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

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. Ann Neurol 1999;45:279–286

Neuroimaging abnormalities in adults with sickle cell anemia

“…[17][18][19][20][21] However, structural brain abnormalities of cortical thickness or basal ganglia volumes in neurologically asymptomatic adults with SCA have not been reported. Therefore, our observation that reduced cortical thickness and reduced volumes of subcortical gray matter are evident in adults with SCA is important.…”

“…5,6,8,9,14,15 However, because a significant proportion of both children and adults with SCA do not have cerebrovascular lesions, 5,13,16 additional CNS factors likely contribute to cognitive dysfunction. Frontal lobe cortical atrophy [17][18][19][20][21] and gray matter growth delays in the basal ganglia and thalamus reported in children and adolescents with SCA [22][23][24] may represent factors contributing to poorer intellectual function in adults with SCA. This study was conducted to evaluate MRI characteristics of neurologically asymptomatic adults with SCA to determine the relationship of these characteristics with IQ.…”

Inverse correlation between cerebral blood flow measured by continuous arterial spin-labeling (CASL) MRI and neurocognitive function in children with sickle cell anemia (SCA)

“…Studies using qualitative interpretation of positron emission tomography (PET) 19 or quantitative MRI suggest that children with decreased regional CBF or low T1 values 20 have lower IQs. However, the inclusion of patients with stroke and SCI in the PET study and of patients with sickle hemoglobin C disease (HbSC) in the MRI study may have confounded those results.…”

Neurological Complications and MRI

“…without cerebrovascular abnormalities). Anaemia severity has shown moderate to large correlations with IQ [41,119,137,138]. Severely anaemic patients (i.e.…”

“…Severely anaemic patients (i.e. haematocrit <20%) have shown poorer performance on both verbal and performance aspects of IQ [119], and have accounted for a significant proportion of variance in FSIQ [64,138] and executive functions [64].Low nocturnal peripheral oxygen saturation was associated with reduced performance on the Tower of London test, which measures strategic planning and rule learning [139]. In the baseline data from the Silent Infarct Trial, a 1% reduction in daytime oxygen saturation was associated with a reduction in 0.75 full scale IQ points [122].…”