Sickle cell disease, which is prevalent among people from Africa, the Mediterranean, and the Middle East, often leads to overt stroke and silent cerebral infarcts. Treatment trials have yet to be done to prevent stroke in adults with the disease.
Researchers reviewed the neurologic effects and pathophysiology of sickle cell disease and how neuroimaging and preventive therapies can combat morbidity in an article published in Lancet Neurology.
Studies have shown that patients with sickle cell disease – especially those who have had silent cerebral infarcts or overt strokes – have cognitive impairment that results in reduced full-scale intelligence quotient (FSIQ) scores. Children may have impaired processing speed, verbal reasoning, executive function, and perceptual reasoning.
Neuroimaging can aid in understanding the effects neurologic injury has on patients with sickle cell disease. To obtain cerebral blood flow (CBF) measurement, neurologists can employ arterial spin labeling (ASL), a noninvasive magnetic resonance imaging (MRI) technique. Cerebrovascular reactivity imaging delivers estimated cerebrovascular reserve capacity, which may be a more sensitive biomarker than resting CBF for stroke risk.
Neurologists can use T2 relaxation under spin tagging (TRUST) MRI to quantify oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen consumption (CMRO2). This technique has indicated that higher OEF is associated with more severe clinical impairment via vasculopathy or infarct.
Asymmetric spin echo (ASE) MRI can evaluate regional OEF. White matter OEF may be associated with decreased functional connectivity. Diffusion tensor imaging (DTI) may identify abnormalities in white matter microstructure linked to neurologic injury and reduced processing speed.
Preventive therapies for patients with sickle cell disease include screenings and monitoring. The American Society of Hematology has recommended patients with sickle cell anemia receive brain MRI screenings for silent cerebral infarcts at least once in childhood and young adulthood, and annual transcranial Doppler sonography (TCD) screening for high risk of stroke is standard. Neurologists can monitor rapid capillary transit, which may indicate impaired oxygen delivery, cerebral infarct risk, and cognitive impairment.
Stroke risk assessment trials regarding new infarct development and hemodynamic impairment and studies of functional changes in CBF, OEF, and cerebrovascular reactivity are underway. Neurocognitive assessments of cognitive outcomes, processing speed, and executive function may be helpful.
Hydroxycarbamide can increase hemoglobin concentrations and reduce OEF and blood flow velocity on TCD. Pharmacologic therapies may prove useful. Monthly blood transfusions are an initial therapy for pediatric patients with elevated TCD velocities and those with new stroke or progressive infarct.
Curative therapies, which can be fatal, include myeloablative gene therapy, autologous myeloablative gene editing, and hematopoietic stem-cell transplantation (HSCT), which is under investigation. The procedure may promote long-term brain health by reducing CBF, OEF, and the disease’s neurologic impact.
“Continuing to improve our knowledge of the unique and heterogeneous neurophysiology that underlies sickle cell disease will guide the development and evaluation of a wide range of disease-modifying and curative treatments,” the study authors concluded. “Neuroscientists and clinicians have a great opportunity to reduce the health-care disparity between stroke prevention in individuals with sickle cell disease and those without.”
Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
1. Jordan LC, DeBaun MR, Donahue MJ. Advances in neuroimaging to improve care in sickle cell disease. Lancet Neurol. 2021;20(5):398-408. doi:10.1016/S1474-4422(20)30490-7