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January 16, 2018; 90 (3) Article

Silent cerebral infarct definitions and full-scale IQ loss in children with sickle cell anemia

Natasha A. Choudhury, Michael R. DeBaun, Mark Rodeghier, Allison A. King, John J. Strouse, Robert C. McKinstry
First published December 20, 2017, DOI: https://doi.org/10.1212/WNL.0000000000004832
Natasha A. Choudhury
From the School of Medicine (N.A.C.), Meharry Medical College; Department of Pediatrics (N.A.C., M.R.D.), Vanderbilt-Meharry Center of Excellence in Sickle Cell Disease, Vanderbilt University Medical Center, Nashville, TN; Rodeghier Consultants (M.R.), Chicago, IL; Program in Occupational Therapy and Department of Pediatrics Hematology/Oncology (A.A.K.) and Pediatric Radiology and Neuroradiology Sections (R.C.M.), Washington University School of Medicine, St. Louis, MO; and Department of Pediatrics and Medicine (J.J.S.), Division of Hematology, Johns Hopkins University School of Medicine, Baltimore, MD.
BA
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Michael R. DeBaun
From the School of Medicine (N.A.C.), Meharry Medical College; Department of Pediatrics (N.A.C., M.R.D.), Vanderbilt-Meharry Center of Excellence in Sickle Cell Disease, Vanderbilt University Medical Center, Nashville, TN; Rodeghier Consultants (M.R.), Chicago, IL; Program in Occupational Therapy and Department of Pediatrics Hematology/Oncology (A.A.K.) and Pediatric Radiology and Neuroradiology Sections (R.C.M.), Washington University School of Medicine, St. Louis, MO; and Department of Pediatrics and Medicine (J.J.S.), Division of Hematology, Johns Hopkins University School of Medicine, Baltimore, MD.
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Mark Rodeghier
From the School of Medicine (N.A.C.), Meharry Medical College; Department of Pediatrics (N.A.C., M.R.D.), Vanderbilt-Meharry Center of Excellence in Sickle Cell Disease, Vanderbilt University Medical Center, Nashville, TN; Rodeghier Consultants (M.R.), Chicago, IL; Program in Occupational Therapy and Department of Pediatrics Hematology/Oncology (A.A.K.) and Pediatric Radiology and Neuroradiology Sections (R.C.M.), Washington University School of Medicine, St. Louis, MO; and Department of Pediatrics and Medicine (J.J.S.), Division of Hematology, Johns Hopkins University School of Medicine, Baltimore, MD.
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Allison A. King
From the School of Medicine (N.A.C.), Meharry Medical College; Department of Pediatrics (N.A.C., M.R.D.), Vanderbilt-Meharry Center of Excellence in Sickle Cell Disease, Vanderbilt University Medical Center, Nashville, TN; Rodeghier Consultants (M.R.), Chicago, IL; Program in Occupational Therapy and Department of Pediatrics Hematology/Oncology (A.A.K.) and Pediatric Radiology and Neuroradiology Sections (R.C.M.), Washington University School of Medicine, St. Louis, MO; and Department of Pediatrics and Medicine (J.J.S.), Division of Hematology, Johns Hopkins University School of Medicine, Baltimore, MD.
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John J. Strouse
From the School of Medicine (N.A.C.), Meharry Medical College; Department of Pediatrics (N.A.C., M.R.D.), Vanderbilt-Meharry Center of Excellence in Sickle Cell Disease, Vanderbilt University Medical Center, Nashville, TN; Rodeghier Consultants (M.R.), Chicago, IL; Program in Occupational Therapy and Department of Pediatrics Hematology/Oncology (A.A.K.) and Pediatric Radiology and Neuroradiology Sections (R.C.M.), Washington University School of Medicine, St. Louis, MO; and Department of Pediatrics and Medicine (J.J.S.), Division of Hematology, Johns Hopkins University School of Medicine, Baltimore, MD.
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Robert C. McKinstry
From the School of Medicine (N.A.C.), Meharry Medical College; Department of Pediatrics (N.A.C., M.R.D.), Vanderbilt-Meharry Center of Excellence in Sickle Cell Disease, Vanderbilt University Medical Center, Nashville, TN; Rodeghier Consultants (M.R.), Chicago, IL; Program in Occupational Therapy and Department of Pediatrics Hematology/Oncology (A.A.K.) and Pediatric Radiology and Neuroradiology Sections (R.C.M.), Washington University School of Medicine, St. Louis, MO; and Department of Pediatrics and Medicine (J.J.S.), Division of Hematology, Johns Hopkins University School of Medicine, Baltimore, MD.
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Citation
Silent cerebral infarct definitions and full-scale IQ loss in children with sickle cell anemia
Natasha A. Choudhury, Michael R. DeBaun, Mark Rodeghier, Allison A. King, John J. Strouse, Robert C. McKinstry
Neurology Jan 2018, 90 (3) e239-e246; DOI: 10.1212/WNL.0000000000004832

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Abstract

Objective To evaluate whether application of the adult definition of silent cerebral infarct (SCI) (T2-weighted hyperintensity ≥5 mm with corresponding T1-weighted hypointensity on MRI) is associated with full-scale IQ (FSIQ) loss in children with sickle cell anemia (SCA), and if so, whether this loss is greater than that of the reference pediatric definition of SCI (T2-weighted hyperintensity ≥3 mm in children on MRI; change in FSIQ −5.2 points; p = 0.017; 95% confidence interval [CI] −9.48 to −0.93).

Methods Among children with SCA screened for SCI in the Silent Cerebral Infarct Transfusion trial, ages 5–14 years, a total of 150 participants (107 with SCIs and 43 without SCIs) were administered the Wechsler Abbreviated Scale of Intelligence. A multivariable linear regression was used to model FSIQ in this population, with varying definitions of SCI independently substituted for the SCI covariate.

Results The adult definition of SCI applied to 27% of the pediatric participants with SCIs and was not associated with a statistically significant change in FSIQ (unstandardized coefficient −3.9 points; p = 0.114; 95% CI −8.75 to 0.95), with predicted mean FSIQ of 92.1 and 96.0, respectively, for those with and without the adult definition of SCI.

Conclusions The adult definition of SCI may be too restrictive and was not associated with significant FSIQ decline in children with SCA. Based on these findings, we find no utility in applying the adult definition of SCI to children with SCA and recommend maintaining the current pediatric definition of SCI in this population.

Glossary

CI=
confidence interval;
FLAIR=
fluid-attenuated inversion recovery;
FSIQ=
full-scale IQ;
GM=
gray matter;
MS=
multiple sclerosis;
SCA=
sickle cell anemia;
SCI=
silent cerebral infarct;
SIT=
Silent Cerebral Infarct Transfusion;
T1W=
T1-weighted;
T2W=
T2-weighted;
TCD=
transcranial Doppler

Footnotes

  • Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Editorial, page 105

  • Received June 25, 2017.
  • Accepted in final form September 26, 2017.
  • Copyright © 2017 American Academy of Neurology
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