Cognitive impairment in children with hemoglobin SS sickle cell disease: relationship to MR imaging findings and hematocrit

Abstract

Background and purpose: Children with hemoglobin SS sickle cell disease are known to suffer cognitive impairment if they have silent infarct, but recent evidence suggests that patients with hemoglobin SS sickle cell disease may be impaired even if they are free of infarction. We test a hypothesis that cognitive impairment in children with hemoglobin SS sickle cell disease is associated with low hematocrit and MR imaging abnormalities.

Methods: A cohort of 49 patients was examined, all of whom had hemoglobin SS sickle cell disease but no history of clinical stroke. The Wechsler scales, which are standardized and age-adjusted, were used to assess cognitive function. Patients also underwent MR imaging examination of the brain, and hematocrit was measured in a subset of 45 patients. MR images were evaluated by at least two readers, and abnormal imaging findings were evaluated by at least three readers. Any lesion was sufficient to be classified as abnormal, with lesions defined to include lacunar infarction, encephalomalacia, or leukoencephalopathy. Hematocrit data were used if obtained within 3 months of psychometric testing and if there were no confounding events in the patients' charts. Wechsler test scores were then evaluated in relation to imaging findings and hematocrit values.

Results: Patients with imaging abnormalities had more cognitive impairment than did patients with normal imaging findings in verbal intelligence quotient (P <.02) and verbal comprehension (P <.01). Patients with low hematocrit had cognitive impairment shown by many performance measures, including full-scale intelligence quotient (P <.006), verbal comprehension (P <.006), and freedom from distractibility (P <.02). Multivariate analysis showed that MR imaging and hematocrit were independent predictors of full-scale intelligence quotient.

Conclusion: Focal brain injury, revealed by MR imaging, is associated with cognitive impairment, but our data suggest that diffuse brain injury may also contribute to impairment. These findings show that impairment is multifactorial and suggest that chronic brain hypoxia is part of the pathophysiology of sickle cell disease.

Fig 1.

Range of abnormalities shown by MR images of young patients with hemoglobin SS sickle cell disease. A, T1-weighted MR image of a 4.3-year-old boy with bilateral lacunae in the centrum semiovale and paraventricular white matter. Image section is 3 cm thick. Image shows multiple lacunae, the largest of which is approximately 7 mm in diameter. B, T1-weighted MR image of a 5.0-year-old girl with multiple small bilateral white matter lacunae in the centrum semiovale and the corona radiata. Image section is 3 cm thick. Image shows several lacunae, the largest of which is approximately 7 mm in diameter. C, T1-weighted MR image of a 5.4-year-old boy with bilateral lacunar infarcts involving both frontal lobes and the centrum semiovale on both sides. Image section is 3 cm thick. Image shows two lacunae, the largest of which is approximately 6 mm in diameter. D, Fluid-attenuated inversion recovery image of an 8.4-year-old boy with bilateral leukoencephalopathy in the centrum semiovale. Image section is 3 cm thick. Image shows abnormally high signal intensity. Because fluid-attenuated inversion recovery images null signal intensity from CSF, this is not a partial volume effect from the ventricle.