Effects of Hydroxyurea on Brain Function in Children with Sickle Cell Anemia

Introduction: Sickle cell anemia (SCA) results in numerous adverse effects on the brain, including ischemic lesions and neurocognitive dysfunction. Hydroxyurea has been utilized extensively for management of SCA, but its effects on brain function have not been established. Methods: We examined prospectively the effects of one year of treatment with hydroxyurea on brain function in a cohort of children with SCA (HbSS/HbSβ0-thalassemia) by baseline and exit evaluations, including comprehensive neurocognitive testing, transcranial Doppler ultrasound (TCD), and brain MRI [silent cerebral infarcts (SCI), gray matter cerebral blood flow (GM-CBF), and blood oxygen level dependent (BOLD) signal from visual stimulation]. Results: Nineteen patients with SCA, mean age 12.4 years (range 7.2-17.8), were evaluated. At baseline, subjects had these mean values: full scale IQ (FSIQ) 81.9, TCD velocity 133 cm/sec, GM-CBF 64.4 ml/100g/min, BOLD signal 2.34% increase, and frequency of SCI 47%. After one year of hydroxyurea, there were significant increases in FSIQ (+2.8, p=0.036) and reading comprehension (+4.8, p=0.016), a significant decrease in TCD velocity (-11.4 cm/sec, p=0.007), and no significant changes in GM-CBF, BOLD, or SCI frequency. Furthermore, FSIQ was associated with higher hemoglobin F (HbF) and lower GM-CBF, but not with hemoglobin level. Discussion: Significant improvement of neurocognition and decreased TCD velocity following one year of treatment support the use of hydroxyurea for improving neurocognitive outcomes in SCA. Understanding the mechanisms of benefit, as indicated by relationships of neurocognitive function with HbF, hemoglobin, and CBF, requires further evaluation.