Epidemiology of Stroke in Sickle Cell Disease

Abstract

Sickle cell disease is the most common cause of stroke in childhood, both ischaemic and haemorrhagic, and it also affects adults with the condition. Without any screening or preventative treatment, the incidence appears to fall within the range 0.5 to 0.9 per 100 patient years of observation. Newborn screening with Penicillin prophylaxis and vaccination leading to reduced bacterial infection may have reduced the incidence, alongside increasing hydroxyurea prescription. Transcranial Doppler screening and prophylactic chronic transfusion for at least an initial year has reduced the incidence of stroke by up to 10-fold in children with time averaged mean of the maximum velocity >200 cm/s. Hydroxyurea also appears to reduce the incidence of first stroke to a similar extent in the same group but the optimal dose remains controversial. The prevention of haemorrhagic stroke at all ages and ischaemic stroke in adults has not yet received the same degree of attention. Although there are fewer studies, silent cerebral infarction on magnetic resonance imaging (MRI), and other neurological conditions, including headache, epilepsy and cognitive dysfunction, are also more prevalent in sickle cell disease compared with age matched controls. Clinical, neuropsychological and quantitative MRI screening may prove useful for understanding epidemiology and aetiology.

Brain Oxygen Extraction and Metabolism in Pediatric Patients With Sickle Cell Disease: Comparison of Four Calibration Models

“…This also leads to hemolysis and decreased hemoglobin, thus decreased arterial oxygen content, resulting in an elevated cerebral blood flow (CBF) in order to compensate for the oxygen demand of the brain (Herold et al, 1986;Hurlet-Jensen et al, 1994a;Li et al, 2020). SCD has been associated with a number of brain physiological disorders, including increased cerebral vasculopathy, reduced cerebrovascular reactivity, and increased risk of overt stroke or silent cerebral infarction (SCI) (Pauling et al, 1949;Hurlet-Jensen et al, 1994b;Miller et al, 2001;Prengler et al, 2002;Switzer et al, 2006;Leung et al, 2016;Juttukonda et al, 2017;Bush et al, 2018a;Jordan and DeBaun, 2018;Václavů et al, 2019;Jacob et al, 2020;Kirkham and Lagunju, 2021;Stotesbury et al, 2021). An increased risk of neurodevelopmental disorders in pediatric SCD patients was also reported (Berkelhammer et al, 2007;Lance et al, 2015Lance et al, , 2021.…”

Hematopoietic Stem Cell Transplantation Stabilizes Cerebral Vasculopathy in High-Risk Pediatric Sickle Cell Disease Patients: Evidence From a Referral Transplant Center

“…This study is one of a few studies that explored the outcome of HSCT in pediatric SCD patients with CV complications specifically [ 20 ]. The incidence of stroke in SCD patients is increased in pediatric age group, which indicates the need for early identification by screening using TCD to detect patients at risk and initiate blood transfusions or refer them for possible HSCT [ 6 , 18 , 20 ]. Unfortunately, most of the patients referred to our center were already symptomatic, due to established vasculopathy and were on regular transfusions.…”

“…The reported prevalence for sickle-cell trait ranges from 2% to 27% [ 1 - 4 ]. Overt stroke occurs in 7-13% of children with SCD and can lead to motor disability, neuropsychological impairment and death [ 5 , 6 ]. Reports on the incidence of stroke in SCD in Saudi Arabia are limited.…”

“…It is expected to be lower considering its less severe phenotype due to the high hemoglobin F percentage (Arab-Indian haplotype) compared to the severe African type seen in the Southwestern region, which all of our patient cohort represents [ 7 ]. SCD patients can present with serious complications, such as cerebral vasculopathy (CV), leading to stroke and other neurologic deficit [ 6 , 8 , 11 , 12 ]. Such clinical manifestation can be elicited by magnetic resonance imaging/angiogram (MRI/MRA) that can show spectrum of radiological abnormalities indicative of infarction, ischemia and atrophy ( Fig.…”

The Severity of Sickle Cell Anemia in Men - The Action of Molecular and Biochemical Markers

“…It is known that stroke is a major driver of mortality and morbidity in patients with sickle cell disease [48] a fact that could be explained by two hypotheses, the first is that the high rate of strokes would be due to the viscosity of sickle cell red cells, which would culminate in thrombosis and consequently ischemia [49]; however, this would not be enough to explain the origin of strokes in the great vessels, which are marked episodes in this disease. The second hypothesis concerns the connection of sickle cells to the vascular endothelium, where activation occurs by direct contact of sickle erythrocytes, heme, free Hb, and ROS induced by hypoxia/reperfusion [50].…”