Intravenous Tissue Plasminogen Research Articles

Factors associated with early improvement after intravenous thrombolytic treatment in acute ischemic stroke

ABSTRACT Objective : The aim of this study was to determine the factors associated with early neurological improvement (ENI) in patients who experienced acute ischemic stroke and were treated with intravenous recombinant tissue plasminogen activator (IV rt-PA), and determine the relationship with the outcome at the first control. Method : This study included 377 patients who were treated with IV rt-PA in Izmir Dokuz Eylül University Hospital between January 2010 and October 2018. ENI was defined as a 4 or more improvement in the National Institutes of Health Stroke Scale (NIHSS) score in the first hour, the twenty-fourth hour and the seventh day when compared to the pretreatment phase. The modified Rankin Scale (mRS) 0–1 score was defined as ‘very good outcome’. Results : The basal NIHSS (p=0.003, p=0.003, p=0.022) was high in the first hour, twenty-fourth hour, and seventh day ENI groups. Blood urea nitrogen (BUN) level was low in the first- and twenty-fourth-hour ENI groups (p=0.007, p=0.020). Furthermore, admission glucose was low at the twenty-fourth hour and on the seventh day ENI groups (p=0.005, p=0.048). A high infarct volume was observed on magnetic resonance imaging (MRI) at the twenty-fourth hour and on the seventh day non-ENI groups (p= <0.001, p= <0.001). Conclusion : Management of factors associated with ENI and determination of treatment strategies accordingly are important for obtaining a better clinical outcome. It can help quickly select patients, who, even though they will not respond to rt-PA, may be appropriate candidates for bridging therapy.

SWATH-MS for prospective identification of protein blood biomarkers of rtPA-associated intracranial hemorrhage in acute ischemic stroke: a pilot study

Intravenous recombinant tissue plasminogen activator (rtPA) is, besides mechanical thrombectomy, the highest class evidence based reperfusion treatment of acute ischemic stroke (AIS). The biggest concern of the therapy is symptomatic intracranial hemorrhage (sICH), which occurs in 3–7% of all treated patients, and is associated with worse functional outcome. Finding a method of the powerful identification of patients at highest risk of sICH, in order to increase the percentage of stroke patients safely treated with rtPA, is one of the most important challenges in stroke research. To address this problem, we designed a complex project to identify blood, neuroimaging, and clinical biomarkers combined for prospective assessment of the risk of rtPA-associated ICH. In this paper we present results of blood proteomic and peptide analysis of pilot 41 AIS patients before rtPA administration (the test ICH group, n = 9 or the controls, without ICH, n = 32). We demonstrated that pre-treatment blood profiles of 15 proteins differ depending on whether the patients develop rtPA-associated ICH or not. SWATH-MS quantification of serum or plasma proteins might allow for robust selection of blood biomarkers to increase the prospective assessment of rtPA-associated ICH over that based solely on clinical and neuroimaging characteristics.

Interventional Mechanical thrombectomy Indications and limitations A Mini-Review

The endovascular clot retrieval in combination with intravenous recombinant tissue plasminogen activator (rtPA) has been established as the 1st choice therapy for the treatment of acute arterial ischemic stroke (AIS) in case of large vessel occlusion. While the results of this therapy in ischemic insults in the anterior stromal region are clearly positive, the results for mechanical thrombectomy in posterior circulation are controversially discussed. In addition, the indication is made by the time window, sizing of the ischemic area, and various scores. The aim of the article is to review the available reports on the use of thromboelastography in acute ischemic stroke patients.

Prognostic analysis of different therapeutic regimens in patients with acute cardiogenic cerebral embolism

BackgroundFew studies focused on the functional outcomes of patients at 3 months after receiving intravenous thrombolysis, anticoagulation, or antiplatelet therapy within 4.5 h of onset of the cardiogenic cerebral embolism (CCE) subtype.MethodsThe purpose of this retrospective study was to analyse the clinical data of patients with acute CCE and compare the 3-month functional prognoses of patients after administration of different antithrombotic therapies within 4.5 h of stroke onset. A total of 335 patients with CCE hospitalized in our institution were included in this study. The patients were stratified according to the hyperacute treatment received, and baseline clinical and laboratory data were analysed. A 3-month modified Rankin scale (mRS) score of 0–2 was defined as an excellent functional outcome.ResultsA total of 335 patients were divided into thrombolytic (n = 78), anticoagulant (n = 88), and antiplatelet therapy groups (n = 169). A total of 164 patients had a good prognosis at 3 months (mRS ≤ 2). After adjustments were made for age and National Institute of Health Stroke Scale (NIHSS) score, each group comprised 38 patients, and there were no significant differences in sex composition, complications, lesion characteristics, or Oxfordshire Community Stroke Project (OSCP) classification among the three groups. The plasma D-dimer level (µg/ml) in the thrombolytic group was significantly higher than those in the anticoagulant and antiplatelet groups [3.07 (1.50,5.62), 1.33 (0.95,1.89), 1.61 (0.76,2.96), P < 0.001]. After one week of treatment, the reduction in NIHSS in the thrombolytic group was significantly greater than those in the other two groups [3.00 (1.00, 8.00), 1.00 (0.00, 5.00), 1.00 (0.00, 2.00), P = 0.025]. A total of 47 patients (41.2 %) had an mRS score of ≤ 2 at 3 months, and 23 patients died (20.2 %). There was no significant difference in the proportion of patients with a good prognosis or the mortality rate among the three groups (P = 0.363, P = 0.683).ConclusionsThrombolytic therapy is effective at improving short-term and 3-month prognoses. Anticoagulant therapy may be a safe and effective treatment option for patients with the cardiac stroke subtype who fail to receive intravenous recombinant tissue plasminogen activator (r-tPA) thrombolysis within 4.5 h in addition to antiplatelet therapy, as recommended by the guidelines.

Aortic dissection diagnosed on stroke computed tomography protocol: a case report

BackgroundAortic dissection is one of the causes of stroke. Because cerebral infarction with aortic dissection is a contraindication to intravenous recombinant tissue plasminogen activator (rt-PA) therapy, exclusion of aortic dissection is necessary prior to its administration. However, imaging takes time to provide a diagnosis, possibly causing delays in surgical treatment.Case presentationA 65-year-old Japanese female patient was transported to the hospital for a suspected stroke, with back pain and left upper and lower extremity palsy which occurred while eating. Upon arrival at the hospital, the left lower limb paralysis had improved, but the left upper limb paralysis remained. Right back pain had also developed. A plain head computed tomography (CT) scan performed 110 minutes after onset showed no acute bleeding or infarction. Subsequent CT perfusion (CTP) showed acute perfusion disturbance in the right hemisphere without infarction, known as ischemic penumbra. The four-dimensional maximum-intensity projection image reconstructed from CTP showed a delayed enhancement at the right internal carotid and right middle cerebral arteries compared to the contralateral side, suggesting a proximal vascular lesion. Contrast helical CT from the neck to abdomen revealed an acute aortic dissection of Stanford type A with false lumen patency. The dissection extended to the proximal right common carotid artery. The patient underwent an emergency total arch replacement and open stent graft. After recovering well, the patient was ambulatory upon discharge from the hospital. The combination of plain head CT, CTP, and helical CT scan from the neck to abdomen enabled us to evaluate for stroke and aortic dissection within a short amount of time, allowing for early therapeutic intervention.ConclusionsWhen acute stroke is suspected due to neurological deficits, plain head CT is the first choice for imaging diagnosis. The addition of cervical CT angiography can reliably exclude stroke due to aortic dissection. CTP can identify ischemic penumbra, which cannot be diagnosed by plain head CT or diffusion-weighted magnetic resonance imaging. These combined stroke CT protocols helped us avoid missing an aortic dissection.

Reader Response: Multimodal CT or MRI for IV Thrombolysis in Ischemic Stroke With Unknown Time of Onset.

We read with interest the article published by Macha et al.1 on multimodal CT or MRI for IV thrombolysis in ischemic stroke with unknown time of onset. Although there were randomized controlled trials already published emphasizing the use of intravenous recombinant tissue plasminogen activator (IV rTPA) beyond the approved time frame (>4.5 hours) in acute ischemic stroke,2,3 your study provided another important aspect: time after receiving the patient in the form of door-to-imaging time, imaging-to-needle time, and door-to-needle time. These studies also supported the use of IV rTPA in an unknown or extended time window with the help of multimodal CT or MRI. Although they concluded that CT imaging led to faster door-to-needle time (45 minutes) compared with MRI-based imaging (75 minutes), they stated that it could change over time because of the availability of more advanced and faster MRI facilities.4 MRI also has added advantages: to perform vascular study without the use of contrast and to provide better visualization of brain parenchyma, which helps in the assessment of microbleeds. Treatment time can be further reduced by using tenecteplase, which can be given as a bolus instead of an infusion over the course of an hour.

Safety and Outcome of Intravenous Recombinant Tissue Plasminogen Activator (rt-PA) in the Nursing Home Residents Following an Acute Ischemic Stroke

Background and Purpose: Intravenous recombinant tissue plasminogen activator (IV rt-PA) is an effective treatment of acute ischemic stroke. The safety and efficacy of IV rt-PA were extensively studied in adults, including both octogenarians and nonagenarians.This study provides safety outcome of exclusive nursing home (NH) residents (dependent on activities of daily living [ADLs]) , who received IV rt-PA. Not much literature or studies are available exclusively on the NH residents. Aim: To assess the safety and outcome of IV rt-PA in patients from NHs who were admitted to our university-based tertiary care hospital, using data from a prospective stroke registry. Methods: Our study is a retrospective review of patients living in nursing facilities, admitted to our neuroscience intensive care unit after receiving IV rt-PA, from January 2010 to June 2018. We reviewed the clinical symptoms, comorbid conditions, medications, diagnostic evaluation, complications, and functional outcomes. The functional outcome was assessed based on the modified Rankin Scale (mRS) at the time of discharge, and 1- and 3-month follow-up. Results: Twenty-eight NH residents (20 [71.4%] were female with a mean age of 80.96 +/− 12.43 years) were identified who had received IV rt-PA for symptoms of acute ischemic stroke. The median mRS on admission was 3, and all of them were dependent on ADL. Twenty-seven (96.5%) patients were treated within the window (≤3 h) for IV rt-PA. There were no IV rt-PA-related violations from both our hospital and outside hospital treatment protocols. The initial computed tomographic (CT) scan of 8 (28.5%) patients revealed evidence of infarction. CT angiogram of head and neck revealed an acute intracranial blood vessel occlusion in 13 (46.4%) patients, and asymptomatic stenosis of intracranial and extracranial blood vessels in 4 (14.2%) patients. Mechanical thrombectomy was attempted in 6 (21.4%) patients and among them, the procedure was unsuccessful in 2 (7.1%) patients due to severe stenosis. One (1/21; 16.6%) patient received an intra-arterial rt-PA, and 5 (5/6;83.3%) patients developed symptomatic intracranial hemorrhage within 24 h following the procedure. Families of 9/28 (32.1%) patients decided to withdraw care. The median mRS on 30 and 90 days follow-up was 4 (interquartile range: 3-6). Conclusion: In this population, mechanical thrombectomy has a high risk for hemorrhagic conversion. IV rt-PA treatment in the NH residents may not improve the outcome of ischemic stroke.

Sex and Race-Ethnic Disparities in Door-to-CT Time in Acute Ischemic Stroke: The Florida Stroke Registry.

BackgroundLess than 40% of acute stroke patients have computed tomography (CT) imaging performed within 25 minutes of hospital arrival. We aimed to examine the race‐ethnic and sex differences in door‐to‐CT (DTCT) ≤25 minutes in the FSR (Florida Stroke Registry).Methods and ResultsData were collected from 2010 to 2018 for 63 265 patients with acute ischemic stroke from the FSR and secondary analysis was performed on 15 877 patients with intravenous tissue plasminogen activator‐treated ischemic stroke. Generalized estimating equation models were used to determine predictors of DTCT ≤25. DTCT ≤25 was achieved in 56% of cases of suspected acute stroke, improving from 36% in 2010 to 72% in 2018. Women (odds ratio [OR], 0.90; 95% CI, 0.87–0.93) and Black (OR, 0.88; CI, 0.84–0.94) patients who had strokes were less likely, and Hispanic patients more likely (OR, 1.07; CI, 1.01–1.14), to achieve DTCT ≤25. In a secondary analysis among intravenous tissue plasminogen activator‐treated patients, 81% of patients achieved DTCT ≤25. In this subgroup, women were less likely to receive DTCT ≤25 (0.85, 0.77–0.94) whereas no significant differences were observed by race or ethnicity.ConclusionsIn the FSR, there was considerable improvement in acute stroke care metric DTCT ≤25 in 2018 in comparison to 2010. However, sex and race‐ethnic disparities persist and require further efforts to improve performance and reduce these disparities.

Abstract P552: Characteristics of Acute Stroke Intervention Therapies During Covid-19

Background and Purpose: We aimed to investigate the characteristics of acute stroke intervention therapies during coronavirus disease 2019 (COVID-19) pandemic. Methods: The data were obtained from a comprehensive stroke center in the central region of the state of Kentucky in the United States. Pre-COVID period, which is before the first confirmed case in Kentucky, from January 1 to March 5 , 2020, was compared with the COVID period from March 6 to May 9, 2020. The variables included were total number of stroke alerts, final diagnosis of stroke, stroke severity scale, thrombolysis including intravenous and intra-arterial tissue plasminogen activator administration and mechanical thrombectomy. The 2 time periods were compared using nonparametric statistics. Results: Total thrombectomies were increased from median, 3( Interquartile range, 1-7) during pre-COVID period to median of 7( Interquartile range, 2-17, p=0.01) during COVID period. Intravenous thrombolysis and adjunct therapy with intra-arterial thrombolysis did not differ between two time periods. Conclusions: We observed an increase in acute stroke intervention therapies during the surge of COVID-19 cases in Kentucky. This observation could be attributed to the increased association of COVID-19 and acute ischemic stroke.

Abstract MP34: Retrospective Analysis on Predictive Factors and Timeline for Early Neurologic Decline and Symptomatic Intracranial Hemorrhage Following Administration of Intravenous Recombinant Tissue Plasminogen Activator for Ischemic Stroke

Introduction: Current guidelines recommend that patients given intravenous tPA (IV tPA) for acute ischemic stroke (AIS) receive comprehensive stroke care for 24 hours post-treatment to monitor key physiologic variables. 1,2,3 Early de-escalation of monitoring is likely feasible in a particular subset of patients, which may have implications in the post-COVID era. 4 In this study, we examined when patients with AIS are susceptible to early neurologic decline (END) and symptomatic intracranial hemorrhage (sICH) after IV tPA and whether those at low clinical risk of neurologic deterioration may be suitable for earlier transition to lower level of care. Methods: We performed a retrospective analysis of AIS receiving IV tPA based on AHA/ASA guidelines. We included those that presented within 4.5 hours of last seen well (LSW) without large vessel occlusion (LVO) or flow-limiting stenosis (FLS) on non-invasive angiographic imaging. Outcomes included END (≥4-point worsening of NIHSS at 24 hours) from any cause, parenchymal hemorrhage (PH1 or PH2), and/ or symptomatic intracranial hemorrhage (sICH; ≥4-point NIHSS worsening with presence of hemorrhage). Results: 1238 patients were included from 1/2013 - 6/2019. END and ICH occurred in 7.4% (91) and 9.4% (116), respectively. 63.7% of patients with END did not have ICH within 24 hours. In those with NIHSS &lt;12, 82% had END within 12 hours and most occurred within 5 hours. Predictive factors included older patients (72.6 ±16.1 vs 69.1 ±14.8, p=0.03), history of tobacco use (OR-2.1 [1.1-4.3], p = 0.04) and hyperlipidemia (OR-1.7 [1.1-2.8] p = 0.02). ICH occurred within 12 hours in 30% of patients, predictors included older age (74.6 ± 12.4 vs 68.8 ± 15.1, p ≤ 0.01), higher NIHSS (14.6 ± 7.3 vs 10.8 ± 7.9, p ≤ 0.01), and higher presentation serum glucose levels (155.1 ± 87.5 vs 140.4 ± 70.5, p = 0.04). Overall, only 2.7% (33) of patients developed sICH. There were no independent predictive factors for delayed ICH (≥ 12 hours). Conclusion: In our selected post-IV tPA patients, a relatively small proportion suffered sICH and END; most often within 12 hours of tPA administration. These findings may support earlier de-escalation of higher acuity monitoring for clinically stable post-IV tPA patients.

Abstract P819: Individualized Patients’ Risk of Post Rt-pa ICH in Acute Ischemic Stroke by Using a Simple Predictive Model

Background and Purpose: A simple and reliable prediction of post intravenous recombination tissue plasminogen activator (rt-PA) intracerebral hemorrhage (ICH) is useful for stroke team to inform individual risk and improve hospitalization care. We aim to develop and validate a simple predictive score model to assess the 24-hour risk of ICH post rt-PA. Methods: This retrospective study included 739 acute ischemic stroke patients who received intravenous rt-PA between October 2005 and June 2020 at Siriraj Hospital, Bangkok, Thailand. Multiple logistic regression was used to evaluate the value of independent variables associated with any ICH and symptomatic intracerebral hemorrhage (SICH) measure by the European Cooperative Acute Stroke Study II (ECASS II) definition. Adjusted ORs of independent variables were converted to point score, summated of point score provide a probability of ICH and SICH. The predictive scores were internal validated in 95 patients and performance tested with an area under a receiver operating characteristic curve (AUC-ROC). Results: From a total of 739 patients, 19.2% had an ICH in which 5.9% was SICH. The predictive model of ICH included hyperdense middle cerebral artery sign (HDMCA) (3 points), initial blood glucose &gt; 180mg/dl (3 points), coronary artery disease (CAD) (2 points), international normalized ratio (INR) &gt; 1.0 (2 points) and 10 year increase of age ( 1 point per 10 year increase; age ≤ 20 year = 1). The performance of the predictive model showed AUC-ROC was 0.72 (95% confidence interval, 0.60 - 0.82) in the derivative cohort and AUC-ROC was 0.74 (95% confidence interval, 0.66 - 0.85) in the validation cohort. Conclusions: This simple predictive model provides a better prediction of a 24-hour risk of ICH post rt-PA in AIS among Thai patients. An individualized ICH risk post rt-PA can assist frontline physicians and relatives in rt-PA decision making process. Further external validation and prospectively confirmed in a larger cohort is recommend.

Efficacy and Safety of Intravenous rtPA in Ischemic Strokes Due to Small-Vessel Occlusion: Systematic Review and Meta-Analysis

Intravenous recombinant tissue plasminogen activator (iv-rtPA) has been routinely used to treat ischemic stroke for 25 years, following large clinical trials. However, there are few prospective studies on the efficacy and safety of this therapy in strokes attributed to cerebral small vessel disease (SVD). We evaluated functional outcome (modified Rankin scale, mRS) and symptomatic intracerebral hemorrhage (sICH) using all available data on the effects of iv-rtPA in SVD-related ischemic stroke (defined either using neuroimaging, clinical features, or both). Using fixed-effect and random-effects models, we calculated the pooled effect estimates with regard to excellent and favorable outcomes (mRS=0–1 and 0–2 respectively, at 3 months), and the rate of sICH. Twenty-three studies fulfilled the eligibility criteria, 11 of which were comparative, and there were only 3 randomized clinical trials. In adjusted analyses, there was an increased odds of excellent outcome (adjusted OR=1.53, 95% CI: 1.29–1.82, I2: 0%) or favorable outcome (adjusted OR=1.68, 95% CI: 1.31–2.15,I2: 0%) in patients who received iv-rtPA compared with placebo. Across the six studies which reported it, the incidence of sICH was higher in the treatment group (M-H RR = 8.83, 95% CI: 2.76–28.27). The pooled rate of sICH in patients with SVD administered iv-rtPA was only 0.72% (95% CI: 0.12%–1.64%). We conclude that when ischemic stroke attributed to SVD is considered separately, available data on the effects of iv-rtPA therapy are insufficient for the highest level of recommendation, but it seems to be safe. Although further therapeutic trials in SVD-related ischemic stroke appear to be justified, our findings should not prevent its continued use for this group of patients in clinical practice.

Stroke and Other Cerebrovascular Diseases

Stroke is a leading cause of neurologic morbidity and mortality, and rapid treatment is key for a good outcome. This review addresses the epidemiology, common presenting symptoms, causes, and treatment of ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage. Current recommendations for the emergent evaluation and treatment of an acute ischemic stroke are highlighted, including recently updated indications and contraindications for intravenous recombinant tissue plasminogen activator administration and recent guidelines for the expanded role of endovascular mechanical embolectomy for stroke due to acute large vessel occlusion. An algorithm of diagnostic evaluations to assist with identification of the cause of ischemic stroke is offered. Evidence-based primary and secondary stroke prevention is discussed, including the ideal choice of antithrombotic based on identified stroke mechanism and optimal risk factor management. Best practice supportive measures for the post-stroke patient are highlighted, including recent guidelines for the management of elevated intracranial pressure. Management of uncommon causes of ischemic stroke is also addressed. This review contains 7 figures, 9 tables, and 84 references. Key Words:Intracerebral hemorrhage, ischemic stroke, recombinant tissue plasminogen activator, subarachnoid hemorrhage, antiplatelet therapy, endovascular therapy

Stroke and Other Cerebrovascular Diseases

Stroke is a leading cause of neurologic morbidity and mortality, and rapid treatment is key for a good outcome. This review addresses the epidemiology, common presenting symptoms, causes, and treatment of ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage. Current recommendations for the emergent evaluation and treatment of an acute ischemic stroke are highlighted, including recently updated indications and contraindications for intravenous recombinant tissue plasminogen activator administration and recent guidelines for the expanded role of endovascular mechanical embolectomy for stroke due to acute large vessel occlusion. An algorithm of diagnostic evaluations to assist with identification of the cause of ischemic stroke is offered. Evidence-based primary and secondary stroke prevention is discussed, including the ideal choice of antithrombotic based on identified stroke mechanism and optimal risk factor management. Best practice supportive measures for the post-stroke patient are highlighted, including recent guidelines for the management of elevated intracranial pressure. Management of uncommon causes of ischemic stroke is also addressed. This review contains 7 figures, 9 tables, and 84 references. Key Words:Intracerebral hemorrhage, ischemic stroke, recombinant tissue plasminogen activator, subarachnoid hemorrhage, antiplatelet therapy, endovascular therapy

Stroke and Other Cerebrovascular Diseases

Stroke is a leading cause of neurologic morbidity and mortality, and rapid treatment is key for a good outcome. This review addresses the epidemiology, common presenting symptoms, causes, and treatment of ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage. Current recommendations for the emergent evaluation and treatment of an acute ischemic stroke are highlighted, including recently updated indications and contraindications for intravenous recombinant tissue plasminogen activator administration and recent guidelines for the expanded role of endovascular mechanical embolectomy for stroke due to acute large vessel occlusion. An algorithm of diagnostic evaluations to assist with identification of the cause of ischemic stroke is offered. Evidence-based primary and secondary stroke prevention is discussed, including the ideal choice of antithrombotic based on identified stroke mechanism and optimal risk factor management. Best practice supportive measures for the post-stroke patient are highlighted, including recent guidelines for the management of elevated intracranial pressure. Management of uncommon causes of ischemic stroke is also addressed. This review contains 7 figures, 9 tables, and 84 references. Key Words:Intracerebral hemorrhage, ischemic stroke, recombinant tissue plasminogen activator, subarachnoid hemorrhage, antiplatelet therapy, endovascular therapy

Stroke and Other Cerebrovascular Diseases

Stroke is a leading cause of neurologic morbidity and mortality, and rapid treatment is key for a good outcome. This review addresses the epidemiology, common presenting symptoms, causes, and treatment of ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage. Current recommendations for the emergent evaluation and treatment of an acute ischemic stroke are highlighted, including recently updated indications and contraindications for intravenous recombinant tissue plasminogen activator administration and recent guidelines for the expanded role of endovascular mechanical embolectomy for stroke due to acute large vessel occlusion. An algorithm of diagnostic evaluations to assist with identification of the cause of ischemic stroke is offered. Evidence-based primary and secondary stroke prevention is discussed, including the ideal choice of antithrombotic based on identified stroke mechanism and optimal risk factor management. Best practice supportive measures for the post-stroke patient are highlighted, including recent guidelines for the management of elevated intracranial pressure. Management of uncommon causes of ischemic stroke is also addressed. This review contains 7 figures, 9 tables, and 84 references. Key Words:Intracerebral hemorrhage, ischemic stroke, recombinant tissue plasminogen activator, subarachnoid hemorrhage, antiplatelet therapy, endovascular therapy

Stroke and Other Cerebrovascular Diseases

Stroke is a leading cause of neurologic morbidity and mortality, and rapid treatment is key for a good outcome. This review addresses the epidemiology, common presenting symptoms, causes, and treatment of ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage. Current recommendations for the emergent evaluation and treatment of an acute ischemic stroke are highlighted, including recently updated indications and contraindications for intravenous recombinant tissue plasminogen activator administration and recent guidelines for the expanded role of endovascular mechanical embolectomy for stroke due to acute large vessel occlusion. An algorithm of diagnostic evaluations to assist with identification of the cause of ischemic stroke is offered. Evidence-based primary and secondary stroke prevention is discussed, including the ideal choice of antithrombotic based on identified stroke mechanism and optimal risk factor management. Best practice supportive measures for the post-stroke patient are highlighted, including recent guidelines for the management of elevated intracranial pressure. Management of uncommon causes of ischemic stroke is also addressed. This review contains 7 figures, 9 tables, and 84 references. Key Words:Intracerebral hemorrhage, ischemic stroke, recombinant tissue plasminogen activator, subarachnoid hemorrhage, antiplatelet therapy, endovascular therapy

Management of acute ischemic stroke in the practice of anesthesiologist

Background. Stroke is a major cause of severe disability. Working capacity is restored only in 10-20 % of stroke survivors. Stroke mortality in Ukraine is twice as high as in Western Europe. About 87 % of all strokes are ischemic strokes (II). Leading risk factors for stroke include hypertension, hypercholesterolemia, smoking, obesity, and diabetes.&#x0D; Objective. To describe the management of acute IS (AIS) in the practice of an anesthesiologist.&#x0D; Materials and methods. Analysis of literature data on this issue.&#x0D; Results and discussion. The ideal therapeutic approach for AIS should include reperfusion, inhibition of inflammatory processes, cytoprotection, prevention of complications and their treatment. Extreme caution should be exercised during thrombolytic therapy, as thrombolysis increases the risk of intracerebral hemorrhage. However, a meta-analysis by Y. Shoujiang et al. (2018) found that symptomatic intracerebral hemorrhage occurs in 1.9 % of patients who had received intravenous recombinant tissue plasminogen activator. These hemorrhages did not increase mortality. Excellent treatment results were observed in 74.8 % of patients with AIS. According to the analysis of the VISTA database, the end result of thrombolytic therapy can be predicted based on the initial severity of stroke on the NIHHS scale. Interestingly, hemorrhagic transformation after thrombolysis is associated with lower serum calcium. Lower blood calcium levels are associated with an increased incidence of cerebral hemorrhage in patients with AIS due to atrial fibrillation or rheumatic heart disease. In the treatment of patients with AIS it is advisable to use Neurocytin (“Yuria-Pharm”), which contains citicoline and a balanced isotonic electrolyte solution. Neurocytin helps to avoid hypocalcemia and, consequently, brain hemorrhages. Citicoline is a multimodal agent with neuroprotective and neuroregenerative properties. Citicoline has a wide therapeutic window, as this substance is effective at different time and biochemical stages of the ischemic cascade. The maximum effect of citicoline is observed in cases when it is administered as early as possible after AIS in patients who cannot undergo reperfusion therapy. Citicoline is able to reduce the size of the ischemic focus in the brain. Intensive blood pressure (BP) control also reduces the risk of intracranial hemorrhages without increasing mortality, although previous studies have suggested that a rapid decrease in BP may exacerbate cerebral ischemia. Endovascular treatment of AIS in the most acute phase involves selective thrombolysis, or mechanical thrombextraction, or thromboaspiration. The therapeutic window for the last two procedures for vessels of the carotid pool is 6 hours. When deciding to perform thromboaspiration, it is mandatory to perform and evaluate computed tomography-perfusiography of the brain. About 80-85 % of patients with AIS do not meet the selection criteria for revascularization therapy. There is also no effective therapy for such patients in the acute period. In recent years, it has been proposed to replace the term “neuroprotection” with the term “brain cell cytoprotection”, as the former does not reflect the direction of the impact on all components of the neurovascular unit and white matter. A separate aspect of brain cytoprotection is protection against ischemic reperfusion injury. For this purpose, edaravon (Ksavron, “Yuria-Pharm”) is used, which eliminates free radicals, reduces calcium flow into the cells, prevents cell adhesion to the endothelium, enhances the release of nitric oxide and inhibits the inflammatory response, neutralizing all stages and consequences of ischemic stroke. In Japan, edaravon has been included into AIS treatment guidelines since 2009. T. Yamaguchi et al. (2017) found that co-administration of edaravon and recombinant tissue plasminogen activator within 4.5 hours after AIS led to less intracranial hemorrhages and better treatment outcomes. Early use of edaravon also reduces mortality. S. Kono et al. (2013) also state that edaravon may be a good adjunct to alteplase to enhance recanalization and reduce the likelihood of hemorrhagic transformation. With the administration of edaravon within the first 24 hours after stroke, one in three patients has no post-stroke sequelae, and 70 % of patients have a significant improvement in general neurological status. If edaravon is prescribed within the first 72 hours after AIS, the general condition improves significantly in half of the patients. Edaravon (Ksavron) increases the frequency of early recanalization during thrombolysis.&#x0D; Conclusions. 1. Citicoline is a multimodal agent with neuroprotective and neuroregenerative properties. 2. Edaravon (Ksavron) is an ischemic cascade blocker for the empirical treatment of AIS or transient ischemic attacks. 3. The combination of edaravon (Ksavron) and citicoline (Neurocytin) as part of comprehensive therapy allows to each the advanced protection of the neurovascular unit in AIS.

Assessing the Clinical Efficacy of Recombinant Tissue Plasminogen Activator on Acute Cerebral Infarction.

To assess the efficacy of intravenous recombinant tissue plasminogen activator (rt-PA) thrombolysis on clinical outcomes and risk of death in patients with acute cerebral infarction. Patients (n = 258) with acute cerebral infarction, treated within 4-5 h of the episode, were grouped according to whether intravenous thrombolysis was performed using rt-PA or not. Both groups received routine treatment for cerebral infarction, but the former received rt-PA intravenously at a dosage of 0.9 mg/kg. The National Institutes of Health Stroke Scale (NIHSS) score, clinical efficacy, and risk of bleeding and death were compared between the two groups. The NIHSS score and clinical effects for the rt-PA group were more favorable than those of its counterpart (P < 0.05), though there was no significant difference in risk of an intracranial hemorrhage. The mortality rate for the rt-PA group was lower than that of the control group (P < 0.05). Administration of intravenous rt-PA thrombolysis within 4.5 h of an acute cerebral infarction had a significant impact and did not increase risk of intracranial hemorrhage or death.

Peripheral embolization following thrombolytic therapy for acute ischemic stroke\u2014a case report

BackgroundIntravenous recombinant tissue plasminogen activator is the only golden approved medical therapy for acute ischemic stroke, guidelines for its injection relay on reducing or preventing associated hemorrhage as a side effect, yet hemorrhage is not the only possible complication, further embolization following injection is also a possibility; in this case report, peripheral embolization following intravenous recombinant tissue plasminogen activator with two possible explanations one related to the treatment and another related to the patient liability is represented.Case presentationA 78-year-old male presenting with acute onset of stroke, received intravenous recombinant tissue plasminogen activator, 16 h later he developed acute limb ischemia.ConclusionPeripheral embolization may happen within hours from intravenous recombinant tissue plasminogen activator administration.