Vascular Instability and Neurological Morbidity in Sickle Cell Disease: An Integrative Framework
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 large...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-08-01
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| Series: | Frontiers in Neurology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fneur.2019.00871/full |
| _version_ | 1818955941255577600 |
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| author | Hanne Stotesbury Jamie M. Kawadler Patrick W. Hales Dawn E. Saunders Dawn E. Saunders Christopher A. Clark Fenella J. Kirkham Fenella J. Kirkham Fenella J. Kirkham Fenella J. Kirkham |
| author_facet | Hanne Stotesbury Jamie M. Kawadler Patrick W. Hales Dawn E. Saunders Dawn E. Saunders Christopher A. Clark Fenella J. Kirkham Fenella J. Kirkham Fenella J. Kirkham Fenella J. Kirkham |
| author_sort | Hanne Stotesbury |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-20T10:46:03Z |
| format | Article |
| id | doaj.art-a38487b6add14a4591bfdaf0e78f94f8 |
| institution | Directory Open Access Journal |
| issn | 1664-2295 |
| language | English |
| last_indexed | 2024-12-20T10:46:03Z |
| publishDate | 2019-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neurology |
| spelling | doaj.art-a38487b6add14a4591bfdaf0e78f94f82022-12-21T19:43:24ZengFrontiers Media S.A.Frontiers in Neurology1664-22952019-08-011010.3389/fneur.2019.00871471261Vascular Instability and Neurological Morbidity in Sickle Cell Disease: An Integrative FrameworkHanne Stotesbury0Jamie M. Kawadler1Patrick W. Hales2Dawn E. Saunders3Dawn E. Saunders4Christopher A. Clark5Fenella J. Kirkham6Fenella J. Kirkham7Fenella J. Kirkham8Fenella J. Kirkham9Developmental Neurosciences, UCL Great Ormond Institute of Child Health, London, United KingdomDevelopmental Neurosciences, UCL Great Ormond Institute of Child Health, London, United KingdomDevelopmental Neurosciences, UCL Great Ormond Institute of Child Health, London, United KingdomDevelopmental Neurosciences, UCL Great Ormond Institute of Child Health, London, United KingdomDepartment of Radiology, Great Ormond Hospital, London, United KingdomDevelopmental Neurosciences, UCL Great Ormond Institute of Child Health, London, United KingdomDevelopmental Neurosciences, UCL Great Ormond Institute of Child Health, London, United KingdomClinical and Experimental Sciences, University of Southampton, Southampton, United KingdomDepartment of Child Health, University Hospital Southampton, Southampton, United KingdomDepartment of Paediatric Neurology, Kings College Hospital NHS Foundation Trust, London, United KingdomIt 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.https://www.frontiersin.org/article/10.3389/fneur.2019.00871/fullsickle cell diseasestrokesilent cerebral infarctioncerebral hemodynamicsvascular instabilityanemia |
| spellingShingle | Hanne Stotesbury Jamie M. Kawadler Patrick W. Hales Dawn E. Saunders Dawn E. Saunders Christopher A. Clark Fenella J. Kirkham Fenella J. Kirkham Fenella J. Kirkham Fenella J. Kirkham Vascular Instability and Neurological Morbidity in Sickle Cell Disease: An Integrative Framework Frontiers in Neurology sickle cell disease stroke silent cerebral infarction cerebral hemodynamics vascular instability anemia |
| title | Vascular Instability and Neurological Morbidity in Sickle Cell Disease: An Integrative Framework |
| title_full | Vascular Instability and Neurological Morbidity in Sickle Cell Disease: An Integrative Framework |
| title_fullStr | Vascular Instability and Neurological Morbidity in Sickle Cell Disease: An Integrative Framework |
| title_full_unstemmed | Vascular Instability and Neurological Morbidity in Sickle Cell Disease: An Integrative Framework |
| title_short | Vascular Instability and Neurological Morbidity in Sickle Cell Disease: An Integrative Framework |
| title_sort | vascular instability and neurological morbidity in sickle cell disease an integrative framework |
| topic | sickle cell disease stroke silent cerebral infarction cerebral hemodynamics vascular instability anemia |
| url | https://www.frontiersin.org/article/10.3389/fneur.2019.00871/full |
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