Acute Silent Cerebral Ischemic Events in Children With Sickle Cell Anemia

Quinn, Charles T.; McKinstry, Robert C.; Dowling, Michael M.; Ball, William S.; Kraut, Michael A.; Casella, James F.; Dlamini, Nomazulu; Ichord, Rebecca; Jordan, Lori C.; Kirkham, Fenella J.; Noetzel, Michael J.; Roach, E. Steve; Strouse, John J.; Kwiatkowski, Janet L.; Hirtz, Deborah; DeBaun, Michael R.

doi:10.1001/jamaneurol.2013.576

Cited by 59 publications

(72 citation statements)

References 24 publications

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“…The present study reports a significant association between the AAE rate and the risk for SCI, strengthening the causal relationship previously suggested. 17,18,29,30 A trend toward significance for the association between intracranial stenosis and SCI was found at the first MRI/MRA assessment. This is in agreement with data from the Philadelphia young cohort study, 12 which assessed 68 (70.8%) of 96 children before age 6 years and found SCI in 18/68 patients, associated with the presence of intracranial stenosis by univariate analysis.…”

Section: Discussionmentioning

confidence: 91%

“…A relationship between cerebrovascular events and/or SCI and acute anemic events 17,18,29,30 has been previously described, but not systematically evaluated in a large newborn cohort. Cerebrovascular episodes have been reported to be as 58 times higher than expected in the 5-week interval after AAE related to B19 infection.…”

Section: Discussionmentioning

confidence: 99%

“…8 3 10 9 /L, and the SEN bS globin gene haplotype (Cooperative Study of Sickle Cell Disease cohort), 9 low baseline hemoglobin level (Créteil 6 and Philadelphia cohorts, 12 and the Silent Infarct Transfusion [SIT] Trial), 14,15 and the presence of intracranial stenosis (Créteil 6,16 and Philadelphia cohorts 12 ). Since then, 2 important findings have been reported: first, acute anemic events (AAE), defined as an hemoglobin concentration of 5.5 g/dL or less, regardless of etiology, with at least a 30% decrease from the patient's clinically established baseline, 17 may be responsible for acute silent cerebral ischemic events, which are identified using diffusion-weighted magnetic resonance imaging (MRI) and can be reversible or result in SCI, 17,18 suggesting that the rate of AAE could be a risk factor for SCI in patients with SCA. Second, despite the apparently predominant involvement of the Circle of Willis in SCA cerebral vasculopathy, the extracranial portion of the internal carotid artery (eICA) can be the site of stenosis and/or occlusion and is also responsible for overt strokes and SCI.…”

Section: Introductionmentioning

confidence: 99%

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Chronic and acute anemia and extracranial internal carotid stenosis are risk factors for silent cerebral infarcts in sickle cell anemia

Bernaudin

Verlhac

Arnaud

et al. 2015

Blood

152

160

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Key Points• Baseline hemoglobin levels lower than 7 g/dL, acute anemia, and extracranial internal carotid stenosis are significant and independent risk factors for SCI in SCA.Early transcranial Doppler (TCD) screening of the Créteil sickle cell anemia (SCA)-newborn cohort, and rapid initiation of transfusion programs, resulted in successful prevention of overt strokes, but a high cumulative risk of silent cerebral infarcts (SCI) remained, suggesting that TCD screening does not identify all patients with SCA at risk for SCI. We hypothesized that episodes of hypoperfusion/hypoxia, as observed during acute chest syndromes or acute anemic events (AAE), and extracranial internal carotid artery (eICA) stenoses, detectable via submandibular Doppler sonography and cervical magnetic resonance angiography (MRA), could also be risk factors for SCI. This study includes 189 stroke-free patients with SCA from the Créteil newborn cohort (1992-2010) followed longitudinally by magnetic resonance imaging/MRA, including cervical MRA at the last assessment. All patients with abnormal TCD and/or intracranial stenoses were placed on a transfusion program. Mean follow-up was 9.9 years (range, 2.2-19.9 years; 1844 patient-years). Annual rates of clinical events were calculated. The cumulative risk for SCI was 39.1% (95% confidence interval [CI], 23.5%-54.7%) by age 18 years, with no plateau. We confirm that baseline hemoglobin level lower than 7 g/dL before age 3 years is a highly significant predictive risk factor for SCI (hazard ratio, 2.97; 95% CI, 1.43-6.17; P 5 .004). Furthermore, we show that AAE rate (odds ratio, 2.64 per unit increase; 95% CI, 1.09-6.38; P 5 .031) and isolated eICA stenosis (odds ratio, 3.19; 95% CI, 1.18-8.70; P 5 .023) are significant and independent risk factors for SCI. (Blood. 2015;125(10):1653-1661

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Section: Discussionmentioning

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Chronic and acute anemia and extracranial internal carotid stenosis are risk factors for silent cerebral infarcts in sickle cell anemia

Bernaudin

Verlhac

Arnaud

et al. 2015

Blood

152

160

View full text Add to dashboard Cite

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“…The presence of acute silent cerebral infarction events (ASCIE), seen as lesions on imaging which may or may not progress to SCI, has been shown to be temporally associated with clinical events [38]. SCI by definition are clinically silent, so timing is unknown; however, it has been postulated that these lesions are the result of recurrent micro-infarctions and recurrent acute hypoxic damage [24,39,40] secondary to severe anaemia, diminished pulmonary function, splenic sequestration, aplastic crisis and acute chest syndrome [41,42].…”

Section: Pathophysiology Of Cerebrovascular Ischaemic Eventsmentioning

confidence: 99%

“…ASCIE [38,40], following acute severe anaemia [24,35,70,71], can be detectable in the first few days after the clinical event using diffusion-weighted imaging (DWI), in which the 'apparent' diffusion coefficient (ADC) is measured within each voxel and representing an index of the mobility of water molecules inside biological tissues. In acute ischaemia, an area of oedema in the brain has a rapid decline in proton density and appears hyperintense on DWI and decreased on an ADC map, persisting for 10-14 days post-event [72], which can differentiate acute stroke from more remote events [24].…”

Section: Acute Silent Cerebral Ischemic Events (Ascie)mentioning

confidence: 99%

Neurological Complications and MRI

Kawadler¹,

Kirkham²

2016

Sickle Cell Disease - Pain and Common Chronic Complications

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Cerebrovascular diseases (cerebral infarction, intracranial haemorrhage and vasculopathy) are common manifestations of sickle cell disease (SCD) associated with significant morbidity and mortality. These neurological complications and potential corresponding neuropsychological compromise may have devastating consequences for a child with SCD. This chapter aims to review the neurological complications in SCD using magnetic resonance imaging (MRI) as both a qualitative and a quantitative tool for detecting abnormality. Advanced MRI pulse sequences, such as high-resolution 3D T1-weighted imaging for brain volumetrics, diffusion tensor imaging for white matter integrity and non-invasive perfusion MRI for cerebral blood flow (CBF) measurement, can provide additional information about the structure and function of brain tissue beyond the scope of conventional clinical imaging. These studies have set to establish quantitative biomarkers that relate to disease severity and neuropsychological sequelae.

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Parent education and biologic factors influence on cognition in sickle cell anemia

King

Strouse

Rodeghier³

et al. 2014

American J Hematol

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155

179

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Children with sickle cell anemia have a high prevalence of silent cerebral infarcts (SCIs) that are associated with decreased full-scale intelligence quotient (FSIQ). While the educational attainment of parents is a known strong predictor of the cognitive development of children in general, the role of parental education in sickle cell anemia along with other factors that adversely affect cognitive function (anemia, cerebral infarcts) is not known. We tested the hypothesis that both the presence of SCI and parental education would impact FSIQ in children with sickle cell anemia. A multicenter, cross-sectional study was conducted in 19 US sites of the Silent Infarct Transfusion Trial among children with sickle cell anemia, age 5–15 years. All were screened for SCIs. Participants with and without SCI were administered the Wechsler Abbreviated Scale of Intelligence. A total of 150 participants (107 with and 43 without SCIs) were included in the analysis. In a multivariable linear regression model for FSIQ, the absence of college education for the head of household was associated with a decrease of 6.2 points (P=0.005); presence of SCI with a 5.2 point decrease (P=0.017); each $1000 of family income per capita with a 0.33 point increase (P=0.023); each increase of 1 year in age with a 0.96 point decrease (P=0.023); and each 1% (absolute) decrease in hemoglobin oxygen saturation with 0.75 point decrease (P=0.030). In conclusion, FSIQ in children with sickle cell anemia is best accounted for by a multivariate model that includes both biologic and socioenvironmental factors.

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Acute Silent Cerebral Ischemic Events in Children With Sickle Cell Anemia

Cited by 59 publications

References 24 publications

Chronic and acute anemia and extracranial internal carotid stenosis are risk factors for silent cerebral infarcts in sickle cell anemia

Chronic and acute anemia and extracranial internal carotid stenosis are risk factors for silent cerebral infarcts in sickle cell anemia

Neurological Complications and MRI

Parent education and biologic factors influence on cognition in sickle cell anemia

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