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Background: Stroke with unknown time of onset can be categorized into 2 groups; wake-up stroke (WUS) and unwitnessed stroke with an onset time unavailable for reasons other than wake-up (non-wake-up unwitnessed stroke, non-WUS). We aimed to assess potential differences in the efficacy and safety of intravenous thrombolysis (IVT) between these subgroups., Methods: Patients with an unknown-onset stroke were evaluated using individual patient-level data of 2 randomized controlled trials (WAKE-UP [Efficacy and Safety of MRI-Based Thrombolysis in Wake-Up Stroke], THAWS [Thrombolysis for Acute Wake-Up and Unclear-Onset Strokes With Alteplase at 0.6 mg/kg]) comparing IVT with placebo or standard treatment from the EOS (Evaluation of Unknown-Onset Stroke Thrombolysis trial) data set. A favorable outcome was prespecified as a modified Rankin Scale score of 0 to 1 at 90 days. Safety outcomes included symptomatic intracranial hemorrhage at 22 to 36 hours and 90-day mortality. The IVT effect was compared between the treatment groups in the WUS and non-WUS with multivariable logistic regression analysis., Results: Six hundred thirty-four patients from 2 trials were analyzed; 542 had WUS (191 women, 272 receiving alteplase), and 92 had non-WUS (42 women, 43 receiving alteplase). Overall, no significant interaction was noted between the mode of onset and treatment effect ( P value for interaction=0.796). In patients with WUS, the frequencies of favorable outcomes were 54.8% and 45.5% in the IVT and control groups, respectively (adjusted odds ratio, 1.47 [95% CI, 1.01-2.16]). Death occurred in 4.0% and 1.9%, respectively ( P =0.162), and symptomatic intracranial hemorrhage in 1.8% and 0.3%, respectively ( P =0.194). In patients with non-WUS, no significant difference was observed in favorable outcomes relative to the control (37.2% versus 29.2%; adjusted odds ratio, 1.76 [0.58-5.37]). One death and one symptomatic intracranial hemorrhage were reported in the IVT group, but none in the control., Conclusions: There was no difference in the effect of IVT between patients with WUS and non-WUS. IVT showed a significant benefit in patients with WUS, while there was insufficient statistical power to detect a substantial benefit in the non-WUS subgroup., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: CRD42020166903., Competing Interests: Disclosures Dr Ma has consulted for Independent Sector. Dr Ringleb has consulted for Boehringer Ingelheim and Daiichi Sankyo Company and reports personal fees from Bayer Healthcare and Bristol-Myers Squibb. Dr Wu reports grants from National Institutes of Health. Dr Schwamm serves as a scientific consultant regarding trial design and conduct to Genentech (late-window thrombolysis) and as a member of steering committee (TIMELESS [A Phase III, Prospective, Double-Blind, Randomized, Placebo-Controlled Trial of Thrombolysis in Imaging-Eligible, Late-Window Patients to Assess the Efficacy and Safety of Tenecteplase] NCT03785678); stroke systems of care consultant to the Massachusetts Dept of Public Health; member of a Data Safety Monitoring Boards (DSMB) for Penumbra (MIND NCT03342664) and for Diffusion Pharma PHAST-TSC (Double-Blind, Randomized, Placebo-Controlled, Phase 2 Study of Efficacy and Safety of Trans Sodium Crocetinate [TSC] Administered Onboard Emergency Vehicles for Treatment of Suspected Stroke; NCT03763929); and delivering continuing medical education lectures for Boehringer Ingelheim and Prime Education: stroke systems of care and improving time to thrombolysis. Dr Warach has consulted for Genentech. Dr Davis reports personal fees from Boehringer Ingelheim. Dr Donnan has consulted for Amgen. Dr Gerloff has consulted for Abbott Canada, Allergan, Amgen, Astra-Zeneca, Bayer Healthcare, and Boehringer Ingelheim and reports grants from Deutsche Forschungsgemeinschaft, Deutsches Zentrum für Luft- und Raumfahrt, European Union, Gemeinnützige Hertie-Stiftung, Merz Farmaceutica Comercial LTDA, and Schilling-Stiftung. Dr Thomalla has consulted for Acandis, Bayer, PORTOLA PHARMACEUTICALS, LLC, and Stryker and reports personal fees from Alexion Pharmaceuticals Inc, Amarin Pharma Inc, Boehringer Ingelheim, Bristol-Myers Squibb, and Daiichi Sankyo Europe GmbH. Dr Kitazono reports grant from Daiichi Sankyo Company LTD. Dr Toyoda has consulted for Otsuka Pharmaceutical and reports personal fees from Abbott Japan, Bayer, Bristol-Myers Squibb, Daiichi Sankyo, and Novartis. Dr Koga has consulted for Janssen Pharmaceuticals, reports personal fees from Daiichi Sankyo Company, Bayer, Bristol-Myers Squibb, Mitsubishi Tanabe Pharma Corporation and Pfizer, and reports grants from Daiichi Sankyo Company LTD, Nippon Boehringer Ingelheim Co Ltd. The other authors report no conflicts.

Intravenous thrombolysis (IVT) treatment with alteplase (rtPA) is an essential part of the routine treatment of patients with ischemic stroke since its introduction in the late 1990s. Rapid treatment is of essential importance. For patients with an unclear time window, various mismatch concepts have been established to identify salvageable brain tissue prior to IVT. Numerous official contraindications for rtPA are not evidence-based; for example, current data from observational studies show that systemic thrombolytic treatment is possible even in patients receiving direct oral anticoagulant (DOAC) treatment. Tenecteplase (TNK) is an alternative thrombolytic agent with some pharmacologic advantages. The most recent guidelines indicate that TNK is particularly advantageous over rtPA in patients treated in combination with endovascular stroke therapy (EST). The combination of IVT and EST should primarily be performed in the 4.5‑h time window in patients without contraindications; in the later time window EST alone is conceivable if it can be performed without delay., (© 2023. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Importance: International guidelines recommend avoiding intravenous thrombolysis (IVT) in patients with ischemic stroke who have a recent intake of a direct oral anticoagulant (DOAC)., Objective: To determine the risk of symptomatic intracranial hemorrhage (sICH) associated with use of IVT in patients with recent DOAC ingestion., Design, Setting, and Participants: This international, multicenter, retrospective cohort study included 64 primary and comprehensive stroke centers across Europe, Asia, Australia, and New Zealand. Consecutive adult patients with ischemic stroke who received IVT (both with and without thrombectomy) were included. Patients whose last known DOAC ingestion was more than 48 hours before stroke onset were excluded. A total of 832 patients with recent DOAC use were compared with 32 375 controls without recent DOAC use. Data were collected from January 2008 to December 2021., Exposures: Prior DOAC therapy (confirmed last ingestion within 48 hours prior to IVT) compared with no prior oral anticoagulation., Main Outcomes and Measures: The main outcome was sICH within 36 hours after IVT, defined as worsening of at least 4 points on the National Institutes of Health Stroke Scale and attributed to radiologically evident intracranial hemorrhage. Outcomes were compared according to different selection strategies (DOAC-level measurements, DOAC reversal treatment, IVT with neither DOAC-level measurement nor idarucizumab). The association of sICH with DOAC plasma levels and very recent ingestions was explored in sensitivity analyses., Results: Of 33 207 included patients, 14 458 (43.5%) were female, and the median (IQR) age was 73 (62-80) years. The median (IQR) National Institutes of Health Stroke Scale score was 9 (5-16). Of the 832 patients taking DOAC, 252 (30.3%) received DOAC reversal before IVT (all idarucizumab), 225 (27.0%) had DOAC-level measurements, and 355 (42.7%) received IVT without measuring DOAC plasma levels or reversal treatment. The unadjusted rate of sICH was 2.5% (95% CI, 1.6-3.8) in patients taking DOACs compared with 4.1% (95% CI, 3.9-4.4) in control patients using no anticoagulants. Recent DOAC ingestion was associated with lower odds of sICH after IVT compared with no anticoagulation (adjusted odds ratio, 0.57; 95% CI, 0.36-0.92). This finding was consistent among the different selection strategies and in sensitivity analyses of patients with detectable plasma levels or very recent ingestion., Conclusions and Relevance: In this study, there was insufficient evidence of excess harm associated with off-label IVT in selected patients after ischemic stroke with recent DOAC ingestion.

Background: There are limited data on intravenous thrombolysis treatment in ischemic stroke patients with prestroke disability., Aim: We aimed to evaluate safety and outcomes of intravenous thrombolysis treatment in stroke patients with prestroke disability., Methods: We analyzed 88,094 patients treated with intravenous thrombolysis, recorded in the Safe Implementation of Treatments in Stroke (SITS) International Thrombolysis Register between January 2003 and December 2017, with available NIHSS data at stroke-onset and after 24 h. Of them, 4566 patients (5.2%) had prestroke disability, defined as a modified Rankin Scale score of 3-5. Safety outcome measures included Symptomatic Intracerebral Hemorrhage, any type of parenchymal hematoma on 24 h imaging scans irrespective of clinical symptoms, and death within seven days. Early outcome measures were 24-h NIHSS improvement (≥4 from baseline to 24 h)., Results: Patients with prestroke disability were older, had more severe strokes, and more comorbidities than patients without prestroke disability. When comparing patients with prestroke disability with patients without prestroke disability, there was however no significant increase in adjusted odds for symptomatic intracerebral hemorrhage (adjusted odds ratio 0.83 (95% CI 0.60-1.15) (absolute difference in proportion 1.17% vs. 1.27%)) or for parenchymal hemorrhage (adjusted odds ratio 0.96 (0.83-1.11) (7.51% vs. 6.34%)). The prestroke disability group had a significantly lower-adjusted odds ratio for a 24-h NIHSS improvement (adjusted odds ratio 0.79 (0.73-0.85) (45.95% vs. 48.45%)) and a higher adjusted odds ratio for seven-day mortality (aOR 1.40 (1.21-1.61) (10.40% vs. 4.93%))., Conclusions: Intravenous thrombolysis in acute ischemic stroke patients with prestroke disability was not associated with an increased risk of symptomatic intracerebral hemorrhage or parenchymal hemorrhage. Prestroke disability was however associated with a higher risk of early mortality compared to patients without prestroke disability.

Background and Purpose: Trimethylamine-N-oxide (TMAO) is a biomarker of the gut microbiome and correlates with the risk of cardiovascular diseases. However, conflicting data exist on the specific role of TMAO in ischaemic stroke patients. We aimed to analyze the time course of TMAO levels in stroke patients compared with controls., Methods: In this prospective, case-control study, patients suffering from ischaemic stroke (onset <24 h) and control patients with less than two cardiovascular risk factors were enrolled. Plasma TMAO levels were analyzed on admission, after 48 h and after 3 months. The primary endpoint was the difference in TMAO levels on admission between stroke patients and controls., Results: A total of 196 patients with ischaemic stroke and 100 controls were included between February 2018 and April 2019. Plasma TMAO levels on admission were significantly higher in stroke patients than in controls [median value 4.09 (2.87-6.49) vs. 3.16 (2.08-5.16) µmol/L, P = 0.001]. There was a significant decrease in TMAO levels in stroke patients after 48 h [median at 48 h, 3.49 (2.30-5.39) µmol/L, P = 0.027]. TMAO levels increased again 3 months after stroke [median 4.23 (2.92-8.13) µmol/L, P = 0.047]. In controls, TMAO levels did not change between admission and after 48 h [median at 48 h, 3.14 (1.63-4.61) µmol/L, P = 0.11]. An inverse correlation between TMAO values and kidney function was found (Spearman rho -0.334, P < 0.001)., Conclusions: Our study emphasizes the importance of the time course of TMAO levels after ischaemic stroke. Future studies should define the time point of TMAO analysis, preferably in the acute phase (<24 h)., (© 2020 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Background and Purpose: In patients with acute ischemic stroke and large vessel occlusion, the prognosis has improved tremendously since the implementation of endovascular thrombectomy (EVT). The effect of EVT on the incidence of malignant middle cerebral artery infarctions (MMI) has not been studied before., Methods: ESTIMATE, a multicenter retrospective study, evaluates data of ischemic stroke patients with occlusion in the anterior circulation in the years of 2007-2015 comparing three treatment options (no therapy; IV-TPA; IV-TPA plus EVT or EVT only). Primary endpoint of the study was the incidence of MMI on follow-up imaging and mortality rates. Secondary endpoints were functional outcome, further clinical and imaging data. Logistic and Cox-regression models with a propensity score weighting approach were applied to evaluate differences between treatment groups., Results: In 2161 patients over 9 years, EVT reduced the MMI rates significantly: patients without acute stroke treatment had increased odds for MMI of 1.57 [95% confidence interval (CI) 1.49-1.65]. In contrast, after treatment with IV-TPA, only we observed an OR of 0.88 (95% CI 0.83-0.94, p < 0.001), and after EVT an OR of 0.80 (95% CI 0.76-0.85, p < 0.001). This was more pronounced in larger pretreatment infarctions (ASPECTS < 5, p < 0.01). IV-TPA also lowers the MMI rates but not to the same extent. EVT-treated patients had increased survival rates (p < 0.05) and the best functional outcome at discharge., Conclusions: The findings of this study illustrate that occurrence of MMI and mortality rates was significantly reduced in patients treated with EVT.

Limited data exist on clot composition and detailed characteristics of arterial thrombi associated with large vessel occlusion in acute ischemic stroke. Advances in endovascular thrombectomy and related imaging modalities have created a unique opportunity to analyze thrombi removed from cerebral arteries. Insights into thrombus composition, etiology, physical properties and neurovascular interactions may lead to future advancements in acute ischemic stroke treatment and improved clinical outcomes. Advances in imaging techniques may enhance clot characterization and inform therapeutic decision-making prior to treatment and reveal stroke etiology to guide secondary prevention. Current imaging techniques can provide some information about thrombi, but there remains much to evaluate about relationships that may exist among thrombus composition, occlusion characteristics and treatment outcomes. Improved pathophysiological characterization of clot types, their properties and how these properties change over time, together with clinical correlates from ongoing studies, may facilitate revascularization with thrombolysis and thrombectomy. Interdisciplinary approaches covering clinical, engineering and scientific aspects of thrombus research will be key to advancing the understanding of thrombi and improving acute ischemic stroke therapy. This consensus statement integrates recent research on clots and thrombi retrieved from cerebral arteries and provides a rationale for further analyses, including current opportunities and limitations.

Background and Purpose: The e-ASPECTS software is a tool for the automated use of ASPECTS. Our aim was to analyze whether baseline e-ASPECT scores correlate with outcome after mechanical thrombectomy., Materials and Methods: Patients with ischemic strokes in the anterior circulation who were admitted between 2010 and 2015, diagnosed by CT, and received mechanical thrombectomy were included. The ASPECTS on baseline CT was scored by e-ASPECTS and 3 expert raters, and interclass correlation coefficients were calculated. The e-ASPECTS was correlated with functional outcome (modified Rankin Scale) at 3 months by using the Spearman rank correlation coefficient. Unfavorable outcome was defined as mRS 4-6 at 3 months, and a poor scan was defined as e-ASPECTS 0-5., Results: Two hundred twenty patients were included, and 147 (67%) were treated with bridging protocols. The median e-ASPECTS was 9 (interquartile range, 8-10). Intraclass correlation coefficients between e-ASPECTS and raters were 0.72, 0.74, and 0.76 (all, P < .001). e-ASPECTS (Spearman rank correlation coefficient = -0.15, P = .027) correlated with mRS at 3 months. Patients with unfavorable outcome had lower e-ASPECTS (median, 8; interquartile range, 7-10 versus median, 9; interquartile range, 8-10; P = .014). Sixteen patients (7.4%) had a poor scan, which was associated with unfavorable outcome (OR, 13.6; 95% CI, 1.8-104). Independent predictors of unfavorable outcome were e-ASPECTS (OR, 0.79; 95% CI, 0.63-0.99), blood sugar (OR, 1.01; 95% CI, 1.004-1.02), atrial fibrillation (OR, 2.64; 95% CI, 1.22-5.69), premorbid mRS (OR, 1.77; 95% CI, 1.21-2.58), NIHSS (OR, 1.11; 95% CI, 1.04-1.19), general anesthesia (OR, 0.24; 95% CI, 0.07-0.84), failed recanalization (OR, 8.47; 95% CI, 3.5-20.2), and symptomatic intracerebral hemorrhage (OR, 25.8; 95% CI, 2.5-268)., Conclusions: The e-ASPECTS correlated with mRS at 3 months and was predictive of unfavorable outcome after mechanical thrombectomy, but further studies in patients with poor scan are needed., (© 2017 by American Journal of Neuroradiology.)

Background and Purpose: In the treatment of acute thromboembolic stroke, the effectiveness and success of thrombus removal when using stent retrievers is variable. In this study, we analyzed the correlation of thrombectomy maneuver count with a good clinical outcome and recanalization success., Materials and Methods: One hundred and four patients with acute occlusion of the middle cerebral artery or the terminal internal carotid artery who were treated with thrombectomy were included in this retrospective study. A good clinical outcome was defined as a 90-day mRS of ≤2, and successful recanalization was defined as TICI 2b-3., Results: The maneuver count ranged between 1-10, with a median of 2. Multivariate logistic regression analyses identified an increasing number of thrombectomy maneuvers as an independent predictor of poor outcome (adjusted OR, 0.59; 95% CI, 0.38-0.87; P = .011) and unsuccessful recanalization (adjusted OR, 0.48; 95% CI, 0.32-0.66; P < .001). A good outcome was significantly more likely if finished within 2 maneuvers compared with 3 or 4 maneuvers, or even more than 4 maneuvers ( P < .001)., Conclusions: An increasing maneuver count correlates strongly with a decreasing probability of both good outcome and recanalization. The probability of successful recanalization decreases below 50% if not achieved within 5 thrombectomy maneuvers. Patients who are recanalized within 2 maneuvers have the best chance of achieving a good clinical outcome., (© 2017 by American Journal of Neuroradiology.)

Background and Purpose: Women have a worse outcome after stroke compared with men, although in intravenous thrombolysis (IVT)-treated patients, women seem to benefit more. Besides sex differences, age has also a possible effect on functional outcome. The interaction of sex on the functional outcome in IVT-treated patients in relation to age remains complex. The purpose of this study was to compare outcome after IVT between women and men with regard to age in a large multicenter European cohort reflecting daily clinical practice of acute stroke care., Methods: Data were obtained from IVT registries of 12 European tertiary hospitals. The primary outcome was poor functional outcome, defined as a modified Rankin scale score of 3 to 6 at 3 months. We stratified outcome by age in decades. Safety measures were symptomatic intracranial hemorrhage and mortality at 3 months., Results: In this cohort, 9495 patients were treated with IVT, and 4170 (43.9%) were women with a mean age of 71.9 years. After adjustments for baseline differences, female sex remained associated with poor functional outcome (odds ratio, 1.15; 95% confidence interval, 1.02-1.31). There was no association between sex and functional outcome when data were stratified by age. Symptomatic intracranial hemorrhage rate was similar in both sexes (adjusted odds ratio, 0.93; 95% confidence interval, 0.73-1.19), whereas mortality was lower among women (adjusted odds ratio, 0.83; 95% confidence interval, 0.70-0.99)., Conclusions: In this large cohort of IVT-treated patients, women more often had poor functional outcome compared with men. This difference was not dependent on age., (© 2017 American Heart Association, Inc.)

Background and Purpose: In Europe intravenous thrombolysis (IVT) for ischaemic stroke is still not approved for patients aged >80 years. However, elderly patients are frequently treated based on individual decision making. In a retrospective observational study a consecutive and prospective stroke registry in southwest Germany was analysed., Methods: The data registry collected 101,349 patients with ischaemic stroke hospitalized from January 2008 to December 2012. Of these, 38,575 (38%) were aged 80 years and older and 10 286 (10.1%) underwent IVT. Favourable outcome at discharge was defined as modified Rankin Scale (mRS) ≤1 or not worse than prior to stroke. Multiple logistic regression models stratified by 10-year age groups were used to assess the relationship between IVT and mRS at discharge, adjusted for patient characteristics, admitting facility and length of hospital stay., Results: The highest IVT rate was 15% in patients aged <50 years, with a continuous decline down to 8% in patients aged ≥90 years. Adjusted odds ratios and 95% confidence intervals for patients 80-89 years of age were 2.20 (1.95-2.47) (P < 0.0001) and 1.25 (0.88-1.78) (P = 0.21) for patients >90 years of age, compared to patients of the same age decade not treated with IVT., Conclusions: The evidence from routine hospital care in southwest Germany indicates that IVT is an effective treatment also for aged patients with ischaemic stroke in an age range between 80 and 89 years. Although no clear evidence for the effectiveness of IVT beyond 90 years was found, treatment should also be carefully considered in these patients. High age should not discourage from treatment., (© 2015 EAN.)

Aim: Aim of the paper was to assess the reliability of preoperative cross-flow determination by transcranial Doppler measurement (TCD) to detect clamping ischemia in patients undergoing carotid endarterectomy with selective shunting., Methods: Retrospective one-to-one matched-pair analysis of 72 patients undergoing carotid endarterectomy with preoperative TCD scanning. Matching criteria were gender, degree of contralateral stenosis and the type of stenosis (asymptomatic or symptomatic)., Results: Patients in need for a secondary shunt insertion had significantly less cross-flow in preoperative TCD measurement (N.=14; 38.89%) compared to the control group (N.=32; 88.89%: P=0.0001%). The sensitivity of the cross-flow determination to predict clamping ischemia was 88.9%, the specificity 61.1%. The risk of developing a clamping ischemia in the absence of a cross-flow was 12 fold higher (OR: 12.6; 95% CI: 3.7-43.3). The existence of circulatory impairment of the MCA was associated with the presence of a collateral flow in the ACoA (OR 3.21; P=0.0531; likelihood ratio test 0.0481). Other factors like renal insufficiency, the degree of stenosis or the stump pressure showed no association with a cross-flow of the ACoA in a multivariate model., Conclusion: TCD scanning is highly reliable to detect cross-flow prior to carotid surgery and thus helpful to identify patients at risk for clamping ischemia and need for shunting.

Background: Sex differences in the structural connectome of the brain are clinically highly relevant, but they have mostly been neglected in stroke trials. We investigated the impact of the interaction sex-by-hemisphere on outcome in stroke patients after intravenous thrombolysis (IVT)., Methods: This is an observational study based on consecutively collected supratentorial stroke patients treated with IVT (n = 1,231). The 3-month modified Rankin scale (mRS) was estimated by adjusted binary (mRS 0-2 for good outcome) and ordinal regression analysis. As baseline characteristics differ substantially between the sexes, we aimed for better covariate balance by employing coarsened exact matching., Results: Sex-by-hemisphere predicted good outcome in the entire cohort (726 left, 505 right hemispheric strokes, p valueinteraction 0.032) and in the matched cohort (338 left, 273 right, p valueinteraction 0.003). Ordinal regression suggested a comparable estimate in the matched cohort (p valueinteraction 0.006). Further investigation revealed relevant between-sex and within-sex risk: right hemispheric strokes in men were 1.54 times (95% confidence intervals (CIs) 1.15-2.01) more likely than in women to achieve mRS 0-2. Women with right hemispheric strokes were 0.72 times (95% CI 0.54-0.92) less likely to reach mRS 0-2 than women with left hemispheric strokes. Conversely, men with right hemispheric strokes were 1.35 times (95% CI 1.06-1.70) more likely to achieve mRS 0-2 than men with left hemispheric strokes., Conclusion: This study suggests that outcomes are different in both sexes after IVT when different hemispheres are affected. Further consideration of this hypothesis in clinical trials might help in guiding individualized, injury-specific treatment approaches for acute ischemic stroke.

Background: Intracerebral hemorrhage (ICH) with intraventricular extension (IVH) is a devastating disease with a particular high mortality. In some aspects, IVH may resemble subarachnoid hemorrhage. The incidence and role of cerebral vasospasm in ICH with IVH are poorly understood. Here, we aimed to analyze the incidence and relationship of cerebral vasospasm to clinical characteristics, in-hospital mortality, and functional outcome at 3 months in patients suffering ICH with IVH., Methods: Patients with ICH and IVH treated on a neurological intensive care unit were prospectively enrolled in a single-center observational study. Vasospasm was defined using established ultrasound criteria. Delayed cerebral ischemia (DCI) was defined as a new hypodensity on follow-up cranial CT. Functional outcome at 3 months was assessed using the modified Rankin Scale., Results: 129 patients with ICH and IVH were screened for the study. 62 patients entered the final analysis. The incidence of significant vasospasm was 37 %. A strong trend was found for the association between all cerebral vasospasm and DCI (P = 0.046). Early (up to 48 h) vasospasm was significantly associated with a DCI (P = 0.033). Overall mortality and outcome after 3 months did not differ between the groups., Conclusion: Cerebral vasospasm seems to be a frequent complication after ICH with IVH and might be associated with DCI. Larger studies are warranted to confirm this hypothesis.

Objective: To study the time dependent effectiveness of thrombolytic therapy for acute ischaemic stroke in daily clinical practice., Design: A retrospective cohort study using data from a large scale, comprehensive population based state-wide stroke registry in Germany., Setting: All 148 hospitals involved in acute stroke care in a large state in southwest Germany with 10.4 million inhabitants., Participants: Data from 84,439 patients with acute ischaemic stroke were analysed, 10,263 (12%) were treated with thrombolytic therapy and 74,176 (88%) were not treated., Main Outcome Measures: Primary endpoint was the dichotomised score on a modified Rankin scale at discharge ("favourable outcome" score 0 or 1 or "unfavourable outcome" score 2-6) analysed by binary logistic regression. Patients treated with recombinant tissue plasminogen activator (rtPA) were categorised according to time from onset of stroke to treatment. Analogous analyses were conducted for the association between rtPA treatment of stroke and in-hospital mortality. As a co-primary endpoint the chance of a lower modified Rankin scale score at discharge was analysed by ordinal logistic regression analysis (shift analysis)., Results: After adjustment for characteristics of patients, hospitals, and treatment, rtPA was associated with better outcome in a time dependent pattern. The number needed to treat ranged from 4.5 (within first 1.5 hours after onset; odds ratio 2.49) to 18.0 (up to 4.5 hours; odds ratio 1.26), while mortality did not vary up to 4.5 hours. Patients treated with rtPA beyond 4.5 hours (including mismatch based approaches) showed a significantly better outcome only in dichotomised analysis (odds ratio 1.25, 95% confidence interval 1.01 to 1.55) but the mortality risk was higher (1.45, 1.08 to 1.92)., Conclusion: The effectiveness of thrombolytic therapy in daily clinical practice might be comparable with the effectiveness shown in randomised clinical trials and pooled analysis. Early treatment was associated with favourable outcome in daily clinical practice, which underlines the importance of speeding up the process for thrombolytic therapy in hospital and before admission to achieve shorter time from door to needle and from onset to treatment for thrombolytic therapy., (© Gumbinger et al 2014.)

Background and Purpose: We previously reported increased benefit and reduced mortality after ultra-early stroke thrombolysis in a single center. We now explored in a large multicenter cohort whether extra benefit of treatment within 90 minutes from symptom onset is uniform across predefined stroke severity subgroups, as compared with later thrombolysis., Methods: Prospectively collected data of consecutive ischemic stroke patients who received i.v. thrombolysis in 10 European stroke centers were merged. Logistic regression tested association between treatment delays, as well as excellent 3-month outcome (modified Rankin scale, 0-1), and mortality. The association was tested separately in tertiles of baseline National Institutes of Health Stroke Scale., Results: In the whole cohort (n=6856), shorter onset-to-treatment time as a continuous variable was significantly associated with excellent outcome (P<0.001). Every fifth patient had onset-to-treatment time≤90 minutes, and these patients had lower frequency of intracranial hemorrhage. After adjusting for age, sex, admission glucose level, and year of treatment, onset-to-treatment time≤90 minutes was associated with excellent outcome in patients with National Institutes of Health Stroke Scale 7 to 12 (odds ratio, 1.37; 95% confidence interval, 1.11-1.70; P=0.004), but not in patients with baseline National Institutes of Health Stroke Scale>12 (odds ratio, 1.00; 95% confidence interval, 0.76-1.32; P=0.99) and baseline National Institutes of Health Stroke Scale 0 to 6 (odds ratio, 1.04; 95% confidence interval, 0.78-1.39; P=0.80). In the latter, however, an independent association (odds ratio, 1.51; 95% confidence interval, 1.14-2.01; P<0.01) was found when considering modified Rankin scale 0 as outcome (to overcome the possible ceiling effect from spontaneous better prognosis of patients with mild symptoms). Ultra-early treatment was not associated with mortality., Conclusions: I.v. thrombolysis within 90 minutes is, compared with later thrombolysis, strongly and independently associated with excellent outcome in patients with moderate and mild stroke severity.

Study registries offer the opportunity to evaluate the effects of new therapies or to observe the consequences of new treatments in clinical practice. The SITS-MOST registry confirmed the validity of findings from randomized trials on intravenous thrombolysis concerning safety and efficacy in the clinical routine. Current study registries concerning new interventional thrombectomy techniques suggest a high recanalization rate; however, the clinical benefit can only be evaluated in randomized, controlled trials. Similarly, the experiences of the BASICS registry on basilar artery occlusion have led to the initiation of a controlled trial. The benefit of hemicraniectomy in malignant middle cerebral artery infarction has been demonstrated by the pooled analysis of three randomized trials. Numerous relevant aspects are currently documented in the DESTINY-R registry. Finally, the recently started RASUNOA registry examines diagnostic and therapeutic aspects of ischemic and hemorrhagic stroke occurring during therapy with new oral anticoagulants.

Background and Purpose: Detection of atrial fibrillation is of vital importance because oral anticoagulation decreases the risk of a stroke by 64%. Current standards for stroke unit treatment require continuous electrocardiogram (ECG) monitoring for at least 24 h. Additionally, a 24-h HOLTER ECG (HOLTER) should be performed in selected patients. It remains unclear whether continuous monitoring at the bedside is equivalent to HOLTER for the detection of atrial fibrillation. Furthermore, we investigate how many additional patients with paroxysmal atrial fibrillation can be identified as a result of a longer duration of continuous monitoring., Methods: In this study, we prospectively compared the detection rates of HOLTER and 24-h monitoring at the Stroke Unit at the University of Heidelberg over a period of 9 months. Continuous monitoring was analyzed by trained nurses, HOLTER by cardiologists., Results: We included 370 patients with ischemic stroke or transient ischemic attack (TIA) in our study. Of these, 192 patients underwent HOLTER. Previously unknown atrial fibrillation was detected in 44 patients, 13 patients had no atrial fibrillation in baseline ECG, but atrial fibrillation was detected by continuous monitoring. In two patients, the HOLTER showed atrial fibrillation; both patients had also been detected by continuous monitoring. Median time to detection of the atrial fibrillation during continuous monitoring was 43 h after hospitalization., Conclusion: In this study, use of HOLTER does not give any additional benefit in comparison with continuous monitoring with intermittent analysis by trained staff alone. The median detection time of 43 h emphasizes the importance of longer continuous monitoring., (© 2011 The Author(s). European Journal of Neurology © 2011 EFNS.)

Background: The emergency management of patients with acute ischemic stroke (IS) using oral anticoagulants (OAC) represents a great challenge. Effective anticoagulation predisposes to bleeding and represents a contraindication for systemic thrombolysis. However, patients on OAC can receive intravenous thrombolysis with recombinant tissue-type plasminogen activator if the international normalized ratio (INR) does not exceed 1.7, but data regarding the risk of hemorrhagic complications are highly controversial. Neurointerventional recanalization of intracranial artery occlusion represents an alternative option in OAC patients with acute IS. The proportion of OAC users among consecutive patients who suffer from acute IS or transient ichemic attacks (TIA) is unknown., Methods: A prospective observational study, consecutively enrolling all patients with IS or TIA admitted to our neurological emergency room (ER), was performed between August 2009 and February 2011. Basic demographic variables, present use of OAC, severity of stroke, cardiovascular risk factors, INR values and the symptom onset to presentation time were recorded. In IS patients on OAC presenting within 4.5 h after symptom onset, management was analyzed. In thrombolysed IS patients, bleeding events were documented. Outcome was assessed after 3 months., Results: During the study period, 12,237 patients were admitted to our neurological ER. IS or TIA were diagnosed in 2,074 (16.9%). Complete data were available for 1,914 of these subjects (92.3%); 53.8% were male (median age: 72 years). 69.7% suffered IS, 30.3% TIA. OAC were being used by 8.7% of all patients. OAC patients were older than non-OAC patients (78 vs. 72 years, p < 0.001). Subtherapeutic INR values (<2.0) were found in 67.3% of OAC patients with IS. 54.8% of all OAC IS patients presented at the ER within ≤4.5 h after the event (57/104). An INR ≤1.7 - compatible with systemic thrombolysis - was present in 33/57 patients (57.9%). Recanalization therapy was performed in 21/57 patients (36.8%). No difference in symptomatic or fatal intracerebral bleedings between thrombolysed patients with and without prior OAC use was observed (p = 0.720 and 0.135, respectively). Multivariable analysis of predictors of the 3-month outcome in IS patients revealed that prior medication with OAC was neither associated with an unfavorable clinical outcome after 3 months in the whole population of stroke patients (p = 0.235) nor in patients in whom recanalization approaches were used (n = 306; p = 0.271)., Conclusions: Oral anticoagulation represents a frequent challenge for the emergency manangement of IS. A considerable proportion of anticoagulated IS patients appears to be eligible for thrombolysis. Establishing standardized treatment procedures in these patients is warranted., (Copyright © 2012 S. Karger AG, Basel.)

Background and Purpose: Direct comparison of symptomatic intracerebral hemorrhage (sICH) rates among different thrombolysis studies is complicated by the variability of definitions of sICH. The prediction of outcome still remains unclear., Methods: Baseline data and clinical courses of patients treated with thrombolytic therapy were collected in a prospective database. The 3-month outcome was evaluated using the modified Rankin Scale. Results of 24-hour follow-up imaging were reevaluated by at least 2 independent raters. Four common definitions of sICH (National Institute of Neurological Disorders and Stroke [NINDS], European Cooperative Acute Stroke Study [ECASS] 2, Safe Implementation of Thrombolysis in Stroke [SITS], ECASS 3) were applied. Kappa interrater statistics were calculated. Our objective was to find the sICH definition with the highest predictive value for mortality, poor (modified Rankin Scale 5 or 6) and unfavorable (modified Rankin Scale ≥3) clinical outcome after 90 days., Results: The data of 314 patients were analyzed. The NINDS definition revealed the highest sICH rate (7.7%); the lowest rate was found for the ECASS 3 definition (3.2%) of sICH. The highest interrater agreement was found for the ECASS 2 definition (κ 0.85) and the lowest for the NINDS definition (κ 0.57). Patients with sICH according to the SITS definition had the highest risk for death (OR, 14.4) and poor outcome (OR, 26.6)., Conclusions: None of the different definitions contains an optimal combination of prediction of mortality and outcome and a high interrater agreement rate. For the clinical evaluation of mortality, we recommend using the SITS definition; for studies needing a high interrater agreement rate, we recommend using the ECASS 2 definition. Due to the lack of 1 single optimal definition, future thrombolytic trials should preferably use different definitions.

Background and Purpose: In acute thromboembolic stroke, mechanical recanalization with stents may result in immediate flow restoration. The Solitaire stent can be used both for flow restoration and thrombectomy. In this single-center experience, we report safety and efficacy data on the application of the Solitaire stent., Materials and Methods: Between March 2009 and July 2010, 18 patients were treated with the Solitaire stent. To evaluate perfusion of the occluded vessel segment before and after the intervention, the TICI score was used (0-3). Clinical outcome was assessed by using the mRS at discharge., Results: Overall, recanalization was successful in 16 of 18 patients (88.8%). There were no procedure-related complications. Mean TICI score after the intervention was 2.3 ± 0.8. In 5 patients, reocclusion of the treated vessel occurred immediately after retrieval of the temporarily opened stent, and permanent stent deployment was performed to maintain stable perfusion. In 3 patients, hemorrhage occurred after successful recanalization. Five patients died (infarction, n = 3; hemorrhage, n = 1; organ failure, n = 1). A good clinical outcome (mRS ≤2) was achieved in 33.3% of the patients, 5.5% had a moderate outcome (mRS, 3/4), and 61.2% had a poor outcome or died (mRS, 5/6)., Conclusions: Application of the Solitaire stent in acute stroke results in a high recanalization rate (88.8%) without procedural complications and with a good outcome in one-third of patients. These results encourage further evaluation of the stent in larger patient populations.

Background: Atrial fibrillation (AF) is a common cause of ischemic stroke and transient ischemic attack (TIA). More extensive diagnostic effort is required to detect paroxysmal AF (pxAF) than persistent AF (pAF); the prevalence of pxAF in stroke patients is unknown. We evaluated the prevalence of pAF and pxAF in ischemic stroke and TIA patients., Methods: Consecutive patients with acute ischemic stroke/TIA were enrolled prospectively. We aimed to detect patients with a history of AF, with AF newly diagnosed in the emergency room (ER), or with newly diagnosed AF during a 3-month period following the event. Differences in the frequency of AF diagnosis with respect to the disposition of patients after ER work-up were assessed., Results: A total of 692 patients were enrolled (male: 52.2%; ischemic stroke: 69.1%; TIA: 30.9%). A previously documented history of AF was present in 19.7% (pAF: 47.1%, pxAF: 52.9%). In 3.8% of patients, AF was newly diagnosed in the ER (pxAF: 61.5%) and in 5.2% during the 3-month follow-up period. The overall prevalence of AF was 28.6% (pxAF: 62.6%). Previously documented pxAF evaded diagnosis at ER presentation in 48.6%. The prevalence of AF increased with age (p < 0.001). Patients with pxAF were younger than those with pAF (p = 0.004) and more often female (p = 0.05). The presence of any AF was associated with higher initial NIHSS scores (p < 0.001) and higher modified Rankin scores after 3 months (p < 0.001)., Conclusion: pxAF occurs more often than pAF in stroke/TIA patients. As effective stroke prevention is available for AF, it is important to develop and evaluate sensitive methods for detecting pxAF., (Copyright © 2011 S. Karger AG, Basel.)

Background and Purpose: Antiplatelets (APs) may increase the risk of symptomatic intracerebral hemorrhage (ICH) following intravenous thrombolysis after ischemic stroke., Methods: We assessed the safety of thrombolysis under APs in 11,865 patients compliant with the European license criteria and recorded between 2002 and 2007 in the Safe Implementation of Treatments in Stroke (SITS) International Stroke Thrombolysis Register (SITS-ISTR). Outcome measures of univariable and multivariable analyses included symptomatic ICH (SICH) per SITS Monitoring Study (SITS-MOST [deterioration in National Institutes of Health Stroke Scale >or=4 plus ICH type 2 within 24 hours]), per European Cooperative Acute Stroke Study II (ECASS II [deterioration in National Institutes of Health Stroke Scale >or=4 plus any ICH]), functional outcome at 3 months and mortality., Results: A total of 3782 (31.9%) patients had received 1 or 2 AP drugs at baseline: 3016 (25.4%) acetylsalicylic acid (ASA), 243 (2.0%) clopidogrel, 175 (1.5%) ASA and dipyridamole, 151 (1.3%) ASA and clopidogrel, and 197 (1.7%) others. Patients receiving APs were 5 years older and had more risk factors than AP naïve patients. Incidences of SICH per SITS-MOST (ECASS II respectively) were as follows: 1.1% (4.1%) AP naïve, 2.5% (6.2%) any AP, 2.5% (5.9%) ASA, 1.7% (4.2%) clopidogrel, 2.3% (5.9%) ASA and dipyridamole, and 4.1% (13.4%) ASA and clopidogrel. In multivariable analyses, the combination of ASA and clopidogrel was associated with increased risk for SICH per ECASS II (odds ratio, 2.11; 95% CI, 1.29 to 3.45; P=0.003). However, we found no significant increase in the risk for mortality or poor functional outcome, irrespective of the AP subgroup or SICH definition., Conclusions: The absolute excess of SICH of 1.4% (2.1%) in the pooled AP group is small compared with the benefit of thrombolysis seen in randomized trials. Although caution is warranted in patients receiving the combination of ASA and clopidogrel, AP treatment should not be considered a contraindication to thrombolysis.

Multiparametric MRI including diffusion and perfusion imaging provides information on the extent of irreversibly damaged ischemic and/or critically hypoperfused tissue. Magnetic resonance angiography provides additional information on vessel status. The concept of perfusion-diffusion mismatch allows the estimation of tissue at risk of infarction which might be salvaged by timely reperfusion. In large case series and nonrandomized cohort studies, perfusion-diffusion mismatch-based thrombolysis was performed not less than 3 h after symptom onset with excellent safety and signs of good efficacy. However no randomised controlled trial has confirmed this to date. Recent studies improved the understanding of the mismatch concept and identified reperfusion unequivocally as an important predictor of the clinical response to thrombolysis. At the moment MRI-based thrombolysis can be performed after 3 h based on individual benefit:risk assessment in experienced stroke centers.

Background: Owing to the fear of an increased bleeding risk, thrombolytic therapy is withheld from many patients with acute stroke > 80 years of age., Objective: To analyse the risk for symptomatic intracranial haemorrhage (sICH), morbidity and mortality after thrombolytic therapy in octogenarians focusing, in particular, on whether patients selected using magnetic resonance imaging (MRI) had a better risk:benefit ratio., Methods: The prospectively collected single-centre data of all patients treated with systemic thrombolytic therapy for acute ischaemic stroke since 1998 (n = 468) were reviewed, and patients > or = 80 years (n = 90) were compared with those aged < 80 years (n = 378). In addition, the group of octogenarians was analysed with respect to initial imaging modality., Results: The overall rate of sICH in the octogenarians was 6.9%, compared with 5.3% in younger patients (p = 0.61). In older patients selected by computed tomography, the rate of sICH was 9.4%; no patient selected by MRI had sICH (p = 0.10). Mortality in the octogenarians selected by computed tomography was 29.7% after 3 months as compared with 26.9% in the patients selected by MRI (p = 1.0). 20.3% of the octogenarians selected by computed tomography and 15.4% of those selected by MRI had a favourable outcome (modified Rankin scale < or = 1) after 3 months (p = 0.77)., Conclusion: Compared with younger patients, octogenarians do not have an increased risk of sICH. The use of MRI to select octogenarians for thrombolytic therapy seemed to decrease the risk of sICH, but did not influence the overall outcome after 3 months.

Background: Clinical studies using ultrasound at diagnostic frequencies in transcranial Doppler devices provided encouraging results in enhancing thrombolysis with tissue plasminogen activator (tPA) in acute stroke. Low-frequency ultrasound does not require complex positioning procedures, penetrates through the skull better, and has been demonstrated to accelerate thrombolysis with tPA in animal experiments in wide cerebrovascular territories without hemorrhagic side effects. We therefore conducted the first multicenter clinical trial to investigate safety of tPA plus low-frequency ultrasound (300 kHz)., Methods: Acute stroke patients within a 6-hour time window were included (National Institutes of Health Stroke Scale scores >4). Magnetic resonance imaging (MRI) was used to document vascular occlusion and to rule out cerebral hemorrhage. Patients were allocated to combination therapy alternately; the first patient received tPA only, the second patient received tPA plus ultrasound, etc. Follow-up included serial MRI directly thereafter and 24 hours later to confirm recanalization and tissue imaging. Clinical recovery was measured after treatment and 3 months later., Results: 26 patients (70.4+/-9.7 years) entered the trial (12 tPA, 14 tPA plus ultrasound). The study was prematurely stopped because 5 of 12 patients from the tPA only group but 13 of 14 patients treated with the tPA plus ultrasound showed signs of bleeding in MRI (P<0.01). Within 3 days of treatment, 5 symptomatic hemorrhages occurred within the tPA plus ultrasound group. At 3 months, neither morbidity nor treatment-related mortality or recanalization rates differed between both groups., Conclusions: This study demonstrated bioeffects from low-frequency ultrasound that caused an increased rate of cerebral hemorrhages in patients concomitantly treated with intravenous tPA.

Background and Purpose: Women experience worse outcomes after stroke compared with men. Prior work has suggested sex-based differences in coagulation and fibrinolysis markers in subjects with acute stroke. We explored whether sex might modify the effect of recombinant tissue plasminogen activator (rtPA) on outcomes in patients with acute ischemic stroke., Methods: Using a combined database including subjects from the National Institute of Neurological Disorders and Stroke (NINDS), Alteplase Thrombolysis for Acute Noninterventional Therapy in Ischemic Stroke (ATLANTIS) A and B, and the Second European Cooperative Acute Stroke Study (ECASS II) trials, we examined 90-day outcomes in patients randomized to rtPA versus placebo by sex. We used logistic regression to control for potential confounders., Results: Among 988 women treated between 0 and 6 hours from symptom onset, patients receiving rtPA were significantly more likely than those receiving placebo to have a modified Rankin Score < or =1 (40.5% versus 30.3%, P<0.0008). Among 1190 men, the trend toward benefit in the overall group did not reach statistical significance (38.5% versus 36.7%, P=0.52). An unadjusted analysis showed that women were significantly more likely to benefit from rtPA compared with men (P=0.04). Controlling for age, baseline National Institutes of Health Stroke Scale, diabetes, symptom onset to treatment time, prior stroke, systolic blood pressure, extent of hypoattenuation on baseline computed tomography scan and several significant interaction terms (including onset to treatment time-by-treatment and systolic blood pressure-by treatment) did not substantially change the strength of the interaction between gender and rtPA treatment (P=0.04)., Conclusions: In this pooled analysis of rtPA in acute ischemic stroke, women benefited more than men, and the usual gender difference in outcome favoring men was not observed in the thrombolytic therapy group. For patients presenting at later time intervals, when the risks and benefits of rtPA are more finely balanced, sex may be an important variable to consider for patient selection.

Objective: The purpose of this study was to examine the safety of carotid endarterectomy (CEA) within 6 weeks after a nondisabling carotid-related ischemic stroke. Endpoints were the perioperative stroke or mortality rate and the incidence rate of cerebral bleedings., Methods: This prospective observational multicenter trial was performed in community and university centers. One hundred sixty-four hospitalized patients with nondisabling carotid-related ischemic stroke were included. The patients were identified clinically with the modified Rankin scale (initial neurologic deficit grade >/= 2, n = 160). Four patients with evidence of ischemic territorial infarction on cerebral computed tomographic (CT) scan but no persisting functional deficit were also included. CEA was performed within 6 weeks after stroke. Neurologic examinations were performed initially, before surgery, 3 days after surgery, and 6 weeks after CEA. Worsening of more than 1 grade on the Rankin scale was considered as a new stroke or stroke extension. Unenhanced CT scans of the brain were performed before and after surgery. CT scans were evaluated blind to clinical patient data. Statistical analysis included univariate and multivariate analysis., Results: The combined stroke or mortality rate within 30 days after CEA was 6.7%. Ten patients had a new ipsilateral stroke or stroke extension, and one patient died after surgery of a myocardial infarction. One patient (0.6%) had parenchymatous cerebral bleeding, and in 10 patients, hemorrhagic transformation within the preexisting ischemic infarction was detected but no infarct extension was observed. In the multivariate analysis, American Society of Anesthesiology (ASA) grades III and IV and decreasing age were significant predictors for an increased perioperative risk. Patients with a higher risk profile (ASA classification grades III and IV) had a high perioperative risk when CEA was performed within the first 3 weeks (14.6% versus 4.8% beyond 3 weeks). Patients without severe concomitant diseases (ASA grades I/II) had a low perioperative risk of 3.4% if CEA was performed within the first 3 weeks., Conclusion: Early CEA within 6 weeks after a carotid-related ischemic stroke can be performed with a perioperative stroke or mortality rate comparable with the results reported in the European Carotid Surgery Trial and the North American Symptomatic Carotid Endarterectomy Trial. The risk of parenchymatous bleeding is low. ASA grades III and IV and decreasing age were predictive of an increased perioperative risk, especially if CEA was performed within the first 3 weeks. Patients at low risk can undergo operation safely within the first 3 weeks. Individual patient selection in an interdisciplinary approach between neurologists, anesthesiologists, and vascular surgeons remains mandatory in these patients.

Background: The use of recombinant tissue plasminogen activator (rtPA) within 3 hours after onset of an ischemic stroke is an established therapy. Because the use of intravenous rtPA beyond a time window of 3 hours after stroke onset is still a matter of debate, we sought to review the evidence for the use of thrombolytic therapy in a time window up to 6 hours after onset of symptoms of ischemic stroke., Summary of Review: The meta-analyses of the major trials (National Institute of Neurological Disorders and Stroke rtPA Stroke Study, European Cooperative Acute Stroke Study [ECASS] I, ECASS II) showed a benefit of thrombolytic therapy with intravenous rtPA even within 6 hours after onset of symptoms of ischemic stroke. The rate of intracerebral hemorrhage was slightly increased in the 6-hour time window compared with the 3-hour time window (odds ratio, 3.23 versus 2.68), but this was without statistical significance because of wide confidence intervals. A positive effect of 37% relative odds reduction with the use of a dichotomization of < or =2 versus > or =3 on the modified Rankin Scale remains for rtPA treatment within 6 hours. However, the Alteplase Thrombolysis for Acute Noninterventional Therapy in Ischemic Stroke (ATLANTIS) Study, in which a 3- to 5-hour time window was used, failed to show a benefit of rtPA. Still, when the results of ATLANTIS are included into meta-analyses such as the Cochrane Library, the positive effect of rtPA treatment in the 6-hour time window remains, with a "number needed to treat" value of 11. Treating patients only within a 3- to 6-hour time window would lead to a number needed to treat value of 25., Conclusions: Consequently, from our point of view it appears unjustified to limit thrombolytic therapy to 3 hours. Because of lack of approvals for 3 to 6 hours, thrombolytic therapy within this time window should be done only as part of an institutional protocol after extensive information is obtained from the patient and the patient's relatives. Better methods for patient selection are required; in particular, newer MRI techniques, such as diffusion- and perfusion-weighted imaging, can play a key role. The aim is to qualify and individualize the time window according to the findings in each patient's imaging results rather than to use a strictly time-defined therapeutic window.

We studied the diagnostic and prognostic value of diffusion- and perfusion-weighted magnetic resonancce imaging (DWI and PWI) for the initial evaluation and follow-up monitoring of patients with stroke that had ensued less than 6 hours previously. Further, we examined the role of vessel patency or occlusion and subsequent recanalization or persistent occlusion for further clinical and morphological stroke progression so as to define categories of patients and facilitate treatment decisions. Fifty-one patients underwent stroke magnetic resonance imaging (DWI, PWI, magnetic resonance angiography, and T2-weighted imaging) within 3.3 +/- 1.29 hours, and, of those, 41 underwent follow-up magnetic resonance imaging on day 2 and 28 on day 5. In addition, we assessed clinical scores (on the National Institutes of Health Stroke Scale, Scandinavian Stroke Scale, Barthel Index, and Modified Rankin Scale) on days 1, 2, 5, 30, and 90 and performed volumetric analysis of lesion volumes. In all, 25 patients had a proximal, 18 a distal, and 8 no vessel occlusion. Furthermore, 15 of 43 patients exhibited recanalization on day 2. Vessel occlusion was associated with a PWI-DWI mismatch on the initial magnetic resonance imaging, vessel patency with a PWI-DWI match (p < 0.0001). Outcome scores and lesion volumes differed significantly between patients experiencing recanalization and those who did not (all p < 0.0001). Acute DWI and PWI lesion volumes correlated poorly with acute clinical scores and only modestly with outcome scores. We have concluded on the basis of this study that early recanalization saves tissue at risk of ischemic infarction and results in significantly smaller infarcts and a significantly better clinical outcome. Patients with proximal vessel occlusions have a larger amount of tissue at risk, a lower recanalization rate, and a worse outcome. Urgent recanalization seems to be of utmost importance for these patients.

Introduction and Development: There appears to be a rationale for the use of thrombolysis in ischemic stroke. Streptokinase should no longer be used to treat acute ischemic stroke. However, thrombolytic treatment with recombinant tissue plasminogen activator (rt-PA) may have an important role in the management of acute stroke. The studies to-date highlight the importance of early intervention and careful patient selection. In the National Institute of Neurological Disorders and Stroke (NINDS) trial, treatment within three hours was associated with an improved functional outcome without an increase in mortality. In the European Cooperative Acute Stroke Study (ECASS), treatment of eligible patients resulted in improved neurologic and functional out come. In the Multicentre Acute Stroke Trial Europe (MAST-E) and Australian Streptokinase Trial (ASK) trials, later intervention was associated with an increased risk of cerebral hemorrhage and poor outcome., Conclusions: Successful use of thrombolytic therapy with rt-PA, therefore, depends on rapid assessment to exclude patients with hemorrhagic stroke or those at risk of hemorrhagic complications. It has been shown to be beneficial in patients treated within three hours who conform to the strict inclusion and exclusion criteria of the NINDS trial. Moreover, after the results of ECASS II, and the recent metaanalyses of all three major rt-PA trials, it seems that with strict selection criteria, expert CT-reading, adherence to the protocols and a stroke unit type approach, the time window for thrombolysis may be as long as six hours in selected patients.

Purpose: The feasibility and safety of combining carotid surgery and thrombolysis for occlusions of the internal carotid artery (ICA) and the middle cerebral artery (MCA), either as a simultaneous or as a staged procedure in acute ischemic strokes, was studied., Methods: A nonrandomized clinical pilot study, which included patients who had severe hemispheric carotid-related ischemic strokes and acute occlusions of the MCA, was performed between January 1994 and January 1998. Exclusion criteria were cerebral coma and major infarction established by means of cerebral computed tomography scan. Clinical outcome was assessed with the modified Rankin scale., Results: Carotid reconstruction and thrombolysis was performed in 14 of 845 patients (1.7%). The ICA was occluded in 11 patients; occlusions of the MCA (mainstem/major branches/distal branch) or the anterior cerebral artery (ACA) were found in 14 patients. In three of the 14 patients, thrombolysis was performed first, followed by carotid enarterectomy (CEA) after clinical improvement (6 to 21 days). In 11 of 14 patients, 0.15 to 1 mIU urokinase was administered intraoperatively, ie, emergency CEA for acute ischemic stroke (n = 5) or surgical reexploration after elective CEA complicated by perioperative intracerebral embolism (n = 6). Thirteen of 14 intracranial embolic occlusions and 10 of 11 ICA occlusions were recanalized successfully (confirmed with angiography or transcranial Doppler studies). Four patients recovered completely (Rankin 0), six patients sustained a minor stroke (Rankin 2/3), two patients had a major stroke (Rankin 4/5), and two patients died. In one patient, hemorrhagic transformation of an ischemic infarction was detectable postoperatively., Conclusion: Combining carotid surgery with thrombolysis (simultaneous or staged procedure) offers a new therapeutic approach in the emergency management of an acute carotid-related stroke. Its efficacy should be evaluated in interdisciplinary studies.