Subject Review. Moyamoya Disease: The Disorder and Surgical Treatment

Subject Review Moyamoya Disease: The Disorder and Surgical Treatment KEISUKE UEKI, M.D.,* FREDRIC B. MEYER, M.D., AND JAMES F. MELLINGER, M.D. Objective: To discuss the clinical features of moyamoya disease, the studies that aid in diagnosing this disorder, and the reported outcomes of surgical treatment. Design: We review the manifestations of moyamoya disease in children and adults and the recent reports of the various surgical procedures. Material and Methods: Moyamoya disease is a chronic cerebrovascular disorder in which stenosis of the major arteries of the circle of Willis at the base of the skull progresses to occlusion. The diagnosis is based on the angiographie findings of the "puff of smoke" appearance of the abnormal capillary vessels at the base of the skull. Three surgical procedures are used to manage this disease: anastomosis of the superficial temporal artery to the middle cerebral artery, encephalomyosynangiosis, and encephaloduroarteriosynangiosis. Results: In children with this disease, cerebral ischémie events, including strokes, occur. In adults, the fragile abnormal vessels can rupture and cause intracerebral hemorrhage. The mortality rate for adults is higher than that for children. Most published reports support the efficacy of surgical treatment in children but not in adults. Conclusion: The natural history of moyamoya disease is poor; neurologic deterioration due to strokes and hemorrhage is progressive. Seizures and intellectual deterioration can occur. (Mayo Clin Proc ; 6:7-757) ACAs = anterior cerebral arteries; AVMs = arteriovenous malformations; CBF = cerebral blood flow; EDAS = encephaloduroarteriosynangiosis; EEG = electroencephalographic; EMS = encephalomyosynangiosis; MCA = middle cerebral artery; PCAs = posterior cerebral arteries; STA = superficial temporal artery; s = transient ischémie attacks Moyamoya disease is a rare, chronic occlusive cerebrovascular disorder characterized by progressive stenosis of the arteries of the circle of Willis. Initially, this stenosis involves the intracranial carotid arteries bilaterally; subsequently, it may progress to involve both the middle cerebral artery (MCA) and the posterior cerebral arteries (PCAs). In conjunction with the progressive stenosis and eventual occlusion of these major arteries at the base of the skull, an abnormal capillary network develops at the base of the brain. These vascular changes can result in ischémie strokes in children and cerebral hemorrhages in adults. Moyamoya disease and its characteristic angiographie findings were first described in Japan by Takeuchi and Shimizu in 57, as bilateral hypogenesis of the internal carotid arteries. Similar cases reported primarily from Japan From the Department of Neurologic Surgery (K.U., F.B.M.) and Section of Child and Adolescent Neurology (J.F.M.), Mayo Clinic Rochester, Rochester, Minnesota. "Current address: Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts. Address reprint requests to Dr. F. B. Meyer, Department of Neurologic Surgery, Mayo Clinic Rochester, First Street SW, Rochester, MN 555. eventually led to the recognition of this disease as a clinical entity. In 68, Kudo first introduced the disease into the English literature as spontaneous occlusion of the circle of Willis. That same year, Nishimoto and Takeuchi reviewed 6 cases from Japan. Suzuki and Takaku first used the term "moyamoya disease" in 6; the Japanese word moyamoya describes the "hazy puff of smoke" appearance of the abnormal capillary vessels at the base of the skull. Although moyamoya disease was once thought to be confined to those of Japanese heritage, it is now known to affect all races. CAUSE Moyamoya disease is a slow progressive occlusion of the major trunks of the intracerebral arteries; occlusion commences at the carotid artery in the cavernous sinus. The cause of moyamoya disease is unknown. Formation of abnormal, small "moyamoya" vessels distal to the narrowing of the carotid arteries is now considered a secondary process in the development of collateral circulation (Fig. I). 5 At autopsy, intimai thickening and medial thinning of the affected carotid arteries are typical findings without evidence of an inflammatory process.5 A genetic contribution has been implicated because of reports of familial cases and a high incidence in persons with Down syndrome.6 7 Mayo Clin Proc ; 6:7-757 7 Mayo Foundation for Medical Education and Research

75 MOYAMOYA DISEASE Mayo Clin Proc, August, Vol 6 CLINICAL FEATURES The onset of moyamoya disease occurs during the first decade of life or during the fourth decade. A female preponderance has been noted. On the basis of the 7 national statistics in Japan, of 58 patients registered, the female-tomale ratio was to 5 in children (5 years of age or younger), to in adults (older than 5 years), and to 8 overall.8 The clinical features differ between children and adults' (Table ). In children, the usual manifestations are ischémie events, such as recurring transient ischémie attacks (s) or complete strokes, that cause various neurologic symptoms including motor, sensory, visual, and speech disturbances. These ischémie attacks are characteristically induced by crying, coughing, or straining. Seizures are common. In adults, hemorrhage of the fragile abnormal vessels is the most common clinical manifestation. In 7 to 8% of patients, the bleeding occurs in the basal ganglia, thalamus, or ventricle. Subarachnoid hemorrhage was reported to be the most common type of bleeding before the availability of computed tomography. Most of those cases, however, were probably intraventricular hemorrhage or rupture of an intracerebral hemorrhage into the ventricle." The prognosis is significantly different between children and adults. Nishimoto8 reported deaths in 58 patients (7.5%); the mortality rate for adults (.%) was higher than that for children (.%). The cause of death was intracranial bleeding in 5 of children (55.5%) and in of adults (6.%) (Table ). In a study of 7 patients, including those who received treatment, Nishimoto and associates reported a good prognosis in 58%; the rest had some degree of disability. The adult cases or the hemorrhagictype of manifestation was associated with the worst prognosis (Table ). Few studies have examined the natural history of patients who have only s because most such patients receive treatment. During follow-up of 7 patients with s who received no treatment, Kurokawa and colleagues' noted that, although the s gradually resolved, one-half to two-thirds of the patients had deteriora- < Fig.. Typical findings in moyamoya disease. A, Anteroposterior angiogram, showing occlusion of carotid artery as it exits cavernous sinus to enter subarachnoid space. Specifically, neither the middle cerebral nor the anterior cerebral artery is visualized. Note large number of hypertrophied lenticulostriate arteries or "moyamoya" vessels (collateral circulation). B, Lateral angiogram, demonstrating only filling of posterior cerebral artery complex. Middle cerebral and anterior cerebral arteries are not visualized. Note "puff of smoke" appearance of large number of moyamoya vessels (arrow). C, Vertebral injection, demonstrating collateral blood flow to anterior circulation (arrow).

Mayo Clin Proc, August, Vol 6 MOYAMOYA DISEASE 75 Table. Clinical Features of Moyamoya Disease in Children and Adults Feature s* Complete strokes Seizures Hemorrhage Others Children (<5 yr) No. % 6 6 7 55 5 Adults (>5 yr) No. % 5 6 8 6 5 65 5 *s = transient ischémie attacks. From Nishimoto and colleagues. By permission of Nyuuron-sha Inc. tion of cognitive function for a duration of 5 to years (Table ). Intracranial aneurysms are known to be associated with moyamoya disease. Characteristically, aneurysms arise in the posterior circulation more frequently in patients with this disease than in the normal population. In a review of aneurysms associated with moyamoya disease, Kwak and coworkers noted that 6.5% of the aneurysms of the major trunk arteries were located in the posterior circulation (Table 5). Aneurysms, potential sources for intracerebral hemorrhage, can also develop in the peripheral arteries, including the abnormal moyamoya vessels.' Arteriovenous malformations (AVMs) are rarely associated with moyamoya disease. In the five reported cases,' 6 the nidus of the AVM was located in the MCA territory and was fed by the abnormal moyamoya vessels. The relationship of these two pathologic conditions is unclear. One possible explanation is thai-dilatation of capillary vessels as a result of the ischemia causes such vessels to evolve into anastomotic channels, from abnormal moyamoya vessels to the venous system that leads to formation of an AVM. Because of the small number of cases, neither the natural history nor the indications for surgical resection of the nidus are known. DIAGNOSTIC TESTS Angiography. Suzuki and Takaku described the natural history of moyamoya disease precisely through angiographie findings; they noted six stages. The earliest observation is stenosis of the carotid artery at its suprasellar position, usually occurring bilaterally (stage ). With progression of the disease, the carotid arteries narrow and the characteristic abnormal vascular network or moyamoya vessels begin to develop at the base of the brain (stage ). These abnormal moyamoya vessels become more prominent as major trunks in the anterior circulation become severely stenotic or occluded (stage ). At this stage, moyamoya disease is diagnosed in most patients. The abnormal moyamoya vessels are considered collateral pathways that are formed in response to the chronic ischemia caused by the stenotic changes of the internal carotid arteries. When all components of the circle of Willis, including the PCAs, are occluded, these moyamoya vessels at the base of the brain begin to diminish, and collateral pathways from extracranial circulation develop (stage ). This development progresses (stage 5), and, finally, the moyamoya vessels at the base of the skull and the major cerebral arteries completely disappear (stage 6). At this final stage, the cerebral hemispheres receive blood through the abnormal extracranial-intracranial anastomosis. The diagnosis of moyamoya disease is based primarily on angiographie findings. No definite diagnostic criteria are internationally accepted. Diagnostic guidelines for moyamoya disease proposed by the Ministry of Health and Welfare of Japan involve four criteria: 8 ( ) stenosis or occlusion of the intracranial internal carotid artery or the adjacent anterior cerebral arteries (ACAs) and MCA, () abnormal vascular network adjacent to the stenosed artery identified during the arterial phase of angiography, () bilateral findings on angiography, and () no other identifiable cause. If the angiographie abnormalities are unilateral, the case is considered questionable. Computed Tomography and Magnetic Resonance Imaging. Both computed tomography and magnetic resonance imaging can visualize characteristic intracranial Table. Cause of Death in of 58 Registered Patients With Moyamoya Disease Patient Pédiatrie Adult Intracranial bleeding 5 (55.5%) (6.%) (6.5%) Modified from Nishimoto. 8 Neurosurgical Society. Cause of death Infarction Other Unknown 8 By permission of The Japan Table. Outcome of 7 Patients With Moyamoya Disease Outcome (%) Initial symptom Good Fair Poor Death Hemorrhage (N = ) Seizure (N = ) Complete stroke (N = 75) * (N = 6) 5 66 7 77 58 5 6 6 7 * = transient ischémie attack. From Nishimoto and colleagues. By permission of Nyuuron-sha Inc.

75 MOYAMOYA DISEASE Mayo Clin Proc, August, Vol 6 Table Follow-Up of 7 Children With s Who Received No Treatment* Outcome s (no. of patients) Persisted Resolved Death Mental function (no. of patients) Normal Impaired Death - *s = transient ischemic attacks. Data from Kurokawa and associates. Follow- up period (yr) 5- -5 7 6 changes in patients with moyamoya disease: () multiple dilated abnormal vessels at the basal ganglia or thalamus (or both), () narrowing or occlusion of major arteries of the circle ofwillis, () parenchymal changes including ischemic infarctions predominantly in watershed areas, and () intracerebral hemorrhages. Usually, magnetic resonance imaging is superior to computed tomography in demonstrating these changes. 7 Cerebral Blood Flow Studies. Cerebral blood flow (CBF) is reported to be significantly decreased in children with moyamoya disease but relatively normal in adults. In a study of patients, Ögawa and coworkers 8 reported that the distribution of CBF was greatest in the occipital regions, which normally is frontal-lobe dominant. This tendency progressed with the advancement of the angiographie stage, a reflection of a pronounced contribution of the posterior circulation to CBF.' 8 In children with moyamoya disease, CBF autoregulation to blood pressure and vascular response to carbon dioxide are impaired. Of interest, the response to hypotension and hypercapnia, which necessitates vasodilatation, is impaired more severely than is the relatively preserved response to hypertension and hypocapnia. 7 Electroencephalography. In children with moyamoya disease, a characteristic electroencephalographic (EEG) finding termed "rebuildup" is found in more than half the cases. This phenomenon is not evident in adult patients. With this phenomenon, a normal buildup is induced by hyperventilation and consists of monophasic slow waves. The EEG findings usually return to normal within to 6 seconds after termination of hyperventilation. Shortly after or even continuous with the normal buildup, another phase of slow waves appears. These slow waves, which are more irregular and of a lower frequency than are the first waves, usually disappear within minutes; however, they may last longer. Although the mechanism is not completely defined, a delayed response in CBF carbon dioxide reactivity is considered the mechanism of this unusual EEG phenomenon. SURGICAL TREATMENT The first surgical procedure for moyamoya disease was perivascular sympathectomy and superior cervical ganglionectomy; the goal was to dilate both the intracranial and the extracranial vessels. Despite encouraging results reported by Suzuki and Kodama, few surgeons currently use this procedure. In 75, Krayenbuhl proposed the possible benefit of extracranial-intracranial anastomosis for revascularization of the ischemic brain in children with moyamoya disease by describing an anastomosis of the superficial temporal artery (STA) to the MCA performed by Yasargil in 7. Since then, several types of direct and indirect revascularization procedures, including some experimental ones, have been proposed and attempted. Currently, three procedures are frequently used: () STA-MCA anastomosis, () encephaloduroarteriosynangiosis (EDAS), and () encephalomyosynangiosis (EMS). Direct anastomosis, such as a STA-MCA bypass, can be effective for revascularization of the brain. Nonetheless, finding both a satisfactory donor and a recipient artery with sufficient caliber in patients with moyamoya disease, especially small children, is difficult. Site Major trunk artery Anterior circulation Internal carotid Middle cerebral Anterior communicating Posterior circulation Basilar Posterior cerebral *Data from Kwak and associates.' Table 5. Site of Aneurysms Associated With Moyamoya Disease in Reported Cases 8 No. 5 Site Peripheral artery Anterior choroidal Posterior choroidal Posterior cerebral Perforators to basal ganglia Others 5 No. 7

Mayo Clin Proc, August, Vol 6 MOYAMOYA DISEASE 75 The EDAS, proposed by Matsushima and associates in 8, is a procedure in which a patent STA is sutured along a longitudinal durai defect to approximate the artery to the brain surface. The EMS was first used for moyamoya disease by Karasawa and colleagues in 77. During this operation, the temporal muscle is sutured to surgical durai defects, approximating the muscle to the surface of the brain. Both the EMS and the EDAS are indirect anastomotic procedures; the goal is to develop neovascularization from the extracranial arterial and soft tissue system to the ischémie brain (Fig. ). These procedures are easier and safer to perform than the STA-MCA anastomosis, especially in small children. The EMS can be combined with the STA- MCA anastomosis. In, Karasawa and coworkers5 reported a series of children with moyamoya disease treated with a STA- MCA anastomosis or EMS (or both); mean follow-up was.6 years. Results were excellent; the incidence of s and major strokes was decreased substantially, and intellectual function was maintained. In, Matsushima and associates6 described their experience with 65 children treated with an EDAS; results were good, including a gradual decrease in s and maintenance of cognitive abilities. Other investigators, however, have questioned the adequacy of blood supply offered by the EDAS only and have stated the superiority of the combination of the EMS and STA-MCA anastomosis.5 7 8 With use of a special design, an EMS procedure can be combined with an EDAS. Recently, Kinugasa and colleagues described a combined procedure of EDAS and EMS (which they labeled EDAMS); results were good. Recent reports of the results of these various procedures are summarized in Table 6.5,6 8" All the indirect procedures increase the blood supply primarily in the MCA territory, but they do not directly benefit the ACA or the PCA territory. Redistribution of blood supply, however, is expected to increase the circulation indirectly in both the ACA and the PCA regions. Endo Fig.. Illustrations of revascularization of brain by using both encephaloduroarteriosynangiosis (EDAS) and encephalomyosynangiosis (EMS). Λ, Skin flap is designed in which temporal artery can be harvested from scalp and dissected free of temporal muscle but preserved in continuity. Horseshoe incision facilitates dissection of temporal muscle off calvarium. B, Large craniotomy is performed to expose parietal cortex. Most of dura is excised to expose surface of brain. Two longitudinal strips of dura are left intact so temporal artery can be sewn directly to these margins and thereby approximate it to surface of brain. Thus, indirect anastomosis between temporal artery and brain parenchyma has been performed (EDAS). C, Temporal muscle is sewn to rest of durai margin. Approximating temporal muscle to surface of brain is termed EMS. >.

75 MOYAMOYA DISEASE Mayo Clin Proc, August, Vol 6 Reference Olds et al, 87 Matsushima et al, 6 Matsushima et al, 8 Karasawa et al, 5 Kinugasaetal, Table 6. Recent Published Outcomes of Surgical Treatment of Moyamoya Disease Procedure STA-MCA or EDAS EDAS STA-MCA + EMS EDAS STA-MCA + EMS EDAS + EMS No. of patients 5 65 t 7t 7 Mean follow-up (yr).5 6. NA.5. Results Excellent, 7; good, 5; fair, No in 7% No No in % Substantially decreased, normal IQ in 6.5% Excellent, 8; good, 5; fair, ; poor, *EDAS = encephaloduroarteriosynangiosis; EMS = encephalomyosynangiosis; NA = not available; STA-MCA : superficial temporal artery-middle cerebral artery anastomosis; = transient ischémie attack. fnumber of procedures. and coworkers reported that bilateral frontal burr holes with durai and arachnoidal incisions induced pronounced neovascularization to the ACA area and improved the circulation in the frontal regions. Miyamoto and associates reported that omentum transpositions to the occipital lobe were effective in improving visual symptoms in 5 patients with moyamoya disease; however, they also noted that 8 of patients with visual symptoms had improvement or stabilization after a STA-MCA anastomosis with or without an EMS. The primary purpose of these revascularization techniques is to prevent ischemia of the brain. Therefore, they are used primarily in children with moyamoya disease, whose symptoms are typically a result of ischemia. Most published reports support the efficacy of these procedures in children. These techniques are also used in adults, although less frequently, to decrease the risk of bleeding by retarding the development of abnormal moyamoya vessels. The effectiveness of these techniques in adults remains unproved. REPORT OF CASES Case. An -year-old boy was brought to our institution because of a 7-month history of recurrent episodes of rightsided weakness, which were sometimes induced by crying or vigorous exercise. During an EEG recording and hyperventilation, he experienced an episode. The EEG showed no spikes but demonstrated semirhythmic generalized.5- to.5-hz activity for minutes after termination of hyperventilation. An angiogram revealed bilateral high-grade stenosis of the supraclinoidal internal carotid artery (Fig. ). Of interest, this boy had one Oriental parent. A left-sided STA-MCA anastomosis was planned; however, an EDAS was performed because of the inability to locate a satisfactory recipient artery. Two branches of the STA (with maintenance of their continuity) were transposed onto the pia-arachnoid surface, and surrounding connective tissue was sewn to the durai edge. An angiogram obtained 7 months postoperatively showed extensive perfusion of the cortical vasculature on the left side fed by the dilated STA through the EDAS. Thus, a right-sided procedure with a STA-pia-arachnoidsynangiosis was performed. During the next months, he experienced only one brief episode of transient weakness; otherwise, he has remained asymptomatic. The referring physician concluded that the patient's symptoms of moyamoya disease had essentially resolved after the procedure. Case. A 6-year-old right-handed girl was brought to our institution because of an 8-month history of episodes of severe headache sometimes accompanied with vomiting, which frequently occurred after vigorous exercise. Initially magnetic resonance imaging and then angiography were performed after a recent episode, the latter of which demonstrated typical findings of bilateral moyamoya disease; 5% stenosis of the left MCA and 6% stenosis of the right MCA were noted. Results of the neurologic assessment were normal. The left side was operated on first. Because the STA was relatively small, an EDAS in combination with an EMS was performed. At months postoperatively, she had had no further spells. A similar procedure was then performed on the right side (Fig. ). She has remained free of symptoms since then. A follow-up angiogram obtained months after the second operation showed retrograde feeding of the MCA by a hypertrophie STA and muscular branches through the pial anastomosis. MAYO CLINIC EXPERIENCE Our experience with patients with moyamoya disease is summarized in Table 7. The mean age of the seven female and three male patients was.5 years. Five patients underwent a STA-MCA anastomosis, two had EDAS procedures,

Mayo Clin Proc, August, Vol 6 MOYAMOYA DISEASE 755 Fig. (case ). A, Preoperative lateral angiogram of -year-old boy, demonstrating typical findings of moyamoya disease. Note moyamoya vessels or blush, which is proliferation of lenticulostriate arteries at base of skull (arrow). B, Postoperative lateral angiogram, demonstrating successful bypass of superficial temporal artery to middle cerebral artery and perfusion of parietal cortex (arrows). and three underwent a combination of an EDAS and EMS operation. Follow-up was months to 7 years (mean, 6. years). No surgical complications were noted. In all patients, ischémie symptoms had diminished. CONCLUSION More than 5 years after moyamoya disease was recognized, it remains an elusive illness. All efforts to determine a cause have been unsuccessful, and the natural history of the disease Fig. (case ). Angiograms obtained months after 6-year-old girl with moyamoya disease underwent right-sided encephaloduromyoarteriosynangiosis. A, Superficial temporal artery is hypertrophied and is perfusing parietal cortex through indirect anastomoses. B, On delayed angiogram, much of blood supply to parietal hemisphere is through this muscle arterial graft.

756 MOYAMOYA DISEASE Mayo Clin Proc, August, Vol 6 Case 5 6 7 8 Table 7. Surgical Results of Mayo Clinic Patients With Moyamoya Disease* Age (yr) and sex 6F 6 F M F F F UM 7F M 6F Initial symptoms, stroke Stroke SAH* SAH, stroke Surgical procedure STA-MCA STA-MCA STA-MCA, repair aneurysm STA-MCA STA-MCA EDAS EDAS EDAS + EMS EDAS + EMS EDAS + EMS Follow-up periodt 7 yr 5 mo yr 8 mo yr mo 8 yr mo 7 yr 8 mo lyr yr mo mo yr 7 mo yr 6 mo Result Excellent, no Good (preop deficit) Good No Excellent Good (preop deficit) Excellent, no Decreased Decreased Decreased *Preop = preoperative; SAH = subarachnoid hemorrhage; for explanation of other abbreviations, see Table 6. fmean follow-up was 6. years. tbleeding from rupture of basilar caput aneurysm. Bleeding from aneurysm of lenticulostriate artery. has been poorly defined. Apparently, with use of conservative measures, patients with moyamoya disease will have persistent cerebrovascular insults. Currently, a surgical procedure for revascularization of the ischémie brain by creating collateral pathways seems to be the most reasonable treatment of moyamoya disease, especially for children with ischémie symptoms. Surgical results, including our own experience, with use of the STA-MCA anastomosis, EDAS, or EMS have shown a beneficial effect; patients' preoperative symptoms have been alleviated. Nonetheless, for children with moyamoya disease who have a future risk for intracranial bleeding, whether surgical revascularization will decrease this risk k unknown. This uncertainty is partly due to the absence of long-term follow-up. The longest mean reported follow-up of years may still be insufficient in light of the slow progression of this disease. ACKNOWLEDGMENT We are indebted to Nicolee C. Fode, R.N., for analysis of the clinical data and editorial assistance, Mary M. Soper for preparation of the submitted manuscript, and Michael A. King for artistic talents. REFERENCES. Takeuchi K, Shimizu K. Hypogenesis of bilateral internal carotid arteries. NoToShinkei 57;:7-. Kudo T. Spontaneous occlusion of the circle of Willis: a disease apparently confined to Japanese. Neurology 68; 8:85-6. Nishimoto A, Takeuchi S. Abnormal cerebrovascular network related to the internal carotid arteries. J Neurosurg 68; :55-6. Suzuki J, Takaku A. Cerebrovascular "moyamoya" disease: disease showing abnormal net-like vessels in base of brain. Arch Neural 6; :88-5. Suzuki J. Moyamoya Disease. Berlin: Springer-Verlag, 86 6. Fukushima Y, Kondo Y, Kuroki Y, Miyake S, Iwamoto H, Sekido K, et al. Are Down syndrome patients predisposed to moyamoya disease? [letter]. Eur J Pediatr 86; :56-57 7. Kitahara T, Ariga N, Yamaura A, Makino H, Maki Y. Familial occurrence of moya-moya disease: report of three Japanese families. J Neurol Neurosurg Psychiatry 7; :8-8. Nishimoto A. Moyamoya disease. Neurol Med Chir 7; :-8. Suzuki J, Kodama N. Moyamoya disease a review. Stroke 8; :-. Nishimoto A, Ueta K, Onbe H. Cooperative study on moyamoya disease in Japan. In: Abstracts of the th Meeting on Surgery for Stroke. Tokyo: Nyuuron-sha, 8: 5-58. Saeki N, Yamaura A, Hoshi S, Sunami K, Ishige N, Hosoi Y. Hemorrhagic type of moyamoya disease. No Shinkei Geka ; :75-7. Kurokawa T, Tomita S, Ueda K, Narazaki O, Hanai T, Hasuo K, et al. Prognosis of occlusive disease of the circle of Willis (moyamoya disease) in children. Pediatr Neurol 85; :7-77. Kwak R, Ito S, Yamamoto N, Kadoya S. Significance of intracranial aneurysms associated with moyamoya disease (part I): differences between intracranial aneurysms associated with moyamoya disease and usual saccular aneurysms review of the literature. Neurol Med Chir 8; :7-. Okada T, Kida Y, Kinomoto T, Sakurai T, Kobayashi T. Arteriovenous malformation associated with moyamoya disease case report. Neurol Med Chir ; :5-8

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