Genetic, laboratory and clinical risk factors in the development of overt ischemic stroke in children with sickle cell disease

Abstract

Cerebrovascular disease, particularly stroke, is one of the most severe clinical complications associated with sickle cell disease and is a significant cause of morbidity in both children and adults. Over the past two decades, considerable advances have been made in the understanding of its natural history and enabled early identification and treatment of children at the highest risk. Transcranial Doppler screening and regular blood transfusions have markedly reduced the risk of stroke in children. However, transcranial Doppler has a limited positive predictive value and the pathophysiology of cerebrovascular disease is not completely understood. In this review, we will focus on the current state of knowledge about risk factors associated with ischemic stroke in patients with sickle cell disease. A search of PubMed was performed to identify studies. Full texts of the included articles were reviewed and data were summarized in a table. The coinheritance of alpha-thalassemia plays a protective role against ischemic stroke. The influence of other genetic risk factors is controversial, still preliminary, and requires confirmatory studies. Recent advances have established the reticulocyte count as the most important laboratory risk factor. Clinical features associated with acute hypoxemia as well as silent infarcts seem to influence the development of strokes in children. However, transcranial Doppler remains the only available clinical prognostic tool to have been validated. If our understanding of the many risk factors associated with stroke advances further, it may be possible to develop useful tools to detect patients at the highest risk early, improving the selection of children requiring intensification therapy.

High fetal hemoglobin level is associated with increased risk of cerebral vasculopathy in children with sickle cell disease in Mayotte

“…This link was not found at the level of phenotypic groups. The studies on this subject obtained different results: G6PD deficiency leads to a hemolytic phenotype according to some French studies [31,32], and does not affect this phenotype according to others [33][34][35][36][37]. Our study investigated three mutations, but did not collect the molecular and clinical expression of G6PD deficiency.…”

miR-155 Knockdown Protects against Cerebral Ischemia and Reperfusion Injury by Targeting MafB

“…e mechanism of CIR is complex, and CIR is regulated by multiple pathways. Studies have shown that oxidative stress, calcium overload, abnormal energy metabolism, immune regulation, inflammatory reaction, and apoptosis are implicated into the pathophysiology of CIR injury, in which inflammatory response and apoptosis are the main factors [4,5]. Roqué et al [6] have demonstrated that excessive proinflammatory cytokines and cytotoxic factors, for instance, tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and nitric oxide (NO), are secreted in microglia with I/R injury and then aggravate the neuronal damage, which is consistent with the study of Fumagalli et al [7].…”

Inhibition of miR-19a protects neurons against ischemic stroke through modulating glucose metabolism and neuronal apoptosis

“…Brain ischemic stroke is known as the commonest cerebrovascular disease and a primary public health problem, characterized by a high incidence and mortality, acute onset, rapid development and severe outcomes, and unfortunately, its incidence is on the rise [1][2][3]. Cerebral ischemic injury, identified as the fundamental pathophysiological basis of ischemic stroke, has a complicated pathogenesis concerning multiple biological events, such as neuronal apoptosis [4,5], astrocyte activation [6,7], proinflammatory reaction and oxidative stress [8,9]. Cerebral ischemia results in brain impairment on account of deprivation of oxygen and glucose resulting from blockage of local blood supply.…”