Toward a Stroke-Free Childhood in Sickle Cell Disease

Abstract

Stroke in childhood is not common outside of congenital heart disease and a few other conditions including sickle cell disease (SCD). The background rates reported have been between 2.3 and 2.7 per 100 000 per year.1–3 Adults, on the contrary, have a background rate of ≈800 per 100 000.4 There are some special conditions that increase the risk including congenital heart disease, trauma, infections (basilar meningitis), cancer, and SCD.5 Stroke rates in SCD were estimated to be high at 500 to 1000 per 100 000.6 The Baltimore Washington Cooperative Young Stroke Study reported data from 1988 to 1991 at rate of 285 per 100 000 children for SCD.7 For children with SCD, this is a long way for a stroke-free childhood. SCD fundamental pathophysiology results from hemoglobin S forming polymer strands inside the red blood cell which causes distortion of the red blood cell, leading to microcirculatory occlusion and accelerated erythrocyte destruction with release of toxic-free hemoglobin into the vascular system.8 How SCD leads to cerebrovascular disease is only partly understood. Although there are many manifestations of vascular pathology in SCD, the one that plays the most prominent role is an intracranial cerebral large artery vasculopathy causing stenosis or occlusion. This unusual vascular disease process was confirmed 90 years ago9 as a cause of large brain infarctions in patients with SCD, typically children, and confirmed with arterial studies much later. In the mid-1980s, a confluence of factors, from disparate worlds, led to the work herein described. Aaslid et al introduced the transcranial Doppler (TCD) for detection of intracranial artery vasospasm in 1982 based on experience in Norway.10 Interest in this tool was at first manifested in neurosurgery but soon its potential as a noninvasive way to assess intracranial arteries became …