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Background: The objective of this study was to establish a predictive model utilizing machine learning techniques to anticipate the likelihood of thrombolysis resistance (TR) in acute ischaemic stroke (AIS) patients undergoing recombinant tissue plasminogen activator (rt-PA) intravenous thrombolysis, given that nearly half of such patients exhibit poor clinical outcomes., Methods: Retrospective clinical data were collected from AIS patients who underwent intravenous thrombolysis with rt-PA at the First Affiliated Hospital of Bengbu Medical University. Thrombolysis resistance was defined as ([National Institutes of Health Stroke Scale (NIHSS) at admission - 24-hour NIHSS] × 100％/ NIHSS at admission) ≤ 30%. In this study, we developed five machine learning models: logistic regression (LR), extreme gradient boosting (XGBoost), support vector machine (SVM), the least absolute shrinkage and selection operator (LASSO), and random forest (RF). We assessed the model's performance by using receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA), and presented the results through a nomogram., Results: This study included a total of 218 patients with AIS who were treated with intravenous thrombolysis, 88 patients experienced TR. Among the five machine learning models, the LASSO model performed the best. The area under the curve (AUC) on the testing group was 0.765 (sensitivity: 0.767, specificity: 0.694, accuracy: 0.727). The apparent curve in the calibration curve was similar to the ideal curve, and DCA showed a positive net benefit. Key features associated with TR included NIHSS at admission, blood glucose, white blood cell count, neutrophil count, and blood urea nitrogen., Conclusion: Machine learning methods with multiple clinical variables can help in early screening of patients at high risk of thrombolysis resistance, particularly in contexts where healthcare resources are limited., (© 2024. The Author(s).)

What Is Known and Objective: Thrombolysis with Alteplase (rtPA) improves functional outcome among selected patients after acute ischaemic stroke. Benefits are most pronounced with early intervention. Our aim is to assess door to needle time (DTNT) for acute stroke after a stroke call-out redesign including addition of an emergency medicine (EM) pharmacist to the team., Methods: A retrospective cohort of stroke patients who received rtPA was compared to a prospective cohort after stroke callout re-design in an adult major referral hospital in metropolitan Melbourne, Australia. All patients who presented during EM pharmacist working hours and were thrombolysed in the ED for stroke from December 2011-June 2014 pre and July 1 st 2014-August 2019 post were included. The primary outcome was DTNT. Secondary outcomes included proportion of patients with a DTNT within 60 min, time to blood pressure (SBP) reduction, intracranial and extracranial bleeding, hospital length of stay (LOS) and mortality., Results and Discussion: There were 218 patients eligible, 64 patients pre and 122 patients post implementation were included. The cohorts were similar in demographics. There was a significant association of time to thrombolysis (HR 1.61; 95% CI: 1.18-2.20; p = 0.003) with the intervention. Median DTNT improved from 73 (IQR 52-111) min to 61 (IQR 47-80) min (p = 0.012). Interrupted time-series analysis did not demonstrate intervention at the single time-point of implementation of the intervention to be associated with the improvement., What Is New and Conclusion: Re-design of the stroke call-out team that included addition of an EM pharmacist was associated with improvements in DTNT. The effect of individual interventions at one point in time could not be demonstrated., (© 2021 John Wiley & Sons Ltd.)

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. TWEETABLE ABSTRACT: 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., (© 2020 John Wiley & Sons Ltd.)

Both intravenous thrombolysis (IVT) and mechanical thrombectomy (MT) are evidence-based treatments for acute ischemic stroke (AIS) in selected cases. Recanalization may occur following IVT without the necessity of further interventions or requiring a subsequent MT procedure. IVT prior to MT (bridging-therapy) may be associated with benefits or hazards. We studied the retrieved clot area and degree of recanalization in patients undergoing MT or bridging-therapy for whom it was possible to collect thrombus material. We collected mechanically extracted thrombi from 550 AIS patients from four International stroke centers. Patients were grouped according to the administration (or not) of IVT before thrombectomy and the mechanical thrombectomy approach used. We assessed the number of passes for clot removal and the mTICI (modified Treatment In Cerebral Ischemia) score to define revascularization outcome. Gross photos of each clot were taken and the clot area was measured with ImageJ software. The non-parametric Kruskal-Wallis test was used for statistical analysis. 255 patients (46.4%) were treated with bridging-therapy while 295 (53.6%) underwent MT alone. By analysing retrieved clot area, we found that clots from patients treated with bridging-therapy were significantly smaller compared to those from patients that underwent MT alone (H 1  = 10.155 p = 0.001*). There was no difference between bridging-therapy and MT alone in terms of number of passes or final mTICI score. Bridging-therapy was associated with significantly smaller retrieved clot area compared to MT alone but it did not influence revascularization outcome.

The benefits and risks of acute reperfusion therapy (RT) in acute ischaemic stroke (AIS) remain uncertain in older patients, especially in nonagenarians. We aimed to assess the impact of RT in this population. Single-center retrospective cohort study comparing patients ≥ 90 years old admitted to a Stroke Unit (2008-2018) with AIS, submitted or not to RT [intravenous thrombolysis(IVT), mechanical thrombectomy(MT) or both]. Baseline characteristics, in-hospital complications and 3-month outcomes were compared. The primary outcome was 3-month "favorable outcome", defined as modified Rankin Scale score 0-2 or equal to pre-stroke. Secondary outcomes were haemorrhagic transformation (HT) and 3 months mortality. We included 167 patients (median age 92 years, 66.5% females); 46.1% underwent RT (59 IVT, 11 MT, 7 both). RT group had higher admission National Institutes of Health Stroke Scale (NIHSS) (16 versus 9.5, p < 0.001). Favorable outcome occurred in only 22% of patients, with no differences between groups; its odds decreased with higher NIHSS scores (OR 0.80, 95%CI 0.73-0.87, p < 0.001) and with the development of in-hospital respiratory infection (OR 0.22, 95%CI 0.07-0.67, p = 0.007). HT occurred in 16.2% of patients, being more prevalent (26.0% versus 7.8%, p = 0.001), symptomatic (14.3% versus 3.3%, p = 0.011) and severe (PH1/2 15.6% versus 2.2%, p = 0.012) in the RT group, although it did not influence the primary outcome. Mortality was 32% at 3 months, with no difference between groups. Although patients submitted to RT had worse admission NIHSS and increased HT, they had similar functional outcome at 3 months. Stroke severity and in-hospital respiratory infections were the most important predictors of 3 months' functional outcome.

Objectives: The aim of this study was to evaluate the effect of alteplase in intravenous thrombolysis of acute ischaemic stroke (AIS) regarding the different time windows of treatment (<3 hours, 3-4.5 hours, >4.5 hours)., Methods: A systematic literature search was conducted from PubMed, Cochrane Library and Embase. 12 clinical randomised controlled trials with 3402 patients with AIS met the inclusion criteria. The primary, secondary and tertiary outcomes were modified Rankin Scale (mRS) scores 0-1, mortality at 90th day after treatment and symptomatic intracerebral haemorrhage within 36 hours, respectively. Network meta-analysis and conventional meta-analysis were carried out for calculating odds ratio (OR), the surface under cumulative ranking curve (SUCRA) and the probabilities of being the best., Results: For mRS, alteplase regardless of time delay was significantly more effective than placebo (OR 1.33-2.17). However, alteplase used within 3 hours after AIS occurrence (SUCRA=98.3%) was significantly more effective (OR=1.64) than that at 3-4.5 hours (SUCRA=43%) and showed the trend of priority (OR=1.47) compared with that beyond 4.5 hours (SUCRA=58%). For the mortality, compared with placebo (SUCRA=64.7%), alteplase within 3 hours was similar to that of 3-4.5 hours whereas alteplase beyond 4.5 hours (SUCRA=7.3%) showed the trend of significantly increasing 85% mortality. For the tertiary outcome, alteplase within 3 hours (SUCRA=19.0%) was comparable with placebo (SUCRA=99.9%) whereas alteplase beyond 3 hours significantly increased (OR 5.89-6.67) the symptomatic intracerebral haemorrhage., Conclusions: Alteplase within 3 hours should be recommended as the best treatment delay for its best efficacy among all the intervention and equivalent safety compared with placebo. Alteplase beyond 3 hours was less effective compared with that within 3 hours and increased the risk of mortality on 3 months as well as symptomatic intracerebral haemorrhage at 36 hours. More head-to-head clinical trials are needed to confirm those findings., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Observe the clinical efficacy of l-3-n-Butylphthalide (NBP) in acute ischemic stroke (AIS) patients within 24 h after intravenous thrombolysis using recombinant tissue plasminogen activator (hereafter termed "IT")., Methods: One-hundred and seventy-eight patients with AIS were divided randomly into two groups: NBP and control. The former was given a NBP injection within 24 h after IT. After intravenous injection of NBP for 8-10 days, patients switched to soft capsules of NBP before or during meals. NBP treatment was continued for ≥30 days after hospital discharge. In the control group, NBP was not injected within 24 h after IT, and NBP capsules were not given after 8-10 days. Both groups were reviewed for CT or MRI 24 h after IT. The National Institutes of Health Stroke Scale (NIHSS) score was calculated. The number of patients with a modified Rankin scale (mRS) 0-2 before, 24 h, and 90 days after IT was documented. Prevalence of cerebral hemorrhage and reocclusion of blood vessels after IT was calculated., Results: There were no differences in sex, age, blood pressure, blood glucose, or cerebral-infarction types between the two groups before treatment. The NIHSS score 24 h after IT and the percentage of mRS scores 0-2 were not significantly different between the two groups. Compared with the control group, the NIHSS score in the NBP group was significantly improved at 90 days, and the number of patients with a mRS score 0-2 increased significantly. There was no significant difference in hemorrhage prevalence after IT between the two groups. Prevalence of blood-vessel occlusion after IT was significantly lower in the NBP group than that in the control group., Conclusion: Use of NBP within 24 h after IT can reduce the prevalence of reocclusion of blood vessels without increasing the risk of cerebral hemorrhage., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Immune cells are involved in all stages of acute ischaemic stroke (AIS) and possess both neuroprotective and neurodamaging properties. It has been suggested that immune system activation after stroke may be associated with the development of haemorrhagic transformation (HT), which is the main complication limiting the clinical use of intravenous thrombolysis with recombinant tissue plasminogen activator (rtPA) for AIS. The purpose of our study was to analyse the association between absolute eosinophil count (AEC) at admission and the occurrence of HT after intravenous rtPA therapy for AIS., Methods: In this retrospective study we enrolled AIS patients who were treated with rtPA within 4.5 h of symptom onset. Baseline stroke severity was evaluated using the National Institutes of Health Stroke Scale (NIHSS). Patients underwent head computed tomography scans at admission which were repeated 24 h after treatment with rtPA or promptly in case of clinical deterioration. HT was defined as blood at any site in the brain on follow-up head computed tomography scans. Spearman's rank correlation test was used to analyse the correlation between AEC and NIHSS scores. The optimal AEC cut-off value for predicting HT was calculated using the area under the receiver operating characteristic curve. Multiple logistic regression was used to determine the association between AEC included as a binary variable and the incidence of HT., Results: The data of 201 patients was analysed (59.7% females; median age 77 years); 23 (11.4%) of them developed HT. The median of AEC was 62.5% greater in the non-HT group compared to the HT group (0.13 ×  10 9 /l and 0.08 × 10 9 /l, respectively, p = 0.026). No correlation was found between AEC and baseline NIHSS scores (r = 0.061, p = 0.393). AEC ≥ 0.11 × 10 9 /l predicted the occurrence of HT with 69.6% sensitivity and 60.7% specificity. AEC ≥ 0.11 × 10 9 /l was independently associated with a 78% reduction in the odds of developing HT (adjusted odds ratio = 0.223, 95% confidence interval = 0.069-0.723, p = 0.012)., Conclusion: Higher values of AEC were associated with lower odds of developing HT, thus, AEC at admission could be considered an independent predictive marker of HT after treatment with rtPA for AIS.

We report a case of a 105-year-old woman who was treated with Alteplase for acute ischaemic stroke (AIS). On arrival, this centenarian woman had sudden-onset aphasia and right-sided hemiparesis, her baseline National Institutes of Health Stroke Scale (NIHSS) score was 21. An acute noncontrast brain CT scan showed only mild white matter disease. After assessing the patient's risk-benefit ratio, the patient was administered intravenous Alteplase (0.9 mg/kg) 2.5 hours after symptom onset. Her right hemiparesis and aphasia eased within 24 hours after Alteplase treatment. At discharge, her NIHSS score had decreased to 1, leaving only mild right facial palsy unresolved. Few clinical data are available on centenarian patients with AIS who undergo intravenous thrombolysis. There are no data on what is the best method to use to manage centenarians. Our successful thrombolysis case indicates that biologically young centenarians may profit from thrombolysis, despite the very high age., (© 2019 John Wiley & Sons Australia, Ltd.)

Background and Purpose: In 1995 intravenous recombinant tissue plasminogen activator (IVRTPA) was the first reperfusion therapy to be approved in patients with acute ischaemic stroke (AIS). The significance and impact of IVRTPA in times of modern endovascular stroke treatment (EST) were analysed in a German academic stroke centre., Methods: A retrospective observational cohort analysis of 1034 patients with suspected AIS presenting at the emergency department in 2014 was performed. Patients were evaluated for baseline characteristics, reperfusion procedures, IVRTPA eligibility, clinical outcome, symptomatic intracranial haemorrhage (sICH) and mortality. Data acquisition was part of an investigator-initiated, prospective and blinded end-point registry., Results: In 718 (69%) patients the diagnosis of symptomatic AIS was confirmed. 419 (58%) patients presented within 4.5 h of symptom onset and of those 260 (62%) received reperfusion therapy (IVRTPA alone, n = 183; combination or bridging therapy, n = 60; EST alone, n = 17). Subtracting cases with absolute contraindications for IVRTPA resulted in an effective thrombolysis rate of 82%. sICH occurred in two patients treated with IVRTPA alone (1.1%). The median door-to-needle interval was 30 min. Fifty (17%) non-EST eligible AIS patients presenting within 4.5 h without absolute contraindications did not receive IVRTPA mainly due to mild or regressive symptoms. Most of these untreated IVRTPA eligible patients (82%) were discharged with a good clinical outcome (modified Rankin Scale ≤ 2)., Conclusions: Intravenous recombinant tissue plasminogen activator remains the most frequently applied reperfusion therapy in AIS patients presenting within 4.5 h of onset in a tertiary stroke centre. An effective thrombolysis rate of over 80% can be achieved without increased rates of sICH., (© 2018 EAN.)

Background: The English National Institute for Health Research Clinical Research Network first established Hyperacute Stroke Research Centres (HSRCs) in 2010 to support multicentre hyperacute (< 9 h) and complex stroke research. We assessed the impact of this investment on research performance and patient outcomes in a post-hoc analysis of country-specific data from a large multicentre clinical trial., Methods: Comparisons of baseline, outcome and trial metric data were made for participants recruited to the alteplase-dose arm of the international Enhanced Control of Hypertension and Thrombolysis Stroke study (ENCHANTED) at National Institute for Health Research Clinical Research Network HSRCs and non-HSRCs between June 2012 and October 2015., Results: Among 774 ENCHANTED United Kingdom participants (41% female; mean age 72 years), 502 (64.9%) were recruited from nine HSRCs and 272 (35.1%) from 24 non-HSRCs. HSRCs had higher monthly recruitment rates (median 1.5, interquartile interval 1.4-2.2 vs. 0.7, 0.5-1.3; p = 0.01) and shorter randomisation-to-treatment times (2.6 vs. 3.1 min; p = 0.01) compared to non-HSRCs. HSRC participants were younger and had milder stroke severity, but clinically important between-group differences in 90-day death or disability outcomes remained after adjustment for minimisation criteria and important baseline variables at randomisation, whether defined by ordinal modified Rankin scale score shift (adjusted OR 0.82, 95% CI 0.62-1.08; p = 0.15), scores 2 to 6 (adjusted OR 0.71, 95% CI 0.50-1.01; p = 0.05), or scores 3 to 6 (adjusted OR 0.82, 95% CI 0.57-1.17; p = 0.27). There was no significant difference in symptomatic intracerebral haemorrhage, nor heterogeneity in the comparative treatment effects between low- and standard-dose alteplase by HSRCs or non-HSRCs., Conclusions: Infrastructure investment in HSRCs was associated with improved research performance metrics, particularly recruitment and time to treatment with clinically important, though not statistically significant, improvements in patient outcomes., Trial Registration: Unique identifier: NCT01422616 .

The 2018 American Heart Association/American Stroke Association (AHA/ASA) guidelines stated that the administration of intravenous recombinant tissue-type plasminogen activator (rTPA) for acute ischaemic stroke is probably safe for patients with small (i.e. <10 mm) unruptured intracranial aneurysms. We present 2 cases of small (2 and 5 mm) lenticulostriate artery (LSA) aneurysms which ruptured immediately following rtPA infusion. The ensuing acute intracranial haemorrhages resulted in the death of one patient and severe functional impairment for the other. Given the limited literature available, the natural history of LSA aneurysms is largely unknown. This report suggests that LSA aneurysms, regardless of size, be considered separately from other conventional aneurysms as "high-risk" lesions and a contraindication to thrombolysis., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Aims: Recombinant tissue plasminogen activator (rt-PA) is the only first-line agent approved by the US Food and Drug Administration to treat acute ischaemic stroke. However, it often causes the serious adverse event (AE) of haemorrhagic transformation. The present study developed a pharmacometric model for the rt-PA treatment effect and AE and, using the developed model, proposed a benefit-to-risk ratio assessment scheme as a supportive tool to optimize treatment outcome., Methods: The data from 336 acute ischaemic stroke patients were used. The treatment effect was assessed based on an improvement in National Institutes of Health Stroke Scale (NIHSS) scores, which were described using an item response theory (IRT)-based disease progression model. Treatment failure and AE probabilities, and their occurrence times, were described by incidence and time-to-event models. Using the developed model, benefit-to-risk ratios were simulated under various scenarios using the global benefit-to-risk trade-off ratio (GBR)., Results: High initial NIHSS score and middle cerebral artery (MCA) stroke were risk factors for treatment failure, where the failure rate with MCA stroke was 2.87-fold higher than with non-MCA stroke. The haemorrhagic transformation time was associated with longitudinal changes in NIHSS scores. The benefit-to-risk ratio simulated was highest in minor stroke severity, with GBR >1 in all scenarios, and the ratio with non-MCA stroke was 2-3 fold higher than with MCA stroke., Conclusions: The study demonstrated the feasibility of applying an IRT model to describing the time course of the rt-PA treatment effect and AE. Benefit-to-risk ratio analyses showed that the treatment was optimal in non-MCA stroke with minor stroke severity., (© 2018 The British Pharmacological Society.)

Background: In acute ischemic stroke (AIS), treatment with intravenous tissue-type plasminogen activator (IV-tPA) is time-sensitive. All stroke centers make continual efforts to reduce door-to-needle time (DNT) with varying success. We present the impact of modifications to our stroke activation protocol on DNT., Methods: We included 404 consecutive patients with AIS receiving IV-tPA between January 2014 and December 2016. First changes in stroke activation protocol were made in March 2015 in the form of prenotification by paramedics, direct transfer from ambulance to computed tomography (CT) scanner, and rapid en route neurological assessment by an emergency physician and neurologist. In March 2016, a second amendment was made where a stroke nurse accompanied the patient to expedite various steps in the treatment pathway, including endovascular treatment in eligible cases., Results: Both protocol amendments resulted in improvement in DNT and door-to-CT time from 84 ± 47 minutes before intervention to 69 ± 33 minutes after protocol amendment 1 to 59 ± 37 minutes after protocol amendment 2. In particular, the second amendment (144 patients) showed significant shortening of DNT compared with the 137 patients before (59 ± 37 minutes versus 69 ± 33 minutes, P = .020), with a higher percentage achieving the target of 60 minutes (68.1% versus 48.2%, P < .001). This finding was attributed to a reduction in both door-to-CT time and CT-to-needle time. This improvement remained consistent over subsequent months., Conclusions: The application of a simple systems-based, multidisciplinary stroke activation protocol may help in significant reduction in DNT. Encouraging increased patient ownership by stroke nurses appeared to be a promising approach for timely administration of definitive acute therapies., (Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Background and Purpose: Neutrophils, a pivotal immune responder to ischaemic brain insult, have been involved in neuroplasticity and increase after stroke. Recombinant tissue plasminogen activator (r-tPA), a promising treatment improving neuroplasticity, promotes neutrophil degranulation. However, the dynamic profile of neutrophils after r-tPA treatment and their effect on neurological recovery after stroke are not well studied., Methods: Cell counts of neutrophils, lymphocytes and their ratio (NLR) were measured on admission and 24 h after r-tPA infusion in 372 consecutively recruited acute ischaemic stroke patients (mean age 64 years). Death or major disability at 3 months after stroke was diagnosed based on the modified Rankin Scale (mRS ≥ 3) obtained by neurologists who were blinded to any hospital records. The longitudinal associations of percentage increase in neutrophils, lymphocytes and the NLR with death or major disability were examined by logistic regression adjusting for covariates including neurological deficits at baseline., Results: Neutrophils exhibited a steeper increase after r-tPA infusion in patients with death or major disability than in those without (P < 0.001). A 10% increase in neutrophils after r-tPA infusion was associated with an 83% increased risk for death or major disability within 3 months after stroke onset [odds ratio (OR) 1.99, P = 0.009]. Increased neutrophils at 24 h after r-tPA (OR 6.30, P < 0.001 after log transformation) but not on admission significantly predicted increased risks for death or major disability within 3 months after stroke onset. A similar phenomenon was also observed for the NLR., Conclusions: A dynamic increase in neutrophils after stroke significantly predicts 3-month death or major disability in acute ischaemic stroke patients receiving r-tPA treatment., (© 2018 EAN.)

Background and Purpose: Recent cross-sectional study data suggest that intravenous thrombolysis (IVT) in patients with in-hospital stroke (IHS) onset is associated with unfavorable functional outcomes at hospital discharge and in-hospital mortality compared to patients with out-of-hospital stroke (OHS) onset treated with IVT. We sought to compare outcomes between IVT-treated patients with IHS and OHS by analysing propensity-score-matched data from the Safe Implementation of Treatments in Stroke-East registry., Methods: We compared the following outcomes for all propensity-score-matched patients: (i) symptomatic intracranial hemorrhage defined with the safe implementation of thrombolysis in stroke-monitoring study criteria, (ii) favorable functional outcome defined as a modified Rankin Scale (mRS) score of 0-1 at 3 months, (iii) functional independence defined as an mRS score of 0-2 at 3 months and (iv) 3-month mortality., Results: Out of a total of 19 077 IVT-treated patients with acute ischaemic stroke, 196 patients with IHS were matched to 5124 patients with OHS, with no differences in all baseline characteristics (P > 0.1). Patients with IHS had longer door-to-needle [90 (interquartile range, IQR, 60-140) vs. 65 (IQR, 47-95) min, P < 0.001] and door-to-imaging [40 (IQR, 20-90) vs. 24 (IQR, 15-35) min, P < 0.001] times compared with patients with OHS. No differences were detected in the rates of symptomatic intracranial hemorrhage (1.6% vs. 1.9%, P = 0.756), favorable functional outcome (46.4% vs. 42.3%, P = 0.257), functional independence (60.7% vs. 60.0%, P = 0.447) and mortality (14.3% vs. 15.1%, P = 0.764). The distribution of 3-month mRS scores was similar in the two groups (P = 0.273)., Conclusions: Our findings underline the safety and efficacy of IVT for IHS. They also underscore the potential of reducing in-hospital delays for timely tissue plasminogen activator delivery in patients with IHS., (© 2017 EAN.)

Background: Tissue plasminogen activator (tPA) treatment for acute ischaemic stroke (AIS) should be given as soon as possible, preferably within 60 min after arrival at hospital. There is great variation in door-to-needle times (DNTs) internationally, nationally and even within the same hospital. Various strategies for improving treatment delays have been presented. The role of emergency physicians (EPs) in treating AIS has been under discussion in recent years. Emergency Medicine (EM) officially became a specialty in Finland in 2013. Practical education of EPs in Kanta-Häme Central Hospital began in October 2012, together with reorganization of the in-hospital treatment path for AIS patients. The main change was shifting the on-call duty regarding stroke patients from internists or neurologists to EPs after the third quarter of 2013., Methods: This was a retrospective study. The data, concerning the characteristics of tPA-treated patients, DNTs and onset-to-treatment times (OTTs) was collected from electronic and paper records. The period studied was 1 year before and 1 year during reorganization, i.e. 2012 and 2013., Results: During the study period a total of 64 tPA treatments were given, 31 before and 33 during reorganization. The median DNT was 54 min in 2012, while it was 28 min in 2013 (p < 0.001). The median OTTs were 139 and 101 min before and during the start of reorganization, respectively (p < 0.001)., Conclusions: Both total and in-hospital delays in the treatment of ischaemic stroke were shortened significantly during reorganization. Emergency physicians are able to treat AIS patients within international time guidelines. Success was based on scrutinized reorganization and good cooperation between neurologists, EPs and radiologists.

What Is Known and Objective: Cerebral systemic thrombolysis (i.v. thrombolysis) with tissue-type plasminogen activator (rt-PA) is the only proven medical therapy for ischaemic stroke. The use of i.v. thrombolysis up to 4·5 h from stroke onset was approved in certain countries in 2008, but its safety and efficacy have not been fully determined to date., Objective: To assess the long-term outcome and complication rate of i.v. thrombolysis performed in the extended 'time window'., Methods: The study included 403 ischaemic stroke patients consecutively treated with i.v. thrombolysis from 2006 to 2012 at three comprehensive stroke centres in Poland. The long-term outcome and the haemorrhagic complications' (HC) rate were compared between subgroups of patients treated within 3 vs. 3-4·5 h from stroke onset., Results and Discussion: About 132 (32·75%) patients were treated between 3 and 4·5 h from stroke onset. Neurological deficits tended to be more severe in patients treated ≤3 than in those treated 3-4·5 h (National Institutes of Health Stroke Scale, NIHSS 12 vs.10 points; P = 0·053); however, the ratio of patients with a favourable outcome (mRS 0-2 points) and mortality did not differ between the two groups (53·9 vs. 58·3, P = 0·39 and 17·7 vs. 21·2, P = 0·39, respectively). The rate of HC also did not differ between the two groups (18·8% vs. 15·1%, P = 0·46)., What Is New and Conclusion: The efficacy of i.v. thrombolysis routinely performed in an extended 'time window' is not reduced when compared to procedures performed within 3 h from symptom onset., (© 2015 John Wiley & Sons Ltd.)

Rationale: Controversy exists over the optimal dose of intravenous (i.v.) recombinant tissue plasminogen activator (rt-PA) and degree of blood pressure (BP) control in acute ischaemic stroke (AIS). Asian studies suggest low-dose (0·6 mg/kg) is more efficacious than standard-dose (0·9 mg/kg) i.v. rt-PA, and guidelines recommend reducing systolic BP to <185 mmHg before and <180 mmHg after use of i.v. rt-PA, despite observational studies indicating better outcomes at much lower (<140 mmHg) systolic BP levels in this patient group., Aims: The study aims to assess in thrombolysis-eligible AIS patients whether: (i) low-dose (0·6 mg/kg body weight; maximum 60 mg) i.v. rt-PA has non-inferior efficacy and lower risk of symptomatic intracerebral haemorrhage (sICH) compared to standard-dose (0·9 mg/kg body weight; maximum 90 mg) i.v. rt-PA; and (ii) early intensive BP lowering (systolic target 130-140 mmHg) has superior efficacy and lower risk of any ICH compared to guideline-recommended BP control (systolic target < 180 mmHg)., Design: The ENhanced Control of Hypertension And Thrombolysis strokE stuDy (ENCHANTED) trial is an independent,2 × 2 quasi-factorial, active-comparison, prospective, randomized, open blinded endpoint (PROBE), clinical trial that is evaluating Arm [A] 'rt-PA dose' and/or Arm [B] 'BP control', using central Internet randomization and data collection in patients fulfilling local criteria for thrombolysis and clinician uncertainty over the study treatments. The treatment arms will be analyzed separately., Study Outcomes: The primary study outcome in both trial Arms is death or disability according to the modified Rankin scale (mRS, scores 2-6) assessed at 90 days. Secondary outcomes include sICH, any ICH, a shift ('improvement') in function across mRS scores, separately on death and disability, early neurological deterioration, recurrent major vascular events, health-related quality of life, length of hospital stay, need for permanent residential care, and health care costs., Results: Following launch of the trial in February 2012, the study has recruited more than 2500 patients across a global network of approximately 100 sites in 15 countries. The required sample sizes are 3300 for Arm [A] and 2300 for Arm [B], which will provide >90% power to detect non-inferiority of low-dose i.v. rt-PA and superiority of intensive BP lowering on the primary clinical outcome, respectively., Conclusions: Low-dose i.v. rt-PA and early intensive BP lowering could provide more affordable and safer use of thrombolysis treatment for patients with AIS worldwide., (© 2015 World Stroke Organization.)

Background and Purpose: The direct bridging concept in acute stroke treatment combines intravenous thrombolysis (IVT) and endovascular treatment (EVT). The frequency and extent of reperfusion obtained already due to IVT were evaluated. Additionally undesired events and the clinical outcome were analysed., Methods: Fifty-seven acute stroke patients treated with direct bridging were analysed for this study. The response to IVT was evaluated according to the modified Thrombolysis in Cerebral Infarction scale (m-TICI). IVT responders (m-TICI ≥2B in digital subtraction angiography) were compared with IVT non-responders (m-TICI <2B in digital subtraction angiography) with respect to clinical outcome and occurrence of undesired events., Results: Fourteen patients (25%) got a change from TICI 0 to ≥2B due to IVT alone. There were otherwise no differences between the IVT responders and IVT non-responders., Conclusions: Intravenous thrombolysis pretreatment in the context of the bridging approach contributes substantially to revascularization., (© 2014 EAN.)

Background: symptomatic intracerebral haemorrhage (ICH) is a major concern of intravenous thrombolysis (IVT) for ischaemic stroke. Asians are considered more vulnerable to ICH than non-Asians. Reports on safety of IVT for Asian octogenarians and nonagenarians are limited., Aims: the aims of our study were to compare the safety of IVT between octogenarians and nonagenarians and between Asian and Western patients., Methods: patients receiving IVT for ischaemic stroke were prospectively registered from four hospitals in Taiwan. Octogenarians and nonagenarians were recruited for analysis. The primary safety outcome measure was symptomatic ICH. The secondary outcome measure was 3-month mortality. We searched the literature on IVT for ischaemic stroke for comparison., Results: from January 2007 to December 2012, a total of 186 (18.3%) ischaemic stroke patients aged 80 and older, including 166 octogenarians and 20 nonagenarians, were recruited from 1,018 patients receiving IVT. Nine (4.8%) of recruited patients had symptomatic ICH, all in the octogenarian group (5.4%). Three-month mortality was 14.1% in recruited patients and without difference between the two age groups (P = 0.558). The results were comparable with reports on Western octogenarians and nonagenarians in the literature., Conclusion: octogenarians and nonagenarians receiving IVT have a similar safety outcome. Asian octogenarians and nonagenarians receiving IVT for ischaemic stroke are not at higher risk of symptomatic ICH and mortality than Western patients., (© The Author 2014. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: Smoking has been associated with improved outcome in thrombolysed patients with myocardial infarction and higher recanalization rates in stroke patients treated with tissue plasminogen activator (tPA). We hypothesized a positive association between smoking and favourable outcome in stroke patients treated with tPA and no such association in acute stroke patients not treated with tPA, suggesting a beneficial effect of smoking on thrombolysis with tPA., Methods: Stroke patients treated with tPA and stroke patients not treated with tPA, but presenting within 6 h after stroke onset, were included in two separate groups. Three groups were defined according to smoking habits: current smoking, previous smoking and no smoking. Functional outcome by modified Rankin Scale (mRS) was assessed after 1 week or at discharge, if discharged earlier. Favourable outcome was defined as mRS 0 or 1., Results: A total of 399 patients were treated with tPA (94 current smokers, 148 previous smokers and 157 non-smokers), whereas 424 patients were not treated with tPA (90 current smokers, 164 previous smokers and 170 non-smokers). Current smoking was independently associated with favourable outcome in patients treated with tPA when adjusted for confounders (OR 2.08, 95% CI 1.09-3.95, P = 0.025). There was no such association in acute stroke patients not treated with tPA (OR 1.26, 95% CI 0.67-2.36, P = 0.472)., Conclusion: Our study showed an association between current smoking and favourable short-term outcome in stroke patients treated with tPA, but not in acute stroke patients not treated with tPA. This may indicate a more effective thrombolysis with tPA in smokers., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The purpose of this study was to evaluate the efficacy and safety of intra-arterial therapy as a rescue strategy after clinically failed intravenous thrombolysis (IVT) in acute ischaemic stroke patients. We conducted a retrospective analysis of consecutive acute ischaemic stroke patients treated with rescue therapy. The results from this study group were compared with those obtained from a control group consisting of 260 consecutive patients treated with IVT alone. The study group consisted of 52 patients with a mean age of 63 years and a median NIHSS score at admission of 17. Recanalization was achieved in 92% with a symptomatic haemorrhage rate of 9.6%. Rescue patients admitted with a severe stroke (NIHSS score >12) had a significantly better outcome at 90 days compared to patients with the same score but treated with IVT alone. No difference was seen for patients with a lower score at admission. This study indicates that rescue therapy may increase the proportion of patients with independent outcome if presenting with a severe stroke (NIHSS score >12) without increasing the rate of symptomatic haemorrhage.

Background: Major neurological improvement (MNI) at 24 hours represents a marker of early recanalization in ischaemic stroke. Although low body temperature is considered neuroprotective in cerebral ischaemia, some studies have suggested that higher body temperature may promote clot lysis in the acute phase of ischaemic stroke. We hypothesized that higher body temperature was associated with MNI in severe stroke patients treated with tPA, suggesting a beneficial effect of higher body temperature on clot lysis and recanalization., Methods: Patients with ischaemic stroke or transient ischaemic attack (TIA) treated with tPA between February 2006 and August 2012 were prospectively included and retrospectively analysed. Body temperature was measured upon admission. MNI was defined by a ≥8 point improvement in NIHSS score at 24 hours as compared to NIHSS score on admission. No significant improvement (no-MNI) was defined by either an increase in NIHSS score or a decrease of ≤2 points at 24 hours in patients with an admission NIHSS score of ≥8., Results: Of the 2351 patients admitted with ischaemic stroke or TIA, 347 patients (14.8%) were treated with tPA. A total of 32 patients (9.2%) had MNI and 56 patients (16.1%) had no-MNI. Patients with MNI had higher body temperatures compared with patients with no-MNI (36.7°C vs 36.3°C, P = 0.004). Higher body temperature was independently associated with MNI when adjusted for confounders (OR 5.16, P = 0.003)., Conclusion: Higher body temperature was independently associated with MNI in severe ischaemic stroke patients treated with tPA. This may suggest a beneficial effect of higher body temperature on clot lysis and recanalization., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background and Purpose: The characteristics of reverse magnetic resonance angiography and diffusion-weighted imaging (MRA-DWI) mismatch (RMM), defined as a large DWI lesion in the absence of major artery occlusion (MAO), remain unknown, especially in patients treated with intravenous recombinant tissue plasminogen activator (rt-PA)., Methods: Patients with stroke in the middle cerebral artery territory were included. Early ischaemic changes (EIC) were assessed with the Alberta Stroke Program Early CT Score on DWI (DWI-ASPECTS). All patients were divided into four groups based on the presence of MAO and a DWI-ASPECTS cut-off value of <7. RMM was defined as DWI-ASPECTS <7 without MAO. Clinical characteristics, symptomatic intracerebral hemorrhage (sICH) and favorable functional outcome (modified Rankin Scale score 0-2) at 90 days were compared amongst the four groups., Results: Of the 486 patients enrolled (167 women, median age 74 years, median initial National Institutes of Health Stroke Scale score 13), reverse MRA-DWI mismatch was observed in 24 (5%). Of the clinical characteristics, cardioembolism was the only factor that was independently associated with RMM [odds ratio (OR) 5.49, 95% confidence interval (CI) 1.25-24.1]. Multivariable analyses revealed that patients with RMM more commonly had sICH than those with DWI-ASPECTS ≥ 7 irrespective of the presence (OR 5.44, 95% CI 1.13-26.1) or absence (13.1, 2.07-83.3) of MAO, and they had a more favorable functional outcome than those with DWI-ASPECTS < 7 plus MAO (7.45, 2.39-23.2)., Conclusion: RMM was observed in 5% of patients treated with rt-PA and associated with cardioembolism. Patients with RMM may benefit from thrombolysis compared with those with EIC with MAO, although increment in the rate of sICH is a concern., (© 2013 The Author(s) European Journal of Neurology © 2013 EFNS.)