The Consensus Statement is formed as a recommendation to the European Stroke Organisation (ESO) on revision of ESO Guidelines. Please note that the final text of the Guidelines, is decided by ESO and that the recommendation in this document may not be the final guidelines version. As soon as the guidelines are confirmed, they will appear on this website as well as on the ESO website www.eso-stroke.org
Karolinska Stroke Update Consensus Statement and Recommentations to the European Stroke Organisation Guidelines Committee
Reperfusion Therapy - Sonothrombolysis
The following Consensus Statement was adopted by the 8th Karolinska Stroke Update meeting on November 15, 2010.
The consensus statement was proposed by the chairman of the session, David Russell, Oslo, and the session secretary Dr Tiago Moreira, Stockholm, together with the speakers of the session. The statement was then finally approved by the participants of the meeting, after listening to the different presentations.
The speakers in this session were Dr Robert Mikulik, Brno and Professor Stephen Meairs, Mannheim.
Controversy to discuss at the 2010 consensus session:
- Which are the current evidence and future perspectives for sonothrombolysis in acute ischaemic stroke?
Background, current evidence
Continuous monitoring with 2 MHz, pulsed wave transcranial Doppler ultrasound during tPA infusion has demonstrated an increased rate of early recanalization with no increase in intracranial bleeding, compared to tPA alone, in a phase II randomized clinical trial [1] (Class II).
Another multicenter clinical trial, however, showed that transcranial Doppler with low-frequency ultrasound (300 kHz) increased the rate of cerebral hemorrhages in patients who were being treated with intravenous tPA [2]. (Class II)
The thrombolytic effects of transcranial Doppler ultrasound can be further facilitated by the administration of microbubbles [3,4,5,6] (Class III). Further, larger clinical randomized trials are necessary.
Future progress with regard to therapeutic bubble sonothrombolysis will be facilitated by the development of dedicated transcranial ultrasound instrumentation. This may include operator-independent instrumentation and information regarding intracranial acoustic pressure and cavitation [7,8].
There is also growing evidence from experimental studies which suggest that therapeutic bubble sonothrombolysis may promote reperfusion in the cerebral microcirculation [9,10]. Moreover, clot lysis may be possible with ultrasound and microbubbles alone [7] (Class IV).
Recommendation
At present, there is not enough evidence to recommend the routine use of transcranial Doppler ultrasound during thrombolysis.
References
1. Alexandrov AV, Molina CA, Grotta JC, et al. Ultrasound-enhanced systemic thrombolysis for acute ischemic stroke. N Engl J Med 2004;351:2170-2178.
2. Daffersthofer M, Gass A, Ringleb P et al. Transcranial low-frequency ultrasound-mediated thrombolysis in brain ischemia: increased risk of hemorrhage with combined ultrasound and tissue plasminogen activator: results of a phase II clinical trial. Stroke 2005;36(7):1441-1446.
3. Molina CA, Ribo M, Rubiera M et al. Microbubble administration accelerates clot lysis during continuous 2-MHz ultrasound monitoring in stroke patients treated with intravenous tissue plasminogen activator. Stroke 2006;37:425-429.
4. Alexandrov AV, Mikulik R, Ribo M et al. A pilot randomized clinical safety study of
sonothrombolysis augmentation with ultrasound-activated perflutren-lipid
microspheres for acute ischemic stroke. Stroke. 2008;39:1464-1469.
5. Molina CA, Barreto AD, Tsivgoulis G et al. Transcranial ultrasound in clinical
sonothrombolysis (TUCSON) trial. Ann Neurol. 2009;66:28-38.
6. Tsivgoulis G, Eggers J, Ribo M et al. Safety and efficacy of ultrasound-enhanced
thrombolysis: a comprehensive review and meta-analysis of randomized and
nonrandomized studies. Stroke;41:280-287.
7. Meairs S, Culp W. Microbubbles for thrombolysis of acute ischemic stroke. Cerebrovasc Dis 2009;27 Suppl 2:55-65.
8. Fatar M, Stroick M, Griebe M et al. Effect of combined ultrasound and microbubbles treatment in an experimental model of cerebral ischemia. Ultrasound Med Biol 2008;34(9):1414-20.
9. Nedelmann M, Ritschel N, Doenges S et al. Combined contrast-enhanced ultrasound and rt-PA treatment is safe and improves impaired microcirculation after reperfusion of middle cerebral artery occlusion. J Cereb Blood Flow Metab 2010; 30(10):1712-20.
10. Xie F, Lof J, Matsunaga T et al. Diagnostic ultrasound combined with glycoprotein IIb/IIIa-targeted microbubbles improves microvascular recovery after acute coronary thrombotic occlusions. Circulation 2009; 17:119(10):1378-85.
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