Clinical Brief
Moyamoya Syndrome in a Child with Down Syndrome Utpal S. Bhalala and Pankaj R. Parekh Department of Pediatrics, Sir Hurkisondas Nurrotamdas Hospital and Research Centre, Mumbai, India.
Abstract. Secondary Moyamoya disease, also known as Moyamoya syndrome has been rarely associated with Down syndrome. In pediatric patients, the usual presentation is that of ischemic stroke. Here is reported a 4-year-old child with Down syndrome and Moyamoya syndrome who presented with acute-onset right hemiplegia. A high index of suspicion is necessary to make the diagnosis. [Indian J Pediatr 2005; 72 (7) : 635-637] E-mail:
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Key words : Cerebrovascular disorders; Down syndrome; Moyamoya disease.
Moyamoya disease or syndrome is believed to be an uncommon cause of stroke in childhood. Moyamoya disease is characterized by progressive idiopathic stenosis with eventual occlusion of large cerebral arteries of Circle of Willis. Over period of time, collaterals develop and give a typical “ puff of smoke “ (Japanese-Moyamoya) appearance on imaging studies. Moyamoya disease is of unknown etiology while. Moyamoya syndrome is secondary to underlying vasculopathy due to autoimmune diseases, sickle cell disorder, CNS infections or rarely Down syndrome. CASE REPORT A 4-year-old maratha boy, third issue, born of nonconsanguinous marriage and residing at mumbai was brought by parents with chief complaints of sudden onset right focal, tonic-clonic convulsions followed by weakness of same side of the body. Patient was apparently alright 8 days back when he had sudden onset, intermittent high grade fever without chills and rigors. It was associated with cough and cold but not with glandular swellings in the neck, headache, irritability forceful vomiting or altered sensorium. Two days following recovery from febrile illness, he developed sudden onset right sided tonicclonic convulsions followed by period of postictal drowsiness. Patient developed weakness of the right side of the body after the convulsion so that he could not move his right upper and lower extremities could not sit without support on right side. Parents noticed drooling of saliva from the right side of the mouth with deviation of angle of mouth to left. The weakness was non-progressive and was not associated with alteration of sensorium , fever or symptoms of raised intracranial tension. There was no history of trauma to head or neck , Correspondence and Reprint requests : Dr. Utpal S. Bhalala, A-203, Rajesh Apartment, Chandavarkar Road, Borivali (West), Mumbai-400 092, Maharashtra, India.
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bleeding tendencies or recurrent episodes of pain in limbs or in abdomen. There was no history suggestive of cardiovascular or renal disorder. There was no similar history of weakness in the past. Family history was not contributory. There was history of advanced maternal age otherwise the antenatal history was normal. He developed respiratory distress and jaundice on day5 of life for which he was shifted to Neonatal Intensive Care Unit (NICU) and put on oxygen, antibiotics and phototherapy. Patient recovered within 20 days of NICU stay and diagnosis of Down syndrome with lower respiratory tract infection was made. Patient had global developmental delay but had a good sense of music. He had adequate caloric and protein intake and was immunized till date. On examination, the patient had clinical features suggestive of Down syndrome. He was alert and conscious. His neurological examination was compatible with right sided hemiplegia and upper motor neuron lesion of right facial nerve. Other cranial nerves were normal. The fundi were normal. The peripheral pulses were normal and regular. The heart sounds were normal with no murmur. No carotid bruits could be detected. Examination of other system was unremarkable. Patient’s routine hematological and biochemical parameters were normal. Analysis of cerebrospinal fluid was also normal. CT scan of brain revealed ill-defined hypodense area in left fronto-parietal region with gyriform enhancement which was consistent withan infarct in territorial distribution of left middle cerebral artery. In view of infarct, echocardiography with color doppler was done which ruled out congenital heart disease and/or infective endocarditis. His lipid profile, coagulation profile, sickling test, antinuclear antibody (ANA), antiphospholipid antibody assay, and urinary homocystine levels were normal. Patient’s Magnetic Resonance Imaging (MRI) and Magnetic Resonance Angiography (MRA) of brain showed a large early subacute infarct in left fronto635
Utpal S. Bhalala and Pankaj R. Parekh temporal and parieto-occipital region (entire left MCA erritory)(Fig 1) with evidence of severe stenosis of distal cavernous and supraclenoid segment of right internal carotid artery (ICA), M1 segment of right middle cerebral artery(MCA), A1 segments of both anterior cerebral arteries(ACA), and origins of both posterior cerebral arteries(PCA). The MRA was reported as consistent with Moyamoya disease (Fig. 2).
Fig 1. Magnetic Resonance Imaging (MRI) of brain showing a large early subacute infarct in left fronto-temporal and parietooccipital region (entire left MCA territory).
Fig 2. Magnetic Resonance Angiography (MRA) of brain showing severe stenosis of distal cavernous and supraclenoid segment of right internal carotid artery (ICA), M1 segment of right middle cerebral artery (MCA), A1 segments of both anterior cerebral arteries (ACA) and origins of both posterior cerebral arteries (PCA).
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DISCUSSION Cerebrovascular accident is rare in childhood with an overall incidence of approximately 2.5 to 2.7 cases per 1,00,000 per year.1 Approximately 20-40% of patients with arterial ischemia do not have identifiable risk factors.2,3 Stroke is most commonly associated with either cardiac or thrombotic disorder or infection. Children with Down syndrome are at increased risk for cerebral infarction. In majority of cases cause is thromboembolism secondary to an underlying cardiac disease with/without infective endocarditis. Since Down syndrome patients have abnormal immune function, they are predisposed to infections like meningitis which may cause cerebral vasculitis and therefore stroke. Rare cause of stroke in Down syndrome can be Moyamoaya syndrome. In an analysis of 37 cases of Down syndrome, seven patients had angiographic features consistent with Moyamoya syndrome.4 Moyamoya disease is slowly progressive, bilateral occlusion of internal carotid arteries starting at carotid siphon with occasional involvement of basilar arteries. Over a period of time, collaterals develop at the base of the brain from anterior and posterior choroidal arteries, basilar artery, and the meningeal arteries. On angiography, these telengiectasias give a typical hazy appearance like a puff of smoke (Japanese-Moyamoya). Infants and young children tend to have acute onset of complete hemiplegia affecting face and limbs. Such episodes tend to recur and outcome is generally poor. 5 When Moyamoya angiographic pattern is associated with an underlying disorder it is called Moyamoya syndrome. Mechanism of Moyamoya syndrome in Down syndrome is not well understood but several hypothesis have been proposed. Patients with Down syndrome are predisposed to vascular disease generally. This is seen in abnormal nail bed capillary morphology, high pulmonary vascular resistance, congenital heart disease, abnormalities of retinal vessels and primary intimal fibrosis6. Vascular dysplasia may lead to a structural defect which forms the basis for Moyamoya disease. It is believed that several proteins encoded on chromosome 21 are associated with an increased risk of vascular disease. These are, a-chain of collagen type 6, Superoxide desmutase 1, Interferon gamma receptor and Cystathione b-synthase.6 Another mechanism which is considered to link the two disorders is autoimmunity. Patients with Down syndrome have an increased prevalence of autoimmune disorders such as autoimmune thyroid disorders.7 Upper cervical subluxation can also produce a cerebral circulatory insufficiency that predisposes to development of Moyamoya disease.8 In our patient, there was no evidence of Atlanto-axial dislocation on cervical spine radiograph. Definitive Indian Journal of Pediatrics, Volume 72—July, 2005
Moyamoya Syndrome in a Child with Down Syndrome diagnosis of Moyamoya disease or syndrome requires the use of appropriate imaging techniques. Conventional cerebral angiography provides a definitive means of visualizing the vasculature. There is however, a 1% chance of stroke after the procedure.9 MRA provides a non-invasive alternative to conventional angiography. Routine angio-graphy is currently indicated if MRA is equivocal or if there is Moyamoya pattern and surgery is planned. The management of Moyamoya disease or syndrome difficult. Medical management includes antithrombotic therapy, correction of underlying cause if present and general supportive measures. Efficacy of antithrombotic therapy in this condition is uncertain. Secondly, there is risk of subarachnoid hemorrhage from the collateral vessels, especially in adolescent patients who are given antithrombotic treatment. Aspirin is recommended in patients with normal perfusion reserve as shown by Positron Emmision Tomography (PET).10 One should make attempt to correct underlying etiopathogenesis. For example, in patient with positive antiphospholipid antibody assay and Moyamoya pattern on the angiography, immunoglobulin therapy should be tried. Surgical treatment includes encephalo-duroarteriosynangiosis, pial synangiosis, multiple burr holes or encephalo-myo-synangiosis. These are indicated when perfusion reserve is reduced on PET scan. Major problems with surgery include cost, complications of the surgery and anesthesia and reperfusion brain injury.10 Although management of Moyamoya disease or syndrome is challanging, prompt action may prevent further neurological damage. This case is being presented
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for the rarity of association of Moyamoya syndrome with Down syndrome. Acknowledgements The author wishes to thank Dr. S. K. P. Matwankar, Director Operations, Sir H. N. Hospital and research center, Mumbai for his kind permission to publish this manuscript.
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