Effects of hydroxyurea on brain function in children with sickle cell anemia

Abstract

Introduction Sickle cell anemia (SCA) results in numerous adverse effects on the brain, including 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 1 year of treatment with hydroxyurea on brain function in 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) 82.8, TCD velocity 133 cm/s, GM‐CBF 64.4 ml/100 g/min, BOLD signal 2.34% increase, and frequency of SCI 47%. After 1 year of hydroxyurea, there were increases in FSIQ (+2, p = .059) and reading passage comprehension (+4, p = .033), a significant decrease in TCD velocity (−11 cm/s, p = .007), and no significant changes in GM‐CBF, BOLD, or SCI frequency. Hemoglobin F (HbF) was associated with passage comprehension, hemoglobin with lower TCD velocity, and lower GM‐CBF with greater working memory. Higher BOLD signal was associated with higher processing speed and lower TCD velocity with higher math fluency. Discussion Improvements in neurocognition and decreased TCD velocity following 1 year of treatment support hydroxyurea use 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.

Health literacy correlates with abbreviated full‐scale IQ in adolescent and young adults with sickle cell disease

“…Early use of hydroxyurea has been documented to reduce detrimental neurocognitive effects of SCD. 34,43 Specifically, improvements in verbal fluency and reading have been reported in adolescents with SCD on hydroxyurea. 42 It is possible that the high prevalence of hydroxyurea exposure in our cohort (58%) might have reduced the strength of the association between cerebrovascular insults and HL, as diseasemodifying therapies may attenuate progression of central nervous system disease.…”

“…42 , More than half of the participants in our study (54/93; 58%) were treated with hydroxyurea. Early use of hydroxyurea has been documented to reduce detrimental neurocognitive effects of SCD 34,43 . Specifically, improvements in verbal fluency and reading have been reported in adolescents with SCD on hydroxyurea 42 .…”

Comment on: Effects of hydroxyurea on brain function in children with sickle cell anemia

“…We have read with great enthusiasm and interest "Effects of hydroxyurea on brain function in children with sickle cell anemia" by Wang et al 1 It was edifying to read the concisely written report, and we applaud the authors for their stupendous accomplishment. The endmost conclusion of the article is that hydroxyurea improves neurophysiological functions and reduces transcranial Doppler ultrasound velocity in the pediatric population.…”

Leveraging mathematical modeling to analyze nonadherence for hydroxyurea therapy in sickle cell disease

“…11,12 Additionally, SCD has a negative impact on health-related quality of life (HRQOL). 13 HU therapy reduces acute SCD-related complications, [14][15][16][17][18] development of end-organ damage, 19,20 mortality, 6 and positively impacts HRQOL. 13,21 Subjects with low adherence to HU have lower fetal hemoglobin (HbF) and mean cell volume (MCV) and experience more fatigue, vaso-occlusive pain, and depression, thus lower HRQOL.…”