title: 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: 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 multivariable 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 children 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.
authors.affiliation: Department of Neurology and Pediatrics, Washington University School of Medicine, Saint Louis, MO, USA.
authors.forename: Mathula
authors.initials: M
authors.lastname: Thangarajh
authors.forename: Genyan
authors.initials: G
authors.lastname: Yang
authors.forename: Dana
authors.initials: D
authors.lastname: Fuchs
authors.forename: Maria R
authors.initials: MR
authors.lastname: Ponisio
authors.forename: Robert C
authors.initials: RC
authors.lastname: McKinstry
authors.forename: Alok
authors.initials: A
authors.lastname: Jaju
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Noetzel
authors.forename: James F
authors.initials: JF
authors.lastname: Casella
authors.forename: Emily
authors.initials: E
authors.lastname: Barron-Casella
authors.forename: W Craig
authors.initials: WC
authors.lastname: Hooper
authors.forename: Sheree L
authors.initials: SL
authors.lastname: Boulet
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Bean
authors.forename: Meredith E
authors.initials: ME
authors.lastname: Pyle
authors.forename: Amanda B
authors.initials: AB
authors.lastname: Payne
authors.forename: Jennifer
authors.initials: J
authors.lastname: Driggers
authors.forename: Heidi A
authors.initials: HA
authors.lastname: Trau
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Vendt
authors.forename: Mark
authors.initials: M
authors.lastname: Rodeghier
authors.forename: Michael R
authors.initials: MR
authors.lastname: DeBaun
mesh_terms: D000293:Adolescent; D000755:Anemia, Sickle Cell / Q000150:complications* / Q000235:genetics* / Q000628:therapy; D001803:Blood Transfusion; D002544:Cerebral Infarction / Q000175:diagnosis* / Q000209:etiology* / Q000628:therapy; D002648:Child; D002675:Child, Preschool; D005260:Female; D005954:Glucosephosphate Dehydrogenase / Q000235:genetics*; D006801:Humans; D018810:Magnetic Resonance Angiography; D008297:Male; D009154:Mutation; D012737:Sex Factors; D055542:alpha-Globins / Q000235:genetics
chemical_list: D055542:alpha-Globins; D005954:Glucosephosphate Dehydrogenase