Editors' note: Thrombolysis for acute ischemic stroke in the unwitnessed or extended therapeutic time window

Neurology ◽  
2020 ◽  
Vol 95 (18) ◽  
pp. 844.1-844
Author(s):  
James E. Siegler ◽  
Steven Galetta
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Time Window ◽  
Therapeutic Time Window

Abstract T P10: Therapeutic Time Window for Endovascular Therapy of Acute Ischemic Stroke Depends on THRIVE Score: A Retrospective Single-center Study

Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Kenichi Todo ◽  
Nobuyuki Sakai ◽  
Tomoyuki Kono ◽  
Taku Hoshi ◽  
Hirotoshi Imamura ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Endovascular Therapy ◽  
Time Window ◽  
Medical Center ◽  
Multivariate Logistic Regression Analysis ◽  
Symptom Duration ◽  
Vascular Events ◽  
Good Outcome ◽  
Therapeutic Time Window

Background and purpose: The outcome after endovascular therapy in acute ischemic stroke is associated with onset-to-reperfusion time (ORT). The Totaled Health Risks in Vascular Events (THRIVE) score is also an important pre-thrapeutic predictor of outcome. We hypothesized that the therapeutic time window is narrower in patients with the higher THRIVE score. Methods: We retrospectively studied consecutive 109 ischemic stroke patients with successful reperfusion after endovascular therapy between October 2005 and March 2014 at a single institute (Kobe City Medical Center General Hospital). Inclusion criteria was as follows: National Institutes of Health Stroke Scale (NIHSS) score ≥8, stroke symptom duration ≤8 h, premorbid modified Rankin Scale (mRS) score ≤2, and thrombolysis myocardial infarction score 2-3. We analyzed the relationships of ORT, THRIVE score, and THRIVE+ORT score with good outcome (mRS ≤2 at 3 months). The THRIVE+ORT score was defined as the sum of the THRIVE score and ORT (h). Results: Median ORT was 5.5 h (IQR; 4.4-7.1 h), median THRIVE score was 5 (IQR; 4-6), and median THRIVE+ORT score was 10.8 (IQR; 9.2-12.5). Good outcome rates for patients with ORT ≤4 h, >4 and ≤6 h, >6 and ≤8 h, and >8h were 50.0%, 45.8%, 37.0%, and 21.4%, respectively (p=0.3), those with THRIVE score ≤3, >3 and ≤5, >5 and ≤7, and >7 were 57.1%, 51.4%, 28.3%, and 20.0%, respectively (p9 and ≤11, >11 and ≤13, and >13 were 64.0%, 44.1%, 34.4%, and 16.7%, respectively (p<0.05). Multivariate logistic regression analysis revealed that THRIVE+ORT score was an independent predictor of good outcome after adjusted for THRIVE score (odds ratio [OR], 1.367; 95% confidence interval [CI], 1.082-1.728) or after adjusted for ORT (OR, 1.517: 95% CI, 1.160-1.983). Conclusion: Our study showed that THRIVE+ORT score was associated with outcome that was independent from THRIVE score or ORT. This is the first report to suggest that patients with the higher THRIVE score require the shorter ORT for good outcome.

Current Perspectives Regarding Stem Cell-based Therapy for Ischemic Stroke

2018 ◽  
Vol 24 (28) ◽  
pp. 3332-3340 ◽  
Author(s):  
Kyeong-Ah Kwak ◽  
Ho-Beom Kwon ◽  
Joo Won Lee ◽  
Young-Seok Park
Keyword(s):  
Clinical Trials ◽  
Stem Cell ◽  
Ischemic Stroke ◽  
Time Window ◽  
Experimental Studies ◽  
Cell Type ◽  
Stroke Treatment ◽  
Cell Based Therapy ◽  
Regenerative Approach ◽  
Therapeutic Time Window

Stroke is a leading cause of death and disability worldwide. Conventional treatment has a limitation of very narrow therapeutic time window and its devastating nature necessitate a novel regenerative approach. Transplanted stem cells resulted in functional recovery through multiple mechanisms including neuroprotection, neurogenesis, angiogenesis, immunomodulation, and anti-inflammatory effects. Despite the promising features shown in experimental studies, results from clinical trials are inconclusive from the perspective of efficacy. The present review presents a synopsis of stem cell research on ischemic stroke treatment according to cell type. Clinical trials to the present are briefly summarized. Finally, the hurdles and issues to be solved are discussed for clinical application.

Abstract TMP2: Is Eptifibatide a Viable and Safe Option as Stand-alone Therapy for Acute Ischemic Stroke Patients?

Stroke ◽  
2016 ◽  
Vol 47 (suppl_1) ◽  
Author(s):  
Daniel Korya ◽  
Mohammad Moussavi ◽  
Siddhart Mehta ◽  
Jaskiran Brar ◽  
Harina Chahal ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Time Window ◽  
T Test ◽  
Bleeding Complications ◽  
Stroke Severity ◽  
Paired Samples ◽  
Group A ◽  
Group B ◽  
Iv Tpa

Introduction: The list of contraindications for IV tPA in acute ischemic stroke (AIS) is often too long and may lead to physicians opting to offer no treatment for certain strokes. An alternative treatment is proposed in cases where IV tPA is not an option due to time-window restrictions or contraindications. We compared the stroke severity, outcomes and safety of IV eptifibatide when compared with IV tPA. Methods: Patients who presented to a community based university affiliated comprehensive stroke center from 2012-15 with AIS over a two-year period were included in the study. Those who qualified for IV tPA, and were treated, were compared with patients who only received IV eptifibatide. The initial NIH Stroke Score (NIHSS), 24-hour NIHSS, discharge NIHSS (DCNIHSS), discharge mRS (DCmRS) and symptomatic ICH rates were compared with a paired samples t-test to determine significance of difference between the means. SPSS Version 22 was used for all data analysis. Results: A total of 864 patients presented with AIS in the evaluated time period and of those 166 met study criteria. There were 119 patients who received IV tPA alone (group A) and 47 patients received eptifibatide (group B). The mean initial NIHSS, 24-NIHSS, DCNIHSS, DCmRS and percent bleeding complications for group A were: 11.2, 10.8, 8.6, 3.1 and 6%. For group B the figures were: 6.7, 4.8, 4.3, 1.7 and 0%, respectively. Group A was compared with group B in a paired samples T-test and yielded -4.3, -6.2, -6, -1.5 (p=.0001 to .04) for initial, 24-hour, discharge NIHSS and discharge mRS, respectively. The difference between initial and discharge NIHSS between the two groups was -2.7 (p=.009), favoring IV tPA. Conclusion: In patients who are either outside the time-window or with contraindications to IV tPA, eptifibatide may be a safe alternative and appears to be efficacious. None of the patients who were started on eptifibatide had bleeding complications and they had a statistically significant improvement in their level of disability and stroke severity at discharge. A limitation of this study is that patients in group A had significantly worse initial NIHSS compared with group B. To better evaluate the efficacy of eptifibatide, a larger, prospective study should be initiated.

Abstract W P32: Association of Low Cerebral Blood Volume With Negative FLAIR Hyperintensity in Acute Ischemic Stroke

Stroke ◽  
2014 ◽  
Vol 45 (suppl_1) ◽  
Author(s):  
Nandakumar Nagaraja ◽  
Marie Luby ◽  
Matthew Edwardson ◽  
Ramin Zand ◽  
Lawrence L Latour
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Blood Volume ◽  
Early Phase ◽  
Cerebral Blood Volume ◽  
Time Window ◽  
Linear Regression Analysis ◽  
Onset Time ◽  
Stroke Onset ◽  
Imaging Biomarker

Objective: FLAIR hyperintensity is being used in clinical trials as a surrogate imaging biomarker for stroke onset time to test the safety of thrombolysis. Studies have shown that patients with negative and positive FLAIR hyperintensity overlap at similar time points from stroke onset in the early phase of acute ischemic stroke (AIS). Hyperintensity on FLAIR MRI likely represents increased tissue water content. We sought to determine if cerebral blood volume (CBV) mediates FLAIR hyperintensity in the early phase of AIS. Methods: AIS patients seen in 2012 were included in the study if i) onset time was known, ii) an MRI with perfusion was performed within 12 hours of onset time, iii) had imaging confirmed vascular occlusion of ICA, M1, or M2. Following co-registration of raw perfusion images with FLAIR, CBV maps were generated using PMA ASIST™ software. Two raters blinded to clinical information separately evaluated the DWI, FLAIR and CBV maps and measured the signal intensity ratio (SIR) for the brightest region on FLAIR normalized by homologous contra-lateral tissue. The SIR was similarly measured for CBV in same region. FLAIR negative was defined as SIR<1.15, “Low CBV” was defined as CBV SIR <0.5. Results: One hundred eighty two patients were screened and 30 met all study criteria; 21 women, with mean age of 71 (± 16) years and median NIHSS 18 (IQR 9-22). Using linear regression analysis, CBV SIR was associated with FLAIR SIR (p <0.049). In the 0-3hr time window, overall CBV was not associated with FLAIR hyperintensity. However, in the 3-7.5hr time window, patients with negative FLAIR were more likely to have low CBV and conversely, patients with positive FLAIR were more likely to have normal CBV. Conclusion: CBV likely mediates FLAIR hyperintensity in 3-7.5hr of stroke onset but it has less impact on FLAIR hyperintensity in the first 3 hours of AIS. Low CBV could be a potential surrogate imaging biomarker in addition to FLAIR hyperintensity in the early phase of AIS.

Peptide5 attenuates rtPA related brain microvascular endothelial cells reperfusion injury via the Wnt/β-catenin signalling pathway

2021 ◽  
Vol 18 ◽  
Author(s):  
Weimin Ren ◽  
Chuyi Huang ◽  
Heling Chu ◽  
Yuping Tang ◽  
Xiaobo Yang
Keyword(s):  
Endothelial Cells ◽  
Ischemic Stroke ◽  
Endothelial Cell ◽  
Cell Injury ◽  
Time Window ◽  
Microvascular Endothelial Cells ◽  
Brain Microvascular Endothelial Cells ◽  
Endothelial Cell Injury ◽  
Endothelial Cell Death ◽  
Therapeutic Time Window

Aims: Brain vascular endothelial cell dysfunction after rtPA treatment is a significant factor associated with poor prognosis, suggesting that alleviation of rtPA-related endothelial cell injury may represent a potential beneficial strategy along with rtPA thrombolysis. Background: Thrombolysis with recombinant tissue plasminogen activator (rtPA) is beneficial for acute ischemic stroke but may increase the risk of hemorrhagic transformation (HT), which is considered ischemia-reperfusion injury. The underlying reason may contribute to brain endothelial injury and dysfunction related to rtPA against ischemic stroke. As previous studies have demonstrated that transiently blocked Cx43 using peptide5 (Cx43 mimetic peptide) during retinal ischemia reduced vascular leakage, it is necessary to know whether this might help decrease side effect of rtPA within the therapeutic time window. Objective: This study aims to investigate the effects of peptide5 on rtPA-related cell injury during hypoxia/reoxygenation (H/R) within the therapeutic time window. Methods: In this study, we established a cell hypoxia/reoxygenation H/R model in cultured primary rat brain microvascular endothelial cells (RBMECs) and evaluated endothelial cell death and permeability after rtPA treatment with or without transient peptide5. In addition, we also investigated the potential signaling pathway to explore the underlying mechanisms preliminarily. Results: The results showed that peptide5 inhibited rtPA-related endothelial cell death and permeability. It also slightly increased tight junction (ZO-1, occluding, claudin-5) and β-catenin mRNA expression, demonstrating that peptide5 might attenuate endothelial cell injury by regulating the Wnt/β-catenin pathway. The following bioinformatic exploration from the GEO dataset GSE37239 was also consistent with our findings. Conclusion: This study showed that the application of peptide5 maintained cell viability and permeability associated with rtPA treatment, revealing a possible pathway that could be exploited to limit rtPA-related endothelial cell injury during ischemic stroke. Furthermore, the altered Wnt/β-catenin signaling pathway demonstrated that signaling pathways associated with Cx43 might have potential applications in the future. This study may provide a new way to attenuate HT and assist the application of rtPA in ischemic stroke.

Abstract TP52: Endovascular Therapy in Patients Over 80 Years of Age With Acute Ischemic Stroke

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Janhavi M Modak ◽  
Syed Daniyal Asad ◽  
Jussie Lima ◽  
Amre Nouh ◽  
Ilene Staff ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Symptom Onset ◽  
Time Window ◽  
Extended Time ◽  
Stroke Patients ◽  
Stroke Outcomes ◽  
Stroke Treatment ◽  
Group A ◽  
Group B

Introduction: Acute ischemic stroke treatment has undergone a paradigm shift, with patients being treated in the extended time window (6-24 hours post symptom onset). The purpose of this study is to assess outcomes in stroke patients above 80 years of age undergoing endovascular treatment (EVT) in the extended time window. Methods: Acute ischemic stroke patients presenting to Hartford Hospital between January 2017 to June 2019 were considered for the study. Stroke outcomes in patients above 80 years of age with anterior circulation ischemic strokes presenting in the extended time window (Group A, n=30) were compared to a younger cohort of patients below 80 years (Group B, n=31). Patients over 80 years treated in the traditional time window (within 6 hours of symptom onset) served as a second set of controls (Group C, n=40). Statistical analysis was performed with a significance level of 0.05 Results: For angiographic results, there were no statistically significant differences in terms of good outcomes (TICI 2b-3) among patients of Group A, when compared to Groups B or C (p>0.05). For the endovascular procedures, no significant differences were noted in the total fluoroscopy time (Median Group A 44.05, Group B 38.1, Group C 35.25 min), total intra-procedure time (Median Group A 144, Group B 143, Group C 126 min) or total radiation exposure (Median Group A 8308, Group B 8960, Group C 8318 uGy-m 2 ). For stroke outcomes, a good clinical outcome was defined as modified Rankin score of 0-2 at discharge. Significantly better outcomes were noted in the younger patients in Group B - 35.4%, when compared to 13.3% in Group A (p=0.03). Comparative outcomes differed in the elderly patients above 80 years, Group A -13.3% vs Group C - 25%, although not statistically significant (p=0.23). There was a significant difference in mortality in patients of Group A - 40% as compared to 12% in the younger cohort, Group B (p= 0.01). Conclusions: In the extended time window, patients above 80 years of age were noted to have a higher mortality, morbidity compared to the younger cohort of patients. No significant differences were noted in the stroke outcomes in patients above 80 years of age when comparing the traditional and the extended time window for stroke treatment.

scholarly journals Perfusion Imaging in the 3-hour Time Window Predicts a tPA-associated Hemorrhage in Acute Ischemic Stroke

2015 ◽  
Vol 19 (3) ◽  
pp. 68-69
Author(s):  
Srikant Rangaraju ◽  
Adam Edwards ◽  
Seena Dehkharghani ◽  
Fadi Nahab
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Perfusion Imaging ◽  
Time Window
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