The risk of subtle brain abnormalities in children with sickle cell disease (SCD) and their relationship to blood hematocrit was determined by prospective comparison of 50 patients and 52 controls studied at St Jude Children’s Research Hospital, Memphis, TN. Using quantitative magnetic resonance imaging to measure T1 (spin-lattice relaxation time) in basal ganglia, and the Wechsler test of intelligence, patients by age 4 years showed a significantly lower T1 (evidence of structural changes at the cellular level) in basal ganglia and cortex, but not in white matter, and mild mental deficiency (IQ, 50-70) in 33%, compared to a published prevalence of 1.45% in controls. Routine conventional MRIs were read as normal. Both the subtle T1 abnormalities on MRI and cognitive deficits were associated with a low hematocrit (Hct). Patients with an Hct of less than 27% had significantly lower IQ scores and significantly lower gray matter Tl, than those with an Hct >27%. SCD was associated with a 23-fold increase in risk of mild mental deficiency. [1]

COMMENT. Young children with sickle cell disease and low hematocrits are at risk of subtle brain abnormalities, only detected by quantitative MRI, and complicated by mild mental deficiency. Brain hypoxia is proposed as the mechanism of this subtle brain damage demonstrated in patients with SCD who are spared more obvious brain pathology, including stroke.

Psychometric tests of intelligence can be more sensitive to subtle neurological abnormalities than conventional MRI scanning in SCD. In the absence of quantitative MRI, the Wechsler IQ test should be used routinely to follow children with SCD, not affected by stroke. The authors suggest that aggressive prophylactic therapy should be considered for possible prevention of brain damage and cognitive impairments in young children with SCD.

In an Editorial in the same issue, Dr GJ Dover of Johns Hopkins University School of Medicine discusses the progressive nature of the neuropathology of SCD [2]. Steen and associates, in the present article, demonstrate the earliest detectable evidence of diffuse tissue hypoxia in the gray matter, as measured by quantitative MRI and IQ tests. Heretofore, the progression of brain pathology in SCD was documented in three ways: 1) subclinical large-vessel occlusion shown by Doppler; 2) clinical and subclinical infarcts seen on CT/MRI radiographic imaging; and 3) increased incidence of massive intracranial hemorrhage in the second and third decades of life.

The inclusion of milder sickle syndromes, and subtle neurologic abnormalities related to a low hematocrit, emphasizes the need for closer patient follow-up and studies of the risk/benefit ratio of chronic prophylactic transfusion therapy or alternative treatments. [3]