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Therapy Insight: stroke risk and its management in patients with sickle cell disease

Nature Clinical Practice Neurology volume 3, pages 264–278 (2007)Cite this article

Abstract

Children with sickle cell disease, a chronic hemolytic anemia, present with a wide variety of neurological syndromes, including ischemic and hemorrhagic stroke, transient ischemic attacks, 'soft neurological signs', seizures, headache, coma, visual loss, altered mental status, cognitive difficulties, and covert or 'silent' infarction. Those with ischemic stroke usually have stenosis or occlusion of the distal internal carotid and proximal middle cerebral arteries. Indefinite transfusion prevents recurrence in most patients who have had a stroke, and can prevent first stroke in those with high transcranial Doppler velocities. High white cell count, low hemoglobin and oxyhemoglobin desaturation predict neurological complications. Other risk factors for overt ischemic stroke include hypertension, previous transient ischemic attack, covert infarction and chest crisis. For hemorrhagic stroke, aneurysms are common in adults but not children, who often present with hypertension after transfusion or corticosteroids. Seizures are particularly common in patients with cerebrovascular disease and covert infarction; the latter is also associated with hyposplenism and infrequent pain. Factors associated with cognitive difficulties include thrombocytosis, infarction, large-vessel disease, and perfusion abnormality on neuroimaging. As well as investigating the role of genes and the possibility that hydroxyurea or blood pressure control reduce neurological complications, we should explore the modifiable effects of poor nutrition, chronic infection, hemolysis and oxyhemoglobin desaturation on stroke risk.

Key Points

  • Neurological complications of sickle cell disease (SCD) include transient ischemic attacks, seizures and covert infarction, as well as ischemic and hemorrhagic stroke

  • Low hemoglobin, high white cell count and oxyhemoglobin desaturation are risk factors for neurological complications in SCD

  • High blood pressure is associated with ischemic and hemorrhagic stroke in SCD

  • Ischemic stroke secondary to stenotic disease of the intracranial large vessels might be predicted using transcranial Doppler ultrasound, and is preventable with lifelong blood transfusion

  • Trials of prevention of primary and secondary infarction by regular blood transfusion, hydroxyurea and overnight respiratory support are ongoing

  • The role of exposure from infancy to chronic infection, hemolysis, poor nutrition and oxyhemoglobin desaturation in determining the risk of neurological complications in SCD should be explored

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Figure 1: Axial T2-weighted MRI (unless otherwise stated)
Figure 2: Voxel-based morphometry comparison of white matter density between controls and patients with sickle cell anemia and covert infarction
Figure 3: Diffusion and perfusion MRI
Figure 4: Transcranial Doppler velocities
Figure 5: Magnetic resonance angiography (MRA)
Figure 6: Magnetic resonance venogram showing obliteration of the left transverse, sigmoid and straight sinuses in a patient with sickle cell anemia

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Acknowledgements

FJ Kirkham's work has been funded by the Wellcome Trust (0353521 B/92/2), Action Research and the Stroke Association (PROG 4), and has benefitted from research and development funding received from the National Health Service Executive.

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  1. Neurosciences Unit, University College London Institute of Child Health, The Wolfson Centre, Mecklenburgh Square, London WC1N 2AP, UK f.kirkham@ich.ucl.ac.uk

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  1. FJ Kirkham is Professor of Paediatric Neurology at University College London Institute of Child Health, London, UK.,

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Kirkham, F. Therapy Insight: stroke risk and its management in patients with sickle cell disease. Nat Rev Neurol 3, 264–278 (2007). https://doi.org/10.1038/ncpneuro0495

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