title: Magnetic resonance imaging/angiography and transcranial Doppler velocities in sickle cell anemia: results from the SWiTCH trial.
abstract: The Stroke With Transfusions Changing to Hydroxyurea (SWiTCH) trial compared standard (transfusions/chelation) to alternative (hydroxyurea/phlebotomy) treatment to prevent recurrent stroke and manage iron overload in children chronically transfused over 7 years before enrollment. Standardized brain magnetic resonance imaging/magnetic resonance angiography (MRA) and transcranial Doppler (TCD) exams were performed at entry and exit, with a central blinded review. A novel MRA vasculopathy grading scale demonstrated frequent severe baseline left/right vessel stenosis (53%/41% ≥Grade 4); 31% had no vessel stenosis on either side. Baseline parenchymal injury was prevalent (85%/79% subcortical, 53%/37% cortical, 50%/35% subcortical and cortical). Most children had low or uninterpretable baseline middle cerebral artery TCD velocities, which were associated with worse stenoses (incidence risk ratio [IRR] = 5.1, P ≤ .0001 and IRR = 4.1, P < .0001) than normal velocities; only 2% to 12% had any conditional/abnormal velocity. Patients with adjudicated stroke (7) and transient ischemic attacks (19 in 11 standard/8 alternative arm subjects) had substantial parenchymal injury/vessel stenosis. At exit, 1 child (alternative arm) had a new silent infarct, and another had worse stenosis. SWiTCH neuroimaging data document severe parenchymal and vascular abnormalities in children with SCA and stroke and support concerns about chronic transfusions lacking effectiveness for preventing progressive cerebrovascular injury. The novel SWiTCH vasculopathy grading scale warrants validation testing and consideration for use in future clinical trials. This trial was registered at www.clinicaltrials.gov as #NCT00122980.
authors.affiliation: St. Jude Children's Research Hospital, Memphis, TN;
authors.forename: Kathleen J
authors.initials: KJ
authors.lastname: Helton
authors.affiliation: Medical University of South Carolina, Charleston, SC;
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Adams
authors.affiliation: Rho Inc., Chapel Hill, NC;
authors.forename: Karen L
authors.initials: KL
authors.lastname: Kesler
authors.affiliation: Rho Inc., Chapel Hill, NC;
authors.forename: Alex
authors.initials: A
authors.lastname: Lockhart
authors.affiliation: Cohen Children's Medical Center, New Hyde Park, NY;
authors.forename: Banu
authors.initials: B
authors.lastname: Aygun
authors.affiliation: Montefiore Medical Center, New York, NY;
authors.forename: Catherine
authors.initials: C
authors.lastname: Driscoll
authors.affiliation: Children's Hospital Boston, Boston, MA;
authors.forename: Matthew M
authors.initials: MM
authors.lastname: Heeney
authors.affiliation: Medical University of South Carolina, Charleston, SC;
authors.forename: Sherron M
authors.initials: SM
authors.lastname: Jackson
authors.affiliation: Pittsburgh Children's Hospital, Pittsburgh, PA;
authors.forename: Lakshmanan
authors.initials: L
authors.lastname: Krishnamurti
authors.affiliation: SUNY-Downstate, Brooklyn, NY;
authors.forename: Scott T
authors.initials: ST
authors.lastname: Miller
authors.affiliation: Wayne State University, Detroit, MI; and.
authors.forename: Sharada A
authors.initials: SA
authors.lastname: Sarnaik
authors.affiliation: Cincinnati Children's Hospital, Cincinnati, OH.
authors.forename: William H
authors.initials: WH
authors.lastname: Schultz
authors.affiliation: Cincinnati Children's Hospital, Cincinnati, OH.
authors.forename: Russell E
authors.initials: RE
authors.lastname: Ware
mesh_terms: D000293:Adolescent; D000755:Anemia, Sickle Cell / Q000150:complications* / Q000175:diagnosis* / Q000628:therapy; D001783:Blood Flow Velocity; D001803:Blood Transfusion; D001921:Brain / Q000098:blood supply / Q000473:pathology; D002560:Cerebrovascular Circulation; D002648:Child; D002675:Child, Preschool; D005260:Female; D059907:Functional Neuroimaging; D006801:Humans; D006918:Hydroxyurea / Q000627:therapeutic use; D018810:Magnetic Resonance Angiography; D008279:Magnetic Resonance Imaging; D008297:Male; D011379:Prognosis; D055502:Secondary Prevention; D020521:Stroke / Q000175:diagnosis* / Q000209:etiology* / Q000517:prevention & control; D017585:Ultrasonography, Doppler, Transcranial; D055815:Young Adult
chemical_list: D006918:Hydroxyurea