High Rate of Complete Recanalization and Dramatic Clinical Recovery During tPA Infusion When Continuously Monitored With 2-MHz Transcranial Doppler Monitoring
To the Editor:
Alexandrov et al1 raise a fascinating possibility in their paper on transcranial Doppler monitoring of recanalization during systemic tPA infusion in acute ischemic stroke. They postulate that ultrasonic energy focused on intracranial thrombus might facilitate thrombolysis. It is easy to imagine how an even more precise beam of energy could be directed at intracranial thrombus with the goal of clot dissolution; why not combine MR angiography with stereotactically delivered magnetic or radiation energy? Could this be a stroke treatment of the future, using technology that exists now?
- Copyright © 2000 by American Heart Association
Alexandrov AV, Demchuk AM, Felberg RA, Christou I, Barber PA, Burgin WS, Malkoff M, Wojner AW, Grotta JC. High rate of recanalization and dramatic clinical recovery during tPA infusion when continuously monitored with 2-MHz transcranial Doppler monitoring. Stroke.. 2000;31:610–614.
I would like to thank Dr Blacker for his letter that highlights an intriguing possibility of using beams, waves, and fields of different physical nature to treat stroke. Indeed, the ideas of thrombolysis with ultrasound alone R1 or combined with a lytic drugR2 have been expressed long ago and since confirmed by many in several in vitro and animal experiments. Technological advances in other areas broadened applications of magnetic resonance into the interventional arena: image guided tracking of vascular guidewiresR3 and better focusing of an electron beam therapy in terms of dose distribution in biological tissues R4 . Improvements in computer technology and development of portable high resolution diagnostic and interventional equipment can one day make these “Star-Trek” visions of future therapies a reality in the emergency rooms and physician offices.
A necessary step, however, has to cover this gap in time: demonstration of safety and efficacy. The first concern is that focusing on a clot any beam or field (that is strong enough to induce or promote clot lysis) may also damage the ischemic tissue. For instance, a prolonged 0.5°C increase in temperature of the ischemic tissue during clot-busting exposure may negate all benefits of early reperfusion. The second problem lies in selection of end points that should be realistic and relevant to the patient. The goal of new clot-disrupting therapies (besides ready availability and reasonable cost) should be to shorten the time to complete recanalization without an increased risk of hemorrhage. If achieved, this can lead to the dramatic recovery during treatment in a larger number of patients that is currently expected.
Enhancement of pharmacological treatment by various physical agents combined with noninvasive monitoring may prove the right direction for stroke therapy. We are embarking on a phase II multicenter randomized trial of intravenous tissue plasminogen activator with or without 2-MHz transcranial Doppler monitoring as the only way to confirm our pilot observations.R5 Until such results become available, all of the above remain an attractive hypothesis.
Trubestein R, Bernard HR, Etzel F., Sobbe A, Cremer A, Stumpff U. Thrombolysis by ultrasound. Clin Sci Mol Med.. 1976;51:697–698.
Tachibana K, Tachibana S. Ultrasonic vibration for boosting fibrinolytic effects of urokinase in vivo. Thromb Haemost.. 1981;46:211. Abstract.
Alexandrov AV, Demchuk AM, Felberg RA, Christou I, Barber PA, Burgin WS, Malkoff M, Wojner AW, Grotta JC. High rate of complete recanalization and dramatic clinical recovery during TPA infusion when continuously monitored by 2 MHz transcranial Doppler monitoring. Stroke. 2000:31:610-614.