Background: Children with sickle cell anemia (SCA) are highly susceptible to stroke and other manifestations of pediatric cerebral vasculopathy. Detailed evaluations of children with SCA in sub-Saharan Africa are limited, especially magnetic resonance imaging and angiography (MRI/MRA). In a sample of Ugandan children receiving care at the Mulago Hospital sickle cell clinic in Kampala and were not on disease-modifying therapy, we examined the range of MR imaging findings, and how those findings correlated with standardized demographic, clinical, neurological and neurocognitive assessments.
Methods: From within a larger sample of 265 participants with HbSS ages 1-12 years not taking disease-modifying therapy and enrolled in the BRAIN SAFE study, a sub-sample of 81 underwent non-contrast MRI/MRA on a 1.5 Telsa scanner. Participants also underwent 3 standardized assessments: neurocognitive testing by experienced testers using the Mullen Scales of Early Learning (for ages 1-4 years) or Kaufman Assessment Battery for Children, 2nd edition (for ages 5-12) (abnormal z-score of -2 or lower), stroke examination (PedsNIHSS) and transcranial Doppler ultrasound (TCD) using criteria for pediatric SCA. Participants undergoing MRI/MRA intentionally included 29 without any abnormal findings. MRI scans included T1- and T2- weighted images, T2 FLAIR and MRA three-dimensional time-of-flight technique. MR scans were interpreted by clinical and research methods, the latter per SWiTCH protocol (Helton, Blood 2014). Adjudication of differing reads was performed by a blinded third neuroradiologist.
Results: A total of 81 children with SCA were examined by MRI/MRA. Mean age was 6.48 ± 2.75 years; 50.6% were male. Mean hemoglobin was 7.26±0.90 g/dl; 75% had hemoglobin <8.0. In all, 16.7% were malnourished using standard international measures established by age and sex. Infarcts and/or arterial stenoses on MRI/MRA were detected in 42 (52%), including 13 (25%) with no other abnormalities detected. There were 35 children (43.2%) who had medium or large infarcts seen; an additional 16 (19.8%) had 1-2 small infarcts. Four had moya moya. Of the 29 children categorized as normal on each of the 3 other tests, 14 (48.3%) had one or more medium or large infarct(s) on MRI, and 3 (10.3%) had 1-2 small infarcts (Figure 1). The proportion of children with malnutrition was higher among those with an abnormal MRI compared to those with a normal MRI, whereas no children with a small infarct was malnourished (29.4% vs. 10.7% vs. 0% p=0.019). A higher proportion of participants with stroke by exam had medium or large infarct(s) compared to participants with normal or small infarct (28.6% vs. 10% vs. 6.3%; p=0.061). Stroke on exam was associated with medium or large infarct(s) compared to normal or small infarct (unadjusted OR 4.2; 95% CI 1.19-14.8), and remained after adjusting for age and hemoglobin (OR 3.90 95%CI 1.10-13.9). The proportion of abnormal psychological testing was higher in the small infarct group than in the group with larger infarct(s) or the normal group (37.5% vs. 28.6% vs. 17.2%; p=0.307).
Conclusion: High prevalence of pediatric cerebral vasculopathy was found on MR scanning. Despite clinical evidence suggesting abnormal neuropsychological testing or a prior stroke, not all of the children who had clinical evidence of neurological disorders had MRI evidence of a stroke. Additionally, a number with no evidence of stroke had infarct(s) on MRI, so-called "silent stroke." The strongest predictors of an abnormal MRI reading included having a detectable stroke or an abnormal TCD. MR imaging is a critical aspect of evaluating cerebral vasculopathy in this patient population, and will be an important measure when prospectively assessing impact in a treatment trial.
No relevant conflicts of interest to declare.
