title: Chronic and acute anemia and extracranial internal carotid stenosis are risk factors for silent cerebral infarcts in sickle cell anemia.
abstract: Early transcranial Doppler (TCD) screening of the Créteil sickle cell anemia (SCA)-newborn cohort, and rapid initiation of transfusion programs, resulted in successful prevention of overt strokes, but a high cumulative risk of silent cerebral infarcts (SCI) remained, suggesting that TCD screening does not identify all patients with SCA at risk for SCI. We hypothesized that episodes of hypoperfusion/hypoxia, as observed during acute chest syndromes or acute anemic events (AAE), and extracranial internal carotid artery (eICA) stenoses, detectable via submandibular Doppler sonography and cervical magnetic resonance angiography (MRA), could also be risk factors for SCI. This study includes 189 stroke-free patients with SCA from the Créteil newborn cohort (1992-2010) followed longitudinally by magnetic resonance imaging/MRA, including cervical MRA at the last assessment. All patients with abnormal TCD and/or intracranial stenoses were placed on a transfusion program. Mean follow-up was 9.9 years (range, 2.2-19.9 years; 1844 patient-years). Annual rates of clinical events were calculated. The cumulative risk for SCI was 39.1% (95% confidence interval [CI], 23.5%-54.7%) by age 18 years, with no plateau. We confirm that baseline hemoglobin level lower than 7 g/dL before age 3 years is a highly significant predictive risk factor for SCI (hazard ratio, 2.97; 95% CI, 1.43-6.17; P = .004). Furthermore, we show that AAE rate (odds ratio, 2.64 per unit increase; 95% CI, 1.09-6.38; P = .031) and isolated eICA stenosis (odds ratio, 3.19; 95% CI, 1.18-8.70; P = .023) are significant and independent risk factors for SCI.
authors.affiliation: Referral Center for Sickle Cell Disease, Department of Pediatrics, Centre Hospitalier Intercommunal, Créteil, University Paris XII, France;
authors.forename: Françoise
authors.initials: F
authors.lastname: Bernaudin
authors.affiliation: Medical Imaging Department, Referral Center for Sickle Cell Disease, Centre Hospitalier Intercommunal, Créteil, France; and.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Verlhac
authors.affiliation: Referral Center for Sickle Cell Disease, Department of Pediatrics, Centre Hospitalier Intercommunal, Créteil, University Paris XII, France;
authors.forename: Cécile
authors.initials: C
authors.lastname: Arnaud
authors.affiliation: Referral Center for Sickle Cell Disease, Department of Pediatrics, Centre Hospitalier Intercommunal, Créteil, University Paris XII, France;
authors.forename: Annie
authors.initials: A
authors.lastname: Kamdem
authors.affiliation: Medical Imaging Department, Referral Center for Sickle Cell Disease, Centre Hospitalier Intercommunal, Créteil, France; and.
authors.forename: Manuela
authors.initials: M
authors.lastname: Vasile
authors.affiliation: Medical Imaging Department, Referral Center for Sickle Cell Disease, Centre Hospitalier Intercommunal, Créteil, France; and.
authors.forename: Florence
authors.initials: F
authors.lastname: Kasbi
authors.affiliation: Department of Pediatrics, Centre Hospitalier Intercommunal, Créteil, University Paris XII, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Hau
authors.affiliation: Department of Pediatrics, Centre Hospitalier Intercommunal, Créteil, University Paris XII, France.
authors.forename: Fouad
authors.initials: F
authors.lastname: Madhi
authors.affiliation: Department of Pediatrics, Centre Hospitalier Intercommunal, Créteil, University Paris XII, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Fourmaux
authors.affiliation: Department of Pediatrics, Centre Hospitalier Intercommunal, Créteil, University Paris XII, France.
authors.forename: Sandra
authors.initials: S
authors.lastname: Biscardi
authors.affiliation: Department of Pediatrics, Centre Hospitalier Intercommunal, Créteil, University Paris XII, France.
authors.forename: Ralph
authors.initials: R
authors.lastname: Epaud
authors.affiliation: Referral Center for Sickle Cell Disease, Department of Pediatrics, Centre Hospitalier Intercommunal, Créteil, University Paris XII, France;
authors.forename: Corinne
authors.initials: C
authors.lastname: Pondarré
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000740:Anemia / Q000097:blood / Q000150:complications*; D000755:Anemia, Sickle Cell / Q000097:blood / Q000150:complications* / Q000235:genetics; D001783:Blood Flow Velocity; D002343:Carotid Artery, Internal; D016893:Carotid Stenosis / Q000150:complications* / Q000175:diagnosis / Q000503:physiopathology; D002544:Cerebral Infarction / Q000175:diagnosis / Q000209:etiology*; D002648:Child; D002675:Child, Preschool; D002908:Chronic Disease; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008137:Longitudinal Studies; D018810:Magnetic Resonance Angiography; D008279:Magnetic Resonance Imaging; D008297:Male; D012307:Risk Factors; D055815:Young Adult