Journal ArticleDOI
Thrombolysis with Alteplase 3 to 4.5 Hours After Acute Ischemic Stroke
Werner Hacke,Markku Kaste,Erich Bluhmki,Miroslav Brozman,Antoni Dávalos,Donata Guidetti,Vincent Larrue,Kennedy R. Lees,Zakaria Medeghri,Thomas Machnig,Dietmar Schneider,Rüdiger von Kummer,Nils Wahlgren,Danilo Toni +13 more
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TLDR
As compared with placebo, intravenous alteplase administered between 3 and 4.5 hours after the onset of symptoms significantly improved clinical outcomes in patients with acute ischemic stroke; altePlase was more frequently associated with symptomatic intracranial hemorrhage.Abstract:
Background Intravenous thrombolysis with alteplase is the only approved treatment for acute ischemic stroke, but its efficacy and safety when administered more than 3 hours after the onset of symptoms have not been established. We tested the efficacy and safety of alteplase administered between 3 and 4.5 hours after the onset of a stroke. Methods After exclusion of patients with a brain hemorrhage or major infarction, as detected on a computed tomographic scan, we randomly assigned patients with acute ischemic stroke in a 1:1 double-blind fashion to receive treatment with intravenous alteplase (0.9 mg per kilogram of body weight) or placebo. The primary end point was disability at 90 days, dichotomized as a favorable outcome (a score of 0 or 1 on the modified Rankin scale, which has a range of 0 to 6, with 0 indicating no symptoms at all and 6 indicating death) or an unfavorable outcome (a score of 2 to 6 on the modified Rankin scale). The secondary end point was a global outcome analysis of four neurologic and disability scores combined. Safety end points included death, symptomatic intracranial hemorrhage, and other serious adverse events. Results We enrolled a total of 821 patients in the study and randomly assigned 418 to the alteplase group and 403 to the placebo group. The median time for the administration of alteplase was 3 hours 59 minutes. More patients had a favorable outcome with alte plase than with placebo (52.4% vs. 45.2%; odds ratio, 1.34; 95% confidence interval [CI], 1.02 to 1.76; P = 0.04). In the global analysis, the outcome was also improved with alteplase as compared with placebo (odds ratio, 1.28; 95% CI, 1.00 to 1.65; P<0.05). The incidence of intracranial hemorrhage was higher with alteplase than with placebo (for any intracranial hemorrhage, 27.0% vs. 17.6%; P = 0.001; for symptomatic intracranial hemorrhage, 2.4% vs. 0.2%; P = 0.008). Mortality did not differ significant ly between the alteplase and placebo groups (7.7% and 8.4%, respectively; P = 0.68). There was no significant difference in the rate of other serious adverse events. Conclusions As compared with placebo, intravenous alteplase administered between 3 and 4.5 hours after the onset of symptoms significantly improved clinical outcomes in patients with acute ischemic stroke; alteplase was more frequently associated with symptomatic intracranial hemorrhage. (ClinicalTrials.gov number, NCT00153036.)read more
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Journal ArticleDOI
Evolution of the Modified Rankin Scale and Its Use in Future Stroke Trials
TL;DR: The 7-level, modified Rankin Scale (mRS) has several major strengths: it covers the entire range of functional outcomes from no symptoms to death, its categories are intuitive and easily grasped by both clinicians and patients, its concurrent validity is demonstrated by strong correlation with measures of stroke pathology and agreement with other stroke scales, and its use has demarcated effective and ineffective acute stroke therapies in trials with appropriately powered sample sizes.
Journal ArticleDOI
Effect of the Use of Ambulance-Based Thrombolysis on Time to Thrombolysis in Acute Ischemic Stroke: A Randomized Clinical Trial
Martin Ebinger,Benjamin Winter,Matthias Wendt,Joachim E. Weber,Carolin Waldschmidt,Michal Rozanski,Alexander Kunz,Peter M. Koch,Philipp A. Kellner,Daniel Gierhake,Kersten Villringer,Jochen B. Fiebach,Ulrike Grittner,Andreas Hartmann,Bruno-Marcel Mackert,Matthias Endres,Heinrich J. Audebert +16 more
TL;DR: Compared with usual care, the use of ambulance-based thrombolysis resulted in decreased time to treatment without an increase in adverse events.
Journal ArticleDOI
Delayed post-ischaemic neuroprotection following systemic neural stem cell transplantation involves multiple mechanisms
Marco Bacigaluppi,Stefano Pluchino,Luca Peruzzotti Jametti,Ertugrul Kilic,Ulkan Kilic,Giuliana Salani,Elena Brambilla,Mark J. West,Giancarlo Comi,Gianvito Martino,Dirk M. Hermann,Dirk M. Hermann +11 more
TL;DR: The effects of a delayed transplantation of adult syngenic NPCs--injected intravenously 72 h after transient middle cerebral artery occlusion--on neurological recovery, histopathology and gene expression and Histopathological analysis revealed a hitherto unreported very delayed neuroprotective effect of NPCs.
Journal ArticleDOI
Matrix Metalloproteinase-2-Mediated Occludin Degradation and Caveolin-1-Mediated Claudin-5 Redistribution Contribute to Blood–Brain Barrier Damage in Early Ischemic Stroke Stage
TL;DR: Investigation of the early molecular events of ischemic BBB damage using in vitro oxygen–glucose deprivation (OGD) and in vivo rat middle cerebral artery occlusion (MCAO) models indicates that cerebral ischemia initiates two rapid parallel processes to cause BBB disruption at early stroke stages relevant to acute thrombolysis.
Journal ArticleDOI
Overcoming the Blood-Brain Barrier: The Role of Nanomaterials in Treating Neurological Diseases.
Denzil Furtado,Mattias Björnmalm,Mattias Björnmalm,Scott Ayton,Ashley I. Bush,Kristian Kempe,Frank Caruso +6 more
TL;DR: The objective is to provide the diverse range of researchers active in the field with an easily accessible guide to the key opportunities and challenges currently facing the nanomaterial‐mediated treatment of neurological diseases.
References
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Thomas Brott,Harold P. Adams,Charles P. Olinger,John R. Marler,William G. Barsan,José Biller,Judith Spilker,R Holleran,Robert Eberle,Vicki S. Hertzberg +9 more
TL;DR: A 15-item neurologic examination stroke scale for use in acute stroke therapy trials was designed and interrater reliability for the scale was found to be high, and test-retest reliability was also high, suggesting acceptable examination and scale validity.
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