scholarly journals Clinical worsening despite intravenous thrombolysis in acute ischemic stroke secondary to carotid plaque rupture

2020 ◽  
Vol 49 (3) ◽  
pp. 497-498
Author(s):  
Fabrizio Sallustio ◽  
Domenico Samà ◽  
Alfredo Paolo Mascolo ◽  
Federico Marrama ◽  
Mauro Fresilli ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Carotid Plaque ◽  
Plaque Rupture ◽  
Intravenous Thrombolysis ◽  
Clinical Worsening

Abstract WP434: Serum MicroRNA Panel as a Candidate Biomarker of Carotid Plaque Rupture and Stroke

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Aaron M Brug ◽  
Sullivan Smith ◽  
Ashton J Brooks ◽  
Daniel J Lightell ◽  
Hernan A Bazan ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Carotid Plaque ◽  
Plaque Rupture ◽  
Rna Seq ◽  
Circulating Mirnas ◽  
Ischemic Event ◽  
Biomarker Panel ◽  
Serum Microrna ◽  
Asymptomatic Patients

Introduction: Atherosclerotic plaque vulnerability and subsequent rupture are mediated by alterations in miRNAs that promote inflammation and fibrous cap thinning, leading to an acute ischemic stroke. Release of these miRNAs from the plaque tissue into the circulation may provide a miRNA profile that serves as a biomarker panel to identify the vulnerable patient at greatest risk of plaque rupture. Methods: Using RNA-Seq methodology, serum microRNA content was compared between patients undergoing carotid endarterectomy (CEA) for 2 distinct clinical phenotypes: patients without previous neurological events but high-grade carotid stenosis (asymptomatic, n=5), and patients with an acute neurological event within 5 days of the CEA (urgent, n=7). Differential expression of miRNAs was performed using the R statistical software and the DESeq2 package. Results: A total of 695 miRNAs detected in sera on RNA-Seq, 54 were significantly different between the asymptomatic and urgent groups. 22 miRNAs were decreased and 32 were increased in the serum of urgent patient’s compared to asymptomatic patients (adjusted p-value < 0.05). Of these miRNAs, miR-21, miR-486, miR-23b, miR-27b, and let-7f were selected for validation as a biomarker panel based on a prior association with vascular disease. A pilot study (n= 6 asymptomatic and 6 urgent) measuring these miRNAs demonstrated that while miR-486 was detectable in all samples and exhibited a 9.4-fold increase (p < 0.10) in the urgent group, the other miRNAs were only detected in a fraction of the samples (33 - 75%). Furthermore, miR-486 alone did not exhibit characteristics of a good indicator of ischemic stroke. A score normalizing the expression of miR-486 to the mean expression of the detectable miRNAs from this panel, did yield a promising C-statistic (0.97 ± 0.08, p < 0.01), suggesting its potential as an indicator of an acute ischemic event. Conclusion: Carotid plaque rupture resulting in an acute ischemic event is associated with alterations in the profile of circulating miRNAs and these may be useful as biomarkers of ischemic stroke. Our pilot data suggest that the development of a score based on a panel of circulating miRNAs may allow for the diagnosis of patients experiencing plaque rupture and an acute ischemic stroke.

scholarly journals Immunohistological Analysis of Neutrophils and Neutrophil Extracellular Traps in Human Thrombemboli Causing Acute Ischemic Stroke

2020 ◽  
Vol 21 (19) ◽  
pp. 7387
Author(s):  
Fabian Essig ◽  
Alexander M. Kollikowski ◽  
Mirko Pham ◽  
László Solymosi ◽  
Guido Stoll ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Plaque Rupture ◽  
Cerebral Arteries ◽  
Structural Complexity ◽  
Intravenous Thrombolysis ◽  
Neutrophil Extracellular Traps ◽  
Border Region ◽  
Imaging Data ◽  
Extracellular Traps

Ischemic stroke caused by thromboembolic occlusion of large cerebral arteries, such as the internal carotid (ICA) and/or the middle cerebral artery (MCA), is treated by mechanical thrombectomy (MT). MT allows salvage of the vessel-occluding thrombemboli, which most frequently originate from the left atrium or the left ventricle of the heart or from sites of plaque rupture within large arteries above the heart. Clot composition may influence the efficacy of (intravenous) thrombolysis and MT, respectively. We analyzed 37 human thrombemboli obtained from acute ischemic stroke patients during MT with special emphasis on histological staining of neutrophils and neutrophil extracellular traps (NETs). We found neutrophils as the main cellular component of cerebral thrombemboli but encountered considerable morphological heterogeneity. Neutrophils accumulated in the border region of fibrin-rich structures indicating possible interaction of neutrophils with distinct structural thrombembolus components. Web-like NETs were found in 35 of 37 thrombemboli in varying amounts. NETs were almost exclusively found within fibrin-rich areas. Importantly, stroke etiology, age and present oral anticoagulation was associated with morphological patterns and the amount of neutrophils. Correlation of histological data and imaging data revealed that relative Hounsfield units of cerebral thrombemboli positively correlated with the amount of red blood cells. In summary, our results demonstrate that neutrophils and NETs are substantial constituents of cerebral thrombemboli and contribute to their structural complexity.

Effect of Cardioembolic Etiology on Intravenous Thrombolysis Efficacy for Acute Ischemic Stroke

2016 ◽  
Vol 13 (3) ◽  
pp. 193-198 ◽  
Author(s):  
Sabrina Anticoli ◽  
Maria Cristina Bravi ◽  
Giovanni Perillo ◽  
Antonio Siniscalchi ◽  
Claudio Pozzessere ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Intravenous Thrombolysis

Association of admission leukocyte count with clinical outcomes in acute ischemic stroke patients undergoing intravenous thrombolysis with recombinant tissue plasminogen activator

2020 ◽  
Vol 17 ◽  
Author(s):  
Jie Chen ◽  
Fu-Liang Zhang ◽  
Shan Lv ◽  
Hang Jin ◽  
Yun Luo ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Leukocyte Count ◽  
Intravenous Thrombolysis ◽  
Recombinant Tissue Plasminogen Activator ◽  
Functional Independence ◽  
Tissue Plasminogen ◽  
Poor Outcomes

Objective:: Increased leukocyte count are positively associated with poor outcomes and all-cause mortality in coronary heart disease, cancer, and ischemic stroke. The role of leukocyte count in acute ischemic stroke (AIS) remains important. We aimed to investigate the association between admission leukocyte count before thrombolysis with recombinant tissue plasminogen activator (rt-PA) and 3-month outcomes in AIS patients. Methods:: This retrospective study included consecutive AIS patients who received intravenous (IV) rt-PA within 4.5 h of symptom onset between January 2016 and December 2018. We assessed outcomes including short-term hemorrhagic transformation (HT), 3-month mortality, and functional independence (modified Rankin Scale [mRS] score of 0–2 or 0–1). Results:: Among 579 patients who received IV rt-PA, 77 (13.3%) exhibited HT at 24 h, 43 (7.4%) died within 3 months, and 211 (36.4%) exhibited functional independence (mRS score: 0–2). Multivariable logistic regression revealed admission leukocyte count as an independent predictor of good and excellent outcomes at 3 months. Each 1-point increase in admission leukocyte count increased the odds of poor outcomes at 3 months by 7.6% (mRS score: 3–6, odds ratio (OR): 1.076, 95% confidence interval (CI): 1.003–1.154, p=0.041) and 7.8% (mRS score: 2–6, OR: 1.078, 95% CI: 1.006–1.154, p=0.033). Multivariable regression analysis revealed no association between HT and 3-month mortality. Admission neutrophil and lymphocyte count were not associated with 3-month functional outcomes or 3-month mortality. Conclusion:: Lower admission leukocyte count independently predicts good and excellent outcomes at 3 months in AIS patients undergoing rt-PA treatment.

scholarly journals Management of acute ischemic stroke in patients with COVID-19 infection: Report of an international panel

2020 ◽  
Vol 15 (5) ◽  
pp. 540-554 ◽  
Author(s):  
Adnan I Qureshi ◽  
Foad Abd-Allah ◽  
Fahmi Al-Senani ◽  
Emrah Aytac ◽  
Afshin Borhani-Haghighi ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Current Knowledge ◽  
Intravenous Thrombolysis ◽  
Adult Patients ◽  
World Health ◽  
Stroke Patients ◽  
International Panel ◽  
Health Organization ◽  
Tract Infections

Background and purpose On 11 March 2020, World Health Organization (WHO) declared the COVID-19 infection a pandemic. The risk of ischemic stroke may be higher in patients with COVID-19 infection similar to those with other respiratory tract infections. We present a comprehensive set of practice implications in a single document for clinicians caring for adult patients with acute ischemic stroke with confirmed or suspected COVID-19 infection. Methods The practice implications were prepared after review of data to reach the consensus among stroke experts from 18 countries. The writers used systematic literature reviews, reference to previously published stroke guidelines, personal files, and expert opinion to summarize existing evidence, indicate gaps in current knowledge, and when appropriate, formulate practice implications. All members of the writing group had opportunities to comment in writing on the practice implications and approved the final version of this document. Results This document with consensus is divided into 18 sections. A total of 41 conclusions and practice implications have been developed. The document includes practice implications for evaluation of stroke patients with caution for stroke team members to avoid COVID-19 exposure, during clinical evaluation and performance of imaging and laboratory procedures with special considerations of intravenous thrombolysis and mechanical thrombectomy in stroke patients with suspected or confirmed COVID-19 infection. Conclusions These practice implications with consensus based on the currently available evidence aim to guide clinicians caring for adult patients with acute ischemic stroke who are suspected of, or confirmed, with COVID-19 infection. Under certain circumstances, however, only limited evidence is available to support these practice implications, suggesting an urgent need for establishing procedures for the management of stroke patients with suspected or confirmed COVID-19 infection.

scholarly journals Acute reperfusion therapies for acute ischemic stroke patients with unknown time of symptom onset or in extended time windows: an individualized approach

2021 ◽  
Vol 14 ◽  
pp. 175628642110211
Author(s):  
Georgios Magoufis ◽  
Apostolos Safouris ◽  
Guy Raphaeli ◽  
Odysseas Kargiotis ◽  
Klearchos Psychogios ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Endovascular Treatment ◽  
Acute Ischemic Stroke ◽  
Symptom Onset ◽  
Time Windows ◽  
Intravenous Thrombolysis ◽  
Inclusion Criteria ◽  
Stroke Patients ◽  
Treatment Algorithms ◽  
Late Presenters

Recent randomized controlled clinical trials (RCTs) have revolutionized acute ischemic stroke care by extending the use of intravenous thrombolysis and endovascular reperfusion therapies in time windows that have been originally considered futile or even unsafe. Both systemic and endovascular reperfusion therapies have been shown to improve outcome in patients with wake-up strokes or symptom onset beyond 4.5 h for intravenous thrombolysis and beyond 6 h for endovascular treatment; however, they require advanced neuroimaging to select stroke patients safely. Experts have proposed simpler imaging algorithms but high-quality data on safety and efficacy are currently missing. RCTs used diverse imaging and clinical inclusion criteria for patient selection during the dawn of this novel stroke treatment paradigm. After taking into consideration the dismal prognosis of nonrecanalized ischemic stroke patients and the substantial clinical benefit of reperfusion therapies in selected late presenters, we propose rescue reperfusion therapies for acute ischemic stroke patients not fulfilling all clinical and imaging inclusion criteria as an option in a subgroup of patients with clinical and radiological profiles suggesting low risk for complications, notably hemorrhagic transformation as well as local or remote parenchymal hemorrhage. Incorporating new data to treatment algorithms may seem perplexing to stroke physicians, since treatment and imaging capabilities of each stroke center may dictate diverse treatment pathways. This narrative review will summarize current data that will assist clinicians in the selection of those late presenters that will most likely benefit from acute reperfusion therapies. Different treatment algorithms are provided according to available neuroimaging and endovascular treatment capabilities.

scholarly journals Incorporation of α2-Plasmin Inhibitor into Fibrin Clots and Its Association with the Clinical Outcome of Acute Ischemic Stroke Patients

Biomolecules ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 347
Author(s):  
Zsuzsa Bagoly ◽  
Barbara Baráth ◽  
Rita Orbán-Kálmándi ◽  
István Szegedi ◽  
Réka Bogáti ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Intracranial Hemorrhage ◽  
Intravenous Thrombolysis ◽  
Fibrin Clot ◽  
Clot Lysis ◽  
Stroke Patients ◽  
Plasmin Inhibitor ◽  
Fibrin Clots

Cross-linking of α2-plasmin inhibitor (α2-PI) to fibrin by activated factor XIII (FXIIIa) is essential for the inhibition of fibrinolysis. Little is known about the factors modifying α2-PI incorporation into the fibrin clot and whether the extent of incorporation has clinical consequences. Herein we calculated the extent of α2-PI incorporation by measuring α2-PI antigen levels from plasma and serum obtained after clotting the plasma by thrombin and Ca2+. The modifying effect of FXIII was studied by spiking of FXIII-A-deficient plasma with purified plasma FXIII. Fibrinogen, FXIII, α2-PI incorporation, in vitro clot-lysis, soluble fibroblast activation protein and α2-PI p.Arg6Trp polymorphism were measured from samples of 57 acute ischemic stroke patients obtained before thrombolysis and of 26 healthy controls. Increasing FXIII levels even at levels above the upper limit of normal increased α2-PI incorporation into the fibrin clot. α2-PI incorporation of controls and patients with good outcomes did not differ significantly (49.4 ± 4.6% vs. 47.4 ± 6.7%, p = 1.000), however it was significantly lower in patients suffering post-lysis intracranial hemorrhage (37.3 ± 14.0%, p = 0.004). In conclusion, increased FXIII levels resulted in elevated incorporation of α2-PI into fibrin clots. In stroke patients undergoing intravenous thrombolysis treatment, α2-PI incorporation shows an association with the outcome of therapy, particularly with thrombolysis-associated intracranial hemorrhage.

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