Intravenous Tissue-type Plasminogen Activator Research Articles

Paradigm Shift in Intra-Arterial Mechanical Thrombectomy for Acute Ischemic Stroke : A Review of Randomized Controlled Trials after 2015.

Three randomized control trials (RCTs), published in 2013, investigated efficacy of mechanical thrombectomy in large vessel occlusions and did not show better results compared to intravenous (IV) recombinant tissue-type plasminogen activator (tPA) alone. However, most clinicians treating stroke consider mechanical thrombectomy as the standard treatment rather than using IV tPA alone. This paradigm shift was based on five RCTs investigating efficacy of mechanical thrombectomy in acute ischemic stroke conducted from 2010 to 2015. They demonstrated that mechanical thrombectomy was effective and safe in acute ischemic stroke with anterior circulation occlusion when performed within 6 hours of stroke onset. There are four reasons underlying the different results observed between the trials conducted in 2013 and 2015. First, the three RCTs of 2013 used low-efficiency thrombectomy devices. Second, the three RCTs used insufficient image selection criteria. Third, following the initial presentation at the hospital, reperfusion treatment required a long time. Fourth, the three RCTs showed a low rate of successful recanalization. Time is the most important factor in the treatment of acute ischemic stroke. However, current trends utilize advanced imaging techniques, such as diffusion-weighted imaging and multi-channel computer tomographic perfusion, to facilitate the detection of core infarction, penumbra, and collateral flows. These efforts demonstrate that patient selection may overcome the barriers of time in specific cases.

The Association between Presentation by EMS and EMS Prenotification with Receipt of Intravenous Tissue-Type Plasminogen Activator in a State Implementing Stroke Systems of Care

Introduction: Collaboration between emergency medical services (EMS) and hospitals receiving stroke patients is critical to ensure prompt, effective treatment, and is a key component of the stroke systems of care (SSoC). The goal of our study was to evaluate the association between presentation by EMS and EMS prenotification with odds of receiving Tissue-type Plasminogen Activator (IV-tPA) in a state implementing SSoC while rigorously accounting for missing data. Methods: We utilized data from the Massachusetts Paul Coverdell Stroke Registry for this study, and analyzed adult patients presenting with ischemic stroke to Massachusetts Coverdell hospitals between 2016 and 2018. Patients with contraindications to IV-tPA were excluded. We used generalized estimating equations to assess associations between presentation by EMS, EMS prenotification, and receipt of IV-tPA. We also performed a sensitivity analysis using multiple imputation to assess the sensitivity of our findings to missing data. Results: We identified 9,230 eligible patients with ischemic stroke during the study period. In multivariate complete case regressions, presentation by EMS and EMS prenotification were associated with statistically significant increased odds of receiving IV-tPA (odds ratio [OR] 1.52, 95% confidence interval [CI] 1.28-1.80, p-value < 0.01; OR 1.75, 95% CI 1.36-2.24, p-value < 0.01, respectively). Analysis of imputed data indicated level or stronger associations. Conclusion: Our analysis indicates that presentation by EMS and EMS prenotification are associated with increased odds of receiving IV-tPA in a state implementing the SSoC. Our results lend importance to the critical role of EMS in the SSoC. Future interventions should work to increase rates of prenotification by EMS and assess inequities in receipt of IV-tPA.

Safety and efficacy of repeated thrombolysis with recombinant tissue- type plasminogen activator in early recurrent ischemic stroke: A systematic review

Thrombolysis with intravenous tissue- type plasminogen activator (IVtPA) is the only approved treatment for patients with acute ischemic stroke. History of stroke for the past three months is an exclusion criteria set by the National Institute of Neurological Disorders and Stroke study. It is unknown whether repeat IVtPA in early ischemic stroke is associated with higher complication rates. The main objective of this review was to determine the safety and efficacy of repeated thrombolysis in patients who had early recurrent ischemic strokes. MEDLINE by PubMed, CENTRAL by The Cochrane Library, HERDIN, SCOPUS and ClinicalTrials.gov websites were searched in August 2018. All studies reporting the use of repeated IVtPA in patients with early recurrent ischemic strokes were included. Data collected include study design, population characteristics, treatment outcomes (symptomatic hemorrhage, functional status in three months, systemic hemorrhage, anaphylaxis). The review included ten articles with a total of 33 patients. One developed hemorrhagic conversion leading to neurologic deterioration and death. Half of the patients with reported functional status three months after the repeated thrombolysis had no or minimal significant disability. One died from spontaneous rupture of previously unidentified infrarenal aortic aneurysm. No anaphylactic reactions were noted. Repeated IVtPA can be safe and efficacious in patients who had early recurrent ischemic stroke. Larger studies are needed to confirm the beneficial effects and risks of repeated IVtPA in patients with early recurrent ischemic strokes.

Endovascular therapy of acute ischemic stroke

Endovascular treatment of acute ischemic stroke has introduced several paradigm shifts in the therapy of cerebral artery occlusion. Until recently, intravenous recombinant tissue-type plasminogen activator was the only evidence-based treatment option. Recent trials have proven the safety and efficacy of endovascular treatment and additional clinical studies are expanding the indication for this therapeutic approach. A prompt and effective revascularization is the mainstay for the treatment of acute ischemic stroke. Thrombectomy with stentrievers and/or thromboaspiration are now recommended as the standard of care for acute ischemic stroke with a proximal cerebral artery occlusion according to specific selection criteria based on patient's characteristics, clinical presentation, timing and neuroimaging. In this review, the main findings from available evidence and the state of art of endovascular therapy of acute ischemic stroke are discussed, requiring that the procedure be performed by trained neurointerventionalists to guarantee the demonstrated safety and efficacy of this treatment.

Intravenous Thrombolysis for Acute Ischemic Stroke After Recent Myocardial Infarction: Case Series and Systematic Review.

Background and Purpose- The safety of IV r-tPA (intravenous tissue-type plasminogen activator) for acute ischemic stroke (AIS) treatment after recent myocardial infarction (MI) is still a matter of debate. We studied the safety of delivering IV r-tPA to AIS patients with a MI within the preceding 3 months. Methods- Retrospective review of consecutive AIS admitted to 2 tertiary university hospitals' and systematic literature review for AIS patients with history of MI in the previous 3 months. Patients were divided into 2 groups: treated or not treated with standard IV r-tPA dose for AIS. Cardiac complications (cardiac rupture/tamponade, intracardiac thrombus embolization, or life-threatening arrhythmias) were compared between groups and assessed by type of MI (non-ST-segment-elevation myocardial infarction [STEMI], or STEMI) and time elapsed between vascular events. Results- One hundred and two patients were included; 46 (45.1%) were derived from literature review. Median age (interquartile range) was 64 (53-75) years old, and 69 (67.6%) were men. Forty-seven (46.1%) received IV r-tPA. In the treated group, 25 (53.2%) and 23 (48.9%) patients had, respectively, concurrent AIS and MI and STEMI, in comparison with 12 (21.8%; P=0.002) and 36 (65.5%; P=0.110) patients in the nontreated. Four (8.5%) IV r-tPA-treated patients died from confirmed or presumed cardiac rupture/ tamponade, all with a STEMI in the week preceding stroke. This complication occurred in 1 (1.8%) patients in the nontreated group (P=0.178). There were no differences in thrombus embolization (1 [2.1%) versus 2 [3.6]; P=1.000) and life-threatening arrhythmias (3 [6.4%) versus 7 [12.7]; P=0.335). No non-STEMI patients receiving IV r-tPA had cardiac complications. Conclusions- In patients with AIS and recent or concurrent MI, MI type and the time elapsed between the 2 events should be taken into consideration when deciding to deliver IV r-tPA. Although recent non-STEMI or concurrent events seem safe, STEMI in the week preceding stroke should prompt caution. The low number of events and publication bias may have influenced our conclusions.

Racial and Ethnic Disparities in the Utilization of Thrombectomy for Acute Stroke.

Background and Purpose- Racial and ethnic disparities in the access to mechanical thrombectomy (MT) for treatment of acute ischemic stroke (AIS) secondary to large vessel occlusion have been previously described. The effect of recent randomized trials validating MT as an effective therapy for AIS secondary to large vessel occlusion on such disparities has not been investigated. Methods- Information on admissions for AIS to endovascular centers occurring between January 2016 and September 2018 was obtained from a national database. The number of patients receiving IV-tPA (intravenous tissue-type plasminogen activator) and MT at each institution was determined, and patient demographics were characterized according to age, sex, race/ethnicity, and insurance status. Comparisons of patients who did and did not undergo MT and between patients of different racial and ethnic backgrounds were performed. Demographic variables independently associated with the utilization of MT were identified using multivariate linear regression analysis. Results- There were 206 853 admissions to 173 endovascular centers during the time period of interest. The overall utilization of MT was 8.4%. The utilization of MT for black/Hispanic patients was lower than that among white/non-Hispanic patients (7.0% versus 9.8%; P<0.001). Black/Hispanic patients were also less likely to receive IV-tPA (16.2% versus 20.5%; P<0.001) and to be admitted to the endovascular center after transfer from a different hospital (20.0% versus 30.1%; P<0.001). On multivariate linear regression analysis, increasing institutional proportions of patients with female sex (β=-0.601; P<0.001), insurance with Medicaid or uninsured status (β=-0.153; P=0.029), and black/Hispanic race/ethnicity (β=-0.062; P=0.046) were independently associated with lower institutional utilization of MT. Conclusions- Despite the mainstream acceptance of MT for the treatment of AIS secondary to large vessel occlusion, racial and ethnic disparities in the utilization of MT persist.

Elevation of high-sensitivity cardiac troponin T at admission is associated with increased 3-month mortality in acute ischemic stroke patients treated with thrombolysis.

BackgroundElevated levels of cardiac troponin T (cTnT) have been associated with unfavorable outcomes in cardiac patients. However, no studies, to date, have discussed the prognostic value of high‐sensitivity cTnT (hs‐cTnT) in thrombolyzed patients with acute ischemic stroke (AIS).HypothesisWe hypothesized that elevated levels of hs‐cTnT would be associated with poorer clinical outcomes in AIS patients treated with intravenous tissue‐type plasminogen activator (IV tPA).MethodsFrom January 2017 to February 2018, a total of 241 AIS patients treated with IV tPA within 4.5 hours of onset were recruited. On admission, patients were stratified into either normal or elevated hs‐cTnT groups according to a cutoff value of 14 ng/L. Multivariable logistic regression analyses were conducted to identify determinants of hs‐cTnT elevation and to detect whether elevated hs‐cTnT was associated with disability and/or mortality.ResultsIn multivariable regression analysis, older age (P < .001) and stroke etiology (P = .024) were significantly associated with elevated hs‐cTnT levels. After adjusting for demographic and clinical characteristics, hs‐cTnT elevation was still significantly associated with 14‐day major disability (modified Rankin Scale (mRS) 3‐5, model 1, P = .019, odds ratio [OR] 2.677; model 2, P = .015, OR 2.834), 14‐day composite unfavorable outcome (mRS 3‐6, model 1, P = .005, OR 3.525; model 2, P = .003, OR 3.976), 30‐day mortality (P = .049, OR 4.545) and 90‐day mortality (P = .049, OR 3.835).ConclusionsElevation of hs‐cTnT at admission is associated with an increased risk of 90‐day mortality in AIS patients treated with IV tPA.

029 Time equals brain – retrospective analysis of thrombolysis in regional australia to determine factors which influence door to needle time

IntroductionMinimising delay in thrombolysis is a key outcome in acute stroke care.MethodsA 3 year retrospective cohort analysis of all acute stroke admissions in Wollongong Hospital, a major regional referral centre in New South Wales, was completed to determine the causes of in-hospital delays for thrombolysis. Data collected included age, baseline National Institute of Health Stroke Scale (NIHSS) score, onset time, arrival time, CT imaging &amp; reporting time and outcomes of the event.ResultsFrom 656 admissions, 70 cases of thrombolysis were recorded 56 cases of endovascular thrombectomy. The mean time from onset to arrival was 85 minutes, from arrival to CT was 31 minutes and from door to needle time (DNT) was 108 minutes. Multiple regression analysis revealed a an inverse linear association between onset to arrival time and DNT. Age, stroke severity and gender were not shown to impact treatment times. The results showed that there was a paradoxical association between arrival time and DNT. The cause for this was not clearly identified but similar to previous studies is likely to be contributed by a lack of urgency when initiating management.1 2ConclusionFor every 30-minute delay in hospital arrival, there was a 13- minute reduction in DNT. In light of this, education trials to promote ‘time equals brain’ understanding amongst stroke first responders is being implemented to aim to reduce DNT to less than 80 minutes. The results of this are anticipated to be available in mid 2019.ReferencesAlbers GW, Bates VE, Clark WM. Intravenous tissue-type plasminogen activator for treatment of acute stroke: The Standard Treatment with Alteplase to Reverse Stroke (STARS) Study. Journal of the American Medical Association 2000; 283:1145–1150.Romano JG, Muller N, Merino JG, Forteza AM, Koch S, Rabinstein AA. In-hospital delays to stroke thrombolysis: paradoxical effct of early arrival. Neurological Research 2007;29:664–666.

Frequency of Blood-Brain Barrier Disruption Post-Endovascular Therapy and Multiple Thrombectomy Passes in Acute Ischemic Stroke Patients.

Background and Purpose- The high prevalence of hyperintense acute reperfusion marker (HARM) seen after endovascular therapy is suggestive of blood-brain barrier disruption and hemorrhage risk and may be attributable to multiple thrombectomy passes needed to achieve recanalization. Methods- Patients with acute stroke were included if they were screened from January 2015 through February 2019, received an acute ischemic stroke diagnosis involving the anterior circulation, treated with or without IV tPA (intravenous tissue-type plasminogen activator), consented to the NINDS Natural History Study, and imaged with a baseline magnetic resonance imaging before receiving endovascular therapy. Consensus image reads for HARM and hemorrhagic transformation were performed. Good clinical outcome was defined as 0-2 using the latest available modified Rankin Scale score. Results- Eighty patients met all study criteria and were included in the analyses. Median age was 65 years, 64% female, 51% black/African American, median admit National Institutes of Health Stroke Scale=19, 56% treated with IV tPA, and 84% achieved Thrombolysis in Cerebral Infarction score of 2b/3. Multiple-pass patients had significantly higher rates of severe HARM at 24 hours (67% versus 29%; P=0.001), any hemorrhagic transformation (60% versus 36%; P=0.04) and poor clinical outcome (67% versus 36%; P=0.008). Only age (odds ratio, 1.1; 95% CI, 1.01-1.12; P=0.022) and severe HARM at 24 hours post-endovascular therapy were significantly associated with multiple passes (odds ratio, 7.2; 95% CI, 1.93-26.92; P=0.003). Conclusions- In this exploratory study, multiple thrombectomy passes are independently associated with a significant increase in blood-brain barrier disruption detected at 24 hours. Patients with HARM post-endovascular therapy had a >7-fold increase in the odds of having multiple- versus single-pass thrombectomy. Clinical Trial Registration- URL: https://www.clinicaltrials.gov. Unique identifier: NCT00009243.

Evaluation of the Accuracy Equivalence of Head CT Interpretations in Acute Stroke Patients Using a Smartphone, a Laptop, or a Medical Workstation

PurposeTo evaluate and compare the clinical performance of observers interpreting head CT images from patients with symptoms of acute stroke with a medical workstation or a smartphone or laptop reading system. Materials and methodsOur institutional review board approved this retrospective study and waived the requirement for informed consent. We employed a factorial design including 2,256 interpretations (188 patients × 4 neuroradiologists × 3 reading systems). Accuracy equivalence tests, at a threshold of 5% and 10%, were performed for the following variables: detection of imaging contraindications for intravenous recombinant tissue-type plasminogen activator administration (eg, hemorrhagic lesions), ischemic lesions, hyperdense arteries, and acute ischemic lesions. For each clinical variable, the sensitivity, specificity, and receiver operating characteristic (ROC) curves were evaluated. ResultsFor each variable, the shapes of the ROC curves were very similar for all of the reading systems, indicating similar observer performance with different specificities and sensitivities. For all the clinical variables, the areas under the ROC curves were equivalent for all of the reading systems at a 10% threshold and were equivalent at a 5% threshold for hemorrhagic lesions, hyperdense middle cerebral artery, and acute ischemic lesion in the middle cerebral artery territory. There was no more than 30 seconds of difference between the reading time of the mobile devices compared with that for the medical workstation. ConclusionThe results of this pilot study showed equivalent diagnostic accuracy when using smartphone and laptops compared with medical monitors to interpret head CT images of patients with symptoms of acute stroke.

Decision Analysis Model for Prehospital Triage of Patients With Acute Stroke.

Background and Purpose- We used a decision analysis approach to analyze triage strategies for patients with acute stroke symptoms while accounting for prehospital large vessel occlusion (LVO) screening methods and key time metrics. Methods- Our decision analysis compared anticipated functional outcomes for patients within the IV-tPA (intravenous tissue-type plasminogen activator) treatment window in the mothership and drip-and-ship frameworks. Key branches of the model included IV-tPA eligibility, presence of an LVO, and endovascular therapy eligibility. Our decision analysis evaluated 2 prehospital LVO screening approaches: (1) no formal screening and (2) the use of clinical LVO screening scales. An excellent outcome was defined as modified Rankin Scale scores 0-1. Probabilities and workflow times were guideline-based or imputed from published studies. In sensitivity analyses, we individually and jointly varied transport time to the nearest primary stroke center, additional time required to transport directly to a comprehensive stroke center, and LVO screening scale predictive probabilities. We evaluated 2 separate scenarios: one in which ideal time metrics were achieved and one under current real-world metrics. Results- In the ideal metrics scenario, the drip-and-ship strategy was almost always favored in the absence of formal LVO screening. For patients screened positive for an LVO, mothership was favored if the additional transport time to the comprehensive stroke center was <3 to 23 minutes. Under real-world conditions, in which primary stroke center workflow is slower than ideal, the mothership strategy was favored in more scenarios, regardless of formal LVO screening. For example, mothership was favored with an additional transport time to the comprehensive stroke center of <32 to 99 minutes for patients screened positive for an LVO and <28 to 39 minutes in the absence of screening. Conclusions- Joint consideration of LVO probability, screening, workflow times, and transport times may improve prehospital stroke triage. Drip-and-ship was more favorable when more ideal primary stroke center workflow times were modeled.

Use of Emergency Medical Services and Timely Treatment Among Ischemic Stroke.

Background and Purpose- Emergency medical services (EMSs) are critical for early treatment of patients with ischemic stroke, yet data on EMS utilization and its association with timely treatment in China are still limited. Methods- We examined data from the Chinese Stroke Center Alliance for patients with ischemic stroke from June 2015 to June 2018. Absolute standardized difference was used for covariates' balance assessments. We used multivariable logistic models with the generalized estimating equations to account for intrahospital clustering in identifying demographic and clinical factors associated with EMS use as well as in evaluating the association of EMS use with timely treatment. Results- Of the 560 447 patients with ischemic stroke analyzed, only 69 841 (12.5%) were transported by EMS. Multivariable-adjusted results indicated that those with younger age, lower levels of education, less insurance coverage, lower income, lower stroke severity, hypertension, diabetes mellitus, and peripheral vascular disease were less likely to use EMS. However, a history of cardiovascular diseases was associated with increased EMS usage. Compared with self-transport, EMS transport was associated with significantly shorter onset-to-door time, door-to-needle time (if prenotification was sent), earlier arrival (adjusted odds ratio [95% CIs] were 2.07 [1.95-2.20] for onset-to-door time ≤2 hours, 2.32 [2.18-2.47] for onset-to-door time ≤3.5 hours), and more rapid treatment (2.96 [2.88-3.05] for IV-tPA [intravenous recombinant tissue-type plasminogen activator] in eligible patients, 1.70 [1.62-1.77] for treatment with IV-tPA by 3 hours if onset-to-door time ≤2 hours, and 1.76 [1.70-1.83] for treatment with IV-tPA by 4.5 hours if onset-to-door time ≤3.5 hours). Conclusions- Although EMS transportation is associated with substantial reductions in prehospital delay and improved likelihood of early arrival and timely treatment, rate of utilization is currently low among Chinese patients with ischemic stroke. Developing an efficient EMS system and promoting culture-adapted education efforts are necessary for improving EMS activation.

Vasospasm as a major complication after acute mechanical thrombectomy with stent retrievers

ObjectiveMechanical thrombectomy using a stent retriever for acute large vessel occlusion is indispensable in stroke treatment, however, vasospasm may occur. The objective of this retrospective study was to investigate which cases are more likely to experience vasospasm after thrombectomy with stent retrievers. MethodsWe included 29 patients diagnosed with acute cardiogenic cerebral embolism who were treated with stent retrievers at our facility from December 2014 to December 2017. Atherothrombotic brain infarction cases were excluded because it was difficult to evaluate for vasospasms. Vasospasm was defined as reversible arterial narrowing of <80% of the normal vessel diameter after usage of the stent retriever. The age, sex, type of stent retriever, occlusion site, number of procedures, thrombolysis in cerebral infarction (TICI) grade, degree of vasospasm, intracranial hemorrhage by the procedure, and neurological outcomes were analyzed. ResultsAmong the 29 cases, 12 (41.4%) resulted in vasospasm; nine cases were mild (20–50% stenosis) and 3 cases were severe (≥50% stenosis). Vasospasm frequently occurred in the distal part of the anterior circulation when compared to the proximal part. In addition, the frequency of vasospasm increased as the number of procedures increased. Pooled analysis showed significant difference in the intravenous tissue-type plasminogen activator group (P = 0.029). There was no significant difference in the other groups. ConclusionStent retrievers appear to cause vasospasm more than expected when including mild cases. Vasospasm tends to occur especially in cases with IV-tPA; prognosis is generally good, and it rarely requires any treatment.

Abstract TP100: Elevation of Admission High-Sensitivity Cardiac Troponin T is Associated With Increased Discharge Disability in Acute Ischemic Stroke Patients Treated With Thrombolysis

Introduction: Elevated levels of cardiac troponin T (cTnT) has been demonstrated to be associated with greater stroke severity, worse clinical outcome and increased mortality. Few studies have discussed the predictive value of high-sensitivity cTnT(hs-cTnT) in thrombolysed patients with acute ischemic stroke (AIS). In the present study, we investigate whether elevated levels of hs-cTnT is associated with greater stroke severity and worse clinical outcomes in Chinese AIS patients treated with intravenous tissue-type plasminogen activator (IV tPA). Methods: From January 2017 to February 2018, we prospectively recruited a total of 249 AIS patients treated with IV tPA within 4.5 hours of onset.Hs-cTnT assays were performed on admission and prior to thrombolysis in all these patients.Patients were stratified into either normal or elevated hs-cTnT groups according to a cut-off value of 14 ng/L of the admission hs-cTnT level. Adjusted odds ratios and related 95% confidence intervals were assessed based on multivariable logistic regression model. Results: In the univariate comparisons, older age, higher NIHSS on admission, lower eGFR, history of diabetes mellitus, coronary heart disease or atrial fibrillation, involvement of insular cortex and cardioembolism were significantly associated with elevated hs-cTnT levels.In the univariate comparisons,hs-cTnT elevation was significantly associated with disability at discharge(14 days mRS &gt; 2) ( p &lt;0.001, OR 3.733, 95% CI 2.019-6.905) and 30 days mortality( p =0.002, OR 8.190, 95% CI 2.101-31.935).After adjusting for demographic and clinical characteristics in multivariable analysis, hs-cTnT elevation was still significantly associated with disability at discharge ( p &lt; 0.05, OR 2.82, 95% CI 1.02-7.77). Thirty days mortality showed an increasing trend ( p = 0.09, OR 4.093, 95% CI 0.81-20.70) in hs-cTnT elevated group. Conclusions: Hs-cTnT elevation is associated with increased disability at discharge in AIS patients treated with IV tPA. Further analyses with regard to neurological severity (NIHSS) and disability (mRS)respectively at the time point of discharge, 30 days and 90 days are in process.

Abstract TP589: Emergency Medicine Physicians Can Reliably Treat Stroke Patients with tPA Using a Checklist

Background: There is uncertainty among many emergency medicine physicians about the decision to give intravenous tissue-type plasminogen activator (tPA) in suspected acute ischemic stroke patients, which limits its use. A checklist approach has been suggested as a solution. Objective: To compare agreement on tPA treatment in suspected acute ischemic stroke patients between vascular neurology and emergency medicine physicians using a checklist. Methods: Every suspected acute stroke patient brought to our comprehensive stroke center emergency room within 4.5 hours from symptom onset was prospectively evaluated simultaneously and independently by vascular neurology fellows (VNF) and emergency medicine residents (EMR). The latter used a tPA screening checklist, which included guideline exclusion criteria to help with their treatment decision. Agreement between the EMR and the VNF and a senior VN faculty was determined using Cohen’s kappa (κ) statistics. Results: Over 5 months, 60 patients were enrolled, age 63±16, 50% female, NIHSS median 6 (IQR: 1,14), premorbid mRS &gt; 2 30%. Eventual etiology was: 10% large vessel atherosclerosis, 18% cardioembolism, 12% small vessel, 12% cryptogenic, and 48% mimic. 25 (42%) were deemed tPA eligible by the EMR, 18 (30%) by the VNF, and 22 (37%) by the VN faculty. Agreement was substantial between EMR and VNF (κ=0.68, 95% CI 0.49 to 0.87) and between EMR and VN faculty (κ=0.69, 95% CI 0.50 to 0.87]). Age, NIHSS, premorbid mRS, gender and race had no effect on agreement. There were no complications in any tPA treated patients. Stroke mimics were the main cause of disagreement between EMR and VNF (κ=0.24, 95% CI -0.15 to 0.63) and between EMR and VN faculty (κ=0.35, 95% CI -0.08 to 0.78). Conclusions: Our data suggest that with the aid of a checklist, emergency medicine physicians can reliably treat acute stroke patients with tPA. Areas for improvement include recognition of stroke mimics. Further studies are warranted to evaluate checklist enhanced tPA treatment in order to allay emergency medicine physician uncertainty and expand the use of tPA.

Cost-effectiveness analysis of mechanical thrombectomy plus tissue-type plasminogen activator compared with tissue-type plasminogen activator alone for acute ischemic stroke in France

Background and purposeRecent studies demonstrated the benefit of mechanical thrombectomy (MT) plus intravenous tissue-type plasminogen activator (IV-tPA) (MT-IV-tPA) in acute ischemic stroke. This study aimed to estimate the cost-utility of MT-IV-tPA compared with IV-tPA alone from the perspective of the French National Health Insurance. MethodsWe developed a decision tree for the first 3 months after stroke onset and a Markov model until 10 years post-stroke. The health states of the Markov model were according to the modified Rankin Scale (mRS): independent (mRS=0-2), dependent (mRS=3-5), dead (mRS=6). Recurrent stroke was the fourth health stage of our model. We conducted systematic literature reviews and meta-analyses to estimate the cost and utility of each health state, and the transition probabilities between health states. A microcosting study was conducted to estimate the cost of MT. We estimated the incremental cost-effectiveness ratio of MT-IV-tPA and conducted a probabilistic analysis in order to estimate the probability that MT-IV-tPA is cost-effective compared to IV-tPA, the expected value of perfect information (EVPI), and the expected value of partial perfect information (EVPPI), given the uncertainty surrounding the value of our model's parameters. ResultsThe total mean (standard deviation (SD) cost of MT was €6708.9 (2357.0). The incremental cost-effectiveness ratio (ICER) of the strategy using IV-tPA combined to MT costs was €14,715 per QALY gained as compared to a strategy using IV-tPA alone. The probabilistic analysis showed that the probability of MT-IV-TPA being cost-effective was 85.4% at threshold willingness-to-pay of €30,000 per QALY gained, reaching 98% at €50,000 per QALY gained. ConclusionAlthough there is no universally accepted willingness-to-pay threshold in France, our analysis suggest that MT combined to IV-tPA can be considered a cost-effective treatment compared with IV-tPA alone.

Neural Stem Cell Transplantation into a Mouse Model of Stroke.

Stroke is the fifth leading cause of death among Americans each year. Current standard-of-care treatment for stroke deploys intravenous tissue-type plasminogen activator (tPA), mechanical thrombolysis, or delivery of fibrinolytics. Although these therapies have reduced stroke-induced damage, therapeutic options still remain limited. Transplantation of patient-specific neural stem (NS) cells represents a promising strategy for the treatment of stroke. Basic science research has shown that transplanted NS cells can differentiate in the brain of rodent models of stroke and promote behavioral recovery. Clinical trials exploring the feasibility of stem cell treatment for stroke are currently being conducted. However, questions remain regarding the optimal means of delivering NS cells, including cell dose, infusion speed, timing of transplantation, anatomic site, and imaging-assisted monitoring and guidance. Of the different available delivery modalities, intravascular NS delivery after stroke represents one practical approach. In this chapter, I provide methods for intravascular delivery of NS cells in a mouse model of stroke. The techniques involved include cell culture of NS cells, flow cytometry of NS cells, modeling stroke via unilateral common carotid artery occlusion, intra-arterial injection of NS cells into the brain, behavior analyses, and immunohistochemistry. Intra-arterial NS cell therapy has the potential to improve functional recovery after ischemic stroke.

Late Hospital Arrival for Thrombolysis after Stroke in Southern Portugal: Who Is at Risk?

Background: Delayed hospital arrival remains the main reason for the low rates of thrombolysis in eligible acute ischemic stroke (AIS) patients. The role of socioeconomic and clinical factors for the prehospital delay of AIS remains poor and has never been studied in Portugal. Objectives: Describe the socioeconomic and clinical factors leading to delayed hospital admission of AIS patients eligible to thrombolysis. Methods: A case-control study with a consecutive thrombolyzed AIS patients from 2010 to 2015. Controls were patients who did not receive thrombolysis because of late hospital arrival. Logistic regression with stepwise forward regression analysis was used to identify independent predictors of delayed admission to receive thrombolysis with intravenous tissue-type plasminogen activator (rtPA). Results: Of the 1247 patients admitted with AIS, 76 (6%) arrived on-time and received intravenous rtPA. Controls were 65.8% (146/222) of the total number of patients included in the study. Overall, the mean age was 73 years (±11, 61), a minority were below 60 years, and 43.7% were women. Being beneficiary of social insertion income (odds ratio [OR]: .286; .124-.662, P = .003), not having any telephone contact (OR: .145; .039-.536, .004) or having exclusive landline (.055; .014-.210, <.001) and posterior circulation stroke (OR: .266; .087-.811, P = .020) decreased the likelihood of hospital arrive on-time rtPA. The use of prehospital ambulance services increased (OR: 6.478; 2.751-15.254, P < .001) the odds of ER on-time arrival for thrombolysis. Conclusions: Poverty, lack of stroke awareness, or difficulties in requesting immediate medical help are the main factors implicated in late-hospital admission for thrombolysis in AIS. Stroke awareness campaigns, promotion of activation of national emergency number and stroke code can increase the rate of thrombolysis.

Post-thrombolysis rupture of small lenticulostriate aneurysms: A report of 2 consecutive cases

The 2018 American Heart Association/American Stroke Association (AHA/ASA) guidelines stated that the administration of intravenous recombinant tissue-type plasminogen activator (rTPA) for acute ischaemic stroke is probably safe for patients with small (i.e. <10 mm) unruptured intracranial aneurysms. We present 2 cases of small (2 and 5 mm) lenticulostriate artery (LSA) aneurysms which ruptured immediately following rtPA infusion. The ensuing acute intracranial haemorrhages resulted in the death of one patient and severe functional impairment for the other. Given the limited literature available, the natural history of LSA aneurysms is largely unknown. This report suggests that LSA aneurysms, regardless of size, be considered separately from other conventional aneurysms as “high-risk” lesions and a contraindication to thrombolysis.

Real-World Outcomes of Acute Ischemic Stroke Treatment with Intravenous Thrombolysis: A Systematic Review and Meta-Analysis

BackgroundEvidence from outside the typical clinical research setting, such as the real-world setting, complements evidence coming from randomized controlled trials. The purpose of this study was to evaluate all available evidence from the real-world observational trials about long-term outcomes of treatment with intravenous (IV) recombinant tissue-type plasminogen activator (rt-PA) compared with not treated with IV rt-PA (non-rt-PA) in patients with acute ischemic stroke. MethodsWe searched PubMed and Embase until March 1, 2018 for observational studies reporting matched or adjusted results comparing IV rt-PA versus non-rt-PA in patients with acute ischemic stroke. Outcomes assessed included all-cause mortality, hospital readmission rates, and independence rates. Hazard ratios with 95% confidence intervals were used as a measure of comparing between patients treated with IV rt-PA and non-rt-PA. ResultsSix observational trials with 16,399 participants were identified. The use of IV rt-PA in acute ischemic stroke patients was associated with a lower risk of mortality (hazard ratio .61; 95% confidence interval, .52-.70; P < .00001), and there was no heterogeneity across trials. There was no evidence of an effect on hospital readmission rates and independence rates. ConclusionsIV rt-PA is associated with reduced long-term mortality in acute ischemic stroke patients.