Subtle brain abnormalities in children with sickle cell disease: Relationship to blood hematocrit

Our objective was to test a hypothesis that subtle brain abnormality can be present in pediatric sickle cell disease (SCD) patients who are clinically free of stroke. Me prospectively compared 50 patients with 52 healthy age- similar controls, using quantitative magnetic resonance imaging. A previous ly validated precise and accurate inversion-recovery method was used to mea sure T1 in a slice at the basal ganglia. We also used the Wechsler test to measure intelligence quotient (IQ) in a randomly selected subset of 27 pati ents. Brain T1 was significantly lower in patients in every gray matter str ucture evaluated but in none of the white matter structures. Regression sug gests that T1 in caudate, nucleus pulvinares, and cerebral cortex was abnor mal by age 4 years. Psychometric testing showed that 33% of patients were f unctioning in the range of mild mental deficiency (Ia 50-70), compared with a published prevalence of 1.45% in inner-city black children. Thus, in our patients, SCD was associated with a 23-fold increase in the risk of mild m ental deficiency. Full-scale IQ of SCD patients was a function of hematocri t (Hct), and when Hct was used to stratify patients, those with an Hct of l ess than 27% had significantly lower psychometric test scores, and signific antly lower gray matter T1, than those with an Hct of 27 or more. Both cogn itive deficits and subtle T1 abnormalities were associated with a low Hct, and both could be present when conventional magnetic resonance imaging find ings were normal. Our findings suggest that chronic hypoxia of brain tissue can occur in SCD patients free of clinical stroke.