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(Stroke. 2005;36:2148.)
© 2005 American Heart Association, Inc.

Original Contributions

Incidence and Clinical Features of Disease Progression in Adult Moyamoya Disease

Satoshi Kuroda, MD, PhD; Tatsuya Ishikawa, MD, PhD; Kiyohiro Houkin, MD, PhD; Rina Nanba, MD, PhD; Masaaki Hokari, MD, PhD Yoshinobu Iwasaki, MD, PhD

From the Department of Neurosurgery (S.K., T.I., R.N., M.H., Y.I.), Hokkaido University Graduate School of Medicine; and the Department of Neurosurgery (K.H.), Sapporo Medical University, Sapporo, Japan

Correspondence to Satoshi Kuroda, Department of Neurosurgery, Hokkaido University Graduate School of Medicine, North 15 West 7, Kita-ku, Sapporo 060-8638, Japan. E-mail skuroda{at}med.hokudai.ac.jp

	Abstract

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Background and Purpose— The progression of occlusive lesions in the major intracranial arteries was believed to be very rare in adult patients with moyamoya disease. The present study aims to clarify the incidence and clinical features of disease progression in adult moyamoya disease.

Methods— For the past 15 years, 120 adult Japanese patients were diagnosed with moyamoya disease. Of these, 63 patients were enrolled in this historical prospective cohort study on a total of 86 nonoperated hemispheres. All were followed up with a mean period of 73.6 months. MRI and magnetic resonance angiography were repeated every 6 to 12 months, and cerebral angiography was performed when disease progression was suspected on MRI and magnetic resonance angiography.

Results— Disease progression occurred in 15 of 86 nonoperated hemispheres (17.4% per hemisphere) or in 15 of 63 patients (23.8% per patient) during the follow-up period. Occlusive arterial lesions progressed in both anterior and posterior circulations, in both symptomatic and asymptomatic patients, and in both bilateral and unilateral types. Eight of 15 patients developed ischemic or hemorrhagic events in relation to disease progression. Multivariate analysis revealed that the odds ratio conferred by a male patient was 0.20 (95% CI, 0.04 to 0.97).

Conclusions— The incidence of disease progression in adult moyamoya disease is much higher than recognized before, and female patients may be at higher risk for it than male patients. Careful follow-up would be essential to prevent additional stroke occurrence in medically treated adult patients with moyamoya disease, even if they are asymptomatic or are diagnosed as having unilateral moyamoya disease.

Key Words: adult • cerebral ischemia • disease progression • moyamoya disease

	Introduction

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Moyamoya disease is characterized by progressive occlusion of the bilateral carotid forks associated with a fine vascular network at the base of brain, the "moyamoya" vessels.¹ The posterior cerebral artery is also involved in 30% of patients with moyamoya disease.² Both children and adults develop moyamoya disease, but their clinical features often differ. Thus, although most pediatric patients develop transient ischemic attack (TIA) or cerebral infarction, about half of adult patients experience intracranial bleeding. In addition, the occlusive lesions in the carotid forks frequently progress in pediatric patients, although it is believed quite rare in adult patients.^3,4 Only 8 cases have previously been reported to demonstrate the progression of occlusive lesions in adult patients with moyamoya disease.^3,5–11 However, there is no report that precisely denoted the incidence and features of stage progression in a large population of adult patients with moyamoya disease.

On the other hand, the recent development of a noninvasive diagnostic technique, magnetic resonance angiography (MRA), has clarified that the prevalence of asymptomatic adult patients with moyamoya disease is much higher than considered before.¹² However, the guideline for the management of asymptomatic adult moyamoya disease has not been established, even in Japan.^12–14 The natural course of adult moyamoya disease should also be elucidated in order to determine appropriate therapeutic strategies for asymptomatic patients. Therefore, in this study, we aimed to clarify the incidence and clinical features of disease progression in adult moyamoya disease.

	Materials and Methods

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Patients and Follow-Up
This study included 120 adult patients who were diagnosed with moyamoya disease at Hokkaido University Hospital and its affiliate hospitals in Sapporo between 1990 and 2004. All of them were >20 years of age at onset and were diagnosed with moyamoya disease based on the guidelines for the diagnosis of moyamoya disease set by the Research Committee on Moyamoya Disease (Spontaneous Occlusion of the Circle of Willis) of the Ministry of Health and Welfare of Japan. Of these 120 patients, 6 (5%) were deceased because of severe intracranial bleeding within 1 month after the onset. Using ¹³³xenon or ¹²³I-IMP single photon emission computed tomography, cerebral blood flow and its reactivity to acetazolamide were quantitatively measured in all of the patients at least 4 weeks after the onset.^15–18 The involved hemisphere was considered as the candidate for surgical revascularization when it had impaired reactivity to acetazolamide.^15–18 As a result, surgical revascularization was performed on 142 sides of 91 patients. Fifty-one patients underwent surgical revascularization on both sides. On the other hand, 40 patients underwent it on 1 side. Surgical procedures included superficial temporal artery to middle cerebral artery anastomosis combined with encephalo-myo-synangiosis or encephalo-duro-arterio-myo-synangiosis in all of these patients.¹⁹ The other 23 patients were medically treated according to the above-mentioned criteria or patients’ request. Therefore, we enrolled 63 patients in this study, for a total of 86 nonoperated sides, and evaluated their natural course (Figure 1). There were 23 male and 40 female patients. Of these, 52 patients were diagnosed with typical "bilateral" moyamoya disease (definite cases). The other 11 patients were diagnosed with "unilateral" moyamoya disease (probable cases). Their mean age at onset was 46.7±10.8 years. Their clinical type included ischemic type in 28 patients, bleeding type in 24, and asymptomatic in 11.

View larger version (16K): [in this window] [in a new window]   Figure 1. Diagram of adult patients with moyamoya disease included in this study.

All 63 patients included in the present study were followed up in the outpatient clinic at Hokkaido University Hospital or its affiliate hospitals. The mean follow-up period was 73.6±49.0 months, ranging from 7 to 181 months. Both MRI and MRA were performed every 6 or 12 months, using a 1.5-T whole-body magnetic resonance imager. When the progression of the occlusive lesion in the major intracranial arteries was suspected, digital subtraction angiography was performed to verify it. Occlusive lesions in the carotid forks were graded according to Suzuki’s angiographical staging.¹

Statistical Analysis
To clarify the predictors of disease progression in adult moyamoya disease, primary comparisons were performed between the patients with and without disease progression. Categorical variables were compared by using a ² test. Continuous variables were expressed as percentage or as mean±SD, and were compared by using the unpaired Student t test. Differences were considered to be statistically significant if the P value was <0.05. Subsequently, a multivariate logistic regression model was conducted to test the effect of gender, onset age, disease type, symptoms at onset, and previous surgery on disease progression. The statistical level of significance was also set at P<0.05. Statistical analysis was completed with StatView version 5.0 (SAS Institute Inc.).²⁰

	Results

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Characteristics of Stage Progression
During follow-up periods, the occlusive lesions in the major intracranial arteries progressed in 15 of 86 sides (17.4% per hemisphere) or in 15 of 63 patients (23.8% per patient). Disease progression was verified in 2 men and 13 women, and their age at onset was 46.9±8.2 years (range, 32 to 60 years). Their symptoms at onset included TIA or cerebral infarction in 9 patients and intracranial bleeding in 4. The remaining 2 patients were asymptomatic when they were diagnosed with moyamoya disease.

Disease progression occurred in 4 of 11 patients (36.4%) with unilateral moyamoya disease and in 11 of 52 patients (21.2%) with bilateral moyamoya disease. Thus, the carotid fork of the contralateral side was involved in 4 patients with unilateral moyamoya disease, which meant progression from unilateral to bilateral type. The interval between their onset and disease progression varied from 1.5 to 8 years (60.0±36.3 months). All of the patients were women. In relation to the progression from unilateral to bilateral type, TIA or intracranial bleeding occurred in 3 patients, and a single photon emission tomography study revealed the deterioration of cerebral hemodynamics in another (case 3). All of them underwent additional bypass surgery (Table 1). On the other hands, 8 of 52 patients with bilateral moyamoya disease showed the progression of the occlusive lesion in the carotid fork. The other 3 patients with bilateral moyamoya disease developed an additional occlusive lesion in the posterior cerebral artery (PCA) during follow-up periods (Table 2). The interval between their onset and disease progression was 28.4±26.3 months, ranging from 1 month to 8 years, and was significantly shorter in patients with bilateral moyamoya disease than in those with unilateral moyamoya disease (P=0.0123). In relation to the disease progression, TIA or cerebral infarction occurred in 5 patients, and cerebral hemodynamics worsened in another 2 (cases 5 and 14). Subsequently, 8 patients underwent bypass surgery.

View this table: [in this window] [in a new window]   TABLE 1. Clinical Features of 4 Adult Patients Who Showed the Progression From Unilateral to Bilateral Moyamoya Disease

View this table: [in this window] [in a new window]   TABLE 2. Clinical Features of 11 Adult Patients With Bilateral Moyamoya Disease Showing the Progression of Occlusive Lesion in the Major Intracranial Arteries

Independent Predictor of Disease Progression
The effects of various clinical factors on disease progression are shown in Table 3. The patients with and without disease progression were categorized into the progression group (n=15) and stable group (n=48), respectively. As the results of univariate analysis, there was no significant difference in onset age, disease type, symptoms at onset, and previous bypass surgery between the 2 groups. However, disease progression was noted in 13 of 40 female patients (32.5%), but in 2 of 23 male patients (8.7%), revealing that the incidence of disease progression was significantly higher in female patients than in male patients (² test, P=0.0327).

View this table: [in this window] [in a new window]   TABLE 3. Clinical Features of the Patients With Stage Progression of Adult Moyamoya Disease (Progression Group) and Without (Stable Group)

As the next step, multivariate logistic regression analysis showed that patients’ gender was an independent predictor of disease progression during follow-up periods (P=0.0463). The odds ratio conferred by a male patient was 0.20 (95% CI, 0.04 to 0.97) for disease progression (Table 3).

Illustrative Cases
Case 14
A 50-year-old female experienced minor head injury because of a traffic accident in March 2001. Because brain MRI and MRA studies strongly suggested the presence of moyamoya disease, cerebral angiography was performed. Right carotid angiography showed the stenosis of the right anterior cerebral artery (Figure 2a). The left cerebral angiography revealed marked stenosis of the left internal carotid artery and middle cerebral artery associated with mild dilatation of the lenticulostriate arteries (Figure 2b). Although she was still asymptomatic, follow-up cerebral angiography in March 2004 showed progression of an occlusive lesion on the left side (Figure 2c). Single photon emission tomography studies also revealed the reduction of cerebral blood flow and its reactivity to acetazolamide. She underwent superficial temporal artery to middle cerebral artery anastomosis and encephalo-duro-arterio-myo-synangiosis. Postoperative course was uneventful.

View larger version (71K): [in this window] [in a new window]   Figure 2. Right (a) and left internal carotid angiograms (b and c) of a 50-year-old woman (case 14), showing progression of an occlusive lesion in the left carotid fork during 3-year follow up (b and c).

Case 15
A 56-year-old female was admitted to our hospital because of a severe headache and consciousness disturbance in March 1996. Plain computed tomography scans revealed intracerebral hematoma in the right putamen (Figure 3a). Cerebral angiography on admission showed the marked stenosis of the bilateral carotid forks. The posterior cerebral arteries were intact. She was diagnosed with moyamoya disease. She completely recovered and was medically followed up because she and her family did not want surgical revascularization. The brain MRI and MRA were annually repeated at an outpatient clinic. Although the posterior cerebral arteries were intact in March 2004 (Figure 3b), a marked stenosis developed in the right posterior cerebral artery in March 2005 (Figure 3c).

View larger version (42K): [in this window] [in a new window]   Figure 3. Plain computed tomography (a) and MRA (b and c) of a 56-year-old woman (case 15), showing the development of an occlusive lesion in the right posterior cerebral artery between March 2004 (b) and March 2005 (c).

	Discussion

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This study is the first to focus on clinical manifestations of the progression in the major intracranial arteries in a large population of patients with adult moyamoya disease. The results clearly showed that the incidence of disease progression was 20% in adult patients with moyamoya disease, which is higher than what was considered before. Disease progression occurred in both unilateral and bilateral moyamoya disease, in both anterior and posterior circulation, and in both symptomatic and asymptomatic patients. An ischemic or hemorrhagic episode was noted in more than half of patients when the occlusive lesions progressed. Multivariate analysis revealed that female patients had a higher risk of disease progression than male patients.

As described above, the disease progression in adult moyamoya disease has previously been recognized as very rare, and 8 patients have been reported to exhibit it as case reports.^3,5–11 In addition, Kawano et al²¹ reported 4 adult patients who showed progression from unilateral to bilateral type in their series of 64 cases with unilateral moyamoya disease, although their clinical data were limited. Clinical information of these 12 patients is summarized in Table 4. Thus, the occlusive lesions in the carotid fork advanced in both sides or in the nonoperated side in 4 adult patients with bilateral moyamoya disease.^3,6–8 In addition, unilateral moyamoya disease has been reported to progress to bilateral type in 8 adult patients.^{5, 9–11, 21} As shown in this study, disease progression occurred within 1 year after the onset in 2 of 4 patients with bilateral moyamoya disease, whereas it occurred 1 to 6 years after the onset in patients with unilateral moyamoya disease. When analyzing 8 patients with sufficient clinical information (case 1 to 5 and 10 to 12), 3 developed ischemic or hemorrhagic episode because of disease progression. Gender difference was not observed in these 8 cases, which is different from the present result. It may result from the difference of patients’ background among the studies. However, Kawano et al²¹ reported female predominance in patients with unilateral moyamoya disease showing progression to a bilateral type, correlating well with the present result.

View this table: [in this window] [in a new window]   TABLE 4. Summary of Clinical Features in 12 Reported Case With Moyamoya Disease Showing Progression of Occlusive Arterial Lesions

Unilateral moyamoya disease accounts for 20% of all of the moyamoya disease in Japan.²² According to previous surveys, unilateral moyamoya disease has been recognized as stable in adults.^21,23,24 However, this study revealed that about one-third of patients progressed to the typical bilateral type. The discrepancy may result from the difference in follow-up periods. Thus, mean follow-up periods were within 3 years in previous studies.^21,23,24 On the other hand, the patients included in this study were followed up for a mean period of 6 years. Because the interval between initial diagnosis and disease progression is significantly longer in unilateral moyamoya disease than in the bilateral type, long-term follow-up would be essential to discuss the prognosis of unilateral moyamoya disease. Indeed, disease progression was confirmed 7 to 8 years after the initial diagnosis in 2 patients (cases 1 and 3, Table 1).

In this study, 3 patients developed additional occlusive lesions in the PCA during follow-up periods. To our best knowledge, there is no report describing the phenomenon in adult moyamoya disease. The development of additional PCA lesions implies the increased risk for recurrent ischemic stroke, because the PCA is playing an important role as a major collateral circulation in moyamoya disease as pointed out before.^2,25,26 In this study, cerebral infarction occurred in 1 patient, and cerebral hemodynamics deteriorated in another 2. Therefore, the importance of carefully observing the whole intracranial arteries should be remembered during follow-up.

Noninvasive examinations using MRI and MRA have revealed that the incidence of asymptomatic moyamoya disease is much higher than believed before.¹² However, the prognosis of asymptomatic patients is still unclear, and the standardized strategy for them has not been established.^12–14 This study revealed that the occlusive arterial lesions advanced in 2 of 11 asymptomatic patients (18.2%) during 3 years, leading to cerebral infarction (case 8) or disturbed cerebral hemodynamics (case 14). The findings should be taken into consideration when establishing the management guideline for asymptomatic patients with moyamoya disease, although additional survey would be necessary on the basis of a larger population of asymptomatic patients. Furthermore, MRI and MRA studies at outpatient clinics could accurately detect disease progression before recurrent onsets including TIA, cerebral infarction, and intracranial bleeding in 7 of 15 patients, suggesting the importance of continuous imaging studies.

Based on multivariate analysis in this study, female gender may be a significant predictor of disease progression in adult moyamoya disease. None of the other factors were related to disease progression. Previous epidemiological surveys have shown that a male-to-female ratio of moyamoya disease is 1:1.8,²⁷ suggesting the female predominance in moyamoya disease. Furthermore, female predominance is more pronounced in familial moyamoya disease. Thus, Kanai et al²⁸ reported that a male-to-female ratio in familial moyamoya disease was 1:3.3. A recent study²⁹ also showed that male-to-female ratios were 1:5 and 1:1.6 in familial and sporadic cases, respectively, indicating enhanced female predominance in familial moyamoya disease. The results strongly suggest that female gender may be highly susceptible to the unknown factors causing moyamoya disease and may promote disease progression more easily.

Recently, the prospective, randomized clinical trial has been accepted to provide the highest level of evidence. The present study has some problems for evidence-based medicine. Thus, this study has bias in the patient selection. The patients who underwent bypass surgery on both sides were excluded, because it is well known that occlusive lesions in the carotid fork rapidly progress and often result in complete occlusion when surgical collaterals start to supply enough blood flow after surgery.^30–32 As a result, this study included the patients who underwent bypass surgery on one side and those who were medically treated and observed their natural course. Therefore, we cannot exclude the possibility that the present results are diluted because less severe patients were included in this study.

In conclusion, the process of occlusive arterial change in adult moyamoya disease is still active. Disease progression can occur in both anterior and posterior circulations, in both symptomatic and asymptomatic patients, and in both unilateral and bilateral types. Careful and long-term neurological and radiological follow-up would be essential in adult patients with moyamoya disease to prevent additional stroke events and to improve their outcome.

	Acknowledgments

 
This study was partly supported by a grant from the Research Committee on Moyamoya Disease, sponsored by the Ministry of Health, Labor and Welfare of Japan.

Received May 9, 2005; accepted June 2, 2005.

	References

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1. Suzuki J, Takaku A. Cerebrovascular "moyamoya" disease. Disease showing abnormal net-like vessels in base of brain. Arch Neurol. 1969; 20: 288–299.[Medline] [Order article via Infotrieve]
2. Kuroda S, Ishikawa T, Houkin K, Iwasaki Y. Clinical significance of posterior cerebral artery stenosis/occlusion in moyamoya disease. No Shinkei Geka. 2002; 30: 1295–1300.[Medline] [Order article via Infotrieve]
3. Shirane R, Mikawa S, Ebina T. A case of adult moyamoya disease showing progressive angiopathy on cerebral angiography. Clin Neurol Neurosurg. 1999; 101: 210–214.[Medline] [Order article via Infotrieve]
4. Ezura M, Yoshimoto T, Fujiwara S, Takahashi A, Shirane R, Mizoi K. Clinical and angiographic follow-up of childhood-onset moyamoya disease. Childs Nerv Syst. 1995; 11: 591–594.[CrossRef][Medline] [Order article via Infotrieve]
5. Fujiwara F, Yamada H, Hayashi S, Tamaki N. A case of adult moyamoya disease showing fulminant clinical course associated with progression from unilateral to bilateral involvement. No Shinkei Geka. 1997; 25: 79–84.[Medline] [Order article via Infotrieve]
6. Takeshita I, Tsukamoto H, Yamaguchi T, Tsukamoto Y, Yokota A. A progressive occlusion of the internal carotid arteries in a case of adult-onset moyamoya disease. Fukuoka Igaku Zasshi. 1995; 86: 367–372.[Medline] [Order article via Infotrieve]
7. Tomida M, Muraki M, Yamasaki K. Angiographically verified progression of moyamoya disease in an adult. Case report. J Neurosurg. 2000; 93: 1055–1057.[Medline] [Order article via Infotrieve]
8. Oka Y, Kusunoki K, Nochide I, Igase K, Sadamoto K, Kohno K, Kumon Y, Sakaki S. A case of adult moyamoya disease progressed after vascular reconstructive surgery. No Shinkei Geka. 2000; 28: 373–378.[Medline] [Order article via Infotrieve]
9. Kagawa R, Okada Y, Moritake K, Takamura M. Magnetic resonance angiography demonstrating adult moyamoya disease progressing from unilateral to bilateral involvement-case report. Neurol Med Chir (Tokyo). 2004; 44: 183–186.[CrossRef][Medline] [Order article via Infotrieve]
10. Wanifuchi H, Takeshita M, Aoki N, Kawamata T, Shiokawa K, Izawa M, Kagawa M, Takakura K. Adult moyamoya disease progressing from unilateral to bilateral involvement. Neurol Med Chir (Tokyo). 1996; 36: 87–90.[Medline] [Order article via Infotrieve]
11. Aoki N, Kagawa M, Wanifuchi H, Takeshita M, Izawa M, Kitamura K. An adult case of moyamoya disease associated with marked advance of occlusive lesion in the bilateral carotid system. No Shinkei Geka. 1989; 17: 399–403.[Medline] [Order article via Infotrieve]
12. Nanba R, Kuroda S, Takeda M, Shichinohe H, Nakayama N, Ishikawa T, Houkin K, Iwasaki Y. Clinical features and outcomes of 10 asymptomatic adult patients with moyamoya disease. No Shinkei Geka. 2003; 31: 1291–1295.[Medline] [Order article via Infotrieve]
13. Akasaki T, Kagiyama S, Omae T, Ohya Y, Ibayashi S, Abe I, Fujishima M. Asymptomatic moyamoya disease associated with coronary and renal artery stenoses-a case report. Jpn Circ J. 1998; 62: 136–138.[CrossRef][Medline] [Order article via Infotrieve]
14. Aoki T, Saiki M, Ishizaki R, Sato T. A case report of the adult patient with asymptomatic moyamoya disease. Pract Curren Neurosurg. 2004; 14: 597–602.
15. Kuroda S, Houkin K, Kamiyama H, Abe H, Mitsumori K. Regional cerebral hemodynamics in childhood moyamoya disease. Childs Nerv Syst. 1995; 11: 584–590.[CrossRef][Medline] [Order article via Infotrieve]
16. Kuroda S, Houkin K, Kamiyama H, Mitsumori K, Iwasaki Y, Abe H. Long-term prognosis of medically treated patients with internal carotid or middle cerebral artery occlusion:can acetazolamide test predict it? Stroke. 2001; 32: 2110–2116.[Abstract/Free Full Text]
17. Kuroda S, Kamiyama H, Abe H, Houkin K, Isobe M, Mitsumori K Acetazolamide test in detecting reduced cerebral perfusion reserve and predicting long-term prognosis in patients with internal carotid artery occlusion. Neurosurgery. 1993; 32: 912–919.[Medline] [Order article via Infotrieve]
18. Kuroda S, Shiga T, Ishikawa T, Houkin K, Narita T, Katoh C, Tamaki N, Iwasaki Y. Reduced blood flow and preserved vasoreactivity characterize oxygen hypometabolism due to incomplete infarction in occlusive carotid artery diseases. J Nucl Med. 2004; 45: 943–949.[Abstract/Free Full Text]
19. Houkin K, Kamiyama H, Takahashi A, Kuroda S, Abe H. Combined revascularization surgery for childhood moyamoya disease: Sta-MCA and encephalo-duro-arterio-myo-synangiosis. Childs Nerv Syst. 1997; 13: 24–29.[Medline] [Order article via Infotrieve]
20. Kuroda S, Houkin K, Ishikawa T, Nakayama N, Ikeda J, Ishii N, Kamiyama H, Iwasaki Y. Determinants of intellectual outcome after surgical revascularization in pediatric moyamoya disease: a multivariate analysis. Childs Nerv Syst. 2004; 20: 302–308.[CrossRef][Medline] [Order article via Infotrieve]
21. Kawano T, Fukui M, Hashimoto N, Yonekawa Y. Follow-up study of patients with "unilateral" moyamoya disease. Neurol Med Chir (Tokyo). 1994; 34: 744–747.[Medline] [Order article via Infotrieve]
22. Ikezaki K, Inamura T, Kawano T, Fukui M Clinical features of probable moyamoya disease in Japan. Clin Neurol Neurosurg. 1997; 99 (Suppl 2): S173–S177.[Medline] [Order article via Infotrieve]
23. Houkin K, Abe H, Yoshimoto T, Takahashi A. Is "unilateral" moyamoya disease different from moyamoya disease? J Neurosurg. 1996; 85: 772–776.[CrossRef][Medline] [Order article via Infotrieve]
24. Hirotsune N, Meguro T, Kawada S, Nakashima H, Ohmoto T. Long-term follow-up study of patients with unilateral moyamoya disease. Clin Neurol Neurosurg. 1997; 99 (Suppl 2): S178–S181.[Medline] [Order article via Infotrieve]
25. Miyamoto S, Kikuchi H, Karasawa J, Nagata I, Ihara I, Yamagata S. Study of the posterior circulation in moyamoya disease. Part 2: visual disturbances and surgical treatment. J Neurosurg. 1986; 65: 454–460.[Medline] [Order article via Infotrieve]
26. Yamada I, Murata Y, Umehara I, Suzuki S, Matsushima Y. SPECT and MRI evaluations of the posterior circulation in moyamoya disease. J Nucl Med. 1996; 37: 1613–1617.[Abstract/Free Full Text]
27. Wakai K, Tamakoshi A, Ikezaki K, Fukui M, Kawamura T, Aoki R, Kojima M, Lin Y, Ohno Y. Epidemiological features of moyamoya disease in Japan: findings from a nationwide survey. Clin Neurol Neurosurg. 1997; 99 (Suppl 2): S1–S5.[CrossRef]
28. Kanai N. A genetic study of spontaneous occlusion of the Circle of Willis (moyamoya disease). J Tokyo Women Med Univ. 1992; 62: 1227–1258.
29. Nanba R, Kuroda S, Tada M, Ishikawa T, Houkin K, Iwasaki Y. Clinical features of familial moyamoya disease. Childs Nerv Syst. in press.
30. Robertson RL, Burrows PE, Barnes PD, Robson CD, Poussaint TY, Scott RM. Angiographic changes after pial synangiosis in childhood moyamoya disease. AJNR Am J Neuroradiol. 1997; 18: 837–845.[Abstract]
31. Okada Y, Shima T, Nishida M, Yamane K, Yamada T, Yamanaka C. Effectiveness of superficial temporal artery-middle cerebral artery anastomosis in adult moyamoya disease: Cerebral hemodynamics and clinical course in ischemic and hemorrhagic varieties. Stroke. 1998; 29: 625–630.[Abstract/Free Full Text]
32. Houkin K, Nakayama N, Kuroda S, Ishikawa T, Nonaka T. How does angiogenesis develop in pediatric moyamoya disease after surgery? A prospective study with MR angiography. Childs Nerv Syst. 2004; 20: 734–741.[Medline] [Order article via Infotrieve]

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This Article Abstract Full Text (PDF) All Versions of this Article: 36/10/2148    most recent 01.STR.0000182256.32489.99v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kuroda, S. Articles by Iwasaki, Y. Search for Related Content PubMed PubMed Citation Articles by Kuroda, S. Articles by Iwasaki, Y. Related Collections Primary and Secondary Stroke Prevention Stroke in Children and the Young