Neutrophil-to-lymphocyte ratio as an independent predictor for unfavorable functional outcome in aneurysmal subarachnoid hemorrhage

Abstract

OBJECTIVEStroke-associated immunosuppression and inflammation are increasingly recognized as factors triggering infections and thus potentially influencing outcome after stroke. Several studies have demonstrated that elevated neutrophil-to-lymphocyte ratio (NLR) is a significant predictor of adverse outcomes for patients with ischemic stroke or intracerebral hemorrhage. Thus far, in patients with subarachnoid hemorrhage the association between NLR and outcome is insufficiently established. The authors sought to investigate the association between NLR on admission and functional outcome in aneurysmal subarachnoid hemorrhage (aSAH).METHODSThis observational study included all consecutive aSAH patients admitted to a German tertiary center over a 5-year period (2008–2012). Data regarding patient demographics and clinical, laboratory, and in-hospital measures, as well as neuroradiological data, were retrieved from institutional databases. Functional outcome was assessed at 3 and 12 months using the modified Rankin Scale (mRS) score and categorized into favorable (mRS score 0–2) and unfavorable (mRS score 3–6). Patients’ radiological and laboratory characteristics were compared between aSAH patients with favorable and those with unfavorable outcome at 3 months. In addition, multivariate analysis was conducted to investigate parameters independently associated with favorable outcome. Receiver operating characteristic (ROC) curve analysis was undertaken to identify the best cutoff for NLR to discriminate between favorable and unfavorable outcome in these patients. To account for imbalances in baseline characteristics, propensity score matching was carried out to assess the influence of NLR on outcome measures.RESULTSOverall, 319 patients with aSAH were included. Patients with unfavorable outcome at 3 months were older, had worse clinical status on admission (Glasgow Coma Scale score and Hunt and Hess grade), greater amount of subarachnoidal and intraventricular hemorrhage (modified Fisher Scale grade and Graeb score), and higher rates of infectious complications (pneumonia and sepsis). A significantly higher NLR on admission was observed in patients with unfavorable outcome according to mRS score (median [IQR] NLR 5.8 [3.0–10.0] for mRS score 0–2 vs NLR 8.3 [4.5–12.6] for mRS score 3–6; p < 0.001). After adjustments, NLR on admission remained a significant predictor for unfavorable outcome in SAH patients (OR [95% CI] 1.014 [1.001–1.027]; p = 0.028). In ROC analysis, an NLR of 7.05 was identified as the best cutoff value to discriminate between favorable and unfavorable outcome (area under the curve = 0.614, p < 0.001, Youden’s index = 0.211; mRS score 3–6: 94/153 [61.4%] for NLR ≥ 7.05 vs 67/166 [40.4%] for NLR < 7.05; p < 0.001). Subanalysis of patients with NLR levels ≥ 7.05 vs < 7.05, performed using 2 propensity score–matched cohorts (n = 133 patients in each group), revealed an increased proportion of patients with unfavorable functional outcome at 3 months in patients with NLR ≥ 7.05 (mRS score 3–6 at 3 months: NLR ≥ 7.05 82/133 [61.7%] vs NLR < 7.05 62/133 [46.6%]; p = 0.014), yet without differences in mortality at 3 months (NLR ≥ 7.05 37/133 [27.8%] vs NLR < 7.05 27/133 [20.3%]; p = 0.131).CONCLUSIONSAmong aSAH patients, NLR represents an independent parameter associated with unfavorable functional outcome. Whether the impact of NLR on functional outcome is related to preexisting comorbidities or represents independent causal relationships in the context of stroke-associated immunosuppression should be investigated in future studies.

The predictive role of the neutrophil–lymphocyte ratio in the prognosis of adult patients with stroke

“…Moreover, in the sensitivity analysis ( Fig. 3), after omitting Giede-Jeppe et al [22] or Goyal et al [25], our results were relatively stable according to the funnel plot and Egger's test (Fig. 5).…”

“…For each study, the following information was carefully extracted: the first author, country, number of patients (male/female), mean age (years), sampling time of the blood, NLR threshold, outcome measure, adjusted odds ratio (OR), and subtype (Table 1). Among the selected studies, there were 6 hemorrhagic stroke studies [13,14,[20][21][22][23] and 7 ischemia stroke studies [11,12,[24][25][26][27][28]. The characteristics of the 13 available studies are listed in Table 1.…”

“…We performed a sensitivity analysis (Fig. 3) and found that the studies by Giede-Jeppe et al [22] and Goyal et al [25] were significant origins of heterogeneity. After excluding these studies, the heterogeneity dropped by 54.4% (ischemia), 79.2% (hemorrhage), and 85.3% (overall).…”

Development and validation of a predictive model for the prognosis in aneurysmal subarachnoid hemorrhage

“…These are enzymes able to degrade any component of the extracellular matrix and play role in brain‐barrier damage and development of secondary brain injury 27 . In addition, the mechanism of NLR‐induced bleeding may be contributed by multifactorial pathophysiology, such as inflammatory reaction, immune dysfunction, and the production of reactive oxygen species (ROS) 5,28‐32 . aSAH can induce the leukocytosis and increased neutrophils by stimulating the systemic cellular responses that can cause the brain injury and delayed cerebral ischemia 33,34 .…”

Neutrophil-Lymphocyte Count Ratio Better Predict Prognosis than Conventional Markers in Critical Patients? A Multiple-Centered Retrospective Cohort Study

“…Neutrophil lymphocyte count ration (NLCR) has been introduced by Zahorec as a rapid, easy-applicable and cost-effective parameter of in ammation and stress in patients of critical conditions [1]. Until recently, the diagnostic and prognostic value of NLCR on myriad medical situations such as bacteremia [2], sepsis [3], myocardial infarction [4], aneurysmal subarachnoid hemorrhage [5], community acquired pneumonia [6], acute kidney injury [7], liver transplantation [8] and even colorectal cancer, remains a hot topic of investigation [9]. Systemic in ammation is an indispensable process of critical disease, and its severity can be generally associated with the short-and long-term outcomes of critical patients [10].…”