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Study suggests stroke-prevention strategy for kids pioneered at MCG is working


The incidence of first stroke in children with sickle cell disease in California has taken a nose-dive since 1998 and the likely reason is a program developed at the Medical College of Georgia to identify and treat kids at risk, a new study says.

The study by the University of California, San Francisco published in the current issue of Blood, looked at nearly two-thirds of the state’s children at high risk for stroke. Researchers found better than an 80 percent reduction in first strokes, a decline that began soon after the National Institutes of Health issued a clinical alert saying regular blood transfusions could dramatically reduce stroke risk.

"Among Californian children with sickle cell disease, stroke rates were relatively stable in the eight years leading up to the STOP study and then declined significantly (by more than 80 percent) over the subsequent two years," writes the research team, led by Dr. Heather J. Fullerton, neurologist.

MCG’s STOP study began in 1995 following 130 at-risk children age 2-16 at 14 sites in the United States and Canada. It found a 90 percent reduction in strokes in patients receiving regular blood transfusions, prompting the NIH to halt the $12.1 million study funded by the National Heart, Lung and Blood Institute 16 months early so that doctors and consumers could learn the news.

"This is the first objective evidence from another source of what we predicted should happen if people followed the strategy that was proven to be effective in the STOP study: that new strokes ought to be reduced significantly," said Dr. Robert J. Adams, MCG neurologist who is second author on the Blood study and was principal investigator on the original STOP study.

California children requiring hospitalization for all reasons related to their sickle cell disease remained stable during the study period of 1991 to 2000, researchers say in the newly published study. "That indicates that declining stroke rates in California’s children do not represent some general advance in sickle cell disease treatment because figures do not indicate that hospitalizations for all problems related to this disease are experiencing similar declines," Dr. Adams says.

Dr. Adams and Dr. Virgil C. McKie, MCG Professor Emeritus of Pediatrics and retired chief of the Section of Pediatric Hematology/Oncology, demonstrated in 1992 that the painless, relatively inexpensive transcranial Doppler is a good way to identify kids at high risk for stroke. The technique measures blood flow rates in the brain. They followed with the first STOP study that identified transfusions as a way to reduce stroke risk. Dr. Adams is principal investigator on STOP II that seeks to identify the optimal duration for transfusions that maximizes stroke prevention and minimizes transfusion-related problems.

A recent study by Dr. Adams and his colleagues published in the May 15, 2004 issue of Blood confirmed the predictive value of transcranial Doppler. Researchers looked at 2,000 children who had been screened. They found that younger children whose blood flow rates approached the threshold for stroke risk are likely to cross that threshold and that older children with normal Doppler studies likely will continue to be stroke free.

Yet, despite significant and growing evidence of the efficacy of transcranial Doppler in identifying children at risk and transfusions to help them, Dr. Adams worries that many children still are not getting screened.

One objective cause for his concern came from a survey presented in 2001 at the American Society of Hematology’s annual meeting. The survey of 236 pediatric hematologists-oncologists who treat children with sickle cell disease showed transcranial Doppler was available to 79 percent of the doctors but only 27 percent were confident that their results using Doppler were reproducible or interpretable. Also, only 36 percent of the doctors said they would strongly recommend transfusions as the best treatment option when children were identified at risk. Children with a 10 percent risk of stroke per year, a risk about 20 times that of a healthy child, are categorized as high risk. The California study showed the majority of those children were between ages 5 and 14.

"I know that when I talk with practitioners around the country who are not involved in STOP, they are doing some screening but not all kids are being screened," Dr. Adams says. He hopes one day that all children with sickle cell will be screened by about age 2. Then the families of those found at risk can at least discuss the contributions and complications of transfusions with their health care providers, he says.

Meanwhile, MCG continues to offer courses in transcranial Doppler screening to help more health care professionals become proficient with the technique. Dr. Adams also is working with researchers at Washington University to see whether magnetic resonance imaging or MRI – a commonly used, albeit more costly study – is a good substitute for transcanial Doppler.

Still, he noted that by the time a type of MRI called magnetic resonance angiogram, which provides three-dimensional images of blood vessels, is abnormal, the child already has significant vessel disease in the brain; transcranial Doppler often can identify problems before they show up on the more costly study. "This suggests we can intervene at a time before the blood vessel disease is established, which is the best time to do it," Dr. Adams says. "It suggests that not only does intervention prevent the clinical event (the stroke) and its resulting disability, it suggests also that it prevents the worsening of vascular disease down the road which is likely to cause further problems."

Toni Baker | EurekAlert!
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