Dataset Information

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.

SUBMITTER: Quinn CT

PROVIDER: S-EPMC3677221 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Acute silent cerebral ischemic events in children with sickle cell anemia.

Quinn Charles T CT McKinstry Robert C RC Dowling Michael M MM Ball William S WS Kraut Michael A MA Casella James F JF Dlamini Nomazulu N Ichord Rebecca N RN Jordan Lori C LC Kirkham Fenella J FJ Noetzel Michael J MJ Roach E Steve ES Strouse John J JJ Kwiatkowski Janet L JL Hirtz Deborah D DeBaun Michael R MR

JAMA neurology 20130101 1

<h4>Background</h4>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.<h4>Objective</h4>To test the hypothesis that acute silent cerebral ischemic events (ASCIEs) are frequent and potentially transient.<h4>Design</h4>Cross-sectional and cohort study of children with SCA screened by magnetic resona ...[more]

PMID: 23108767

Similar Datasets

Project description:BackgroundSilent cerebral infarcts (SCI) in sickle cell anemia (SCA) are associated with future strokes and cognitive impairment, warranting early diagnosis and treatment. Detection of SCI, however, is limited by their small size, especially when neuroradiologists are unavailable. We hypothesized that deep learning may permit automated SCI detection in children and young adults with SCA as a tool to identify the presence and extent of SCI in clinical and research settings.MethodsWe utilized UNet-a deep learning model-for fully automated SCI segmentation. We trained and optimized UNet using brain magnetic resonance imaging from the SIT trial (Silent Infarct Transfusion). Neuroradiologists provided the ground truth for SCI diagnosis, while a vascular neurologist manually delineated SCI on fluid-attenuated inversion recovery and provided the ground truth for SCI segmentation. UNet was optimized for the highest spatial overlap between automatic and manual delineation (dice similarity coefficient). The optimized UNet was externally validated using an independent single-center prospective cohort of SCA participants. Model performance was evaluated through sensitivity and accuracy (%correct cases) for SCI diagnosis, dice similarity coefficient, intraclass correlation coefficient (metric of volumetric agreement), and Spearman correlation.ResultsThe SIT trial (n=926; 31% with SCI; median age, 8.9 years) and external validation (n=80; 50% with SCI; age, 11.5 years) cohorts had small median lesion volumes of 0.40 and 0.25 mL, respectively. Compared with the neuroradiology diagnosis, UNet predicted SCI presence with 100% sensitivity and 74% accuracy. In magnetic resonance imaging with SCI, UNet reached a moderate spatial agreement (dice similarity coefficient, 0.48) and high volumetric agreement (intraclass correlation coefficient, 0.76; ρ=0.72; P<0.001) between automatic and manual segmentations.ConclusionsUNet, trained using a large pediatric SCA magnetic resonance imaging data set, sensitively detected small SCI in children and young adults with SCA. While additional training is needed, UNet may be integrated into the clinical workflow as a screening tool, aiding in SCI diagnosis.

Project description:BackgroundSilent cerebral infarcts are the most common neurologic injury in children with sickle cell anemia and are associated with the recurrence of an infarct (stroke or silent cerebral infarct). We tested the hypothesis that the incidence of the recurrence of an infarct would be lower among children who underwent regular blood-transfusion therapy than among those who received standard care.MethodsIn this randomized, single-blind clinical trial, we randomly assigned children with sickle cell anemia to receive regular blood transfusions (transfusion group) or standard care (observation group). Participants were between 5 and 15 years of age, with no history of stroke and with one or more silent cerebral infarcts on magnetic resonance imaging and a neurologic examination showing no abnormalities corresponding to these lesions. The primary end point was the recurrence of an infarct, defined as a stroke or a new or enlarged silent cerebral infarct.ResultsA total of 196 children (mean age, 10 years) were randomly assigned to the observation or transfusion group and were followed for a median of 3 years. In the transfusion group, 6 of 99 children (6%) had an end-point event (1 had a stroke, and 5 had new or enlarged silent cerebral infarcts). In the observation group, 14 of 97 children (14%) had an end-point event (7 had strokes, and 7 had new or enlarged silent cerebral infarcts). The incidence of the primary end point in the transfusion and observation groups was 2.0 and 4.8 events, respectively, per 100 years at risk, corresponding to an incidence rate ratio of 0.41 (95% confidence interval, 0.12 to 0.99; P=0.04).ConclusionsRegular blood-transfusion therapy significantly reduced the incidence of the recurrence of cerebral infarct in children with sickle cell anemia. (Funded by the National Institute of Neurological Disorders and Stroke and others; Silent Cerebral Infarct Multi-Center Clinical Trial ClinicalTrials.gov number, NCT00072761, and Current Controlled Trials number, ISRCTN52713285.).

Project description:Research in sickle cell anemia (SCA) has used, with limited race-matched control data, binary categorization of patients according to the presence or absence of silent cerebral infarction (SCI). SCI have primarily been identified using low-resolution MRI, with radiological definitions varying in lesion length and the requirement for abnormality on both fluid attenuated inversion recovery (FLAIR) and T1-weighted images. We aimed to assess the effect of published SCI definitions on global, regional, and lobar lesion metrics and their value in predicting cognition. One hundred and six patients with SCA and 48 controls aged 8-30 years underwent 3T MRI with a high-resolution FLAIR sequence and Wechsler cognitive assessment. Prevalence, number, and volume of lesions were calculated using a semi-automated pipeline for SCI defined as: (1) Liberal: any length (L-SCI); (2) Traditional: >3 mm in greatest dimension (T-SCI); (3) Restrictive; >3 mm in greatest dimension with a corresponding T1-weighted hypo-intensity (R-SCI). Globally, as hypothesized, there were large effects of SCI definition on lesion metrics in patients and controls, with prevalence varying from 24-42% in patients, and 4-23% in controls. However, contrary to hypotheses, there was no effect of any global metric on cognition. Regionally, there was a consistent distribution of SCI in frontal and parietal deep and juxta-cortical regions across definitions and metrics in patients, but no consistent distribution in controls. Effects of regional SCI metrics on cognitive performance were of small magnitude; some were paradoxical. These findings expose the challenges associated with the widespread use of SCI presence as a biomarker of white-matter injury and cognitive dysfunction in cross-sectional high-resolution MRI studies in patients with SCA. The findings indicate that with high-resolution MRI: (1) radiological definitions have a large effect on resulting lesion groups, numbers, and volumes; (2) there is a non-negligible prevalence of lesions in young healthy controls; and (3) at the group-level, there is no cross-sectional association between global lesion metrics and general cognitive impairment irrespective of lesion definition and metric. With high-resolution multi-modal MRI, the dichotomy of presence or absence of SCI does not appear to be a sensitive biomarker for the detection of functionally significant pathology; the search for appropriate endpoints for clinical treatment trials should continue.

Project description:Silent cerebral infarction (SCI) is the most commonly reported radiological abnormality in patients with sickle cell anemia (SCA) and is associated with future clinical stroke risk. To date, there have been few histological and quantitative MRI studies of SCI and multiple radiological definitions exist. As a result, the tissue characteristics and composition of SCI remain elusive. The objective of this work was therefore to investigate the composition of segmented SCI lesions using quantitative MRI for R 2* and quantitative magnetic susceptibility mapping (QSM). 211 SCI lesions were segmented from 32 participants with SCA and 6 controls. SCI were segmented according to two definitions (FLAIR+/-T1w-based threshold) using a semi-automated pipeline. Magnetic susceptibility (χ) and R 2* maps were calculated from a multi-echo gradient echo sequence and mean SCI values were compared to an equivalent region of interest in normal appearing white matter (NAWM). SCI χ and R 2* were investigated as a function of SCI definition, patient demographics, anatomical location, and cognition. Compared to NAWM, SCI were significantly less diamagnetic (χ = -0.0067 ppm vs. -0.0153 ppm, p < 0.001) and had significantly lower R 2* (16.7 s-1 vs. 19.2 s-1, p < 0.001). SCI definition had a significant effect on the mean SCI χ and R 2* , with lesions becoming significantly less diamagnetic and having significantly lower R 2* after the application of a more stringent T1w-based threshold. SCI-NAWM R 2* decrease was significantly greater in patients with SCA compared with controls (-2.84 s-1 vs. -0.64 s-1, p < 0.0001). No significant association was observed between mean SCI-NAWM χ or R2* differences and subject age, lesion anatomical location, or cognition. The increased χ and decreased R 2* in SCI relative to NAWM observed in both patients and controls is indicative of lower myelin or increased water content within the segmented lesions. The significant SCI-NAWM R 2* differences observed between SCI in patients with SCA and controls suggests there may be differences in tissue composition relative to NAWM in SCI in the two populations. Quantitative MRI techniques such as QSM and R 2* mapping can be used to enhance our understanding of the pathophysiology and composition of SCI in patients with SCA as well as controls.

Dataset Information

Acute silent cerebral ischemic events in children with sickle cell anemia.

Background

Objective

Design

Setting

Patients

Main outcome measure

Results

Conclusions

Publications

Acute silent cerebral ischemic events in children with sickle cell anemia.

Similar Datasets

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