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Subtle brain abnormalities in children with sickle cell disease: relationship to blood hematocrit
R G Steen1, X Xiong, R K Mulhern
1Department of Diagnostic Imaging, St Jude Children's Research Hospital, Memphis, TN 38105-2794, USA.
Insights
Pediatric sickle cell disease (SCD) patients show subtle brain abnormalities and a 23-fold increased risk of mild mental deficiency, even without clinical stroke. These cognitive and MRI T1 changes are linked to low hematocrit levels.
Area of Science:
- Neurology
- Pediatrics
- Radiology
Background:
- Sickle cell disease (SCD) is a genetic blood disorder.
- Neurological complications in SCD are common, but subtle brain changes in asymptomatic children are not well understood.
- Early detection of brain abnormalities is crucial for timely intervention.
Purpose of the Study:
- To investigate subtle brain abnormalities in pediatric sickle cell disease (SCD) patients without clinical stroke.
- To determine the association between these abnormalities, cognitive function, and hematocrit levels.
Main Methods:
- Prospective comparison of 50 pediatric SCD patients with 52 healthy controls.
- Quantitative magnetic resonance imaging (MRI) using an inversion-recovery method to measure T1 relaxation times in gray and white matter.
- Wechsler intelligence testing on a subset of patients.
Main Results:
- Significantly lower T1 values in all evaluated gray matter structures of SCD patients compared to controls.
- Abnormal T1 values detected in caudate, nucleus pulvinares, and cerebral cortex by age 4.
- 33% of SCD patients exhibited mild mental deficiency (IQ 50-70), a 23-fold increase compared to the general population.
- Lower IQ scores and gray matter T1 abnormalities correlated with lower hematocrit (Hct < 27%).
Conclusions:
- Subtle brain abnormalities and cognitive deficits, including mild mental deficiency, are prevalent in pediatric SCD patients even without clinical stroke.
- Chronic brain hypoxia, indicated by altered T1 relaxation times, may underlie these findings.
- Low hematocrit is a significant factor associated with both cognitive impairment and MRI-detected brain abnormalities in pediatric SCD.
Abstract:
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. We prospectively compared 50 patients with 52 healthy age-similar controls, using quantitative magnetic resonance imaging. A previously validated precise and accurate inversion-recovery method was used to measure 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 patients. Brain T1 was significantly lower in patients in every gray matter structure evaluated but in none of the white matter structures. Regression suggests that T1 in caudate, nucleus pulvinares, and cerebral cortex was abnormal by age 4 years. Psychometric testing showed that 33% of patients were functioning in the range of mild mental deficiency (IQ, 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 mental deficiency. Full-scale IQ of SCD patients was a function of hematocrit (Hct), and when Hct was used to stratify patients, those with an Hct of less than 27% had significantly lower psychometric test scores, and significantly lower gray matter T1, than those with an Hct of 27 or more. Both cognitive deficits and subtle T1 abnormalities were associated with a low Hct, and both could be present when conventional magnetic resonance imaging findings were normal. Our findings suggest that chronic hypoxia of brain tissue can occur in SCD patients free of clinical stroke.