Moyamoya Disease and Down Syndrome Muferet Erguven, Murat Deveci and Tahsin Turgut Department of Pediatrics, SSK G6ztepe Educational Hospital, Istanbul, Turkey Abstract. Moyamoya disease is an obstruction of the internal carotids and of the afferent and efferent channels of Willis polygon, which causes a collateral circulation, responsible for the typical angiographic image of a "puff of smoke" (Moyamoya, in Japanese). Its etiology is unknown, and it might be congenital or acquired. The clinical features are cerebral ischemia, recurrent transient ischaemic attacks, sensorimotor paralysis, convulsions and migraine-like headaches. We report a 2 years and 9 months old boy with Down syndrome and Moyamoya disease who presented with focal convulsions. [Indian J Pediatr 2005; 72 (8) : 697-699] E-mail: m4deveci@yahoo.com Key words : Convulsions; Down syndrome; Moyamoya disease; Puff of smoke; Willis polygon. Moyamoya disease is a chronic vasculopathy that leads to single or usually double sided blockage in intracranial zones of internal and external carotid arteries which are responsible for circulation in the frontal regions of the brain. "Moyamoya" is a Japanese word meaning "puff of smoke" and is used to identify classical angiographic look of multiple small intracranial vessels. 1,2 This disease causes cerebrovascular insufficiency which leads to formation of reticular multiple anastomosis and collaterals between internal and external carotid arteries. Occurrence of this very rare disease accompanying with Down Syndrome is more frequent when compared to normal population. 3 CASE REPORT A male patient of 2 years and 9 months of age was admitted to our clinic with lower respiratory tract infection and focal convulsions. Patient had history of generalized convulsions on three different occasions. The patient was the ninth and the last child of a couple who were second degree relatives; and were approximately 47 years old. Seven sisters were alive and healthy. His brother (third child) had died due to an undiagnosed disease when he was only 20 days old. On physical examination, child had facies suggestive of Down Syndrome (Fig. 1). On systemic examination, respiratory system revealed bilateral coarse crepitations, cardiovascular, gastrointestinal and genitourinary system examinations were normal. On neurological examination; left arm's activity was less than normal. A mild hypotonia was noticed in all other extremities, and a mild increase in deep tendon reflexes was observed. The laboratory findings revealed a normal urine analysis, while hemogram revealed hypochromic microcytic anemia. Correspondenceand Reprintrequests : Dr. Murat Deveci,Caferaga mah. K~laptanc~sk. No:13/3 34710Kad~k6y-Ystanbul/Turkey. Indian Journal of Pediatrics, Volume 72--August, 2005 Fig. 1. Routine biochemical tests were normal; HbAI: 96.4% (N: 95.5-97.5%), HbA2: 3.6% (N: 2.5-4-5%), HbF: Negative (N: < 3%), HbS: Negative (N: Negative), Protein C: 73% (N: 70-140%), Protein S: 103% (N: 60-140%), Antithrombin III: %105 (N: 75-125%). No pathology was found in tests for inborn errors of metabolism. EEG was found to be showing fast baseline activity. In cranial MRI; parenchymal atrophy was observed in frontal and parietal regions, and hemorrhagic infarct zone was observed in right frontal region. With cranial MR angiography, there was gradual thinning in intracranial internal carotid artery. With A1-M1 cranial MR angiography; gradual thinning in intracranial internal carotid artery, occlusion in A1-M1, occlusion in posterior cerebral artery, vascular reticular formation on Willis polygon which was 697 Muferet Erguven et al s u s p e c t e d to be b e c a u s e of M o y a M o y a , a n d recanalization of A2 segment via this vascular web were observed (Fig. 2). Fig. 2. DISCUSSION When searching the reasons for repeated convulsions in the patient, we observed bilateral ischemic regions in cranial MR. After e x c l u d i n g cardiac, i n f l a m m a t o r y , metabolic, hematolologic and cerebrovascular diseases which m a y cause cerebrovascular blockage; based on cranial MR a n g i o g r a p h y , M o y a m o y a disease was diagnosed. Etiology of the disease is currently not clearly known. According to its relations with some HLA types such as HLA B51, the disease is thought to be having hereditary tendencies and having genetic factors in its pathogenesis. There are no clinical characteristic s y m p t o m s of the disease. In children, the disease usually causes transient ischemic attacks a c c o m p a n y i n g w i t h h e m i p a r e s i s , convulsions or other focal neurological findings. In the present case, seizures were the prominent symptoms. T h e r e m a y be i n t r a v e n t r i c u l a r a n d s u b a r a c h n o i d hemorrhage. Imaging techniques are used in diagnosis? Multiple infarct and atrophic regions are observed in CT and MRI. Exact diagnosis is via cerebral angiography or MR a n g i o g r a p h y . 5 Characteristic findings o b s e r v e d t h r o u g h these m e t h o d s are occlusion in intracranial internal carotid artery and abnormal vascular reticulation. This abnormal vascular reticulation is called "Moyamoya vessels". These pathologies are usually bilateral. But if these are congenital or developing later are still a matter of discussion. This is because of the fact that the disease has two peaks: the first decade and the third decade. Also the disease is more frequent when accompanying with diseases like Down syndrome, neurofibromatosis and tuberous sclerosis. The patient was in first decade and had D o w n syndrome. In some cases with m o y a m o y a disease, coexistence of protein C or S deficiency has been reported. 6,7However, this case had normal protein C and 698 S levels. It is hard to predict the prognosis, because the natural p r o g r e s s of the disease is c u r r e n t l y u n k n o w n . In autopsies, serious occlusive changes are o b s e r v e d in intracranial internal carotid artery and arteries of Willis p o l y g o n . These c h a n g e s are c a u s e d b y i n t i m a l proliferation and subepithelial hyperplasia and fibrosis. Adventitih and media of the vessels are normal. There are no inflammatory cells or atheroma found on the vessels. In medical treatment, steroids, and with some cases aspirin, ticlopidine, vasodilators and anticoagulants are used? There are various different modalities in surgery and s a t i s f a c t o r y results are o b t a i n e d b y EDAS (encephaloduroar teriosynangiosis).9,i0 Moyamoya is a truly rare disease (with incidence of 1/ 1.000.000 a year), but its incidence in patients with Down syndrome has been noted to be three times the estimated i n c i d e n c e of m o y a m o y a disease in the g e n e r a l population. 11In an analysis of stroke in 37 children with D o w n s y n d r o m e , seven patients were f o u n d to have angiographic abnormalities consistent with m o y a m o y a disease. 12 The a b n o r m a l i t i e s associated w i t h D o w n syndrome may create a vulnerability for the development of m o y a m o y a disease. Several p r o t e i n s e n c o d e d on c h r o m o s o m e 21, including s u p e r o x i d e d i s m u t a s e 1, interferon gamma receptor, cystathionine Gsynthase and ~i-chains of collagen type VI, are associated with an increased risk for vascular diseases. 13-~5 In c o n c l u s i o n , m o y a m o y a disease s h o u l d be c o n s i d e r e d in distinctive diagnosis of n e u r o l o g i c a l abnormalities in patients with Down syndrome having m u l t i p l e cerebral infarcts and r e l a t e d n e u r o l o g i c a l findings. Magnetic r e s o n a n c e a n g i o g r a p h y is an i m p o r t a n t i m a g i n g t e c h n i q u e for d i a g n o s i s of this condition. REFERENCES 1. Gorrotxategi P, Regulion MJ, Gaztanaga R et al. Moyamoya disease in a child with multiple malformations. Rev Neurol 1995; 23(120) : 403-405. 2. Javanovic Z. Risk factors for stroke in young people. Srp Arh Celok Lek 1996; 124(9-10):232-235. 3. Gordon N, Isler W. Childhood moyanoya disease. 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