Analysis of the association of MPO and MMP-9 with stroke severity and outcome

ObjectiveIn acute cerebral ischemia, circulating neutrophil count and neutrophil-to-lymphocyte ratio (NLR) are positively associated with stroke severity and worse outcomes. Mediators of this effect are unknown. We aimed to investigate (1) the relationship between plasma matrix metalloproteinase-9 (MMP-9) and myeloperoxidase (MPO) concentrations with stroke severity and outcome and (2) MMP-9 and MPO release after ex vivo stimulation of neutrophils by recombinant tissue plasminogen activator (rtPA).MethodsWe analyzed data collected in 255 patients with supratentorial cerebral infarcts recruited within 48 hours of symptoms onset irrespective of rtPA treatment. The endpoints were excellent outcome (modified Rankin Scale score 0–1), symptomatic intracerebral hemorrhage (European Cooperative Acute Stroke Study–II definition), and death at 3 months. The role of rtPA treatment on peripheral neutrophil degranulation was investigated in 18 patients within 4.5 hours and after 72 hours.ResultsNeutrophil counts, NLR, and MPO plasma concentrations, but not MMP-9, were positively correlated with stroke severity. Higher neutrophil counts and NLR were independently associated with worse outcomes and higher mortality rates at month 3. Higher MPO plasma concentrations, but not MMP-9, were associated with worse outcome. Neutrophil-derived MMP-9, after ex vivo rtPA stimulation, but not MPO, were higher after 72 hours in patients treated by IV rtPA but not associated with hemorrhagic transformation.ConclusionsNeutrophil counts, NLR, and MPO plasma concentrations are associated with worse outcome in patients with acute cerebral ischemia, in contrast to MMP-9. Further investigations are needed to deepen our knowledge on MPO’s role in the deleterious effect of neutrophils because it could represent a potential therapeutic target.

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Abstract TMP90: Frequency and Risk Factors for Early Neurological Deterioration Among Hyperacute Cerebral Ischemia Patients Treated With and Without Thrombolysis

Stroke ◽

10.1161/str.51.suppl_1.tmp90 ◽

2020 ◽

Vol 51 (Suppl_1) ◽

Author(s):

Christa D Brown ◽

Gilda Avila-Rinek ◽

Nerses Sanossian ◽

Sidney Starkman ◽

Scott Hamilton ◽

...

Keyword(s):

Risk Factors ◽

Cerebral Ischemia ◽

Fold Increase ◽

Information Criteria ◽

Neurological Deterioration ◽

Stroke Severity ◽

Acute Cerebral Ischemia ◽

Early Neurological Deterioration ◽

Prior Stroke ◽

Iv Tpa

Background: Early neurological deterioration (END) is a feared complication of acute cerebral ischemia. However, estimates of END frequency vary widely, rates have not been systematically examined in hyperacute patients presenting within the first 2h of onset, nor separately in patients treated with and without thrombolysis, and risk factors for END have not been well delineated. Methods: We analyzed patients with a final diagnosis of acute cerebral ischemia in the NIH FAST-MAG Phase 3 multicenter clinical trial. END was defined as worsening post-admission by ≥ 4 NIHSS points up to Day 4. We separately analyzed patients who did and did not receive IV tPA. Results: Among 1245 acute cerebral ischemia patients transported by EMS to 55 stroke centers, time from last known well (LKW) to ED arrival was median 59 mins (IQR 80-46), and 36.1% received IV tPA. Overall, 211 (16.9%) experienced END by Day 4, with a greater proportion of END in tPA than non-tPA patients (21.2% vs 14.5%, p=0.003). In multivariate analysis, from 26 candidate variables, among tPA recipients, independent predictors of END were: age (OR 1.03/year, 95%CI 1.01-1.05), diastolic BP (OR 1.01/mm Hg, 95%CI 1.00-1.03), prior stroke (OR 1.65, 95%CI 0.98-2.77), glucose (OR 11.06/10 fold increase, 95%CI 1.90-64.44), and worse ASPECTS score (OR 0.85/point, 95%CI 0.78-0.92). Among non-tPA recipients, independent predictors of END were: more severe NIHSS (OR 1.08/point, 95%CI 1.05-1.11), glucose (OR 8.88/10 fold increase, 95%CI 1.83-43.12), and h/o hypertension (OR 2.62/mm Hg, 95%CI 1.25-5.48), with Akaike information criteria identifying SBP, shorter LKW-to-ED time, and absence of anticoagulant agents as additional contributors. C statistics for these models were 0.68 for tPA patients and 0.73 for non-tPA patients. Conclusions: Among hyperacute cerebral ischemia patients, END occurs in 1 in 5 who receive tPA, and 1 in 7 who do not receive tPA. Greater initial stroke severity (on neurologic exam or imaging), higher glucose, and hypertension increase risk of END for both lytic and non-lytic patients, with older age and prior stroke additionally increasing END risk with tPA. Models based on these risk factors show fair to good performance identifying patients who will experience END after hospital admission.

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Abstract W P26: Meta-analysis Of Studies Using Solitaire And Trevo Pro Stent Retriever Devices For Mechanical Thromboembolectomy In Acute Cerebral Ischemia

Stroke ◽

10.1161/str.45.suppl_1.wp26 ◽

2014 ◽

Vol 45 (suppl_1) ◽

Author(s):

Vikram Jadhav ◽

Mushtaq H Qureshi ◽

Malik M Adil ◽

Amna Zarar ◽

Nidaullah Mian ◽

...

Keyword(s):

Cerebral Ischemia ◽

Publication Bias ◽

Mechanical Thrombectomy ◽

Meta Analysis ◽

Analysis Software ◽

Symptomatic Intracerebral Hemorrhage ◽

Acute Cerebral Ischemia ◽

Random Models ◽

Log Odds ◽

Event Rates

Objective: To report rates of recanalization and symptomatic intracerebral hemorrhage (SICH) after mechanical thromboembolectomy using Solitaire and Trevo Pro devices in acute cerebral ischemia using meta-analysis of published studies. Methods: We identified all studies that used Solitaire or Trevo devices for mechanical thromboembolectomy in treatment of acute cerebral ischemia using a search on PubMed and Cochrane libraries, stroke trials database, proceedings of neurology and neurosurgery related conferences, and supplemented by a review of bibliographies of selected publications. Recanalization was assessed using TICI >2a and rates of SICH were recorded. For the meta-analysis, forest plots and statistical analysis including event rates [ER] with 95% confidence intervals [CI] based on both fixed and random models were performed using Comprehensive Meta-Analysis Software. The presence of publication bias was interrogated by funnel plot of Standard Error by log odds ratio. Results: Eighteen studies with Solitaire device and five with Trevo device were identified and included in the meta-analysis. There were a total of 433/505 (85%, ER 0.85 [CI] 0.80-0.88, P<0.001) successful recanalizations with Solitaire device whereas 196/243 (80%, ER 0.80 [CI] 0.74-0.85, P<0.001) successful recanalizations were noted with Trevo device. The incidence of SICH was 45/505 (9%, ER 0.09 [CI] 0.06-0.14, P<0.001) with Solitaire device and 17/243 (6%, ER 0.06 [CI] 0.049-0129, P<0.001) with Trevo device after mechanical thrombectomy. There was no publication bias. Conclusions: Meta-analysis of studies reveals similar rates for recanalization and SICH after mechanical thromboembolectomy using Solitaire or Trevo Pro devices.

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Stroke Severity and Incidence of Acute Large Vessel Occlusions in Patients with Hyper-Acute Cerebral Ischemia: Results from a Prospective Cohort Study Based on CT-Angiography (CTA)

International Journal of Stroke ◽

10.1111/ijs.12383 ◽

2014 ◽

Vol 10 (3) ◽

pp. 336-342 ◽

Cited By ~ 35

Author(s):

C. K. Hansen ◽

A. Christensen ◽

C. Ovesen ◽

I. Havsteen ◽

H. Christensen

Keyword(s):

Cohort Study ◽

Cerebral Ischemia ◽

Ct Angiography ◽

Prospective Cohort Study ◽

Prospective Cohort ◽

Large Vessel ◽

Stroke Severity ◽

Acute Cerebral Ischemia

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Abstract 214: The Field Administration of Stroke Therapy - Magnesium (FAST-MAG) Phase 3 Trial: Primary Results

Stroke ◽

10.1161/str.45.suppl_1.214 ◽

2014 ◽

Vol 45 (suppl_1) ◽

Author(s):

Jeffrey L Saver ◽

Marc Eckstein ◽

Samuel Stratton ◽

Frank Pratt ◽

Scott Hamilton ◽

...

Keyword(s):

Cerebral Ischemia ◽

Los Angeles ◽

Magnesium Sulfate ◽

Symptom Onset ◽

Stroke Severity ◽

Neuroprotective Agents ◽

Phase 3 ◽

Double Blind ◽

Golden Hour ◽

Acute Cerebral Ischemia

BACKGROUND: Magnesium is neuroprotective in preclinical models of stroke and has been safe and shown signals of potential efficacy when delivered early after onset of human cerebral ischemia. Delayed initiation of neuroprotective agents has hindered past neuroprotective agent trials. We performed a multicenter, randomized, double-blind, placebo-controlled phase 3, trial to test whether paramedic initiation of intravenous magnesium sulfate within 2 hours of symptom onset improves the longterm functional outcome of hyperacute stroke patients. METHODS: Inclusion criteria were: 1) likely stroke as identified by the Los Angeles Prehospital Stroke Screen (LAPSS), 2) age 40-95, 3) symptom onset within 2 hours of treatment initiation, 4) deficit present ≥ 15 minutes. Trial sites included 315 ambulances, 40 EMS agencies, and 60 receiving hospitals throughout Los Angeles and Orange Counties, with 2988 paramedics trained in study procedures. From Jan 2005 - Dec 2012, paramedics in the field administered a loading dose (4 grams over 15 minutes) of magnesium sulfate (Mg) or matched saline placebo. Upon arrival in an ED, a maintenance infusion followed: 16 grams Mg or matched placebo over 24 hours. The primary endpoint was the modified Rankin Scale measure of global disability at 90 days. RESULTS: Among the 1700 enrolled patients, mean age was 69 (SD 13.6), 42.7% were female, median pretreatment stroke severity on the Los Angeles Motor Scale (LAMS) was 4.0, and median early post-treatment NIHSS stroke severity on ED arrival was 9.0. Final diagnosis of the presenting event was acute cerebral ischemia in 73.0%, acute hemorrhagic stroke in 23.2%, and stroke-mimicking condition in 3.8%. The median time from last known well to start of study infusion was 48 minutes (IQR 37 - 68). The proportion of patients receiving study infusion within the first hour after last known well was 74.1%. CONCLUSION: Prehospital initiation of neuroprotective agents can be performed in a large phase 3 acute stroke trial, permitting rapid drug start, with treatment in the first, “golden” hour in three-quarters of patients. The study blind will be broken in late fall and the first public presentation of trial efficacy results presented at the ISC meeting.

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Investigation of the correlation of allele polymorphism of renin-angiotensin system genes, nitric oxide synthase and folate cycle with the severity of ischemic stroke

Kazan medical journal ◽

10.17816/kmj2018-404 ◽

2018 ◽

Vol 99 (3) ◽

pp. 404-408

Author(s):

O A Levashova ◽

N I Baranova ◽

I G Zolkornyaev

Keyword(s):

Ischemic Stroke ◽

Cerebral Ischemia ◽

Renin Angiotensin System ◽

Mthfr Gene ◽

Stroke Severity ◽

C677t Polymorphism ◽

Angiotensin System ◽

Renin Angiotensin ◽

Acute Cerebral Ischemia ◽

Folate Cycle

Aim. To study the frequency of polymorphic gene variants encoding proteins of renin-angiotensin system [AGT Thr174Met (rs 4762), AGT Met235Thr (rs699), AGTR1 A1166C (rs5186)], endothelial factors [NOS3 C786T (rs2070744)], and folate cycle enzymes [MTHFR C677T (rs1801133)] in patients with various ischemic stroke severity. Methods. 98 patients with ischemic stroke verified by magnetic resonance imaging and computed tomography scan of the brain, were examined. The severity of stroke was assessed by National Institutes of Health Stroke Scale. The allelic variants of genes were typified by polymerase chain reaction with the detection of amplification products in the «real time» mode. Results. The analysis of genetic polymorphism frequency of renin-angiotensin system did not reveal statistically significant differences in the study groups. The polymorphism of NOSC786T gene in the study was also not associated with the severity of ischemic stroke. Among the studied polymorphic variants, only the C677T polymorphism of MTHFR gene was revealed to be reliably associated with severe course of acute cerebral ischemia. Conclusion. C677T polymorphism of MTHFR gene is reliably associated with severe course of acute cerebral ischemia; carriage of 677T allele of MTHFR gene in the studied category of patients can cause an increased level of homocysteine and have an adverse effect on the course of acute cerebral ischemia.

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Role of SWI in Early Detection of Hemorrhagic Transformation in Acute Cerebral Ischemia

Indian Journal of Public Health Research & Development ◽

10.37506/v11/i2/2020/ijphrd/195068 ◽

2020 ◽

Vol 11 (2) ◽

pp. 1679

Author(s):

Mohammad Mohammad Ameen ◽

Mohammad Farghaly Ameen ◽

Manal Fayz Abousamra ◽

Ahmed Mohammad Yassen

Keyword(s):

Cerebral Ischemia ◽

Early Detection ◽

Hemorrhagic Transformation ◽

Acute Cerebral Ischemia

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Safety and predictors of stroke mimics in The Norwegian Tenecteplase Stroke Trial (NOR-TEST)

International Journal of Stroke ◽

10.1177/1747493018790015 ◽

2018 ◽

Vol 14 (5) ◽

pp. 508-516 ◽

Cited By ~ 2

Author(s):

Christopher Elnan Kvistad ◽

Vojtech Novotny ◽

Halvor Næss ◽

Guri Hagberg ◽

Hege Ihle-Hansen ◽

...

Keyword(s):

Ischemic Stroke ◽

Cerebral Ischemia ◽

Transient Ischemic Attack ◽

Sensory Loss ◽

Stroke Mimics ◽

Symptomatic Intracerebral Hemorrhage ◽

Acute Cerebral Ischemia ◽

Stroke Mimic ◽

Ischemic Attack ◽

Stroke Trial

Background Stroke mimics are frequently treated with thrombolysis in clinical practice and thrombolytic trials. Although alteplase in stroke mimics has proven to be safe, safety of tenecteplase in stroke mimics has not been assessed in an ischemic stroke study setting. We aimed to assess clinical characteristics and safety of stroke mimics treated with thrombolysis in the Norwegian Tenecteplase Stroke Trial. We also aimed to identify possible predictors of stroke mimics as compared to patients with acute cerebral ischemia. Methods Norwegian Tenecteplase Stroke Trial was a phase-3 trial investigating safety and efficacy of tenecteplase vs. alteplase in patients with suspected acute cerebral ischemia. Two groups were defined based on diagnose at discharge: patients with a different diagnose than ischemic stroke or transient ischemic attack (stroke mimics group) and patients diagnosed with ischemic stroke or transient ischemic attack (acute cerebral ischemia group). Logistic regression analyses were performed with stroke mimics vs. acute cerebral ischemia as dependent variable to identify predictors of stroke mimics. Results Of 1091 randomized patients, 181 (16.6%) were stroke mimics. Migraine (22.2%) and peripheral vertigo (11.4%) were the two most frequent stroke mimic-diagnoses. There was no symptomatic intracerebral hemorrhage in the stroke mimics group. Stroke mimics were independently associated with age ≤60 years (OR 2.75, p < 0.001), female sex (OR 1.48, p = 0.026), no history of myocardial infarction (OR 2.03, p = 0.045), systolic BP ≤ 150 mmHg (OR 2.33, p < 0.001), NIHSS ≤ 6 points (OR 1.83, p = 0.011), sensory loss (OR 1.55, p = 0.015), and no facial paresis (OR 2.41, p < 0.001) on admission. Conclusion Thrombolysis with tenecteplase seems to be as safe as with alteplase in stroke mimics. Predictors were identified for stroke mimics which may contribute to differentiate stroke mimics from acute cerebral ischemia in future stroke trials.

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Omentin Is Independently Associated with Stroke Severity and Ipsilateral Carotid Artery Stenosis in Patients with Acute Cerebral Ischemia

Journal of Clinical Medicine ◽

10.3390/jcm10245797 ◽

2021 ◽

Vol 10 (24) ◽

pp. 5797

Author(s):

Maria Chondrogianni ◽

Vaia Lambadiari ◽

Aristeidis H. Katsanos ◽

Maria Ioanna Stefanou ◽

Lina Palaiodimou ◽

...

Keyword(s):

Cerebral Ischemia ◽

Linear Regression ◽

Carotid Stenosis ◽

Clinical Characteristics ◽

Regression Coefficient ◽

Stroke Severity ◽

Linear Regression Coefficient ◽

Nihss Score ◽

Acute Cerebral Ischemia ◽

Ischemic Attack

Mounting evidence indicates an association between adipokines and inflammation-related atherosclerosis. Here, we sought to investigate the association of vaspin and omentin with clinical characteristics and outcomes of patients with acute cerebral ischemia (ACI). Consecutive ACI patients were evaluated within 24 h from symptom-onset. Stroke aetiology was classified using TOAST criteria. Adipokines were assayed using quantikine enzyme immunoassay commercially available kits. Stroke severity was assessed by NIHSS-score, and ipsilateral carotid stenosis (≥50% by NASCET criteria) by ultrasound and CT/MR angiography. Major cerebrovascular events were assessed at three months. We included 135 ACI patients (05 (78%) and 30 (22%) with acute ischemic stroke and transient ischemic attack, respectively; mean age ± SD: 59 ± 10 years; 68% men; median NIHSS-score: 3 (IQR:1–7)). Omentin was strongly correlated to admission stroke severity (Spearman rho coefficient: +0.303; p < 0.001). Patients with ipsilateral carotid stenosis had higher omentin levels compared to patients without stenosis (13.3 ± 8.9 ng/mL vs. 9.5 ± 5.5 ng/mL, p = 0.014). Increasing omentin levels were independently associated with higher stroke severity (linear regression coefficient = 0.290; 95%CI: 0.063–0.516; p = 0.002) and ipsilateral carotid stenosis (linear regression coefficient = 3.411; 95%CI: 0.194–6.628; p = 0.038). No association of vaspin with clinical characteristics and outcomes was found. Circulating omentin may represent a biomarker for the presence of atherosclerotic plaque, associated with higher stroke severity in ACI patients.

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