Risk factor analysis of cerebral white matter hyperintensities in children with sickle cell disease.
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.
Department of Paediatric Haematology, Immunology and Infectious Diseases, Emma Children's Hospital, Academic Medical Centre, Amsterdam, The Netherlands.
Veronica
V
van der Land
Department of Radiology, Academic Medical Centre, Amsterdam, The Netherlands.
Henri J M M
HJ
Mutsaerts
Department of Paediatric Neurology, Emma Children's Hospital, Academic Medical Centre, Amsterdam, The Netherlands.
Marc
M
Engelen
Department of Paediatric Haematology, Immunology and Infectious Diseases, Emma Children's Hospital, Academic Medical Centre, Amsterdam, The Netherlands.
Harriët
H
Heijboer
Department of Clinical Chemistry and Haematology, University Medical Centre, Utrecht, The Netherlands.
Mark
M
Roest
Department Immunopathology and Blood Coagulation, Sanquin Diagnostic Services, Amsterdam, The Netherlands.
Martine J
MJ
Hollestelle
Department of Paediatric Haematology, Immunology and Infectious Diseases, Emma Children's Hospital, Academic Medical Centre, Amsterdam, The Netherlands.
Taco W
TW
Kuijpers
Department of Neurology, Academic Medical Centre, Amsterdam, The Netherlands.
Paul J
PJ
Nederkoorn
Department of Paediatric Oncology and Haematology, Sophia Children's Hospital, Erasmus Medical Centre, Rotterdam, The Netherlands.
Marjon H
MH
Cnossen
Department of Radiology, Academic Medical Centre, Amsterdam, The Netherlands.
Charles B L M
CB
Majoie
Department of Radiology, Academic Medical Centre, Amsterdam, The Netherlands.
Aart J
AJ
Nederveen
Department of Paediatric Haematology, Immunology and Infectious Diseases, Emma Children's Hospital, Academic Medical Centre, Amsterdam, The Netherlands.
Karin
K
Fijnvandraat
D000293:Adolescent; D000755:Anemia, Sickle Cell / Q000097:blood / Q000150:complications*; D001777:Blood Coagulation / Q000502:physiology; D002544:Cerebral Infarction / Q000097:blood / Q000209:etiology* / Q000473:pathology; D002560:Cerebrovascular Circulation / Q000502:physiology; D002648:Child; D004730:Endothelium, Vascular / Q000503:physiopathology; D005260:Female; D005319:Fetal Hemoglobin / Q000378:metabolism; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D011446:Prospective Studies; D012307:Risk Factors; D012737:Sex Factors; D066127:White Matter / Q000473:pathology*
D005319:Fetal Hemoglobin
cerebral blood flow; sickle cell disease; white matter hyperintensities