Cerebral Vasculopathy In Sickle Cell Anemia: Diagnosis, Therapeutic Clinical Trials And The Potential For Prevention (pp. 19-58)
Authors: Powars, Darleen R. (LAC+USC Medical Center, Los Angeles, CA)
Abstract: Cerebral vasculopathy in children with sickle cell anemia (Hb SS) was originally thought to be relatively infrequent until several seminal natural history studies were reported during the decades of 1970 and 1980. At that time, overt clinical stroke was identified to occur in 7.8 to 10% of Hb SS children. Recent data based on marked refinements in neuroimaging technology demonstrate that nearly 50% of children with sickle cell anemia have both large and small vessel central nervous system infarctions. In 10 to 15% of children, completed infarctions are found in the regional distribution of the large cerebral blood vessels. They are overly symptomatic with hemiparesis. Incomplete (silent) infarctions are identified in one-third of children and are often microvascular in distribution marked by more subtle cognitive and neurofunctional disability. Over time, the circulating sickle red cell damages the endothelium of the vasculature. This is mediated by several adhesion molecules, intracellular red cell dehydration and a deleterious effect on nitric oxide (NO) synthesis. Decreased circulating levels of NO are thought to be caused by the constantly elevated levels of free intravascular hemoglobin resulting from the lifelong hemolytic anemia. The pathophysiology of sickle induced neurovasculopathy, clinical risk factors, rate of progression of dsabling manifestations and potential treatment modalities are presented in this chapter.