Document Detail

Ultrasound enhanced thrombolysis for stroke.
MedLine Citation:
PMID:  18706065     Owner:  NLM     Status:  MEDLINE    
In the pivotal clinical trials of intravenous tissue plasminogen activator (TPA) therapy, a low rate of early arterial recanalization was suspected because only a few stroke patients may have had early dramatic clinical improvement. Tissue plasminogen activator activity can be enhanced with ultrasound, including 2 MHz transcranial Doppler (TCD). Transcranial Doppler identifies residual blood flow signals around thrombi, and, by delivering mechanical pressure waves, exposes more thrombus surface to circulating TPA. For the first time in clinical medicine, the international multicenter CLOTBUST trial showed that ultrasound enhances the thrombolytic activity of a drug in humans, thereby confirming multidisciplinary experimental research conducted worldwide for the past 30 years. In the CLOTBUST trial, the dramatic clinical recovery from stroke coupled with complete recanalization within 2 h after TPA bolus occurred in 25% of patients treated with TPA+TCD compared with 8% who received TPA alone (P=0.02). Complete clearance of a thrombus and dramatic recovery of brain functions during treatment are feasible goals for ultrasound-enhanced thrombolysis that can lead to sustained recovery. An early boost in brain perfusion seen in the target CLOTBUST group resulted in a trend of 13% more patients achieving favorable outcome at 3 months. To further enhance the ability of TPA to break up thrombi, current ongoing clinical trials include phase II studies of 2 MHz TCD with ultrasound contrast agents or (microbubbles): TCD+TPA+Levovist; TCD+TPA+MRX nano-platform (C(3)F(8)). Intra-arterial TPA delivery can be enhanced with 1 x 7-2 x 1 MHz pulsed wave ultrasound (EKOS catheter, IMS trial). Dose escalation studies of microbubbles, ultrasound exposure, and the development of an operator-independent ultrasound device are underway.
Andrei V Alexandrov
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Review    
Journal Detail:
Title:  International journal of stroke : official journal of the International Stroke Society     Volume:  1     ISSN:  1747-4949     ISO Abbreviation:  -     Publication Date:  2006 Feb 
Date Detail:
Created Date:  2008-08-18     Completed Date:  2008-11-18     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101274068     Medline TA:  Int J Stroke     Country:  England    
Other Details:
Languages:  eng     Pagination:  26-9     Citation Subset:  IM    
Stroke Research and Neurosonology Program, Barrow Neurologic Institute, Phoenix, AZ, USA.
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MeSH Terms
Combined Modality Therapy
Controlled Clinical Trials as Topic
Infusions, Intravenous
Stroke / diagnosis,  therapy*,  ultrasonography
Tissue Plasminogen Activator / administration & dosage,  therapeutic use
Ultrasonic Therapy / methods
Ultrasonography, Doppler, Transcranial / methods*
Grant Support
1 K23 NS-02 229-01/NS/NINDS NIH HHS
Reg. No./Substance:
EC Plasminogen Activator

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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