Stroke among Children with Sickle Cell Anemia in Mulago Hospital, Uganda

  

    
Variable 
    
STROKE 
  
  

    
N=46 (%)
  
  

    
Malaria prophylaxis
  
  

    
Yes
    
43(93.5)
  
  

    
No
    
3(6.5)
  
  

    
Pneumococcal vaccine use
  
  

    
Yes
    
4(8.7)
  
  

    
No
    
42(91.3)
  
  

    
Hydroxyurea Use
  
  

    
Yes
    
4 (8.7)
  
  

    
No
    
42(91.3)
  
  

    
Ever received blood transfusion
  
  

    
Yes
    
44( 95.7)
  
  

    
No
    
2 (4.3)
  
  

    
Number of blood transfusions
  
  

    
>1
    
33(71.7)
  
  

    
0-1¹
    
13(28.3)
  
  

    
N: Number of    children.
      
 
  

Table 5: Intervention received by sickle cell anemia children with STROKE.

Discussion

In this paper, we describe the clinical presentation of children with SCA stroke and their hematological indices. We have also described interventions in these same children.

Clinical presentation of children with cerebrovascular accident

Most of the patients with stroke presented with a history of change in behavior, seizures, headache, confusion and weakness of the limbs. A history of change in behaviour was recorded in a third of our patients with SCA stroke. Some studies have described mental status changes in children who present with stroke [13]. In our study, seizures were reported in one out of five children with SCA stroke. This finding is similar to what Kehinde and others have reported from Nigeria. It’s however much lower than the 55% reported by George and Frank-Briggs also from Nigeria [14]. The pathophysiology of seizures in stroke is unclear but it has been postulated that vasculopathy which is associated with SCA may be a key factor in seizure development [14,15].

Headache was reported in one in five children with SCA stroke. Again this is similar to findings by Kehinde who found that 24% of stroke patients presented with a headache [13]. However studies from Saudi Arabia by Zakaria and others found a lower prevalence of headache of one in nine children with SCA stroke [12].

Confusion was similarly reported in one in five children with SCA stroke in our study. This finding was much higher than was reported in a Jamaican cohort of SCA children where the prevalence was only 6%. The mechanism of confusion in SCA stroke is not known but it has been associated with severe bacterial infection and vaso-occlusive crisis [16,17]. In this study, we did not look for evidence of severe bacterial infection.

Other complaints associated with stroke included loss of sight and hearing. In this study, these occurred in 1 out of 16 children. This was similar to findings from a large cohort study done in Lagos, Nigeria [14]. The cause of loss of sight and hearing is possibly due to ischemia from vascular occlusions [15,18].

Motor deficits

Hemiplegia was the commonest clinical sign presenting in four out of five children with SCA stroke. This finding is similar to what other studies in Jamaica [16] and Saudi Arabia [12] had found. However, one study in Nigeria found that hemiplegia was present in half the children with SCA-related stroke [14]. This was much lower than what we found in the current study. Hemiplegia is thought to be due to ischemia from large cerebral artery occlusion as a result of the sickle cells and it could also result from of hemorrhage [15,19].

In our study monoplegia was recorded in 1 in 10 of children with SCA stroke. This was higher than what was reported in a natural history of stroke study by Powars and others [19]. Monoplegia may be due to occlusion of the blood vessels that supply the brachial plexus [15].

Quadriplegia occurred in one out of ten children with SCArelated stroke. Similar findings were reported by Powars and others in California [21]. All our quadriplegic patients had recurrent stroke. This finding is similar to what has been reported elsewhere [21]. Patients with quadriplegia have had both right and left hemiplegia with brain CT scans showing bilateral low density areas indicative of injury of the cerebral tissues [4].

Other neurological signs

Speech deficit (aphasia): In this study speech deficit (aphasia) occurred in one in five children with SCA stroke. This is higher than what Saudi [12] and Nigerian [14] authors have reported. Our prevalence of speech deficits was lower than what was reported in the USA, and Jamaica [4,16].

Limb ataxia: Limb ataxia was the second commonest neurological finding in our study. It affected one in three children. This was much higher than that reported by Powars and others. Limb ataxia results from a dysfunction in the cerebellum and can be a result of stroke which leads to poor control of movements of the limbs [4,19,20].

Facial nerve palsy: Facial nerve palsy occurred in one in five of our SCA stroke patients. This is higher than what has been reported from the USA and Nigeria [14,20]. Cranial nerve palsies do occur as a result of occlusion of the major cerebral artery. In children with SCA stroke facial nerve palsies may be due to occlusion of the same vessel.

Lung crepitations: We found that a larger proportion of children with stroke had crepitations in their lungs. This was not surprising finding because several studies have shown a direct correlation between lung infections. In children with acute chest syndrome (ACS), the risk for stroke is higher compared to a child without ACS [21]. This finding does advance the pathophysiology of stroke in children with sickle cell anemia. The presence of a lung infection does predispose the child to hypoxia. This triggers a cascade of sickling and leads to worsening of the oxygenation of the lungs [21]. High Blood pressure more likely to have a high blood pressure. This was similar to studies by Ohene-Frempong in the USA and by Balkaran in Jamaica [4,16,19]. However, the blood pressure readings were taken after the occurrence of the primary outcome of this study. It is therefore, difficult to attribute the high blood pressure as a predictor for stroke in these children.

Hepatomegaly: Hepatomegaly is a common clinical finding in children with sickle cell anemia as a result of chronic haemolysis. We found that children with stroke were about four times more likely to have an enlarged liver as compared to those without a stroke. The association between stroke and hepatomegaly has not been described elsewhere. This finding does suggest that hepatomegally can be used as a marker for severity of illness in children with sickle cell anaemia [22]. However, there is no biological explanation that explains the risk of stroke as a result of a hepatomegaly [16,19].

Hematological indices: The children with SCA stroke are managed with chronic transfusions as standard of care to prevent recurrence of stroke by maintaining HbS levels below 30% [23]. In our study, only 1 in 10 children with SCA stroke had an HbS<30%. This was due to the poor follow up by patients in our clinic who live in various parts of the country. In addition it is the only sickle cell clinic in Uganda. This is a disturbing finding since we know that SCA children who’s HbS are above 30% are at a risk of getting recurrent stroke In our comparative group no child had an HbS<30% thus putting all the children at a high risk for stroke.

Interventions

Hydroxyurea: Children with stroke were started on Hydroxyurea due to the complication. In our children with stroke, only 4 out 46 where started on Hydroxyurea. The role of Hydroxyurea in stroke prevention is based on its ability to induce HbF levels which subsequently reduce the HbS levels in children with SCA. Hydroxyurea as a medication in the prevention of primary stroke is still controversial [24]. Some studies support its use, while others have found no added advantage in its role in stroke prevention [25]. In our setting, no policy has been approved for Hydroxyurea use. However, some clinicians have introduced the medication for use in specific patients. These patients’s are considered at a high risk for severe complications of SCA.

Blood transfusion: Children with SCA stroke received multiple blood transfusions.. This is because children with sickle cell anemia stroke receive multiple transfusions as their standard of care in the hospital. Chronic transfusion programs have been shown to prevent recurrence of stroke in children with sickle cell anemia [23]. In our setting, chronic transfusions programs are a challenge because of the inability of the caregivers to attend the clinic as regularly as suggested by the clinician. This puts our children with stroke at a future risk of recurrent stroke.

Study limitations: This study had a number of limitations.

Recall bias by parents/caregiver/patient on description of symptoms prior to onset of stroke is a real issue. In order to reduce on this bias, we tried to limit the recall questions to three months.

Inability to screen the study participants using Trans-Cranial Doppler (TCD) ultrasound for cerebral vessel speeds. This was due to lack of local expertise in TCD screening.

Our inability to have CT or MRI scans for the children with stroke limited our ability to describe the areas affected in the brain. This was as a result of lack of funding.

Conclusion

We conclude that SCA patients with stroke presented commonly with: behaviour changes, headache and seizures; hemiplegia, aphasia and limb ataxia. Only a very small number of the SCA children, regardless of their stroke status, had HbS<30%. Further research is needed to determine the risk factors for stroke in our population.

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