Search

Background: Landmark thrombectomy trials have provided evidence that selected patients with large ischemic stroke benefit from successful endovascular therapy, commonly defined as incomplete (modified Thrombolysis In Cerebral Infarction (mTICI) 2b) or complete reperfusion (mTICI 3). We aimed to investigate whether mTICI 3 improves functional outcomes compared with mTICI 2b in large ischemic strokes., Methods: This retrospective multicenter cohort study was conducted to compare mTICI 2b versus mTICI 3 in large ischemic strokes in the anterior circulation. Patients enrolled in the German Stroke Registry between 2015-2021 were analyzed. Large ischemic stroke was defined as an Alberta Stroke Program Early CT Score (ASPECTS) of 3-5. Patients were matched by final mTICI grade using propensity score matching. Primary outcome was the 90-day modified Rankin Scale (mRS) score., Results: After matching, 226 patients were included. Baseline and imaging characteristics were balanced between mTICI 2b and mTICI 3 patients. There was no shift on the mRS favoring mTICI 3 compared with mTICI 2b in large ischemic strokes (adjusted common odds ratio (acOR) 1.12, 95% confidence interval (95% CI) 0.64 to 1.94, P=0.70). The rate of symptomatic intracranial hemorrhage was higher in mTICI 2b than in mTICI 3 patients (12.6% vs 4.5%, P=0.03). Mortality at 90 days did not differ between mTICI 3 and mTICI 2b (33.6% vs 37.2%; adjusted OR 0.69, 95% CI 0.33 to 1.45, P=0.33)., Conclusions: In endovascular therapy for large ischemic strokes, mTICI 3 was not associated with better 90-day functional outcomes compared with mTICI 2b. This study suggests that mTICI 2b might be warranted as the final angiographic result, questioning the benefit/risk ratio of additional maneuvers to seek for mTICI 3 in large ischemic strokes., Trial Registration Number: NCT03356392., Competing Interests: Competing interests: TDF reported grants from the German Research Foundation (DFG; Project Number: 411621970). GB reported receiving personal fees from Eppdata GmbH and compensation as a speaker from Balt outside the submitted work. HK reported an ownership stake in Eppdata GmbH and compensation from Eppdata GmbH for consultant services outside the submitted work. GH reported receiving personal fees from Acandis, Alexion, Amarin, Bayer, Boehringer Ingelheim, Bristol Myers Squibb/Pfizer, Daiichi Sankyo, Portola, and Stryker outside the submitted work. JF reported compensation from Acandis, Cerenovus, MicroVention, Medtronic, Penumbra, Phenox, Roche, Stryker, Tonbridge and stock holdings in Eppdata GmbH and Tegus Medical outside the submitted work. FF reported receiving personal fees from Eppdata GmbH outside the submitted work., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Purpose: In wake-up stroke, CT-based quantitative net water uptake (NWU) might serve as an alternative tool to MRI to guide intravenous thrombolysis with alteplase (IVT). An important complication after IVT is symptomatic intracerebral haemorrhage (sICH). As NWU directly implies ischaemic lesion progression, reflecting blood-brain barrier injury, we hypothesised that NWU predicts sICH in patients who had a ischaemic stroke undergoing thrombectomy with unknown onset., Methods: Consecutive analysis of all patients who had unknown onset anterior circulation ischaemic stroke who underwent CT at baseline and endovascular treatment between December 2016 and October 2020. Quantitative NWU was assessed on baseline CT. The primary endpoint was sICH. The association of NWU and other baseline parameters to sICH was investigated using inverse-probability weighting (IPW) analysis., Results: A total of 88 patients were included, of which 46 patients (52.3%) received IVT. The median NWU was 10.7% (IQR: 5.1-17.7). The proportion of patients with any haemorrhage and sICH were 35.2% and 13.6%. NWU at baseline was significantly higher in patients with sICH (19.1% vs 9.6%, p<0.0001) and the median Alberta Stroke Program Early CT Score (ASPECTS) was lower (5 vs 8, p<0.0001). Following IPW, there was no association between IVT and sICH in unadjusted analysis. However, after adjusting for ASPECTS and NWU, there was a significant association between IVT administration and sICH (14.6%, 95% CI: 3.3% to 25.6%, p<0.01)., Conclusion: In patients with ischaemic stroke with unknown onset, the combination of high NWU with IVT is directly linked to higher rates of sICH. Besides ASPECTS for evaluating the extent of the early infarct lesion, quantitative NWU could be used as an imaging biomarker to assess the degree of blood-brain barrier damage in order to predict the risk of sICH in patients with wake up stroke., Competing Interests: Competing interests: JF: German Ministry of Science and Education (BMBF), German Ministry of Economy and Innovation (BMWi), German Research Foundation (DFG), European Union (EU), Hamburgische Investitions- und Förderbank (IFB). GT: Grants by the European Union (Grant No. 278276 und 634809) and Deutsche Forschungsgemeinschaft (SFB 936, Projekt C2). AK: research collaboration agreement: Siemens Healthcare (company involved in CT/MRI distribution). All other authors reported no relationships with commercial firms whose products could be affected by the present study., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The aim of the present European Stroke Organisation (ESO) guideline is to provide evidence-based recommendations on the acute management of patients with basilar artery occlusion (BAO). These guidelines were prepared following the Standard Operational Procedure of the ESO and according to the GRADE methodology.Although BAO accounts for only 1-2% of all strokes, it has very poor natural outcome. We identified 10 relevant clinical situations and formulated the corresponding Population Intervention Comparator Outcomes (PICO) questions, based on which a systematic literature search and review was performed. The working group consisted of 10 voting members (five representing ESO and five representing the European Society of Minimally Invasive Neurological Therapy (ESMINT)) and three non-voting junior members. The certainty of evidence was generally very low. In many PICOs, available data were scarce or lacking, hence, we provided expert consensus statements.First, we compared intravenous thrombolysis (IVT) to no IVT, but specific BAO-related data do not exist. Yet, historically, IVT was standard of care for BAO patients who were also included (although in small numbers) in IVT trials. Non-randomized studies of IVT-only cohorts showed a high proportion of favorable outcomes. Expert Consensus suggests using IVT up to 24 hours unless otherwise contraindicated. We further suggest IVT plus endovascular treatment (EVT) over direct EVT. EVT on top of best medical treatment (BMT) was compared with BMT alone within 6 and 6-24 hours from last seen well. In both time windows, we observed a different effect of treatment depending on a) the region where the patients were treated (Europe vs Asia), b) on the proportion of IVT in the BMT arm, and c) on the initial stroke severity. In case of high proportion of IVT in the BMT group and in patients with a National Institutes of Health Stroke Scale (NIHSS) score below 10, EVT plus BMT was not found better than BMT alone. Based on very low certainty of evidence, we suggest EVT+BMT over BMT alone (this is based on results of patients with at least 10 NIHSS points and a low proportion of IVT in BMT). For patients with an NIHSS score below 10, we found no evidence to recommend EVT over BMT. In fact, BMT was non-significantly better and safer than EVT. Furthermore, we found a stronger treatment effect of EVT+BMT over BMT alone in proximal and middle locations of BAO compared with distal location. While recommendations for patients without extensive early ischemic changes in the posterior fossa can, in general, follow those of other PICOs, we formulated an Expert Consensus Statement suggesting against reperfusion therapy in those with extensive bilateral and/or brainstem ischemic changes. Another Expert Consensus suggests reperfusion therapy regardless of collateral scores. Based on limited evidence, we suggest direct aspiration over stent retriever as the first-line strategy of mechanical thrombectomy. As an Expert Consensus, we suggest rescue percutaneous transluminal angioplasty and/or stenting after a failed EVT procedure. Finally, based on very low certainty of evidence, we suggest add-on antithrombotic treatment during EVT or within 24 hours after EVT in patients with no concomitant IVT and in whom EVT was complicated (defined as failed or imminent re-occlusion, or need for additional stenting or angioplasty)., Competing Interests: Competing interests: All authors have completed a declaration of competing interests and details are available in online supplemental table 1., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Background The combination of intravenous thrombolysis (IVT) with mechanical thrombectomy (MT) may have clinical benefits for patients with medium vessel occlusion. Purpose To examine whether MT combined with IVT is associated with different outcomes than MT alone in patients with acute ischemic stroke (AIS) and medium vessel occlusion. Materials and Methods This retrospective study included consecutive adult patients with AIS and medium vessel occlusion treated with MT or MT with IVT at 37 academic centers in North America, Asia, and Europe. Data were collected from September 2017 to July 2021. Propensity score matching was performed to reduce confounding. Univariable and multivariable logistic regression analyses were performed to test the association between the addition of IVT treatment and different functional and safety outcomes. Results After propensity score matching, 670 patients (median age, 75 years [IQR, 64-82 years]; 356 female) were included in the analysis; 335 underwent MT alone and 335 underwent MT with IVT. Median onset to puncture (350 vs 210 minutes, P < .001) and onset to recanalization (397 vs 273 minutes, P < .001) times were higher in the MT group than the MT with IVT group, respectively. In the univariable regression analysis, the addition of IVT was associated with higher odds of a modified Rankin Scale (mRS) score 0-2 (odds ratio [OR], 1.44; 95% CI: 1.06, 1.96; P = .019); however, this association was not observed in the multivariable analysis (OR, 1.37; 95% CI: 0.99, 1.89; P = .054). In the multivariable analysis, the addition of IVT also showed no evidence of an association with the odds of first-pass effect (OR, 1.27; 95% CI: 0.9, 1.79; P = .17), Thrombolysis in Cerebral Infarction grades 2b-3 (OR, 1.64; 95% CI: 0.99, 2.73; P = .055), mRS scores 0-1 (OR, 1.27; 95% CI: 0.91, 1.76; P = .16), mortality (OR, 0.78; 95% CI: 0.49, 1.24; P = .29), or intracranial hemorrhage (OR, 1.25; 95% CI: 0.88, 1.76; P = .21). Conclusion Adjunctive IVT may not provide benefit to MT in patients with AIS caused by distal and medium vessel occlusion. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Wojak in this issue.

Thrombolysis with recombinant tissue plasminogen activator in acute ischemic stroke aims to restore compromised blood flow and prevent further neuronal damage. Despite the proven clinical efficacy of this treatment, little is known about the short-term effects of systemic thrombolysis on structural brain connectivity. In this secondary analysis of the WAKE-UP trial, we used MRI-derived measures of infarct size and estimated structural network disruption to establish that thrombolysis is associated not only with less infarct growth, but also with reduced loss of large-scale connectivity between grey-matter areas after stroke. In a causal mediation analysis, infarct growth mediated a non-significant 8.3% (CI 95% [-8.0, 32.6]%) of the clinical effect of thrombolysis on functional outcome. The proportion mediated jointly through infarct growth and change of structural connectivity, especially in the border zone around the infarct core, however, was as high as 33.4% (CI 95% [8.8, 77.4]%). Preservation of structural connectivity is thus an important determinant of treatment success and favourable functional outcome in addition to lesion volume. It might, in the future, serve as an imaging endpoint in clinical trials or as a target for therapeutic interventions.

A recent randomized controlled trial DIRECT-MT (Direct Intra-Arterial Thrombectomy to Revascularize AIS Patients With Large Vessel Occlusion Efficiently in Chinese Tertiary Hospitals) compared the safety and efficacy of mechanical thrombectomy (MT) versus combined intravenous thrombolysis (IVT) and MT for acute large vessel occlusion. The current study utilized a prospective, nationwide registry to validate the results of the DIRECT-MT trial in a real-world practice setting. Subjects were selected from a prospective cohort of acute large vessel occlusion patients undergoing endovascular treatment at 111 hospitals from 26 provinces in China (ANGEL-ACT registry [Endovascular Treatment Key Technique and Emergency Work Flow Improvement of Acute Ischemic Stroke]) between November 2017 and March 2019. All patients eligible for IVT and receiving MT were reviewed and then grouped according to whether prior IVT or not (MT and combined IVT+MT). After a 1:1 propensity score matching, the outcome measures including the 90-day modified Rankin Scale, successful recanalization, door-to-puncture time, symptomatic intracranial hemorrhage, and intraprocedural embolization were compared. A total of 1026 patients, 600 in the MT group and 426 in the combined group, were included. Among 788 patients identified after matching, there were no significant differences in the 90-day modified Rankin Scale (median, 3 versus 3 points; P=0.82) and successful recanalization (86.6% versus 89.3%; P=0.23) between the two groups; however, patients of the MT group had a shorter door-to-puncture time (median, 112 versus 136 minutes; β=−45.02 [95% CI, −68.31 to −21.74]), lower rates of symptomatic intracranial hemorrhage (5.5% versus 10.1%; odds ratio, 0.52 [95% CI, 0.30–0.91]), and embolization (4.6% versus 8.1%; odds ratio, 0.54 [95% CI, 0.30–0.98]) than those of the combined group. This matched-control study largely confirmed the findings of the DIRECT-MT trial in a real-world practice setting, suggesting that MT may carry similar effectiveness to combined IVT+MT for acute large vessel occlusion patients, despite MT alone seems to be associated with a shorter in-hospital delay until procedure, lower risks of symptomatic intracranial hemorrhage, and embolization. URL: https://www.clinicaltrials.gov; Unique identifier: NCT03370939

Importance: Clinical evidence of the potential treatment benefit of mechanical thrombectomy for posterior circulation distal, medium vessel occlusion (DMVO) is sparse., Objective: To investigate the frequency as well as the clinical and safety outcomes of mechanical thrombectomy for isolated posterior circulation DMVO stroke and to compare them with the outcomes of standard medical treatment with or without intravenous thrombolysis (IVT) in daily clinical practice., Design, Setting, and Participants: This multicenter case-control study analyzed patients who were treated for primary distal occlusion of the posterior cerebral artery (PCA) of the P2 or P3 segment. These patients received mechanical thrombectomy or standard medical treatment (with or without IVT) at 1 of 23 comprehensive stroke centers in Europe, the United States, and Asia between January 1, 2010, and June 30, 2020. All patients who met the inclusion criteria were matched using 1:1 propensity score matching., Interventions: Mechanical thrombectomy or standard medical treatment with or without IVT., Main Outcomes and Measures: Clinical end point was the improvement of National Institutes of Health Stroke Scale (NIHSS) scores at discharge from baseline. Safety end point was the occurrence of symptomatic intracranial hemorrhage and hemorrhagic complications were classified based on the Second European-Australasian Acute Stroke Study (ECASSII). Functional outcome was evaluated with the modified Rankin Scale (mRS) score at 90-day follow-up., Results: Of 243 patients from all participating centers who met the inclusion criteria, 184 patients were matched. Among these patients, the median (interquartile range [IQR]) age was 74 (62-81) years and 95 (51.6%) were female individuals. Posterior circulation DMVOs were located in the P2 segment of the PCA in 149 patients (81.0%) and in the P3 segment in 35 patients (19.0%). At discharge, the mean NIHSS score decrease was -2.4 points (95% CI, -3.2 to -1.6) in the standard medical treatment cohort and -3.9 points (95% CI, -5.4 to -2.5) in the mechanical thrombectomy cohort, with a mean difference of -1.5 points (95% CI, 3.2 to -0.8; P = .06). Significant treatment effects of mechanical thrombectomy were observed in the subgroup of patients who had higher NIHSS scores on admission of 10 points or higher (mean difference, -5.6; 95% CI, -10.9 to -0.2; P = .04) and in the subgroup of patients without IVT (mean difference, -3.0; 95% CI, -5.0 to -0.9; P = .005). Symptomatic intracranial hemorrhage occurred in 4 of 92 patients (4.3%) in each treatment cohort., Conclusions and Relevance: This study suggested that, although rarely performed at comprehensive stroke centers, mechanical thrombectomy for posterior circulation DMVO is a safe, and technically feasible treatment option for occlusions of the P2 or P3 segment of the PCA compared with standard medical treatment with or without IVT.

Purpose: In acute ischemic stroke with unknown time of onset, magnetic resonance (MR)-based diffusion-weighted imaging (DWI) and fluid-attenuated inversion recovery (FLAIR) estimates lesion age to guide intravenous thrombolysis. Computed tomography (CT)-based quantitative net water uptake (NWU) may be a potential alternative. The purpose of this study was to directly compare CT-based NWU to magnetic resonance imaging (MRI) at identifying patients with lesion age < 4.5 hours from symptom onset., Methods: Fifty patients with acute anterior circulation stroke were analyzed with both imaging modalities at admission between 0.5 and 8.0 hours after known symptom onset. DWI-FLAIR lesion mismatch was rated and NWU was measured in admission CT. An established NWU threshold (11.5%) was used to classify patients within and beyond 4.5 hours. Multiparametric MRI signal was compared with NWU using logistic regression analyses. The empirical distribution of NWU was analyzed in a consecutive cohort of patients with wake-up stroke., Results: The median time between CT and MRI was 35 minutes (interquartile range [IQR] = 24-50). The accuracy of DWI-FLAIR mismatch was 68.8% (95% confidence interval [CI] = 53.7-81.3%) with a sensitivity of 58% and specificity of 82%. The accuracy of NWU threshold was 86.0% (95% CI = 73.3-94.2%) with a sensitivity of 91% and specificity of 78%. The area under the curve (AUC) of multiparametric MRI signal to classify lesion age <4.5 hours was 0.86 (95% CI = 0.64-0.97), and the AUC of quantitative NWU was 0.91 (95% CI = 0.78-0.98). Among 87 patients with wake-up stroke, 46 patients (53%) showed low NWU (< 11.5%)., Conclusion: The predictive power of CT-based lesion water imaging to identify patients within the time window of thrombolysis was comparable to multiparametric DWI-FLAIR MRI. A significant proportion of patients with wake-up stroke exhibit low NWU and may therefore be potentially suitable for thrombolysis. ANN NEUROL 2020;88:1144-1152., (© 2020 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

In patients undergoing mechanical thrombectomy, achieving complete (Thrombolysis in Cerebral Infarction 3) rather than incomplete successful reperfusion (Thrombolysis in Cerebral Infarction 2b) is associated with better functional outcome. Despite technical improvements, incomplete reperfusion remains the final angiographic result in 40% of patients according to recent trials. As most incomplete reperfusions are caused by distal vessel occlusions, they are potentially amenable to rescue strategies. While observational data suggest a net benefit of up to 20% in functional independence of incomplete versus complete reperfusions, the net benefit of secondary improvement from Thrombolysis in Cerebral Infarction 2b to 3 reperfusion might differ due to lengthier procedures and delayed reperfusion. Current strategies to tackle distal vessel occlusions consist of distal (microcatheter) aspiration, small adjustable stent retrievers, and administration of intra-arterial thrombolytics. While there are promising reports evaluating those techniques, all available studies show relevant limitations in terms of selection bias, single-center design, or nonconsecutive patient inclusion. Besides an assessment of risks associated with rescue maneuvers, we advocate that the decision-making process should also include a consideration of potential outcomes if complete reperfusion would successfully be achieved. These include (1) a futile angiographic improvement (hypoperfused territory is already infarcted), (2) an unnecessary angiographic improvement (the patient would not have developed infarction if no rescue maneuver was performed), and (3) a successful rescue maneuver with clinical benefit. Currently there is paucity of data on how these scenarios can be predicted and the decision whether to treat or to stop in a patient with incomplete reperfusion involves many unknowns. To advance the status quo, we outline current knowledge gaps and avenues of potential research regarding this clinically important question.

Purpose: Lacunar infarcts are thought to result from occlusion of small penetrating arteries due to microatheroma and lipohyalinosis, pathognomonic for cerebral small vessel disease (CSVD). Concurrent embolic ischemic lesions indicate a different stroke mechanism. The purpose of this study was to examine the clinical characteristics and outcome of patients with lacunar infarcts and concurrent embolic infarcts on diffusion-weighted imaging (DWI)., Methods: All patients screened for the WAKE-UP trial (ClinicalTrials.gov number, NCT01525290) were reviewed for acute lacunar infarcts and concurrent embolic lesions on baseline DWI. Clinical characteristics and outcome were compared between lacunar infarct patients with and without concurrent embolic lesions., Results: Of 244 patients with an acute lacunar infarct, 20 (8.2%) had concurrent acute embolic infarcts. Compared to patients with a lacunar infarct only, patients with concurrent embolic infarcts were older (mean age 69 years vs. 63 years; p = 0.031), more severely affected (median National Institutes of Health Stroke Scale [NIHSS] score 5 vs. 4; p = 0.046), and-among those randomized-had worse functional outcome at 90 days (median modified Rankin Scale [mRS] 3 vs. 1; p = 0.011)., Conclusion: Approximately 8% of lacunar infarct patients show concurrent embolic lesions suggesting a stroke etiology other than CSVD. These patients are more severely affected and have a worse functional outcome illustrating the need for a thorough diagnostic work-up of possible embolic sources even in patients with an imaging-defined diagnosis of lacunar infarcts.

Background and Purpose- Relative signal intensity of acute ischemic stroke lesions in fluid-attenuated inversion recovery (fluid-attenuated inversion recovery relative signal intensity [FLAIR-rSI]) magnetic resonance imaging is associated with time elapsed since stroke onset with higher intensities signifying longer time intervals. In the randomized controlled WAKE-UP trial (Efficacy and Safety of MRI-Based Thrombolysis in Wake-Up Stroke Trial), intravenous alteplase was effective in patients with unknown onset stroke selected by visual assessment of diffusion weighted imaging fluid-attenuated inversion recovery mismatch, that is, in those with no marked fluid-attenuated inversion recovery hyperintensity in the region of the acute diffusion weighted imaging lesion. In this post hoc analysis, we investigated whether quantitatively measured FLAIR-rSI modifies treatment effect of intravenous alteplase. Methods- FLAIR-rSI of stroke lesions was measured relative to signal intensity in a mirrored region in the contralesional hemisphere. The relationship between FLAIR-rSI and treatment effect on functional outcome assessed by the modified Rankin Scale (mRS) after 90 days was analyzed by binary logistic regression using different end points, that is, favorable outcome defined as mRS score of 0 to 1, independent outcome defined as mRS score of 0 to 2, ordinal analysis of mRS scores (shift analysis). All models were adjusted for National Institutes of Health Stroke Scale at symptom onset and stroke lesion volume. Results- FLAIR-rSI was successfully quantified in stroke lesions in 433 patients (86% of 503 patients included in WAKE-UP). Mean FLAIR-rSI was 1.06 (SD, 0.09). Interaction of FLAIR-rSI and treatment effect was not significant for mRS score of 0 to 1 ( P =0.169) and shift analysis ( P =0.086) but reached significance for mRS score of 0 to 2 ( P =0.004). We observed a smooth continuing trend of decreasing treatment effects in relation to clinical end points with increasing FLAIR-rSI. Conclusions- In patients in whom no marked parenchymal fluid-attenuated inversion recovery hyperintensity was detected by visual judgement in the WAKE-UP trial, higher FLAIR-rSI of diffusion weighted imaging lesions was associated with decreased treatment effects of intravenous thrombolysis. This parallels the known association of treatment effect and elapsing time of stroke onset.

Background and Purpose- Health systems are faced with the challenge of ensuring fast access to appropriate therapy for patients with acute stroke. The paradigms primarily discussed are mothership and drip and ship. Less attention has been focused on the drip-and-drive (DD) paradigm. Our aim was to analyze whether and under what conditions DD would predict the greatest probability of good outcome for patients with suspected ischemic stroke in Northwestern Germany. Methods- Conditional probability models based on the decay curves for endovascular therapy and intravenous thrombolysis were created to determine the best transport paradigm, and results were displayed using map visualizations. Our study area consisted of the federal states of Lower Saxony, Hamburg, and Schleswig-Holstein in Northwestern Germany covering an area of 64 065 km 2 with a population of 12 703 561 in 2017 (198 persons per km 2 ). In several scenarios, the catchment area, that is, the region that would result in the greatest probability of good outcomes, was calculated for each of the mothership, drip-and-ship, and the DD paradigms. Several different treatment time parameters were varied including onset-to-first-medical-response time, ambulance-on-scene time, door-to-needle time at primary stroke center, needle-to-door time, door-to-needle time at comprehensive stroke center, door-to-groin-puncture time, needle-to-interventionalist-leave time, and interventionalist-arrival-to-groin-puncture time. Results- The mothership paradigm had the largest catchment area; however, the DD catchment area was larger than the drip-and-ship catchment area so long as the needle-to-interventionalist-leave time and the interventionalist-arrival-to-groin-puncture time remain <40 minutes each. A slowed workflow in the DD paradigm resulted in a decrease of the DD catchment area to 1221 km 2 (2%). Conclusions- Our study suggests the largest catchment area for the mothership paradigm and a larger catchment area of DD paradigm compared with the drip-and-ship paradigm in Northwestern Germany in most scenarios. The existence of different paradigms allows the spread of capacities, shares the cost and hospital income, and gives primary stroke centers the possibility to provide endovascular therapy services 24/7.

Background: Under current guidelines, intravenous thrombolysis is used to treat acute stroke only if it can be ascertained that the time since the onset of symptoms was less than 4.5 hours. We sought to determine whether patients with stroke with an unknown time of onset and features suggesting recent cerebral infarction on magnetic resonance imaging (MRI) would benefit from thrombolysis with the use of intravenous alteplase., Methods: In a multicenter trial, we randomly assigned patients who had an unknown time of onset of stroke to receive either intravenous alteplase or placebo. All the patients had an ischemic lesion that was visible on MRI diffusion-weighted imaging but no parenchymal hyperintensity on fluid-attenuated inversion recovery (FLAIR), which indicated that the stroke had occurred approximately within the previous 4.5 hours. We excluded patients for whom thrombectomy was planned. The primary end point was favorable outcome, as defined by a score of 0 or 1 on the modified Rankin scale of neurologic disability (which ranges from 0 [no symptoms] to 6 [death]) at 90 days. A secondary outcome was the likelihood that alteplase would lead to lower ordinal scores on the modified Rankin scale than would placebo (shift analysis)., Results: The trial was stopped early owing to cessation of funding after the enrollment of 503 of an anticipated 800 patients. Of these patients, 254 were randomly assigned to receive alteplase and 249 to receive placebo. A favorable outcome at 90 days was reported in 131 of 246 patients (53.3%) in the alteplase group and in 102 of 244 patients (41.8%) in the placebo group (adjusted odds ratio, 1.61; 95% confidence interval [CI], 1.09 to 2.36; P=0.02). The median score on the modified Rankin scale at 90 days was 1 in the alteplase group and 2 in the placebo group (adjusted common odds ratio, 1.62; 95% CI, 1.17 to 2.23; P=0.003). There were 10 deaths (4.1%) in the alteplase group and 3 (1.2%) in the placebo group (odds ratio, 3.38; 95% CI, 0.92 to 12.52; P=0.07). The rate of symptomatic intracranial hemorrhage was 2.0% in the alteplase group and 0.4% in the placebo group (odds ratio, 4.95; 95% CI, 0.57 to 42.87; P=0.15)., Conclusions: In patients with acute stroke with an unknown time of onset, intravenous alteplase guided by a mismatch between diffusion-weighted imaging and FLAIR in the region of ischemia resulted in a significantly better functional outcome and numerically more intracranial hemorrhages than placebo at 90 days. (Funded by the European Union Seventh Framework Program; WAKE-UP ClinicalTrials.gov number, NCT01525290; and EudraCT number, 2011-005906-32 .).

Background Diffusion-weighted imaging (DWI) and fluid-attenuated inversion recovery (FLAIR) mismatch was suggested to identify stroke patients with unknown time of symptom onset likely to be within the time window for thrombolysis. Aims We aimed to study clinical characteristics associated with DWI-FLAIR mismatch in patients with unknown onset stroke. Methods We analyzed baseline MRI and clinical data from patients with acute ischemic stroke proven by DWI from WAKE-UP, an investigator-initiated, randomized, placebo-controlled trial of MRI-based thrombolysis in stroke patients with unknown time of symptom onset. Clinical characteristics were compared between patients with and without DWI-FLAIR mismatch. Results Of 699 patients included, 418 (59.8%) presented with DWI-FLAIR mismatch. A shorter delay between last seen well and symptom recognition (p = 0.0063), a shorter delay between symptom recognition and arrival at hospital (p = 0.0025), and history of atrial fibrillation (p = 0.19) were predictors of DWI-FLAIR mismatch in multivariate analysis. All other characteristics were comparable between groups. Conclusions There are only minor differences in measured clinical characteristics between unknown symptom onset stroke patients with and without DWI-FLAIR mismatch. DWI-FLAIR mismatch as an indicator of stroke onset within 4.5 h shows no relevant association with commonly collected clinical characteristics of stroke patients. Clinical Trial Registration URL: http://www.clinicaltrials.gov . Unique identifier: NCT01525290; URL: https://www.clinicaltrialsregister.eu . Unique identifier: 2011-005906-32.

Objective: To determine whether the manner of consent, i.e., informed consent by patients themselves or informed consent by proxy, affects clinical characteristics of samples of acute stroke patients enrolled in clinical trials., Methods: We analyzed the manner of obtaining informed consent in the first 1,005 patients from WAKE-UP, an investigator-initiated, randomized, placebo-controlled trial of MRI-based thrombolysis in stroke patients with unknown time of symptom onset running in 6 European countries. Patients providing informed consent by themselves were compared with patients enrolled by proxy consent. Baseline clinical measures were compared between groups., Results: In 359 (35.7%) patients, informed consent was by proxy. Patients with proxy consent were older (median 71 vs 66 years, p < 0.0001) and had a higher frequency of arterial hypertension (58.2% vs 43.4%, p < 0.0001). They showed higher scores on the NIH Stroke Scale (median 11 vs 5, p < 0.0001) and more frequently aphasia (73.7% vs 20.0%, p < 0.0001). The rate of proxy consent varied among countries ( p < 0.0001), ranging from 77.1% in Spain to 1.2% in Denmark., Conclusions: Patients recruited by proxy consent were older, had more severe strokes, and had higher prevalence of aphasia than those with capacity to give personal consent. Variations in the manner of consent across countries may influence trial results., Clinicaltrialsgov and Clinicaltrialsregistereu Identifiers: NCT01525290 (clinicaltrials.gov); 2011-005906-32 (clinicaltrialsregister.eu)., (Copyright © 2017 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

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.

Aim and hypothesis Using a new study design, we investigate whether next-generation mechanical thrombectomy devices improve clinical outcomes in ischemic stroke patients. We hypothesize that this new methodology is superior to intravenous tissue plasminogen activator therapy alone. Methods and design ERic Acute StrokE Recanalization is an investigator-initiated prospective single-arm, multicenter, controlled, open label study to compare the safety and effectiveness of a new recanalization device and distal access catheter in acute ischemic stroke patients with symptoms attributable to acute ischemic stroke and vessel occlusion of the internal cerebral artery or middle cerebral artery. Study outcome The primary effectiveness endpoint is the volume of saved tissue. Volume of saved tissue is defined as difference of the actual infarct volume and the brain volume that is predicted to develop infarction by using an optimized high-level machine learning model that is trained on data from a historical cohort treated with IV tissue plasminogen activator. Sample size estimates Based on own preliminary data, 45 patients fulfilling all inclusion criteria need to complete the study to show an efficacy >38% with a power of 80% and a one-sided alpha error risk of 0.05 (based on a one sample t-test). Discussion ERic Acute StrokE Recanalization is the first prospective study in interventional stroke therapy to use predictive analytics as primary and secondary endpoint. Such trial design cannot replace randomized controlled trials with clinical endpoints. However, ERic Acute StrokE Recanalization could serve as an exemplary trial design for evaluating nonpivotal neurovascular interventions.

Purpose: Susceptibility vessel sign (SVS) may likely influence recanalization after thrombolysis. We assessed, through the European sequential MRI database "I-KNOW," the relationship between the presence of SVS on T2-weighted gradient echo imaging, its angiographic counterpart on magnetic resonance angiography and its subsequent impact on recanalization after thrombolysis., Materials and Methods: Initial clinical and MRI characteristics and early follow up were analyzed in acute ischemic stroke patients treated with rt-Pa within 4.5 hours. Patients underwent multimodal MRI at admission. Sequential imaging performed 3 hours, 2 days and 1 month later allowed the analysis of SVS changes and recanalization., Results: Fifty patients were included in the study. SVS was observed in 54% of cases at admission. SVS was still present in 46% patients at 3 hours, 16% at 2 days, and 0% at 1 month. It was an independent predictor of no recanalization after thrombolysis (P = .04). After 3 hours, SVS disappeared in only 4 cases, and was not linked with recanalization on MRA. Conversely, when SVS persisted, a partial or complete recanalization was observed in 9 and 6 cases, respectively., Conclusions: SVS is a predictor of lower recanalization rate. Its disappearance is not necessarily correlated with recanalization., (Copyright © 2015 by the American Society of Neuroimaging.)

Background: To assess the differences across continental regions in terms of stroke imaging obtained for making acute revascularization therapy decisions, and to identify obstacles to participating in randomized trials involving multimodal imaging., Methods: STroke Imaging Repository (STIR) and Virtual International Stroke Trials Archive (VISTA)-Imaging circulated an online survey through its website, through the websites of national professional societies from multiple countries as well as through email distribution lists from STIR and the above mentioned societies., Results: We received responses from 223 centers (2 from Africa, 38 from Asia, 10 from Australia, 101 from Europe, 4 from Middle East, 55 from North America, 13 from South America). In combination, the sites surveyed administered acute revascularization therapy to a total of 25,326 acute stroke patients in 2012. Seventy-three percent of these patients received intravenous (i.v.) tissue plasminogen activator (tPA), and 27%, endovascular therapy. Vascular imaging was routinely obtained in 79% (152/193) of sites for endovascular therapy decisions, and also as part of standard IV tPA treatment decisions at 46% (92/198) of sites. Modality, availability and use of acute vascular and perfusion imaging before revascularization varied substantially between geographical areas. The main obstacles to participate in randomized trials involving multimodal imaging included: mainly insufficient research support and staff (50%, 79/158) and infrequent use of multimodal imaging (27%, 43/158) ., Conclusion: There were significant variations among sites and geographical areas in terms of stroke imaging work-up used tomake decisions both for intravenous and endovascular revascularization. Clinical trials using advanced imaging as a selection tool for acute revascularization therapy should address the need for additional resources and technical support, and take into consideration the lack of routine use of such techniques in trial planning., Competing Interests: Conflicts of Interest: None declared., (© 2015 World Stroke Organization.)

Background and Purpose: Patients with right hemispheric stroke (RHS) have been reported to have fewer good outcomes after thrombolysis. We aimed at evaluating outcome after stroke thrombolysis with regards to the affected hemisphere controlling for stroke lesion volume as a potential confounder., Methods: We retrospectively analyzed data from a prospective study of patients with acute stroke treated with intravenous tissue-type plasminogen activator, based on magnetic resonance imaging criteria within 6 hours of symptom onset. Neurological deficit was assessed by the National Institutes of Health Stroke Scale. Lesion volume on acute perfusion imaging, diffusion-weighted imaging (DWI) and perfusion imaging/DWI mismatch were measured. Clinical outcome was assessed after 90 days using the modified Rankin Scale, and relation to affected hemisphere was studied by multivariate analysis., Results: Of 173 patients, 55 (32%) presented with RHS, whereas 118 (68%) had left HS. Baseline National Institutes of Health Stroke Scale was lower in RHS (11.7 versus 13.6; P=0.031). There were no differences in DWI lesion volume (11.0 versus 17.8 mL; P=0.519), perfusion imaging lesion volume (98.9 versus 118.3 mL; P=0.395), perfusion imaging/DWI mismatch (60 versus 85.05 mL; P=0.283). Clinical outcome was also comparable for both groups (modified Rankin Scale, 0-1; P=0.327). In multivariate analysis, DWI lesion volume (P<0.001) and age were associated with modified Rankin Scale at day 90, whereas affected hemisphere was not., Conclusions: We did not find differences between RHS and left HS with regards to stroke lesions volumes or outcome after thrombolysis. Previously reported hemisphere-related differences in stroke outcome may partly results from imbalances in stroke lesion volume between RHS and left HS., (© 2015 American Heart Association, Inc.)

Rationale: In about 20% of acute ischemic stroke patients stroke occurs during sleep. These patients are generally excluded from intravenous thrombolysis. MRI can identify patients within the time-window for thrombolysis (≤4·5 h from symptom onset) by a mismatch between the acute ischemic lesion visible on diffusion weighted imaging (DWI) but not visible on fluid-attenuated inversion recovery (FLAIR) imaging., Aims and Hypothesis: The study aims to test the efficacy and safety of MRI-guided thrombolysis with tissue plasminogen activator (rtPA) in ischemic stroke patients with unknown time of symptom onset, e.g., waking up with stroke symptoms. We hypothesize that stroke patients with unknown time of symptom onset with a DWI-FLAIR-mismatch pattern on MRI will have improved outcome when treated with rtPA compared to placebo., Design: WAKE-UP is an investigator initiated, European, multicentre, randomized, double-blind, placebo-controlled clinical trial. Patients with unknown time of symptom onset who fulfil clinical inclusion criteria (disabling neurological deficit, no contraindications against thrombolysis) will be studied by MRI. Patients with MRI findings of a DWI-FLAIR-mismatch will be randomised to either treatment with rtPA or placebo., Study Outcome: The primary efficacy endpoint will be favourable outcome defined by modified Rankin Scale 0-1 at day 90. The primary safety outcome measures will be mortality and death or dependency defined by modified Rankin Scale 4-6 at 90 days., Discussion: If positive, WAKE-UP is expected to change clinical practice making effective and safe treatment available for a large group of acute stroke patients currently excluded from specific acute therapy., (© 2013 The Authors. International Journal of Stroke © 2013 World Stroke Organization.)

Background and Purpose: WAKE-UP is a randomized, placebo-controlled MRI-based trial of thrombolysis in wake-up stroke using the mismatch between a lesion's visibility in diffusion-weighted imaging and fluid-attenuated inversion recovery (FLAIR) sequences as its main imaging inclusion criterion. Visual judgment of lesion conspicuity on FLAIR is however methodically limited by moderate inter-rater agreement. We therefore sought to improve rating homogeneity by incorporating quantitative signal intensity measurements., Methods: One hundred forty-three data sets of patients with acute ischemic stroke were visually rated by 8 raters with respect to WAKE-UP study inclusion and exclusion criteria, and inter-rater agreement was calculated. A subanalysis was performed on 45 cases to determine a threshold value of relative signal intensity (rSI) between the ischemic lesion and contralateral healthy tissue which best corresponded to a visually established verdict of FLAIR positivity. The usefulness of this threshold in improving inter-rater agreement was evaluated in an additional sample of 50 patients., Results: Inter-rater agreement for inclusion into the WAKE-UP trial was 73% with a free-marginal κ of 0.46. A threshold of rSI which best correlated with the visual rating of lesions as FLAIR positive was 1.20. The addition of rSI measurements to visual evaluation did not change the inter-rater agreement., Conclusions: Introducing a semiquantitative measure for FLAIR rSI did not improve the agreement between individual raters. However, enhancing visual assessment with rSI measurements can provide reassurance to local investigators in cases of uncertainty.

Low recanalization rates and poor clinical outcome have been reported after intravenous thrombolysis (IV-tPA) in carotid-T occlusion (CTO). We studied clinical outcome and imaging findings of MRI-based intravenous thrombolysis in CTO. Data of patients with acute ischemic stroke and CTO treated with IV-tPA within 6 h of symptom onset based on MRI criteria were retrospectively analyzed. Vessel occlusion was defined based on MR angiography. Acute diffusion and perfusion lesion volumes and final infarct volumes after 3-7 days were delineated. The National Institutes of Health Stroke Scale (NIHSS) was used to assess the neurological deficit on admission. Recanalization was evaluated after 24 h. Clinical outcome was assessed using the modified Rankin Scale (mRS) after 90 days. Clinical and imaging data were compared to patients with middle cerebral artery main stem occlusion (MCAO). A total of 20 patients with CTO and 51 patients with MCAO were studied. Onset to treatment time, NIHSS on admission, initial diffusion and perfusion lesion volumes, and recanalization rates after 24 h were similar between groups. Final infarct volume was larger for CTO (82 vs. 30 ml, p = 0.006). Although overall outcome was not significantly different between groups (p = 0.251), independent outcome (mRS 0-2) tended to be less frequent in CTO (17 vs. 39 %), while poor outcome (mRS 4-6) appeared more common (72 vs. 43 %). The proportion of patients with good clinical outcome after intravenous thrombolysis in CTO is small. Moreover, final infarct volume is larger and clinical outcome appears to be worse compared to MCAO.

Background and Purpose: Stroke magnetic resonance imaging with perfusion and diffusion weighting has shown its potential to select patients likely to benefit from intravenous thrombolysis with tissue-type plasminogen activator (IV-tPA). We aimed to determine the predictors of favorable outcome in magnetic resonance imaging-selected, acute stroke patients treated with IV-tPA., Methods: We analyzed the data of acute ischemic stroke patients from a prospective, multicenter, observational study of magnetic resonance imaging-based IV-tPA treatment initiated ≤6 hours from symptom onset. Neurologic deficit on admission was assessed by the National Institutes of Health Stroke Scale. Clinical outcome was assessed after 90 days according to the modified Rankin Scale. Favorable outcome was defined as a modified Rankin Scale score of 0 to 1. Patients were compared regarding baseline parameters. Multivariate regression analysis was used to identify predictors of favorable outcome., Results: Of 174 patients, 83 (48%) reached a favorable outcome. They were younger (median age, 62 versus 67 years; P=0.001), had a lower National Institutes of Health Stroke Scale score on admission (median, 11 versus 15; P<0.001), and had smaller diffusion-weighted imaging lesions (median, 12.9 versus 20 mL; P=0.001). Perfusion-weighted imaging lesion volumes and onset-to-treatment time were comparable between the groups. Age (P=0.017), National Institutes of Health Stroke Scale score on admission (P<0.001), and diffusion-weighted imaging lesion volume (P=0.047) were identified as independent predictors of favorable outcome., Conclusions: A lower age, lower National Institutes of Health Stroke Scale score on admission, and smaller pretreatment diffusion-weighted imaging lesion volume were found to be associated with a favorable outcome after treatment with IV-tPA. Pretreatment perfusion lesion volume and onset-to-treatment time were not associated with outcome when patients were selected for IV-tPA by magnetic resonance imaging within 6 hours of symptom onset.

Introduction: Acute stroke multimodal CT imaging (MMCT: non-enhanced CT, CT angiography, and CT perfusion (CTP)) may show normal results despite persistent clinical stroke. We prospectively evaluated the sensitivity/specificity of MMCT infarct detection and the clinical outcome in patients with normal MMCT findings., Methods: From April 2007 to April 2008, all patients with acute hemispheric stroke within 6 h of symptom onset who underwent complete MMCT and MRI follow-up imaging were included. MMCT analysis included occlusion type, early infarct hypodensities (EIH), mean transit time (MTT), and cerebral blood volume (CBV) maps according to Alberta Stroke Program Early CT Score (ASPECTS). Clinical assessment included symptom onset to CT scan (≤3 h/>3 h), the National Institute of Health Stroke Scale score (admission/discharge), and the modified Rankin scale (mRS) 90 days after stroke onset., Results: One hundred seven were included (mean age, 68.4 years; ≤3 h, n = 84; >3 h, n = 23; intravenous thrombolysis (IVT), n = 51; ≤3 h, n = 40; >3 h, n = 11). In patients with normal MMCT on admission (n = 54), follow-up MRT detected brain infarctions in 23 patients (lacunar strokes, n = 16; infratentorial strokes, n = 4; territorial infarction, n = 3). Sensitivity/specificity/positive predictive value/negative predictive value of any infarct detection was 69.5%/99.8%/99.9%/57.2% and of a any territorial infarct detection was 93.9%/99.9%/99.9%/93.6%, respectively. In univariate regression analysis (time to CT scan, ≤3 h/>3 h; IVT: yes/no; ASPECTS EIH/CBV/MTT, 10/<10), only the evidence of normal CTP (ASPECTS MTT = 10) had a statistically significant impact (p = 0.02) on a good outcome (mRS 0.1)., Conclusion: MMCT sensitivity in acute lacunar or infratentorial stroke was poor. But, we found a high specifity and a fairly good sensitivity in territorial infarct detection. In acute stroke patients with normal MMCT findings on admission, a good clinical prognosis can be expected.

Background: Treatment with intravenous tissue plasminogen activator (IV-tPA) is usually not recommended in patients with minor stroke. Clinical and imaging outcome were studied after IV-tPA treatment based on MRI criteria in patients with minor stroke., Methods: Data were analysed retrospectively of acute ischaemic stroke patients with minor stroke (National Institutes of Health Stroke Scale (NIHSS) score <4). All patients were studied by stroke MRI including perfusion and diffusion weighted imaging (PWI and DWI) and treated with IV-tPA for < or =6 h. Final infarct volume was delineated on follow-up MRI. Clinical outcome was assessed after 90 days using the modified Rankin Scale (mRS)., Results: Six patients with a median NIHSS on admission of 2 (range 0-3) were treated with IV-tPA based on MRI criteria. In all patients, occlusion of the middle cerebral artery (MCA) was detected (MCA branch n = 2, MCA trunk n = 3, MCA trifurcation n = 1), and the PWI lesion (41, 25-60 ml) exceeded the DWI lesion (4, 1-23 ml). Final infarct volume was 9 (2-29) ml. Favourable outcome (mRS 0-1) was seen in 5/6 patients and independent outcome (mRS = 2) in one patient. No intracerebral haemorrhages occurred., Conclusion: Treatment with IV-tPA based on MRI criteria was safe and appeared to be effective in this small series of patients with minor stroke.

Introduction: The objective of our study was to determine whether the combination of hypointense spots ("cerebral microbleeds," CMBs) with a leukoaraiosis is associated with the risk of parenchymal hematoma (PH) after thrombolytic therapy., Patients and Methods: We analyzed magnetic resonance imaging (MRI) scans acquired within 6 hours after symptom onset from 100 ischemic stroke patients. Multiparametric MRI including a T2*-weighted (T2*w) MRI and fluid attenuated inversion recovery (FLAIR) was performed before thrombolysis in all patients. Initial T2*w imaging was rated by two independent observers for the presence of CMBs smaller than 5 mm. White matter changes were evaluated using an adapted scale of Fazekas and Schmidt. PH was defined in follow-up imaging., Findings: A PH was observed in seven per 100 patients. CMBs were detected by observer 1 in 22 and observer 2 in 20 patients. We found a very low sensitivity (0.14) for prediction of PH by the presence of CMBs. We found a concordant increase in the rate of PH when the periventricular hyperintensity in FLAIR was larger than a thin lining. Sensitivity was good-to-perfect (0.86 and 1.00, observers 1 and 2) and specificity was substantial (0.65 and 0.66). Using the combination of a periventricular matter lesion (PVML)>1 and the presence of CMBs did not improve the prediction of PH., Discussion: A marked periventricular hyperintensity in FLAIR imaging seems to be associated with a substantially increased risk of PH. A combination of CMBs with leukoaraiosis scores did not appear to be beneficial for prognosis.

Background and Purpose: Pretreatment lesion size on diffusion-weighted imaging (DWI) is a risk factor for symptomatic intracerebral hemorrhage (sICH) associated with thrombolytic treatment. Here, we investigated whether the Alberta Stroke Programme Early CT Score (ASPECTS) applied to DWI images (DWI-ASPECTS) predicts sICH risk accurately., Methods: In this retrospective multicenter study, prospectively collected data of 217 patients with anterior circulation stroke treated with intravenous or intraarterial thrombolysis within 6 hours after symptom onset were analyzed. Pretreatment DWI-ASPECTS scores were assessed by 2 independent investigators. For bleeding risk analysis, DWI-ASPECTS scores were either categorized into 0 to 7 (n=105) or 8 to 10 (n=112) or in 3 groups of similar sample size (DWI-ASPECTS 0 to 5 [n=69], 6 to 7 [n=70], and 8 to 10 [n=78])., Results: DWI-ASPECTS scores correlated well with the DWI lesion volume (r=0.77, P<0.001, Spearman Rank test). Interobserver reliability for the assessment of DWI-ASPECTS was moderate (weighted kappa 0.441 [95% CI 0.373 to 0.509]). Twenty-three (10.6%) patients developed sICH. The sICH rate was significantly higher in patients with DWI-ASPECTS scores 0 to 7 (n=21, 15.1%) as compared to patients with DWI-ASPECTS scores 8 to 10 (n=2, 2.6%, P=0.004). sICH risk was 20.3%, 10%, and 2.6% in the 0 to 5, 6 to 7, and 8 to 10 DWI-ASPECTS groups, respectively. DWI-ASPECTS remained an independent prognostic factor for sICH after adjustment for clinical baseline variables (age, NIHSS, time to thrombolysis)., Conclusions: DWI-ASPECTS predicts sICH risk after thrombolysis and may be helpful to contributing to quick sICH risk assessment before thrombolytic therapy.

Acute vertebrobasilar occlusions (VBO) are dramatic clinical events with a mortality of up to 90% under standard medical treatment. If VBO is suspected a diagnosis of the vessel status has to be achieved immediately. For this purpose CT/CTA and MRI/MRA are equivalent diagnostic tools in the emergency setting. In contrast to the anterior circulation, local endovascular treatment is the established therapy for the posterior circulation as an underlying arteriosclerotic stenosis remains in 50% of the cases after intravenous fibrinolysis. Nevertheless, systemic fibrinolysis is considered the preferred option in cases where a neurointerventional center cannot be reached within a reasonable time frame and the patient can subsequently be transported for local therapy of a residual stenosis in order to prevent reocclusion ("drip and ship"). Profound clinical and pathophysiological knowledge is the absolute prerequisite for the correct application of state-of-the-art neurointerventional therapy. This review paper focuses on the clinical and pathophysiological details that are crucial for decision-making.

This article summarizes recent developments concerning MRI-based risk assessment of symptomatic intracerebral hemorrhage (sICH) associated with thrombolytic therapy for acute stroke. Special attention is paid to three imaging parameters: cerebral microangiopathy, lesion size on diffusion weighted imaging (DWI), and the role of cerebral microbleeds. Both severe cerebral microangiopathy and increasing lesion size on DWI are now established risk factors for sICH following thrombolysis, while the presence of a single or few microbleeds is not associated with a substantially elevated sICH risk.

Background: In intra-arterial (IA) thrombolysis trials, higher rates of symptomatic intracerebral haemorrhage (sICH) were found than in trials with intravenous (IV) recombinant tissue plasminogen activator (tPA); this observation could have been due to the inclusion of more severely affected patients in IA thrombolysis trials. In the present study, we investigated the rate of sICH in IA and combined IV + IA thrombolysis versus IV thrombolysis after adjusting for differences in clinical and MRI parameters., Methods: In this multicenter study, we systematically analyzed data from 645 patients with anterior-circulation strokes treated with either IV or IA thrombolysis within 6 h following symptom onset. Thrombolytic regimens included (1) IV tPA treatment (n = 536) and (2) IA treatment with either tPA or urokinase (n = 74) or (3) combined IV + IA treatment with either tPA or urokinase (n = 35)., Results: 44 (6.8%) patients developed sICH. sICH patients had significantly higher scores on the National Institutes of Health Stroke Scale (NIHSS) at admission and pretreatment DWI lesions. The sICH risk was 5.2% (n = 28) in IV thrombolysis, which is significantly lower than in IA (12.5%, n = 9) or IV + IA thrombolysis (20%, n = 7). In a binary logistic regression analysis including age, NIHSS score, time to thrombolysis, initial diffusion weighted imaging lesion size, mode of thrombolytic treatment and thrombolytic agent, the mode of thrombolytic treatment remained an independent predictor for sICH. The odds ratio for IA or IV + IA versus IV treatment was 3.466 (1.19-10.01, 95% CI, p < 0.05)., Conclusion: In this series, IA and IV + IA thrombolysis is associated with an increased sICH risk as compared to IV thrombolysis, and this risk is independent of differences in baseline parameters such as age, initial NIHSS score or pretreatment lesion size., (Copyright 2009 S. Karger AG, Basel.)

Objective: The risk for symptomatic intracerebral hemorrhage (sICH) associated with thrombolytic treatment has not been evaluated in large studies using diffusion-weighted imaging (DWI). Here, we investigated the relation between pretreatment DWI lesion size and the risk for sICH after thrombolysis., Methods: In this retrospective multicenter study, prospectively collected data from 645 patients with anterior circulation stroke treated with intravenous or intraarterial thrombolysis within 6 hours (<3 hours: n = 320) after symptom onset were pooled. Patients were categorized according to the pretreatment DWI lesion size into three prespecified groups: small (< or =10 ml; n = 218), moderate (10-100 ml; n = 371), and large (>100 ml; n = 56) DWI lesions., Results: In total, 44 (6.8%) patients experienced development of sICH. The sICH rate was significantly different between subgroups: 2.8, 7.8, and 16.1% in patients with small, moderate, and large DWI lesions, respectively (p < 0.05). This translates to a 5.8 (2.8)-fold greater sICH risk for patients with large DWI lesions as compared with patients with small (or moderate) DWI lesions. The results were similar in the large subgroup (n = 536) of patients treated with intravenous tissue plasminogen activator. DWI lesion size remained an independent risk factor when including National Institutes of Health Stroke Scale, age, time to thrombolysis, and leukoariosis in a logistic regression analysis., Interpretation: This multicenter study provides estimates of sICH risk in potential candidates for thrombolysis. The sICH risk increases gradually with increasing DWI lesion size, indicating that the potential benefit of therapy needs to be balanced carefully against the risk for sICH, especially in patients with large DWI lesions.

Background and Purpose: The use of intravenous thrombolysis is restricted to a minority of patients by the rigid 3-hour time window. This window may be extended by using modern imaging-based selection algorithms. We assessed safety and efficacy of MRI-based thrombolysis within and beyond 3 hours compared with standard CT-based thrombolysis., Methods: Five European stroke centers pooled the core data of their CT- and MRI-based prospective thrombolysis databases. Safety outcomes were predefined as symptomatic intracranial hemorrhage and mortality. Primary efficacy outcome was a favorable outcome (modified Rankin Scale 0 to 1). We performed univariate and multivariate analyses for all end points, including age, National Institutes of Health Stroke Scale, treatment group (CT <3 hours, MRI <3 hours and >3 hours), and onset to treatment time as variables., Results: A total of 1210 patients were included (CT <3 hours: N=714; MRI <3 hours: N=316; MRI >3 hours: N=180). Median age, National Institutes of Health Stroke Scale, and onset to treatment time were 69, 67, and 68.5 years (P=0.66); 12, 13, and 14 points (P=0.019); and 130, 135, and 240 minutes (P<0.001). Symptomatic intracranial hemorrhage rates were 5.3%, 2.8%, and 4.4% (P=0.213); mortality was 13.7%, 11.7%, and 13.3% (P=0.68). Favorable outcome occurred in 35.4%, 37.0%, and 40% (P=0.51). Age and National Institutes of Health Stroke Scale were independent predictors for all safety and efficacy outcomes. The overall use of MRI significantly reduced symptomatic intracranial hemorrhage (OR: 0.520, 95% CI: 0.270 to 0.999, P=0.05). Beyond 3 hours, the use of MRI significantly predicted a favorable outcome (OR: 1.467; 95% CI: 1.017 to 2.117, P=0.040). Within 3 hours and for all secondary end points, there was a trend in favor of MRI-based selection over standard <3-hour CT-based treatment., Conclusions: Despite significantly longer time windows and significantly higher baseline National Institutes of Health Stroke Scale scores, MRI-based thrombolysis is safer and potentially more efficacious than standard CT-based thrombolysis.

Background and Purpose: There has been speculation that the risk of secondary symptomatic intracranial hemorrhage (SICH) may be increased after thrombolytic therapy in ischemic stroke patients who have cerebral microbleeds (CMBs) on T2*-weighted magnetic resonance imaging. Because of this concern, some centers withhold potentially beneficial thrombolytic therapy from these patients., Methods: We analyzed magnetic resonance imaging data acquired within 6 hours after symptom onset from 570 ischemic stroke patients treated with intravenous tissue plasminogen activator in 13 centers in Europe, North America, and Asia. Baseline T2*-weighted magnetic resonance images were evaluated for the presence of CMBs. The primary end point was SICH, defined as clinical deterioration with an increase in the National Institutes of Health Stroke Scale score by >or=4 points, temporally related to a parenchymal hematoma on follow-up-imaging., Results: A total of 242 CMBs were detected in 86 of 570 patients (15.1%). The number of CMBs ranged from 1 to 77 in the individual patient, with >or=5 CMBs in 6 of 570 patients (1.1%). Proportions of patients with SICH were 5.8% (95% CI, 1.9 to 13.0) in the presence of CMBs and 2.7% (95% CI, 1.4 to 4.5) in patients without CMBs (P=0.170, Fisher's exact test), resulting in no significant absolute increase in the risk of SICH of 3.1% (95% CI, -2.0 to 8.3)., Conclusions: The data suggest that if there is any increased risk of SICH attributable to CMBs, it is likely to be small and unlikely to exceed the benefits of thrombolytic therapy. No reliable conclusion regarding risk in the rare patient with multiple CMBs can be reached.

Background and Purpose: The aim of the study was to evaluate whether leukoaraiosis (LA) is a risk factor for symptomatic intracerebral hemorrhage (sICH) in patients treated with thrombolysis for acute stroke., Methods: In this retrospective, multicenter analysis, we evaluated data from acute anterior circulation stroke patients (n=449; <6 hours after symptom onset) treated with thrombolysis. All patients had received standard magnetic resonance imaging evaluation before thrombolysis, including a high-quality T2-weighted sequence. For the analysis, LA in the deep white matter was dichotomized into absent or mild versus moderate or severe (corresponding to Fazekas scores of 0 to 1 versus 2 to 3)., Results: The rate of sICH was significantly more frequent in patients with moderate to severe LA of the deep white matter (n=12 of 114; 10.5%) than in patients without relevant LA (n=13 of 335; 3.8%), corresponding to an odds ratio of 2.9 (95% CI, 1.29 to 6.59; P=0.015). In a logistic-regression analysis (including age, National Institutes of Health Stroke Scale score at presentation, and type of thrombolytic treatment), LA remained a significant independent risk factor (odds ratio, 2.9; P=0.03)., Conclusions: LA of the deep white matter is an independent risk factor for sICH after thrombolytic treatment for acute stroke.

Background and Purpose: We compared outcome and symptomatic bleeding complications of intravenous tissue plasminogen activator (IV-tPA) within 6 hours of symptom onset in MRI-selected patients with acute middle cerebral artery infarction with the pooled data of the large stroke tPA trials., Methods: Patients were examined by perfusion-weighted and diffusion-weighted imaging < or =6 hours. Within 3 hours, patients were treated according to Second European-Australasian Acute Stroke Study (ECASS II) criteria. After 3 to 6 hours, treatment with IV-tPA was performed based on MRI findings. Favorable outcome was assessed after 90 days using a dichotomized modified Rankin scale score of 0 to 1. Intracerebral bleeding complications were assessed on follow-up MRI or computed tomography. Data were compared with the pooled placebo and pooled tPA patients of the ATLANTIS, ECASS, and National Institute of Neurological Disorders and Stroke (NINDS) tPA trials., Results: From 174 MRI-selected tPA patients, 62% (n=108) were treated in < or =3 hours and 38% (n=66) after 3 to 6 hours. Favorable outcome was more frequent in MRI-selected tPA patients (48% [95% CI, 39 to 54]) compared with pooled placebo (33% [95% CI, 31 to 36]; P<0.001) and pooled tPA patients (40% [95% CI, 37 to 42]; P=0.046). Odds ratios for favorable outcome in the MRI-selected tPA group were 1.82 (1.32 to 2.51) compared with the pooled placebo and 1.39 (1.01 to 1.92) compared with the pooled tPA group. The rate of symptomatic intracerebral hemorrhage in MRI-selected tPA patients (3% [95% CI, 0 to 5]) was lower than in the pooled tPA group (8% [95% CI, 7 to 10]; P=0.012) and comparable to the pooled placebo group (2% [95% CI, 1 to 3]; P=0.392)., Conclusions: This study supports that it is safe and effective to expand the time window for IV-tPA up to 6 hours in patients with tissue at risk as defined by MRI.

Background and Purpose: Information on safety and efficacy of intravenous thrombolysis with tissue plasminogen activator (tPA) (IV-tPA) in very old acute ischemic stroke (AIS) patients is scarce. We studied outcome and severe hemorrhagic complications in patients aged 80 and older., Methods: We analyzed data of AIS patients, treated with IV-tPA, in 3 German stroke centers. Neurologic deficit on admission was assessed using the National Institutes of Health Stroke Scale (NIHSS). Outcome was assessed after 90 days using the Modified Rankin Scale (MRS), and favorable outcome was defined as a MRS score of 0 to 1. Severe intracerebral bleeding complications were assessed on follow-up magnetic resonance imaging or cranial computed tomography. Data were compared between patients <80 years of age and patients aged > or =80 years., Results: A total of 228 patients were treated with IV-tPA; 38 (16%) were 80 years or older. There was no difference in NIHSS on admission or onset to treatment time between younger and older patients. Less patients > or =80 years of age achieved a favorable outcome (26.3 versus 46.8%, P=0.021), and mortality was higher in older patients (21.1 versus 5.3%, P=0.004). There was no difference in the rate of parenchymal hemorrhage (6.3%<80 years versus 5.3%> or =80 years, P=1.000) and symptomatic intracerebral hemorrhage (2.6%<80 years versus 2.6%> or =80 years, P=1.000) between both groups., Conclusions: There is no increase in severe intracerebral hemorrhage after IV-tPA in very old patients, but outcome is worse as compared with younger patients. There is no evidence to exclude ischemic stroke patients from thrombolysis based on a predefined age threshold.

Background: To evaluate the effect of occlusion type and fibrinolytic agent on recanalization success and clinical outcome in patients undergoing local intra-arterial fibrinolysis (LIF) in acute hemispheric stroke., Methods: LIF was performed in 137 patients with angiographically established occlusion in the carotid circulation within 6 h of stroke onset. Retrospective analysis included recanalization success, recanalization time, type of occlusion and fibrinolytic treatment mode. Five types of occlusion were categorized: intracranial bifurcation (carotid 'T') of the internal carotid artery (ICA; n = 35); proximal segment of the middle cerebral artery (MCA; n = 66); distal segment of the MCA (n = 20); extracranial ICA with MCA embolism (n = 8); multiple peripheral branches of the anterior cerebral artery and the MCA (n = 8). Neurologic outcome was evaluated after 3 months by Barthel Index (BI) as good (BI >90), moderate (BI 50-90), poor (BI <50) or death., Results: Recanalization was achieved in 74 patients (54%). Mean recanalization time in recanalized patients was 91 min. Neurologic outcome was good in 48 patients (35%), moderate in 34 (25%), poor in 30 (22%) and 25 died (18%). Outcome was significantly better in recanalized than in nonrecanalized patients (p < 0.001). Treatment results were significantly better in proximal and distal MCA occlusion than in carotid 'T' occlusions (p < 0.001). Recanalization success hardly differed between urokinase and rt-PA. Combined treatment with rt-PA and lys-plasminogen tended toward a faster recanalization. Parenchymal hemorrhage occurred in 13 patients (9%)., Conclusion: The type of occlusion is of high prognostic value for successful fibrinolysis in the anterior circulation. However, recanalization is a time-consuming process even with an intra-arterial approach. Recanalization did not differ between type or dosage of plasminogen activators. Further innovative attempts are warranted towards hastening recanalization time in endovascular acute stroke treatment., (Copyright 2003 S. Karger AG, Basel)

Copyright of Der Nervenarzt is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)