Document Detail

Ultrasound-enhanced thrombolysis in acute ischemic stroke: potential, failures, and safety.
MedLine Citation:
PMID:  17599707     Owner:  NLM     Status:  MEDLINE    
Experimental and pilot clinical evidence shows that thrombolysis with intravenous tissue plasminogen activator (TPA) can be enhanced with ultrasound. Ultrasound delivers mechanical pressure waves to the clot, thus exposing more thrombus surface to circulating drug. The international multicenter phase II CLOTBUST trial showed that, in patients with acute ischemic stroke, transcranial Doppler (TCD) monitoring augments TPA-induced arterial recanalization, with a nonsignificant trend toward an increased rate of recovery from stroke, compared with placebo. In the CLOTBUST trial, the dramatic clinical recovery from stroke coupled with complete recanalization within 2 hours after TPA bolus occurred in 25% of patients treated with TPA + TCD (n = 63), compared with 8% of those who received TPA alone (n = 63, P = 0.02). Different results were achieved in smaller studies that used transcranial color-coded duplex sonography (TCCD) and a nonimaging therapeutic ultrasound system. The findings of the TRUMBI trial (26 patients) underscored the adverse bioeffects of mid-kilohertz (300 kHz) ultrasound, such as promotion of bleeding in brain areas both affected and unaffected by ischemia. Exposure to multifrequency, multielement duplex ultrasound resulted in a trend toward a higher risk of hemorrhagic transformation. To further enhance the ability of TPA to break up thrombi, current ongoing clinical trials include phase II studies of a single-beam, 2-MHz TCD with perflutren lipid microspheres. Enhancement of intra-arterial TPA delivery is being clinically tested with 1.7-2.1 MHz pulsed-wave ultrasound (EKOS catheter). Multinational dose escalation studies of microspheres and the development of an operator-independent ultrasound device are underway.
Georgios Tsivgoulis; Andrei V Alexandrov
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Review    
Journal Detail:
Title:  Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics     Volume:  4     ISSN:  1933-7213     ISO Abbreviation:  -     Publication Date:  2007 Jul 
Date Detail:
Created Date:  2007-06-29     Completed Date:  2007-10-12     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  101290381     Medline TA:  Neurotherapeutics     Country:  United States    
Other Details:
Languages:  eng     Pagination:  420-7     Citation Subset:  IM    
Comprehensive Stroke Center, Department of Neurology, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
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MeSH Terms
Clinical Trials as Topic
Fibrinolytic Agents / therapeutic use*
Stroke / therapy*
Thrombolytic Therapy / methods*
Tissue Plasminogen Activator / therapeutic use*
Ultrasonic Therapy*
Ultrasonography, Doppler, Transcranial*
Grant Support
1 K23 NS-02229-01/NS/NINDS NIH HHS
Reg. No./Substance:
0/Fibrinolytic Agents; EC Plasminogen Activator

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