March 4, 2010 (San Antonio, Texas) — Sonothrombolysis — the process of using ultrasonography to augment thrombolytic therapy — appears to be safe and effective in evacuating blood clots in patients with spontaneous intraventricular hemorrhage (IVH) and intracerebral hemorrhage (ICH).
A small safety study presented here at the International Stroke Conference 2010 shows that the combination of tissue plasminogen activator (tPA) and 24 hours of continuous ultrasonography produced significant hemorrhage reductions compared with baseline with no significant episodes of rebleeding on clinical and computed tomographic (CT) assessment.
In addition, outcomes at 30 days as measured by the National Institutes of Health Stroke Scale (NIHSS) showed significant improvement in 7 of 9 patients included in the study.
"There's really no good proven treatment to evacuate hemorrhage [in this patient population]," principal investigator David W. Newell, MD, executive director, Swedish Neuroscience Institute, Seattle, Washington, told reporters attending a press conference here.
|Dr. David W. Newell|
Previous modalities to evacuate hemorrhage have met with limited success and have included surgical treatments and stereotactic aspiration, where catheters are placed into the hemorrhage and mechanical retrieval devices are used to remove the clot, Dr. Newell explained.
It has been known for some time that ultrasonography had a pronounced effect in promoting the thrombolytic to dissolve clots, and it has been used for this purpose to dissolve peripheral clots in the venous and arterial systems, as well as pulmonary emboli, and transcranially to treat middle cerebral artery clots.
No Effective Treatment
Known as the Safety of Lysis with EKOS Ultrasound in the Treatment of Intracerebral and Intraventricular Hemorrhage (SLEUTH) study, this new research, added Dr. Newell, shows promise as a minimally invasive treatment option for ICH, which accounts for approximately 15% to 20% of the 800,000 strokes that occur in the United States every year.
Although there is no effect of ultrasonography on the actual chemical reaction of the clot breakdown, it is thought to assist in "pushing" the tPA through the clot to help break it down, explained Dr. Newell.
Previous research led by Daniel F. Hanley, professor of neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, showed that catheter-based clot lysis using low-dose tPA is safe and significantly improved outcomes in patients with IVH.
In this study, known as the Clot Lysis: Evaluating Accelerated Resolution of Intraventricular Hemorrhage (CLEAR-IVF) trial, Dr. Hanley (who is also a coinvestigator in the SLEUTH trial) and colleagues demonstrated that administration of 1 mg of tPA every 8 hours to a maximum of 4 days was effective in evacuating intracerebral clots and reduced expected mortality by 70%.
According to Dr. Newell, this current work is an attempt to extend the results of CLEAR-IVF to determine whether the addition of ultrasonography to catheter-based tPA is safe and has the potential to hasten clot lysis.
For the study, the investigators screened 33 patients with IVH or ICH between November 2008 and July 2009 and enrolled 9 subjects — 6 with ICH and 3 with IVH.
Faster Rate of Lysis
The age of the patients ranged from 38 to 83 years (mean age, 63 years); 6 were male and 3 female. All had symptoms for <12 hours before diagnostic CT scan and had spontaneous ICH >25 mL and/or IVH obstructing the third and/or fourth ventricles.
Using a portable neuronavigation system, the investigators stereotactically placed a ventricular drainage catheter and ultrasound microcatheter through a burr hole in the skull directly into the center of the IVH or ICH. Patients with ICH were given three 3-mg doses of tPA every 8 hours, and those with IVH received three 1-mg doses of the thrombolytic agent every 8 hours.
In addition, all patients received 24 hours of continuous ultrasonography delivered via the ultrasound microcatheter, and the clot was allowed to drain passively via gravity drainage.
Patients were monitored for rebleeding 6 times during the 24-hour period using a portable CT scan, which was brought to the bedside
The investigators found that the mean percentage volume reduction after 24 hours of treatment compared with baseline scans was 59% for ICH and 45.1% for IVH. The researchers report that there were no significant instances of rebleeding.
The addition of ultrasonography also had a significantly faster rate of lysis during the first 24 hours of treatment for both ICH and IVH compared with previous studies, including CLEAR-IVF, which used the same protocol but without ultrasonography and took 3 to 4 days for the clot to resolve.
Of the 9 patients in the study, 1 died and 1 with ICH was excluded from the final analysis because of a catheter breakage. At 30-day follow-up, researchers observed a significant reduction in NIHSS scores with an average overall decrease of 8.5 points — from 17 at baseline to 8.5 at 30 days.
Dr. Newell said these encouraging results warrant larger, clinical trials of catheter drainage testing sonothrombolysis in this patient population.
Treatment for the Untreatable?
Commenting on the study for Medscape Neurology, Cheryl Bushnell, MD, MHS, assistant professor of neurology, Wake Forest University, Winston-Salem, North Carolina, said the finding are promising and show the potential to treat a largely "untreatable" population.
However, she added, there is clearly a need for larger studies. Dr. Bushnell told Medscape Neurology that if findings from future research are positive, then "many more patients will have to be enrolled, but if it is proven to be safe and efficacious, patients with intracerebral hemorrhages will not only have a better chance of survival but will survive with much better outcomes.
"It is also a very nice team approach to treating patients with intracerebral hemorrhages, including neurosurgeons, neurologists, interventionalists, and perhaps sonographers. It is all very exciting, and I look forward to seeing more about this procedure in the future," Dr. Bushnell said.
The study authors have disclosed no relevant financial relationships.
International Stroke Conference (ICS) 2010: Abstract 192. Presented February 25, 2010.
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Cite this: Sonothrombolysis Effective in Clot Evacuation in Intracerebral Hemorrhage - Medscape - Mar 04, 2010.