Regional brain volumes and their relationship to neurocognitive outcomes in children with severe hemophilia A.

The effect of factor VIII (FVIII) deficiency on neurocognitive outcomes in children with hemophilia A (HA) is not well characterized. This study aimed to examine differences in brain volume and neurocognition between children with severe HA and healthy controls.This single-center study included 32 males aged 6 to 16 years, 9 with severe FVIII deficiency and 23 healthy controls. Volumetric data from magnetic resonance imaging and neurocognitive testing were compared using linear models including age to evaluate the association between regional brain volume and function. Cerebellar gray matter volume was significantly smaller in the HA cohort than in healthy controls (estimate, -0.375; 95% confidence interval [CI], -0.732 to -0.019; t = 2.07;  = .049). A reduction in cerebellar gray matter was associated with neurocognitive executive dysfunction as noted by abnormal scores on 2 executive function assessments: the Delis-Kaplan Executive Function System, total switching accuracy (estimate, 0.549; 95% CI, -0.876 to 0.221; t = -3.28;  = .003) and total correct category switching (estimate, 0.538; 95% CI, -0.868 to 0.207; t = -3.19;  = .004), and the Behavior Rating Inventory of Executive Function, behavioral regulation index score (estimate, 0.531; 95% CI, 0.228-0.835; t = 3.44;  = .002). Our study provides key insights into the lower brain volumes found in patients with HA and the corresponding executive dysfunction. Quantitative brain volume assessment in patients with HA may provide an integrated measure and with further research could be a useful clinical tool when assessing risk for neurocognitive dysfunction.