Acute silent cerebral ischemic events in children with sickle cell anemia

Abstract

Background: Irregular, sporadic episodes of ischemic brain injury are known to occur in sickle cell anemia (SCA), resulting in overt stroke and silent cerebral infarction. Ongoing ischemia in other organs is common in SCA but has never been documented in the brain.

Objective: To test the hypothesis that acute silent cerebral ischemic events (ASCIEs) are frequent and potentially transient.

Design: Cross-sectional and cohort study of children with SCA screened by magnetic resonance imaging (MRI) of the brain for a randomized clinical trial.

Setting: Clinical trial setting in tertiary care centers.

Patients: Asymptomatic children with SCA without known stroke, neurologic injury, or epilepsy not receiving treatment with transfusions or hydroxyurea.

Main outcome measure: Incidence of ASCIEs calculated using single diffusion-weighted MRI scans (acute ischemic events that occurred within 10 days of the MRI).

Results: Acute silent cerebral ischemic events were detected on 1.3% of MRIs (10 of 771) in 652 children (mean age, 10.0 years), with an incidence of 47.3 events per 100 patient-years (95% CI, 22.7-87.2). Two of 10 children with ASCIEs had follow-up MRIs of the brain; only 1 had silent cerebral infarction in the same location as the previously detected ASCIE.

Conclusions: Children with SCA experience ongoing (chronic, intermittent) cerebral ischemia, sometimes reversible, far more frequently than previously recognized. The brain in SCA is at constant threat of ischemia.

Figures

Figure 1

Diagrams of magnetic resonance images (MRIs) and patients. A, Diagram shows how the final 2 MRI groups, the acute silent cerebral ischemic events (ASCIEs) incidence population and the silent cerebral infarction (SCI) incidence population (filled gray rectangles), were assembled to calculate the incidence rates. The 440 paired MRIs (220 patients) are the subjects who agreed to further screening after the initial MRI and possible randomization (not the entire screening population). A few patients may have had more than 1 screening or prerandomization MRI to qualify. The numbers in each box indicate the total number of MRIs considered and how many were screening or prerandomization MRIs (total [screening/prerandomization]). B, Diagram shows the degree of overlap between these 2 MRI groups, the ASCIE incidence population and the SCI incidence population, because some patients’ MRIs were used for both determinations. The number of MRIs is shown in the Venn diagram (some patients had more than 1 MRI). DWI indicates diffusion-weighted imaging.

Figure 2

Progression of an acute silent cerebral ischemic event to silent cerebral infarction. Initial screening magnetic resonance imaging (MRI) (A–C). A, A focus of restricted diffusion on diffusion-weighted imaging, with a corresponding region of decreased signal on the apparent diffusivity coefficient maps shown in panel B. These findings indicate that the cerebral ischemia occurred within the 10 days preceding the magnetic resonance imaging (MRI). The same lesion is shown on the T2–fluid-attenuated inversion recovery sequence in panel C. D, The lesion on a second MRI 4 months later on T2–fluid-attenuated inversion recovery sequence meets the study definition of silent cerebral infarction. The lesion is indicated by an arrow in all panels.

Figure 3

Radiographic resolution of an acute silent cerebral ischemic event. Initial screening magnetic resonance images (A–D). A, A focus of restricted diffusion on diffusion-weighted imaging, with a corresponding region of decreased signal on the apparent diffusivity coefficient maps shown in panel B. These findings indicate that the cerebral ischemia occurred within the 10 days preceding the magnetic resonance image. The same lesion is shown on the T2–fluid-attenuated inversion recovery sequences in the axial (C) and coronal (D) planes. The lack of any detectable lesion on a second magnetic resonance image 10 months later on T2–fluid-attenuated inversion recovery sequences in either the axial or coronal planes is shown (E and F). The region of interest is indicated by an arrow in all panels.