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Overt ischaemic stroke is one of the most devastating complications in children with sickle cell disease ( SCD). The compensatory response to anaemia in SCD includes an increase in cerebral blood flow ( CBF) by accessing cerebrovascular dilatory reserve. Exhaustion of dilatory reserve secondary to anaemic stress may lead to cerebral ischaemia. The purpose of this study was to investigate CBF and cerebrovascular reactivity ( CVR) using magnetic resonance imaging ( MRI) in children with SCD and to correlate these with haematological markers of anaemia. Baseline CBF was measured using arterial spin labelling. Blood-oxygen level-dependent MRI in response to a CO2 stimulus was used to acquire CVR. In total, 28 children with SCD (23 not on any disease-modifying treatment, 5 on chronic transfusion) and 22 healthy controls were imaged using MRI. Transfusion patients were imaged at two time points to assess the effect of changes in haematocrit after a transfusion cycle. In children with SCD, CBF was significantly elevated compared to healthy controls, while CVR was significantly reduced. Both measures were significantly correlated with haematocrit. For transfusion patients, CBF decreased and CVR increased following a transfusion cycle. Lastly, a significant correlation was observed between CBF and CVR in both children with SCD and healthy controls. [ABSTRACT FROM AUTHOR]

Sickle cell disease induces specific brain alterations that involve both the macrocirculation and the microcirculation. The main overt neurovascular complications in children are infarctive stroke, transient ischaemic attack and cerebral haemorrhage. Silent cerebral infarction, cognitive dysfunction and recurrent headache are also common. Cerebrovascular disease selectively affects children with the Hb SS or HbS-β0 genotypes (i.e. sickle cell anaemia). The incidence of stroke peaks between 2 and 5 years of age (1·02/100 patient-years) and increases with the severity of the anaemia. Most strokes can be prevented by annual transcranial Doppler screening from 2 to 16 years of age and providing chronic blood transfusion when this investigation shows elevated blood-flow velocities. The role for hydroxycarbamide in children with abnormal transcranial Doppler findings is under investigation. After a stroke, chronic blood transfusion is very strongly recommended, unless haematopoietic stem cell transplantation can be performed. Routine magnetic resonance imaging shows that more than one-third of children have silent cerebral infarction, which is associated with cognitive impairments. Screening for silent infarcts seems legitimate, since their presence may lead to supportive treatments. The role for more aggressive interventions such as hydroxycarbamide or chronic blood transfusion is debated. [ABSTRACT FROM AUTHOR]

Chronic transfusions to maintain haemoglobin S (HbS) ≤30% are the mainstay of treatment for children with sickle cell anaemia (SCA) and previous stroke. This HbS target is often hard to maintain, however, and values achieved in current practice are unknown. In preparation for the Phase III Stroke With Transfusions Changing to Hydroxyurea (SWiTCH) trial, we collected data on 295 children with SCA and stroke who received transfusions at 23 institutions. The overall average pre-transfusion %HbS was 35 ± 11% (institutional range 22–51%). Receiving scheduled transfusions on time was the most predictive variable for maintaining HbS at the ≤30% goal. [ABSTRACT FROM AUTHOR]

High cerebral blood flow velocity (CBFv) and low haemoglobin oxygen saturation (SpO2) predict neurological complications in sickle cell anaemia (SCA) but any association is unclear. In a cross-sectional study of 105 Kenyan children, mean CBFv was 120 ± 34·9 cm/s; 3 had conditional CBFv (170–199 cm/s) but none had abnormal CBFv (>200 cm/s). After adjustment for age and haematocrit, CBFv ≥150 cm/s was predicted by SpO2 ≤ 95% and history of fever. Four years later, 10 children were lost to follow-up, none had suffered neurological events and 11/95 (12%) had died, predicted by history of fever but not low SpO2. Natural history of SCA in Africa may be different from North America and Europe. [ABSTRACT FROM AUTHOR]

Steady-state haemoglobin (Hb) desaturation is a common finding in sickle cell anaemia (Hb SS) that could predispose to stroke by limiting oxygen delivery to the brain. To determine its association with the risk of overt stroke, we examined the relationship between daytime Hb saturation measured by pulse oximetry (SpO2) and cerebral artery blood flow velocity measured by transcranial Doppler ultrasonography (TCD), an established risk factor for overt stroke in Hb SS. We studied 181 children using multivariate models to control for known determinants of TCD velocity, including age, haematocrit, and a measure of stenosis. We found that SpO2 correlated significantly and inversely with TCD velocity in both the right and left middle cerebral arteries. Hb desaturation was associated with increased cerebral artery blood flow velocities and increased odds of abnormal TCD velocities, hence increased risk of stroke. About 5% of the variation in TCD velocity could be ascribed to Hb saturation while controlling for other determinants of TCD velocity. In conclusion, Hb saturation is a determinant of TCD velocity and a risk factor for stroke in children with Hb SS. [ABSTRACT FROM AUTHOR]

Haemoglobin (Hb) desaturation could increase the risk of stroke in sickle cell anaemia (SS) by perturbing endothelial function and limiting oxygen delivery to the brain. We performed a nested case–control study of the Dallas Newborn Cohort to determine whether daytime steady-state Hb desaturation was associated with overt stroke in children with SS. Cases had SS and overt ischaemic strokes. Controls had comparable genotypes but no overt stroke. Cases had lower prestroke steady-state pulse oximetry values (SpO2) than controls, and cases’ SpO2 fell even lower as the time to impending stroke decreased. The odds ratio for stroke was 1·32 for each 1% decrease in SpO2. In conclusion, steady-state Hb desaturation is a risk factor for overt ischaemic stroke in children with SS. Decline in SpO2 over time further increases this risk. Hb desaturation is easily measured, potentially modifiable, and could be used to identify children with SS at increased risk of stroke. [ABSTRACT FROM AUTHOR]

Stroke is an uncommon but increasingly recognised cause of mortality and long-term neurological morbidity in children. A significant number of these events appear to be caused by thromboembolic disease and, as with other childhood thrombotic problems, the incidence of central nervous system events appears highest during the neonatal period. In contrast to peripheral arterial and venous thrombotic problems, it is likely that a proportion of cerebral thromboembolic events occur either in utero or perinatally and reflect different risk factors from those occurring in older infants and children. The pathophysiology of perinatal stroke is complex and in many cases is likely to be multifactorial. It is now recognised that risk factors may relate to both maternal and placental problems as well as fetal and neonatal disorders. Large prospective studies of perinatal stroke are currently lacking and efforts to define the relative contribution from each of these areas are at an early stage. The complex nature of these disorders requires collaboration between a number of different disciplines including obstetrics, fetal medicine, pathology, neonatology and neurology. Of particular interest to haematologists is the possible impact of prothrombotic abnormalities in the pathophysiology of these events and also the potential for the use of antithrombotic agents in both management and prevention. [ABSTRACT FROM AUTHOR]

Reports an evidence-based analysis of management options for cerebrovascular disease in children with sickle cell anemia (SS). Complications of SS; Identification of predictive risk factors for cerebral ischemia in young children; Details on the utility of several neuroimaging modalities; Summary of available clinical trials; Recommendations for management using an intention-to-treat strategy.

Provides a summary of the management advances of sickle cell disease. Description of the disease; Interventions needed to prevent deaths due to overwhelming bacterial infections; Percentage of children with sickle cell anemia who develop a stroke due to cerebrovascular occlusion; Control of sickle cell retinopathy with laser photocoagulation.