Magnetic resonance angiography‐defined intracranial vasculopathy is associated with silent cerebral infarcts and glucose‐6‐phosphate dehydrogenase mutation in children with sickle cell anaemia

Abstract

Summary Silent cerebral infarct (SCI) is the most commonly recognized cause of neurological injury in sickle cell anaemia (SCA). We tested the hypothesis that magnetic resonance angiography (MRA)-defined vasculopathy is associated with SCI. Furthermore, we examined genetic variations in glucose-6-phosphate dehydrogenase (G6PD) and HBA (α-globin) genes to determine their association with intracranial vasculopathy in children with SCA. Magnetic resonance imaging (MRI) of the brain and MRA of the cerebral vasculature were available in 516 paediatric patients with SCA, enrolled in the Silent Infarct Transfusion (SIT) Trial. All patients were screened for G6PD mutations and HBA deletions. SCI were present in 41.5%(214 of 516) of SIT Trial children. The frequency of intracranial vasculopathy with and without SCI was 15.9% and 6.3%, respectively (p<0.001). Using a multivariate logistic regression model, only the presence of a SCI was associated with increased odds of vasculopathy (p=0.0007, odds ratio (OR) 2.84; 95% Confidence Interval (CI)=1.55-5.21). Among male patients with SCA, G6PD status was associated with vasculopathy (p=0.04, OR 2.78; 95% CI=1.04-7.42), while no significant association was noted for HBA deletions. Intracranial vasculopathy was observed in a minority of children with SCA, and when present, was associated with G6PD status in males and SCI.

Large-Vessel Vasculopathy in Children With Sickle Cell Disease: A Magnetic Resonance Imaging Study of Infarct Topography and Focal Atrophy

“…11,26–29 The borderzone, also referred to as the “watershed region”, consists of the area supplied by the terminal collaterals of two adjacent large vessels, such as the anterior cerebral artery and middle cerebral artery. The borderzone is suspected to have lower cerebral blood flow (CBF) relative to other areas of the brain and be uniquely sensitive to states of hypoperfusion, such as in adults with ipsilateral internal carotid artery occlusion.…”

Guidelines for the Primary Prevention of Stroke

“…579 The SIT Trial found that 2 variations in the G6PD gene that are linked to reduced enzymatic function, rs1050828 and rs1050829, were associated with vasculopathy in male participants with SCD (OR, 2.78; 95% CI, 1.04–7.42; P =0.04). 580 Further validation of these findings is required before these genetic variations can be used for stroke risk prediction.…”

Minireview: Clinical severity in sickle cell disease: the challenges of definition and prognostication

“…Some studies indicate no association between G6PD deficiency and stroke or cerebral vasculopathy, 17,23,24 while others do show an increased frequency of magnetic resonance index (MRI)- or transcranial Doppler (TCD)-defined cerebral vasculopathy. 18,25,26 These conflicting data limit the prognostic utility of G6PD deficiency.…”