Magnetic resonance imaging/angiography and transcranial Doppler velocities in sickle cell anemia: results from the SWiTCH trial
Kathleen J Helton, Robert J Adams, Karen L Kesler, Alex Lockhart, Banu Aygun, Catherine Driscoll, Matthew M Heeney, Sherron M Jackson, Lakshmanan Krishnamurti, Scott T Miller, Sharada A Sarnaik, William H Schultz, Russell E Ware, SWiTCH Investigators, Brigitta U Mueller, Bogdan Dinu, Matthew Heeney, Meredith Anderson, Amber Smith, Janet L Kwiatkowski, Kim Smith-Whitley, Jeffrey Olson, Vanessa Nixon, LaVerne Murphy, Lakshmanan Krishnamurti, Regina McCollum, Alexis Thompson, Jillian Prado, Kelly Verel, Ashley Brummel, Gerald Woods, Julie Routhieaux, Anne Mehrhof, Kristin Stegenga, Lori Luchtman-Jones, Caterina Minniti, Sheronda D Brown, Tracy Boswell, Ryan Burnett, Karen Kalinyak, Laurie Vanderah, Monique Lumpkin, Tammy Nordheim, Sharon Singh, Ellen Muir, Margaret T Lee, Genia Billote, Charles Daeschner, Diana Wyn Gordon, Cynthia Brown, William Owen, Anthony Villella, Terri Forsyth, Annette Slade, Lorrie Coggsdale, Clark Brown, Ifeyinwa Osunkwo, Peter Lane, Brian Philbrook, Terrell Faircloth, Korin Cherry, Eldrida Carter Randall, Ann Martha Felder, James Rhodes, Paul Scott, Danielle Jirovec, Lindsey Nelson, Sherron M Jackson, Mary Ellen Cavalier, Lisa Kuisel, Jessica Peterson, Betsy Rackoff, Cynthia Gauger, Mary Warde, Ramamoorthy Nagasubramanian, Leslie Natal, Dawn Cook, Rafael Barilari, JoAnne Neville, Banu Aygun, Winfred C Wang, Eileen Hansbury, Jennifer Larkin, Laura Martino, Lane Faughnan, Scott Miller, Kathy Rey, Lezlie Woods, Catherine Driscoll, Lakeisha N Nicholls, Zora R Rogers, Leah Adix, Roxana Mars, Brad Cook, Jennifer Marshall, Lee Hilliard, Jeanine Dumas, Lindley Webb, Annelle Reed, Ofelia Alvarez, Patrice Williams, Mary Donovan, Rathi Iyer, Mary Gail Smith, Stephanie Pepper, Glenda Thomas, Gloria Bishop, Cindy Kendig, Teresa Walker, Elizabeth Yang, Lesley Ann Owen, Sharada Sarnaik, Mary Murphy, Cynthia Burnett, Clarissa Shavers, Kathleen J Helton, Robert J Adams, Karen L Kesler, Alex Lockhart, Banu Aygun, Catherine Driscoll, Matthew M Heeney, Sherron M Jackson, Lakshmanan Krishnamurti, Scott T Miller, Sharada A Sarnaik, William H Schultz, Russell E Ware, SWiTCH Investigators, Brigitta U Mueller, Bogdan Dinu, Matthew Heeney, Meredith Anderson, Amber Smith, Janet L Kwiatkowski, Kim Smith-Whitley, Jeffrey Olson, Vanessa Nixon, LaVerne Murphy, Lakshmanan Krishnamurti, Regina McCollum, Alexis Thompson, Jillian Prado, Kelly Verel, Ashley Brummel, Gerald Woods, Julie Routhieaux, Anne Mehrhof, Kristin Stegenga, Lori Luchtman-Jones, Caterina Minniti, Sheronda D Brown, Tracy Boswell, Ryan Burnett, Karen Kalinyak, Laurie Vanderah, Monique Lumpkin, Tammy Nordheim, Sharon Singh, Ellen Muir, Margaret T Lee, Genia Billote, Charles Daeschner, Diana Wyn Gordon, Cynthia Brown, William Owen, Anthony Villella, Terri Forsyth, Annette Slade, Lorrie Coggsdale, Clark Brown, Ifeyinwa Osunkwo, Peter Lane, Brian Philbrook, Terrell Faircloth, Korin Cherry, Eldrida Carter Randall, Ann Martha Felder, James Rhodes, Paul Scott, Danielle Jirovec, Lindsey Nelson, Sherron M Jackson, Mary Ellen Cavalier, Lisa Kuisel, Jessica Peterson, Betsy Rackoff, Cynthia Gauger, Mary Warde, Ramamoorthy Nagasubramanian, Leslie Natal, Dawn Cook, Rafael Barilari, JoAnne Neville, Banu Aygun, Winfred C Wang, Eileen Hansbury, Jennifer Larkin, Laura Martino, Lane Faughnan, Scott Miller, Kathy Rey, Lezlie Woods, Catherine Driscoll, Lakeisha N Nicholls, Zora R Rogers, Leah Adix, Roxana Mars, Brad Cook, Jennifer Marshall, Lee Hilliard, Jeanine Dumas, Lindley Webb, Annelle Reed, Ofelia Alvarez, Patrice Williams, Mary Donovan, Rathi Iyer, Mary Gail Smith, Stephanie Pepper, Glenda Thomas, Gloria Bishop, Cindy Kendig, Teresa Walker, Elizabeth Yang, Lesley Ann Owen, Sharada Sarnaik, Mary Murphy, Cynthia Burnett, Clarissa Shavers
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.
© 2014 by The American Society of Hematology.
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Source: PubMed