Age of Onset of High Transcranial Doppler Measurements Predicts Discrepant Cognitive Profiles in Children with Sickle Cell Disease

Background: Children with Sickle Cell Disease (SCD) have documented compromises in neurocognitive functioning, with notable weaknesses in executive functioning. There is limited published research to define the impact of SCD on the development of visual spatial processing, which is the brain's ability to use and interpret visual stimuli and then apply it to novel situations. We hypothesized that the risk for deficits in visual spatial processing is correlated to high velocity transcranial dopplers (TCD) measurements and the age at which a high TCD velocity first occurred. Our team hypothesized that younger age at time of initial high TCD is associated with a larger impact on visual spatial skills in school aged children.

Methods: This review includes data from standard of care practices within our pediatric multidisciplinary sickle cell program. Our clinic began offering neurocognitive screenings in January 2023 to patients who are school entry age (between 5 to 6 years old) or older. Children are identified to participate in screening based on age, parental interest, and provider recommendation. Patients ranging in age from 5 to 15 years of age were screened using either the Weschler Preschool and Primary Scale of Intelligence, fourth edition (WPPSI-IV) or the Wechsler Intelligence Scale for Children, fifth edition (WISC-V). Retrospective chart reviews were performed to identify relevant data including TCD and MRI results.

The Visual Spatial Index (VSI) is a primary index obtained from the Wechsler standard batteries. VSI assesses a child's ability to construct designs utilizing visual spatial reasoning, attention to visual detail, and visual-motor integration. The average child can demonstrate these skills at age 5 by mentally rotating an object such as a block and matching it with a picture or into a shaped hole. This requires the appropriate development of the basal ganglia, thalamus, parietal lobe, and temporal lobe.

The Mean Index Score (MIS) is a broad representation of all cognitive domains measured on the assessment. The difference between the obtained VSI score and a child's MIS is used to determine whether a statistically significant difference exists within the Wechsler assessment system. The difference between the VSI and MIS is compared to a critical value, and if the difference of the VSI and MIS is greater than the critical value then we can say with confidence (p<0.05) that the difference in scores is not due to chance. Chi-square was then used to explore the relationship between the presence of a high TCD before age 5 (the age at which primary visual spatial skills are onboard) and the presence of a statistically significant visual spatial skill weakness.

Results: 11 children (mean age 9.73 years; 82% Hemoglobin SS and 18% Hemoglobin SC) were assessed during the first 6 months of this new protocol. 27% (3) of the children had both a high TCD prior to age 5 and a statistically significant (p<0.05) visual spatial weakness, 9% (1) had only high TCD before age 5 but not VSI weakness, and 64% (7) had neither. Due to the small sample size, we used Fisher's exact to test the hypothesis that these two categorical variables (high TCD velocity before age 5 and VSI weakness) were related (P<0.05, P=0.024). We rejected the null hypothesis and found evidence to support a relationship between the presence of high velocities in early childhood and visual spatial skills deficit. Therefore, there is clinical indication that high TCD velocities in early childhood impact the development of visual spatial skills.

Conclusion: The impact of sickle cell disease on brain development has been explored, but most published data focus on broad executive functioning skills. Our data yields evidence that the presence of high velocities in the brain before age five may be predictive of future visual spatial abilities as measured using standardized measures (i.e., Wechsler Assessments). It is anticipated that further data exploration will inform the optimization of standard of care practices within our clinic. This may include medical practices such as neuroimaging, changing how we communicate with children and their families, and enhanced practices for supporting students at school through IEPs.