Cerebral blood flow and neurocognitive function in children with sickle cell disease

Sickle cell disease (SOD) is a severe inherited disorder that affects at least 1600 newborns each year in the United States and approximately 200,000 in Africa. Neurological complications including stroke, silent cerebral infarct, and cognitive impairment are common in children with sickle cell anemia (HbSS) and contribute greatly to morbidity. Elevated cerebral blood flow velocity (CBFV) as measured by transcranial Doppler ultrasound can identify children at greatly increased risk of stroke; regular transfusions to maintain sickle hemoglobin less than 30% can reduce the risk of stroke by 90%. However, the relationship between CBFV and other measures of cerebral blood flow (CBF) and cognitive function in HbSS is less well defined. This dissertation will describe a series of studies designed to identify additional risk factors for cognitive impairment in HbSS.;The first chapter is a systematic review of published studies including information on CBF or CBFV and cognitive testing in people with SOD. This review supports an association between increased CBF or CBFV and lower intelligence quotient.;The next chapter describes our pilot study of CBF [measured by continuous arterial spin-labeled (CASL) MRI], hematological parameters, and cognitive function in 24 children with HbSS and no known history of stroke. The results of this study suggest that increased CBF and increased white blood cell count in this population is associated with lower performance and full scale IQ.;In the third chapter, we evaluate the relationship of CBFV to cognitive function in children with HbSS with and without evidence of silent cerebral infarct. We did not identify a significant relationship with CBFV, but did identify a significant decrease in full scale IQ and poorer performance in specific domains of cognition in children with HbSS and increasing age or lower socioeconomic status.;The final chapter outlines future directions for research in the central nervous system complications of SOD. We propose a longitudinal study of CBF, CBFV, cognitive function, and MRI of the brain to examine the sensitivity and specificity of these techniques and biomarkers to identify children that will develop cognitive impairment, stroke, or silent infarct over a three year interval.