Prevalence of intracranial stenosis and silent cerebral infarcts in children with sickle cell anemia and low risk of stroke

Authors

  • Michal Arkuszewski,

    1. Department of Radiology, Division of Neuroradiology, University of Pennsylvania, Philadelphia, PA, USA
    2. Department of Neurology, Medical University of Silesia, Katowice, Poland
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  • Jaroslaw Krejza,

    Corresponding author
    1. Al-Imam Muhammad Ibn Saud Islamic University, Riyadh, Saudi Arabia
    2. Department of Nuclear Medicine, Medical University of Gdansk, Gdansk, Poland
    • Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland Medical Center, Baltimore, MD, USA
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  • Rong Chen,

    1. Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland Medical Center, Baltimore, MD, USA
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  • Rebecca Ichord,

    1. Department of Neurology, Children's Hospital of Philadelphia, Philadelphia, PA, USA
    2. Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA, USA
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  • Janet L. Kwiatkowski,

    1. Department of Hematology, Children's Hospital of Philadelphia, Philadelphia, PA, USA
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  • Michel Bilello,

    1. Department of Radiology, Division of Neuroradiology, University of Pennsylvania, Philadelphia, PA, USA
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  • Robert Zimmerman,

    1. Department of Radiology, Children's Hospital of Philadelphia, Philadelphia, PA, USA
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  • Kwaku Ohene-Frempong,

    1. Department of Hematology, Children's Hospital of Philadelphia, Philadelphia, PA, USA
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  • Elias R. Melhem

    1. Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland Medical Center, Baltimore, MD, USA
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  • Conflicts of interest: The authors declare no potential conflict of interest.
  • Funding: Study supported by NIH grant (5-R01 NS-046717).

Correspondence: Jaroslaw Krejza, Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland Medical Center; 22 S. Greene Street, Baltimore, MD 21201, USA.

E-mail: jkrejza@me.com

Dear Editor

Many children with sickle cell disease (SCD) have silent cerebral infarcts (SCI) that are predictive of stroke [1, 2]. The prevalence of SCI on magnetic resonance (MR) scans is about 22% by age 11 years, but reaches 40% in those with abnormal transcranial Doppler ultrasound (TCD) results [3]. The distribution of SCI supports the role of large-vessel stenosis in developing stroke [4]; however, the utility of TCD in identifying arterial stenosis in children at high risk of stroke is limited [5]. Neurologically intact children with TCD velocity (<170 cm/s) but with undetected stenosis might be denied the stroke-preventive benefits of transfusions. High prevalence of stenosis may indicate implementing more aggressive screening approach, for instance, by performing TCD and MR angiography.

We studied a carefully selected cohort of 67 neurologically intact children with SCD without prior clinically overt stroke or transient ischemic attack (median age 8·8 years; range 2·3–13·1 years; 33 females) with TCD velocity <170 cm/s to determine prevalence of stenosis and explore its association with occurrences of SCI. We found 10 mild-to-moderate stenoses in seven children (10%), including four with isolated left terminal internal carotid artery stenosis and three with multiple intracranial stenoses. We found SCI in 26 children (38%), median number of SCI was two (range limits: 1 ÷ 9), median volume of infarcts was 171 mm3 (range limits: 7 ÷ 1060 mm3), and median infarct volume in relation to total brain volume was 0·020% (range limits: 0·001 ÷ 0·101%). The number and volume of infarcts were significantly higher in children with arterial stenosis (both P = 0·023; example on Fig. 1).

Figure 1.

Magnetic resonance images obtained from a 7·5-year-old, neurologically intact boy with sickle cell anemia. (a) 3D magnetic resonance angiographic image of intracranial vessels shows 25–49% stenosis of the left ICA and 50–74% stenosis of the left MCA (arrowheads). (b, c, d) Magnetic resonance images (FLAIR sequence) in sagittal (b) and axial (c, d) planes show multiple silent infarcts in the left hemisphere (arrows).

We showed that over 10% of low-risk SCD children who are free of clinically overt stroke have intracranial stenosis associated with higher number and volume of SCI. Given the reported association of SCI with risk of overt stroke [1], it is likely that children with normal TCD velocities who have arterial stenosis are at higher risk of clinically overt stroke compared to children without arterial stenosis. Although we did not evaluate the risk of stroke or neurologic functional impairment in children with arterial stenosis alone or in association with SCI, our findings suggest that this association deserves further study.

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