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Clinical Trial
. 2014 Aug 7;124(6):891-8.
doi: 10.1182/blood-2013-12-545186. Epub 2014 Jun 9.

Magnetic resonance imaging/angiography and transcranial Doppler velocities in sickle cell anemia: results from the SWiTCH trial

Kathleen J Helton  1 , Robert J Adams  2 , Karen L Kesler  3 , Alex Lockhart  3 , Banu Aygun  4 , Catherine Driscoll  5 , Matthew M Heeney  6 , Sherron M Jackson  2 , Lakshmanan Krishnamurti  7 , Scott T Miller  8 , Sharada A Sarnaik  9 , William H Schultz  10 , Russell E Ware  10 ; SWiTCH Investigators
Collaborators, Affiliations
Clinical Trial

Magnetic resonance imaging/angiography and transcranial Doppler velocities in sickle cell anemia: results from the SWiTCH trial

Kathleen J Helton et al. Blood. .

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.

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Figures

Figure 1
Figure 1
Grading of vascular occlusion based on MRA. Each cerebral hemisphere and its corresponding vessels were reported separately because they represent functionally and structurally independent systems. Vessels occlusions of ≤5 mm in length are not counted. Stenosis is scored as mild (25-49%), moderate (50-74%), severe (75-99%), or occlusion (>99%).
Figure 2
Figure 2
SWiTCH TCD velocity results by cerebral hemisphere and study time point.
Figure 3
Figure 3
Segmental stenosis in SWiTCH subjects by TCD velocity, vessel region, and hemisphere. (A) Baseline studies. (B) Exit studies.
See this image and copyright information in PMC

Comment in

References

    1. Powars D, Wilson B, Imbus C, Pegelow C, Allen J. The natural history of stroke in sickle cell disease. Am J Med. 1978;65(3):461–471. - PubMed
    1. Ohene-Frempong K. Stroke in sickle cell disease: demographic, clinical, and therapeutic considerations. Semin Hematol. 1991;28(3):213–219. - PubMed
    1. Wang WC, Langston JW, Steen RG, et al. Abnormalities of the central nervous system in very young children with sickle cell anemia. J Pediatr. 1998;132(6):994–998. - PubMed
    1. Steen RG, Emudianughe T, Hankins GM, et al. Brain imaging findings in pediatric patients with sickle cell disease. Radiology. 2003;228(1):216–225. - PubMed
    1. Leikin SL, Gallagher D, Kinney TR, Sloane D, Klug P, Rida W Cooperative Study of Sickle Cell Disease. Mortality in children and adolescents with sickle cell disease. Pediatrics. 1989;84(3):500–508. - PubMed

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