TY - JOUR
T1 - Silent infarcts in sickle cell disease occur in the border zone region and are associated with low cerebral blood flow
AU - Ford, Andria L.
AU - Ragan, Dustin K.
AU - Fellah, Slim
AU - Binkley, Michael M.
AU - Fields, Melanie E.
AU - Guilliams, Kristin P.
AU - An, Hongyu
AU - Jordan, Lori C.
AU - McKinstry, Robert C.
AU - Lee, Jin Moo
AU - DeBaun, Michael R.
N1 - Funding Information:
This work was supported by the National Institutes of Health (NIH) National Heart, Lung, and Blood Institute (R01HL129241, A.L.F; K23HL136904 and K12HL087197, M.E.F.); NIH National Institute of Neurological Disorders and Stroke (5U01NS042804, 3U01NS042804, American Recovery Reinvestment ACT supplementary grant, M.R.D.; R01NS085419, R01NS084028, R01NS094692, R21AG05533301, J.-M.L.; R01NS082561 and P30NS098577, H.A.; K23NS099472, K.P.G.); Child Neurology Foundation (K.P.G.); Pediatric Critical Care and Trauma Scientist Development Program (K12 HD04734, K.P.G.); Washington University St. Louis, Clinical and Translational Science Award (UL1 TR000448, K.P.G., M.E.F.); and Vanderbilt University Medical Center, Clinical and Translational Science Award UL1TR000445 (M.R.D.).
Publisher Copyright:
© 2018 by The American Society of Hematology.
PY - 2018/10/18
Y1 - 2018/10/18
N2 - Silent cerebral infarcts (SCIs) are associated with cognitive impairment in sickle cell anemia (SCA). SCI risk factors include low hemoglobin and elevated systolic blood pressure; however, mechanisms underlying their development are unclear. Using the largest prospective study evaluating SCIs in pediatric SCA, we identified brain regions with increased SCI density. We tested the hypothesis that infarct density is greatest within regions in which cerebral blood flow is lowest, further restricting cerebral oxygen delivery in the setting of chronic anemia. Neuroradiology and neurology committees reached a consensus of SCIs in 286 children in the Silent Infarct Transfusion (SIT) Trial. Each infarct was outlined and coregistered to a brain atlas to create an infarct density map. To evaluate cerebral blood flow as a function of infarct density, pseudocontinuous arterial spin labeling was performed in an independent pediatric SCA cohort. Blood flow maps were aligned to the SIT Trial infarct density map. Mean blood flow within low, moderate, and high infarct density regions from the SIT Trial were compared. Logistic regression evaluated clinical and imaging predictors of overt stroke at 3-year follow-up. The SIT Trial infarct density map revealed increased SCI density in the deep white matter of the frontal and parietal lobes. A relatively small region, measuring 5.6% of brain volume, encompassed SCIs from 90% of children. Cerebral blood flow was lowest in the region of highest infarct density (P < .001). Baseline infarct volume and reticulocyte count predicted overt stroke. In pediatric SCA, SCIs are symmetrically located in the deep white matter where minimum cerebral blood flow occurs. (Blood. 2018;132(16):1714-1723).
AB - Silent cerebral infarcts (SCIs) are associated with cognitive impairment in sickle cell anemia (SCA). SCI risk factors include low hemoglobin and elevated systolic blood pressure; however, mechanisms underlying their development are unclear. Using the largest prospective study evaluating SCIs in pediatric SCA, we identified brain regions with increased SCI density. We tested the hypothesis that infarct density is greatest within regions in which cerebral blood flow is lowest, further restricting cerebral oxygen delivery in the setting of chronic anemia. Neuroradiology and neurology committees reached a consensus of SCIs in 286 children in the Silent Infarct Transfusion (SIT) Trial. Each infarct was outlined and coregistered to a brain atlas to create an infarct density map. To evaluate cerebral blood flow as a function of infarct density, pseudocontinuous arterial spin labeling was performed in an independent pediatric SCA cohort. Blood flow maps were aligned to the SIT Trial infarct density map. Mean blood flow within low, moderate, and high infarct density regions from the SIT Trial were compared. Logistic regression evaluated clinical and imaging predictors of overt stroke at 3-year follow-up. The SIT Trial infarct density map revealed increased SCI density in the deep white matter of the frontal and parietal lobes. A relatively small region, measuring 5.6% of brain volume, encompassed SCIs from 90% of children. Cerebral blood flow was lowest in the region of highest infarct density (P < .001). Baseline infarct volume and reticulocyte count predicted overt stroke. In pediatric SCA, SCIs are symmetrically located in the deep white matter where minimum cerebral blood flow occurs. (Blood. 2018;132(16):1714-1723).
UR - http://www.scopus.com/inward/record.url?scp=85055079713&partnerID=8YFLogxK
U2 - 10.1182/blood-2018-04-841247
DO - 10.1182/blood-2018-04-841247
M3 - Article
C2 - 30061156
AN - SCOPUS:85055079713
SN - 0006-4971
VL - 132
SP - 1714
EP - 1723
JO - Blood
JF - Blood
IS - 16
ER -