Ischemic Stroke In Clinical Practice Research Articles

Linarin ameliorates ischemia-reperfusion injury by the inhibition of endoplasmic reticulum stress targeting AKR1B1

Due to various factors, there is still a lack of effective neuroprotective agents for ischemic stroke in clinical practice. Neuroinflammation and neuronal apoptosis mediated by endoplasmic reticulum stress are some of the important pathological mechanisms in ischemic stroke. Linarin has been reported to have anti-inflammation, antioxidant, and anti-apoptotic effects in myocardial ischemia, osteoarthritis, and kidney disease. Whether it exerts neuroprotective functions in ischemic stroke has not been investigated. The results showed that linarin could reduce the infarct volume in cerebral ischemia animal models, improve the neurological function scores and suppress the expression of inflammatory factors mediating the NF-κB. Meanwhile, it could protect the neurons from OGD/R-induced-apoptosis, which was related to the PERK-eIF2α pathway. Our results suggested linarin could inhibit neuronal inflammation and apoptosis induced by endoplasmic reticulum stress. Furthermore, the neuroprotective effect of linarin may be related to the inhibition of AKR1B1. Our study offers new insight into protecting against ischemia-reperfusion injury by linarin treatment in stroke.

Intermittent hypoxia protects against hypoxic-ischemic brain damage by inducing functional angiogenesis

Ischemic stroke (IS) induces neurological damage due to cerebrovascular occlusion. Restoring blood perfusion to the ischemic brain area in a timely fashion is the most effective treatment strategy. Hypoxia is an effective way of restoring blood perfusion by improving cerebrovascular microcirculation, while the effect varies greatly depending on hypoxic mode. This study aimed to screen for the optimal hypoxic mode to improve cerebrovascular microcirculation and prevent IS. Here, we found that compared with continuous hypoxia (CH), intermittent hypoxia (IH) significantly improved cerebral blood flow and oxygen saturation in mice without causing neurological impairment. By analyzing cerebrovascular microcirculation from mice, we found that the IH mode (13%, 5*10) with 13% O2, 5 min interval, and 10 cycles per day significantly improved the cerebrovascular microcirculation by promoting angiogenesis without affecting the integrity of the blood-brain barrier. In addition, IH (13%, 5*10) treatment of distal middle cerebral artery occlusion (dMCAO) mice significantly alleviated neurological dysfunction and reduced cerebral infarct volume by improving cerebrovascular microcirculation. CH had none of these positive effects. In summary, our study screened for an appropriate intermittent hypoxic mode that could improve cerebrovascular microcirculation, laying a theoretical foundation for the prevention and treatment of IS in clinical practice.

Impact of Oral Contraceptive on Induction of Ischemic Stroke in Female Rats

Background and Aim: There are evidences for role of oral contraceptives on the induction of ischemic stroke in clinical practice, but pathophysiological mechanism underlying these close relationships remains unknown. Furthermore, the impact of oral contraceptive on induction of ischemic stroke in female rats has not been previously studied. This study investigated the induction of ischemic stroke by dose-dependent oral contraceptive in rats. Methods: Wistar 30 rats were randomly chosen and divided into three groups: High dose group-1 received daily oral contraceptive (OC), ethinylestradiol (20 mg/kg orally for 16 days) and low dose group-2 (5 mg/kg orally for 16 days) while control group received daily oral saline. The number of neurons per slice in the CA1 hippocampal region and the changes of neurological score as behavioral testing were measured in each group. Results: We demonstrated the number of neurons per slice in the CA1 hippocampal region in both high and low dose of oral contraceptive decreased in female rats, in particular, in high group was significantly decreased compared with control group. In addition, a neurological deficit was evident in dose-dependent of oral contraceptive. Further studies are needed to confirm the pathological mechanisms by oral contraceptives but our data provide that oral contraceptive, ethinylestradiol may induce ischemic stroke in dose-dependent.

Abstract WP162: Primary Results Of Mechanical Thrombectomy For Acute Ischemic Stroke In Clinical Practice: K-net Registry

Background: Endovascular treatment (EVT) for acute large vessel occlusion has been found to be effective in several randomized controlled trials. We conducted a prospective cohort study to evaluate the real-world efficacy of EVT in patients with acute ischemic stroke in a metropolitan area with a high population density and a large number of comprehensive stroke centers. Methods: We analyzed the Kanagawa Intravenous and Endovascular Treatment of Acute Ischemic Stroke registry, a prospective, multicenter observational study of patients treated by EVT and/or intravenous tissue-type plasminogen activator (tPA), in Kanagawa, Japan. Of the 2488 patients enrolled from January 2018 to June 2020, 1764 patients treated with EVT were included. The primary outcome was a good outcome, which was defined as a modified Rankin Scale (mRS) of 0 to 2 at 90 days. Secondary analysis included predicting a good outcome using multivariate logistic regression analysis. Results: The median age was 77 years and the median National Institute of Health Stroke Scale (NIHSS) score was 18. Pretreatment mRS score 0-2 was 87%, and direct transport was 92%. The rate of occlusion in anterior circulation was 90.3%. Successful recanalization was observed in 88.7%. The median time from onset to recanalization was 193 minutes. Good outcomes at 90 days were 43.3% in anterior circulation and 41.9% in posterior circulation. Furthermore, 49.3% of patients with anterior circulation obstruction who had pre-stroke mRS 0-2 had good outcome, which was higher than the HERMES trial. Overall mortality was 12.6%. Significant predictors for a good outcome were: age, male, direct transfer, NIHSS score, Alberta Stroke Program Early Computed Tomography Score, intravenous tPA, and successful recanalization. Conclusions: EVT in routine clinical use in a metropolitan area showed comparable good outcomes and lower mortality compared to previous registries and RCTs, despite the high proportion of patients with older age, pretreatment mRS score of > 2, posterior circulation occlusion, and higher NIHSS. Those results may have been associated with more direct transport and faster onset-to-recanalization times.

Endovascular Treatment of Acute Ischemic Stroke in Clinical Practice: Analysis of Workflow and Outcome in a Tertiary Care Center.

Background and Purpose: Pre- and intra-hospital workflow in mechanical recanalization of large cervicocephalic arteries in patients with acute ischemic stroke still needs optimization. In this study, we analyze workflow and outcome in our routine care of stroke patients undergoing mechanical thrombectomy as a precondition for such optimization.Methods: Processes of pre- and intra-hospital management, causes of treatment delay, imaging results (Alberta Stroke Program Early Computed Tomography Score, localization of vessel occlusion), recanalization (modified thrombolysis in cerebral infarction score), and patient outcome (modified Rankin scale at discharge and at the end of inpatient rehabilitation) were analyzed for all patients who underwent mechanical thrombectomy between April 1, 2016, and September 30, 2018, at our site.Results: Finally, data of 282 patients were considered, of whom 150 (53%) had been referred from external hospitals. Recanalization success and patient outcome were similar to randomized controlled thrombectomy studies and registries. Delay in treatment occurred when medical treatment of a hypertensive crisis, epileptic fits, vomiting, or agitation was mandatory but also due to missing prenotification of the hospital emergency staff by the rescue service, multiple mode or repeated brain imaging, and transfer from another hospital. Even transfer from external hospitals located within a 10-km radius of our endovascular treatment center led to a median increase of the onset-to-groin time of ~60 min.Conclusion: The analysis revealed several starting points for an improvement in the workflow of thrombectomy in our center. Analyses of workflow and treatment results should be carried out regularly to identify the potential for optimization of operational procedures and selection criteria for patients who could benefit from endovascular treatment.

Longxuetongluo Capsule protects against cerebral ischemia/reperfusion injury through endoplasmic reticulum stress and MAPK-mediated mechanisms

IntroductionLongxuetongluo Capsule (LTC) is wildly applied to treat ischemic stroke in clinical practice in China. However, the pharmacological mechanism of LTC on ischemic stroke is still unstated. ObjectiveOur research was designed to study the protective effect of LTC against cerebral ischemia–reperfusion (I/R) injury and reveal the underlying mechanism both in vivo and in vitro. MethodsPC12 cells treated with glucose deprivation/reperfusion (OGD/R) were used to simulate in vitro ischemia/reperfusion (I/R) injury. The cell viability, apoptosis rate, and protein expressions of PC12 cells were evaluated. In vivo validation of the protective effect of LTC was carried out by middle cerebral artery occlusion (MCAO)/reperfusion treatment, and the underlying mechanism of its anti-apoptosis ability was further revealed by immunohistochemistry staining and Western blotting. ResultsIn the current study, we observed that LTC effectively inhibited oxygen-glucose deprivation/reperfusion (OGD/R) induced apoptosis of PC12 cells through suppressing the cleavage of poly ADP-ribose polymerase (PARP), caspase-3, and caspase-9. Further investigation revealed that OGD/R insult remarkably triggered the endoplasmic reticulum stress responses (ER stress) to induce PC12 cell apoptosis. LTC treatment alleviated OGD/R induced ER stress by inhibiting the activation of protein kinase RNA (PKR)-like ER kinase (PERK)/eukaryotic translation initiation factor 2 (eIF2α) and inositol requiring enzyme 1 (IRE1)/tumor necrosis factor receptor-associated factor 2 (TRAF2) pathways. Additionally, LTC also restrained the OGD/R-induced PC12 cell apoptosis by reversing the activated mitogen-activated protein kinase (MAPK) through IRE1/TRAF2 pathway. Animal studies demonstrated LTC significantly restricted the infarct region induced by middle cerebral artery occlusion (MCAO)/reperfusion, the activation of ER stress and apoptosis of neuronal cells had also been suppressed by LTC in the penumbra region. ConclusionLTC protects the cerebral neuronal cell against ischemia/reperfusion injury through ER stress and MAPK-mediated mechanisms.

Sex Differences in Outcome After Thrombectomy for Acute Ischemic Stroke are Explained by Confounding Factors

PurposeThe aim of this study was to analyze sex differences in outcome after thrombectomy for acute ischemic stroke in clinical practice in a large prospective multicenter registry.MethodsData of consecutive stroke patients treated with thrombectomy (June 2015–April 2018) derived from an industry-independent registry (German Stroke Registry–Endovascular Treatment) were prospectively analyzed. Multivariable binary logistic regression analyses were applied to determine whether sex is a predictor of functional independence outcome (defined as a modified Rankin scale [mRS] 0–2) 90 days after stroke.ResultsIn total, 2316 patients were included in the analysis, 1170 (50.5%) were female and 1146 (49.5%) were male. Women were older (median age 78 vs. 72 years; p < 0.001) and more frequently had a prestroke functional impairment defined by mRS >1 (24.8% vs. 14.1%; p < 0.001). In unadjusted analyses, independent outcome at 90 days was less frequent in women (33.2%) than men (40.6%; p < 0.001). Likewise, mortality was higher in women than in men (30.7% vs. 26.4%; p = 0.024). In adjusted regression analyses, however, sex was not associated with outcome. Lower age, a lower baseline National Institutes of Health Stroke Scale score, a higher Alberta Stroke Program Early CT score, prestroke functional independence, successful reperfusion, and concomitant intravenous thrombolysis therapy predicted independent outcome.ConclusionWomen showed a worse functional outcome after thrombectomy for acute ischemic stroke in clinical practice; however, after adjustment for crucial confounders sex was not a predictor of outcome. The difference in outcome thus appears to result from differences in confounding factors such as age and prestroke functional status.

Microglia-associated neuroinflammation is a potential therapeutic target for ischemic stroke.

Microglia-associated neuroinflammation plays an important role in the pathophysiology of ischemic stroke. Microglial activation and polarization, and the inflammatory response mediated by these cells play important roles in the development, progression and outcome of brain injury after ischemic stroke. Currently, there is no effective strategy for treating ischemic stroke in clinical practice. Therefore, it is clinically important to study the role and regulation of microglia in stroke. In this review, we discuss the involvement of microglia in the neuroinflammatory process in ischemic stroke, with the aim of providing a better understanding of the relationship between ischemic stroke and microglia.

Ischemic stroke in clinical practice

Ischemic stroke in clinical practice

Implementation of multiphase computed tomography angiography in management of patients with acute ischemic stroke in clinical practice

Multiphase computed tomography angiography (CTA) provides information on the status of major cranial arteries and extent of brain collateralization. The purpose of the study was to determine whether implementation of multiphase CTA in routine clinical practice was feasible, safe and useful. Patients with acute ischemic stroke (NIHSS ≥ 6) were included. Multiphase CTA was performed. Duration of performing multiphase CTA, inter-rater correlation and incidence of contrast-induced nephropathy (CIN) were studied. Infarct volume, incidence of hemorrhagic transformation, the rates of favorable outcome and death were compared between those with poor and intermediate-good collateralization. Multiphase CTA was performed in 108 patients. Mean duration on each multiphase CTA study was 4.8 min. Inter-rater reliability was intermediate-good (weighted kappa 0.7569, p < 0.001). CIN occurred in 3 patients (2.8%). There were no major intracranial/extracranial artery occlusion in 31 patients (29%) and there were severe stenosis or occlusions in 77 patients (71%). In the subgroup of patients with major artery severe stenosis or occlusion, 36 patients (36/77, 47%) had poor collateralization. Despite non-significant difference in acute treatment, the patients with poor collateralization had larger infarct (123 vs 35 cc, p < 0.001) and poorer outcomes (mean modified Rankin scale 3.86 vs 2.73, p = 0.011), while the differences in symptomatic hemorrhagic transformation (2.6 vs 7%, p = 0.385) and death rate (14 vs 12%, p = 0.825) were non-significant, as compared to those with intermediate-good collateralization. Multiphase CTA was feasible and safe. Besides the status of major arteries, multiphase CTA provided information on collateralization, which was associated with the size of infarct and clinical outcomes.

Genetic Predisposition to Ischemic Stroke: A Polygenic Risk Score.

The prediction of genetic predispositions to ischemic stroke (IS) may allow the identification of individuals at elevated risk and thereby prevent IS in clinical practice. Previously developed weighted multilocus genetic risk scores showed limited predictive ability for IS. Here, we investigated the predictive ability of a newer method, polygenic risk score (polyGRS), based on the idea that a few strong signals, as well as several weaker signals, can be collectively informative to determine IS risk. We genotyped 13 214 Japanese individuals with IS and 26 470 controls (derivation samples) and generated both multilocus genetic risk scores and polyGRS, using the same derivation data set. The predictive abilities of each scoring system were then assessed using 2 independent sets of Japanese samples (KyushuU and JPJM data sets). In both validation data sets, polyGRS was shown to be significantly associated with IS, but weighted multilocus genetic risk scores was not. Comparing the highest with the lowest polyGRS quintile, the odds ratios for IS were 1.75 (95% confidence interval, 1.33-2.31) and 1.99 (95% confidence interval, 1.19-3.33) in the KyushuU and JPJM samples, respectively. Using the KyushuU samples, the addition of polyGRS to a nongenetic risk model resulted in a significant improvement of the predictive ability (net reclassification improvement=0.151; P<0.001). The polyGRS was shown to be superior to weighted multilocus genetic risk scores as an IS prediction model. Thus, together with the nongenetic risk factors, polyGRS will provide valuable information for individual risk assessment and management of modifiable risk factors.

Use of Strategies to Improve Door-to-Needle Times With Tissue-Type Plasminogen Activator in Acute Ischemic Stroke in Clinical Practice: Findings from Target: Stroke.

The implementation of Target: Stroke Phase I, the first stage of the American Heart Association's national quality improvement initiative to accelerate door-to-needle (DTN) times, was associated with an average 15-minute reduction in DTN times. Stroke phase II was launched in April 2014 with a goal of promoting further reduction in treatment times for tissue-type plasminogen activator (tPA) administration. We conducted a second survey of Get With The Guidelines-Stroke hospitals regarding strategies used to reduce delays after Target: Stroke and quantify their association with DTN times. A total of 16 901 ischemic stroke patients were treated with intravenous tPA within 4.5 hours of symptom onset from 888 surveyed hospitals between June 2014 and April 2015. The patient-level median DTN time was 56 minutes (interquartile range, 42-75), with 59.3% of patients receiving intravenous tPA within 60 minutes and 30.4% within 45 minutes after hospital arrival. Most hospitals reported routinely using a majority of Target: Stroke key practice strategies, although direct transport of patients to computed tomographic/magenetic resonance imaging scanner, premix of tPA ahead of time, initiation of tPA in brain imaging suite, and prompt data feedback to emergency medical services providers were used less frequently. Overall, we identified 16 strategies associated with significant reductions in DTN times. Combined, a total of 20 minutes (95% confidence intervals 15-25 minutes) could be saved if all strategies were implemented. Get With The Guidelines-Stroke hospitals have initiated a majority of Target: Stroke-recommended strategies to reduce DTN times in acute ischemic stroke. Nevertheless, certain strategies were infrequently practiced and represent a potential immediate target for further improvements.

Ischemic Stroke in Children and Young Adults with Sickle Cell Disease (SCD) in the Post-STOP Era

Background: The Stroke Prevention Trial in Sickle Cell Anemia (STOP) and Optimizing Primary Stroke Prevention in Sickle Cell Anemia (STOP 2) established routine transcranial Doppler ultrasound (TCD) screening with indefinite chronic red cell transfusions (CRCT) for children with abnormal TCD as standard of care. To identify children at high-risk of stroke, annual TCD screening is recommended from ages 2 to 16 years, with more frequent monitoring if the result is not normal. A reduction in stroke incidence in children with SCD has been reported in several clinical series and analyses utilizing large hospital databases when comparing rates before and after the publication of the STOP study in 1998. We sought to determine the rate of first ischemic stroke in a multicenter cohort of children who had previously participated in the STOP and/or STOP 2 trials and to determine whether these strokes were screening or treatment failures.Subjects and Methods: Between 1995 and 2005, STOP and STOP 2 (STOP/2) were conducted at 26 sites in the US and Canada. These studies included 3,835 children, ages 2 to 16 y with SCD type SS or S-beta-0-thalassemia. Participation in STOP/2 ranged from a single screening TCD to randomization. STOP 2 also had an observational arm for children on CRCT for abnormal TCD whose TCD had not reverted to normal. The Post-STOP study was designed to follow-up the outcomes of children who participated in one or both trials. 19 of the 26 original study sites participated in Post-STOP, contributing a total of 3,539 (92%) of the STOP/2 subjects. After exit from STOP/2, these children received TCD screening and treatment according to local practices. Data abstractors visited each clinical site and obtained retrospective data from STOP/2 study exit to 2012-2014 (depending on site) including follow-up TCD and brain imaging results, clinical information, and laboratory results. Two vascular neurologists, blinded to STOP/2 status and prior TCD and neuroimaging results, reviewed source records to confirm all ischemic strokes, defined as a symptomatic cerebral infarction; discordant opinions were resolved through discussion. For the first Post-STOP ischemic stroke, prior TCD result and treatment history subsequently were analyzed.Results: Of the 3,539 subjects, follow-up data were available for 2,850 (81%). Twelve children who had a stroke during STOP or STOP2 were excluded from these analyses resulting in data on 2,838 subjects. The mean age at the start of Post-STOP was 10.5 y and mean duration of follow-up after exiting STOP/2 was 9.1 y. A total of 69 first ischemic strokes occurred in the Post-STOP observation period (incidence 0.27 per 100 pt years). The mean age at time of stroke was 14.4±6.2 (median 13.8, range 3.5-28.9) y. Twenty-five of the 69 patients (36%) had documented abnormal TCD (STOP/2 or Post-STOP) prior to the stroke; 15 (60%) were receiving CRCT and 9 (36%) were not (treatment data not available for 1 subject). Among the 44 subjects without documented abnormal TCD, 29 (66%) had not had TCD re-screen in the Post-STOP period prior to the event; 7 of these 29 (24%) were 16 y or older at the start of Post-STOP, which is beyond the recommended screening age. Four of the 44 (9%) patients had inadequate TCD in Post-STOP (1 to 10.7 y prior to event). Six (14%) had normal TCD more than a year before the event (1.2 - 4 y); all but one of these children were younger than 16 y at the time of that TCD. Only 5 (11%) had a documented normal TCD less than 1 year prior to the event.Conclusions: In the Post-STOP era, the rate of first ischemic stroke was substantially lower than that reported in the Cooperative Study of Sickle Cell Disease, prior to implementation of TCD screening. Many (39%) of the Post-STOP ischemic strokes were associated with a failure to re-screen according to current guidelines, while only 11% occurred in children who had had recent low-risk TCD. Among those known to be at high risk prior to stroke, treatment refusal or inadequate treatment may have contributed. While TCD screening and treatment are effective at reducing ischemic stroke in clinical practice, significant gaps in screening and treatment, even at sites experienced in the STOP protocol, remain to be addressed. Closing these gaps should provide yet further reduction of ischemic stroke in SCD. DisclosuresNo relevant conflicts of interest to declare.

Prevention of ischemic stroke in clinical practice: a role of internists and general practitioners.

Stroke constitutes a substantial clinical and socio-economic burden. It is currently the third cause of death worldwide and results in mortality or disability in every third patient at the end of the first year following an acute cerebrovascular event. Although in-hospital mortality rates in stroke patients have decreased, prevention and cardiovascular risk control remain critical for improving the prognosis and reducing stroke burden worldwide. The definitions of stroke and transient ischemic attack (TIA) have been recently modified following the findings from neuroimaging and thrombolysis research. Both stroke and TIA are recurrent and preventable disorders. Both patients with stroke and those with TIA require prompt clinical workup, risk assessment, and appropriate management because the risk of recurrence, stroke, and coronary events is significant. The 5 most common cardiovascular risk factors (high blood pressure, smoking, abdominal obesity, diet, and lack of physical activity) are responsible for 80% of the cases. Stroke prevention involves lifestyle modification and specific treatment. Secondary prevention of ischemic stroke involves early treatment (antiplatelets and carotid interventions) and long-term management including lifestyle changes, antihypertensive therapy, antiplatelets, antithrombotic drugs in patients with atrial fibrillation, and the use of statins and other lipid-lowering drugs. Stroke patients are at risk of depression, dementia, epilepsy, and other complications that also require targeted treatment.

Evolving Role of Endovascular Treatment of Acute Ischemic Stroke

The perceived advantages of endovascular treatment for acute ischemic stroke in terms of recanalization, the multimodal and targeted approaches, and perhaps the more permissive rules on devices than on medications for their licensing favored the assumption that endovascular treatment is superior to intravenous thrombolysis for acute treatment of ischemic stroke, and its adoption in more advanced stroke centers. However, this assumption has been questioned by recent clinical trial experience showing that endovascular treatment is not superior to intravenous thrombolysis. The new evidence has changed the perception and the importance of conducting randomized trials in this area. This summary examines the background and outcomes of the latest experience with endovascular techniques in acute stroke treatment based on historical data. The new challenge is how to study the latest generation of devices called stent retrievers, which are faster in recanalizing and easier to use, in selected patients with acute ischemic stroke. In the meantime, the available evidence does not provide support for the use of endovascular treatment of acute ischemic stroke in clinical practice.

Changes in T2 relaxation time after stroke reflect clearing processes

CT and MR imaging techniques are frequently used for the diagnosis and progress monitoring of ischemic stroke in clinical practice and research. After stroke, both methods are characterized by a transient pseudo-normalized imaging signal, the so-called fogging phenomenon. This study evaluates potential pathophysiological changes associated with fogging, as well as its influence on the correct determination of the ischemic lesion in a rat stroke model. Male spontaneously hypertensive rats were subjected to permanent middle cerebral artery occlusion. Ischemic lesion volume, brain edema and gray scale value spread within the ischemic lesion were determined on T2-weighted MR sequences at days 1, 4, 8, 11 and 29 after stroke onset, and compared with immunohistochemistry for astrogliosis, microglia/macrophage infiltration and angiogenesis. All animals showed MR fogging at days 4, 8 and 11 after stroke. The transient normalization of T2 signals occurred independently from the development of infarct volumes, but coincided well with the spatio-temporal occurrence of necrosis, angiogenesis and microglia/macrophage infiltration. Our results suggest that the fogging effect reflects the clearance of necrotic tissue within the ischemic lesion and is thus not relevant for the determination of the lesion volume.

CT-based intravenous thrombolysis 3-4·5 hours after acute ischemic stroke in clinical practice

<title/>Background: Outcome of stroke patients selected with cerebral computed tomography for intravenous thrombolysis administered in clinical routine from 3 to 4·5 hours after symptoms onset is not well investigated. Aim of this single-center, prospective, observational study was to compare the safety and efficacy of intravenous alteplase given in routine clinical praxis 181-270 minutes (late) and within 180 minutes (early) after stroke onset in patients selected with cerebral computed tomography.Methods: A total of 454 consecutive patients underwent intravenous thrombolysis within 4·5 hours after stroke onset. Sixty of 454 patients were excluded (inclusion in a controlled-randomized trial, n = 51; stroke mimics, n = 9). Of remaining 394 patients, 100 were included in the late group, and 294 were included in the early group. The outcome parameters of symptomatic intracranial hemorrhage at 24 hours, and mortality and favorable outcome (modified Rankin scale score 0-1) at 3 months, and its predictors were investigated.Results: In the late cohort, median baseline National Institutes of Health Stroke Scale score was lower (9·5, interquartile range (IQR): 5-13; 11·3, IQR: 6-16; P = 0·01), and median time-to-treatment was longer (209, IQR: 190-222 minutes; 142, IQR: 125-170 minutes; P<0·0001) than in the early group. The incidence of symptomatic intracranial hemorrhage (2·0% versus 2·4%; P = 1·0), death (9·0% versus 9·9%; P = 1·0) and favorable outcome (58·0% versus 51·5%; P = 0·3) did not differ between the late and early cohorts.Conclusion: These data suggest that intravenous alteplase administered 181-270 minutes after symptoms onset in stroke patients selected with cerebral computed tomography is also beneficial in real-life clinical practice.

Tissue plasminogen activator for acute ischemic stroke in clinical practice: a meta-analysis of safety data.

Concerns persist regarding the safety of tissue plasminogen activator (tPA) therapy for acute ischemic stroke. Numerous case series of clinical experience with tPA have been published that provide additional data on the safety of thrombolytic therapy. This is a meta-analysis of 15 published, open-label studies that broadly followed approved indications and guidelines for tPA use in nonselective patient populations. In 2639 treated patients, the symptomatic intracerebral hemorrhage rate was 5.2% (95% confidence interval, 4.3 to 6.0), slightly lower than the 6.4% rate in the treated group of the randomized, placebo-controlled National Institute of Neurological Disorders and Stroke (NINDS) trial. The mean total death rate (13.4%) and proportion of subjects achieving a very favorable outcome (37.1%) were comparable to the NINDS trial results. Protocol deviations were reported in 19.8%. Comparing across studies showed that the mortality rate was correlated with the percentage of protocol violations (r=0.67, P=0.018). Postapproval data support the safety of intravenous thrombolytic therapy with tPA for acute ischemic stroke, especially when established treatment guidelines are followed.

Markers of increased risk of intracerebral hemorrhage after intravenous recombinant tissue plasminogen activator therapy for acute ischemic stroke in clinical practice: the multicenter rt-PA acute stroke survey

Markers of increased risk of intracerebral hemorrhage after intravenous recombinant tissue plasminogen activator therapy for acute ischemic stroke in clinical practice: the multicenter rt-PA acute stroke survey

Markers of increased risk of intracerebral hemorrhage after intravenous recombinant tissue plasminogen activator therapy for acute ischemic stroke in clinical practice: the Multicenter rt-PA Stroke Survey.

Intravenous recombinant tissue plasminogen activator (rtPA) is an effective therapy for acute ischemic stroke, but it is associated with risk of intracerebral hemorrhage (ICH). Our aim was to identify, in a large cohort of patients, readily available baseline factors that are associated with thrombolysis-related ICH. In a multicenter retrospective and prospective investigation of individual data from 1205 patients treated in routine clinical practice with intravenous rtPA within 3 hours of stroke symptom onset, 72 patients (6%) developed symptomatic ICH and 86 additional patients (7%) had asymptomatic ICH identified on a routine follow-up CT. In analyses based on clinical variables alone, the main attributes associated with ICH were a history of diabetes mellitus and cardiac disease, increasing stroke severity, advancing age, use of antiplatelet agents other than aspirin before stroke onset, and elevated pretreatment mean blood pressure. In additional analyses that incorporated baseline CT and laboratory findings (in a subset of patients), the main associations were early ischemic CT changes, in particular if exceeding one third of middle cerebral artery territory; increasing stroke severity; diabetes mellitus or elevated serum glucose; and lower platelet counts. Final independent attributes associated with parenchymatous hematoma, defined by purely radiologically based criteria, were similar to those of symptomatic ICH. Readily available factors can identify acute ischemic stroke patients at high and low risk for rtPA-related ICH. These factors require confirmation in a prospective cohort before clinical implementation.