20 Cardiovascular Medicine FA M I LY P R A C T I C E N E W S • F e b r u a r y 1 , 2 0 0 5

Ultrasound Plus Clot Buster Better for Acute StrokeB Y R O B E R T F I N N

San Francisco Bureau

Patients suffering from acute ischemicstroke are significantly more likelyto achieve recanalization and/or ear-

ly or dramatic clinical recovery if throm-bolytic therapy is combined with contin-uous transcranial Doppler sonography,according to a study by Andrei V. Alexan-drov, M.D., of the University of Texas,Houston, and colleagues.

Of 63 patients receiving ultrasound com-bined with tissue plasminogen activator (t-PA), 31 (49%) achieved recanalizationand/or clinical recovery within 2 hours,compared with 19 of 63 patients (30%) whoreceived t-PA combined with sham sonog-raphy. Within 2 hours, 16 (25%) of the pa-tients in the treatment group experiencedboth recanalization and clinical recovery,compared with 5 (8%) of the control group.Both differences were statistically signifi-cant (N. Engl. J. Med. 2004;351:2170-8).

All patients had occlusions of the mid-dle cerebral artery, and all were treatedwithin 3 hours of the onset of symptoms.The patients were randomly assigned tothe treatment or the control group.

Known as the Combined Lysis ofThrombus in Brain Ischemia Using Tran-scranial Ultrasound and Systemic t-PA(CLOTBUST) trial, the study was fundedin part by the National Institute of Neu-rological Disorders and Stroke, a unit ofthe National Institutes of Health.

This phase II study, although not de-signed to look at clinical outcomes 3months after treatment, showed that of the53 patients eligible for follow-up, 22 (42%)had achieved a modified Rankin score of 0or 1, compared with 4 of the 15 eligible pa-tients (27%) in the control group.Investigators calculated that a phase IIIstudy would need just 274 patients in eachgroup to replicate the results with statisti-cal significance.

“At our center, it’s the standard of careright now,” he said. “Both [t-PA and tran-scranial Doppler sonography] are FDA-ap-proved technologies, and the trial was ex-

empt frominvestigationalnew drug statusby FDA be-cause these re-sults would notchange the la-bels. Right nowin our institu-tion, when wegive systemic t-PA within 3hours [after astroke], we al-ways put a t r a n s c r a n i a l

Doppler probe on the scalp to help the pa-tient pass the clot faster.”

Nevertheless, “I will not stand here andrecommend that everybody else should dothe same,” Dr. Alexandrov said. “The rea-son is that to do it right, you have to passthrough a very lengthy and labor-intensetraining that is not a routine part of anyneurology residency. To do the protocol,you need 1-6 months of daily practicing ofthis technique under supervision, andthat’s something that very few programscan do in the United States.”

Dr. Alexandrov is involved in an effortto design an operator-independent devicethat would obviate the need for an expe-rienced operator. With such a device, “anemergency department physician coulddo it, a neurologist could do it, and a nursecould mount the ultrasound machine onthe head,” he said.

The mechanism by which transcranialDoppler sonography improves thrombol-ysis is still unclear. In a commentary ac-companying Dr. Alexandrov’s paper,Joseph F. Polak, M.D., of Tufts University,Boston, weighs a number of the possibil-ities (N. Engl. J. Med. 2004;351:2154-5).

It’s clear that the mechanism does notinvolve cavitation, which ultrasound athigh energies can cause. It’s also unlike-ly that the relatively low energies used intranscranial Doppler ultrasound couldaccelerate thrombolysis by producingheat.

Dr. Alexandrov believes that the com-bined treatment works because ultrasoundis causing a gentle mechanical pressurewave, which delivers more t-PA moleculesto and through the clot.

The study was sparked by a observation,Dr. Alexandrov said. “Patients who werewearing these transducers for diagnosticpurposes started to move their paralyzedarms and legs and to talk to us much fasterthan we ever expected otherwise.” ■

Patients ‘wearingthese transducersfor diagnosticpurposes startedto move theirparalyzed armsand legs and totalk to us muchfaster than weever expected.’