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Stroke, sonothrombolysis, alteplase

Aliona Nacu, Christopher E Kvistad, Nicola Logallo, Halvor Naess, Ulrike Waje-Andreassen, Anne Hege Aamodt, Ragnar Solhoff, Christian Lund, Håkon Tobro, Ole Morten Rønning, Rolf Salvesen, Titto T Idicula, Lars Thomassen
BACKGROUND: Ultrasound accelerates thrombolysis with tPA (sonothrombolysis). Ultrasound in the absence of tPA also accelerates clot break-up (sonolysis). Adding intravenous gaseous microbubbles may potentiate the effect of ultrasound in both sonothrombolysis and sonolysis. The Norwegian Sonothrombolysis in Acute Stroke Study aims in a pragmatic approach to assess the effect and safety of contrast enhanced ultrasound treatment in unselected acute ischaemic stroke patients. METHODS/DESIGN: Acute ischaemic stroke patients ≥ 18 years, with or without visible arterial occlusion on computed tomography angiography (CTA) and treatable ≤ 4(½) hours after symptom onset, are included in NOR-SASS...
July 11, 2015: BMC Neurology
Michal Haršány, Georgios Tsivgoulis, Andrei V Alexandrov
Acute ischemic stroke is a medical emergency requiring urgent treatment. Randomized clinical trial and Phase IV data have provided unequivocal evidence that intravenous thrombolysis with recombinant tissue plasminogen activator (rt-PA) improves early functional outcomes by restoring brain perfusion. Moreover, these studies have shed substantial light on the factors which are associated with more favorable outcome with tPA and are related to the highest benefit-to-risk ratio. Stroke physicians should consider vascular imaging techniques to aid decision making with thrombolytic therapy...
August 2014: Expert Review of Neurotherapeutics
Kazunori Toyoda
Intravenous thrombolysis using alteplase was approved for clinical use for acute ischemic stroke treatment in Japan in 2005, on the basis of the results of a domestic clinical trial, Japan Alteplase Clinical Trial. This therapeutic strategy has become the standard strategy during the following 8 years. However, this therapy still has room for improvement. One of the important drawbacks of intravenous thrombolysis is the limited therapeutic time window. On the basis of the results of the European Cooperative Acute Stroke Study III and the pooled analysis, the current time window is within 4...
July 2013: Brain and Nerve, Shinkei Kenkyū No Shinpo
Jun Shimizu, Takahiro Fukuda, Toshiaki Abe, Makoto Ogihara, Jun Kubota, Akira Sasaki, Takashi Azuma, Kazuaki Sasaki, Keiko Shimizu, Takao Oishi, Shin-Ichiro Umemura, Hiroshi Furuhata
We investigated the safety of transcranial-targeting midfrequency (0.1 to 1 MHz) ultrasonic thrombolysis for acute ischemic stroke. We applied a new therapeutic and imaging transducer to healthy Macaca monkey brains via sonication of the ipsilateral middle cerebral artery through an acoustic temporal window. Young adult cynomolgus monkeys (Macaca fascicularis) were assigned to a group without sonication (control), a group maintained for 1 d after sonication (C1) and a group maintained for 7 d after sonication (C7; n = 3 for each)...
June 2012: Ultrasound in Medicine & Biology
Rocco S Calabro, Giuseppe Gervasi, Placido Bramanti, Anna Cavallini
Stroke is the third leading cause of death and the main cause of permanent disability in western countries. Reperfusion within 3 hours of symptoms-onset is the most beneficial of all therapeutic strategies for acute ischemic stroke. Alteplase has been the first thrombolytic treatment approved by FDA. However, its use is still limited to specific patient subgroups and may be complicated by severe side effects, including massive cerebral hemorrhages. This review is aimed at investigating the current and future treatment strategies in ischemic stroke, including new fibrinolytic drugs, sonothrombolysis, mechanical clot retrievals, and recent patents...
April 2012: Recent Patents on Cardiovascular Drug Discovery
Marta Rubiera, Andrei V Alexandrov
Multiple in vitro and animal models have demonstrated the efficacy of ultrasound to enhance fibrinolysis. Mechanical pressure waves produced by ultrasound energy improve the delivery and penetration of alteplase (recombinant tissue plasminogen activator [tPA]) inside the clot. In human stroke, the CLOTBUST phase II trial showed that the combination of alteplase plus 2 hours of continuous transcranial Doppler (TCD) increased recanalization rates, producing a trend toward better functional outcomes compared with alteplase alone...
2010: American Journal of Cardiovascular Drugs: Drugs, Devices, and Other Interventions
Kazunori Toyoda
After the success of the 1995 National Institutes of Neurological Disorders and Stroke (NINDS) study using intravenous (i.v.) recombinant tissue plasminogen activator (rt-PA, alteplase) within 3 hours in acute stroke, this therapy was approved worldwide and has been a standard therapy for acute stroke patients. In Japan, IV alteplase at a dose of 0.6 mg/kg was approved in 2005 after a multicenter study using this low dose of alteplase (Japan Alteplase Clinical Trial [J-ACT]). IV rt-PA can drastically improve stroke outcomes...
November 2009: Rinshō Shinkeigaku, Clinical Neurology
Takahiro Nakashima, Kazuo Minematsu
The US Food and Drug Administration (FDA) approved the use of intravenous (IV) recombinant tissue plasminogen activator (rt-PA) in 1996, on the basis of the results of the National Institute of Neurological Disorders and Stroke (NINDS) rt-PA Stroke Study. IV rt-PA therapy at a dose of 0.9 mg/kg has been approved internationally for the treatment of hyperacute ischemic stroke. After a dose comparison study using duteplase and a multicenter study using a single dose of alteplase (Japan Alteplase Clinical Trial: J-ACT), the administration of IV rt-PA therapy at a dose of 0...
September 2009: Brain and Nerve, Shinkei Kenkyū No Shinpo
Kazuo Minematsu
Japan Alteplase Clinical Trial (J-ACT), a prospective multicenter clinical trial, demonstrated good clinical outcome in patients treated with 0.6 mg/kg of alteplase, being similar to that with 0.9 mg/kg of alteplase in the National Institute of Neurological Disorders and Stroke (NINDS) study. On that basis, intravenous aplteplase therapy was approved in Japan in October, 2005. This therapy resulted in better efficacy and similar safety in our stroke care unit (SCU) as compared to J-ACT or other clinical studies performed outside Japan...
November 2008: Rinshō Shinkeigaku, Clinical Neurology
Michael Daffertshofer, Michael Hennerici
Intravenous alteplase (recombinant tissue plasminogen activator) has been shown to be beneficial within a short 3 h window after stroke. Ultrasound has a thrombolytic capacity that can be used for pure mechanical thrombolysis or improvement of enzyme-mediated thrombolysis. Mechanical thrombolysis with ultrasound needs high intensities at the clot (>2 W/cm2) that may have unwanted side-effects, whereas improvement of enzymatic thrombolysis can be done at the safer energy levels used in diagnostic ultrasound...
May 2003: Lancet Neurology
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