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Table of Contents    
Year : 2017  |  Volume : 65  |  Issue : 1  |  Page : 20-21

Sonothrombolysis: An effective adjunct to intravenous tissue plasminogen activator therapy in acute ischemic stroke

Department of Neurosurgery and Neuroendovascular Therapy, Osaka Medical College, 2-7, Daigaku-machi, Takatsuki, 569-8686, Osaka, Japan

Date of Web Publication12-Jan-2017

Correspondence Address:
Dr. Shigeru Miyachi
Department of Neurosurgery and Neuroendovascular Therapy Osaka Medical College 2-7, Daigaku-machi, Takatsuki, 569-8686, Osaka
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0028-3886.198180

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How to cite this article:
Miyachi S. Sonothrombolysis: An effective adjunct to intravenous tissue plasminogen activator therapy in acute ischemic stroke. Neurol India 2017;65:20-1

How to cite this URL:
Miyachi S. Sonothrombolysis: An effective adjunct to intravenous tissue plasminogen activator therapy in acute ischemic stroke. Neurol India [serial online] 2017 [cited 2021 Oct 27];65:20-1. Available from:

Sonothrombolysis is one of the promising methods designed to enhance the effects of intravenous tissue plasminogen activator (IV tPA) therapy. Its efficacy had been reported in the experimental work published over 20 years ago. Lu et al.,[1] reported that microbubble-mediated sonothrombolysis improved the outcomes of microthrombi-induced acute ischemic stroke in an experimental occlusion model. Recently, several new clinical studies have been reported. In particular, the Combined Lysis of Thrombus in Brain Ischemia With Transcranial Ultrasound and Systemic tPA (CLOTBUST) trial has been the most significant study that addresses the clinical application of this treatment option.[2] The authors from this study concluded that outcomes for patients treated with a combination of 1-MHz focused ultrasound pulses with microbuble administration strongly enhanced the enzymatic thrombolytic efficacy of IV-tPA therapy. From a technical point of view, transcranial Doppler (TCD) monitoring may be a reasonable non-invasive and time-saving method and also may be advantageous in confirming recanalization without injection of a contrast material.[3]

According to Barreto et al.,[4] this method of sonothrombolysis is an operator-independent device, and is considered safe with achievement of higher recanalization rates in combination with systemic tPA. Moreover, thrombectomy requires an experienced operator, involves a more advanced technique and is much more invasive than sonothrombolysis. However, the successful use of this new method of sonothrombolysis also seems to depend on the operator's skill and ability because it is difficult to keep the TCD monitor precisely at the best detectable position. An extensive training with a potentially steep learning curve may be a challenge for achieving consistent detection of the occluded and non-signalled vessels especially while operating within the tight time-constraints in an acute stroke setting.

Currently, the recommended and most effective method for achieving acute recanalization following IV-tPA includes the mechanical thrombectomy with aspiration or stentriever, as has been approved in the American Heart Association/American Stroke Association (AHA/ASA) guidelines.[5] However, Renhard et al.,[6] demonstrated that sonothrombolysis is not less inferior to thrombectomy in the case of middle cerebral artery occlusion. Prospective studies have not been undertaken yet; however, this method has proven to be a valid adjunct to IV-tPA. In contrast, the authors pointed out that the result and outcome for the patients with internal carotid artery terminal (T)-occlusion demonstrated no superiority using this method. This result may indicate that small amounts of clots can be shattered, while large emboli are more difficult to fragment for the main vessel to be recanalized. Some pieces of broken clot may also migrate and occlude the distal branches. Actually, mechanical thrombolysis with a micro-guidewire has been previously performed using a transarterial approach for the cases demonstrating very hard clots. This method dates back to the time when local intraarterial fibrinolysis was performed using urokinase. However, such aggressive maneuvers carry a high risk of showering of emboli into the distal circulation. In this sense, the indications for sonothrombolysis should be tailored and defined based on the clot position and size.

Although this new method of sonothrombolysis is not a first-choice treatment, as the authors addressed in the study in focus,[7] it may be one of the supportive options to enhance the effect of IV-tPA, especially under conditions where there is lack of specialized radiological equipment, stroke specialists, and staff to handle the emergency care. We look forward to the result of on-going randomized trials to judge the efficacy of sonothrombolysis.[8]

  References Top

Lu Y, Wang J, Huang R, Chen G, Zhong L, Shen S, Zhang C, Li X, Cao S, Liao W, Liao Y, Bin J. Microbubble-mediated sonothrombolysis improves outcome after thrombotic microembolism-induced acute ischemic stroke. Stroke 2016;47:1344-53.  Back to cited text no. 1
Papadopoulos N, Yiallouras C, Damianou C. The enhancing effect of focused ultrasound on TNK-tissue plasminogen activator-induced thrombolysis using an in vitro circulating flow model. J Stroke Cerebrovasc Dis 2016; pii: S1052-3057(16) 30270-1. doi: 10.1016/j.jstrokecerebrovasdis.2016.07.052.  Back to cited text no. 2
Saqqur M, Uchino K, Demchuk AM, Molina CA, Garami Z, Calleja S, et al; CLOTBUST Investigators. Site of arterial occlusion identified by transcranial Doppler predicts the response to intravenous thrombolysis for stroke. Stroke 2007;38:948-54  Back to cited text no. 3
Barreto AD, Alexandrov AV, Shen L, Sisson A, Bursaw AW, Sahota P, et al. CLOTBUST-Hands Free: Pilot safety study of a novel operator-independent ultrasound device in patients with acute ischemic stroke. Stroke. 2013;44:3376-81.  Back to cited text no. 4
Powers WJ, Derdeyn CP, Biller J, Coffey CS, Hoh BL, Jauch EC, et al. 2015 American Heart Association/American Stroke Association focused update of the 2013 guidelines for the early management of patients with acute ischemic stroke regarding endovascular treatment: A guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2015;46:3020-35.  Back to cited text no. 5
Reinhard M1, Taschner CA, Hörsch N, Allignol A, Maurer CJ, Niesen WD, et al. Endovascular treatment versus sonothrombolysis for acute ischemic stroke. Cerebrovasc Dis 2015;40:205-14.  Back to cited text no. 6
Aaron S, Mani S, Prabhakar AT, Suresh Babu P, Kumar S, Benjamin RN, et al. Sonothrombolysis for acute ischemic stroke: Break through to the other side. Neurol India 2017;65:52-7.  Back to cited text no. 7
  Medknow Journal  
Nacu A, Kvistad CE, Logallo N, Naess H, Waje-Andreassen U, Aamodt AH, et al. A pragmatic approach to sonothrombolysis in acute ischaemic stroke: The Norwegian randomised controlled sonothrombolysis in acute stroke study (NOR-SASS). BMC Neurol 2015;15:110.  Back to cited text no. 8


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