Silent Cerebral Infarctions in Children and Adolescents with Hemoglobin SC Disease

Children with sickle cell disease (SCD), especially sickle cell anemia, are at high risk of overt and silent cerebral infarctions, leading to physical and cognitive deficits. Less is known about the risks of cerebral infarction in children with Hemoglobin SC (Hb SC). Prior studies have found a prevalence of silent cerebral infarction of 5.8%¹ to 46%² in children with Hb SC disease. We sought to define the prevalence of cerebral infarctions in a population of children and adolescents with Hb SC disease, and to identify medical risk factors for cerebral infarctions.

Since 2006, screening brain magnetic resonance imaging (MRI) exams have been performed on all children with SCD followed at St. Louis Children's Hospital at approximately age 6 years. Furthermore, brain MRI is performed if patients present with possible stroke symptoms, such as severe headache, visual changes, weakness, or seizures. Cerebral infarctions were defined as T2- or FLAIR-weighted hyperintensities visible in at least 2 planes; silent infarcts were diagnosed when the patient had no neurological symptoms that correlated with the infarct lesions. Human Studies Committee approval and waiver of consent was obtained prior to reviewing all brain MRIs from children with Hb SC disease. SPSS version 20 was used for statistical analysis.

Between January 2004 and May 2012, 95 children and adolescents with Hb SC disease underwent brain MRI; 54% were male. Forty-nine children (51.6%) had no neurological symptoms at the time of the initial MRI; of the 46 children with neurological symptoms, poor school performance (16 children, 16.8%) and headaches (15 children, 15.8%) were cited most commonly. Neurological symptoms provoking MRI included unilateral hearing loss (2 children) and Bell's palsy (3 children).

Prevalence of silent infarctions was 14.7% (14/95 children). Seven (50%) of subjects with silent infarctions were male. The mean age at identification of cerebral infarction was 11.9 years (range, 6.2–19.3 years). Five of the infarctions were identified by screening asymptomatic children. Nine children were found to have infarctions while experiencing neurological symptoms; in all cases, the infarct lesions did not explain the presenting neurological symptoms. Among 84 children with initial MRIs that were free of infarctions, 3 developed silent cerebral infarctions subsequently. There was no association between silent cerebral infarctions and a history of asthma, headaches, school difficulties, or school failure.

In all cases, the silent cerebral infarctions were located in periventricular, frontal, or parietal white matter; there were no lobar strokes identified. Infarcts ranged in size from 1 mm to 1 cm. All children with silent cerebral infarctions were referred for neurocognitive testing and evaluation for an individualized educational plan. Ten of the 14 children with silent infarctions have had followup MRIs, ranging from 0.1 to 6.4 years following the initial MRI. None have had progressive silent infarct lesions or overt strokes.

Magnetic resonance angiography (MRA) was performed in 83 subjects. None of the children had arterial stenosis or occlusion, moyamoya, or aneurysms. Five subjects had subtle irregularities of cerebral arteries noted on MRA, but none progressed to more severe abnormalities.

Approximately 15% of children and adolescents with Hb SC disease in this retrospective cohort have silent cerebral infarctions, a much higher prevalence than was found in the Cooperative Study of Sickle Cell Disease.¹ The prevalence is lower than that of Steen et al's cohort,² perhaps due to the fact that our center screens all school-aged children. Clinically significant angiographic abnormalities were not identified in this cohort. Children with silent cerebral infarctions should be referred for neurocognitive testing. Further work is needed to define risk factors and treatments for children with silent cerebral infarctions in Hb SC disease.

No relevant conflicts of interest to declare.