Use Of tPA Research Articles

Abstract TP9: Variability in Endovascular Thrombectomy Treatment in San Diego County

Background: Endovascular thrombectomy (EVT) after Acute Ischemic Stroke (AIS) has shown to improve outcomes in multiple large clinical trials. Most participating centers, however, were large academic hospitals. We studied EVT use in a community setting covering a population of 3.2 million that includes 16 teaching and non-teaching facilities of variable sizes across San Diego County. This provides one of the first comprehensive community-based analyses on early adoption of EVT. Methods: We included all AIS cases treated at an EVT-capable stroke receiving center from the San Diego County EMS Stroke Registry from July 2016 through June 2017. Documented groin puncture date and time indicated EVT treatment. We analyzed the frequency of EVT by center, baseline demographics, admission source, treatment times, use of tPA and discharge disposition. Results: In total, 3,033 AIS patients were treated from July 2016 through June 2017; 266 (8.8%) underwent EVT. The rate per center varied from 1.7 to 17.5%. The mean (±SD) initial NIHSS was 18.0 (±8.4); mean age 74.4(±14.2) years; 48.9% women, 64.7% arrived by EMS, 29.0% by interfacility transfer, 55.3% received tPA, in-hospital mortality was 15.0%, discharge to home 20.7%, to nursing facility 24.4%. Last known well (LKW) was documented in 249 cases (93.6%) of which 201 (80.7%) received EVT within 6 hours of LKW. Mean (±SD) LKW to EVT time for EMS cases was 4.9(±5.9) hours versus 5.8(±6.4) hours for interfacility transfers. The range of mean LKW to EVT was 0.7 hours to 71.4 hours (IQR=2.7-5.3 hours). Arrival to EVT time was documented in 253 cases (95.1%), of which 40.3% received EVT within 90 minutes of arrival at the treating center. The frequency of treatment within 90 minutes from arrival varied between centers from 0.0% to 63.0%. The mean (±SD) time from arrival to EVT was 2.5(±3.9) hours, ranging from 1.6 hours to 11.5 hours between centers (IQR=1.2-2.5 hours). Conclusion: Endovascular thrombectomy treatment rates vary across centers within San Diego County. The overall treatment rate is 8.8%. Nearly three in ten patients arrived to an embolectomy capable center via interfacility transfer, with slightly longer last known well to treatment times. Continued analysis will provide data to support future policy and protocol changes.

Abstract WP300: Characteristics and Prognosis of Transfer Patients to a Comprehensive Stroke Center in the Stroke Belt

Background: The stroke belt has a higher stroke mortality rate compared to other regions of the United States with Alabama recording about 3,000 deaths yearly. The University of Alabama at Birmingham (UAB) is the only comprehensive stroke center (CSC) in Alabama equipped to manage the most complex stroke patients. Objective: The purpose of this study was to determine the characteristics and prognosis of patients transferred to a comprehensive stroke center in the stroke belt. Methods: Data was abstracted from the electronic health records of patients admitted to the stroke service between 2016 and 2018. We assessed differences between transfer and non-transfer patients in terms of demographics, stroke severity, insurance, administration of alteplase (t-PA) and thrombectomy (IA). We also evaluated the relationship between the Alabama state stroke designation of the originating hospital including non-stroke centers (level 0), acute stroke ready hospitals, ASRH (level 3), primary stroke centers, PSC (level 2) and direct admissions to UAB (level 1) and characteristics and prognosis of patients. Results: 1107 patients were assessed for the study with 402(36%) being transfers. Race, NIHSS,TPA and IA use, discharge disposition were associated with the level of stroke center, as shown in the table. Level 2 centers transferred patients with more severe strokes, and a higher proportion of TPA and IA use. Non-transfer patients had the best outcome with Home as their primary discharge location compared to patients transferred from level 2 stroke centers. Conclusion: About 36% of our stroke discharge volume is a result of patients transferred to UAB from outside hospitals. We conclude that Level 2 stroke centers are appropriately transferring patients with more severe stroke to CSCs compared to transfers from non-stroke centers and acute stroke ready hospitals. Some of the patients transferred to a CSC from non-stroke centers and ASRHs could be managed at PSCs.

Abstract 86: Nationwide Differences in Care and Outcomes of Acute Ischemic Stroke

Background: Acute Ischemic Stroke (AIS) remains a leading cause of mortality and morbidity in United States, and poses a major socio-economic burden. Efforts are underway to standardize systems of care for acute stroke treatment. We aim to assess if, despite the attempts towards standardization, regional difference in stroke care practice pattern, cost and/ or outcomes persist. Methods: Healthcare Cost and Utilization Project's Nationwide Inpatient Sample database was reviewed from 2002 to 2014. Hospitalizations with AIS were identified using ICD-9-CM codes 433.xx-436, tPA use by procedure code 99.10. Care is determined based on tPA utilization, length of stay, and cost of hospitalization. Outcomes are determined based on discharge disposition (home or facility) and death. These were further analyzed based on regions; Northeast, South, Midwest and West. Multivariate linear regression model and Cochran Armitage trend test used for the analysis. Results: AIS admissions increased throughout the US, more so in the South. There is an increase in tPA utilization all regions, which is significantly higher in the West compared to other regions. Midwest and South have significantly lower cost of hospitalization compared to West despite having higher length of stay. (Graph). Conclusion: AIS care is noted to be remarkably non-uniform across the USA. This lack of uniformity seems to affect outcomes. Further studies are required to determine the causation of these findings.

Abstract WP37: Real-World Applicability of Thrombectomy in Anterior Circulation Large Vessel Occlusion Strokes Treated in the Extended Window: Analysis of the Prospective Trevo Registry

Background: Two recent trials showed a strong benefit of thrombectomy in the extended window. However, these studies were performed in selected centers and utilized strict inclusion criteria. We aim to evaluate the outcomes of thrombectomy in a large prospective cohort treated outside the rigid clinical trial setting. Methods: Trevo Registry patients with ICA, MCA-M1 or M2 occlusions and pre-morbid mRS0-2 were categorized according to time-from-last-seen-well (TLSW) to puncture as early (0-6hours) vs. late (6-24hours). Uni- and multivariate analyzes were performed to identify good outcome (90-day mRS0-2) predictors. Subgroup analyses were performed for the basic DAWN (age >=18, NIHSS >=10, ICA or M1 occlusion, pre-morbid mRS 0-1) and DEFUSE 3 (age 18-90, NIHSS >=6, ICA or MCA-M1 occlusion, mRS 0-2) trial criteria. Results: As compared to the late (n=430), early patients (n=1173) were older (70 vs 68, p=0.011) and had higher IV tPA use (69 vs 25%, p<0.001), lower smoking frequency (33 vs 40%, p=0.011), larger baseline infarcts (21.2 vs 15.6 cc, p=0.045), less frequent ICA occlusions (18 vs 24%, p=0.015), and a trend towards higher admission NIHSS (16 vs 15, p=0.09). Despite significantly longer TLSW to puncture (3.5 vs 9.6 h, p<0.001), late patients had similar rates of mTICI2b-3 (92 vs 94%, p=0.20), good outcomes (60 vs 56%, p=0.128), symptomatic ICH (1.5 vs.1.4%, p=0.84), and 90-day-mortality (10.9 vs.11.4%, p=0.79). Age (OR 0.96, 95%CI [0.96-0.97]), admission-NIHSS (0.91 [0.89-0.93]), baseline mRS (0.49 [0.40-0.60]), ASPECTS >= 6 (1.37 [1.07-1.75]), DM (0.58 [0.44-0.77]), and time to treatment (0.98 [0.97-1.00]) were independent predictors of good outcomes. Imaging modality did not predict outcomes. Similar findings were observed in the early versus late DAWN-like (n=709 vs 257) and DEFUSE 3-like (n=855 vs 273) cohorts. There was great similarity between the outcomes of the Trevo Registry subsets vs their analogous RCTs: early DAWN-like vs SWIFT Prime (90-day mRS 0-2: 57.5 vs 60%; 90-day mRS 6: 11.% vs 9%), Late DAWN-like vs DAWN (50.2 vs 48.6%; 10.6 vs 18%), and Late DEFUSE 3-like vs DEFUSE 3 (52 vs 45%; 10.3 vs 14%). Conclusions: Our study provides favorable data for the generalizability of the safety and efficacy of thrombectomy in the “real-world” setting.

Abstract WP284: Tpa for Patients Found to Have Stroke Mimics is Safe via Telemedicine

Introduction: tPA use is safe over telemedicine (TM) in acute ischemic stroke (AIS). Risk of tPA for stroke mimics (SM) is low when administered in-person. Assessment of SM over TM may differ than in-person given physical barriers. We evaluated differences between patients with a final diagnosis of SM versus AIS, who were treated with tPA via TM. Methods: We identified patients in our TM stroke registry (9/2015-12/2017) who received tPA for suspected AIS. We compared baseline patient characteristics and comorbidities, along with outcomes after tPA, between AIS and SM patients. Results: 693 patients received tPA via TM. Of these, 16.6% were found to have SM (13.2% were noted for in-person evaluations at our Comprehensive Stroke Center). SM patients were younger, less likely to have hypertension and atrial fibrillation, but more likely to have self-reported history of stroke, TIA, or seizure (Table 1). SM patients presented with milder stroke and less likely with face droop (Table 1). Adverse events from tPA in SM patients were minimal, with no observed symptomatic hemorrhages. mRS, discharge disposition, and length of stay were better for SM than AIS patients (Table 2). Door-to-needle time was six minutes longer for SM than AIS patients via TM (Table 2). Conclusion: In circumstances over TM where the diagnosis of AIS is unclear, tPA may take longer to consider but is safe to administer. Certain comorbidities and presenting symptoms may help differentiate SM from AIS via TM.

Abstract TP355: Rate of Deep Vein Thrombosis in Patients When Pharmacological DVT Prophylaxis is Delayed Due to IV tPA Use

Introduction: Deep vein thrombosis (DVT) is associated with pulmonary embolism and reduced post stroke recovery. After thrombolysis, current US guidelines recommend a delay of 24 hours before initiation of pharmacological DVT prophylaxis. We sought to determine the rate of DVT in post-tPA patients with delayed pharmacological prophylaxis. Methods: Using GWTG stroke registry data from three large comprehensive stroke centers in the Northeast, South and West, we analyzed 13,420 consecutive stroke admissions from 02/2002 - 06/2018. Rates of DVT were compared between those with delayed prophylaxis due to post-tPA vs. all others. Chi-square was used for categorial data, T-Test for parametric continuous and Wilcoxon for non-parametric continuous variables. Multiple regression analysis (MV) was used to identify associations. Results: Of the 13,420 patients, 2974 (22.2%) received IV-tPA, 772 (5.8%) underwent EVT, 252 (1.9%) only EVT and 3279 (24.4%) received IV-tPA and/or EVT. There was a total of 536 (4.0%) patients with a documented DVT during the in-hospital stay. The rate of DVT in patients who received IV-tPA was significantly higher than in those who did not (4.6% vs 3.8%, p=0.036). Rates of DVT were 3.8% in patients not receiving tPA or EVT, 4.6% in IV tPA only group, 4.0% in EVT only group and 4.4% in IV tPA and/or EVT group. On univariate analysis Caucasian race, atrial fibrillation, smoking, weakness on presentation and use of IV tPA was significantly associated with DVT. On MV, only age, Caucasian race and a history of smoking was remained significantly associated with DVT. Conclusion: Although the NINDS tPA trial delayed DVT ppx initiation to 24 hrs, ECASS 3 allowed DVT ppx in post tPA patients without delay. Our analysis shows that post-thrombolysis patients with delayed DVT ppx had higher rates of DVT, although this effect did not remain significant on MV analysis. Larger studies to assess the safety of delaying DVT ppx in post tPA patients are warranted.

Abstract WP100: Temporal Trend in the Rates of sICH and Serious Hemorrhage After IV Thrombolysis Among Patients on Dual Antiplatelet Therapy

Introduction: Previous studies have shown conflicting results regarding the risk of symptomatic intracerebral hemorrhage (sICH) following thrombolysis for acute ischemic stroke in the setting of dual antiplatelet therapy (DAPT) use prior to the index stroke. We explored the temporal trend in the rates of sICH and the safety of IV tPA among patients treated with thrombolytics while on DAPT. Methods: Using local GWTG stroke registry data from three large comprehensive stroke centers in Northeast, South and West, we included 2,851 confirmed stroke patients who received tPA from 01/2008 - 06/2018 and plotted the temporal trend of sICH frequency over time, using the GWTG definition of ICH documented by imaging within 36 hours of thrombolysis and with clinical deterioration attributable to hemorrhage. We compared rates of sICH and serious systemic hemorrhage (>3 transfused units of blood within 7 days) between 3 groups of patients stratified by prior antiplatelet use: Group 1- no antiplatelet use, Group 2- monotherapy, Group 3 - DAPT. Results: Of the total 2,851 patients treated with IV tPA, 132 (4.6%) had sICH and 27 (0.9%) had serious systemic hemorrhage. Temporal trends showed a decrease in the overall rates of sICH from 2008 to 2017. The proportion of cases differed by group with 68.7% in Group 1, 31.3% in Group 2 and 4.0% in Group 3. Within Group 2, aspirin was the most common drug (28.1% Aspirin, 2.5% Clopidogrel, 0.7% others). Rates of sICH did not differ by Group (4.5%, 4.8% and 3.5% in Group 1, 2 and 3 respectively (NS). Conclusion: Rates of sICH after IV tPA decreased overtime in our centers, perhaps due to tPA use in milder stroke patients, and better patient selection and post-tPA management. The rate of sICH was similar in patients with no, single or dual antiplatelet therapy before the stroke, suggesting that the concurrent use of DAPT is not a concern prior to thrombolysis. Further studies are needed to confirm our findings.

Abstract TP391: The Smoking Paradox - Does it Exist in Acute Ischemic Stroke Patients Receiving Endovascular Therapy?

Introduction: A “smoking paradox” has been observed in GWTG data whereby patients with an active smoking history paradoxically have lower post stroke mortality and better outcomes after IV thrombolysis than non-smokers. We sought to determine if this effect was present in acute ischemic stroke (AIS) patients who underwent endovascular therapy (EVT). Methods: Using local GWTG stroke registry data from three large comprehensive stroke centers in the Northeast, South and West, we analyzed 13,420 consecutive stroke admissions from 01/2006 - 04/2018 and included all patients with EVT stratified by smoking status. We compared good clinical outcome (discharge to home versus other) and in-hospital mortality using Chi-square for categorial data, T-Test for parametric continuous and Wilcoxon for non-parametric continuous variables. We used multiple regression analysis to identify associations. Results: We identified 772 patients who underwent EVT. Of those, 128 (16%) were smokers. Smokers were younger, more frequently male and presented with fewer stroke risk factors such as CAD/MI and atrial fibrillation. Overall NIHSS was similar, but smokers had a higher frequency of weakness at presentation. (Table). IV tPA use and in-hospital complications (pneumonia and deep vein thrombosis) were similar across the groups. Smoking was associated with good outcome in univariate analysis (OR 1.90; 95% CI 1.25, 2.89, p<0.001) but in multivariable analysis, only age was independently associated with good outcome (OR 0.97; 95% CI 0.96, 0.99, p<0/001) or in-hospital mortality (OR 1.03; 95% CI 1.02, 1.05, p<0.001). Conclusion: Unlike after IV tPA alone, smoking was not associated with a good outcome after multivariable adjustment in AIS patients receiving EVT. This may be due to differences in patient selection, stroke subtype or the effect size of EVT treatment. Replication in independent data sets is needed to confirm this observation.

Abstract TMP13: NIH Stroke Scale Items Associated With Poor Outcomes in Patients 'Too Good To Treat' With IV Alteplase

Introduction: Prior reports showed poor outcomes in patients who did not receive IV tPA after acute ischemic stroke (AIS), due to mild or rapidly improving symptoms. (“too good to treat”, TGTT). Many factors have been associated with poor outcomes in this group of patients. We sought to evaluate individual NIHSS items associated with poor outcomes in these TGTT patients who didn’t receive thrombolysis. Methods: Using the GWTG stroke registry data from a large comprehensive stroke center in the Northeast, we analyzed 9,215 consecutive stroke admissions from 02/2002 - 04/2018 and identified patients who did not receive IV tPA due to TGTT. NIHSS items were grouped into Level of Consciousness (LOC), Language, Vision, Motor, Sensory and Coordination. Factors associated with poor outcome (defined as all discharge locations other than home) and in-hospital mortality were evaluated by univariate and multivariable regression with significance at p<0.05. Results: Of the 9, 215 analyzed patients, 444 (4.8%) didn’t received tPA due to being TGTT despite presenting within 4.5 hours of last know well. Patients with poor outcomes were more likely to be older, female, have a history of diabetes, atrial fibrillation, and present more often with deficits in level of consciousness, vision, motor, language and sensation. On multivariable analysis, age (OR 1.06, 95% CI (1.04, 1.08)), diabetes (OR 3.65, 95% CI (2.00, 6.71)), and deficits in LOC (OR 4.91, 95% CI (2.35, 10.24)) and strength (OR 4.65, 95% CI (2.79, 7.74)) were independently associated with poor outcome. Factors independently associated with in-hospital mortality were age, and deficits in LOC and strength. Conclusion: Half of all patients who did not receive thrombolysis due to TGTT in our sample had poor outcomes and 8.8% of those died in-hospital. Advanced age, and initial deficits in LOC and strength were strong predictors of a poor outcome. When present in milder strokes, these factors warrant careful consideration for tPA use.

Abstract TP35: Rates of Endovascular Therapy in Acute Ischemic Stroke Patients With NIHSS < 6 and Outcomes

Introduction: Prior reports showed poor outcomes in patients who did not receive IV tPA after acute ischemic stroke (AIS), due to mild or rapidly improving symptoms. (“too good to treat”, TGTT). Many factors have been associated with poor outcomes in this group of patients. We sought to evaluate individual NIHSS items associated with poor outcomes in these TGTT patients who didn’t receive thrombolysis. Methods: Using the GWTG stroke registry data from a large comprehensive stroke center in the Northeast, we analyzed 9,215 consecutive stroke admissions from 02/2002 - 04/2018 and identified patients who did not receive IV tPA due to TGTT. NIHSS items were grouped into Level of Consciousness (LOC), Language, Vision, Motor, Sensory and Coordination. Factors associated with poor outcome (defined as all discharge locations other than home) and in-hospital mortality were evaluated by univariate and multivariable regression with significance at p<0.05. Results: Of the 9, 215 analyzed patients, 444 (4.8%) didn’t received tPA due to being TGTT despite presenting within 4.5 hours of last know well. Patients with poor outcomes were more likely to be older, female, have a history of diabetes, atrial fibrillation, and present more often with deficits in level of consciousness, vision, motor, language and sensation. On multivariable analysis, age (OR 1.06, 95% CI (1.04, 1.08)), diabetes (OR 3.65, 95% CI (2.00, 6.71)), and deficits in LOC (OR 4.91, 95% CI (2.35, 10.24)) and strength (OR 4.65, 95% CI (2.79, 7.74)) were independently associated with poor outcome. Factors independently associated with in-hospital mortality were age, and deficits in LOC and strength. Conclusion: Half of all patients who did not receive thrombolysis due to TGTT in our sample had poor outcomes and 8.8% of those died in-hospital. Advanced age, and initial deficits in LOC and strength were strong predictors of a poor outcome. When present in milder strokes, these factors warrant careful consideration for tPA use.

Abstract WP394: Impact of MRI/A versus CTA/P versus Direct Angiosuite Triage Protocols in Stroke Care Performance and Outcome of Transferred Patients for Endovascular Thrombectomy

Introduction: Transferred thrombectomy patients face additional time delays that might worsen outcome when compared to direct admission. In 2015, we moved from an MRI/A to a CTA/P protocol to decrease treatment times in transferred patients. In 2017, we initiated a direct admission to angiosuite (DAN) strategy. Herein, we aim to describe procedural and clinical outcomes in transfer patients with acute LVO stroke triaged by these protocols. Method: We reviewed demographics, clot location, and treatment times for all thrombectomies from 2013 to June 2018. Primary outcome was MRS at 90 days. Secondary outcomes were door to groin time, difference between NIHSS at admission and discharge (ΔNIHSS). Distributions are analyzed with Wilcoxon Rank, chi-squared and Fisher’s Exact Tests. Logistic regression is used to evaluate MRS and mortality outcomes and adjusted for clot location, admission NIHSS and tPA use. Results: The analysis includes 178 patients: 25 MRI/A, 130 CT/A/P, and 23 DAN. The groups significantly differ by tPA (16% vs 4% vs 13%, p=0.03), NIHSS at arrival (median 16 vs 17 vs 21, continuous p=0.03) and clot location (ICA 8% vs 20% vs 35%, BA 24% vs 10% vs 26%, p=0.01) for MRI, CT, and DAN respectively. There is significant reduction in median door to groin time between all groups (MRI 170 min., CT 84 min., DAN 16 min., p<0.001). The median ΔNIHSS is significantly different between CT and MRI (10 vs 4, p=0.01) and borderline significant between DAN and MRI (11 vs 4, p=0.07). There is a trend towards decrease disability (MRS 4-5) for DAN patients when compared to MRI at both discharge (OR=0.847, 95% CI 0.18, 4.10) and 90 days (OR=0.38, 95% CI 0.07, 2.10). There is significant increased risk of mortality when comparing DAN and MRI at 90 days (p=0.02). Conclusion: DAN is feasible with faster procedural times and may have clinical benefit in select patients. RCTs are needed to assess the advantages and harm of decreasing imaging in benefit of time.

Impact of Participation in a Telestroke Network on Clinical Outcomes.

A telestroke program, known as the Remote Evaluation for Acute Ischemic Stroke program, has been implemented in Georgia since 2003. This study examined whether a hospital's participation in a telestroke network was associated with improvement in clinical outcomes and quality indicators. An observational study was conducted using data from the Georgia Coverdell Acute Stroke Registry between September 2005 and September 2016 for patients aged ≥18 years with ischemic stroke. We use a difference-in-differences approach to compare the following clinical outcomes and quality indicators among those admitted at hospitals within and outside of the Remote Evaluation for Acute Ischemic Stroke network: tPA (tissue-type plasminogen activator) use, complications related to tPA use, door-to-needle time, ambulation at discharge, discharge status, and destination. Logistic regression models and a propensity score weighting approach were performed to adjust for patients' age, sex, race, insurance coverage, arrival mode, ambulatory status before the current stroke, stroke severity, medical history, admission time, and hospital bed size. A total of 25 494 patients with ischemic stroke admitted at 15 nonteaching hospitals located outside of the Atlanta metropolitan area were included in the analysis. After propensity score weighting, hospitals participated in a telestroke network was not associated with a significant increase in the rate of tPA use, while it was significantly associated with a modest decline in the rate of complications related to tPA (-5.9%; 95% CI, -9.2% to -2.6%). Telestroke participation showed no significant difference in other clinical outcomes and quality measures except for a marginally significant decrease in in-hospital mortality (-1.1%; 95% CI, -2.2% to -0.1%). Although a slight decrease in tPA complication was observed among hospitals participating in the telestroke network, overall the impact of telestroke participation on a hospital's stroke care quality was not statistically significant based on our observational study.

Evidence-Based Performance Measures and Outcomes in Patients With Acute Ischemic Stroke.

Stroke is the leading cause of death in China. Despite the wide dissemination of evidence-based guidelines, data about adherence to these in routine clinical practice are scarce. We conducted a study using a nationwide registry to evaluate the implementation of evidence-based stroke performance indicators and associated guidelines, for patients with an ischemic stroke in China. The China National Stroke Registry is a prospective cohort study, including 12 416 patients diagnosed with acute ischemic stroke from 132 hospitals across China, for 1 year beginning September 2007. Twelve performance indicators were selected to evaluate the quality of stroke care. Multivariable Cox models were used to determine the association between optimal compliance and clinical outcomes. Conformity with performance measures ranged from a median of 6.5% for the use of intravenous tPA (tissue-type plasminogen activator) to 81.8% for early use of antithrombotics. The optimal compliance with all in-hospital measures was associated with 1-year death after admission (hazard ratio, 0.66; 95% CI, 0.55-0.79). The optimal compliance with all discharge measures was associated with the 1-year death after discharge (hazard ratio, 0.55; 95% CI, 0.44-0.69), 1-year stroke recurrence (hazard ratio, 0.81; 95% CI, 0.70-0.93), and favorable functional outcomes (defined as modified Rankin Scale score of ≤2) (hazard ratio, 1.10; 95% CI, 1.04-1.16). Adherence to evidence-based ischemic stroke care measures in China revealed substantial gaps, and select measures were associated with improved outcomes. These findings support the need for ongoing quality measurement and improvement in stroke care in China.

Expansion Of Telestroke Services Improves Quality Of Care Provided In Super Rural Areas.

Telestroke is a telemedicine intervention that facilitates communication between stroke centers and lower-resourced facilities to optimize acute stroke management. Using administrative claims data, we assessed trends in telestroke use among fee-for-service Medicare beneficiaries with acute ischemic stroke and the association between providing telestroke services and intravenous tissue plasminogen activator (IV tPA) and mechanical thrombectomy use, mortality, and medical expenditures, by urban versus rural county of residence in the period 2008-15. The proportion of ischemic stroke cases receiving telestroke increased from 0.4 to 3.8 per 1,000 cases, with usage highest among younger, male, non-Hispanic white, and patients in rural or super rural areas (super rural is the bottom quartile of rural areas. Compared with patients receiving usual care, those receiving telestroke had greater IV tPA and mechanical thrombectomy use regardless of county type, while those in super rural counties had lower thirty-day all-cause mortality. Despite increased telestroke use, rural patients remained less likely than urban patients to receive IV tPA. The findings suggest that telestroke service expansion efforts have increased, especially in rural and super rural counties, and have improved outcomes.

MRI-Guided High-Intensity Focused Ultrasound as an Emerging Therapy for Stroke: A Review.

Stroke, either ischemic or hemorrhagic, accounts for significantly high morbidity and mortality rates around the globe effecting millions of lives annually. For the past few decades, ultrasound has been extensively investigated to promote clot lysis for the treatment of stroke, myocardial infarction, and acute peripheral arterial occlusions, with or without the use of tPA or contrast agents. In the age of modern minimal invasive techniques, magnetic resonance imaging-guided high-intensity focused ultrasound is a new emerging modality that seems to promise therapeutic utilities for both ischemic and hemorrhagic stroke. High-intensity focused ultrasound causes thermal heating as the tissue absorbs the mechanical energy transmitted by the ultrasonic waves leading to tissue denaturation and coagulation. Several in-vitro and in-vivo studies have demonstrated the viability of this technology for sonothrombolysis in both types of stroke and have warranted clinical trials. Apart from safety and efficacy, initiation of trials would further enable answers regarding its practical application in a clinical setup. Though this technology has been under study for treatment of various brain diseases for some decades now, relatively very few neurologists and even neurosurgeons seem to be acquainted with it. The aim of this review is to provide basic understanding of this powerful technology and discuss its clinical application and potential role as an emerging viable therapeutic option for the future management of stroke.

Epidemiology and Outcomes of Ischemic Stroke and Transient Ischemic Attack in the Adult and Geriatric Population

Background: Rate of ischemic strokes and transient ischemic attacks (TIAs) increases with age. There is lack of evidence on how age affects treatment strategies and outcomes. Our aim is to compare epidemiology of ischemic strokes and TIAs in adult and geriatric populations including risk factors, treatment delivered, and outcomes. Design: We designed a retrospective cross-sectional review of patients admitted to neurology with diagnosis of stroke or TIA from 2010 to 2015. Obtained variables were: age, sex, risk factors, acute therapy, National Institutes of Health Stroke Scale on admission and discharge, and disposition. Means, confidence intervals, or percentages were calculated as appropriate. Results: Around 1,457 patients were divided into two groups: younger than 80 (n = 968) and 80 and older (n = 487). Rates of stroke and TIA were similar across younger and older groups (11% versus 12% TIA and 89% versus 88% stroke, respectively). Younger patients had lower admission National Institutes of Health Stroke Scale (mean 4.64 versus 7.84 in older group) and greater improvement on discharge (mean change −1.51 versus −1.29 accordingly). Older patients received tissue-type plasminogen activator (tPA) more often than younger patients, but no difference in rates of thrombectomy between groups. Older patients were more likely to have hypertension, atrial fibrillation, coronary artery disease, and less likely to be a smoker. On discharge, younger patients with stroke were discharged home or to acute rehab more frequently, regardless of tPA administration. Conclusions: Older patients had more comorbidities, received tPA more often, and had worse outcomes regardless of use of intravenous tPA or thrombectomy, and were more frequently institutionalized after discharge.

The Use of tPA in the Treatment of Frostbite: A Systematic Review.

The use of tissue plasminogen activator (tPA) for the treatment of frostbite has been reported and advocated, but its efficacy has not been well established. We conducted a systematic review to guide physicians on the role of tPA in the treatment of frostbite. Our hypothesis was that the use of tPA improves clinical outcomes, as measured by amputation rate. We searched MEDLINE (PubMed) and EMBASE for primary research articles on the use of tPA for the treatment of extremity frostbite. Information related to study design, outcomes, and complications was extracted. A total of 204 citations were screened, and then 35 abstracts and 24 reports were reviewed. Fifteen studies met the standard for final review. One randomized, prospective study; 3 cohort studies; 8 case series; and 3 case reports were found. A total of 208 patients were treated. Differences in protocols, inclusion criteria, and outcomes measures prevented combining the study results. In all the studies, the authors reported that the use of tPA was or may have been useful in reducing amputation rates or increasing tissue salvage. Complication rates ranged from 0% to 100%, with a combined rate of 13%. The quality of the evidence was low. Due to the low scientific quality of the studies, the efficacy of tPA in reducing amputation rates cannot currently be established. Randomized, prospective trials or well-controlled cohort studies are needed to better assess the role of tPA. Consideration should be given to limiting its use to research protocols.

Neutrophils in tPA-induced hemorrhagic transformations: Main culprit, accomplice or innocent bystander?

The risk of intracerebral hemorrhage still greatly limits the use of tPA in stroke patients. Research is ongoing in order to identify the pathophysiological mechanisms at play, detect predictive biomarkers and discover new pharmacological targets to develop preventive or curative treatments. Going through experimental and clinical studies, this review focuses on the role of neutrophils as key predictive biomarkers for thrombolysis-induced hemorrhages and as pharmacological targets to limit their occurrence. To date, there are no established pharmacological modulators of neutrophils for ischemic stroke and its hemorrhagic complications. Several strategies are under evaluation, including lipid-lowering drugs, free radical scavengers, or minocycline, as well as non-pharmacological interventions such as physical exercise.

THE FIBRINOLYTIC ALTERATION ASSOCIATED WITH DAILY ADMINISTRATION OF SILDENAFIL

Objective: The objective of this study was to determine the fibrinolytic alteration associated with daily administration of sildenafil.Methods: A total of 12 adult male rabbits without mortality rate had been fed standard and subdivided into four groups; their average weight was 1.5, 2.5, 1.9, and 2 kg randomly selected during the period of March 2012–July 2013. Depending on weight, the control groups (2.25 mg/1.5 kg day) and sildenafil groups (3 mg/2 kg/day, 2.85 mg/1.9 kg/day, and 1.7 mg/2.5 kg/day) were injected by normal saline and sildenafil concentration, respectively to create four groups, every group was composed of three rabbits; saline rabbit (control group, n=3) and sildenafil rabbits (sildenafil group, n=9). All rabbit’s plasma samples have been investigated for prothrombin time, activated partial thromboplastin time, fibrinogen, plasminogen activator inhibitor-1 (PAI-1), prothrombin fragment 1+2, tissues plasminogen activator (tPA), plasmin antiplasmin (PAP), plasminogen, and D-dimer after 24 h of administration.Results: The PAP level was significantly (p<0.05) decreased following sildenafil injection. Sildenafil-injected (3 mg/ml) rabbits had decreased the means of PAI-1 and mean tPA, as early as 1-day post-injection, with a considerable lower PAP first determined 3 days after injection that continued into each rabbit 2 and 3.Conclusion: Better strategies are to initiate and manipulate this drug ought to reduce the chance of each thrombosis and hemorrhage, at the same time as minimizing the need for laboratory monitoring with the aid of the use of PAI-1, tPA, and PAP checks.

Impact of Bradykinin Generation During Thrombolysis in Ischemic Stroke.

Ischemic stroke is one of the leading causes of death and disability worldwide. Current medical management in the acute phase is based on the activation of the fibrinolytic cascade by intravenous injection of a plasminogen activator (such as tissue-type plasminogen activator, tPA) that promotes restauration of the cerebral blood flow and improves stroke outcome. Unfortunately, the use of tPA is associated with deleterious effects such as hemorrhagic transformation, symptomatic brain edema, and angioedema, which limit the efficacy of this therapeutic strategy. Preclinical and clinical evidence suggests that intravenous thrombolysis generates large amounts of bradykinin, a peptide with potent pro-inflammatory, and pro-edematous effects. This tPA-triggered generation of bradykinin could participate in the deleterious effects of thrombolysis and is a potential target to improve neurological outcome in tPA-treated patients. The present review aims at summarizing current evidence linking thrombolysis, bradykinin generation, and neurovascular damage.