Sickle cell disease, which is widespread in people from Africa, the Mediterranean, and the Middle East, often results in overt stroke and silent brain infarction. Treatment attempts still need to be made to prevent stroke in adults with this disease.
In an article published in Lancet Neurology, researchers examined the neurological effects and pathophysiology of sickle cell disease and how neuroimaging and preventive therapies can combat morbidity.
Studies have shown that patients with sickle cell disease – especially those with silent cerebral infarctions or open strokes – have cognitive impairments that lead to a reduced FSIQ (full-scale intelligence quotient). Children may have impairments in processing speed, verbal thinking, executive function and perceptual thinking.
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Neuroimaging can help understand the effects of neurological injury on patients with sickle cell disease. To maintain cerebral blood flow (CBF) When measuring, neurologists can use arterial spin labeling (ASL), a non-invasive magnetic resonance imaging (MRI) scan. Cerebrovascular reactivity imaging provides an estimated cerebrovascular reserve capacity, which may be a more sensitive biomarker of stroke risk than resting CBF.
Neurologists can use T2 relaxation under spin-tagging MRI (TRUST) to quantify oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen consumption (CMRO2). This technique has shown that higher OEF is associated with more severe clinical impairment from vasculopathy or infarction.
Asymmetric spin echo MRI (ASE) can assess the regional OEF. White matter OEF may be associated with decreased functional connectivity. Diffusion tensor imaging (DTI) can identify abnormalities in the white matter microstructure that are associated with neurological injury and decreased processing speed.
Preventive therapies for patients with sickle cell disease include screening and monitoring. The American Society of Hematology has recommended that patients with sickle cell anemia have an MRI scan of the brain for silent cerebral infarction at least once in childhood and adolescence. Annual transcranial Doppler sonography screening (TCD) for a high risk of stroke is standard. Neurologists can monitor rapid capillary transit, which can indicate impaired oxygen delivery, a risk of cerebral infarction, and cognitive impairment.
Studies to assess the risk of stroke in relation to the development of new infarcts and hemodynamic impairment as well as studies of functional changes in CBF, OEF and cerebrovascular reactivity are ongoing. Neurocognitive assessments of cognitive outcomes, processing speed, and executive function can be helpful.
Hydroxycarbamide can increase hemoglobin levels and decrease OEF and blood flow rates in TCD. Pharmacological therapies can prove useful. Monthly blood transfusions are first line therapy for pediatric patients with increased TCD rates and those with recent stroke or progressive infarction.
Curative therapies that can be fatal include myeloablative gene therapy, autologous myeloablative gene editing, and hematopoietic stem cell transplant (HSCT), which is currently under investigation. The procedure can promote long-term brain health by reducing CBF, OEF, and the neurological effects of the disease.
“The continued improvement of our knowledge of the unique and heterogeneous neurophysiology underlying sickle cell disease will guide the development and evaluation of a wide range of disease-modifying and curative treatments,” concluded the study authors. “Neuroscientists and clinicians have a great opportunity to narrow the health gaps between stroke prevention in those with and without sickle cell disease.”
Disclosure: Some of the study’s authors stated links with biotech, pharmaceutical, and / or device companies. For a full list of the authors’ information, see the original reference.
References
1. Jordan LC, DeBaun MR, Donahue MJ. Advances in imaging to improve care for sickle cell disease. Lancet Neurol. 2021; 20 (5): 398- 408. doi: 10.1016 / S1474-4422 (20) 30490-7
