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Silent, Dark and Deep: Where Sickle Cell Anemia Does its Worst

Ministrokes in children with sickle cell anemia occur most often in an oxygen-restricted 'borderzone region' of the brain.

Valerie Brown, Contributor
Friday, August 31, 2018


About 100,000 Americans have sickle cell disease, a heritable blood disorder with several forms. Sickle cell anemia is the most severe form, and one of its most common consequences is silent cerebral infarcts -- events in which small areas of the brain die from lack of oxygen. These lesions, usually unnoticed at the time, accumulate with age, and children with SCIs often suffer cognitive deficits that impair their functionality, including success at school. By age 32, more than half of sickle cell anemia victims have suffered SCIs.

Researchers have long understood that SCIs are a consequence of low blood flow, because sickle cell red blood cells cannot deliver hemoglobin efficiently. But now researchers at Washington University School of Medicine and Vanderbilt University have determined where SCIs tend to cluster: It’s in an area of the brain with very little cerebral blood flow, one of several so-called borderzone regions. These regions occur at the boundaries of arterial territories, where the tissue is furthest from its blood supply.

Reporting in the August issue of Blood Journal, Andria L. Ford and colleagues selected a six-year cohort from the Silent Infarct Transfusion trial, a prospective, randomized clinical trial for children with sickle cell anemia and SCIs. This cohort comprised 289 children whose MRIs revealed lesions suggestive of infarcts as interpreted by a vascular neurologist. All the children’s infarcts were mapped onto a common brain template to visualize the location and density of SCIs.

SCIs in 90 percent of the children occurred in a small brain region deep in the white matter of the frontal lobes. This borderzone region is located in the frontal and parietal lobes where two major arterial territories meet.

To determine the relationship of SCIs to blood flow, the researchers analyzed MRI data that quantified blood supply in the brains of an independent set of children with sickle cell anemia. When they compared these independent blood flow results to their SCI density map, they saw that the region where most of the infarcts occurred had the lowest blood flow in the cerebrum and constituted only 5.6 percent of the total brain volume.

The researchers suggest that their results could help lead to therapies to increase blood flow in these specific regions and lower the incidence of SCIs.