ◽

Author(s):

Claudia Ditz ◽

Björn Machner ◽

Hannes Schacht ◽

Alexander Neumann ◽

Peter Schramm ◽

...

Keyword(s):

Subarachnoid Hemorrhage ◽

Cerebral Ischemia ◽

Functional Outcome ◽

Antiplatelet Therapy ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Delayed Cerebral Ischemia ◽

Control Group ◽

Lesion Volume ◽

Single Center ◽

Single Center Experience

AbstractPlatelet activation has been postulated to be involved in the pathogenesis of delayed cerebral ischemia (DCI) and cerebral vasospasm (CVS) after aneurysmal subarachnoid hemorrhage (aSAH). The aim of this study was to investigate potentially beneficial effects of antiplatelet therapy (APT) on angiographic CVS, DCI-related infarction and functional outcome in endovascularly treated aSAH patients. Retrospective single-center analysis of aSAH patients treated by endovascular aneurysm obliteration. Based on the post-interventional medical regime, patients were assigned to either an APT group or a control group not receiving APT. A subgroup analysis separately investigated those APT patients with aspirin monotherapy (MAPT) and those receiving dual treatment (aspirin plus clopidogrel, DAPT). Clinical and radiological characteristics were compared between groups. Possible predictors for angiographic CVS, DCI-related infarction, and an unfavorable functional outcome (modified Rankin scale ≥ 3) were analyzed. Of 160 patients, 85 (53%) had received APT (n = 29 MAPT, n = 56 DAPT). APT was independently associated with a lower incidence of an unfavorable functional outcome (OR 0.40 [0.19–0.87], P = 0.021) after 3 months. APT did not reduce the incidence of angiographic CVS or DCI-related infarction. The pattern of angiographic CVS or DCI-related infarction as well as the rate of intracranial hemorrhage did not differ between groups. However, the lesion volume of DCI-related infarctions was significantly reduced in the DAPT subgroup (P = 0.011). Post-interventional APT in endovascularly treated aSAH patients is associated with better functional outcome at 3 months. The beneficial effect of APT might be mediated by reduction of the size of DCI-related infarctions.

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