| Home | E-Submission | Sitemap | Editorial Office
top_img
Journal of Korean Neurosurgical Society > Volume 57(6); 2015 > Article
Phi, Wang, Lee, and Kim: Moyamoya Syndrome: A Window of Moyamoya Disease

Abstract

Moyamoya-like vasculopathy develops in association with various systemic diseases and conditions, which is termed moyamoya syndrome. Relatively common diseases and conditions are related to moyamoya syndrome, including neurofibromatosis type 1, Down syndrome, thyroid disease, and cranial irradiation. Moyamoya syndrome shares phenotypical characteristics with idiopathic moyamoya disease. However, they differ in other details, including clinical presentations, natural history, and treatment considerations. The study of moyamoya syndrome can provide clinicians and researchers with valuable knowledge and insight. Although it is infrequently encountered in clinical practice, moyamoya-like vasculopathy can severely complicate outcomes for patients with various underlying diseases when the clinician fails to expect or diagnose moyamoya syndrome development. Furthermore, moyamoya syndrome could be used as a doorway to more enigmatic moyamoya disease in research. More comprehensive survey and investigation are required to uncover the secrets of all the moyamoya-like phenomena.

INTRODUCTION

Moyamoya disease is characterized by progressive stenosis and occlusions of distal internal carotid arteries (ICAs) and their major branches. The vascular stenosis/occlusion is accompanied by the growth of small collateral vessels in the bottom of cerebrum, hence the name came 'moyamoya' (which describes a puff of smoke in Japanese)27). The disease usually involves bilateral hemispheres, although in some patients, the arterial stenosis/occlusion occurs in only one side, which is called unilateral (probable) moyamoya disease. The more specific definition of moyamoya disease is 'an idiopathic occlusion of bilateral vessels of the circle of Willis'41). This consensus definition entails the most crucial characteristics of the disease, i.e., the specific location (the circle of Willis), the pathophysiological nature (vascular occlusion), bilateral involvement, and most importantly, the etiology (idiopathic). As stated in the definition, the moyamoya disease etiology is unknown to date. There is an obvious familial tendency, in which there is a 6-12% risk of developing the disease if a person has a first-degree relative with moyamoya disease25,44). There is also an ethnic predilection for Asian populations, especially for people with Korean and Japanese ancestry. The moyamoya disease incidences in East Asia is about 10 times that of Western countries54). Genetic linkage studies revealed putative chromosomal locations linked to moyamoya disease14,1631,53). The recent discovery of a strong disease-associated genetic locus in the ring finger protein (RNF) 213 gene supports the presence of weak areas in human genome that lead to moyamoya susceptibility22,32). Apart from the genetic hypotheses, various environmental factors have been proposed as etiological factors of moyamoya disease. They include infectious agents, immunological responses with cellular components and autoantibodies, and hemodynamic stress to specific vascular loci, just to name a few 36,4247,52). Nonetheless, the causal relationships for this enigmatic disease remain elusive and the entire picture of the genetic/environmental contributions to moyamoya pathogenesis is still awaiting more investigation and elaboration.
Typical angiographic findings of moyamoya disease, the stenosis/occlusion of distal ICA and development of basal collaterals are not specific to the disease. Hence, we will use a provisional term, moyamoya-like vasculopathy to denote the phenomenon. Sometimes, moyamoya-like vasculopathy develops in patients with other well-characterized diseases or syndromes41). In these patients, the condition is called moyamoya syndrome rather than moyamoya disease because the underlying disease/syndrome may be associated with cerebral vasculopathy pathogenesis. There are many types of moyamoya-associated diseases and conditions (Table 1). However, clinicians have noticed that some diseases have more frequent associations with moyamoya-like vasculopathy. These include neurofibromatosis type 1 (NF-1), Down syndrome, Grave's disease, therapeutic irradiation, sickle cell anemia, and others.
Delving into the moyamoya syndrome has two important meanings. First, moyamoya-type vasculopathy, i.e., the location-specific stenosis/occlusion of vessels around the distal internal carotid arteries, is a disease-defining feature; however, it should be considered a phenomenon in itself if devoid of etiological connotations. In other words, (idiopathic) moyamoya disease and moyamoya syndrome share a phenotype of cerebral vasculopathy, at least to some degree. If they have a similar phenotype, then they may have a common pathogenesis in vascular occlusion and collateral vessel development. Many of the moyamoya-associated conditions have well-recognized etiologies and pathogenic mechanisms. Therefore, researching individual moyamoya syndrome can open up a novel avenue in the quest for describing the moyamoya disease etiology and pathogenetic mechanisms. For example, NF-1 is caused by germline haploinsufficiency of the NF1 allele, and its protein is a key component of the RAS-RAF signaling pathways20). NF1-haploin-sufficient mice, which display some hallmarks of human NF-1, have been widely used in research fields17). Because the lack of a pertinent animal model is a major obstacle in moyamoya disease research, moyamoya syndrome with NF-1 may serve as a good substitute.
Second, moyamoya-like vasculopathy, which produces symptoms and stroke in certain occasions, is a serious complication of individual moyamoya-associated diseases and syndromes. Many of the moyamoya-associated conditions are uncommon entities and usually only a small fraction of the patients develop moyamoya syndrome during the course of the underlying illness. Nonetheless, failure to diagnose moyamoya syndrome in these patients in time may lead to severe stroke and neurological deficits, which could be prevented with appropriate treatments. Frequently, the apparent clinical features of an underlying disease make timely diagnoses of moyamoya syndrome difficult. For instance, headache and transient ischemic attack (TIA), the most frequent symptoms of moyamoya syndrome, may be difficult to detect in patients with Down syndrome18).Therefore, clinicians managing these patients should have knowledge of moyamoya syndrome and make a screening plan for selected patient groups.
In this article, several major diseases and syndromes frequently associated with moyamoya syndrome are briefly reviewed, especially with regard to their clinical characteristics and pathogenetic mechanisms.

NF-1

NF-1, also known as von-Recklinghausen disease, is a syndrome caused by a germline loss of one NF1 gene allele. NF-1 is an autosomal dominant disorder with a relatively high incidence in the population, affecting approximately 1 in every 2500 to 3000 children20). NF-1 involves multiple organs, including the brain, peripheral nerves, eyes, skin, and bones. Common cerebral manifestations in NF-1 patients include optic glioma, macrocephaly, focal areas of signal intensity on magnetic resonance images (MRI), and learning and cognitive disabilities. NF-1 occasionally causes systemic vasculopathy such as renal arterial stenosis, and some patients develop cerebral vasculopathy (Fig. 1)12,30). Cerebral vasculopathy encompasses stenosis/occlusion and aneurysmal dilatation. In children, the stenosis/occlusion type predominates over the aneurysmal dilataion type45).
There are 4 large-sized studies that reported the prevalence of cerebral vasculopathy in NF-1 patients (Table 2)5,1239,40). Rosser et al.40) reported the smallest prevalence value (2.5%) and Rea et al.39) suggested the largest prevalence rate (6.4%). The differences may result from the various proportions of patients who were administered brain MRI and, more importantly, brain magnetic resonance angiography (MRA) for screening examinations in each study. Taking these differences in mind, approximately 1 in 20 NF-1 patients (~5%) develops cerebral vasculopathy. Not all stenosis/occlusion type cerebral vasculopathy cases are moyamoya-like in NF-1 patients. Some patients have typical moyamoya-type stenoses; however, others display diffuse narrowing of the petrous or moyamoya-like ICA or stenosis of the distal middle cerebral artery without moyamoya vessels. A small portion of these patients also have aneurysmal dilation in their major vessels5,39). The proportion of moyamoya-like vasculopathy is quite variable in the published studies. Rea et al.39) reported that 13 of their 17 observed patients had cerebral vasculopathy and Ghosh et al.12) found that 7 of their 15 observed patients exhibited moyamoya-like vasculopathy. In a study by Cairns and North5), only 1 of their patients was thought to have moyamoya-like vasculopathy. In these 4 published studies, about half of cerebral vasculopathy patients had moyamoya syndrome (23 patients among 47 cerebral vasculopathy patients)
It is intriguing that the majority of these moyamoya-like vasculopathy cases were unilateral. In the 23 patients with moyamoya-like vasculopathy in these 4 published studies, 19 patients had a unilateral abnormality. It is also noteworthy that only 8 of the 23 patients were symptomatic and 9 patients had clinical or radiological progressions during their follow-ups. The majority of asymptomatic patients in these studies were followed up with or without medication, such as aspirin. Surgery was usually reserved for the symptomatic and/or progressive patients.
The relatively low likelihood of symptomatic progression is contrasted with the high probability of pediatric moyamoya disease, in which about two thirds of patients experience symptomatic progression over time41). Routine MRI screening can help detect cerebral vasculopathy early in NF-1 patients before any related symptoms appear. In this regard, the proportions of bilateral and symptomatic patients were much higher (62% and 76%, respectively) in a surgical series of NF1-associated moyamoya syndrome patients, reflecting biases that were inherent in the observational and surgical patient cohorts26).
Approximately 15% of NF-1 patients have an optic glioma. Cerebral vasculopathy is more frequently observed in patients with an optic glioma12,39). It was postulated that certain types of growth factors secreted from optic gliomas may contributed to vasculopathy development39). Furthermore, NF-1 patients have a threefold increased risk of developing moyamoya syndrome after irradiation for brain tumors, including optic gliomas, compared with non-NF-1 patients receiving the same treatment48).
Neurofibromin, the product of NF1 gene is expressed in vascular endothelial cells and smooth muscle cells. NF1 is a tumor-suppressor gene that inhibits cell cycle progression34). The loss of NF1 can evoke inappropriate proliferation of vascular endothelial cells and smooth muscle cells leading to vascular wall thickening and stenosis. In an in vitro study, NF1 gene knock-down lead to increased proliferation of cultured human umbilical vein endothelial cell (HUVEC) and abnormal vascular morphogenesis1). Downstream targets of NF1, e.g., the RAS-RAF pathway and mTOR signaling cascade proteins, were activated in HUVECs. Furthermore, treatment of rapamycin, a mTOR inhibitor, restored the abnormal vascular network that was induced by NF1 knockdown. In a conditional NF1 knockout mouse model in smooth muscle cells, hyper-proliferative neointimal responses were observed after vascular injury51). Why the NF1-dependent signaling pathways disruption occurs in cerebral vessels and only in a minority of patients needs to be further elucidated.
Routine brain MRI of NF1 patients is controversial. Some advocate brain MRI screening; however, others object to this because of the need for sedation in children, the high cost, and the low likelihood of intervention for frequently observed lesions20). Current guidelines for the NF-1 diagnoses and patient management do not advocate for routine neuroimaging applications for asymptomatic patients50). Considering the relatively low incidence of cerebral vasculopathy, especially for symptomatic cases, routine MRA screening is also not feasible. Careful clinical monitoring should be given to patients for possible TIAs, seizures, and neurological deficits development, and MRA should be reserved for symptomatic patients. Patients with optic gliomas and/or a history of cranial irradiation need special attention because they have higher risks of developing cerebral vasculopathy.
The surgical treatment for symptomatic NF1-associated moyamoya syndrome is similar to that of moyamoya disease. Encephaloduroarteriosynangiosis (EDAS), pial synangiosis, and direct bypass surgery have been applied to these patients5,26). However, there have only been a few large-scale studies dealing with surgical outcomes. A study from Boston Children's Hospital showed that 95% of 32 NF1-patients had a stable or improved neurological status long after pial synangiosis surgery26). Two patients had perioperative cerebral infarctions. However, during the follow-up periods, 5 patients developed new infarctions. Prior cranial irradiation was associated with new-onset infarctions after surgery.

DOWN SYNDROME

Moyamoya syndrome is observed in the Down syndrome population at a higher frequency than expected (Fig. 2). Although the association of these conditions has been recognized for a long time, it is a rare occurrence. There are scarce data regarding the incidence of concurrent moyamoya syndrome in Down syndrome patients. However, in a recently published study analyzing a nationwide admission database in the United States, the estimated Down syndrome prevalence was 3.8% in patients admitted with moyamoya disease21). The majority of patients were white and Hispanic, and 15% of the patients had ischemic strokes. This 3.8% concurrent prevalence may be an overestimate or limited to specific ethnic backgrounds, because Down syndrome is never represented in moyamoya disease populations to such a high degree in East Asian countries (personal communications).
The largest clinical series on Down syndrome with moyamoya syndrome included 16 surgically treated patients. All of these patients were symptomatic with focal neurological deficits and had bilateral involvement. The presenting symptoms were TIAs in 10 patients and infarctions in 6 patients; however, preoperative MRIs demonstrated that 15 patients had evidence of an infarction. Although this study contained only surgically treated patients, moyamoya syndrome associated with Down syndrome appears to be a clinically aggressive disorder. The surgical outcomes in this study were fair. Two patients had perioperative infarction and no patients experienced further infarctions during the follow-up period.
The pathogenetic mechanism of moyamoya syndrome that develops in Down syndrome patients is still obscure. Cardiac anomalies are found in 40-50% of Down syndrome patients, suggesting that the syndrome affects vascular system development in the whole body49). Markedly increased numbers of retinal vessels crossing the optic disc were observed in Down syndrome patients2). A low diabetic retinopathy prevalence, despite longstanding diabetes mellitus, and a markedly low solid cancer incidence were reported in Down syndrome patients11,13). Parsa and Almer37) postulated that the reduced systemic angiogenesis and high endostatin levels observed in Down syndrome patients inhibited proliferative diabetic retinopathy and solid cancer growth, and promoted early branching of retinal vessels. This reduced angiogenesis capacity may be a link between Down syndrome and moyamoya disease.
Down syndrome is also associated with immunological abnormalities and these patients are prone to thyroid diseases and acute lymphocytic leukemia (ALL)38). In the surgical series previously mentioned, 1 patient had Hashimoto's thyroiditis and type 2 diabetes mellitus, and 2 patients had Graves' disease. Another patient in the study had ALL and received cranial irradiation.18) It is well known that moyamoya disease patients occasionally have thyroid dysfunctions35). The coexistence of moyamoya disease, Graves' disease, and type 2 diabetes mellitus was reported in Japanese patients46). Although the precise mechanism is still unknown, there is accumulating evidence that immunological triggering occurs in moyamoya disease. The immune dysregulation in Down syndrome may contribute to moyamoya syndrome development in some of the patients29).

THYROID DISEASE

As stated in the Down syndrome section, thyroid dysfunction has been strongly associated with moyamoya syndrome. Ohba et al.35) reviewed the reports of 31 patients with concurrent Graves' disease and intracranial arterial steno-occlusive disease published in the literature. There was a female predominance (28 women vs. 3 men) and the mean age was 29.3 years (range 10 to 54 years). All of the patients presented with an infarction and/or TIAs and there was no hemorrhagic presentation, which was not consistent with the usual presentation pattern of adult moyamoya disease. All of these patients, except 2 patients, were in a thyrotoxic state when the ischemic event occurred.
High levels of thyroid hormone can induce pathological vascular changes by altering the sensitivity to sympathetic stimuli35). In untreated Graves' disease patients, increased stiffness of the common carotid arteries was observed with untrasonography7). Hyperactivated hemodynamic states in thyrotoxicosis also contributes to cerebral infarction development when the vascular reserve is diminished by longstanding pathological changes15).
Another hypothesis regarding moyamoya syndrome pathogenesis in Graves' disease entails the role of the immune system. Graves' disease is caused by the presence of serum autoantibodies to thyroid-stimulating hormone receptors10). An interesting study reported that moyamoya disease patients had significantly elevated levels of thyroid autoantibodies than non-moyamoya stroke patients and healthy controls, although all of the patients and controls were in a euthyroid state24). Therefore, autoimmune mechanisms may play a role in the pathogenesis, beyond the hemodynamic and sympathetic augmentation by excessive thyroid hormone. Moyamoya disease is also associated with other autoimmune diseases, such as antiphospholipid antibody syndrome, systemic lupus erythematosus, and ulcerative colitis, which further supports the autoimmune hypothesis3,1943).
The optimal treatment of Graves' disease-associated moyamoya syndrome is unclear as of yet. In a review by Ohba et al.35) 16 patients received only medical anti-thyroid therapy and 11 patients received revascularization surgery. The treatment outcome was generally good and there was no apparent difference in the outcomes between the medical and surgical therapies. Appropriate anti-thyroid therapy can restore normal hemodynamic stress to the brain and lower the risks of ischemic attacks and infarction. However, revascularization surgery can reinforce brain perfusion when the vascular reserve is severely reduced by anatomical changes in the vessels. Im et al.15) emphasized that revascularization surgery was warranted when a hampered cerebral vascular reserve was documented with single photon emission computed tomography because the future infarction risk was high in the event of a thyrotoxicosis relapse. To prevent perioperative infarction, keeping the patient in a strict euthyroid state before and after surgery is of paramount importance15).

CRANIAL IRRADIATION

Although radiation induces damage to small-sized vasculature early, the endothelium of medium to large-sized vessels is also affected by the radiation in a delayed fashion33). Concomitant disruption of the microcirculation that supplies large vessels can exacerbate the damage. Intimal fibrosis and foamy cell accumulation ensues with resultant vascular stenosis and occlusion6,9). As a result of these pathophysiological changes in the cerebral vasculature, according to the Childhood Cancer Survivor Study, the relative risk for stroke is 37.2 for brain tumor survivors previously treated with radiation4). The cumulative stroke incidence at 25 years from the initial diagnosis was 6.9%4). Many of the cancer survivors suffering from stroke have a steno-occlusive disease reminiscent of moyamoya disease33). The incidence of this phenomenon is unclear, but a study reported that in 345 pediatric patients who were treated with radiation for various brain tumors, vascular abnormalities developed in 33 patients (9.6%) and 12 (3.5%) of them had vasculopathy compatible with moyamoya syndrome48).
The risk of developing moyamoya syndrome is highest for patients who are irradiated for tumors typically located around the circle of Willis where the moyamoya pathognomonic vascular changes occur, such as optic glioma, craniopharyngioma, and germ cell tumors23). Optic glioma is of particular interest. According to the study mentioned above, in the 12 moyamoya syndrome patients, 10 patients received radiation for an optic glioma48). Many optic gliomas develop on the NF-1 background. NF-1 is an independent risk factor for moyamoya syndrome33). Therefore, there is an additive or even synergistic risk for moyamoya vasculopathy if these factors, which include NF-1, optic glioma, and irradiation, are combined in the same patient. There seems to present a dose-response relationship between radiation and moyamoya syndrome with increasing risks with escalating radiation dosage, especially over 50 Gy48). It is noteworthy that NF-1 patients are vulnerable to lower dose radiation. In a study of 54 patients with radiation-induced moyamoya syndrome, the average radiation dose was 46.5 Gy for NF-1 patients and 58.1 Gy for patients without NF-18). Radiation-induced moyamoya syndrome occurs predominantly in children. Studies suggested that younger age at the time of irradiation increased the risk of moyamoya syndrome8,33). The time interval between irradiation and moyamoya symptoms onset is 2-5 years, but it is highly variable33,48).
The majority of patients with radiation-induced moyamoya syndrome are symptomatic48). Historically, they were mostly treated with revascularization surgery28). However, there is no consensus regarding the optimal management, largely because of the rarity of this condition.

CONCLUSIONS

Exploration of moyamoya syndrome can provide us with a different insight into moyamoya disease pathogenesis. It also confers a clinically valuable guide to manage the tricky diseases associated with moyamoya syndrome. And more importantly, many of the associated conditions were often weirdly interrelated. The interrelationship of NF-1, optic glioma, and irradiation is one example, and the immunological hypothesis binding Down syndrome, Graves' disease, and moyamoya disease together is another. More comprehensive epidemiological, genetic, and clinical studies will reveal the unknown facts and hidden links connecting all moyamoya-like vascular phenomena in the future.

Acknowledgements

This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI12C0066) and a grant [No. 0320140410 (2014-1219)] from the Seoul National University Hospital.

References

1. Bajaj A, Li QF, Zheng Q, Pumiglia K : Loss of NF1 expression in human endothelial cells promotes autonomous proliferation and altered vascular morphogenesis. PLoS One 7 : e49222, 2012
crossref pmid pmc
2. Berk AT, Saatci AO, Erçal MD, Tunç M, Ergin M : Ocular findings in 55 patients with Down's syndrome. Ophthalmic Genet 17 : 15-19, 1996
crossref pmid
3. Booth F, Yanofsky R, Ross IB, Lawrence P, Oen K : Primary antiphospholipid syndrome with moyamoya-like vascular changes. Pediatr Neurosurg 31 : 45-48, 1999
crossref pmid
4. Bowers DC, Liu Y, Leisenring W, McNeil E, Stovall M, Gurney JG, et al : Late-occurring stroke among long-term survivors of childhood leukemia and brain tumors : a report from the Childhood Cancer Survivor Study. J Clin Oncol 24 : 5277-5282, 2006
crossref pmid
5. Cairns AG, North KN : Cerebrovascular dysplasia in neurofibromatosis type 1. J Neurol Neurosurg Psychiatry 79 : 1165-1170, 2008
crossref pmid
6. Chiang CS, Hong JH, Stalder A, Sun JR, Withers HR, McBride WH : Delayed molecular responses to brain irradiation. Int J Radiat Biol 72 : 45-53, 1997
crossref pmid
7. Czarkowski M, Hilgertner L, Powałowski T, Radomski D : The stiffness of the common carotid artery in patients with Graves' disease. Int Angiol 21 : 152-157, 2002
pmid
8. Desai SS, Paulino AC, Mai WY, Teh BS : Radiation-induced moyamoya syndrome. Int J Radiat Oncol Biol Phys 65 : 1222-1227, 2006
crossref pmid
9. Fajardo LF : The pathology of ionizing radiation as defined by morphologic patterns. Acta Oncol 44 : 13-22, 2005
crossref pmid
10. Franklyn JA, Boelaert K : Thyrotoxicosis. Lancet 379 : 1155-1166, 2012
crossref pmid
11. Fulcher T, Griffin M, Crowley S, Firth R, Acheson R, O'Meara N : Diabetic retinopathy in Down's syndrome. Br J Ophthalmol 82 : 407-409, 1998
crossref pmid pmc
12. Ghosh PS, Rothner AD, Emch TM, Friedman NR, Moodley M : Cerebral vasculopathy in children with neurofibromatosis type 1. J Child Neurol 28 : 95-101, 2013
crossref pmid
13. Hasle H, Clemmensen IH, Mikkelsen M : Risks of leukaemia and solid tumours in individuals with Down's syndrome. Lancet 355 : 165-169, 2000
crossref pmid
14. Ikeda H, Sasaki T, Yoshimoto T, Fukui M, Arinami T : Mapping of a familial moyamoya disease gene to chromosome 3p24.2-p26. Am J Hum Genet 64 : 533-537, 1999
crossref pmid pmc
15. Im SH, Oh CW, Kwon OK, Kim JE, Han DH : Moyamoya disease associated with Graves disease : special considerations regarding clinical significance and management. J Neurosurg 102 : 1013-1017, 2005
crossref pmid
16. Inoue TK, Ikezaki K, Sasazuki T, Matsushima T, Fukui M : Linkage analysis of moyamoya disease on chromosome 6. J Child Neurol 15 : 179-182, 2000
crossref pmid
17. Jacks T, Shih TS, Schmitt EM, Bronson RT, Bernards A, Weinberg RA : Tumour predisposition in mice heterozygous for a targeted mutation in Nf1. Nat Genet 7 : 353-361, 1994
crossref pmid
18. Jea A, Smith ER, Robertson R, Scott RM : Moyamoya syndrome associated with Down syndrome : outcome after surgical revascularization. Pediatrics 116 : e694-e701, 2005
crossref pmid
19. Jeong HC, Kim YJ, Yoon W, Joo SP, Lee SS, Park YW : Moyamoya syndrome associated with systemic lupus erythematosus. Lupus 17 : 679-682, 2008
crossref pmid
20. Jett K, Friedman JM : Clinical and genetic aspects of neurofibromatosis 1. Genet Med 12 : 1-11, 2010
crossref pmid
21. Kainth DS, Chaudhry SA, Kainth HS, Suri FK, Qureshi AI : Prevalence and characteristics of concurrent down syndrome in patients with moyamoya disease. Neurosurgery 72 : 210-215, discussion 2152013
crossref pmid
22. Kamada F, Aoki Y, Narisawa A, Abe Y, Komatsuzaki S, Kikuchi A, et al : A genome-wide association study identifies RNF213 as the first Moyamoya disease gene. J Hum Genet 56 : 34-40, 2011
crossref pmid
23. Keene DL, Johnston DL, Grimard L, Michaud J, Vassilyadi M, Ventureyra E : Vascular complications of cranial radiation. Childs Nerv Syst 22 : 547-555, 2006
crossref pmid
24. Kim SJ, Heo KG, Shin HY, Bang OY, Kim GM, Chung CS, et al : Association of thyroid autoantibodies with moyamoya-type cerebrovascular disease : a prospective study. Stroke 41 : 173-176, 2010
crossref pmid
25. Kim SK, Cho BK, Phi JH, Lee JY, Chae JH, Kim KJ, et al : Pediatric moyamoya disease : an analysis of 410 consecutive cases. Ann Neurol 68 : 92-101, 2010
crossref pmid
26. Koss M, Scott RM, Irons MB, Smith ER, Ullrich NJ : Moyamoya syndrome associated with neurofibromatosis Type 1 : perioperative and long-term outcome after surgical revascularization. J Neurosurg Pediatr 11 : 417-425, 2013
crossref pmid
27. Kuroda S, Houkin K : Moyamoya disease : current concepts and future perspectives. Lancet Neurol 7 : 1056-1066, 2008
crossref pmid
28. Lee HS, Seol HJ, Kong DS, Shin HJ : Moyamoya syndrome precipitated by cranial irradiation for craniopharyngioma in children. J Korean Neurosurg Soc 50 : 535-537, 2011
crossref pmid pmc
29. Leno C, Mateo I, Cid C, Berciano J, Sedano C : Autoimmunity in Down's syndrome : another possible mechanism of Moyamoya disease. Stroke 29 : 868-869, 1998
crossref pmid
30. Malav IC, Kothari SS : Renal artery stenosis due to neurofibromatosis. Ann Pediatr Cardiol 2 : 167-169, 2009
crossref pmid pmc
31. Mineharu Y, Liu W, Inoue K, Matsuura N, Inoue S, Takenaka K, et al : Autosomal dominant moyamoya disease maps to chromosome 17q25.3. Neurology 70(24 Pt 2):2357-2363, 2008
crossref pmid
32. Miyatake S, Miyake N, Touho H, Nishimura-Tadaki A, Kondo Y, Okada I, et al : Homozygous c.14576G>A variant of RNF213 predicts early-onset and severe form of moyamoya disease. Neurology 78 : 803-810, 2012
crossref pmid
33. Morris B, Partap S, Yeom K, Gibbs IC, Fisher PG, King AA : Cerebrovascular disease in childhood cancer survivors : a Children's Oncology Group Report. Neurology 73 : 1906-1913, 2009
crossref pmid pmc
34. Norton KK, Xu J, Gutmann DH : Expression of the neurofibromatosis I gene product, neurofibromin, in blood vessel endothelial cells and smooth muscle. Neurobiol Dis 2 : 13-21, 1995
crossref pmid
35. Ohba S, Nakagawa T, Murakami H : Concurrent Graves' disease and intracranial arterial stenosis/occlusion : special considerations regarding the state of thyroid function, etiology, and treatment. Neurosurg Rev 34 : 297-304, discussion 3042011
crossref pmid
36. Panegyres PK, Morris JG, O'Neill PJ, Balleine R : Moyamoya-like disease with inflammation. Eur Neurol 33 : 260-263, 1993
crossref pmid
37. Parsa CF, Almer Z : Supranumerary optic disc vessels may indicate reduced systemic angiogenesis in Down syndrome. Br J Ophthalmol 92 : 432-433, 2008
crossref pmid
38. Ram G, Chinen J : Infections and immunodeficiency in Down syndrome. Clin Exp Immunol 164 : 9-16, 2011
crossref pmid pmc
39. Rea D, Brandsema JF, Armstrong D, Parkin PC, deVeber G, MacGregor D, et al : Cerebral arteriopathy in children with neurofibromatosis type 1. Pediatrics 124 : e476-e483, 2009
crossref pmid
40. Rosser TL, Vezina G, Packer RJ : Cerebrovascular abnormalities in a population of children with neurofibromatosis type 1. Neurology 64 : 553-555, 2005
crossref pmid
41. Scott RM, Smith ER : Moyamoya disease and moyamoya syndrome. N Engl J Med 360 : 1226-1237, 2009
crossref pmid
42. Seol HJ, Shin DC, Kim YS, Shim EB, Kim SK, Cho BK, et al : Computational analysis of hemodynamics using a two-dimensional model in moyamoya disease. J Neurosurg Pediatr 5 : 297-301, 2010
crossref pmid
43. Shanahan P, Hutchinson M, Bohan A, O'Donoghue D, Sheahan K, Owens A : Hemichorea, moya-moya, and ulcerative colitis. Mov Disord 16 : 570-572, 2001
crossref pmid
44. Smith ER, Scott RM : Moyamoya : epidemiology, presentation, and diagnosis. Neurosurg Clin N Am 21 : 543-551, 2010
crossref pmid
45. Sobata E, Ohkuma H, Suzuki S : Cerebrovascular disorders associated with von Recklinghausen's neurofibromatosis : a case report. Neurosurgery 22 : 544-549, 1988
crossref pmid
46. Suzuki S, Mitsuyama T, Horiba A, Fukushima S, Hashimoto N, Kawamata T : Moyamoya disease complicated by Graves' disease and type 2 diabetes mellitus : report of two cases. Clin Neurol Neurosurg 113 : 325-329, 2011
crossref pmid
47. Tanigawara T, Yamada H, Sakai N, Andoh T, Deguchi K, Iwamura M : Studies on cytomegalovirus and Epstein-Barr virus infection in moyamoya disease. Clin Neurol Neurosurg 99(Suppl 2):S225-S228, 1997
crossref pmid
48. Ullrich NJ, Robertson R, Kinnamon DD, Scott RM, Kieran MW, Turner CD, et al : Moyamoya following cranial irradiation for primary brain tumors in children. Neurology 68 : 932-938, 2007
crossref pmid
49. Vis JC, Duffels MG, Winter MM, Weijerman ME, Cobben JM, Huisman SA, et al : Down syndrome : a cardiovascular perspective. J Intellect Disabil Res 53 : 419-425, 2009
crossref pmid
50. Williams VC, Lucas J, Babcock MA, Gutmann DH, Korf B, Maria BL : Neurofibromatosis type 1 revisited. Pediatrics 123 : 124-133, 2009
crossref pmid
51. Xu J, Ismat FA, Wang T, Yang J, Epstein JA : NF1 regulates a Ras-dependent vascular smooth muscle proliferative injury response. Circulation 116 : 2148-2156, 2007
crossref pmid
52. Yamada H, Deguchi K, Tanigawara T, Takenaka K, Nishimura Y, Shinoda J, et al : The relationship between moyamoya disease and bacterial infection. Clin Neurol Neurosurg 99(Suppl 2):S221-S224, 1997
crossref pmid
53. Yamauchi T, Tada M, Houkin K, Tanaka T, Nakamura Y, Kuroda S, et al : Linkage of familial moyamoya disease (spontaneous occlusion of the circle of Willis) to chromosome 17q25. Stroke 31 : 930-935, 2000
crossref pmid
54. Yonekawa Y, Ogata N, Kaku Y, Taub E, Imhof HG : Moyamoya disease in Europe, past and present status. Clin Neurol Neurosurg 99(Suppl 2):S58-S60, 1997
crossref pmid
Fig. 1

Images of a boy with neurofibromatosis type 1. A : Magnetic resonance image (MRI) taken at age 7 revealed a thickened optic chiasm with gadolinium enhancement, suggesting the presence of an optic glioma. The boy experienced symptomatic progression of the optic glioma and received cranial irradiation (50.4 Gy) for treatment at age 9. B : Magnetic resonance angiography (MRA) was taken 4 years after the radiation therapy. Note the luminal narrowing of bilateral middle cerebral arteries (right side more severe) and the invisible horizontal portion of the right anterior cerebral artery. C : A markedly decreased vascular reserve in the right hemisphere was shown after infusion of diamox in single photon emission computed tomography. D : A delayed time-to-peak in the right hemisphere was also observed in a perfusion MRI. At that time, the patient was asymptomatic and no treatment was recommended. One year later, the patient began to complain of morning headaches, with increasing intensity over time. Encephaloduroarteriosynangiosis was performed on the right side. After surgery, the patient was free of headaches.

jkns-57-408-g001
Fig. 2

A 9-year-old girl with Down syndrome had recurrent vomiting for 2 years. Examination of gastrointestinal system revealed no causes of the vomiting. A : A brain magnetic resonance image (MRI) was taken and an old small infarction was found in the left anterior watershed zone. The left middle cerebral artery trunk was invisible (not shown). B : A delayed time-to-peak in the left middle cerebral artery territory was observed in perfusion MRI. C and D : A subsequent angiography revealed a normal-looking right internal carotid artery and a near occlusion of left distal internal carotid artery with minute collateral vessel formation. Moyamoya syndrome was diagnosed. Although it was unclear that her vomiting was related to the cerebral vasculopathy, a pre-existing infarction warranted a surgical intervention. Encephaloduroarteriosynangiosis was performed on the left side. After surgery, her vomiting frequency decreased significantly. This patient illustrates the difficulty in evaluating neurological symptoms in Down syndrome patients.

jkns-57-408-g002
Table 1

Moyamoya syndrome-associated diseases and conditions

jkns-57-408-i001
Table 2

Summary of the large-scale studies on the prevalence of moyamoya syndrome in NF-1 patients

jkns-57-408-i002

*Denotes the number of patients with each characteristic among the patients with moyamoya-like vasculopathy

Editorial Office
#402, 27 Chilparo, Jung-gu, Seoul 04511, Korea
TEL: +82-02-525-7552   FAX: +82-02-525-7554   E-mail: kns61@neurosurgery.or.kr
About |  Browse Articles |  Current Issue |  For Authors and Reviewers
Copyright © Korean Neurosurgical Society. All rights reserved.                 developed in m2community
Close layer
prev next