Moyamoya Syndrome Associated with Protein C and S Deficiency as a Neurological Complication in Children with Sickle Cell Disease

Case Report

Austin J Clin Case Rep. 2021; 8(3): 1202.

Moyamoya Syndrome Associated with Protein C and S Deficiency as a Neurological Complication in Children with Sickle Cell Disease

Yassien M¹*, El-Shanshory M² and Asslan M³

¹Department of Neurology, Tanta University, Egypt

²Department of Pediatrics, Tanta University, Egypt

³Department of Hematology, Tanta University, Egypt

*Corresponding author: Marwa Yassien, Department of Neurology, Tanta University, Faculty of Medicine, Egypt

Received: March 08, 2021; Accepted: March 18, 2021; Published: March 25, 2021


Background: Sickle Cell Disease (SCD) is an autosomal recessive hemoglobinopathy containing mutant sickle cell Hemoglobin (HbS). Acute and chronic organ dysfunction, chronic hemolytic anemia, and recurrent painful episodes are the main features of sickle cell disease. There is a wide variety of neurological complications, including: headache, cognitive difficulties, seizures, visual loss, ischemic and hemorrhagic stroke, transient ischemic attacks, soft neurological signs coma, altered mental status and covert or silent infarction. Moyamoya is an uncommon cerebral vasculopathy that’s also found in children with SCD.

Case Presentation: Here, we reported two children diagnosed with SCD who presented with headache, recurrent ischemic strokes, seizures and cognitive decline. They showed abnormalities on different neuroimaging including: CT and /or MRI, MRA and/or CT angiography, also transcranial color coded duplex, EEG and Stanford-Binet Intelligence scales-Fifth Edition. They also showed abnormal level of protein C and protein S. They also had irregular blood transfusion and were diagnosed as Moyamoya syndrome.

Conclusion: According to our findings, Moyamoya syndrome was a rare complication of SCD in children, but should be considered with proper approach, diagnosis and management.

Keywords: SCD; Neurological complications; Moyamoya; Diagnosis


Sickle Cell Disease (SCD) is an autosomal recessive hemoglobin disorder. It is a qualitative hemoglobinopathy resulting from a structural change in the sequence of amino acids on the beta globin chain of the hemoglobin molecule due to a point mutation. It is characterized by hemoglobin polymerization, erythrocyte stiffening, and subsequent vaso-occlusion [1,2].

The different sickle cell syndromes that result from distinct inheritance pattern of the sickle cell gene (beta S gene) are divided into sickle cell disease and sickle cell trait. Sickle cell disease is associated with chronic anemia and recurrent visceral pain. The sickle cell trait is largely asymptomatic [3]. The prevalence of SCD is 0.3% in Egypt, where the carrier rate varies from 9 to 22% [4].

Children with sickle cell disease, present with a wide variety of neurological syndromes, including ischemic and hemorrhagic stroke, transient ischemic attacks, soft neurological signs, seizures, headache, coma, visual loss, altered mental status, cognitive difficulties, and covert or ‘silent’ infarction [5].

Moyamoya is an uncommon cerebral vasculopathy, characterized by typical angiographic changes associated with subsequent clinical features. In moyamoya, steno-occlusive changes in the main cerebral arteries and decrease in the cerebral perfusion pressure, resulting in the formation of a fine network in neovascularization [6,7].

These collaterals show evidence of stress related to increased flow, including the combination of the fragmented elastic lamina, thinned media in the vessel wall, and the presence of microaneurysms; these findings help to explain why some patients present with hemorrhage. Other Moyamoya related vessels are collapse, and their lumen thrombosis could cause ischemic symptoms [8,9].

Moyamoya syndrome even found in sickle cell trait patients, but as a rare neurological complication, but it is found more in sickle cell disease patients [10,11].

Children and adults with MM may have different clinical presentations; the symptoms and clinical course vary widely, ranging from being asymptomatic to manifesting as severe neurologic deficits. Children more commonly have ischemic events and may experience hemiparesis, monoparesis, sensory impairment, involuntary movements, headaches, dizziness, seizures, mental retardation, or persistent neurologic deficits. In adults, symptoms and signs are similar to those in children, but sudden onset intraventricular, subarachnoid, or intracerebral hemorrhage is more common [12].

Case Presentation

Case 1

A male child aged 9 years diagnosed at the age of 1 year with SCD with negative family history for SCD and positive consanguinity. He presented at first by recurrent attacks of episodic left temporal headache with migraine like character 3 years ago which became chronic 1 year later. Also, he experienced poor scholastic achievement (Stanford Binet IQ: 68) 2 years ago followed by repeated attacks of TIAs in the form of right side weakness one year ago followed 2 weeks later by 2 attacks of focal fits over right side of the body . There was past history of old left ischemic hemiplegia with dysarthria one and half years ago with partial improvement with residual deficit with history of post stroke seizures 1 month later on Levetiracetam, hydroxyurea, aspocid regular ttt, but irregular blood transfusion. He was scheduled for Hematopoietic Stem Cell Transplant (HSCT), but later after diagnosis with moyamoya syndrome 6 months ago with MRI, MRA, TCCD and CT angiography, he was planned to undergo Encephaloduroarteriosynangiosis (EDAS). Serum levels of protein C and protein S were reduced (55 IU/dl for protein C, 45 IU/dl for protein S). We were still waiting for results of this intervention, which was postponed for covid-19 epidemic (Figures 1a-1f).