Occlusion of Large Cerebral Vessels in Sickle-Cell Anemia

Stockman, J.A.; Nigro, Michael A.; Mishkin, Mark M.; Oski, Frank A.

doi:10.1056/nejm197210262871703

Cited by 327 publications

(146 citation statements)

References 13 publications

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“…SCA is also the most common cause of childhood stroke in general. The etiology of stroke in children with SCA is incompletely understood, but is known to be due to obstruction of the large intracranial vessels [2]. Systems analysis of causative factors of childhood stroke using RNA microarray data from blood outgrowth endothelial cells (BOECs) indicated the importance of the inflammation signaling pathway as a risk factor [3].…”

Section: Introductionmentioning

confidence: 99%

Proinflammatory phenotype with imbalance of KLF2 and RelA: Risk of childhood stroke with sickle cell anemia

et al. 2009

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Altered inflammation signaling within the cerebral vasculature may be an important risk factor for stroke in children with sickle cell anemia (SCA). This study examines how differential expression of NFjB/p65 (RelA), KLF2, and other transcription factors may act as switches in inflammation signaling leading to observed differences between non-SCA (NS) African Americans and African Americans with SCA who are either at risk (AR) or not at risk (NAR) of childhood stroke based on occurrence of Circle of Willis disease. Clover/ Transfac analysis was used to identify overrepresented transcription factor binding motifs on genes associated with inflammation. Transcription factor binding motifs for the NFjB family and RFX1 were overrepresented on inflammation signaling gene set analysis. Variations in protein expression were determined by flow cytometry of blood outgrowth endothelial cells (BOECs) from NS, AR, and NAR donors and Western blots of protein extracts from both unstimulated and TNFa/IL1b-stimulated BOECs. BOECs from patients with SCA had more cytoplasmic-derived RelA compared with NS BOECs. Sickle BOECs also had heightened responses to inflammatory stimuli compared with NS BOECs, as shown by increased nuclear RelA, and intracellular adhesion molecule (ICAM) response to TNFa/IL1b stimulation. Multiple control points in RelA signaling were associated with risk of childhood stroke. The ratio of proinflammatory factor RelA to anti-inflammatory factor KLF2 was greater in BOECs from AR donors than NS donors. Group risk of childhood stroke with SCA was greatest among individuals who exhibited increased expression of proinflammatory transcription factors and decreased expression of transcription factors that suppress inflammation. Am. J. Hematol. 85:18-23, 2010. V

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Section: Introductionmentioning

confidence: 99%

Proinflammatory phenotype with imbalance of KLF2 and RelA: Risk of childhood stroke with sickle cell anemia

et al. 2009

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“…The majority of stroke occurrences in SCD patients younger than 20 years are either ischemic or result from infarction (Adams et al, 2003;Hoppe et al, 2003), while the incidence of intracranial hemorrhagic stroke is more common in older SCD patient populations (Powars et al, 1978). Although stroke can result from multiple factors such as hemorrhage, cerebral infarction, or embolism, occlusive vasculopathy remains the most common cause of cardiovascular disease in SCD patients (Stockman et al, 1972).…”

Section: Stroke In Scdmentioning

confidence: 99%

Genetics of Sickle Cell-Associated Cardiovascular Disease: An Expert Review with Lessons Learned in Africa

Geard

Pule

Chelo

et al. 2016

OMICS: A Journal of Integrative Biology

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Sickle cell disease (SCD) vastly impacts the African continent and is associated with cardiovascular diseases. Stroke, kidney disease, and pulmonary hypertension are considered as proxies of severity in SCD with several genomic loci implicated in their heritability. The present expert review examined the current data on epidemiology and genetic risk factors of stroke, pulmonary hypertension, and kidney disease associated with SCD, as indexed in PubMed Ò and Google Scholar Ò . Studies collectively show that stroke and kidney disease each affect *10% of SCD patients, with pulmonary hypertension displaying a higher prevalence of 30% among adults with SCD. There is some evidence that these epidemiology figures may be an underestimate in SCD patients living in Africa. A modest number of publications have identified genetic factors involved in pathways regulating inflammation, coagulation, cell adhesion, heme degradation, a-globin and c-globin production, and others, which contribute to the development risk of targeted cardiovascular phenotypes. However, in most cases, these studies have not been validated across populations. There is therefore an urgent need for large-scale genome-wide association, wholeexome and whole-genome studies, and multiomics research on cardiovascular diseases associated with SCD, particularly in Africa, to allow for proportional investment of global research funding on diseases that greatly impact the African continent. Ultimately, this will cultivate socially responsible research investments and identification of at-risk individuals with improved preventive medicine, which should be a cornerstone of global precision medicine.

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“…Overt stroke is usually associated with large vessel arterial disease, with evidence of stenosis in the internal carotid artery distribution [16], and pathologies are frequently seen in brain tissue within the anterior cerebral and middle cerebral artery territories [17][18][19]. Transcranial Doppler (TCD) may be used to screen for high cerebral blood flow (CBF) velocities consistent with stenosis or hyperaemia; although conventional angiography is rarely justified, magnetic resonance angiography may confirm focal stenosis but is not essential for management.…”

Section: Pathophysiology Of Cerebrovascular Ischaemic Eventsmentioning

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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Occlusion of Large Cerebral Vessels in Sickle-Cell Anemia

Cited by 327 publications

References 13 publications

Proinflammatory phenotype with imbalance of KLF2 and RelA: Risk of childhood stroke with sickle cell anemia

Proinflammatory phenotype with imbalance of KLF2 and RelA: Risk of childhood stroke with sickle cell anemia

Genetics of Sickle Cell-Associated Cardiovascular Disease: An Expert Review with Lessons Learned in Africa

Neurological Complications and MRI

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