Children with SCA generally have high TCD velocities in all cerebral blood vessels compared to age-matched controls [1
], but there are few data available about velocities in infants with SCA less than 2 years of age. Hogan et al. reported that infants with SCA had MCA velocities of 50 – 112 cm/sec (median 70) at 3 months of age, 50–160 cm/sec (median 89) at 9 months of age and 51–120 cm/sec (median 97) at 12 months of age [9
]. However, the sample size of this study was very small (n=14), TCD typically was recorded while the infant was sleeping, and there was no information provided about stroke.
Hogan et al. performed serial studies and did show an inverse relationship with developmental testing and TCD derived velocity as has been reported in older children with SCA [10
]. We showed no correlation with cognitive testing and increasing velocity but Hogan et al. evaluated patients serially which might have made their correlations with the Bailey Infant Neurodevelopmental Screener more robust. It is possible that our study at exit will show a better correlation of TCD with cognitive function.
The BABY HUG study provides TCD data on the largest sample of infants with SCA to date, with adequate baseline TCD evaluations obtained on 192 subjects. All but four (2%) were normal by STOP criteria as compared to 9.3% abnormal and 17.6% conditional in STOP screening of children 2–16 years of age [2
]. Baseline TCD velocities varied inversely with the hemoglobin level when adjusted for age as expected, and the direct association with the reticulocyte count was anticipated because of the known inverse relationship between Hb level and reticulocyte count
The correlation of TCD velocity with increasing age is of particular interest. Velocities of the basal cerebral arteries have been found to be age dependent in healthy children with normal hemoglobin levels [1
]. For example, the mean MCA velocity is low soon after birth (24 cm/sec) but increases rapidly during the first three months of life to 42 cm/sec, probably related in part to the physiologic anemia of infancy. Subsequently, the mean MCA velocity rises slowly to 74 ± 14 cm/sec at 3–12 months of age and 85 ± 10 cm/sec between the ages of one and three years. The highest values occur between the ages of four and six years with peak MCA velocity approaching 100 cm/sec [11
]. After that, velocities decrease linearly (mean MCA velocity 80 cm/sec at 10–18 years of age). We found a similar developmental trend in infants with SCA. The average TAMM MCA velocity of 111 cm/s in infants with SCA is higher than in normal children without anemia but substantially lower than observed in the STOP trial (approximately 140 cm/sec), in which all patients were age 2 years or greater and there was no significant age effect over this older range [12
Another factor that could affect TCD velocity is vascular stenosis [13
]. In SCA the earliest onset of large vessel stenosis is not known. Wang et al previously reported MRA findings in a baseline subset of very young children with SCA from the BABY HUG study [5
], and MRA showed no occlusion or significant stenosis in any patient. The trend of increasing velocity with age observed in our study is more likely related to anemia and developmental demands for increased blood flow, not unlike what is seen in normal children, although our subjects had higher velocities overall.
In the same study, 3 children who underwent MRI had silent infarcts (13%; 3 out of 23 MRI performed) [5
]. The silent infarct group had velocity asymmetries not found in the non-silent infarct group but the numbers are small and conclusions difficult to derive [5
Cerebral blood flow (CBF) elevation and age may be independent risk factors for AIS in SCA, independent of vasculopathy [13
]; therefore, the absolute TCD velocity that predicts AIS in the one year-old may be different than in the four year-old. Our categorization of TCD values as normal, conditional or abnormal based on the STOP trial results is, in the present study, arbitrary, although based on established norms in older SCA children. Different norms for this younger age group may be necessary if one year-olds truly have “abnormal” velocities that are predictive of stroke. Data obtained from TCD exams of subjects when they exit the BABY HUG study (following two years of HU or placebo) will help determine if our subjects’ baseline velocities within the normal to conditional range (by STOP criteria), will yield predictive information on the risks for developing markedly high velocities, vasculopathy and later stroke.