Sickle cell disease (SCD) is a group of inherited haemoglobinopathies [1]. Sickle cell anaemia, which is the most common form of sickle cell disease in Sub-Saharan Africa (SSA) refers specifically to homozygosity for the βs allele and is recognised by the World Health Organisation (WHO) as a global public health concern, associated with high morbidity and mortality [2] [3] [4] [5] [6]. In Cameroon, the prevalence of the sickle cell trait is estimated to be 18.2% for the heterozygous form and 2% - 3% for the homozygous SS forms [7].

Sickle cell anaemia is the most common cause of stroke in children [2] [3] [8]. Stroke, which is also known as cerebrovascular accident (CVA) is defined by the Cooperative Study of Sickle Cell Disease (CSSCD) as an acute neurologic syndrome due to vascular occlusion or haemorrhage in which neurologic symptoms lasted more than 24 hours or until death [9]. Approximately 11 percent of children with SCD will have a stroke before age 20, and without secondary prevention more than half of these will have recurrent stroke within two years of the initial stroke [10] [11]. An estimated prevalence of 7.8% was found in Jamaica, 9.1% in Nigeria and 6.7% in Cameroon [2] [12] [13]. Infarction accounts for 75% of strokes in SCD and is the most common stroke type in children [14]. The average age for the first recognized cerebral infarct is 7.7 years with most occurring between the ages 5 and 15 years [15].

Several risk factors, as well as associated factors have been identified by the CSSCD: for ischemic stroke, prior transient ischemic attack (TIA), frequency of acute chest syndrome (ACS), ACS in the 2 weeks preceding the event, and systolic blood pressure among others [10] [16]. For haemorrhagic strokes, identified risk factors include older age, low steady state hemoglobin and high steady state leucocyte count [16]. The outcome following stroke in SCD patients depends mainly on the severity of the stroke, the type of stroke, and how prompt the management is taken into action. A study carried out over a 5-year period by Portnoy et al. revealed that 24.7% of sickle cell patients developed hemiplegia following their stroke [17]. Deficits in executive function and attention have been found in those with overt and silent infarcts too [1]. Mortality rate following a stroke event in under 5 sickle cell children in Sub-Saharan Africa varies greatly from 10% - 90% [18] [19].

Very few studies on stroke in sickle cell patients have been carried out in Cameroon. We therefore aimed to determine the risk factors for overt stroke and outcome at discharge in sickle cell disease patients followed at two sickle cell treatment centers in Cameroon.

Out of the 1734 patients admitted during the study period who fulfilled the inclusion criteria, 57 cases of stroke were identified. A total of 1000 files were reviewed, cases included. The corresponding 798 matched controls were selected from these files which made a total of 855 patients. 119 of these patients were excluded with 8 of them being cases and 111 controls because they were either unreachable or refused to participate in the study. Hence, the total number of patients enrolled was 736 with 49 cases and 687 controls. This is depicted in Figure 1.

Our study population included sickle cell children aged 6 months to 16 years. Majority of patients enrolled were males. Within the “stroke” population, not all patients had a brain CT-scan (mostly because of financial constraints). Of those who could do the scan, all were found to have ischemic strokes. The prevalence of stroke among sickle cell disease patients was found to be 6.7% in a study carried out in Cameroon [12], 9.1% in Nigeria and 7.8% in Jamaica [2] [13]. From our study a prevalence of 3.29% was found. These disparities might be explained by the difference in study designs used in these studies.

Several factors were assessed to determine any potential association with the occurrence of overt stroke. From this study, no association was found between age below 5 years and occurrence of stroke. Ostendorf A.P et al. in 2017 [14] stated that the age of occurrence of stroke was between 5 and 15 years. This

seems to defend the idea that overt stroke is a disease of the older child. No association was found between stroke occurrence and the male gender. Having had many (>3) episodes of acute chest syndrome in a year or within the last two weeks may predispose someone to overt stroke. Ohene-Frempong et al. [10] also evidenced these as factors associated to the occurrence of stroke. It can be explained by the fact that increase in acute chest syndrome, which is either due to the vaso-occlusion or to infection (pulmonary disease), can lead to hypoxia at the level of the damaged cerebral vessels and precipitate stroke. Strouse J.J found out an association between the use of NSAIDs, a history of blood transfusion in the previous 2 weeks and the occurrence of overt stroke. The author argued that NSAIDs caused bleeding, due to its effect on platelet function, hence haemorrhage was highly possible and blood transfusion had a deleterious effect on the viscosity of blood or the regulation of cerebral blood flow [21]. However, in our study, this association was not found. It can be postulated that this is because our sample had only ischemic strokes.

Patients with SCD typically have HbF levels ranging from 1% to 20% and those with genetic mutations leading to hereditary persistence of HbF (HPFH) can have HbF levels that reach 30% to 40% of the total haemoglobin with a ratio of 1.1:1. Some studies identified haemoglobin F as a protective factor for stroke [13]. However, this association was not found in our study.

In studies carried out in Nigeria and the USA [10] [22], low steady state haemoglobin, high steady state leucocytes and history of prior TIA have been found to have an association with the occurrence of overt stroke, and this correlates with the current study. Sickle cell patients are known to have lower haemoglobin levels and higher leucocytes than non-sicklers. Constant high white blood cell count even when in steady state, can slowly cause damage to the cerebral vessel walls, therefore, increasing the risk for stroke. Conversely, constant low haemoglobin level increases the risk for decreased blood perfusion at the level of the cerebral arteries, hence hypoxia, ischaemia and subsequently stroke. A history of previous stroke was associated with occurrence of a subsequent stroke.

Stroke outcome in our population was assessed using the modified Rankin scale (mRs) structured interview to evaluate dependency of the activities of daily living due to disability. The outcome, which was evaluated at discharge was classified into good and poor outcome. Patients who had “no more symptoms at discharge”, or “very slight symptoms which did not affect the daily activities” were classified as good outcome, while patients who had “evident motor deficits”, which had an “impact on their daily activities”, as well as patients who “died while in the hospital” were classified as poor outcome. From this study, it was found out that the majority (67.3%) of the population had a good outcome at discharge. A similar study carried out by Aksu et al., who described the short term neurological outcomes of paediatric stroke, had 61% of their population with a favorable outcome [23]. Similar results were obtained in 1999 by Edward A.et al. where, 64% of their study population were totally independent in the activities of daily living at discharge [24]. It could be postulated that the better outcome in children is due to the high plasticity of the child brain. Moreover, most cases of strokes in children are of ischemic types, which are known to have better prognosis than hemorrhagic strokes. Some studies have reported female gender and younger age as risk factors for poor outcome [24], but this association was not found in the current study. Our youngest sickle cell patient with stroke was 4 years old. Young children may not be as handicapped as adults because the injured areas of the brain may not yet be in use [24]. The interval between stroke onset and admission to the hospital, as well as the length of hospital stay were not associated with poor stroke outcome at discharge. Jorgensen H.S. et al. [25], however reported an association between an interval of >12 hours between onset of stroke and admission at hospital as a predictor of poor outcome.

Clinical presentation at admission is also highly predictive of the stroke outcome. The most common presentation from our study population was hemiplegia, followed by aphasia. Hemiplegia was similarly found as the most common clinical presentation in a study carried out in Cameroon by Obama et al. [26]. No association was found between the presence of hemiplegia and poor stroke outcome, contrarily to a study carried out by Edward et al. [23]. Aphasia at presentation predicted a poor stroke outcome in our population. Though the type and severity of aphasia was not taken into consideration, several studies show aphasia as being prognostic a sign for poor stroke outcome [27] [28] [29]. Aphasia was associated with increased lengths of stay in both the acute stroke and acute rehabilitation settings, more short- and long-term complications, worse performance in activities of daily living, increased financial costs, and increased risk of mortality.

There was no association between the age of the patient and the occurrence nor outcome of stroke. A prevalence of 3.29% for stroke in the sickle cell population was found. History of previous stroke, prior TIA, history of acute chest syndrome in the 2 weeks prior to the stroke and high steady state leucocytes are all risk factors for stroke. The mortality rate was low (4.1%) and majority of our stroke patients had a good outcome at discharge. Aphasia was the only independent factor associated with poor stroke outcome.

· The study was retrospective and thus data capture was difficult because of a great amount of missing data. Moreover, since the study was conducted in two central level hospitals, many stroke cases at peripheral level (district hospitals and health centres) and community level could have been missed and thus these results may not be truly representative of the population of Cameroon.

· Many patients with sudden neurological deficit were not able to afford a cerebral CT scan. This gives great bias in our statistical analyses since many cases were clinically diagnosed and no radiological confirmation could be made. Moreover, since outpatients who consulted with neurological deficit were not included in this study, this constitutes another study bias.

Authors extend their gratitude to LHD and Centre Mere Enfant Chantal Biya, family and friends and everyone who participated in this research work.

The authors declare that they have no competing interests.

EKI collected data from files of patients. EKI, EEC, DM designed the study. EKI and MMLE wrote the manuscript. EEC and DM supervised this work. MMLE, EKI, EEC, DM, MA, NLEE, MR, and NPY contributed to scientifically reviewing the manuscript for intellectual inputs. All authors reviewed the final manuscript and agreed for submission.

Charlotte, E.E., Nicole, A.Y.A., Ingrid, E.K., Edgar, M.M.L., Eleonore, N.L.E., Ritha, M., Yolande, D.P., Patricia, E., Mbanya, D. and Awa, M. (2021) Risk Factors and Outcome of Overt Stroke in Sickle Cell Patients Admitted in Two Reference Hospitals in Yaounde and Douala. Open Journal of Pediatrics, 11, 503-516. https://doi.org/10.4236/ojped.2021.113047