Association of enlarged perivascular space burden with silent cerebral infarcts in children with sickle cell disease

Children with sickle cell disease (SCD) have enlarged perivascular spaces (ePVS) in their basal ganglia (BG) and centrum semiovale (CSO) visible on magnetic resonance imaging (MRI). ePVS are dilated fluid-filled spaces around penetrating arterioles and venules of the brain parenchyma and are a marker of cerebral small vessel disease in adults. We used the T2-weighted MRI from the Silent Cerebral Infarct Transfusion Trial to (1) quantify the ePVS burden in children with the severe SCD genotypes and (2) evaluate for an association between ePVS burden and silent cerebral infarcts (SCIs) adjusted for laboratory/imaging measures of SCD severity. The study included 929/1191 (78%) of participants with a median age of 8.9 (5-15) years, 48% female, and 48% had a high ePVS burden in at least one region. More children with a higher ePVS burden in the BG and whole brain had at least one SCI, whereas there was no difference in SCI based on ePVS burden status in the CSO. In multivariable logistic regression, high ePVS burden was associated with the presence of SCI in the BG and whole brain only. ePVS may become a useful neuroimaging biomarker of SCD-related neurological disease.