(Stroke. 1996;27:2131-2135.)
© 1996 American Heart Association, Inc.
Articles |
Moyamoya and Down Syndrome
Clinical and Radiological Features
the Neurology Service (S.C.C.) and the Pediatric Neurology Unit (E.C.D.), Massachusetts General Hospital, and the Radiology Service (R.L.R.) and Neurosurgery Service (R.M.S.), Children's Hospital, Harvard Medical School, Boston, Mass; and the Clinical Investigator Training Program, Harvard-MIT Division of Health Sciences and Technology and Beth Israel–Deaconess Medical Center in collaboration with Pfizer Inc (S.C.C.).
Correspondence to Dr Steven C. Cramer, Bigelow 1256, Massachusetts General Hospital, Fruit St, Boston, MA 02114.
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Abstract |
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Background and Purpose Moyamoya disease is a chronic occlusive cerebrovascular disorder characterized by progressive stenosis of the supraclinoid internal carotid artery, with the secondary development of enlarged basal collateral vessels. It may occur as a primary disease or as a syndrome in association with a variety of conditions, and its pathogenesis remains unexplained. There are relatively few reports describing the occurrence of moyamoya in Down syndrome. The aim of this study is to describe the clinical and radiological features of moyamoya syndrome associated with Down syndrome (MM-DS) and to explore theories of moyamoya pathogenesis in these patients.
Methods Seven children with MM-DS underwent brain imaging, transfemoral angiography, and serial neurological exams. Neurological deficits, poststroke recovery, radiographic infarct characteristics, and angiographic abnormalities were reviewed.
Results The clinical and radiological features of primary moyamoya disease overlap with those of MM-DS. Hemiplegia and aphasia were the most common presentations. Motor recovery was excellent in five of seven cases. Cerebral infarcts were superficial or deep and can occur in a watershed distribution. Angiography demonstrated involvement of the internal carotid artery and its branches bilaterally in all seven cases and the posterior cerebral arteries in four cases.
Conclusions The clinical and radiological features of MM-DS overlap with primary moyamoya disease. We postulate that a protein encoded on chromosome 21 may be related to the pathogenesis of moyamoya disease. Although the neuronal substrate is abnormal in Down syndrome patients, recovery from hemiplegic stroke in patients with MM-DS is comparable to recovery in patients with primary moyamoya.
Key Words: Down syndrome • moyamoya disease • recovery • stroke
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Introduction |
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Moyamoya disease is a chronic occlusive cerebrovascular disorder characterized by progressive stenosis of the arteries of the circle of Willis. The process initially involves the intracranial internal carotid arteries and progresses to involve the middle, anterior, and posterior cerebral arteries. Secondarily, small collateral vessels arise distal to stenosed or occluded vessels.1 Moyamoya disease occurs with a bimodal onset. A peak in children in their first decade is associated with ischemic strokes, while a peak in adults in their fourth decade is associated with hemorrhagic strokes. Hemiparesis is the most common symptom of presentation.2 3 Moyamoya disease affects all ethnic groups, although cases are much more frequently encountered in Japan.2 4 Its etiology remains undetermined.
Primary and secondary forms of the disease are recognized. In 1988, the Japanese Ministry of Health and Welfare defined moyamoya disease as idiopathic bilateral stenosis of arteries of the circle of Willis with collateral vascular networks, demonstrated on angiography. Secondary forms of this vascular pattern are termed moyamoya syndrome and have been identified with increased incidence in a number of conditions.2
Moyamoya syndrome has been estimated to occur more often in children with Down syndrome than in the general pediatric population,5 yet only 13 examples have been reported in the English literature.5 6 7 8 9 10 11 12 13 14 15 In these case reports, comparison of clinical features with those of primary moyamoya disease and assessment of degree of recovery were not detailed, and no standardized staging of angiographic abnormalities was reported.
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Subjects and Methods |
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Five cases of MM-DS were retrospectively identified from a personal series (R.M.S.) of 50 cases of moyamoya surgically treated at Children's Hospital of Boston. Two cases (patients 6 and 7) were prospectively identified and evaluated during a 1-year period from 10 cases of stroke in children, including one case of moyamoya disease without Down syndrome, admitted to the Massachusetts General Hospital pediatric neurology service. Chromosomal confirmation of Down syndrome was determined by the referring physician. All case subjects were examined by at least one of the authors. In each case, medical records, brain imaging, and transfemoral cerebral angiograms were reviewed. Moyamoya abnormality seen on internal carotid artery angiograms was graded according to the six-stage system of Suzuki and Takaku.3
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Results |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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The Table
summarizes the features of our MM-DS case subjects. Age ranged from 2 to 18 years. Hemiparesis occurred with stroke in all subjects; in five of seven subjects, some degree of aphasia was present. All subjects had multiple infarcts, which were bilateral in six of the seven. The median follow-up after most recent stroke was 18 months. In five subjects, neurological deficits were noted before this stroke. Patient 3 had several episodes of transient right arm weakness with dysphasia during the year before her most recent stroke. Patient 4 had an infarct with right hemiparesis and decreased speech 1 month before her most recent stroke; these were improving when the infarct extended with hemorrhage. Before his most recent stroke, patient 5 had completely recovered from the right hemiparesis and decreased speech caused by bihemispheric infarcts 1 year prior. Patient 6 had left hemiparesis from which he substantially recovered 17 months before his most recent stroke. Patient 7 had decreased speech output, some right visual field loss, and right hemiplegia 16 months before his most recent stroke. At that time, motor and language recovery were rapid and complete.
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Angiogram confirmed bilateral moyamoya changes in the internal carotid artery and its branches in all subjects, ranging from stage 2 to stage 6.3 In four subjects, stenosis or occlusion was also observed in the posterior circulation. Patients 1 through 5 received bilateral pial synangiosis and were subsequently stroke-free during the follow-up interval. Five subjects had excellent motor recovery after the index stroke, with minimal or no residual weakness. Two subjects (patients 3 and 4) had significant motor improvement with residual deficits. The Figure demonstrates typical angiographic and MRI features.
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Discussion |
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The clinical features of our seven and the 13 previously reported MM-DS case subjects (Table
) are similar to those of primary moyamoya disease. Reported mortality rates in the primary disease have been low: 4.3%,16 9.8%,17 and 13%.18 None of the seven children in our series has died. The average age of onset in our series is 7 years, typical of childhood moyamoya disease17 18 and similar to the average age (5 years) of affected subjects with Down syndrome reported in the literature.5 6 7 8 9 10 11 12 13 14 15 The ratio of males to females in moyamoya disease is 1:1.4,2 compared with 1:1.1 in the 20 cases of MM-DS. Hemiplegia is the most common mode of presentation in children with moyamoya disease2 3 19 and was present in all seven of our subjects. Transient, and often recurrent, weakness is common4 and was seen in several of our subjects. Ischemic stroke in moyamoya disease affects both the cerebral cortex, often in watershed areas,1 20 and deeper structures.21 22 Brain imaging demonstrates multiple bilateral infarcts,21 less often in the posterior circulation. These patterns were seen in our subjects with MM-DS.
Motor recovery in MM-DS is generally good even after multiple and bilateral strokes, comparable to recovery described in studies of idiopathic moyamoya disease. Of 187 cases of moyamoya disease,17 10% of subjects had no residual deficit after the infarct, 29% had minimal residual deficit, 21% were independent, 14% were partially dependent, and 7% were dependent. Moritake et al23 found recovery to be good in 57%, fair in 22%, and poor in 20%. Consistent with such reports is the good motor recovery in five of our seven subjects and in eight of the nine previous reports of MM-DS in which outcome is described, or 81% overall good recovery (Table). The good recovery from hemiplegia in MM-DS is noteworthy because many stroke recovery mechanisms rely on neuronal adaptations, including synaptogenesis, axonal growth, dendritic growth, and changes in neurotransmitters.24 25 26 27 Among the extensive neuronal abnormalities found in Down syndrome28 29 30 are atrophy of cortical dendrites and reduced synaptogenesis; of note, motor cortex is affected.31
Angiographic features in our seven cases of MM-DS resemble those of primary moyamoya disease and range from mild to severe. Occlusion of the posterior cerebral artery, present in four of our subjects, is seen with increased severity of the disease.3 21 32 Occlusion of the vertebral artery as seen in patient 7 is rare, reported in only three of 90 cases of moyamoya disease.32 Although unilateral presentations of moyamoya disease have been reported,18 19 bilateral involvement was present in all of our subjects, possibly reflecting the difficulty in making an early diagnosis in patients with Down syndrome rather than a vascular pathology specific to these patients. Angiograms for patient 1 are shown in the Figure. Patients 1 through 5 underwent bilateral pial synangiosis, a modification of encephaloduroarteriosynangiosis,33 34 35 36 and have subsequently been stroke-free during a follow-up interval ranging from 1.3 to 4 years (Table). Pial synangiosis consistently results in luxuriant collateralization to the operated hemisphere (Figure).34
Patient 4 received a course of cranial irradiation, an alternate mechanism for production of moyamoya syndrome. However, the interval of less than 10 months between her radiation exposure and the discovery of her vascular abnormality is much shorter than the usual several years for post–cranial radiation changes.37
The association of trisomy-21 with moyamoya syndrome may provide an opportunity for a better understanding of both MM-DS and idiopathic moyamoya disease. Several proteins encoded on chromosome 21, including superoxide dismutase 1, interferon gamma receptor, and cystathionine ß-synthase,38 affect arterial physiology. Each protein may reduce arterial narrowing39 40 41 and may explain the rare incidence of atheroma in patients with Down syndrome.42 Collagen type VI, found in large-artery intima43 and increased in cerebral arteries by some vascular insults,44 has its 
-chains encoded on chromosome 21.38 A role for collagen in the genesis of moyamoya is suggested by the report of a familial form of moyamoya disease associated with abnormal connective tissue.45 Mito and Becker46 reported an autopsy of a 4-year-old with Down syndrome and stroke in whom the vessels leading to the infarct showed intimal thickening with collagen deposition, a histological feature characteristic of moyamoya disease.47 Underproduction of collagen type III may account for vascular frailty in Ehlers-Danlos syndrome type IV.48 Conversely, excessive vascular thickening may be related to overexpression of collagen type VI in some forms of moyamoya syndrome. Further studies are needed to test this hypothesis.
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Acknowledgments |
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This study was supported by a grant from the National Stroke Association (to S.C.C.).
Received April 15, 1996; revision received July 23, 1996; accepted August 23, 1996.
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References |
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1. Ueki K, Meyer FB, Mellinger JF. Moyamoya disease: the disorder and surgical treatment. Mayo Clin Proc. 1994;69:749-757.[Medline] [Order article via Infotrieve]
2. Yonekawa Y, Goto Y, Ogata N. Moyamoya disease: diagnosis, treatment, and recent achievement. In: Barnett HJM, Mohr JP, Stein BM, Yatsu FM, eds. Stroke: Pathophysiology, Diagnosis, and Management. New York, NY: Churchill Livingstone Inc; 1992:721-748.
3.
Suzuki J, Takaku A. Cerebrovascular `moyamoya' disease: disease showing abnormal net-like vessels in base of brain. Arch Neurol. 1969;20:288-299.
4.
Suzuki J, Kodama N. Moyamoya disease: a review. Stroke. 1983;14:104-109.
5. Fukushima Y, Kondo Y, Kuroki Y, Miyake S, Iwamoto H, Sekido K, Yamaguchi K. Are Down syndrome patients predisposed to moyamoya disease? Eur J Pediatr. 1986;144:516-517.[Medline] [Order article via Infotrieve]
6.
Schrager GO, Cohen SJ, Vigman MP. Acute hemiplegia and cortical blindness due to moya moya disease: report of a case in a child with Down's syndrome. Pediatrics. 1977;60:33-37.
7. Pearson E, Lenn NJ, Cail WS. Moyamoya and other causes of stroke in patients with Down syndrome. Pediatr Neurol. 1985;1:174-179.[Medline] [Order article via Infotrieve]
8. van Erven PMM, Gabreels FJM, Thijssen HOM, Renier WO. The moya-moya syndrome: a report of two children. Clin Neurol Neurosurg. 1982;84:179-189.[Medline] [Order article via Infotrieve]
9. Takanashi J-i, Sugita K, Honda A, Niimi H. Moyamoya syndrome in a patient with Down syndrome presenting with chorea. Pediatr Neurol.. 1993;9:396-398.[Medline] [Order article via Infotrieve]
10. Storm W, Uhlenbrock D. Magnetic resonance imaging of moyamoya disease in a child with Down's syndrome. J Ment Defic Res. 1989;33:507-510.
11. Outwater EK, Platenberg RC, Wolpert SM. Moyamoya disease in Down syndrome. AJNR Am J Neuroradiol. 1989;10:S23-S24.
12. Vicari S, Albertini G. Moyamoya disease in Down's syndrome: a report of two cases. J Ment Defic Res. 1991;35:392-397.
13. Berg JM, Armstrong D. On the association of moyamoya disease with Down's syndrome. J Ment Defic Res. 1991;35:398-403.
14. Goldstein EM, Singer HS. Moyamoya-like disease in Down's syndrome. Pediatr Neurosurg. 1990-91;16:14-16.
15. Aylett SE, Britton JA, DeSousa CMCP. Down syndrome and moyamoya disease: presentation with subarachnoid hemorrhage. Pediatr Neurol. 1996;14:259-261.[Medline] [Order article via Infotrieve]
16. Nishimoto A. Moyamoya disease. Neurol Med Chir. 1979;19:221-228.
17. Kitamura K, Fukui M, Oka K, Matsushima T, Kurokawa T, Hasuo K. Moyamoya disease. In: Toole JF, ed. Handbook of Clinical Neurology. New York, NY: Elsevier Science Publishers BV; 1989;55:293-306.
18. Olds MV, Griebel RW, Hoffman HJ, Craven M, Chuang S, Schutz H. The surgical treatment of childhood moyamoya disease. J Neurosurg. 1987;66:675-680.[Medline] [Order article via Infotrieve]
19. Matsushima T, Inoue T, Natori Y, Fujii K, Fukui M, Hasuo K, Kuwabara Y. Children with unilateral occlusion or stenosis of the ICA associated with surrounding moyamoya vessels: `unilateral' moyamoya disease. Acta Neurochir (Wien). 1994;131:196-202.[Medline] [Order article via Infotrieve]
20.
Bruno A, Adams HP, Biller J, Rezai K, Cornell S, Aschenbrener CA. Cerebral infarction due to moyamoya disease in young adults. Stroke. 1988;19:826-833.
21. Jayakumar PN, Arya BYT, Vasudev MK, Srinivasa Babu CR, Rehman JM. Moyamoya disease: computed tomographic and angiographic correlation in 10 caucasoid patients. Acta Neurol Scand. 1991;84:339-343.[Medline] [Order article via Infotrieve]
22. Takanashi J, Sugita K, Ishii M, Tanabe Y, Ito C, Date H, Niimi H. Moyamoya syndrome in young children: MR comparison with adult onset. AJNR Am J Neuroradiol. 1993;14:1139-1143.[Abstract]
23. Moritake K, Handa H, Yonekawa Y, Taki W, Okuno T. Follow-up study on the relationship between age at onset of illness and outcome in patients with `moyamoya disease.' Neurol Surg. 1986;14:957-963.
24. Kaas JH. The reorganization of sensory and motor maps in adult mammals. In: Gazzaniga MS, ed. The Cognitive Neurosciences. Cambridge, Mass: MIT Press; 1995:51-72.
25. Jones TA, Schallert T. Use-dependent growth of pyramidal neurons after neocortical damage. J Neurosci. 1994;14:2140-2152.[Abstract]
26. Chong MS, Reynolds ML, Irwin N, Coggeshall RE, Emson PC, Benowitz LI, Woolf CJ. GAP-43 expression in primary sensory neurons following central axotomy. J Neurosci. 1994;14:4375-4384.[Abstract]
27.
Stroemer R, Kent T, Hulsebosch C. Neocortical neural sprouting, synaptogenesis, and behavioral recovery after neocortical infarction in rats. Stroke. 1995;26:2135-2144.
28. Becker LE, Mito T, Takashima S, Onodera K, Friend WC. Association of phenotypic abnormalities of Down syndrome with an imbalance of genes on chromosome 21. APMIS. 1993;101(suppl 40):57-70.
29. Becker L, Mito T, Takashima S, Onodera K. Growth and development of the brain in Down syndrome. Prog Clin Biol Res. 1991;373:133-152.[Medline] [Order article via Infotrieve]
30. Takashima S, Iida K, Mito T, Arima M. Dendritic and histochemical development and ageing in patients with Down's syndrome. J Intellect Disabil Res. 1994;38:265-273.
31. Marin-Padilla M. Pyramidal cell abnormalities in the motor cortex of a child with Down's syndrome: a Golgi study. J Comp Neurol. 1976;167:63-82.[Medline] [Order article via Infotrieve]
32. Miyamoto M, Kikuchi H, Karasawa J, Nagata I, Ikota T, Takeuchi S. Study of the posterior circulation in moyamoya disease. J Neurosurg. 1984;61:1032-1037.[Medline] [Order article via Infotrieve]
33. Scott RM. Surgical treatment of moyamoya syndrome in children. Pediatr Neurosurg. 1995;22:39-48.[Medline] [Order article via Infotrieve]
34. Adelson PD, Scott RM. Pial synangiosis for moyamoya syndrome in children. Pediatr Neurosurg. 1995;23:26-33.[Medline] [Order article via Infotrieve]
35.
Rooney CM, Kaye EM, Scott RM, Klucznik RP, Rosman NP. Modified encephaloduroarteriosynangiosis as a surgical treatment of childhood moyamoya disease: report of five cases. J Child Neurol. 1991;6:24-31.
36. Scott RM, Renkens KL. Ischemic strokes in moyamoya syndrome. In: Cheek WR, ed. Pediatric Neurosurgery: Surgery of the Developing Nervous System. Philadelphia, Pa: WB Saunders; 1994: 515-523.
37.
Bitzer M, Topka H. Progressive cerebral occlusive disease after radiation therapy. Stroke. 1995;26:131-136.
38. Korenberg JR. Toward a molecular understanding of Down syndrome. Prog Clin Biol Res. 1993;384:87-115.[Medline] [Order article via Infotrieve]
39. Nordstrom M, Kjellstrom T. Age dependency of cystathionine beta-synthase activity in human fibroblasts in homocyst(e)inemia and atherosclerotic vascular disease. Atherosclerosis. 1992;94:213-221.[Medline] [Order article via Infotrieve]
40.
Hansson GK, Holm J. Interferon-
inhibits arterial stenosis after injury. Circulation. 1991;84:1266-1272.
41. Park JW, Braun P, Mertens S, Heinrich KW. Ischemia: reperfusion injury and restenosis after coronary angioplasty. Ann N Y Acad Sci. 1992;669:215-236.[Medline] [Order article via Infotrieve]
42. Murdoch JC, Rodger JC, Rao SS, Fletcher CD, Dunnigan MG. Down's syndrome: an atheroma-free model? Br Med J. 1977;2:226-228.
43.
Hessle H, Engvall E. Type VI collagen: studies on its localization, structure, and biosynthetic form with monoclonal antibodies. J Biol Chem. 1984;259:3955-3961.
44. Roggendorf W, Opitz H, Schuppan D. Altered expression of collagen type VI in brain vessels of patients with chronic hypertension. Acta Neuropathol (Berl). 1988;77:55-60.[Medline] [Order article via Infotrieve]
45. Richman DP, Watts HG, Parson D, Schmid K, Glimcher MJ. Familial moyamoya associated with biochemical abnormalities of connective tissue. Neurology. 1977;27:382. Abstract.
46. Mito T, Becker LE. Vascular dysplasia in Down syndrome: a possible relationship to moyamoya disease. Brain Dev. 1992;14:248-251.[Medline] [Order article via Infotrieve]
47.
Takebayashi S, Matsuo K, Kaneko M. Ultrastructural studies of cerebral arteries and collateral vessels in moyamoya disease. Stroke. 1984;15:728-732.
48. North KN, Whiteman DAH, Pepin MG, Byers PH. Cerebrovascular complications in Ehlers-Danlos syndrome type IV. Ann Neurol. 1995;38:960-964.[Medline] [Order article via Infotrieve]
49. Fukuyama Y, Osawa M, Kanai N. Moyamoya disease (syndrome) and the Down syndrome. Brain Dev.. 1992;14:254-256.[Medline] [Order article via Infotrieve]
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