Sickle cell disease (SCD) is a lifelong blood disorder that is most often characterized by vaso-occlusive crises and joint damage. In addition, patients with this disorder experience numerous multisystemic complications, including cerebral infarction.
From a young age, individuals with SCD are at a high risk of developing cerebrovascular complications. If SCD remains untreated, stroke (ischemic or hemorrhagic) occurs in roughly 8% of pediatric patients with this condition. While stroke often leads to clear signs of neurologic deficits, a stroke can occur without any manifestations. These are commonly termed “silent cerebral infarcts.” Nonetheless, silent cerebral infarcts can be detected via magnetic resonance imaging (MRI) of the brain.
The average age of overt stroke onset is a mere 7.7 years, which means that children and teenagers with SCD are likely to experience some form of stroke, even if they are silent. Even when an infarction/stenosis does not rise to the level of a stroke, pediatric patients with SCD are known to have a high rate of morbidities involving the major cerebral arteries.
Characteristics of SCD-Related Stroke
In Cureus, Parikh and colleagues conducted a literature review to understand the clinical and neuropsychologic characteristics of stroke in pediatric patients.
Read more about SCD etiology
In the United States, SCD is the most frequent cause of stroke, both hemorrhagic and ischemic, among pediatric patients. The incidence of stroke increases 221-fold in pediatric patients with SCD compared with healthy children. In addition, they have a 41-fold increased chance of ischemic stroke, and a 7-fold increase chance of hemorrhagic stroke. Patients with SCD have a lifelong stroke risk of around 33%.
Parikh et al reported that one of the first signs that a patient has suffered from a severe episode of stroke is hemiparesis, a condition commonly observed in stroke unrelated to SCD. If prophylaxis is not administered, the risk of recurrence rises up to 67% of cases.
Patients with SCD are also known to suffer from a number of common ailments—these may or may not be a consequence of transient ischemic attacks/stroke/silent cerebral infarcts. For example, many patients with SCD complain of a headache — this occurs in nearly half of patients with SCD. In the instance of persistent, painful headaches, neuroimaging should be considered to rule out cerebral hemorrhage.
On the subject of cerebral hemorrhage, many patients with SCD are at risk for intracranial hemorrhage — intraparenchymal, subarachnoid, intraventricular, or spontaneous subdural hemorrhage. According to Parikh and colleagues, patients who have had a previous infarction are at an increased risk for bleeding as they become older.
Risk Factors for Stroke
In Pediatric Neurology, Hirtz and Kirkham presented a number of risk factors that predisposes an individual with SCD to cerebrovascular complications. Given the devastating effects of cerebrovascular events, the identification of evidence-based risk factors can help reduce their occurrence.
Among the risk factors for stroke is acute illness, such as acute chest crisis. Splenic sequestration or infection (ie, parvovirus B19) can trigger acute anemic events, which are a risk factor for silent cerebral infarcts. A study found that around 18% of children with SCD experience a silent cerebral infarct following an illness associated with acute anemia.
Read more about SCD treatment
Patients with known SCD-related vasculopathies are at an increased risk for stroke. Vasculopathies often lead to some form of anemia; its most significant clinical effect is that it raises baseline cerebral blood flow, which reduces the ability of the cerebral vasculature to increase cerebral blood flow when required. Coupled with the presence of HbSS (the most severe form of sickle cell anemia) in SCD, the blood becomes increasingly viscous, complicating the tissue delivery of oxygen.
Scientists have always been keen to explore if environmental factors increase the risk for certain pathologies. Although studies involving environmental factors are difficult to be carried out (given the challenges of producing a control environment), epidemiologic research indicates that there is difference in the prevalence of SCD-related stroke among higher- and lower-income countries. One of the main suspects of SCD-related stroke is air pollution, as particulate matter exposure may increase blood viscosity in the carotid artery. However, nitric oxide and carbon monoxide may be beneficial in the sense that they promote a leftward shift in the hemoglobin-oxygen dissociation curve.
Patients with SCD with a history of stroke are also found to perform more poorly on neuropsychologic measures compared with children with silent cerebral infarcts or those without MRI abnormalities. Studies indicate that patients with SCD who have experienced a stroke tend to perform more poorly on intelligent quotient (IQ) tests compared with their healthy peers. The association between stroke and lower cognition in SCD is highly likely to be causative in the sense that a patient experiences cognitive difficulties due to stroke, as opposed to a patient being at risk for stroke due to abnormal cognitive function.
In conclusion, we must recognize that any cerebrovascular event in such young children is a threat to their well-being, both in the short- and long-term. Given the high disease burden of SCD, it is vital that clinicians identify ways to reduce the risk of these incidents.
“Interventions directed at early diagnosis and remedial plans to address school problems are important to minimize the consequences of stroke in children with SCD,” Hirtz and Kirkham wrote.
This article originally appeared on Rare Disease Advisor
- Parikh T, Goti A, Yashi K, et al. Pediatric sickle cell disease and stroke: a literature review. Cureus. 2023;15(1):e34003. doi:10.7759/cureus.34003
- Hirtz D, Kirkham FJ. Sickle cell disease and stroke. Pediatr Neurol. 2019;95:34-41. doi:10.1016/j.pediatrneurol.2019.02.018