scholarly journals Early and Sustained Increases in Leukotriene B4 Levels Are Associated with Poor Clinical Outcome in Ischemic Stroke Patients

2019 ◽  
Vol 17 (1) ◽  
pp. 282-293 ◽  
Author(s):  
Su Jing Chan ◽  
Mary P. E. Ng ◽  
Hui Zhao ◽  
Geelyn J. L. Ng ◽  
Chuan De Foo ◽  
...  

Abstract Leukotriene B4 (LTB4) has been implicated in ischemic stroke pathology. We examined the prognostic significance of LTB4 levels in patients with acute middle cerebral artery (MCA) infarction and their mechanisms in rat stroke models. In ischemic stroke patients with middle cerebral artery infarction, plasma LTB4 levels were found to increase rapidly, roughly doubling within 24 h when compared to initial post-stroke levels. Further analyses indicate that poor functional recovery is associated with early and more sustained increase in LTB4 rather than the peak levels. Results from studies using a rat embolic stroke model showed increased 5-lipoxygenase (5-LOX) expression in the ipsilateral infarcted cortex compared with sham control or respective contralateral regions at 24 h post-stroke with a concomitant increase in LTB4 levels. In addition, neutrophil influx was also observed in the infarcted cortex. Double immunostaining indicated that neutrophils express 5-LOX and leukotriene A4 hydrolase (LTA4H), highlighting the pivotal contributions of neutrophils as a source of LTB4. Importantly, rise in plasma LTB4 levels corresponded with an increase in LTB4 amount in the infarcted cortex, thereby supporting the use of plasma as a surrogate for brain LTB4 levels. Pre-stroke LTB4 loading increased brain infarct volume in tMCAO rats. Conversely, administration of the 5-LOX-activating protein (FLAP) inhibitor BAY-X1005 or B-leukotriene receptor (BLTR) antagonist LY255283 decreased the infarct volume by a similar extent. To conclude, targeted interruption of the LTB4 pathway might be a viable treatment strategy for acute ischemic stroke.

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Frans Kauw ◽  
Marie Louise E Bernsen ◽  
Hugo W de Jong ◽  
L. Jaap Kappelle ◽  
Birgitta K Velthuis ◽  
...  

Introduction: Prediction models may guide decisions in the management of patients at risk for malignant middle cerebral artery infarction. The ratio of intracranial cerebrospinal fluid (CSF) volume to intracranial volume (ICV) has been identified as a predictor of malignant edema in ischemic stroke patients treated with intravenous thrombolysis. The added predictive value in stroke patients who received endovascular treatment is unknown. Methods: Patients with available thin-slice non-contrast CT data on admission were selected from the MR CLEAN Registry, which is a prospective national multicenter registry of patients with large vessel occlusion who were treated with endovascular treatment between 2014 and 2017. Baseline characteristics and CT imaging data were collected. The CSF/ICV ratio was automatically measured on baseline thin-slice non-contrast CT. The primary outcome was the formation of malignant edema based on clinical and imaging features on follow-up. A previously built logistic regression model was fitted and included the following baseline predictors: age, National Institutes of Health Stroke Scale, Alberta Stroke Program Early CT score, poor collateral filling and reperfusion. An extended model with the CSF/ICV ratio was compared to the previous model by using the likelihood ratio test. Odds ratios (OR), areas under the receiver operating characteristic curve (AUROC) and 95% confidence intervals (CI) were reported. Results: Of the included 683 patients 40 (6%) developed malignant edema. The CSF/ICV ratio of the group with malignant edema (mean 9±5%) was lower than the group without malignant edema (mean 14±6%, P<0.001). In the extended model, the CSF/ICV ratio was associated with the formation of malignant edema (per one percent decrease OR 1.2, 95% CI 1.1-1.3, P<0.001). In addition, the discriminative performance of the model with the CSF/ICV ratio (AUROC 0.87, 95% CI 0.82-0.91) was higher than that of the model without the CSF/ICV ratio (AUROC 0.84, 0.78-0.89, P<0.001). Conclusions: The CSF/ICV ratio improves the prediction of malignant edema formation in ischemic stroke patients who received endovascular treatment.


2017 ◽  
Vol 43 (3-4) ◽  
pp. 200-205 ◽  
Author(s):  
Verena van Ginneken ◽  
Daniel Gierhake ◽  
Heinrich J. Audebert ◽  
Jochen B. Fiebach

Background: Early recanalization in ischemic stroke is associated with favorable outcome. However, limited data are available on the effect of recanalization on infarct growth and functional outcome in stroke with distal middle cerebral artery (MCA) pathology. This study was aimed at determining the effect of recanalization in acute stroke patients with perfusion-diffusion mismatch and occlusion or high-grade stenosis of a distal MCA branch. Methods: We prospectively examined 34 consecutive stroke patients with perfusion-diffusion mismatch and M3 or M4 pathology within 24 h of symptom onset. The MRI protocol consisted of diffusion-weighted images (DWI), fluid-attenuated inversion recovery (FLAIR), T2*, perfusion-weighted imaging, time-of-flight magnetic resonance angiography at days 0, 1, and 4-6. Volume measurements were performed with MRIcron. Infarct growth was defined as the difference between lesion volumes on FLAIR at days 4-6 and DWI at day 0. Certified raters assessed modified Rankin Scale scores at discharge and day 90. Results: Twenty-four patients (71%) showed recanalization at day 1. Infarct growth was modest (median 2.4 mL, 95% CI 0.8-6.7) and not significantly different between patients with and without recanalization (p = 0.87). Functional outcome at discharge was good with 70% of patients suffering no significant disabilities. There was no association between functional outcome at discharge and recanalization (OR 2.1, 95% CI 0.4-13.0, p = 0.40) or infarct volume at days 4-6 (p = 0.40). Conclusions: The high rate of spontaneous recanalization and good functional outcome in patients with distal MCA pathology might obscure a potential benefit from recanalization in this population.


2016 ◽  
Vol 10 (1) ◽  
pp. 29-33 ◽  
Author(s):  
Michael E Maniskas ◽  
Jill M Roberts ◽  
Rebecca Trueman ◽  
Annastazia E Learoyd ◽  
Amanda Gorman ◽  
...  

BackgroundNitroglycerin (also known as glyceryl trinitrate (GTN)), a vasodilator best known for treatment of ischemic heart disease, has also been investigated for its potential therapeutic benefit in ischemic stroke. The completed Efficacy of Nitric Oxide in Stroke trial suggested that GTN has therapeutic benefit with acute (within 6 hours) transdermal systemic sustained release therapy.ObjectiveTo examine an alternative use of GTN as an acute therapy for ischemic stroke following successful recanalization.MethodsWe administered GTN IA following transient middle cerebral artery occlusion in mice. Because no standard dose of GTN is available following emergent large vessel occlusion, we performed a dose–response (3.12, 6.25, 12.5, and 25 µg/µL) analysis. Next, we looked at blood perfusion (flow) through the middle cerebral artery using laser Doppler flowmetry. Functional outcomes, including forced motor movement rotor rod, were assessed in the 3.12, 6.25, and 12.5 µg/µL groups. Histological analysis was performed using cresyl violet for infarct volume, and glial fibrillary activating protein (GFAP) and NeuN immunohistochemistry for astrocyte activation and mature neuron survival, respectively.ResultsOverall, we found that acute post-stroke IA GTN had little effect on vessel dilatation after 15 min. Functional analysis showed a significant difference between GTN (3.12 and 6.25 µg/µL) and control at post-stroke day 1. Histological measures showed a significant reduction in infarct volume and GFAP immunoreactivity and a significant increase in NeuN.ConclusionsThese results demonstrate that acute IA GTN is neuroprotective in experimental ischemic stroke and warrants further study as a potentially new stroke therapy.


2020 ◽  
Vol 38 (4) ◽  
pp. 311-321
Author(s):  
Jiaying Zhu ◽  
Mengmeng Ma ◽  
Jinghuan Fang ◽  
Jiajia Bao ◽  
Shuju Dong ◽  
...  

Background: Statin therapy has been shown to be effective in the prevention of ischemic stroke. In addition, recent studies have suggested that prior statin therapy could lower the initial stroke severity and improve stroke functional outcomes in the event of stroke. It was speculated that prestroke statin use may enhance collateral circulation and result in favorable functional outcomes. Objective: The aim of the study was to investigate the association of prestroke statin use with leptomeningeal collaterals and to determine the association of prestroke statin use with stroke severity and functional outcome in acute ischemic stroke patients. Methods: We prospectively and consecutively enrolled 239 acute ischemic stroke patients with acute infarction due to occlusion of the middle cerebral artery within 24 h in the neurology department of West China Hospital from May 2011 to April 2017. Computed tomographic angiography (CTA) imaging was performed for all patients to detect middle cerebral artery thrombus; regional leptomeningeal collateral score (rLMCS) was used to assess the degree of collateral circulation; the National Institutes of Health Stroke Scale (NIHSS) was used to measure stroke severity at admission; the modified Rankin scale (mRS) was used to measure outcome at 90 days; and premorbid medications were recorded. Univariate and multivariate analyses were performed. Results: Overall, 239 patients met the inclusion criteria. Fifty-four patients used statins, and 185 did not use statins before stroke onset. Prestroke statin use was independently associated with good collateral circulation (rLMCS > 10) (odds ratio [OR], 4.786; 95% confidence interval [CI], 1.195–19.171; P = 0.027). Prestroke statin use was not independently associated with lower stroke severity (NIHSS score≤14) (OR, 1.955; 95% CI, 0.657–5.816; p = 0.228), but prestroke statin use was independently associated with favorable outcome (mRS score≤2) (OR, 3.868; 95% CI, 1.325–11.289; P = 0.013). Conclusions: Our findings suggest that prestroke statin use was associated with good leptomeningeal collaterals and clinical outcomes in acute ischemic stroke (AIS) patients presenting with occlusion of the middle cerebral artery. However, clinical studies should be conducted to verify this claim.


2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Hussen Abdu ◽  
Fentaw Tadese ◽  
Girma Seyoum

Background. Distinguishing the category of stroke plays a vital role in planning patient care. Simple clinical findings help distinguish the type of stroke. However, there is a need for diagnostic imaging. In Ethiopia, stroke is the most common neurological condition in patients admitted to hospitals. Yet, there are limited data on comparisons of stroke subtypes. Thus, this study was designed to determine the prevalence of stroke and to compare ischemic and hemorrhagic strokes. Methods. A retrospective cross-sectional study design was employed. Medical records containing complete information and confirmed diagnosis using imaging techniques were included. The data were entered into SPSS version 24.0 for analysis. Results with a P value of <0.05 were considered statistically significant. Results. From a total of 312 stroke patients, 204 (65.4%) patients were admitted due to ischemic stroke. More females, 59 (18.9%), were admitted for hemorrhagic stroke than males. In both ischemic, 175 (56.1%) and hemorrhagic, 91 (29.2%) stroke cases, most of the patients were 45 years and above. Middle cerebral artery territory was the most common site of arterial territory infarctions in ischemic stroke, 158 (50.7%). Middle cerebral artery territory also was the most common site of hematoma in hemorrhagic stroke, 91 (29.2%). Infarctions in more than one lobe of the cerebrum (16.4%) and intracerebral hemorrhage in multiple areas of the cerebrum (7.4%) were observed in ischemic as well as hemorrhagic stroke cases. Most of the ischemic, 124 (39.8%), and hemorrhagic, 39 (12.5%), stroke patients presented loss of sensation and weakness of body parts. Hypertension was observed in 124 (39.8%) ischemic and 73 (23.4%) hemorrhagic stroke patients. The mortality rate of ischemic stroke, 47 (15.3%), was two times higher than hemorrhagic stroke, 20 (6.5%). Hypertension was the most common predictor of death in both ischemic and hemorrhagic stroke cases. Conclusions. Ischemic stroke is a common type of stroke in the medical ward of the study hospital. More females were affected by hemorrhagic stroke than males. Middle cerebral artery territory was the most affected area of the brain in both ischemic and hemorrhagic strokes. Most ischemic and hemorrhagic stroke patients were admitted due to loss of sensation and weakness of body parts. Hypertension was the most common risk factor of stroke as well as a predictor of stroke-related deaths. Identification of the stroke subtypes may be important in the management of stroke. Thus, health professionals, government officials, community leaders, and the population at large could be involved in creating awareness about antecedent risk factors and clinical presentations of stroke subtypes.


Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Terrance Chiang ◽  
Sean Harvey ◽  
Arjun V Pendharkar ◽  
Michelle Y Cheng ◽  
Gary K Steinberg

Introduction: Manual scoring of behavior tests is commonly used for assessing motor deficits after stroke, however, it is labor intensive and subject to bias. These limitations lead to inconsistent assessment between research groups and non-reproducible data. In this study, we investigated the feasibility of an automated motor deficit assessment system, Erasmus ladder, in two ischemic stroke models. Methods: Distal middle cerebral artery occlusion (dMCAO n=10) or transient middle cerebral artery occlusion (tMCAO 30 minutes, n=15) were performed on male C57BL6J mice (11-13 weeks) to generate cortical ischemic stroke, with. Naïve mice (n=10) were used as controls. Immunohistochemistry was performed on brains collected at post-stroke day (PD) 30 to assess for infarct size (MAP2) and inflammation (CD68). Mice without infarct in both cortex and striatum were excluded from the study. Behavior was assessed using Erasmus ladder at pre-stroke baseline (4 unperturbed and 4 perturbed sessions) and on PD 7, 14, 21, and 28 (all perturbed sessions). Results: Erasmus ladder detected significant motor deficits in the tMCAO model, specifically in the pre- and post- perturbed times as well as several key step types (HH long). Analyses in the tMCAO model reveal changes in various step patterns and their capability to react to the perturbation (obstacle). These significant motor deficits after tMCAO were detectable until PD28. We also observed a sustained decline in the use of affected limb compared to unaffected limb until PD28. While this trend is also present in dMCAO model, motor deficits were detected in the dMCAO only at early timepoints (PD7) and the difference subsided by PD28. Conclusion: We have assessed the data collected by Erasmus ladder on mice that underwent two commonly used stroke models (tMCAO and dMCAO). Our data showed that Erasmus ladder can detect long term motor deficit including reduced use of affected limb, step pattern, and motor reaction to obstacle. This automated instrument is effective in detecting motor deficits in the tMCAO model and thus, can be used to evaluate treatments for enhancing recovery after stroke.


2019 ◽  
Vol 14 (3) ◽  
pp. 306-309 ◽  
Author(s):  
Ying Zhou ◽  
Wansi Zhong ◽  
Anli Wang ◽  
Wanyun Huang ◽  
Shenqiang Yan ◽  
...  

Background Early neurological deterioration occurs in approximately 10% acute ischemic stroke patients after thrombolysis. Over half of the early neurological deterioration occurred without known causes and is called unexplained early neurological deterioration. Aims We aimed to explore the development of early neurological deterioration at 24 h after thrombolysis, and whether it could be predicted by the presence of baseline hypoperfusion in lenticulostriate arteries territory in acute ischemic stroke patients. Methods We retrospectively reviewed our prospectively collected database of acute ischemic stroke patients in the unilateral middle cerebral artery territory who had baseline perfusion image and received thrombolysis. Unexplained early neurological deterioration was defined as ≥ 2 points increase of National Institutes of Health Stroke Scale (NIHSS) from baseline to 24 h, without known causes. Hypoperfusion lesions in different territories were identified on perfusion maps. Results A total of 306 patients were included in analysis. Patients with pure lenticulostriate arteries hypoperfusion (defined as the presence of hypoperfusion in lenticulostriate artery territory, but not in middle cerebral artery terminal branch territory) were more likely to have unexplained early neurological deterioration than others (27.6% vs. 6.1%; OR, 5.974; p = 0.001), after adjusting for age, baseline NIHSS and onset to treatment time. Conclusions Patients presenting hypoperfusion in pure lenticulostriate arteries territory were easier to experience unexplained early neurological deterioration.


2013 ◽  
Vol 2013 ◽  
pp. 1-4 ◽  
Author(s):  
Luciano A. Sposato ◽  
Valeria Salutto ◽  
Diego E. Beratti ◽  
Paula Monti ◽  
Patricia M. Riccio ◽  
...  

Background. Recurrent ischemic stroke is associated with adverse neurological outcome in patients with atrial fibrillation. There is very scarce information regarding the neurological outcome of atrial fibrillation patients undergoing repeated systemic thrombolysis after early recurrent ischemic stroke.Clinical Case and Discussion. We describe a case of a 76-year-old woman with known paroxysmal atrial fibrillation who was admitted because of an acute right middle cerebral artery ischemic stroke and who underwent repeated systemic thrombolysis within 110 hours. The patient underwent systemic thrombolysis after the first ischemic stroke with almost complete neurological recovery. On the fourth day after treatment, an acute left middle cerebral artery ischemic stroke was diagnosed and she was treated with full-dose intravenous recombinant tissue plasminogen activator. A hemorrhagic transformation of the left middle cerebral artery infarction was noted on follow-up cranial computed tomographic scans. The patient did not recover from the second cerebrovascular event and died 25 days after admission.Conclusion. To the best of our knowledge, this is the second case reporting the adverse neurological outcome of a patient with diagnosis of atrial fibrillation undergoing repeated systemic thrombolysis after early recurrent ischemic stroke. Our report represents a contribution to the scarce available evidence suggesting that repeated systemic thrombolysis for recurrent ischemic stroke should be avoided.


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