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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). [ABSTRACT FROM AUTHOR]

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, placebocontrolled 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. [ABSTRACT FROM AUTHOR]

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 Inter Cert). 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. [ABSTRACT FROM AUTHOR]

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. [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]