The severity of anaemia depletes cerebrovascular dilatory reserve in children with sickle cell disease: a quantitative magnetic resonance imaging study

Abstract

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 CO 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.

Hydroxycarbamide and white matter integrity in pediatric sickle cell disease

“…A significant relationship was also found between skew and kurtosis mean diffusivity histogram measures and CVR in healthy controls. This research group has previously shown that CVR was significantly reduced in children with SCD and that lower CVR in this population is associated with lower hematocrit levels and region‐specific cortical thinning (Kim et al , ; Kosinski et al , ). Taken together, these findings suggest that reduced CVR is associated with changes in white matter seen in children with SCD and that the beneficial effects of hydroxycarbamide on anaemia may contribute to improvements in CVR and white matter microstructural integrity.…”

Stroke in sickle cell anaemia is more than stenosis and thrombosis: the role of anaemia and hyperemia in ischaemia

“…The STOP (Stroke Prevention Trial in Sickle Cell Anaemia) clinical trial of transfusion in SCD demonstrated the association between increased CBF velocities as detected by Transcranial Doppler scan (TCD) and stroke risk (Adams et al, 1998). Kosinski et al (2016) provide evidence that cerebrovascular reactivity (CVR) is related to the severity of anaemia in SCD. Children without stroke were randomly assigned to treatment with blood transfusion or no (standard) treatment.…”

“…But these two risk factors do not correlate directly with the 'occlusive vascular' and the 'haemodynamic ischaemic' models of stroke discussed above. The children included in the study reported by Kosinski et al (2016) did not have steno-occlusive disease (although disease of the neck vessels may not have been completely excluded) but presumably, the exhausted cerebrovascular reserve in vessels distal to areas of stenosis only further heightens stroke risk in affected children. Children with TCD velocities >170 cm/s had a stroke risk of 7% over 36 months and children with TCD velocities >200 cm/s had a stroke risk of 40% over 36 months.…”

“…In the extended follow-up of the STOP trial, Lee et al (2006) also reported that all six patients who developed stroke had elevated TCD velocities, but only two had abnormal MRAs. demonstrated by Kosinski et al (2016) needs to be explored in children with sickle vasculopathy and focal hypoperfusion, and the mechanisms of ischaemic injury in SCD warrant reexamination with these more sophisticated techniques. The children included in the study reported by Kosinski et al (2016) did not have steno-occlusive disease (although disease of the neck vessels may not have been completely excluded) but presumably, the exhausted cerebrovascular reserve in vessels distal to areas of stenosis only further heightens stroke risk in affected children.…”

“…This would suggest that steno-occlusive disease is not necessarily the sole or major cause of stroke in SCD, and that cerebral haemodynamics have a significant role. It is not clear how much of the problem of cerebral ischaemia in SCD is due to the sickle haemoglobin and how much is due to the anaemia, but more of these dynamic assessments of CBF and vascular reserve that Kosinski et al (2016) provide are needed, including measures of cerebral metabolism (Jordan et al, 2016), ideally at the bedside (Nur et al, 2009). Kosinski et al (2016) provide evidence that cerebrovascular reactivity (CVR) is related to the severity of anaemia in SCD.…”