Silent cerebral infarcts: a review on a prevalent and progressive cause of neurologic injury in sickle cell anemia

Abstract

Silent cerebral infarct (SCI) is the most common form of neurologic disease in children with sickle cell anemia (SCA). SCI is defined as abnormal magnetic resonance imaging (MRI) of the brain in the setting of a normal neurologic examination without a history or physical findings associated with an overt stroke. SCI occurs in 27% of this population before their sixth, and 37% by their 14th birthdays. In adults with SCA, the clinical history of SCI is poorly defined, although recent evidence suggests that they too may have ongoing risk of progressive injury. Risk factors for SCI include male sex, lower baseline hemoglobin concentration, higher baseline systolic blood pressure, and previous seizures. Specific morbidity associated with SCI includes a decrement in general intellectual abilities, poor academic achievement, progression to overt stroke, and progressive SCI. In addition, children with previous stroke continue to have both overt strokes and new SCI despite receiving regular blood transfusion therapy for secondary stroke prevention. Studies that only include overt stroke as a measure of CNS injury significantly underestimate the total cerebral injury burden in this population. In this review, we describe the epidemiology, natural history, morbidity, medical management, and potential therapeutic options for SCI in SCA. IntroductionOne of the most devastating medical complications of sickle cell anemia (SCA) is cerebral injury, which limits the full potential of the developing child and adult. The most common neurologic injury in SCA is silent cerebral infarct (SCI). Although there are few studies, SCI occurs in approximately one-quarter of children with SCA before their sixth birthday 1 and approximately one-third before their 14th birthday. 2 The first evidence that SCI had clinical significance was published in a cross-sectional computed tomography (CT) scan study of 25 patients. Five had cerebral infarcts but only 4 had a focal neurologic deficit (overt stroke). 3 The investigators referred to the fifth patient as having a covert stroke, 3 a term also used by others. 4 The term SCI or silent stroke has gained widespread use to describe this condition because the Cooperative Study of Sickle Cell Disease (CSSCD) used standard clinical magnetic resonance imaging (MRI) to define the radiologic parameters. 5 Subsequently, only a few studies of SCI have been completed. Until recently, the clinical importance of identifying SCI did not seem to justify the expense of MRI requiring sedation or anesthesia in preschool children, particularly in the absence of an effective intervention. Despite being the most common type of cerebral injury among children and adults with SCA, relatively little is known about the cause and optimal therapy of SCI. We will review the current literature on definition, epidemiology, natural history, clinical significance, medical management, and potential therapeutic options for the treatment of SCI in SCA. Definition of SCI in children with SCAThe largest longitudinal cohort study to a...

Cerebrovascular events in sickle cell‐beta thalassemia treated with hydroxyurea: A single center prospective survey in adult Italians

“…Silent cerebral infarction is a risk factor for overt stroke in SCD [6,7] and can only be identified by brain MRI. Although a benefit of blood transfusion in silent cerebral infarction has been suggested, a standard of treatment has not emerged and high-level evidence to support the use of HU or transfusion in silent cerebral infarction is lacking [4].…”

Neurological Complications and MRI

“…SCI have been reported in very young children; 4/39 children (10%) with SCA and no history of stroke between 7 and 48 months of age had SCI [9]; 3/23 children (13%) at an average age of 13.7 months had SCI [10]; and 18/65 children (27.7%) with SCA who were asymptomatic had SCI [31]. A French study showed incidence of SCI as 28.2% by 8 years and 37.4% by 14 years [66].…”

“…More common than overt stroke, up to 35% of children will show evidence of SCI [31], diagnosed using MRI as a lesion seen in two planes of a scan with no history of stroke [9,30,32,33]. In children with evidence of SCI on MRI, there is a 14-fold increase in the risk of clinical stroke [34] and further SCI [16].…”

Assessment of cerebral blood flow with magnetic resonance imaging in children with sickle cell disease: A quantitative comparison with transcranial Doppler ultrasonography

“…To date, there is no established association between TCD and SCI (DeBaun, Armstrong, et al, 2012), illustrated by the high cumulative risk for SCI observed in patients without abnormal…”