KISSIMMEE, FLA. — The administration of microbubbles bolsters the combined thrombolytic effects of ultrasound-enhanced systemic thrombolysis and tissue plasminogen activator and improves outcomes in patients with atherothrombotic stroke, Dr. Marta Rubiera reported at the 31st International Stroke Conference.
In a study of 155 consecutive patients with stroke attributable to middle cerebral artery (MCA) occlusion, patients were allocated to one of three groups. One group received intravenous tissue plasminogen activator (TPA) treatment plus continuous 2-hour, 2-MHz-pulsed-wave transcranial Doppler ultrasound and three intravenous doses of galactose-based microbubbles given at 2, 20, and 40 minutes after TPA bolus. The remaining patients received TPA and ultrasound without microbubble administration or TPA with placebo monitoring.
The 2-hour complete recanalization rate was significantly higher in the microbubble group, compared with the ultrasound and control groups (42% vs. 40% and 24%, respectively), said Dr. Rubiera of the Hospital Vall d'Hebron, Barcelona.
The differences were significant only for those with atherothrombotic stroke, compared with cardioembolic and “undetermined” or “other” types of strokes (which comprised 24%, 49%, 23%, and 4% of stroke types in the study, respectively). In the 37 patients with atherothrombotic stroke, micro-bubbles increased the success rate of 2-hour recanalization 1.5-fold over TPA plus ultrasound (39% vs. 26%), and nearly twofold over TPA alone (39% vs. 21%).
Furthermore, at 3-month follow-up atherothrombotic stroke was significantly associated with a poor outcome in the ultrasound and control groups, but not in the microbubble group, as determined by modified Rankin Scale score, Dr. Rubiera noted.
Patients in the study had a median National Institutes of Health Stroke Scale (NIHSS) score of 16. On transcranial Doppler ultrasound, 76% of the 155 patients had occlusion of the proximal MCA, and 24% had occlusion of the distal MCA. Of those 37 patients with atherothrombotic stroke, 96% had occlusion of both the MCA and internal carotid artery (ICA) occlusion. Patients in all stroke subtype categories were similar with regard to baseline NIHSS, clot locations, and time to treatment.
Ultrasound used for monitoring has been shown to safely enhance thrombolysis by accelerating the transport and penetration of TPA into the clot, according to Dr. Rubiera and her associates.
Microbubbles, small air- or gas-filled microspheres approved for use in Europe and Japan as a contrast agent for ultrasound, appear to disrupt blood clots via cavitation. In a recently published article on the effects of microbubbles on clot lysis during ultrasound monitoring, Dr. Rubiera and her colleagues explained that by acting as cavitation nuclei, microbubbles lower the amount of energy needed for cavitation, and that high-acoustic-pressure ultrasound induces nonlinear oscillations of microbubbles. This process leads to continuous absorption of energy, which eventually causes the bubbles to explode, releasing the absorbed energy, they noted.
“Thus ultrasound-mediated microbubble destruction may further accelerate the clot-dissolving effect of ultrasound,” they wrote (Stroke 2006;37:425–9).
The expanded data presented at the conference, which was sponsored by the American Stroke Association, provide further evidence that microbubble administration during continuous ultrasound monitoring and systemic thrombolysis improves recanalization and outcomes in patients with tandem ICA and MCA occlusion, Dr. Rubiera concluded.