Search

Objective: To investigate differences in procedure times, safety, and efficacy outcomes comparing 2 different protocols to enable thrombolysis in the extended or unknown time window after stroke onset with either multimodal CT or MRI., Methods: Patients with ischemic stroke in the extended or unknown time window who received IV thrombolysis between January 2011 and May 2019 were identified from an institutional registry. Imaging-based selection was done by multimodal CT or MRI according to institutional treatment algorithms., Results: IV thrombolysis was performed in 100 patients (54.3%) based on multimodal CT imaging and in 84 patients (45.7%) based on MRI. Baseline clinical data, including stroke severity and time from last seen normal to hospital admission, were similar in patients with CT and MRI. Door-to-needle times were shorter in patients with CT-based selection (median [interquartile range] 45 [37-62] minutes vs 75 [59-90] minutes; mean difference [95% confidence interval (CI)] -28 minutes [-35 to -21]). No differences were detected regarding the incidence of symptomatic intracranial hemorrhage (2 [2.0%] vs 4 [4.8%]; adjusted odds ratio [aOR] [95% CI] 0.47 [0.08-2.83]) and favorable outcome at day 90 (25 [33.8%] vs 33 [42.9%]; aOR 0.95 [0.45-2.02])., Conclusion: IV thrombolysis in ischemic stroke in the unknown or extended time window appeared safe in CT- and MRI-selected patients, while the use of CT imaging led to faster door-to-needle times., Classification of Evidence: This study provides Class IV evidence that for patients with ischemic stroke in the extended or unknown time window, imaging-based selection for IV thrombolysis by multimodal CT compared to MRI led to shorter door-to-needle times., (© 2020 American Academy of Neurology.)

Background: Stroke thrombolysis with alteplase is currently recommended 0-4·5 h after stroke onset. We aimed to determine whether perfusion imaging can identify patients with salvageable brain tissue with symptoms 4·5 h or more from stroke onset or with symptoms on waking who might benefit from thrombolysis., Methods: In this systematic review and meta-analysis of individual patient data, we searched PubMed for randomised trials published in English between Jan 1, 2006, and March 1, 2019. We also reviewed the reference list of a previous systematic review of thrombolysis and searched ClinicalTrials.gov for interventional studies of ischaemic stroke. Studies of alteplase versus placebo in patients (aged ≥18 years) with ischaemic stroke treated more than 4·5 h after onset, or with wake-up stroke, who were imaged with perfusion-diffusion MRI or CT perfusion were eligible for inclusion. The primary outcome was excellent functional outcome (modified Rankin Scale [mRS] score 0-1) at 3 months, adjusted for baseline age and clinical severity. Safety outcomes were death and symptomatic intracerebral haemorrhage. We calculated odds ratios, adjusted for baseline age and National Institutes of Health Stroke Scale score, using mixed-effects logistic regression models. This study is registered with PROSPERO, number CRD42019128036., Findings: We identified three trials that met eligibility criteria: EXTEND, ECASS4-EXTEND, and EPITHET. Of the 414 patients included in the three trials, 213 (51%) were assigned to receive alteplase and 201 (49%) were assigned to receive placebo. Overall, 211 patients in the alteplase group and 199 patients in the placebo group had mRS assessment data at 3 months and thus were included in the analysis of the primary outcome. 76 (36%) of 211 patients in the alteplase group and 58 (29%) of 199 patients in the placebo group had achieved excellent functional outcome at 3 months (adjusted odds ratio [OR] 1·86, 95% CI 1·15-2·99, p=0·011). Symptomatic intracerebral haemorrhage was more common in the alteplase group than the placebo group (ten [5%] of 213 patients vs one [<1%] of 201 patients in the placebo group; adjusted OR 9·7, 95% CI 1·23-76·55, p=0·031). 29 (14%) of 213 patients in the alteplase group and 18 (9%) of 201 patients in the placebo group died (adjusted OR 1·55, 0·81-2·96, p=0·66)., Interpretation: Patients with ischaemic stroke 4·5-9 h from stroke onset or wake-up stroke with salvageable brain tissue who were treated with alteplase achieved better functional outcomes than did patients given placebo. The rate of symptomatic intracerebral haemorrhage was higher with alteplase, but this increase did not negate the overall net benefit of thrombolysis., Funding: None., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Intravenous thrombolysis with alteplase within a time window up to 4.5 h is the only approved pharmacological treatment for acute ischemic stroke. We studied whether acute ischemic stroke patients with penumbral tissue identified on magnetic resonance imaging 4.5-9 h after symptom onset benefit from intravenous thrombolysis compared to placebo., Methods: Acute ischemic stroke patients with salvageable brain tissue identified on a magnetic resonance imaging were randomly assigned to receive standard dose alteplase or placebo. The primary end point was disability at 90 days assessed by the modified Rankin scale, which has a range of 0-6 (with 0 indicating no symptoms at all and 6 indicating death). Safety end points included death, symptomatic intracranial hemorrhage, and other serious adverse events., Results: The trial was stopped early for slow recruitment after the enrollment of 119 (61 alteplase, 58 placebo) of 264 patients planned. Median time to intravenous thrombolysis was 7 h 42 min. The primary endpoint showed no significant difference in the modified Rankin scale distribution at day 90 (odds ratio alteplase versus placebo, 1.20; 95% CI, 0.63-2.27, P = 0.58). One symptomatic intracranial hemorrhage occurred in the alteplase group. Mortality at 90 days did not differ significantly between the two groups (11.5 and 6.8%, respectively; P = 0.53)., Conclusions: Intravenous alteplase administered between 4.5 and 9 h after the onset of symptoms in patients with salvageable tissue did not result in a significant benefit over placebo. (Supported by Boehringer Ingelheim, Germany; ISRCTN 71616222).

Background and Purpose- Oral angioedema (OA) is a rare but life-threatening complication in patients with ischemic stroke receiving intravenous thrombolysis with r-tPA (recombinant tissue-type plasminogen activator). This study intended to determine associations between thrombolysis-related OA and ischemic stroke lesion sites using a voxel-wise lesion analysis. Methods- Prospective registry data were used to identify ischemic stroke patients with thrombolysis-related OA between 2002 and 2018. For the study registry, ethics approval was obtained by the Ethics Committee of the Friedrich-Alexander Universität (FAU) Erlangen-Nürnberg (clinical registry registration: 377&#95;17Bc). Ischemic stroke patients with thrombolysis treatment but without OA admitted in the years 2011 and 2012 comprised the control group. Ischemic lesions were manually outlined on magnetic resonance imaging (1.5T or 3T) or computed tomographic scans and transformed into stereotaxic space. We determined the lesion overlap and compared the absence or presence of OA voxel-wise between patients with and without lesions in a given voxel using the Liebermeister test. Stroke severity was rated using the National Institutes of Health Stroke Scale score, and blood pressure, heart rate, blood glucose levels, and body temperature were determined on admission. Results- Fifteen ischemic stroke patients with thrombolysis-related OA were identified. The voxel-wise analysis yielded associations between OA and ischemic lesions in the insulo-opercular region with a right hemispheric dominance. Mean blood pressure was significantly lower in patients with OA than in controls. Age, National Institutes of Health Stroke Scale scores, infarct volumes, heart rate, and blood glucose levels did not differ between patients with and without OA. Conclusions- The voxel-wise analysis linked thrombolysis-related OA to right insulo-opercular lesions. The lower blood pressure in patients with thrombolysis-related OA may reflect bradykinin effects causing vasodilatation and increasing vascular permeability.

Introduction: The management of acute ischemic stroke in patients on direct oral anticoagulants (DOACs) is challenging. However, the substance-specific plasma level could guide treatment decisions on recanalization therapies. We present a plasma-level-based protocol for emergency treatment of stroke patients on oral anticoagulants. Bleeding complications and clinical outcome for patients on DOACs are reported and compared to patients on vitamin K antagonists (VKAs)., Methods: In patients with acute ischemic stroke and suspected use of DOACs within 48 h prior to hospital admission, plasma levels were measured using the calibrated Xa-activity (apixaban, edoxaban, rivaroxaban) or the Hemoclot®-assay (dabigatran). Levels <50 ng/mL were supportive for thrombolysis, while high values >100 ng/mL excluded patients from recombinant tissue plasminogen activator use. For patients on VKAs, the cutoff was set at international normalized ratio of 1.7. Endovascular thrombectomy of a large vessel occlusion was performed independently from coagulation testing. Consecutive patients were included in an observational registry., Results: Five hundred and twenty-two patients (261 on VKAs and 261 on DOACs) were included. Thirty patients (11.5%) on VKAs and 24 (9.2%) on DOACs received thrombolysis, followed by mechanical thrombectomy in 10 and 14 patients, respectively. Seventeen patients in each group received thrombectomy only. Symptomatic intracranial hemorrhage associated with thrombolysis occurred in 1 patient on VKA (3.3%) and 1 on DOAC (4.2%; p = 0.872). The turnaround time of specific assays did not show a significant delay in comparison to standard coagulation parameters., Conclusion: DOAC plasma levels could support decisions on emergency treatment of ischemic stroke. Systemic thrombolysis below suggested thresholds appears preliminary feasible and safe without an excess in bleeding complications., (© 2019 S. Karger AG, Basel.)

Background: The SPAN-100 index adds patient age and baseline NIHSS-score and was introduced to predict clinical outcome after acute ischemic stroke (AIS). Even with high NIHSS-scores younger patients cannot reach a SPAN-100-positive status (index ≥100). We aimed to evaluate the SPAN-100 index among a large, contemporary cohort of i.v.-thrombolysed AIS-patients and exclusively among older patients who can at least theoretically achieve SPAN-100-positivity., Methods: The SPAN-100 index was applied to AIS-patients receiving i.v.-thrombolysis (IVT) in our institution between 01/2006 and 01/2013. Clinical outcome and symptomatic intracerebral hemorrhage rates were compared between SPAN-100-positive and -negative patients. Furthermore we excluded patients < 65 years, without any theoretical chance to achieve SPAN-100-positivity, and re-evaluated the index (SPAN 65 -100 index)., Results: SPAN-100-positive IVT-patients (124/1002) had a 9-fold increased risk for unfavorable outcome compared to SPAN-negative patients (OR 9.39; 95% CI 5.87-15.02; p <  0.001). The odds ratio for mortality was 7.48 (95% CI 4.90-11.43; p <  0.001). No association was found between SPAN-100-positivity and sICH-incidence (OR 0.88; 95% CI 0.31-2.53; p = 0.810). SPAN 65 -100-positivity (124/741) was associated with an 8-fold increased risk for unfavorable outcome (OR 7.6; 95% CI 4.71-12.22; p <  0.001) but not associated with higher sICH-rates (OR 0.86; 95% CI 0.29-2.53; p <  0.001)., Conclusions: Also for patients ≥65 years the SPAN-100 index can be a fast, easy method to predict clinical outcome of IVT-patients in everyday practice. However, it should not be used to determine the risk of sICH after IVT. Based on a SPAN-positive status IVT should not be withheld from AIS-patients merely because of feared sICH-complications.

Background and Purpose: Mechanical thrombectomy, in addition to intravenous (i.v.) thrombolysis is recommended for treatment of acute stroke in patients with large vessel occlusions (LVO) in the anterior circulation up to 6 h after symptom onset. We compared thrombectomy rates of eight university hospitals of the MIRACUM consortium to analyze the implementation of this guideline in clinical routine., Methods: Anonymized billing data in a standardized format were loaded into a local i2b2 data warehouse by applying already existing extract, transform and load (ETL) routines. A locally executed uniform SQL (structured query language) query delivered aggregated site data for all inpatients with a discharge diagnosis of ischemic stroke (ICD-10 I63) containing counts for type of acute treatment, type of admission and age groups, which were centrally analyzed with R., Results: From 2014 to 2016, the thrombectomy rate almost doubled from a mean of 4.7% to 9.6%, although significant differences between centers exist (range in 2016: 5.8-17%). The number of drip-and-ship procedures increased in 3 out of 8 centers. There was no evidence for a decrease in thrombectomy rates during weekends/holiday or among patients older than 80 years, but this age group is more likely to receive i.v. recombinant tissue plasminogen activator (rtPA)., Conclusion: The observed increase of thrombectomy rates and drip-and-ship procedures without a significant difference between weekdays and weekends or patients of different ages is substantiating a rapid implementation of stroke guidelines within the analyzed neurovascular centers. The prototype of the MIRACUM Data Integration Center already contributes to health services research in Germany.

Rationale and Hypothesis: Thrombolytic therapy with recombinant tissue plasminogen activator (rt-PA) is an effective and approved therapy for acute ischemic stroke within 4.5 h of onset except for USA, Canada, Croatia, and Moldovia with a current 3 h label. We hypothesized that ischemic stroke patients selected with significant penumbral mismatch on magnetic resonance imaging (MRI) at 4.5-9 h after onset of stroke will have improved clinical outcomes when given intravenous rt-PA (alteplase) compared to placebo., Study Design: ECASS-4: ExTEND is an investigator driven, phase 3, randomized, multi-center, double-blind, placebo-controlled study. Ischemic stroke patients presenting within 4.5 and 9 h of stroke onset, who fulfil clinical requirements (National Institutes of Health Stroke Score (NIHSS) 4-26 and pre-stroke modified Rankin Scale (mRS) 0-1) will undergo MRI. Patients who meet imaging criteria (infarct core volume <100 ml, perfusion lesion: infarct core mismatch ratio >1.2 and perfusion lesion minimum volume of 20 ml) additionally will be randomized to either rt-PA or placebo., Study Outcome: The primary outcome measure will be the categorical shift in the mRS at day 90. Clinical secondary outcomes will be disability at day 90 dichotomized as favorable outcome mRS 0-1 at day 90. Tertiary endpoints include reduction in the NIHSS by 11 or more points or reaching 0-1 at day 90, reperfusion and recanalization at 24 h post stroke as well as depression, life quality, and cognitive impairment at day 90. Safety endpoints will include symptomatic intracranial hemorrhage (ICH) and death., (© 2016 World Stroke Organization.)

Background: Perfusion computed tomography (PCT) has emerged as alternative to magnetic resonance imaging (MRI) for assessment of patients clinically qualifying for off-label thrombolysis within 4.5 to 9 hours after onset of ischemic stroke. However, disadvantage of PCT is its often limited anatomic coverage with only 2 or 3 slices when using a 4- to 64-section scanner. Our purpose was therefore to evaluate the value of 2- and 3-slice perfusion compared to whole-brain perfusion., Methods: One hundred twenty-five patients undergoing MRI beyond 4.5 hours after symptom onset with supratentorial perfusion deficit were selected retrospectively. Accordingly to PCT slice positioning, 2 or 3 slices of the whole-brain perfusion weighted imaging data set were depicted. Volumes of infarct (using cerebral blood volume) and penumbra (using time-to-peak and cerebral blood volume) were calculated, and results were compared with 2- and 3-slice-derived volumes, respectively., Results: Whole-brain imaging revealed a mismatch of more than 20% in 68.8% of patients (defined as 100%). Two-slice imaging detected a perfusion deficit in 72% and a mismatch in 48.8% (sensitivity = 70.9%). Three-slice imaging detected a perfusion deficit in 76% and a mismatch in 50.4% (sensitivity = 73.3%). Although there was no significant difference between 2- and 3-slice imaging (P > .23), both techniques revealed significantly less patients with mismatch compared to whole-brain coverage (P < .01)., Conclusions: Two- and 3-slice imaging like obtained with PCT on most installed CT systems to assess perfusion deficits with subsequent mismatch calculation in acute stroke outside the 4.5-hour time window is significantly inferior to whole-brain coverage and, hence, has to be considered as a less-than-ideal solution., (Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Background: Stroke care networks with and without telemedicine have been established in several countries over the last decade to provide specialized stroke expertise to patients in rural areas. Acute consultation is a first step in the management of stroke, but not the only one. Methods of standardization of care and treatment are much needed. So far, quality management systems have only been used for single stroke units. To the best of our knowledge, we are the first stroke network worldwide to aim for certification of a network-wide quality management system., Methods: The Stroke Network Using Telemedicine in Northern Bavaria (STENO), currently with 20 associated medical institutions, is one of the world's largest stroke networks, caring for over 5000 stroke patients each year. In 2010, we initiated the implementation of a network-wide 'total' quality management system according to ISO standard 9001:2008 in cooperation with the German Stroke Society and a third-party certification organization (LGA InterCert)., Results: Certification according to ISO 9001:2008 was awarded in March 2011 and maintained over a complete certification cycle of 3 years without major deviation from the norm in three external third-party audits. Thrombolysis rate significantly increased from 8·2% (2009) to 12·8% (2012)., Conclusions: Certified quality management within a large stroke network using telemedicine is possible and might improve stroke care procedures and thrombolysis rates. Outcome studies comparing conventional stroke care and telestroke care are inevitable., (© 2014 World Stroke Organization.)

Background: Intraventricular fibrinolysis (IVF) in subarachnoid hemorrhage (SAH) is an emerging strategy aiming to hasten clot lysis, treat hydrocephalus, and reduce permanent shunt rates. Because of clinical heterogeneity of investigated patient effects of IVF on permanent shunt incidence and functional outcome are widely debated. The present study is the first to investigate solely endovascular-treated SAH patients., Methods: Overall, 88 consecutive patients with aneurysmal SAH requiring external ventricular drain placement and endovascular aneurysm closure were included. Functional outcome and shunt dependency were assessed 90 days after event. A matched controlled sub-analysis was carried out to investigate the effects of IVF treatment (n = 14; matching criteria: age, neuro-status and imaging). Multivariate modeling was performed to identify independent predictors for permanent shunt dependency., Results: In IVF-patients neurological status was significantly poorer [Hunt&Hess: IVF = 4(3-5) vs. non-IVF = 3(1-5); p = 0.035] and the extent of ventricular hemorrhage was increased [Graeb Score: IVF = 7(6-8) vs. non-IVF = 3(1-4); p ≤ 0.001]. Consecutive matched controlled sub-analysis revealed no significant therapeutic effect of IVF with respect to shunt dependency rate and functional outcome. Multivariate analysis revealed Graeb score [OR = 1.34(1.02-1.76); p = 0.035] and sepsis [OR = 11.23(2.28-55.27); p = 0.003] as independent predictors for shunt dependency, whereas IVF did not exert significant effects (p = 0.820)., Conclusions: In endovascular-treated SAH patients IVF neither reduced permanent shunt dependency nor influenced functional outcome. Despite established effects on intraventricular clot resolution IVF appears less powerful in SAH as compared to ICH. Given the reported positive effects of lumbar drainage (LD) in SAH, a prospective analysis of a combined treatment approach of IVF and subsequent lumbar drain sOeems warranted aiming to reduce permanent shunting and improve functional outcome.

Objective: Contradictory results were reported for the outcome after endovascular recanalization (ERT) in acute anterior circulation ischemic stroke. We assessed whether a clinical/perfusion CT cerebral blood volume (CBV) mismatch concept (CPM) can identify patients who will benefit from reperfusion therapy., Methods: Imaging and clinical data of 58 consecutive ERT cases with acute anterior circulation stroke (ICA, M1, proximal M2) undergoing intraarterial thrombectomy within 4.5h after symptom onset were analyzed retrospectively. CPM was defined as NIHSS≥8 and PCT CBV ASPECTS≥7. Minor CBV lesion was defined as PCT CBV ASPECTS≥7., Results: All baseline characteristics other than blood glucose did not differ between the paired groups. Revascularization was achieved in 87.9% of all patients without significant difference between the paired groups. Favorable clinical outcome after 3 months (mRS≤2) resulted in 29.3% of all patients, in contrast to 47.4% of the CPM positive and 52.2% of the minor CBV lesion groups., Conclusion: CPM can identify patients who will benefit from reperfusion therapy in acute anterior circulation ischemic stroke., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Purpose of Review: Bloody cerebrospinal fluid (CSF) is a major cause of morbidity and mortality in intraventricular hemorrhage (IVH) and subarachnoid hemorrhage (SAH). Different treatment strategies aiming at faster clearance of bloody CSF have emerged. The present review focuses on recent developments in the investigation of those treatments., Recent Findings: Intraventricular fibrinolysis (IVF) for accelerated IVH-resolution has been clinically tested since the early 1990s. The lately summarized evidence from smaller studies indicates that IVF may result in a benefit in mortality and outcome. Recent investigations have elucidated different aspects of IVF, mainly related to safety. Neuroendoscopy has also emerged as a minimally invasive technique allowing fast removal of IVH. The capability of lumbar drainage to reduce vasospasm after SAH has been tested in a large trial., Summary: IVF is relatively well tolerated and accelerates clot clearance after IVH. The effect of IVF on clinical outcome and mortality is currently being investigated in a large-scale phase III clinical trial. Neuroendoscopy is feasible for the treatment of IVH, however, larger trials are lacking. Lumbar drainage reduces the incidence of vasospasm after SAH. An ongoing phase III trial has been designed to test its influence on outcome. Lumbar drainage may also reduce shunt-dependency after IVH.

Background: Intravenous thrombolysis for acute stroke is more efficient the earlier the treatment is initiated. In-hospital delays account for a significant proportion of avoidable time loss before treatment is initiated. Paradoxically, studies have reported longer door-to-needle times the earlier the patients arrive ('three-hour effect'). Hypothesis We hypothesized that a standardized thrombolysis procedure carried out in a specialized neurological emergency room can minimize in-hospital delays and erase the 'three-hour effect'., Methods: Onset-to-door and door-to-needle times of 246 consecutive thrombolysis patients were analyzed. A standardized protocol designed to minimize in-hospital delays was tested using a resident-based stroke team within a neurological emergency room. Correlation of onset-to-door and door-to-needle times was measured as well as differences in treatment times for daytime versus night hours and weekend vs. weekday. Outcome, rate of symptomatic intracranial hemorrhage and mortality were compared with the results of SITS-MOST., Results: Median door-to-needle time was 25 min compared with a mean of 68 min in SITS-MOST. door-to-needle time did not correlate with onset-to-door time (Pearson's r = -0 · 097; P = 0 · 13) and patients arriving within 90 min from symptom onset showed comparable door-to-needle times with patients arriving within 90-180 min. Neither treatment on weekends nor during night hours led to significant in-hospital treatment delays. Outcome and safety parameters were comparable with those observed in SITS-MOST., Conclusions: By applying a standardized and diligently monitored thrombolysis protocol, carried out by a specialized stroke team within a neurological emergency room, in-hospital delays can be minimized. This allows improvement of door-to-needle times irrespective of the time to arrival and treatment during off-hours., (© 2011 The Authors. International Journal of Stroke © 2011 World Stroke Organization.)

Intraventricular hemorrhage (IVH) has been associated with poor prognosis in patients with spontaneous intracerebral hemorrhage. Several factors contribute to the deleterious effects of IVH, including direct mass effects of the ventricular blood clot on ependymal and subependymal brain structures, mechanical and inflammatory impairment of the Pacchioni granulations by blood and its breakdown products, and disturbance of physiological cerebrospinal fluid (CSF) circulation. Acute obstructive hydrocephalus represents a major life-threatening complication of IVH and is usually treated with an external ventricular drainage (EVD). However, treatment with EVD alone is frequently not sufficiently effective due to obstruction of the catheter by blood. In the past two decades, intraventricular fibrinolysis (IVF) has been increasingly used for maintenance of EVD functionality and acceleration of ventricular clot resolution in such patients. Unfortunately, there is no prospective, randomized controlled trial addressing the effect of IVF on clinical outcome. The available data on IVF consist of small retrospective case series, case reports, and a few prospective case-control studies, which are the subject of the present review article. All these studies, when considered in their entirety, suggest that IVF has a positive impact on mortality and functional outcome, and could be considered as a treatment option for selected patients.

Background and Purpose: The aim of the current study was to investigate the dose-dependent efficacy of intraventricular fibrinolysis (IVF) in patients with severe intraventricular hemorrhage (IVH)., Methods: Patients with intracerebral hemorrhage, severe IVH, and obstructive hydrocephalus with the need for external ventricular drainage were treated with IVF through external ventricular drainage. The time course of IVH resolution and the safety profile were compared between patients treated with high-dose IVF (4 mg alteplase every 12 hours, maximum 20 mg; n=32) and low-dose IVF (1 mg alteplase every 8 hours, maximum 12 mg; n=22). CT scans on Days 1 to 4, 7 ± 1 and 10 ± 1 after admission, were analyzed volumetrically. Outcome was assessed after 3 months., Results: The overall effect of IVF dosage was not significantly different between the 2 groups (F=1.3, P=0.25). The course of IVH volume in the third and fourth ventricles was similar with high- and low-dose IVF. High-dose IVF resulted in lower total IVH volumes on Days 7 (4.4 ± 4.2 mL versus 8.8 ± 8.1 mL; P=0.01) and 10 (1.4 ± 2.8 mL versus 4.9 ± 65.8 mL; P=0.005). Total clot half-life was 78 ± 43 hours in the low-dose and 56 ± 25 hours in the high-dose group (P=0.02). One asymptomatic ventricular bleeding, 2 cases of ventriculitis, and 1 death due to pulmonary embolism occurred in the high-dose group. There was no difference in outcome at 3 months., Conclusions: Low-dose IVF (3 mg alteplase/day) has a similar effect on IVH clearance from the third and fourth ventricles and a similar safety profile when compared with high-dose IVF (8 mg alteplase/day).

The Penumbra Stroke System (PSS) was cleared for use in patients with ischemic stroke by the FDA in January 2008. We describe our experience of using this new system in acute large vessel occlusive disease following thrombolysis. Fifteen consecutive patients (mean age 60 years) suffering from acute ischemic stroke were treated with the PSS after intravenous or intra-arterial standard treatment with tissue plasminogen activator (n = 14) or ReoPro (n = 1). All patients presented with TIMI 3 before use of the PSS. Carotid stenting (n = 3) and intracranial balloon angioplasty or stenting (n = 2) were performed if indicated. Neurological evaluation was performed using the NIHSS score and the mRS score. Initial median NIHSS score in 12 patients with occlusions in the anterior circulation was 15; three patients with basilar artery occlusion presented with coma. Median symptom to procedure start time was 151 min. In the anterior circulation, 9 of the 12 target vessels were recanalised successfully (TIMI 2 and 3). The rate of patients with independent clinical outcome (mRS

Background and Purpose: While intravenous recombinant tissue plasminogen activator (rt-PA) has been approved for acute stroke therapy within 3 hours, the optimum management of basilar artery occlusion (BAO) is still a matter of debate. We compared intraarterial thrombolysis with the combined bridging approach of intravenous abciximab and intraarterial thrombolysis with rt-PA (bridging therapy) in an observational, longitudinal, monocenter study., Methods: Between 1998 and 2006, information for 106 patients with acute BAO were prospectively entered into a local database. Patients eligible for treatment received either intraarterial thrombolysis with rt-PA alone (intraarterial thrombolysis) or were treated with intravenous abciximab and intraarterial rt-PA (bridging therapy). Outcome parameters were recanalization of the basilar artery according to Trial in Myocardial Infarction criteria, survival, and reduction of severe disability and death at 3 months. Logistic regression was used to identify independent predictors for recanalization, survival, and clinical outcome., Results: Of a total of 106 patients with confirmed BAO, 87 patients underwent subsequent angiography. Among those, 75 patients were identified who received the full treatment protocol. Patients in the bridging group had a better recanalization rate (83.7% vs 62.5%; P=0.03), a higher survival rate (58.1% vs 25%; P=0.01), and a better chance for an outcome with no or only mild to moderate disability (modified Rankin Scale score, 0-3; 34.9% vs 12.5%; P=0.02). Symptomatic intracerebral hemorrhage rates were comparable in both groups (14% in the bridging group vs 18.8%; P=0.41). Independent predictors for recanalization were age (OR, 0.95; 95% CI, 0.91-0.99), atrial fibrillation (OR, 6.53; 95% CI, 1.14-37.49), and bridging therapy (OR, 3.37; 95% CI, 1.02 to 11.18). Independent prognostic factors for outcome were Glasgow coma scale score at presentation (OR, 1.24; 95% CI, 1.03-1.45) and the combination of bridging therapy with successful recanalization (OR, 3.744; 95% CI, 1.04-13.43)., Conclusions: Bridging therapy for acute BAO with intravenous abciximab and intraarterial rt-PA appears to be safe and yields higher recanalization and improved survival rates, as well as an overall improved chance for a better outcome.

Thrombolysis (T) is limited by reperfusion-associated injury and the short therapeutic window after stroke onset. The present study investigates whether hypothermia alone or in combination with thrombolysis has beneficial effects after experimental thromboembolic stroke. Wistar rats (n = 60) were subjected to thromboembolic occlusion (TE) of the middle cerebral artery (MCA). Thrombolysis (T) was performed with intravenous recombinant tissue-plasminogen activator (rt-PA) 1 h (early T) or 3 h (late T) after TE. Hypothermia (Hy) was applied for 4 h at 33 degrees C started 1 h after TE. Experimental groups included control (C), early thrombolysis (ET), late thrombolysis (LT), hypothermia (Hy), early thrombolysis plus hypothermia (ET+Hy), and late thrombolysis plus hypothermia (LT+Hy). Animals were investigated by MRI and silver infarct staining (SIS) to assess the cerebral infarct size. All animals of group Hy survived, in contrast to 40% in group C (P < 0.05). ET+HY and LT+Hy showed a trend towards better survival as compared to ET and LT alone. PWI parameters were not significantly different between ET versus ET+HY and LT versus LT+Hy, but rt-PA administration led to improved cerebral perfusion in MRI. Significant differences in infarct volumes (T2/SIS) were found after 24 h in all treatment groups versus the control group (P < 0.05). The lesion volume calculated from T2 was significantly smaller in ET (16% +/- 5%), ET+Hy (10 +/- 4%), and LT+Hy (20% +/- 9%) after 5.5 h (10.8% +/- 4.8%) versus C (42% +/- 15%), (P < 0.05). These data indicate that hypothermia improves survival and decreases infarct volume. However, there were no significant differences between the use of rt-PA alone or in combination with hypothermia. Further studies are needed to confirm these effects, also several days after stroke onset.

Purpose: Endovascular therapy (EVT) of large-vessel occlusion in acute ischemic stroke (AIS) may be performed in general anesthesia (GA) or conscious sedation (CS). We intended to determine the contribution of ischemic cerebral lesion sites on the physician's decision between GA and CS using voxel-based lesion symptom mapping (VLSM). Methods: In a prospective local database, we sought patients with documented AIS and EVT. Age, stroke severity, lesion volume, vigilance, and aphasia scores were compared between EVT patients with GA and CS. The ischemic lesions were analyzed on CT or MRI scans and transformed into stereotaxic space. We determined the lesion overlap and assessed whether GA or CS is associated with specific cerebral lesion sites using the voxel-wise Liebermeister test. Results: One hundred seventy-nine patients with AIS and EVT were included in the analysis. The VLSM analysis yielded associations between GA and ischemic lesions in the left hemispheric middle cerebral artery territory and posterior circulation areas. Stroke severity and lesion volume were significantly higher in the GA group. The prevalence of aphasia and aphasia severity was significantly higher and parameters of vigilance lower in the GA group. Conclusions: The VLSM analysis showed associations between GA and ischemic lesions in the left hemispheric middle cerebral artery territory and posterior circulation areas including the thalamus that are known to cause neurologic deficits, such as aphasia or compromised vigilance, in AIS-patients with EVT. Our data suggest that higher disability, clinical impairment due to neurological deficits like aphasia, or reduced alertness of affected patients may influence the physician's decision on using GA in EVT. [ABSTRACT FROM AUTHOR]

Objective: A voxel-based statistical approach on computer tomographic data in patients with intracerebral hemorrhage (ICH) and acute intraventricular hemorrhage (IVH) was used to evaluate spatial and temporal patterns of intraventricular blood in patients treated with intraventricular fibrinolysis (IVF) or without.Methods: IVH shapes were systematically assessed three dimensionally in patients with supratentorial ICH at three intervals of time (day of admission, day 4 ± 1, day 7+). The boundaries of the intraventricular blood clot were delineated on computed tomography (CT) scans using dedicated software. The CT scan and the IVH shape were transferred into stereotaxic space. In a second step, voxel-based statistics on group level were used to correlate the distribution of intraventricular blood with the interval and the treatment group.Results: Altogether 45 patients, 29 with IVF therapy and 16 without, were eligible to be included into this study. We found significant (false discovery rate [FDR] correction, q < .05) reduction of the intraventricular blood between day of admission and day 7 + for the third and fourth ventricle and parts of both lateral ventricles. In addition, we were able to show a significant difference between the IVF therapy and the conventionally treated group at day 4 ± 1 for the third ventricle.Conclusions: The data indicate that voxel-based analysis on group level can be used to compare the time course and the distribution of intraventricular hemorrhage. This technique could be an interesting tool for future research on ICH with IVH. [ABSTRACT FROM AUTHOR]

Telemedicine is in increasing use in clinical neuroscience such as acute stroke care, especially by applying remote audiovisual communication for patient evaluation. However, telephone consultation was also used linking stroke centres to smaller hospitals. We compared costs of telestroke services using audiovisual and telephone communication in different organizational models. Within a small network in Northern Bavaria video-based teleconsultation (VTC) and telephone advice (TA) was provided for evaluation of acute stroke patients on a weekly rotation. The costs of the admissions process with or without one of both methods of telemedicine were calculated and compared from the perspective of the spoke hospital. Different levels of service and network size were modelled and costs of transfers as well as loss of revenues were calculated. Yearly total labour costs were 415,000 € for an on-site service VTC-service compared to 61,000 € in an on-call service. Additional costs for one teleconsultation were 109.55 € in VTC and 49.82 € in TA (VTC/TA ratio 2.2). The ratio decreased to 0.8 when accounting for costs of transfer and loss of reimbursement for all patients transferred as transfer of patients to the stroke centre was more frequent after TA (9.1 vs. 14.9 %full-time on-site ser). Costs of one QALY gained by using VTC instead of TA ranged from 115.00 € to 515.86 € depending on the different models. In the first view TA looks like the less expensive method as it is easy to access and works without additional costs. When accounting for all disadvantages TA becomes slightly more expensive. In telestroke care VTC should be recommended as the method of choice also from an economic perspective. [ABSTRACT FROM AUTHOR]

Occlusion of a brain vessel leads to a critical reduction in cerebral perfusion and, within minutes, to ischemic infarction with a central infarct core of irreversibly damaged brain tissue and a more or less large area of hypoperfused but still vital brain tissue (the ischemic penumbra), which can be salvaged by rapid restoration of blood flow. Therefore, the underlying rationale for the introduction and application of thrombolytic agents is the lysis of an obliterating thrombus and thus reestablishment of cerebral blood flow by cerebrovascular recanalization with subsequent reperfusion. After introduction of thrombolytic therapy for the treatment of acute myocardial infarction in the early 1990s, major trials for the evaluation of this new therapeutic approach to ischemic stroke were initiated. There are in general two strategies in thrombolytic therapy, a local (intraarterial) approach and a systemic (intravenous) application of the thrombolytic agent. Only the latter has been proven to be effective in larger randomized trials and is a Class 1/Level A recommendation in national or international guidelines. This review summarizes the evidence for thrombolytic therapy of acute ischemic stroke with emphasis on progress regarding the approved intravenous treatment. Finally intraarterial approaches as well as combined systemic and interventional therapies are discussed. [ABSTRACT FROM AUTHOR]

The European Hypothermia Stroke Research Workshop was held in January 2010, in response to the alarming prospects of a significant increase of stroke expected in the coming years globally. Considering that a minority of patients (around 10%) are currently eligible for thrombolytic treatment, there is a need for an efficacious, cost-effective novel therapy that can be implemented broadly within European health care systems. Accordingly, the primary objective of the workshop was the definition of a research agenda aiming to assess the therapeutic benefits of hypothermia in patients with acute ischaemic stroke. The meeting was organised by the European Stroke Research Network for Hypothermia (EuroHyp) and attended by the representatives of World Stroke Organisation, European Stroke Organisation, Stroke Alliance for Europe, Society for Cryobiology and other organisations - specifically the European Space Agency, and small- and medium-sized enterprises based in EU member states. The participants adopted the 'Hypothermia for Stroke - Call to Action 2010', a declaration specifying the priorities for hypothermia research in acute ischaemic stroke. The research programme outlined - a clinical study programme designed to identify and validate therapeutic cooling as a novel treatment providing benefit to a large number of stroke patients - contains a well-integrated series of Phase II studies aiming to refine the intervention (depth, duration, and mode of cooling; antishivering strategy; patient selection) and a pivotal Phase III clinical trial. The proposed integrated Phase II and III clinical study programme would test the effectiveness of this optimised intervention, and would allow the development of evidence-based Clinical Practice Guidelines describing the optimal use of therapeutic hypothermia as a treatment strategy for stroke. [ABSTRACT FROM AUTHOR]

Background: The SPAN-100 index adds patient age and baseline NIHSS-score and was introduced to predict clinical outcome after acute ischemic stroke (AIS). Even with high NIHSS-scores younger patients cannot reach a SPAN-100-positive status (index ≥100). We aimed to evaluate the SPAN-100 index among a large, contemporary cohort of i.v.-thrombolysed AIS-patients and exclusively among older patients who can at least theoretically achieve SPAN-100-positivity.Methods: The SPAN-100 index was applied to AIS-patients receiving i.v.-thrombolysis (IVT) in our institution between 01/2006 and 01/2013. Clinical outcome and symptomatic intracerebral hemorrhage rates were compared between SPAN-100-positive and -negative patients. Furthermore we excluded patients < 65 years, without any theoretical chance to achieve SPAN-100-positivity, and re-evaluated the index (SPAN65-100 index).Results: SPAN-100-positive IVT-patients (124/1002) had a 9-fold increased risk for unfavorable outcome compared to SPAN-negative patients (OR 9.39; 95% CI 5.87-15.02; p <  0.001). The odds ratio for mortality was 7.48 (95% CI 4.90-11.43; p <  0.001). No association was found between SPAN-100-positivity and sICH-incidence (OR 0.88; 95% CI 0.31-2.53; p = 0.810). SPAN65-100-positivity (124/741) was associated with an 8-fold increased risk for unfavorable outcome (OR 7.6; 95% CI 4.71-12.22; p <  0.001) but not associated with higher sICH-rates (OR 0.86; 95% CI 0.29-2.53; p <  0.001).Conclusions: Also for patients ≥65 years the SPAN-100 index can be a fast, easy method to predict clinical outcome of IVT-patients in everyday practice. However, it should not be used to determine the risk of sICH after IVT. Based on a SPAN-positive status IVT should not be withheld from AIS-patients merely because of feared sICH-complications. [ABSTRACT FROM AUTHOR]