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Risk factor analysis of cerebral white matter hyperintensities in children with sickle cell disease
Veronica van der Land1, Henri J M M Mutsaerts2, Marc Engelen3
1Department of Paediatric Haematology, Immunology and Infectious Diseases, Emma Children's Hospital, Academic Medical Centre, Amsterdam, The Netherlands.
Insights
High fetal hemoglobin (HbF) may protect children with sickle cell disease (SCD) from white matter hyperintensities (WMHs). Endothelial dysfunction might reduce cerebral blood flow (CBF), contributing to WMHs in SCD.
Area of Science:
- Neurology
- Hematology
- Pediatrics
Background:
- Sickle cell disease (SCD) is associated with silent cerebral infarcts, appearing as white matter hyperintensities (WMHs) on MRI.
- The etiology of WMHs in SCD is thought to involve vaso-occlusion and reduced cerebral blood flow (CBF).
Purpose of the Study:
- To explore the relationship between WMHs and markers of endothelial dysfunction and CBF in children with SCD.
- To quantify WMH volume using 3.0 Tesla MRI.
Main Methods:
- Included 40 children with HbSS or HbSβ(0) thalassaemia (mean age 12.1 years).
- Assessed WMH volume via MRI, correlating with fetal hemoglobin (HbF) levels, ADAMTS13 activity, and CBF.
- Analyzed risk factors including sex and glucose-6-phosphate dehydrogenase deficiency.
Main Results:
- Boys had a significantly higher risk of developing WMHs (OR 4.5).
- Lower HbF levels correlated with larger WMH volumes (P=0.04).
- Lower ADAMTS13 levels were associated with reduced white matter CBF (P=0.03), suggesting endothelial dysfunction impacts CBF.
Conclusions:
- Elevated HbF may offer protection against WMHs in pediatric SCD.
- Endothelial dysfunction appears to be a contributing factor to WMH development by impairing CBF in children with SCD.
Abstract:
Sickle cell disease (SCD) is complicated by silent cerebral infarcts, visible as white matter hyperintensities (WMHs) on magnetic resonance imaging (MRI). Both local vaso-occlusion, elicited by endothelial dysfunction, and insufficiency of cerebral blood flow (CBF) have been proposed to be involved in the aetiology. We performed an explorative study to investigate the associations between WMHs and markers of endothelial dysfunction and CBF by quantifying WMH volume on 3.0 Tesla MRI. We included 40 children with HbSS or HbSβ(0) thalassaemia, with a mean age of 12.1 ± 2.6 years. Boys demonstrated an increased risk for WMHs (odds ratio 4.5, 95% confidence interval 1.2-17.4), unrelated to glucose-6-phosphate dehydrogenase deficiency. In patients with WMHs, lower fetal haemoglobin (HbF) was associated with a larger WMH volume (regression coefficient = -0.62, R2 = 0.5, P = 0.04). Lower ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) levels were associated with lower CBF in the white matter (regression coefficient = 0.07, R2 = 0.15, P = 0.03), suggesting that endothelial dysfunction could potentially hamper CBF. The findings of our explorative study suggest that a high level of HbF may be protective for WMHs and that endothelial dysfunction may contribute to the development of WMHs by reducing CBF.
