Ultrasound enhanced tPA for stroke

An article in yesterday’s NEJM on Ultrasound-enhanced systemic thrombolysis for acute ischemic stroke was the first I had seen on thrombolysis for CVA in quite a while (the last major trial on t-PA for stroke published in the NEJM, which I reviewed here, was 9 years ago). And a quick PubMed search yielded this study from Cleveland, which indicates that only about 2% of strokes nationwide receive t-PA, mainly because of the 3 hour time requirement from onset of symptoms.

Ultrasound energy has been shown to facilitate the activity of fibrinolytic agents. Experimental work with lower frequency (Kilohertz) ultrasound in conjunction with t-PA had previously shown an increased risk of hemorrhage. This effect has not been noted with higher frequency (MHz) transcranial diagnostic ultrasound which has been used to look at the patency of cerebral arteries. The current phase II trial was designed to examine the effects of continuous, high frequency transcranial doppler monitoring, in conjunction with t-PA, on hemorrhage, patency and recovery rates.

126 stroke patients who presented early with evidence of abnormal flow through the middle cerebral artery were randomized into two groups of 63 patients. Both groups received t-PA, and both groups had transcranial doppler measurements that checked the flow at 0, 30, 60, 90 and 120 minutes. Patients in the target, ultrasound group had diagnostic ultrasound insonation that was continuous for the two hours; patients in the placebo group only received the diagnostic ultrasound at the prespecified times.

Patients in the target ultrasound group did better, in terms of both recanalization and clinical improvement (NS, however), without any difference in intracranial hemorrhage:

Continuous ultrasound Placebo ultrasound
Complete recanalization within 2 hours 46% 18% (p<0.001)
Clinical recovery within 2 hours 29% 21% (NS)
Favorable outcome at 3 months (modified Rankin score of 0 or 1) 42% 29% (NS)

These results are encouraging and presumably more studies will be undertaken to see what the optimal ultrasound approach should be (energy level, duration of therapy). If this pans out, the benefit of thrombolytic therapy would be more convincing than it is at present, and might bolster enthusiasm for its use. The addition of another technological requirement to stroke management would complicate matters somewhat, and might make a more effective case for centralizing stroke treatment.

Most fascinating is a report, cited by Medpundit, that indicates a possible beneficial effect of ultrasound alone in the management of stroke! This comes from an anecdotal report by a physician in Scotland.