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Reperfusion therapies are recommended for patients with hemodynamic instability or high-risk acute pulmonary embolism (PE). Lower doses of tissue plasminogen activator (rt-PA) could be considered to improve bleeding complications. The aim of this study was to evaluate the efficacy and safety of a reduced dose of rt-PA for the treatment of acute PE, compared with anticoagulation and standard dose. PubMed Central, Scopus, Web of Science and Embase were searched for all relevant randomized studies and prospective observational studies that compared reduced dose of rt-PA with anticoagulation alone or standard dose of rt-PA in patients with acute PE. The risk ratios (RR, with 95% CI) were calculated according to the value of I2. Outcomes were described as bleeding events, all-cause death, and recurrence of PE. Thirteen articles, including four observational studies (4223 patients) and nine RCTs (780 patients), were included. In comparing reduced dose of rt-PA with anticoagulant, a greater incidence of total bleeding events in low dose was showed (RR, 5.08 (95% CI, (1.39-18.6), I2 = 0.0%). In the standard dose rt-PA vs. reduced dose, there was a greater incidence of total bleeding events in the standard dose of rt-PA, RR 1.48 (95% CI, (1.00-2.19), I2 = 0.0%) was shown. There were no statistical differences in recurrent PE or all-cause mortality. It concluded that in the absence of the benefit of a standard dose of rt-PA in comparison with dose reduction, a reduced dose of rt-PA showed a lower rate of total bleeding events and similar efficacy regarding mortality and PE recurrence rate. [ABSTRACT FROM AUTHOR]

Background: Following an acute ischemic stroke (AIS), rapidly initiated reperfusion therapies [i. e., intravenous thrombolysis (IVT) and endovascular treatment (EVT)] demonstrate robust clinical efficacy. However, only a subset of these patients can benefit from these therapies due to their short treatment windows and potential complications. In addition, many patients despite successful reperfusion still have unfavorable outcomes. Thus, neuroprotection strategies are urgently needed for AIS patients. Chlorpromazine and promethazine (C+P) have been employed in clinical practice for antipsychotic and sedative purposes. A clinical study has also shown a neuroprotective effect of C+P on patients with cerebral hemorrhage and subarachnoid hemorrhage. The safety, feasibility, and preliminary efficacy of intravenous administration of C+P in AIS patients within 24 h of onset will be elucidated. Methods: A prospective randomized controlled trial is proposed with AIS patients. Participants will be randomly allocated to an intervention group and a control group with a 1:1 ratio (n = 30) and will be treated with standard therapies according to the current stroke guidelines. Participants allocated to the intervention group will receive intravenous administration of C+P (chlorpromazine 50 mg and promethazine 50 mg) within 24 h of symptom onset. The primary outcome is safety (mainly hypotension), while the secondary outcomes include changes in functional outcome and infarction volume. Discussions: This study on Rapid Intervention of Chlorpromazine and Promethazine for Hibernation-like Effect in Stroke (RICHES) will be the first prospective randomized controlled trial to ascertain the safety, feasibility, and preliminary efficacy of intravenous C+P as a neuroprotection strategy in AIS patients. These results will provide parameters for future studies, provide insights into treatment effects, and neuroprotection with phenothiazine in AIS. Clinical Trial Registration: www.chictr.org.cn, identifier: ChiCTR2000038727. [ABSTRACT FROM AUTHOR]

Thrombolysis with recombinant tissue plasminogen activator (rt-PA) is a mainstay of acute ischemic stroke treatment but is associated with bleeding complications, especially after prolonged large vessel occlusion. Recently, inhibition of the NLRP3 inflammasome led to preserved blood–brain barrier (BBB) integrity in experimental stroke in vivo. To further address the potential of NLRP3 inflammasome inhibition as adjunct stroke treatment we used immortalized brain derived endothelial cells (bEnd5) as an in vitro model of the BBB. We treated bEnd5 with rt-PA in combination with the NLRP3 specific inhibitor MCC950 or vehicle under normoxic as well as ischemic (OGD) conditions. We found that rt-PA exerted a cytotoxic effect on bEnd5 cells under OGD confirming that rt-PA is harmful to the BBB. This detrimental effect could be significantly reduced by MCC950 treatment. Moreover, under ischemic conditions, the Cell Index—a sensible indicator for a patent BBB—and the protein expression of Zonula occludens 1 stabilized after MCC950 treatment. At the same time, the extent of endothelial cell death and NLRP3 expression decreased. In conclusion, NLRP3 inhibition can protect the BBB from rt-PA-induced damage and thereby potentially increase the narrow time window for safe thrombolysis in stroke.

Historically, safety of intravenous recombinant tissue plasminogen activator (IV rt‐PA) for the treatment of acute ischaemic stroke (AIS) is limited to use within 4.5 hours from symptom onset. Recent studies suggest the treatment window may be extended when patients have salvageable brain tissue on advanced neuroimaging. This paper describes a novel use of IV rt‐PA for treatment of AIS in a pregnant patient within an extended‐time window (>4.5 hours, and <9 hours) based on advanced neuroimaging with a favourable outcome. Novel use of IV rt‐PA for treatment of AIS in pregnancy within an extended‐time window based on advanced imaging with a favourable outcome. Novel use of IV rt‐PA for treatment of AIS in pregnancy within an extended‐time window based on advanced imaging with a favourable outcome. [ABSTRACT FROM AUTHOR]

Pseudoxanthoma elasticum is a rare cause for ischaemic stroke. Little is known about acute and secondary prevention strategies in these subjects given the increased risk of gastrointestinal and urinary bleedings. Here we present the case of a 62 years old man affected by pseudoxanthoma elasticum who presented with acute ischaemic stroke and was successfully treated with intravenous thrombolysis. Neurological signs improved after intravenous thrombolysis without bleeding complication. To our knowledge, this is the first case of pseudoxanthoma elasticum—related stroke undergoing intravenous thrombolysis. [ABSTRACT FROM AUTHOR]

Acute ischemic stroke patients with intravenous (IV) recombinant tissue plasminogen activator (rt-PA) thrombolysis have different outcomes. The degree of thrombolysis depends largely on the delicate balance of coagulation and fibrinolysis. Thus, our study aimed to investigate the prognostic value of routine coagulation parameters in acute stroke patients treated with rt-PA. From December 2016 to October 2018, consecutive patients treated with standard-dose IV rt-PA within 4.5 h of stroke onset were collected in Beijing Tiantan Hospital. Routine coagulation parameters, including platelet count, mean platelet volume, platelet distribution width, prothrombin time (PT), activated partial thromboplastin time, thrombin time, and fibrinogen, were measured at baseline (h0) and 24 h (h24) after thrombolysis. The change of coagulation parameters was defined as the (h24-h0)/h0 ratio. The prognosis included short-term outcome at 24 h and functional outcome at 3 months. A total of 267 patients were investigated (188 men and 79 women) with a mean age of 60.88 ± 12.31 years. In total, 9 patients had early neurological deterioration within 24 h, and 99 patients had an unfavorable outcome at the 3-month visit. In multivariate logistic regression, the (h24-h0)/h0 of PT was associated with unfavorable functional outcomes at 3 months (odds ratio: 1.42, 95% confidence interval: 1.02-2.28). While the change of other coagulation parameters failed to show any correlation with short-term or long-term prognosis. In conclusion, the prolongation of PT from baseline to 24 h after IV rt-PA increases the risk of 3-month unfavorable outcomes in acute stroke patients. [ABSTRACT FROM AUTHOR]

Objective: In this study, we assessed the efficacy and safety of various thrombolytic treatment protocols in patients with hyperacute cerebral infarction., Methods: Patients diagnosed with acute ischemic stroke within 6 h of symptom onset and with brain computer tomography angiography confirming the absence of major vessel stenosis or occlusion were eligible for this study. The enrolled patients were subsequently randomized into two groups: all the groups received the standard intravenous thrombolysis treatment with rt-PA (0.9 mg/kg), and the experimental group underwent sequential intra-arterial thrombolysis treatment with alteplase (0.3 mg/kg, with a maximum dose of 22 mg), administered directly into the target vessel via a microcatheter. Both groups were closely monitored for changes in their National Institutes of Health Stroke Scale (NIHSS) score, modified Rankin scale score, hemorrhage rate, all-cause mortality rate, and the rate of favorable outcomes at 90 ± 7 days., Results: Ninety-four participants were enrolled in this study, with both the control and experimental groups initiating intravenous injection of rt-PA at a median time of 29 min. For the experimental group, the median time for arterial puncture was 123 min. Baseline data for both groups were similar ( P  > 0.05). Hemorrhagic transformation occurred in 24.47 % (23 patients), with a lower intracranial hemorrhage rate observed in the experimental group compared to the control group (15.2 % vs 33.3 %, P  < 0.05). Asymptomatic hemorrhage rates were 8.7 % for the experimental group and 12.5 % for the control group, with no hemorrhage detected in other locations. Post-treatment median NIHSS scores were lower in the experimental group than in the control group (7 vs 9, P  < 0.05), but short-term NIHSS scores were similar ( P  > 0.05). A higher proportion of patients in the experimental group achieved favorable outcomes compared to the control group (87.0 % vs 43.8 %, P  < 0.05)., Conclusion: In patients with acute ischemic stroke with an onset time of ≤6 h and no major intracranial vessel occlusion, combining rt-PA intravenous thrombolysis with intra-arterial thrombolysis via a microcatheter might yield superior functional outcomes., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

The effects of thrombolysis in seizure and epilepsy after acute ischemic stroke have been poorly explored. In this study, we examine risk factors and consequences of intravenous rt-PA for treatment of acute ischemic stroke. In a retrospective cohort study we evaluate risk factors for seizure and epilepsy after stroke thrombolysis, as well as the impact of seizures and epilepsy in outcome of stroke patients. In our cohort, mean age of patients was 67.2 years old (SD = 13.1) and 79 of them (51.6%) were male and. Initial NIHSS mean score were 10.95 (SD = 6.25). Three months NIHSS mean score was 2.09 (SD = 3.55). Eighty seven (56.9%) patients were mRS of 0–1 after thrombolysis. Hemorrhagic transformation was observed in 22 (14.4%) patients. Twenty-one (13.7%) patients had seizures and 15 (9.8%) patients developed epilepsy after thrombolysis. Seizures were independently associated with hemorrhagic transformation (OR = 3.26; 95% CI = 1.08–9.78; p = 0.035) and with mRS ≥ 2 at 3 months after stroke (OR = 3.51; 95% CI = 1.20–10.32; p = 0.022). Hemorrhagic transformation (OR = 3.55; 95% CI = 1.11–11.34; p = 0.033) and mRS ≥ 2 at 3 months (OR = 5.82; 95% CI = 1.45–23.42; p = 0.013) were variables independently associated with post-stroke epilepsy. In our study, independent risks factors for poor outcome in stroke thrombolysis were age (OR = 1.03; 95% CI = 1.01–1.06; p = 0.011), higher NIHSS (OR = 1.08; 95% CI = 1.03–1.14; p = 0.001), hemorrhagic transformation (OR = 2.33; 95% CI = 1.11–4.76; p = 0.024), seizures (OR = 3.07; 95% CI = 1.22–7.75; p = 0.018) and large cortical area (ASPECTS ≤ 7) (OR = 2.04; 95% CI = 1.04–3.84; p = 0.036). Concluding, in this retrospective cohort study, the neurological impairment after thrombolysis (but not before) and hemorrhagic transformation remained independent risk factors for seizures or post-stroke epilepsy after thrombolysis. Moreover, we observed that seizures emerged as an independent risk factor for poor outcome after thrombolysis therapy in stroke patients (OR = 3.07; 95% CI = 1.22–7.75; p = 0.018).

François Zhu,1,2 Benjamin Gory,2,3 Gioia Mione,1 Lisa Humbertjean,1 Anne-Laure Derelle,2 Sébastien Richard1,4 1Department of Neurology, Stroke Unit, University Hospital of Nancy, Nancy Cedex, France; 2Department of Diagnostic and Therapeutic Neuroradiology, University Hospital of Nancy, Nancy Cedex, France; 3INSERM U1254, IADI F-54000, Nancy, France; 4Centre d’Investigation Clinique Plurithématique Pierre Drouin, CIC-P 1433 INSERM U1116, University Hospital of Nancy, Vandoeuvre-lès-Nancy, France Abstract: Cerebral infarction due to acute embolism in the large artery during pregnancy is a rare but severe condition threatening both the mother’s and child’s life. Physicians lack diagnostic and therapeutic guidance to manage this particular situation due to the paucity of published cases. Furthermore, the pathogeny is poorly known, rendering preventive strategies difficult. We describe the case of a young woman presenting cryptogenic acute cerebral infarction during the first trimester of pregnancy who was successfully treated with combined reperfusion therapy. We reviewed the literature to collect data about pathogeny and management. A 28-year-old pregnant woman was diagnosed with acute cerebral infarction due to left middle cerebral artery occlusion at 9 weeks of gestation. Endovascular thrombectomy combined with intravenous thrombolysis allowed cerebral reperfusion leading to a decrease in the National Institute of Health Stroke Score from 13 to 1 at 24 hours. Comprehensive etiological investigation was negative. Anticoagulation therapy with low-molecular-weight heparin was administered as preventive treatment during the pregnancy and postpartum. Neither the mother nor the child experienced any complications: the baby was born by normal vaginal delivery and the outcome was good at 1 year. We identified 21 other cases of patients treated with reperfusion therapies, four of which consisted of endovascular thrombectomy, and only one a combined strategy. Pregnant women with acute cerebral infarction due to arterial occlusion can benefit from combined reperfusion therapy. More cases should be collected to assess treatment in these patients, to understand pathogeny, and propose the best preventive strategy. Keywords: pregnancy, acute cerebral infarction, stroke, rt-PA, thrombolysis, endovascular thrombectomy

Background: Myxoma may cause systemic embolization and frequently presents as ischemic stroke. Case Presentation: There have been debates about whether it is safe to use recombinant tissue plasminogen activator (rt-PA) in patients with cardiac myxoma who referred with ischemic stroke to the hospital's emergency. Results: The patient was a young case of atrial myxoma with initial presentation of acute cerebral infarction symptoms who was treated with intravenous rt-PA with no complications. Conclusion: The case provides an evidence of the efficacy and safety of intravenous rt-PA in cases of cardiac myxoma. However, we cannot always expect thrombolytic therapy to be effective, especially in tumor emboli. [ABSTRACT FROM AUTHOR]

The sudden worldwide outbreak of Coronavirus Disease 2019 (COVID-19) has certainly provided new challenges in the management of acute ischaemic stroke, and the risk-benefit ratio of intravenous thrombolysis in COVID-19 positive patients is not well known. We describe four COVID-19 patients treated with intravenous thrombolysis for acute ischaemic stroke. Although rt-PA administration is the main therapeutic strategy, our patients experienced unpredictable complications and showed atypical features: the overall mortality was very high. In conclusion, in this article, we provide information about these cases and discuss the possible explanation behind this trend. [ABSTRACT FROM AUTHOR]

Background: The administration of recombinant tissue plasminogen activator (rt-PA) has increased the focus on acute ischemic stroke (AIS) as an emergency condition. The emergency physicians have to rapidly recognize the patients who are candidates for rt-PA and refer them to the specialized stroke team within the proper time window. The knowledge of the emergency physicians about the benefit and the drawbacks of this therapy is crucial and it affects their attitudes towards its use. Objective: To apply a survey on the Egyptian emergency physicians aiming to investigate their knowledge about the use rt-PA therapy in AIS. Methodology: A self-administered questionnaire was sent to the emergency physicians who are working in three Egyptian governorates. Results: Out of 120 emergency physicians, the total knowledge of the study group was good with a score of 7 ± 1.8/11. Most of the participants mentioned the correct answers (over 50%) for all items except for one question regarding the blood glucose control before the use of rt-PA. Significant positive correlation was noted between the knowledge score and the age. Conclusions: The surveyed emergency physicians had a good knowledge about the use of rt-PA in AIS, yet, this knowledge is mainly theoretical. Therefore, tutorials, clinical training, and active engagement in the stroke care team are warranted to improve their clinical practice. [ABSTRACT FROM AUTHOR]

Background: Stroke is the leading cause of death and disability. Nowadays, the standard treatment is Intravenous thrombolytic with alteplase (t-PA) within 4.5 hours after the stroke onset. However, some patients who arrived to the hospital within 4.5 hours after stroke onset haven't received the alteplase. Objective: To investigate the barriers to thrombolysis drug (alteplase) in acute ischemic stroke patients who arrived at the hospital within 4.5 hours after the stroke onset. Materials and Methods: A retrospective study of ischemic stroke patients who developed stroke symptoms and arrived at the hospital within 4.5 hours but did not receive the thrombolytic drug (non-treatment group). Data were collected at the North-East hospital of Thailand from the hospital stroke registry and the patient record from October 2014 to September 2015. The study focused on the reasons for which this group of patients was excluded from receiving the thrombolytic drug. Factors associated with the non-treatment group were investigated using multivariable logistic regression. Results: Of a total 229 patients who were diagnosed with acute ischemic stroke and arrived within 4.5 hours after stroke onset, 61 patients underwent thrombolytic therapy with alteplase. Of the 168 patients who did not receive the alteplase, the main reasons for this were mild or improving symptoms, contraindication to alteplase and uncertain onset time (including wake-up strokes). Factors associated with the non-treatment group were door time over three hours and patients who had an underlying history of hypertension or an old cerebrovascular accident (CVA). These patients were less likely to receive the thrombolytic drug. While patients with a National Institute of Health Stroke Scale (NIHSS) between 8 and 12, were more likely to receive the treatment. Conclusion: Barriers to use of the thrombolytic drug in acute ischemic stroke in Thai patients included mild or improved symptoms, relative contraindication to alteplase and uncertain onset time. In order to increase alteplase administration, the revision of relative contraindication in mild symptoms, seizure at onset of stroke and wake-up stroke or stroke with an uncertain time of onset should be considered. The application of neuroimaging can be useful to select the eligible cases. [ABSTRACT FROM AUTHOR]

Bladder dysfunction may occur in acute stroke patients and as a consequence the risk of urinary retention, incontinence and urinary tract infections increases. The literature is sparse regarding occurrence of bladder dysfunction in acute stroke and if catheterization should be performed to prevent bladder overdistension in acute stroke thromboly-sis. The aim of this study was to investigate the safety of implementing a new selective and "watchful waiting strategy" for intermittent catheterization during acute stroke thrombolysis. From November 2018 to June 2019, we conducted a prospective cohort study before and after implementing (in March 2019) a selective and watchful waiting strategy for intermittent catheterization. Data were collected on nurse-administered registration forms for ischemic stroke patients treated with thrombolysis. In both periods urogenital complications were registered. We found no significant differences between period 1 (before) and 2 (after) in the occurrence of urinary tract infections and/or macroscopic urogenital bleeding episodes. However, for developing blood in the 24hour urine analysis we found a significant reduction in period 2 compared to period 1, 8 (23%) vs 3 (7%) respectively. Applying a selective and watchful waiting strategy towards urinary catheterization in acute ischemic stroke patients treated with intravenous thrombolysis did not increase the risk of urogenital complications, and the discomfort associated with catheterization was limited to fewer patients. [ABSTRACT FROM AUTHOR]

Recombinant tissue plasminogen activator (rt-PA) has proven effective in the treatment of acute ischemic stroke, despite the increased risk of hemorrhagic transformation (HT), its major associated complication. Although it is known that HT is related to blood brain barrier (BBB) disruption, the underlying mechanisms are not well established. We assessed time-dependent effects of rt-PA on the bEnd.3 murine brain endothelial cell line subjected either to normoxia or to 2.5 h of oxygen and glucose deprivation (OGD), evaluating a longer period than has previously been done, beyond 6 h post-reoxygenation. Parameters of cell viability, metabolic activity, ionic and transcellular permeability, as well as levels of claudin-5, zonula occludens-1 (ZO-1) and bradykinin B2 receptor (B2R) protein expression were analyzed at 24, 48 and 72 h post-reoxygenation with or without the administration of rt-PA. rt-PA treatment increased both the ionic and transcellular permeability until 72 h and did not modify cell viability or metabolic activity or the expression of claudin-5, ZO-1 and B2R under normoxia at any analyzed time. Under OGD conditions, rt-PA exacerbated OGD effects on metabolic activity from 48 to 72 h, increased transcellular permeability from 24 to 72 h, significantly decreased ZO-1 protein levels at the plasma membrane and increased B2R glycosylation at 72 h post-reoxygenation. Our findings suggest that a long-term analysis is necessary to elucidate time-dependent molecular mechanisms associated to BBB breakdown due to rt-PA administration under ischemia. Thus, protective BBB therapies after ischemic stroke and rt-PA treatment should be explored at least until 72 h after OGD and rt-PA administration. • rt-PA administration exacerbates OGD effects on bEnd.3 metabolic activity over period exceeding 24 h post-reoxygenation. • rt-PA administration extends the OGD/reoxygenation-induced transcellular permeability for at least 72 h post-reoxygenation. • In presence of rt-PA, reduced ZO-1 protein levels are only observed after 72 h post-reoxygenation • In bEnd.3 cells, B2R glycosylated form is increased after OGD and rt-PA treatment at 72 h of reoxygenation. [ABSTRACT FROM AUTHOR]

The effects of thrombolysis in seizure and epilepsy after acute ischemic stroke have been poorly explored. In this study, we examine risk factors and consequences of intravenous rt-PA for treatment of acute ischemic stroke. In a retrospective cohort study we evaluate risk factors for seizure and epilepsy after stroke thrombolysis, as well as the impact of seizures and epilepsy in outcome of stroke patients. In our cohort, mean age of patients was 67.2 years old (SD = 13.1) and 79 of them (51.6%) were male and. Initial NIHSS mean score were 10.95 (SD = 6.25). Three months NIHSS mean score was 2.09 (SD = 3.55). Eighty seven (56.9%) patients were mRS of 0–1 after thrombolysis. Hemorrhagic transformation was observed in 22 (14.4%) patients. Twenty-one (13.7%) patients had seizures and 15 (9.8%) patients developed epilepsy after thrombolysis. Seizures were independently associated with hemorrhagic transformation (OR = 3.26; 95% CI = 1.08–9.78; p = 0.035) and with mRS ≥ 2 at 3 months after stroke (OR = 3.51; 95% CI = 1.20–10.32; p = 0.022). Hemorrhagic transformation (OR = 3.55; 95% CI = 1.11–11.34; p = 0.033) and mRS ≥ 2 at 3 months (OR = 5.82; 95% CI = 1.45–23.42; p = 0.013) were variables independently associated with post-stroke epilepsy. In our study, independent risks factors for poor outcome in stroke thrombolysis were age (OR = 1.03; 95% CI = 1.01–1.06; p = 0.011), higher NIHSS (OR = 1.08; 95% CI = 1.03–1.14; p = 0.001), hemorrhagic transformation (OR = 2.33; 95% CI = 1.11–4.76; p = 0.024), seizures (OR = 3.07; 95% CI = 1.22–7.75; p = 0.018) and large cortical area (ASPECTS ≤ 7) (OR = 2.04; 95% CI = 1.04–3.84; p = 0.036). Concluding, in this retrospective cohort study, the neurological impairment after thrombolysis (but not before) and hemorrhagic transformation remained independent risk factors for seizures or post-stroke epilepsy after thrombolysis. Moreover, we observed that seizures emerged as an independent risk factor for poor outcome after thrombolysis therapy in stroke patients (OR = 3.07; 95% CI = 1.22–7.75; p = 0.018). [ABSTRACT FROM AUTHOR]

Acute ischemic stroke is a public health issue worldwide. Currently, the effective treatment for acute ischemic stroke is an intravenous recombinant tissue plasminogen activator (rt-PA). The follow-up CT brain after the rt-PA is still controversial. This study was a retrospective study with an aim to evaluate roles of CT brain after rt-PA treatment. The inclusion criteria were all consecutive adult patients diagnosed as acute ischemic stroke who received the rt-PA. The patients were categorized into two groups by the presence of the follow-up CT brain. For those who performed the CT brain, results of the CT brain or management were correlated with clinical status at 24 hours after the rt-PA and stroke types. There were 211 eligible patients. Of those, 86 patients (40.76%) performed the CT brain after the rt-PA treatment within 24 to 36 hours. For the CT brain group, hemorrhagic transformation occurred the highest in those without clinical improvement with the NIHSS at 24 hours over 10 (14/32 patients; 43.75%). The overall hemorrhagic transformation was 23 patients (26.74%). Regarding stroke type, the intracerebral hemorrhage was found mostly in large arterial stroke (16 patients). While, the malignant middle cerebral artery infarction was found in seven patients (8.14%); five patients with large arterial stroke and two patients with cardioembolic stroke. In conclusion, the follow-up CT brain after the rt-PA treatment may be performed in selected cases such as those without clinical improvement with the NIHSS of over 10 or large arterial/cardioembolic stroke. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the factors associated with poor treatment outcomes of acute ischemic stroke after intravenous recombinant tissue plasminogen activator (rt-PA) therapy from 7 hospitals in Northeastern Thailand. Materials and Methods: The present study was a retrospective analytical study. Data were obtained from medical records of acute ischemic stroke patients who reached hospital within 4.5 hours after onset and received rt-PA during 2008 May to 2012 April. The authors evaluated time and process to access hospital, duration of treatment process, and factor associated with good and poor clinical outcomes. Results: During the study period, 778 patients met the study criteria. Mean onset-to-door time was 1.85+1.05 hours. Previous visiting medical center unavailable for rt-PA made patients delay reaching hospitals (OR 1.62 (95% CI 1.28 to 2.04), p-value <0.001). Mean onset-to-needle time was 3.08+1.11 hours. Factors leading to poor outcome were atrial fibrillation (AF) (OR 2.38 (95% CI 1.33 to 4.23), p-value = 0.003) and onset-to-needle time more than 180 minutes (OR 14.78 (95% CI 7.91 to 27.62), p-value <0.001). Conclusion: Patients came to hospital late because of previously visiting medical centers where rt-PA-was unavailable. Atrial fibrillation and onset-to-needle time more than 180 minutes associated to poor outcome. [ABSTRACT FROM AUTHOR]

Despite campaigns to increase public awareness of stroke symptoms by advocating FAST (Face-Arms-Speech-Time), some stroke patients still show delays in the recognition of and response to stroke symptoms and miss the golden first 4.5 h to receive rt-PA (recombinant tissue plasminogen activator) treatment. The aim of this study was to explore how acute ischemic stroke patients with prehospital delay seek help and undergo the decision process before arriving at the hospital. A qualitative approach using a grounded theory was applied. There were 24 ischemic stroke patients recruited by purposive sampling. Our main findings were: “Hesitating and puzzling” was the core category to describe and guide the process of acute ischemic stroke patients with prehospital delay. During the process, “Awareness the sudden change of physical sensation and/or function” was the antecedent category. In the prehospital delay experience, the following five interaction categories were identified: (1) “Self-judgment and interpretation according to previous experience,” (2) “Puzzling and doubting—it may only be a minor problem,” (3) “Self-treatment or seeking medical attention nearby,” (4) “Unexpected symptoms getting worse” needing immediate advanced medical help and (5) “Rushing to ER with different transportation—self-alerting that serious disease is coming.” Eventually, the patients “Regret to delay seeking treatment and become a disable person.” The process of prehospital delay provides some hidden cues for patients to increase their knowledge about strokes. The study emphasizes the importance of educating community residents about identifying stroke symptoms, breaking the myth of folk therapy, and seeking medical attention immediately. These results will assist healthcare providers by offering references for designing patient-centric educational strategies for preventing stroke prehospital delay to improve the quality of stroke medical care.

Background and objectives Although the intravenous tissue plasminogen activator (rt-PA) has been shown to be effective in the treatment of acute ischemic stroke (AIS), only a small proportion of stroke patients receive this drug. The low administration rate is mainly due to the delayed presentation of patients to the emergency department (ED) or the lack of a stroke team/unit in most of the hospitals. Thus, the aim of this study is to analyze ED time targets and the rate of rt-PA intravenous administration after the initial admission of patients with AIS in an ED from a traditional healthcare center (without a neurologist or stroke team/unit). : To analyze which factors influence the administration of rt-PA, we split the general sample ( Methods: = 202) into two groups: group No rt-PA ( n = 137) and group rt-PA ( n = 137) and group rt-PA ( n = 65). This is based on the performing or no intravenous thrombolysis. Results: Analyzing ED time targets for all samples, we found that the median onset-to-ED door time was 180 min (IQR, 120-217.5 min), door-to-physician time was 4 min (IQR, 3-7 min), door-to-CT time was 52 min (IQR, 48-55 min), and door-in-door-out time was 61 min (IQR, 59-65 min). ED time targets such as door-to-physician time ( p = 0.245), door-to-CT time ( p = 0.219), door-in-door-out time ( p = 0.24), NIHSS at admission to the Neurology department ( p = 0.9) did not have a statistically significant effect on the administration or no rt-PA treatment in patients included in our study. Only the highest door-to-CT time was statistically significantly correlated with the death outcome. p In our study, the iv rt-PA administration rate was 32.18%. A statistically significant correlation between the highest door-to-CT time and death outcome was found. Conclusion: In our study, the iv rt-PA administration rate was 32.18%. A statistically significant correlation between the highest door-to-CT time and death outcome was found., Competing Interests: The authors declare no conflicts of interest.

Background: To determine whether it is possible to predict intravenous thrombolytic therapy (IVT) outcome after 3 months in acute ischemic stroke patients who are candidate to receive recombinant tissue plasminogen activator (rt-PA), before rt-PA administration based on their risk factors and some available laboratory results. Methods: We enrolled 118 ischemic stroke patients who were treated with standard dose of Alteplase in our hospital. Baseline characteristics, door-to-needle time (DTN), onset-totreatment time (OTT), the National Institute Health Stroke Scale (NIHSS), systolic and diastolic blood pressure on admission, history of diabetes, hypertension, dyslipidemia, coronary artery disease (CAD), previous ischemic stroke, atrial fibrillation (AF), laboratory results were retrospectively collected. The modified Rankin Scale (mRS) was recorded after 3 months of admission and patients were divided into good (mRS? 2) and poor (mRS>2) outcome groups. Chi-square test and t-test were used for categorical and continuous variables, respectively. Predictors for outcome after 3 months were studied by multivariable logistic regression. Results: Good outcome was seen in 60 (51%) patients and poor outcome was seen in 58 (49%) patients. Significant predictors for outcome at 3 months according to multivariable regression analysis were NIHSS score (odds ratio [OR], 0.61; 95% confidence interval [CI], 0.498-0.750; p<0.001), SBP (OR, 0.95; 95% CI, 0.925-0.991; P=0.01), AF (OR, 0.09; 95% CI, 0.013- 0.708; P=0.02), CAD (OR, 17.08; 95% CI, 0.013-0.708; p=0.003). Conclusion: Higher NIHSS score, higher SBP on admission, AF and history of CAD could be the independent predictors of outcome after IVT in acute ischemic stroke patients. [ABSTRACT FROM AUTHOR]

Background: UCHealth's Mobile Stroke Unit (MSU) at University of Colorado Hospital is an ambulance equipped with a computed tomography (CT) scanner and tele-stroke capabilities that began clinical operation in Aurora, Colorado January 2016. As one of the first MSU's in the United States, it was necessary to design unique and dynamic information technology infrastructure. This includes high-speed cellular connectivity, Health Insurance Portability and Accountability Act compliance, cloud-based and remote access to electronic medical records (EMR), and reliable and rapid image transfer. Here we describe novel technologies incorporated into the MSU. Technological data-handling aspects of the MSU were reviewed. Functions evaluated include wireless connectivity while in transit, EMR access and manipulation in the field, CT with image transfer from the MSU to the hospital's Picture Archiving Communication System (PACS), and video and audio communication for neurological assessment.Methods/results: The MSU wireless system was designed with redundancy to avoid dropped signals during data transfer. Two separate Internet Protocol destinations with split-tunnel architecture are assigned, for videoconferencing and for EMR data transfer. Brain images acquired in the ambulance CT scanner are transferred initially to an onboard laptop, then via Citrix Receiver to the hospital-based PACS server where they can be viewed in PACS or EMR by the stroke neurologist, neuroradiologist, and other providers. PACS and Radiology Information System are 2 of the XenApps utilized by CT technologists on board the MSU.Discussion/conclusions: These technologies will serve as a blueprint for development of similar units elsewhere, and as a framework for improvement in this technology. [ABSTRACT FROM AUTHOR]

Introduction: Intravenous (IV) thrombolysis with alteplase (rt-PA) is effective in ischaemic stroke. The primary objective was to evaluate predictors of functional outcome in acute ischaemic stroke (AIS) patients treated with IV rt-PA. The secondary objective was to assess the outcome with the modified Rankin scale (mRS). We also examined the predictive value of the Totaled Health Risks in Vascular Events (THRIVE) score.Methods: AIS patients treated with IV rt-PA from February 2012 to August 2016 were recruited. Demographic data, National Institutes of Health Stroke Scale (NIHSS) scores, timing and neuroradiological findings were recorded. Patients received a dose of 0.9 mg/kg IV rt-PA within 4.5 hours of symptom onset. mRS score was evaluated at discharge and three months, and good and poor clinical outcomes were defined as scores of 0-2 and 3-6, respectively. Baseline THRIVE scores were assessed.Results: 36 patients received IV rt-PA. 20 (55.6%) patients had an mRS score of 0-2 at three months. Based on THRIVE score, 86.1% had a good or moderately good prognosis. On univariate analysis, poor outcome was associated with NIHSS score before rt-PA (p = 0.03), THRIVE score (p = 0.02), stroke subtype (p = 0.049) and diabetes mellitus (DM; p = 0.06). Multiple logistic regression showed that outcome was significantly associated with NIHSS score before rt-PA (p = 0.032) and DM (p = 0.010).Conclusion: Our newly developed Malaysian IV rt-PA service is safe, with similar outcomes to the published literature. Functional outcome after thrombolysis was associated with baseline NIHSS score and DM. [ABSTRACT FROM AUTHOR]

To investigate whether ultra-early recombinant tissue-plasminogen activator (rt-PA) administration can improve patient outcomes on mechanical thrombectomy (MT) in patients with large vessel occlusion (LVO). Participants comprised rt-PA-eligible 204 patients with internal carotid artery or middle cerebral artery occlusion in the SKIP trial, who were randomly assigned to receive mechanical thrombectomy alone or combined intravenous thrombolysis (rt-PA: alteplase at 0.6 mg/kg) plus mechanical thrombectomy. We assessed associations between onset-to-puncture time and onset-to-rt-PA administration time and frequency of favorable outcome at 90 days and any intracerebral hemorrhage (ICH) at 36 h after onset. As a cut-off onset-to-puncture time for favorable outcome, receiver operating characteristic curves defined 2.5 h (57% sensitivity, 62% specificity). For onset-to-puncture times ≤2.5 h and > 2.5 h, frequencies of favorable outcomes were 72% and 63% (p = 0.402) in patients with rt-PA therapy and 44% and 58% (p = 0.212) in patients without rt-PA therapy, respectively. In terms of onset-to-rt-PA administration time, frequencies of favorable outcomes among patients with ultra-early rt-PA administration at ≤100, >100 min after onset, and without rt-PA therapy with onset-to-puncture time ≤ 2.5 h, and with and without rt-PA therapy with onset-to-puncture time > 2.5 h were 84% and 64%, 63%, and 44% and 58%, respectively (p = 0.025). Frequencies of any ICH among those patients were 37% and 32%, 32%, and 63% and 40%, respectively (p = 0.006). Ultra-early rt-PA administration should improve patient outcomes on mechanical thrombectomy among patients with LVO. Relatively late rt-PA administration might increase the frequency of any ICH. • The benefits of rt-PA depend on the time of administration after stroke onset. • To investigate the impact of ultra-early rt-PA on clinical outcome before mechanical thrombectomy. • The rt-PA-eligible 204 patients with ICA or MCA occlusion were included. • Combined ultra-early rt-PA with thrombectomy had the best clinical outcome. • Relatively late rt-PA before thrombectomy might increase the frequency of any intracranial hemorrhages. [ABSTRACT FROM AUTHOR]

Background: Thrombolysis in the elderly is still a matter of debate. Recently, the Third International Stroke Trial (IST-3) suggested that recombinant tissue plasminogen activator (rt-PA) improves functional outcome, without a substantial absolute increase in symptomatic intracranial hemorrhage, even in older patients. The aim of the current prospective study is to describe safety and functional outcome in a cohort of patients treated by intravenous rt-PA in an Italian stroke unit “real world setting”. Methods: All the consecutive patients treated with rt-PA between 2006 and 2010 in an Italian province with 290,000 inhabitants were enrolled. Total and symptomatic (associated with a 4-point worsening on the National Institutes of Health Stroke Scale [NIHSS] score) hemorrhages were evaluated, as safety measures, along with disability (at 3-month modified Rankin scale) as effectiveness measure. Results: One hundred and eighty-seven patients were treated with rt-PA; 90 males (48.1%); average age 75.1 (±11.9) years; 79 (42.2%) patients aged ≥80 years. Patients aged ≥80 years had a higher NIHSS score at stroke onset (13.5 vs. 10.9). No significant difference was found between patients aged

W artykule przedstawiono, jak w ostatnich 20 latach rozwijały się metody przyczynowego – a więc rekanalizującego – leczenia w ostrej fazie niedokrwiennego udaru mózgu. Najwcześniejsze sposoby reperfuzji mózgu, wciąż stosowane, opierają się na dożylnym podaniu środka trombolitycznego; dzięki dopracowaniu protokołów leczenia udało się poszerzyć okno terapeutyczne dla tej metody z 3 godzin do 4,5 godziny (standardowo), a w niektórych przypadkach – nawet do 6 godzin. Kolejnym etapem rozwoju metod reperfuzji mózgu było lokalne, dotętnicze podawanie leku trombolitycznego. Wreszcie pojawiły się mechaniczne procedury wewnątrznaczyniowe, pozwalające poszerzyć okno terapeutyczne do 8 godzin. Najbardziej zaawansowane podejścia, łączące dwie lub trzy metody, umożliwiają bezpieczne i skuteczne leczenie chorych nawet w ciągu 12 godzin od wystąpienia objawów udaru mózgu. Stwarza to nowe perspektywy rozwoju neurologii naczyniowej i radiologii neurointerwencyjnej. W przyszłości pacjenci doznający niedokrwiennego udaru mózgu będą zatem mieć znacznie większe szanse na przeżycie i sprawne funkcjonowanie niż jeszcze bardzo niedawno.

Highlights • 2-BFI (0.5 h) combined with rt-PA (6 h) can reduce infarct damages in eMCAO rats. • 2-BFI (0.5 h) combined with rt-PA (6 h) can decrease apoptosis cells in eMCAO rats. • 2-BFI (0.5 h) combined with rt-PA (6 h) can inhibit BAX/BCL-2 levels in eMCAO rats. Abstract Stroke is the third leading cause of death and disability in developing countries. The effective therapy for acute ischemic stroke is thrombolysis with recombinant tissue plasminogen activator (rt-PA) within 4.5 h of stroke onset. An effective post-ischemic neuroprotectant would extend the advantages of rt-PA, and protect against complications of thrombolysis. We previously reported that 2-(2-benzofuranyl)-2-imidazoline (2-BFI), a newly discovered ligand for high-affinity type 2 imidazoline receptor (I2R), provides neuroprotection against ischemic stroke in rats. Here we investigated the protective effects of 2-BFI in combination with delayed intravenous rt-PA after stroke induced by embolic middle cerebral artery occlusion (eMCAO) in rats. Infarct size was determined using 2,3,5-triphenyltrazolium chloride staining, while neurological deficit was assessed based on neurological score. Numbers of apoptotic cells in vivo were estimated using TUNEL stain, and expression of the pro-apoptotic protein BAX and anti-apoptotic protein BCL-2 were quantified by Western blotting. The results showed that 2-BFI (3 mg/kg) administered at 0.5 h after embolic MCAO combined with rt-PA (10 mg/kg) administered at 6 h reduced brain infarct size, mitigated neurological deficit, decreased the number of TUNEL-positive cells, down-regulated BAX expression, and up-regulated BCL-2 expression. These findings suggest that 2-BFI may extend the therapeutic window of rt-PA to 6 h after embolic stroke onset in rats. [ABSTRACT FROM AUTHOR]

The purpose of this study was to compare the efficacy and safety associated with catheter-directed thrombolysis (CDT) using either recombinant tissue plasminogen activator (rt-PA) or urokinase (UK) for subacute deep venous thrombosis (DVT). From January 2014 to December 2016, we conducted a retrospective analysis on a total of 49 patients who underwent consistent CDT with either rt-PA (rt-PA-CDT group) or UK (UK-CDT group) treatment. The thrombolytic rate of the rt-PA-CDT group was significantly higher than that of the UK-CDT group (87.5% vs 60%, respectively; χ2 = 4.751; P = .029). The rt-PA-CDT group exhibited an improved grade III thrombolytic rate (9 patients vs 3 patients; χ2 = 5.144; P = .023). The time for the rt-PA-CDT group to achieve a grade III thrombolytic rate was shorter than that of the UK-CDT group (5.01 ± 1.09 days vs 6.43 ± 1.69 days, respectively; t = −2.187; P = .044). No severe complications were seen in either group and mild complications rates were 16.7% and 20.0% (χ2 = .091; P = .763). The clinical efficacy rates at discharge were 91.7% and 76.0%, respectively (χ2 = 2.200; P = .138). In conclusion, CDT with a continuous infusion of low-dose rt-PA resulted in safe and effective thrombolysis in the great majority of patients with proximal DVT in the subacute phase. Furthermore, rt-PA was significantly better than UK in terms of the thrombolytic rate. In our study, rt-PA-CDT improved the thrombolytic rate of grade III thrombus and achieved a grade III thrombolytic rate in a shorter time than UK-CDT. [ABSTRACT FROM AUTHOR]

Background: Ischemic stroke (IS) is defined as a focal neurologic deficit of sudden onset and of presumed ischemic origin that lasts at least 24 hours and is not associated with hemorrhage on computed tomography (CT) or magnetic resonance imaging (MRI) of the brain. About 87% of strokes are ischemic, the rest being hemorrhagic. Bleeding can develop inside areas of ischemia, a condition known as "hemorrhagic transformation" (HT). Definitive therapy within the first few hours is aimed to removing the blockage by breaking the clot down (thrombolysis), or by removing it mechanically (thrombectomy). Aim of the Work: was to correlate the safety of recombinant tissue plasminogen activator (rt-PA) in acute ischemic stroke (AIS) patients in Egypt. Subjects and Methods: A number of case series of patients with AIS who were treated at Stroke Units of Al-Azhar University Hospitals and Almaadi Military Hospital over a period of 1years within a time window were reported. Results: we observed a statistically significant correlation between AIS patients who were treated by thrombolysis in time window and vascular risk factors and many important infrastructure-logistic factors. Conclusions: It could be concluded that thrombolytic therapy is a good standard treatment in time window but many barriers in developing countries were found. [ABSTRACT FROM AUTHOR]

Background: Intravenous recombinant tissue-type plasminogen activator (rt-PA) with/without endovascular treatment is not as effective in atherosclerotic steno-occlusive acute ischemic stroke. Urgent superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis is effective to some extent in progressing stroke, but the safety of STA-MCA anastomosis soon after rt-PA therapy is unknown. Our aim was to clarify the safety of STA-MCA anastomosis within 24 h after intravenous rt-PA.Method: From 2005 to 2015, rt-PA was administered to 225 patients presenting with acute ischemic stroke according to the Japanese Stroke Guidelines, in our institution. Five patients underwent urgent STA-MCA anastomosis after rt-PA administration with or without endovascular recanalization. Clinical time course, surgical complications, and patients’ prognosis were investigated.Results: The average of patient age was 65.4 years (range 49-77 years); three patients had internal carotid artery occlusion, and two patients had middle cerebral artery occlusion. The median National Institutes of Health Stroke Scale score on admission was 12.4 (range 6-17 points) and operation occurred 10.6 h (range 5.3-23.6 h) after intravenous rt-PA administration. Hemostasis was achieved during standard STA-MCA anastomosis, and there were no hemorrhagic complications.Conclusions: In our consecutive cases, urgent STA-MCA anastomosis after at least 5.3 h after intravenous rt-PA was performed safely without hemorrhagic complications. [ABSTRACT FROM AUTHOR]

Background: There is a widespread belief that Asians are more susceptible to hemorrhagic transformation (HT) after receiving recombinant tissue-type plasminogen activator (rt-PA) for acute ischemic stroke (AIS). However, this has not been examined in clinical practice. This study aims to compare the incidence of symptomatic hemorrhagic transformation (SHT) among thrombolysis-treated AIS patients in China and in the United States.Methods: We compared 212 consecutive patients receiving thrombolysis within 4.5 hours of onset ± endovascular therapy from an American (n = 86) and a Chinese Stroke Center (n = 126). SHT was defined using various definitions based on the National Institute for Neurological Disorders and Stroke Recombinant Tissue Plasminogen Activator (NINDS rt-PA) trials, European-Australian Cooperative Acute Stroke Study 2 (ECASS2), and a modified version of Safe Implementation of Thrombolysis in Stroke-Monitoring Study (mSITS-MOST) study criteria. We used Firth logistic regression to adjust for confounding variables and to identify potential predictors.Results: American patients were older, and had higher prevalence of diabetes, hypertension, cardiac disease, and prestroke use of antithrombotics. They also had higher baseline serum glucose, shorter onset-to-treatment time, and fewer endovascular treatments. The rates of SHT were higher in the American cohort compared to the Chinese cohort: 18.6% versus 14.3% based on NINDS definition of SHT; 15.1% versus 12.7% based on ECASS2; and 11.6% versus 7.2% based on mSITS-MOST. However, none of these differences were significant (unadjusted and adjusted P values > .05). Fatal HT was comparable in Americans versus Chinese (8.1% versus 8.7%). Serum glucose emerged as an independent predictor of SHT (P = .024).Conclusions: In our cohorts, the rate of SHT after thrombolysis is equivalent between Chinese and North American stroke patients. [ABSTRACT FROM AUTHOR]

Thrombolysis with recombinant tissue plasminogen activator (rt-PA) is the only pharmacological approved treatment for ischemic stroke, despite its associated increasing risk of hemorrhagic transformation. Since many of rt-PA effects in blood-brain barrier (BBB) are not well characterized, the study of protein changes in BBB cells after rt-PA administration may help to understand its adverse effects. Our aim was to analyze protein levels of four commonly used housekeeping proteins: β-Actin, α-Tubulin, GAPDH and HPRT in bEnd.3 endothelial cell line subjected to oxygen and glucose deprivation (OGD) conditions and rt-PA treatment to determine their reliability as Western blot loading controls. bEnd.3 monolayers were subjected to 2.5 h of OGD and reperfusion with/without 20 μg/ml of rt-PA. At 3, 6, 24 and 72 h post-OGD, protein levels were analyzed by Western blot using Stain-Free technology. OGD significantly decreased β-Actin, α-Tubulin, GAPDH and HPRT protein levels at 3, 6, 24 and 72 h post-OGD without significant rt-PA treatment effects except for the GAPDH levels increase in control condition at 3 h post-OGD. The present study clearly demonstrated that β-Actin, α-Tubulin, GAPDH and HPRT proteins are not suitable as loading controls for Western Blot analysis in bEnd.3 cells after OGD. Significance We reported altered levels of β-Actin, α-Tubulin, GAPDH and HPRT housekeeping proteins in bEnd.3 endothelial cell line after an ischemic insult. Therefore, we demonstrated that these proteins are not suitable as loading controls for Western Blot analysis in our experimental conditions and we recommended the use of Stain-Free gels as an alternative to traditional housekeeping proteins normalization. [ABSTRACT FROM AUTHOR]

Introduction: Cardiac and electrocardiography (ECG) abnormalities are common in acute ischemic stroke (AIS) patients. Aim of the research: To evaluate the relationship between selected cardiovascular factors and the long-term outcome, the presence of hemorrhagic transformation (HT), symptomatic intracerebral hemorrhage (SICH) and mortality in Caucasian patients with AIS treated with intravenous thrombolysis (i.v. thrombolysis) in routine practice. Material and methods: We prospectively evaluated 286 stroke patients in terms of the impact of cardiovascular factors and changes in the transthoracic echocardiogram (TTE) on the safety and effectiveness of intravenous (i.v.) thrombolysis. Results: In the analyzed group we found atrial fibrillation (AF) in 35.3% of patients and cardiogenic stroke in 31.5% of patients. The first abnormal ECG (p = 0.02) and the presence of AF (p = 0.002) were higher in patients with an unfavorable outcome (modified Rankin Scale, 3-6 points) and in patients who died within 3 months' follow-up (p = 0.02, p = 0.004 respectively). Only median NIHSS score at the time of admission was associated with cardiogenic stroke (p = 0.01). There was no impact of TTE findings on safety and efficacy of i.v. thrombolysis. No significant differences in the long-term outcome, HT and SICH rates and mortality between the subgroups of patients with cardiogenic stroke and patients with other types of strokes were observed. Multivariate analysis showed the impact of AF on the long-term unfavorable outcome (p = 0.02) and mortality rate (p = 0.04). Conclusions: Atrial fibrillation is a strong predictor of unfavorable long-term outcome and death in patients with AIS treated with i.v. thrombolysis in routine practice. Further studies assessing cardiac function in patients undergoing i.v. thrombolysis are needed. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To investigate the curative effect of tirofiban combined with recombinant tissue-plasminogen activator (rt-PA) selective intra-arterial thrombolysis on acute middle cerebral artery occlusion (MCAO). MATERIALS AND METHODS: A total of 60 adult male Japanese white rabbits weighing 2.5-3.0 kg were selected, and the acute cerebral infarction model was established via autologous thromboembolism of middle cerebral artery. Rabbits were randomly divided into 4 groups: tirofiban group (Ti group, 5 μg/kg, n=15), rt-PA group (rt-PA group, 2 mg/kg, n=15), tirofiban + rt- PA group (Ti + rt-PA group, 3 μg/kg Ti + 1 mg/kg rt-PA, n=15), and control group (Co group, n=15). The vascular recanalization rate of intra-arterial thrombolysis was observed via digital subtraction angiography (DSA), relative apparent diffusion coefficient (rADC) was observed via diffusion-weighted imaging (DWI), and neurologic impairment was observed via modified Bederson's scoring method. Rabbits were executed after 24 h, then the volume of cerebral infarction was measured via triphenyl tetrazolium chloride (TTC) staining, pathological examinations were performed using the optical microscope and electron microscope, and immunohistochemical examination was performed for brain-derived neurotrophic factor (BDNF). RESULTS: In Ti + rt-PA group, the vascular recanalization rate was 91.7%, and there was no significant bleeding in pathological examination. The rADC value, neurologic impairment score and cerebral infarction area in Ti + rt-PA group were superior to those in Co group, Ti group and rt-PA group. Immunohistochemical results of BDNF showed that the expression of BDNF in Ti + rt-PA group was increased compared with those in Co group, Ti group and rt-PA group. In Ti group and rt-PA group, there were neuronal degeneration, moderate organelle swelling, moderate mitochondrial swelling, enlarged volume and decreased number of cristae, and rupture and disappearance of some mitochondrial cristae. In Co group, neuronal karyopyknosis, nuclear chromatolysis and disappearance of cellular structure could be seen. Results of electron microscopy showed that the shape of neuronal nuclei in Ti + rt-PA group was basically normal, and there were mild mitochondrial swelling and enlarged volume of cristae. CONCLUSIONS: Early application of tirofiban combined with rt-PA in intra-arterial thrombolysis for ultra-early cerebral ischemia can improve the recanalization rate of cerebral artery. The time of cerebral ischemia and hypoxia is short, and the neuronal ischemia-reperfusion injury is mild, whose thrombolysis effect is better than the single application of tirofiban or rt-PA. [ABSTRACT FROM AUTHOR]

Introduction: In this study, we aimed to identify the factors associated with early neurological improvement (ENI) in acute stroke patients treated with intravenous recombinant tissue plasminogen activator (IV rt-PA), and to determine the association between ENI and outcomes at 3 months after stroke. Methods: Patients with acute ischemic stroke who were treated with IV rt-PA within 4.5 hours of symptom onset from February 2009 to December 2016 were included in the study at the stroke center of Eskişehir Osmangazi University Medical Faculty. ENI was defined as an improvement in National Institutes of Health Stroke Scale (NIHSS) score of >8 points compared to the pretreatment score or an NIHSS score of 0 or 1 at 24 hours after stroke. We assessed the outcomes at 3 months after treatment using the modified Rankin Scale (mRS) score, and mRS scores of 0-1 were defined as 'very good' outcomes. Results: ENI was observed in 43.9% of 355 patients included in the study. Very good outcome at the 3rd month was detected in 80.1% of the patients with ENI, and in 15.6% of the patients without ENI (p<0.001). Patients with ENI were younger (p=0.025), and had lower NIHSS scores (p=0.027) and higher ASPECT scores (p=0.008) than those without. The ENI group had lower serum glucose levels at the time of admission (p< 0.001). Additionally, the presence of diabetes mellitus, hypertension, and hyperdense artery sign were more frequent in the ENI group (p=0.001, p=0.024, and p<0.001, respectively). Finally, multiple regression analysis showed a significant relationship between serum glucose level, hyperdense artery sign, and ENI. Conclusion: There is a significant relationship between ENI and very good outcome at 3 months in acute stroke patients who received IV rt-PA. Therefore, the management of factors such as serum glucose level, NIHSS score, ASPECT score and presence of hyperdense artery sign which are related to ENI, and the determination of treatment strategies according to them are important issues for achieving a better outcome in acute ischemic stroke. [ABSTRACT FROM AUTHOR]

Background The recommended maximum age and time window for intravenous alteplase treatment of acute ischemic stroke differs between the Europe Union and United States. Aims We compared the effects of alteplase in cohorts defined by the current Europe Union or United States marketing approval labels, and by hypothetical revisions of the labels that would remove the Europe Union upper age limit or extend the United States treatment time window to 4.5 h. Methods We assessed outcomes in an individual-patient-data meta-analysis of eight randomized trials of intravenous alteplase (0.9 mg/kg) versus control for acute ischemic stroke. Outcomes included: excellent outcome (modified Rankin score 0–1) at 3–6 months, the distribution of modified Rankin score, symptomatic intracerebral hemorrhage, and 90-day mortality. Results Alteplase increased the odds of modified Rankin score 0–1 among 2449/6136 (40%) patients who met the current European Union label and 3491 (57%) patients who met the age-revised label (odds ratio 1.42, 95% CI 1.21−1.68 and 1.43, 1.23−1.65, respectively), but not in those outside the age-revised label (1.06, 0.90−1.26). By 90 days, there was no increased mortality in the current and age-revised cohorts (hazard ratios 0.98, 95% CI 0.76−1.25 and 1.01, 0.86–1.19, respectively) but mortality remained higher outside the age-revised label (1.19, 0.99–1.42). Similarly, alteplase increased the odds of modified Rankin score 0-1 among 1174/6136 (19%) patients who met the current US approval and 3326 (54%) who met a 4.5-h revised approval (odds ratio 1.55, 1.19−2.01 and 1.37, 1.17−1.59, respectively), but not for those outside the 4.5-h revised approval (1.14, 0.97−1.34). By 90 days, no increased mortality remained for the current and 4.5-h revised label cohorts (hazard ratios 0.99, 0.77−1.26 and 1.02, 0.87–1.20, respectively) but mortality remained higher outside the 4.5-h revised approval (1.17, 0.98–1.41). Conclusions An age-revised European Union label or 4.5-h-revised United States label would each increase the number of patients deriving net benefit from alteplase by 90 days after acute ischemic stroke, without excess mortality. [ABSTRACT FROM AUTHOR]

Background: When symptoms of cerebral infarction are recognized in a patient, he or she should be transported to a hospital and should be started on the appropriate treatments. The effectiveness of delayed treatment of cerebral infarction with respect to the initial diagnosis or perception of the disease is still unclear.Methods: We retrospectively investigated whether the functional outcomes would improve if patients with cerebral infarction were transported to the hospital with minimum delay. One-hundred twenty-two patients who were transported to Mishuku Hospital from January 2012 to August 2015 were included. We conducted multiple regression analyses. The criterion variable included the BI at discharge, and the explanatory variables were age, sex, days of hospital stay, the Barthel Index (BI) on admission, time from symptom onset to hospital arrival, time from emergency medical service perception to hospital arrival, recombinant tissue plasminogen activator (rt-PA) treatment, and the occluded artery type.Results: In all 122 cases, the BI at the time of discharge was not related to onset time (P = .453) but was significantly related to perception time (P = .026). BI scores at discharge were high for young patients (P = .002) and for patients with short hospital stays (P <.001). In the rt-PA group (52 cases), BI scores at discharge were also high when the perception time was short (P = .036).Conclusions: A short interval between perception and hospital arrival improves the functional outcomes for patients with cerebral infarction. Thus, patients with cerebral infarctions must be treated with minimal delay after diagnosis of the condition. [ABSTRACT FROM AUTHOR]

El tratamiento con activador recombinante del plasminógeno tisular (sigla en inglés rt-PA), aplicado por vía intravenosa (VIV) es el procedimiento de primera línea en casos de ataque cerebrovascular agudo (ACVA) en una ventana de 4,5 horas. En Colombia hay una experiencia publicada del uso exitoso de este medicamento. En el número actual se publica una nueva experiencia del uso de rt-PA en el caribe colombiano, de gran utilidad para reseñar los artículos publicados en Colombia acerca del tema.

Purpose: This paper presents the initial experience with thrombolysis for acute ischaemic stroke at Hospital de Base do Distrito Federal (HBDF), Brazil, and the difficulties associated with the implementation of this treatment. Method: A retrospective study was performed using the medical records of all patients with acute stroke who were treated with intravenous alteplase in our department, between May 2011 and April 2012. Results: The thrombolytic therapy was administered to 32 patients. The mean time between the ictus and the start of stroke therapy start was 195 (60-270) minutes. Sixteen patients demonstrated a significant clinical improvement (decrease in National Institute Health Stroke Scale [NIHSS] score≥4 points in 24 hours); 6 patients were discharged with an NIHSS score of 0 and 2 demonstrated haemorrhagic transformation. Conclusions: The results of our study are similar to those reported in the literature, although we have been dealing with difficulties, such as the lack of a stroke unit.

Background and Purpose: To evaluate risk factors for intracerebral hemorrhages and the clinical effects of these hemorrhages in patients treated with recombinant tissue plasminogen activator (rt-PA) for acute stroke. Methods: In this prospective analysis, data were collected for patients with acute anterior circulation stroke who received intravenous (IV) rt-PA within 4.5 hours of symptom onset, after computed tomography (CT) between December 2008 and July 2013. Copies of head CT scans were obtained 24 hours after starting treatment. Intracerebral hemorrhages were classified according to the European-Australasian Acute Stroke Study (ECASS) classification. The definition of Safe Implementation of Thrombolysis in Stroke (SITS) was used for symptomatic intracerebral hemorrhage (sICH). The clinical outcomes of the patients were determined using the modified Rankin scale (mRS) at 90 days after treatment. Results: Asymptomatic intracerebral hemorrhage (aICH) was observed in 50 (22.6%) of 221 patients and symptomatic intracerebral hemorrhage (sICH) was observed in 9 (4.1%). Multivariate analysis showed that the baseline glucose level and Alberta Stroke Program Early CT (ASPECT) score were associated with sICH. However, only the baseline ASPECT score was related to aICH. Patients with sICH and aICH both had higher mRS scores and mortality rates at 90 days compared with those without. Conclusions: The presence of early ischemic changes on CT and hyperglycemia at the time of admission are independent risk factors for sICH in patients treated with IV rt-PA. Therefore, care must be taken in the evaluation and management of these factors. [ABSTRACT FROM AUTHOR]

Acute ischemic stroke is inadequately treated in the USA and worldwide due to a lengthy history of neuroprotective drug failures in clinical trials. The majority of victims must endure life-long disabilities that not only affect their livelihood, but also have an enormous societal economic impact. The rapid development of a neuroprotective or cytoprotective compound would allow future stroke victims to receive a treatment to reduce disabilities and further promote recovery of function. This opinion article reviews in detail the enormous costs associated with developing a small molecule to treat stroke, as well as providing a timely overview of the cell-death time-course and relationship to the ischemic cascade. Distinct temporal patterns of cell-death of neurovascular unit components provide opportunities to intervene and optimize new cytoprotective strategies. However, adequate research funding is mandatory to allow stroke researchers to develop and test their novel therapeutic approach to treat stroke victims. [ABSTRACT FROM AUTHOR]