Multicenter Prospective Study of Children With Sickle Cell Disease: Radiographic and Psychometric Correlation

Abstract

After obtaining familial informed consent, between January 1996 and July 1997, 173 children (5 to 15 years old) with sickle cell disease were enrolled in a prospective multicenter study using blood screening, transcranial Doppler ultrasonography (n = 143), cerebral magnetic resonance imaging (n = 144), and neuropsychologic performance evaluation (n = 156) (Wechsler Intelligence tests WISC-III, WIPPSI-R), which were also performed in 76 sibling controls (5 to 15 years old). Among the 173 patients with sickle cell disease (155 homozygous for hemoglobin SS, 8 sickle cell beta0 thalassemia, 3 sickle cell beta+ thalassemia, 7 sickle cell hemoglobin C disease SC), 12 (6.9%) had a history of overt stroke, and the incidence of abnormal transcranial Doppler ultrasonography (defined as mean middle cerebral artery velocity > 200 cm/sec or absent) was 8.4% in the overall study population and 9.6% in patients with homozygous sickle cell anemia The silent stroke rate was 15%. Significantly impaired cognitive functioning was observed in sickle cell disease patients with a history of stroke (Performance IQ and Full Scale IQ), but also in patients with silent strokes (Similarities, Vocabulary, and Verbal Comprehension). However, infarcts on magnetic resonance imaging were not the only factors of cognitive deficit: Verbal IQ, Performance IQ, and Full Scale IQ were strongly impaired in patients with severe chronic anemia (hematocrit < or = 20%) and in those with thrombocytosis (platelets > 500 x 10(9)/L). Multivariate logistic regression analysis showed that abnormal magnetic resonance imaging (odds ratio [OR] = 2.76) (P = .047), hematocrit < or =20% (OR = 5.85) (P = .005), and platelets > 500 x 10(9)/L (OR = 3.99) (P = .004) were independent factors of cognitive deficiency (Full Scale IQ < 75) in sickle cell disease patients. The unfavorable effect of low hematocrit has already been suggested, but this is the first report concerning an effect of thrombocytosis and showing that silent stroke alone is not a factor of cognitive deficit when not associated with low hematocrit or thrombocytosis. The effect of hydroxyurea, which is known to increase hematocrit and decrease platelet count, on cognitive functioning of sickle cell patients should be evaluated prospectively.

Neurocognitive deficits in children with sickle cell disease: a comprehensive profile

“…This percentage is similar to the percentage reported in a French study [5] and is expected to have profound consequences for academic functioning. It is surprising to note; however, that relatively few children with SCD in our sample (14%) received special educational services.…”

“…Children with SCD and overt strokes seem to be most impaired, with a decrease of approximately 14 Full-scale IQ points [3], while children with silent infarcts have been described to score 4-7 Full-scale IQ points lower than children with normal MRI [4,5]. However, it appears that there are cognitive effects of SCD for children with normal MRI as well [6][7][8].…”

Evolution of sickle cell disease from a life‐threatening disease of children to a chronic disease of adults: The last 40 years

“…Magnetic resonance imaging (MRI) is the only method to detect SCI. Children with a previous SCI are at increased risk for stroke, new or enlarging silent cerebral infarcts [81], poor academic achievement [82], and lower performance on intelligence tests when compared with children with SCA with normal neuroimaging, or children without SCA [83]. Based on the morbid and progressive nature of SCI, the NINDS sponsored the Silent Infarct Transfusion (SIT) trial, a multicenter randomized trial in which children with SCA and SCI were assigned to receive standard care (observation group) or regular blood-transfusion therapy (transfusion group).…”

“…The much higher burden of stroke in adults compared with children with SCD may be due to the widespread use of TCD screening coupled with regular blood transfusion therapy in children with SCA, as well as the growing adult SCD population. Survivors of overt stroke demonstrate global neurocognitive impairment [103]; and multiple prospective studies have identified lower IQ scores, learning difficulties, and impairment of executive function in children without strokes and with normal imaging studies [83,103,104]. These neurological impairments increase with age [103].…”

Transcranial Doppler in children

“…In Memphis, the stroke rate decreased from 0.46 to 0.18 per 100 person-years after the TCD screening rate reached 99% [25]. In a newborn SCA-cohort of Creteil, France, including 217 SS/Sβ0 thalassaemia patients, early and annually screened with TCD since 1992, the cumulative stroke risk by age 18 was 1.9% (95% CI, 0.6-5.9) [14,26,27]. In Philadelphia, the incidence of overt stroke in the post-TCD period was 0.06 per 100 patient-years, compared with 0.67 per 100 patient-years in the pre-TCD period [28].…”