TY - JOUR
T1 - Risk factor analysis of cerebral white matter hyperintensities in children with sickle cell disease
AU - van der Land, Veronica
AU - Mutsaerts, Henri J.M.M.
AU - Engelen, Marc
AU - Heijboer, Harriët
AU - Roest, Mark
AU - Hollestelle, Martine J.
AU - Kuijpers, Taco W.
AU - Nederkoorn, Paul J.
AU - Cnossen, Marjon H.
AU - Majoie, Charles B.L.M.
AU - Nederveen, Aart J.
AU - Fijnvandraat, Karin
PY - 2016/1/1
Y1 - 2016/1/1
N2 - 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 HbSβ0thalassaemia, 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 = 0·25, 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.
AB - 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 HbSβ0thalassaemia, 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 = 0·25, 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.
KW - Cerebral blood flow
KW - Sickle cell disease
KW - White matter hyperintensities
UR - http://www.scopus.com/inward/record.url?scp=84954028324&partnerID=8YFLogxK
U2 - https://doi.org/10.1111/bjh.13819
DO - https://doi.org/10.1111/bjh.13819
M3 - Article
C2 - 26492630
SN - 0007-1048
VL - 172
SP - 274
EP - 284
JO - British journal of haematology
JF - British journal of haematology
IS - 2
ER -