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Stroke and Sickle Cell Disease
Introduction
Sickle cell disease (SCD) is a powerful risk factor for stroke. Individuals with SCD are at risk for hemolytic anemia, painful vaso-occlusive crises, infection, and cerebrovascular disorders. Those with sickle cell anemia (SCA), defined as homozygous hemoglobin S or hemoglobin S-beta thalassemia, have an even greater risk for stroke beginning in early childhood, as up to 10% will have stroke without primary prevention. Red blood cells sickle under conditions of low blood oxygen tension due to a missense mutation in the beta hemoglobin protein substituting valine in place of glutamic acid. This causes a decrease in hemoglobin solubility under low oxygen tension and subsequent crystallization, distorting the red blood cell membrane. The sickled cells increase blood viscosity, enhance cellular adhesion, and cause vascular endothelial injury. Therefore, individuals with SCD have increased risk for cerebrovascular injuries including silent cerebral infarctions, overt ischemic stroke, and intracranial hemorrhage among other neurological complications. Prompt identification of individuals at risk for cerebrovascular complications of SCD, diagnosis and treatment of acute stroke, and secondary prevention strategies are crucial to limiting morbidity and mortality in individuals with SCD.
Silent Cerebral Infarctions
Silent cerebral infarcts, those that are not associated with abnormalities on neurological exam, occur in 30–35% of children with SCA and are likely secondary to acute hemodynamic instability in the setting of chronic anemia ( Fig. 118.1A ). Children with SCA and silent infarcts have an increased risk for overt ischemic stroke and neurocognitive deficits. The Silent Cerebral Infarct Multi-Center Clinical Trial (SIT) was a large, randomized trial of regular blood transfusions in children with SCA and silent or overt stroke that demonstrated a strong protective effect (relative risk reduction 58%) in decreasing the incidence of overt stroke or enlarged silent cerebral infarct . Although screening neuroimaging should not be routinely performed , regular transfusion therapy is beneficial after identifying a child with silent cerebral infarcts in order to decrease their future risk for overt cerebral infarction.
Overt Cerebral Ischemic Infarction
Prevalence and Pathophysiology
Cerebral infarction is the most recognizable neurological complication in SCD patients ( Fig. 118.1B ). Infarction accounts for 75% of the strokes in SCD and is the most common stroke type in children. The average age for the first recognized cerebral infarct is 7.7 years with most occurring between ages 5 and 15 years. Markers of risk for cerebrovascular disease have been difficult to determine and in the majority of cases, no predisposing factors are recognized.
Large vessel occlusive disease occurs in the proximal anterior cranial vessels, most commonly in the intracranial portion of the internal carotid artery (ICA) ( Fig. 118.1C ) beyond the origin of the ophthalmic artery. This vasculopathy may be due to repeated trauma from sickled cells in areas of flow turbulence. Sickled cells have a higher viscosity and an increased adherence to the vascular endothelium, causing rheological injury, direct mechanical trauma, and endothelial damage leading to thrombus formation. Reparative processes may also contribute to pathology through smooth muscle hypertrophy, vessel wall thickening, and stenosis.
Chronic anemia causes increased cerebral blood flow (CBF) due to arteriolar vasodilation. This dilation may alter the vasomotor regulatory responses to CBF decreases during arterial occlusion or decrease in hematocrit. The latter explains why an acute decrease in hematocrit or other exacerbations of SCD are at times associated with cerebral infarction.
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