Recombinant Tissue-Type Plasminogen Activator Study of Wake-Up Ischemic Strokes Guided by Rapid MRI

Background: rt-PA intravenous thrombolytic therapy and its efficacy have been widely recognized and proved for strokes. However, for patients with wake-up ischemic stroke (WUIS), they lose the opportunity to receive rt-PA intravenous thrombolytic therapy because of the difficulty of determining the onset time window. Aim: This study is aimed at investigating the intravenous thrombolytic therapy of WUIS guided by rapid MRI. Methods: Data were collected from patients with acute ischemic stroke within 4.5 h and from WUIS patients with uncertain onset time window, who received the treatment of rt-PA intravenous thrombolytic therapy in our hospital from November 2006 to April 2018. The improved Rankin scale was used to evaluate neurological function recovery. According to the Rankin scale score, patients were divided into two groups: those with good prognosis (modified Rankin scale [mRS] score 0–1) and those with poor prognosis (mRS score 2–6). Results: A total of 253 patients received rt-PA intravenous thrombolysis after head MRI evaluation; this included 177 cases of acute ischemic stroke and 76 cases of WUIS (which contains 2 death cases, 0.8% mortality; 3 cases of symptomatic bleeding, 1.2% bleeding rate; and 5 cases of aggravation, 2.0% aggravation rate). There was no statistical difference between the baseline data from the acute ischemic stroke patients with 4.5 h onset time window and the baseline data from the WUIS patients with undetermined onset time window, when the treatment was guided by rapid MRI. There were also no significant statistical differences in National Institutes of Health Stroke Scale score, Rankin scale score, symptomatic bleeding, death and aggravation of the disease between the 2 groups at 24 h, 3 days, and 7 days after admission (p < 0.05). Conclusion: According to the characteristic of undetermined onset time window of WUIS, more WUIS patients would be benefited from the rt-PA intravenous thrombolytic treatment when it is conducted under the guidance of rapid MRI.

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Neuroimaging Prediction of Hemorrhagic Transformation for Acute Ischemic Stroke

Cerebrovascular Diseases ◽

10.1159/000521150 ◽

2022 ◽

pp. 1-11

Author(s):

Lan Hong ◽

Tzu-Ming Hsu ◽

Yiran Zhang ◽

Xin Cheng

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Time Window ◽

Treatment Strategies ◽

Onset Time ◽

Intravenous Thrombolysis ◽

Reperfusion Therapy ◽

Hemorrhagic Transformation ◽

Advanced Technology ◽

Future Research

Background: Hemorrhagic transformation (HT) is a common complication of acute ischemic stroke, often resulting from reperfusion therapy. Early prediction of HT can enable stroke neurologists to undertake measures to avoid clinical deterioration and make optimal treatment strategies. Moreover, the trend of extending the time window for reperfusion therapy (both for intravenous thrombolysis and endovascular treatment) further requires more precise detection of HT tendency. Summary: In this review, we summarized and discussed the neuroimaging markers of HT prediction of acute ischemic stroke patients, mainly focusing on neuroimaging markers of ischemic degree and neuroimaging markers of blood-brain barrier permeability. This review is aimed to provide a concise introduction of HT prediction and to elicit possibilities of future research combining advanced technology to improve the accessibility and accuracy of HT prediction under emergent clinical settings. Key Messages: Substantial studies have utilized neuroimaging, blood biomarkers, and clinical variables to predict HT occurrence. Although huge progress has been made, more individualized and precise HT prediction using simple and robust imaging predictors combining stroke onset time should be the future goal of development.

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

Stroke ◽

10.1161/str.45.suppl_1.wp32 ◽

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.

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The Role of Personality Associated with In-Hospital Delay in Intravenous Thrombolysis for Acute Ischemic Stroke

10.21203/rs.3.rs-104374/v1 ◽

2020 ◽

Author(s):

Zhenchan Lu ◽

Caixia Qiu ◽

Xiangyan Yang ◽

Honggang Ma ◽

Shuang Shen ◽

...

Keyword(s):

Ischemic Stroke ◽

Thrombolytic Therapy ◽

Personality Traits ◽

Acute Ischemic Stroke ◽

Big Five ◽

Multivariable Analysis ◽

Intravenous Thrombolysis ◽

Big Five Personality ◽

Effective Strategies

Abstract Background: Decreasing the in-hospital delay is one of the critical effective strategies for thrombolytic therapy for acute ischemic stroke. we examined whether physician personality traits are associated with in-hospital delay in conducting treatment of intravenous thrombolysis for acute ischemic stroke among neurologists.Methods: Overall 354 consecutive patients who received intravenous thrombolysis during a 2.5 year-period in emergency department were included. Self-reported questionnaires of the Big Five Inventory and demographic characteristics were distributed among 13 neurologists. Multivariable analysis was performed to explore the effects of the Big Five Personality Traits on in-hospital delay for acute ischemic stroke. Results: The traits of agreeableness in all physicians decreased the likelihood of in-hospital delay (OR: 0.831, 95% CI: 0.766-0.901, p<0.001). The traits of openness in female physicians (OR:0.646; 95% CI:0.469-0.890; p=0.008) and the traits of extraversion in male physicians (OR:0.613; 95% CI: 0.475-0.791; p<0.001) decreased the likelihood of in-hospital delay. The traits of conscientiousness in female (OR: 1.713, 95% CI: 1.209–2.427; p=0.002) and the traits of openness in male (OR: 1.431; 95% CI: 1.802-1.892; p=0.012) increased the likelihood of in-hospital delay. Conclusions: The study demonstrate that the personality traits of physician are associated with in-hospital delay for thrombolytic therapy in acute ischemic stroke.

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Abstract WMP117: Patterns of All Bleeding Complications Associated with r-tPA Use-experience of an Acadamic Center in China

Stroke ◽

10.1161/str.48.suppl_1.wmp117 ◽

2017 ◽

Vol 48 (suppl_1) ◽

Author(s):

Hong Chang ◽

Xiaojuan Wang ◽

Yuchen Qiao ◽

Jie Zhao ◽

Haiqing Song

Keyword(s):

Risk Factors ◽

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Intravenous Thrombolysis ◽

Tissue Type ◽

Bleeding Complications ◽

High Systolic Blood Pressure ◽

Gingival Bleeding ◽

Hemorrhagic Event ◽

Hemorrhagic Complications

Background and objective: Rapid administration of intravenous recombinant tissue-type plasminogen activator (rt-PA) is the standard treatment for patients with acute ischemic stroke (AIS). While hemorrhage represents as an important and unpredictable complication of thrombolytic treatment, few studies have specifically assessed the prevalence and predictors of bleeding complications among AIS patients in Asia. We assessed characteristics of hemorrhagic complications after intravenous thrombolysis in Chinese AIS patients. Methods: This single-academic-center study retrospectively evaluated 351 acute ischemic stroke patients who received rt-PA intravenously from April 2011 to April 2016. The occurrence and characteristics of any hemorrhagic complications, as well as their associated risk factors were recorded and summarized. Multivariate logistic regression was conducted to analyze significant predictors of bleeding. Results: 134 (38.1%) patients experienced one hemorrhagic event in one or more locations The top seven common sites were gingiva (49.3%), skin (18.3%), urinary system (10.4%), digestive tract (7.5%), intra-cranial cavity (7.5%), mouth (4.4%) and nasal cavity (2.2%). All the gingival bleeding occurred during 1 to 24 hours after thrombolysis and was the first sign of bleeding. Intracranial hemorrhage (both symptomatic and asymptomatic) occurred in 16 patients, of whom 4 presented first with gingival bleeding. Multivariate analysis showed that high systolic blood pressure (SBP) and National Institutes of Health Stroke Scale (NIHSS) score were independent risk factors for hemorrhage post thrombolysis (P<0.05). Conclusions: One out of three AIS patients in this study had a bleeding complication. The most common site of initial hemorrhage after intravenous thrombolysis was gingival, which frequently occurred as the initial bleeding site within 24 hours after thrombolysis. Consistent with literature, elevated SBP and higher NIHSS were the two key predictors of bleeding risk.

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Dabigatran Reversal Before Intravenous Tenecteplase in Acute Ischemic Stroke

Stroke ◽

10.1161/strokeaha.119.028327 ◽

2020 ◽

Vol 51 (5) ◽

pp. 1616-1619 ◽

Cited By ~ 2

Author(s):

James Beharry ◽

Michael J. Waters ◽

Roy Drew ◽

John N. Fink ◽

Duncan Wilson ◽

...

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Functional Outcome ◽

Scale Score ◽

Clinical Laboratory ◽

Intravenous Thrombolysis ◽

Interquartile Range ◽

Large Vessel ◽

Large Vessel Occlusion ◽

Vessel Occlusion

Background and Purpose— Reversal of dabigatran before intravenous thrombolysis in patients with acute ischemic stroke has been well described using alteplase but experience with intravenous tenecteplase is limited. Tenecteplase seems at least noninferior to alteplase in patients with intracranial large vessel occlusion. We report on the experience of dabigatran reversal before tenecteplase thrombolysis for acute ischemic stroke. Methods— We included consecutive patients with ischemic stroke receiving dabigatran prestroke treated with intravenous tenecteplase after receiving idarucizumab. Patients were from 2 centers in New Zealand and Australia. We reported the clinical, laboratory, and radiological characteristics and their functional outcome. Results— We identified 13 patients receiving intravenous tenecteplase after dabigatran reversal. Nine (69%) were male, median age was 79 (interquartile range, 69–85) and median baseline National Institutes of Health Stroke Scale score was 6 (interquartile range, 4–21). Atrial fibrillation was the indication for dabigatran therapy in all patients. All patients had a prolonged thrombin clotting time (median, 80 seconds [interquartile range, 57–113]). Seven patients with large vessel occlusion were referred for endovascular thrombectomy, 2 of these patients (29%) had early recanalization with tenecteplase abrogating thrombectomy. No patients had parenchymal hemorrhage or symptomatic hemorrhagic transformation. Favorable functional outcome (modified Rankin Scale score, 0–2) occurred in 8 (62%) patients. Two deaths occurred from large territory infarction. Conclusions— Our experience suggests intravenous thrombolysis with tenecteplase following dabigatran reversal using idarucizumab may be safe in selected patients with acute ischemic stroke. Further studies are required to more precisely estimate the efficacy and risk of clinically significant hemorrhage.

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Intravenous thrombolysis in acute ischemic stroke patients with negative CT perfusion: a case series

Acta Radiologica Short Reports ◽

10.1177/2047981614543219 ◽

2014 ◽

Vol 3 (7) ◽

pp. 204798161454321

Author(s):

Ratnesh Mehra ◽

Chiu Yuen To ◽

Omar Qahwash ◽

Boyd Richards ◽

Richard D Fessler

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Ct Perfusion ◽

Case Series ◽

Intravenous Thrombolysis ◽

Hemorrhagic Transformation ◽

Tissue Type ◽

Stroke Patients ◽

Radiographic Findings ◽

Type Plasminogen Activator

Background Computed tomography perfusion (CTP) is a commonly used modality of neurophysiologic imaging to aid the selection of acute ischemic stroke patients for neuroendovascular intervention by identifying the presence of penumbra versus infarcted brain tissue. However many patients present with evidence of cerebral ischemia with normal CTP, and in that case, should intravenous thrombolytics be given? Purpose To demonstrate if tissue-type plasminogen activator (tPA)-eligible stroke patients without perfusion defects demonstrated on CTP would benefit from administration of intravenous thrombolytics. Material and Methods We retrospectively identified patients presenting with acute ischemic symptoms who received intravenous tPA (IV-tPA) from January to June 2012 without a perfusion defect on CTP. Clinical and radiographic findings including the NIHSS at presentation, 24 h, and at discharge, symptomatic and asymptomatic hemorrhagic transformation, and the modified Rankin score at 30 days were collected. A reduction of NIHSS of greater than 4 points or resolution of symptoms was considered significant. Results Seventeen patients were identified with a mean NIHSS of 8.2 prior to administration of intravenous thrombolytics, 3.5 after 24 h, and 2.5 at discharge. Among them, 13 patients had significant improvement of NIHSS with a mean reduction of 6.15 points at 24 h. One patient initially improved but had delayed hemorrhagic transformation and died. Two patients had improvement in NIHSS but were not significant and two patients had increased in NIHSS at 24 h, although one eventually improved at discharge. There was no asymptomatic hemorrhagic transformation. Mean mRS at 3 months is 1.76. Conclusion The failure to identify a perfusion deficit by CTP should not be used as a contraindication for intravenous thrombolytics. Criteria for administration of intravenous thrombolytics should still be based on time from symptom onset as previously published by NINDS.

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Using thrombin time to evaluate the efficacy of anticoagulant therapy for acute cerebral infarction

10.21203/rs.3.rs-46163/v1 ◽

2020 ◽

Author(s):

Qianqian Li ◽

Tingjiao Liu ◽

Shanshan Yang

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Time Window ◽

Intravenous Thrombolysis ◽

Clinical Effectiveness ◽

Complete Recovery ◽

Initial Therapy ◽

Thrombin Time ◽

Risk Of Hemorrhage ◽

The Relationship

Abstract Background Although intravenous thrombolysis therapy has been considered as a significant progress in the treatment of acute ischemic stroke, there are limited effective treatments for patients with onset ischemic symptom that beyond six hours during acute ischemic stroke. In this study, we investigated the effectiveness of the intravenous argatroban therapy in acute ischemic stroke patients who cannot be treated with intravenous thrombolysis due to the limited time window. Methods One hundred and eighty patients with acute ischemic stroke that had beyond six hours ischemic symptom were admitted to our hospital and were analyzed retrospectively. Levels of activated partial thromboplastin time (aPTT), prothrombin time (PT) and thrombin time (TT) in peripheral blood of these patients were measured by ELISA at 24 hours post initial therapy. Results We found that plasma TT was significantly prolonged after 24 hours of argatroban treatment. aPTT showed slightly increased prolongation after 24 hours of argatroban treatment. PT also showed slightly prolonged after treatment, however, there was no difference from the basal line. We further investigated the relationship between the level of TT and the clinical effectiveness and safety of intravenous argatroban therapy. We found that when TT was between 40 and 80 seconds, intravenous argatroban effectively promoted the complete recovery rates without increasing the risk of hemorrhage. Conclusion Our study implies that TT assay might be useful for guiding regular dose of agratroban for therapy.

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Impact of Initial Imaging Protocol on Likelihood of Endovascular Stroke Therapy

Stroke ◽

10.1161/strokeaha.120.030122 ◽

2020 ◽

Vol 51 (10) ◽

pp. 3055-3063 ◽

Cited By ~ 1

Author(s):

Victor Lopez-Rivera ◽

Rania Abdelkhaleq ◽

Jose-Miguel Yamal ◽

Noopur Singh ◽

Sean I. Savitz ◽

...

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Odds Ratio ◽

Time Window ◽

Tissue Type ◽

Stroke Therapy ◽

Imaging Protocol ◽

Head Ct ◽

The Impact ◽

Endovascular Stroke Therapy

Background and Purpose: Noncontrast head CT and CT perfusion (CTP) are both used to screen for endovascular stroke therapy (EST), but the impact of imaging strategy on likelihood of EST is undetermined. Here, we examine the influence of CTP utilization on likelihood of EST in patients with large vessel occlusion (LVO). Methods: We identified patients with acute ischemic stroke at 4 comprehensive stroke centers. All 4 hospitals had 24/7 CTP and EST capability and were covered by a single physician group (Neurology, NeuroIntervention, NeuroICU). All centers performed noncontrast head CT and CT angiography in the initial evaluation. One center also performed CTP routinely with high CTP utilization (CTP-H), and the others performed CTP optionally with lower utilization (CTP-L). Primary outcome was likelihood of EST. Multivariable logistic regression was used to determine whether facility type (CTP-H versus CTP-L) was associated with EST adjusting for age, prestroke mRS, National Institutes of Health Stroke Scale, Alberta Stroke Program Early CT Score, LVO location, time window, and intravenous tPA (tissue-type plasminogen activator). Results: Among 3107 patients with acute ischemic stroke, 715 had LVO, of which 403 (56%) presented to CTP-H and 312 (44%) presented to CTP-L. CTP utilization among LVO patients was greater at CTP-H centers (72% versus 18%, CTP-H versus CTP-L, P <0.01). In univariable analysis, EST rates for patients with LVO were similar between CTP-H versus CTP-L (46% versus 49%). In multivariable analysis, patients with LVO were less likely to undergo EST at CTP-H (odds ratio, 0.59 [0.41–0.85]). This finding was maintained in multiple patient subsets including late time window, anterior circulation LVO, and direct presentation patients. Ninety-day functional independence (odds ratio, 1.04 [0.70–1.54]) was not different, nor were rates of post-EST PH-2 hemorrhage (1% versus 1%). Conclusions: We identified an increased likelihood for undergoing EST in centers with lower CTP utilization, which was not associated with worse clinical outcomes or increased hemorrhage. These findings suggest under-treatment bias with routine CTP.

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Thrombolytic treatment in the oldest-old patient with acute ischemic stroke: an update on current evidence

Italian Journal of Medicine ◽

10.4081/itjm.2013.160 ◽

2013 ◽

pp. 160-165

Author(s):

Fabiola Maioli ◽

Gaetano Procaccianti ◽

Valeria Nativio ◽

Giorgia Arnone ◽

Roberto Nardi ◽

...

Keyword(s):

Ischemic Stroke ◽

Thrombolytic Therapy ◽

Acute Ischemic Stroke ◽

Oldest Old ◽

Intravenous Thrombolysis ◽

Cognitive Status ◽

Screening Tools ◽

Current Evidence ◽

Thrombolytic Treatment ◽

Old Patients

The incidence of ischemic stroke rises exponentially with age, with a steep increase in the age interval between 75 and 85 years. Thrombolytic therapy restores cerebral blood flow in patients with acute ischemic stroke of any etiology by using drugs that dissolve blood clots. Infusion for 1 h of alteplase at the dose of 0.9 mg/kg within 3 h of the start of the symptoms is associated to a 30% increase in the likelihood of gaining a favorable outcome with respect to placebo. There is strong evidence that selected patients with ischemic stroke may benefit from intravenous thrombolysis when treated within 3 h. The aim of the study was to evaluate available evidence for the efficacy and safety of thrombolytic therapy in patients with ischemic stroke aged 80 years and over. Compared to younger stroke patients treated with thrombolytic therapy, those aged 80 years and over have higher acute mortality due to symptomatic intracranial hemorrhage. However, functional outcome at six months is significantly better for over-80-year-olds than younger patients. There is a need for screening tools that take into account pre-stroke functional and cognitive status that are able to identify those over-80-year-old patients with ischemic stroke who can most benefit from thrombolytic treatment. Available evidence supports further recruitment of oldest-old patients into ongoing trials of thrombolysis.

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Abstract 58: The Iscore Predicts Efficacy Of Thrombolytic Therapy For Acute Ischemic Stroke

Stroke ◽

10.1161/str.43.suppl_1.a58 ◽

2012 ◽

Vol 43 (suppl_1) ◽

Author(s):

Gustavo Saposnik ◽

Jiming Fang ◽

Moira Kapral ◽

Jack Tu ◽

Muhammad Mamdani ◽

...

Keyword(s):

Ischemic Stroke ◽

Thrombolytic Therapy ◽

Acute Ischemic Stroke ◽

Clinical Response ◽

Intravenous Thrombolysis ◽

Hemorrhagic Transformation ◽

Neurological Deterioration ◽

Stroke Severity ◽

Risk Of Death ◽

Poor Outcome

Background: The iScore is a validated tool developed to estimate the risk of death and functional outcomes early after an acute ischemic stroke. It includes demographics, stroke severity and subtype, vascular risk factors, cancer, renal failure, and pre-admission functional status. Limited information is available to predict the clinical response after intravenous thrombolytic therapy (tPA). Objective: To determine the ability of the iScore to predict the clinical response and risk of hemorrhagic transformation after tPA. Methods: We applied the iScore ( www.sorcan.ca/iscore ) to patients presenting with an acute ischemic stroke at 11 stroke centres in Ontario, Canada, between 2003 and 2008, identified from the Registry of the Canadian Stroke Network (RCSN). We compared outcomes between patients receiving and not receiving tPA adjusting for differences in baseline characteristics through matching by propensity scores. Three groups were defined a priori as per the iScore (low risk 180). Outcome Measures: Poor outcome, the primary outcome measure, was defined as disability at discharge or death at 30 days. Secondary outcomes included disability at discharge, neurological deterioration and intracranial hemorrhage (any type and symptomatic). Results: Among 12,686 patients with an acute ischemic stroke, 1696 (13.4%) received intravenous thrombolysis. Overall, 589 tPA patients were matched with 589 non-tPA patients (low iScore risk), 682 tPA were matched with 682 non-tPA patients (medium iScore risk) and 419 tPA patients were matched with 419 non-tPA patients (high iScore risk). There was good matching in all three groups. Higher iScore was associated with poor functional outcome in both the tPA and non-tPA groups (p<0.001). Among those with low and medium iScore risk, tPA use was associated with lower risk of poor outcome (Low iScore RR 0.74; 95%CI 0.67-0.84; medium iScore RR 0.88; 95%CI 0.84-0.93). There was no difference in clinical outcomes between matched patients receiving and not receiving tPA in the highest iScore group (RR 0.97; 95%CI 0.94-1.01). Similar results were observed for disability at discharge and length of stay. The incident risk of neurological deterioration and hemorrhagic transformation (any or symptomatic) increased with the iScore risk ( Figure ). Conclusion: The iScore appears to predict clinical response and risk of hemorrhagic complications after tPA for an acute ischemic stroke. Patients with high iScores may not benefit from tPA and have higher risk of hemorrhagic transformation, though this finding should be validated independently (underway) before clinical use.

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