Objectives: Symptomatic hemorrhagic transformation (sHT) is a life-threatening complication of acute ischemic stroke (AIS). The early identification of the patients at increased risk of sHT can have clinically relevant implications. The aim of this study was to explore the validity and accuracy of the neutrophil-to-lymphocyte ratio (NLR) in predicting sHT in patients with AIS undergoing revascularization. Methods: Consecutive patients hospitalized for AIS who underwent intravenous thrombolysis, mechanical thrombectomy or both were identified. The NLR values were estimated at admission. The study endpoint was the occurrence of sHT within 24 h from stroke treatment. Results: Fifty-one patients with AIS were included, with a median age of 67 (interquartile range, 55–78) years. sHT occurred in 10 (19.6%) patients. Patients who developed sHT had higher NLR at admission. NLR was an independent predictor of sHT and showed good discriminatory power (area under the curve 0.81). In a multivariable analysis, NLR and systolic blood pressure were independently associated with sHT. Conclusions: NLR at admission can accurately predict sHT in patients with AIS undergoing revascularization.

Background: Hemorrhagic transformation (HT) is a complication that occurs spontaneously or after thrombolysis in acute ischemic stroke (AIS) and can increase morbidity and mortality. The association of biomarkers with the risk of HT has been variably reported. We conducted a systematic review of the literature and meta-analysis and sought to compare blood biomarkers associated with HT and its subtypes by evaluating its predictability and correlation with outcome in AIS. Methods: The study protocol was registered in the PROSPERO database (CRD42020201334) and adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Among 2,230 articles identified from Cochrane Library, PubMed, and Web of Science databases, 30 quality-appraised articles were found eligible. Meta-analysis was conducted for matrix metalloproteinase-9 (MMP-9), cellular fibronectin (c-Fn), ferritin, S100 calcium-binding protein B (S100B), and neutrophil-lymphocyte ratio (NLR). We also reviewed biomarkers for correlation with the functional outcome at 90 days from stroke onset (poor outcome modified Rankin scale >2). Results: The pooled diagnostic odds ratio (DOR_pooled) was the highest for baseline c-Fn levels (299.253 [95% CI, 20.508–4,366.709]), followed by MMP-9 (DOR_pooled, 29.571 [95% CI 17.750–49.267]) and ferritin (DOR_pooled, 24.032 [95% CI 2.557–225.871]). However, wide confidence intervals for ferritin and c-Fn suggested lesser reliability of the markers. Patients with MMP-9 levels ≥140 ng/mL were 29.5 times at higher risk of developing symptomatic HT after AIS (area under the curve = 0.881). S100B (DOR_pooled, 6.286 [95% CI, 1.861–21.230]) and NLR (DOR_pooled, 5.036 [95% CI, 2.898–8.749]) had lower diagnostic accuracies. Among the markers not included for meta-analysis, caveolin-1, thrombin-activated fibrinolysis inhibitor, plasminogen activator inhibitor-1, and soluble ST2 were highly sensitive. Elevated levels of MMP-9, ferritin, and NLR were found to be associated with poor functional outcomes and mortality. Conclusion: Of the 5 biomarkers, there was enough evidence that MMP-9 has higher diagnostic accuracy for predicting the risk of HT before thrombolysis. MMP-9, ferritin, and NLR also predicted poor short-term outcomes.

Background and Objectives: Ischaemic stroke (IS) is the leading cause of death and disability worldwide. All stages of cerebral ischaemia, but especially acute phase, are associated with inflammatory response. Recent studies showed that neutrophil-to-lymphocyte ratio (NLR) and lymphocyte-to-monocyte ratio (LMR) may be used to assess inflammation in IS. To test whether there is a relationship between these parameters and type of stroke treatment, we analysed NLR and LMR in IS patients treated with three different modalities. Materials and Methods: The study included 58 adults with acute IS. A total of 28 patients received intravenous thrombolysis. In another 10 patients, the thrombolytic therapy was followed by thrombectomy and 20 patients did not undergo causal treatment. Blood samples were obtained within 24 h of the stroke diagnosis to calculate NLR and LMR. Next, NLR and LMR of the study subgroups were compared. Results: Our study revealed that NLR was significantly higher in patients treated with thrombectomy following thrombolysis, compared to no causal treatment. Statistical analysis demonstrated that patients with high National Institutes of Health Stroke Scale (NIHSS) scores presented higher NLR than in those with low NIHSS scores. Additionally, patients with high-sensitivity C-reactive protein (hs-CRP) ≥ 3 mg/L presented with significantly higher NLR and significantly lower LMR than the group of patients with lower hs-CRP (<3 mg/L). Conclusions: The main finding of this pilot study was that NLR in IS patients treated using thrombectomy following thrombolysis was markedly higher than that in other treatment groups, which was associated with increased severity of the disease in these patients. Therefore, patients with higher NLR may be expected to have more severe stroke. The link between stroke severity and NLR deserves further study.

The worsening of neurological status that occurs early after acute ischemic stroke (AIS) remains a serious issue, and the inflammatory response plays a key role in stroke pathobiology. Recently, endovascular treatment (EVT) has revolutionized the management and outcome of patients with AIS due to either extracranial carotid disease or intracranial disease. The neutrophil-to-lymphocyte ratio (NLR) represents an easily available inflammatory biomarker. The aim of the study was to assess the relationship between the NLR at admission and the occurrence of early neurological deterioration (END) in patients with AIS who underwent EVT. Patients with AIS and proximal arterial occlusion in the anterior circulation undergoing EVT were retrospectively identified. Absolute neutrophil count (ANC) and absolute lymphocyte count (ALC) were collected from admission blood work to calculate the NLR. The study outcome was END defined as an increase in at least 4 points in NIHSS score or death between baseline and 24 h after the ischemic event. Patients included were 211, and END occurred in 30 (14.2%). Patients with older age (OR = 1.07, 95% CI: 1.02–1.13), higher serum glucose (OR = 1.01, 95% CI: 1.01–1.02), and higher NLR (OR = 1.011, 95% CI: 1.04–1.18) had an increased risk of END. The best predictive cut-off value of NLR was 6.4, and END occurred in 24.1% and 3.9% of the patients with NLR ≥ 6.4 and <6.4, respectively (p < 0.001). In patients with AIS undergoing EVT, higher NLR values predicted a higher risk of END. Biomarkers able to identify inflammatory mechanisms might identify novel treatment targets and enhance proof-of-concept trials of immunomodulation in stroke.

The goal of this study was to determine the levels of factor VII (FVII), factor VIIa–antithrombin complexes (FVIIa-AT), total tissue factor (TF), and tissue factor-bearing microparticles (MPs-TF) in patients with acute ischemic stroke. Further, we sought evidence of an association between hemostatic markers, time of blood sampling, type of treatment, and patient outcomes. Venous blood samples were collected from 33 patients on the first day and on the seventh day after stroke diagnosis. Age-matched controls were also included (n = 20). Plasma levels of FVII, FVIIa-AT, total TF, and MPs-TF were measured by enzyme-linked immunosorbent assay. We divided patients into 2 groups: thrombolysis group (n = 13) and nonthrombolysis group (n = 20). Furthermore, evaluation of the National Institutes of Health Stroke Scale and the Barthel Index was performed on the first day and the seventh day. Patients with ischemic stroke showed significantly lower plasma FVII, FVIIa-AT, and total TF levels than controls (median, 112.25% vs 132.05%, P = .004; 107.97 pmol/L vs 154.94 pmol/L, P < .001; 81.74 pg/mL vs 105.71 pg/mL, P < .001, respectively). In contrast, levels of plasma MPs-TF were significantly higher in patients with stroke compared to healthy controls (1.60 pg/mL vs 0.74 pg/mL, P < .001). Additionally, the thrombolysis group had lower FVII levels on the seventh day compared to the first day (median, 109.80% vs 115.74%, P = .04). Factor VII, FVIIa-AT, and total TF are decreased, while MPs-TF are elevated in patients with ischemic stroke. We observed a slight but significant effect of alteplase on FVII plasma levels.