Understanding sickle cell brain drain

Hulbert, Monica L.; Ford, Andria L.

doi:10.1182/blood-2014-06-582403

Cited by 12 publications

(11 citation statements)

References 9 publications

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“…Whilst vaso-occlusive, thrombotic, and/or embolic events may contribute to some ischemic insults in SCD, several authors have argued that the high density of overt and silent infarction and microstructural abnormalities in watershed regions may point to hemodynamic compromise or “brain drain” as a more common contributor (32, 140). Historically, in non-SCD patients, watershed infarcts have been associated with hemodynamic causes, and are sometimes referred to as hemodynamic strokes (141, 142).…”

Section: Hemodynamic Compromisementioning

confidence: 99%

“…There have been reports of hemodynamic changes consistent with a similar model of hemodynamic compromise in patients with SCD, including altered CaO 2 , CBF (156–161), CVR (162–164), and OEF (165–167). Whilst vaso-occlusion, vasculopathy, and emboli are all flow-restricting phenomena that may contribute to hemodynamic compromise, some hemodynamic changes may represent compensatory responses to physiological stressors associated with SCD pathophysiology (140), including anemia and hypoxia. In the following subsections, we consider research on aspects of CMRO 2 in SCD in turn.…”

Section: Hemodynamic Compromisementioning

confidence: 99%

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Vascular Instability and Neurological Morbidity in Sickle Cell Disease: An Integrative Framework

et al. 2019

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It is well-established that patients with sickle cell disease (SCD) are at substantial risk of neurological complications, including overt and silent stroke, microstructural injury, and cognitive difficulties. Yet the underlying mechanisms remain poorly understood, partly because findings have largely been considered in isolation. Here, we review mechanistic pathways for which there is accumulating evidence and propose an integrative systems-biology framework for understanding neurological risk. Drawing upon work from other vascular beds in SCD, as well as the wider stroke literature, we propose that macro-circulatory hyper-perfusion, regions of relative micro-circulatory hypo-perfusion, and an exhaustion of cerebral reserve mechanisms, together lead to a state of cerebral vascular instability. We suggest that in this state, tissue oxygen supply is fragile and easily perturbed by changes in clinical condition, with the potential for stroke and/or microstructural injury if metabolic demand exceeds tissue oxygenation. This framework brings together recent developments in the field, highlights outstanding questions, and offers a first step toward a linking pathophysiological explanation of neurological risk that may help inform future screening and treatment strategies.

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Section: Hemodynamic Compromisementioning

confidence: 99%

Section: Hemodynamic Compromisementioning

confidence: 99%

Vascular Instability and Neurological Morbidity in Sickle Cell Disease: An Integrative Framework

et al. 2019

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“…[12][13][14][15][16] Unfortunately, hyperemic vasodilation, impaired cerebrovascular autoregulation, and limited vascular reserve [17][18][19] leave the brain vulnerable and ill-equipped to respond to increased metabolic demand or reduced blood oxygen content; consequently, the tissue is susceptible to infarction. 20 Transcranial Doppler ultrasound (TCD) is the standard screening tool for overt stroke risk in pediatric SCD. [21][22][23] Through timely initiation of transfusion therapy in patients whose TCD-measured middle cerebral artery blood flow velocity (CBFV) is >200 cm∕s, the risk of overt stroke in children has significantly diminished by more than 80%.…”

Section: Introductionmentioning

confidence: 99%

Noninvasive optical assessment of resting-state cerebral blood flow in children with sickle cell disease

et al. 2019

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Sickle cell disease (SCD) is a genetic blood disorder that has profound effects on the brain. Chronic anemia combined with both macro-and microvascular perfusion abnormalities that arise from stenosis or occlusion of blood vessels increased blood viscosity, adherence of red blood cells to the vascular endothelium, and impaired autoregulatory mechanisms in SCD patients all culminate in susceptibility to cerebral infarction. Indeed, the risk of stroke is 250 times higher in children with SCD than in the general population. Unfortunately, while transcranial Doppler ultrasound (TCD) has been widely clinically adopted to longitudinally monitor macrovascular perfusion in these patients, routine clinical screening of microvascular perfusion abnormalities is challenging with current modalities (e.g., positron emission tomography and magnetic resonance imaging) given their high-cost, requirement for sedation in children <6 year, and need for trained personnel. We assess the feasibility of a low-cost, noninvasive optical technique known as diffuse correlation spectroscopy (DCS) to quantify an index of resting-state cortical cerebral blood flow (BFI) in 11 children with SCD along with 11 sex-and age-matched healthy controls. As expected, BFI was significantly higher in SCD subjects compared to healthy controls (p < 0.001). Within SCD subjects, BFI was inversely proportional to resting-state arterial hemoglobin levels (p ¼ 0.012), consistent with expected anemia-induced compensatory vasodilation that aims to maintain adequate oxygen delivery to the tissue. Further, in a subset of patients measured with TCD (n ¼ 7), DCSmeasured blood flow was correlated with TCD-measured blood flow velocity in middle cerebral artery (R s ¼ 0.68), although the trend was not statistically significant (p ¼ 0.11). These results are consistent with those of several previous studies using traditional neuroimaging techniques, suggesting that DCS may be a promising low-cost tool for assessment of tissue-level CBF in pediatric SCD.

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“…While the ability of TCD to predict and prevent overt stroke in children with SCD (Adams, McKie, Hsu, et al, 1998) is clinically accepted, there is a recognized trade-off between sensitivity and specificity. While the clinical utility of TCD for predicting overt stroke risk is not under question, it has recently been proposed by Hulbert & Ford (2014) that we begin to move beyond global TCD measurements to regional MRI measurements to better understand tissue-level pathophysiology. Our findings suggest that global TCD values can be only used as a surrogate marker for tissue-level physiology, if measurements of diameter and density are available, which may undermine the potential of CBF TCD for tissuelevel applications.…”

Section: Discussionmentioning

confidence: 99%

Assessment of cerebral blood flow with magnetic resonance imaging in children with sickle cell disease: A quantitative comparison with transcranial Doppler ultrasonography

et al. 2017

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Understanding sickle cell brain drain

Cited by 12 publications

References 9 publications

Vascular Instability and Neurological Morbidity in Sickle Cell Disease: An Integrative Framework

Vascular Instability and Neurological Morbidity in Sickle Cell Disease: An Integrative Framework

Noninvasive optical assessment of resting-state cerebral blood flow in children with sickle cell disease

Assessment of cerebral blood flow with magnetic resonance imaging in children with sickle cell disease: A quantitative comparison with transcranial Doppler ultrasonography

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