The reported incidence of all types of stroke in childhood is relatively low, with 2.6 occurring per 100,000 white children and 3.1 per 100,000 in black children (Broderick et al. Child Neurol 1993). However, additional analyses indicate that children with sickle cell disease (SCD) face a huge relative risk of ischemic stroke compared with a healthy population (RR=220; Earley et al. Neurology 1998). Chronic blood transfusion therapy has been employed as secondary prevention of stroke in patients with SCD for over 30 years. This session discussed the epidemiology of SCD as well as the risks and benefits of using chronic transfusion therapy in primary stroke prevention.

Robert J. Adams, MD, Medical University of South Carolina, Charleston, SC, gave an overview of the Stroke Prevention Trial in Sickle Cell Anemia (STOP). Transfusion of every child with SCD is not warranted due to the high number needed (200) to save one child from a stroke, side effects, inconvenience to families, and cost. The STOP trial therefore sought to identify children at highest risk of stroke using transcranial Doppler ultrasound (TCD; Figure 1). Children were screened using TCD, and those with 2 measurements ≥200 cm/s were randomized to either periodic transfusion or standard care (including occasional transfusion). The study found that periodic transfusion reduced the risk of stroke by 92%, reduced other complications, and led to better height and weight gain (Adams et al. NEJM 1998).

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Figure 1.

Stroke Risk Identification Using TCD.

The presentation by Heather Fullerton, MD, University of California, San Francisco, CA, addressed whether the STOP trial findings influenced treatment of SCD patients. Using a California-wide database, Dr. Fullerton and colleagues found a downward trend in strokes in patients with SCD post-1998, the year that the STOP results were published. Data from a Kaiser Permanente cohort showed an upward trend in the numbers of SCD patients obtaining a first TCD post-1998, suggesting that the decrease in strokes were related to the identification of high-risk patients. “We definitely have some cause for optimism. We think that the stroke rates are declining, and we think this is due to implementation of this primary stroke prevention strategy,” commented Dr. Fullerton. Obstacles remain, however. In a survey of 207 hematologists, 9 of 10 reported issues with acquiring TCDs, citing poor patient adherence and lack of facility availability. “This is really an issue for our neurology community, who is trying to make this [technology] increasingly available to these children,” said Dr. Fullerton.

Michael DeBaun, MD, MPH, Washington University, St. Louis, MO, gave an overview of silent cerebral infarctions and future research in SCD-associated stroke prevention. Silent cerebral infarct is defined as an increased signal on T2-weighted imaging that is not accompanied by focal neurologic deficits. “We think about one-fifth of children who have a diagnosis of hemoglobin SS will have a silent cerebral infarct before their 18^th birthday,” said Dr. DeBaun. Silent strokes cause significant cognitive deficits in these patients, leading to problems in learning and poor school performance. The objective of the Silent Cerebral Infarct Transfusion Trial (SITT) is to determine if prophylactic transfusions will result in a reduction of both clinically evident and silent strokes in children with SCD. The trial is ongoing, has randomized 127 patients to date, and will last approximately 6 years. The results of this trial should provide valuable insight into the natural history of SCD and further the understanding of the risks and benefits of transfusion therapy.