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

Stotesbury, H; Kawadler, JM; Hales, PW; Saunders, DE; Clark, CA; Kirkham, FJ; (2019) Vascular Instability and Neurological Morbidity in Sickle Cell Disease: An Integrative Framework. Frontiers in Neurology , 10 , Article 871. 10.3389/fneur.2019.00871. Green open access

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Abstract

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.

Type: Article
Title: Vascular Instability and Neurological Morbidity in Sickle Cell Disease: An Integrative Framework
Open access status: An open access version is available from UCL Discovery
DOI: 10.3389/fneur.2019.00871
Publisher version: http://dx.doi.org/10.3389/fneur.2019.00871
Language: English
Additional information: © 2019 Stotesbury, Kawadler, Hales, Saunders, Clark and Kirkham. This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/).
Keywords: sickle cell disease, stroke, silent cerebral infarction, cerebral hemodynamics, vascular instability, anemia, oxygen extraction fraction, cerebrovascular reserve
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Developmental Neurosciences Dept
URI: https://discovery.ucl.ac.uk/id/eprint/10080539
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