Stroke & Vascular Disorders

Updated 10.26.2023
Released 09.18.1995
Expires For CME 10.26.2026

Moyamoya disease

Authors: Aneesh B Singhal MD, Eva A Rocha MD PhD

Editor: Steven R Levine MD

Introduction

Overview

In this article, the authors provide a comprehensive overview of moyamoya disease, including advances in the genetics and molecular biology of moyamoya disease, the role of newer imaging techniques, and the surgical management of moyamoya disease.

Key points

	• Moyamoya disease is an idiopathic non-atherosclerotic vasculopathy with characteristic angiographic abnormalities involving the terminal internal carotid artery and its branches.
	• Similar angiographic changes have been associated with diverse conditions, including neurofibromatosis, craniopharyngioma, Down syndrome, sickle cell disease, Graves disease, and the use of vasoconstrictive drugs such as cocaine.
	• Patients can be asymptomatic or present with ischemic or hemorrhagic strokes. Other manifestations include intellectual dysfunction, seizures, and movement disorders.
	• Early surgical intervention (eg, encephalo-duro-arterio-synangiosis) before the establishment of irreversible hemodynamic change appears to be effective in preventing complications from progressive arterial stenosis and collateral formation.

Historical note and terminology

Moyamoya disease is a nonatherosclerotic and noninflammatory condition characterized by progressive stenosis of the terminal internal carotid artery and the proximal portions of the anterior cerebral and middle cerebral arteries (105; 169). The disease is usually bilateral but can be unilateral. It may begin as an asymptomatic isolated stenosis of the middle cerebral artery stem, progressing to symptomatic moyamoya disease over a few years (25). The term "moyamoya disease" is used when the internal carotid artery stenoses and associated collaterals are observed and when no associated diseases are identified. "Moyamoya phenomenon" is used to describe the extensive collateralization of the circle of Willis arteries associated with severe unilateral or bilateral internal carotid artery stenosis or occlusion in the presence of conditions such as sickle cell disease, atherosclerosis, cranial irradiation, and neurofibromatosis. Synonyms include "idiopathic progressive occlusive disease of the circle of Willis," "spontaneous occlusion of the circle of Willis" (100) "cerebral basal rete mirabile," and "cerebral juxtabasilar telangiectasia."

The history of moyamoya disease is fascinating. Shimizu and Takeuchi published the first case of moyamoya disease in 1957(172). Suzuki was the first to use the Japanese term "moyamoya" to describe the hazy, cloudy “puff of smoke” appearance of the network of dilated, abnormal microvasculature occurring in the region of the circle of Willis (177). These authors also described the six stages of angiographic progression, from stage 1 (narrowing of the carotid artery) to stage 6 when moyamoya vessels disappear and the external carotid arteries supply collateral flow. In 1964, Nishimoto published a series of 24 cases, including three new cases and 21 cases from the literature. The first autopsy report by Maki in 1965 demonstrated a narrowing of the lumen of the internal carotid artery, with intimal thickening but no abnormality of the media or adventitia and no inflammatory changes (128). In 1967, the proceedings of the Japan Neurosurgical Society were published and included a discussion of moyamoya disease (99). In 1968, Kudo published 12 cases and proposed that the dilated penetrating arteries represented an attempt to form collaterals in response to progressive occlusion of the main affected arteries (100). The same year, Nishimoto published a collection of 96 cases (149); therefore, the disease is sometimes referred to as “Nishimoto disease” or “Nishimoto-Takeuchi-Kudo disease.”

Tavares reported the first non-Japanese cases in 1969 (187). He described 10 cases and discussed the three major collateral pathways: (1) the circle of Willis, (2) leptomeningeal arteries, and (3) transdural vessels. Since Tavares' report, cases have been reported from all over the world. Large single and multicenter co-operative studies have described the clinical features of patient populations from various countries, including the United States, and the studies have highlighted differences between Caucasians and Eastern populations (22; 206; 97; 43; 134; 17; 46).

In 1978, the Research Committee on Moyamoya Disease organized by the Japanese Ministry of Health and Welfare published diagnostic criteria for moyamoya disease. The original criteria have undergone five revisions; the latest diagnostic criteria were published in 2021 (103).

Clinical manifestations

Presentation and course

Epidemiological studies have shown that nearly 18% of individuals with moyamoya disease are asymptomatic (11; 102). However, asymptomatic disease is not benign, imparting an annual stroke risk exceeding 3% (104). The disease may begin as an asymptomatic isolated stenosis of the middle cerebral artery stem, progressing to symptomatic moyamoya disease over a few years (25).

The Ministry of Health and Welfare of Japan has defined four types of moyamoya disease: ischemic, hemorrhagic, epileptic, and “other.” Symptoms typically result from cerebral ischemia, infarction, or hemorrhage, depending on the adequacy or the rupture of the delicate developing collateral vessels. There appears to be an “unsteady state” during collateral development, with higher susceptibility for transient ischemic attacks or stroke at younger ages. Patients who develop adequate collaterals can remain asymptomatic until, or if, they have a hemorrhage. The risk of hemorrhage increases with age. In the Japanese population, the most common age of presentation is five to 10 years. A bimodal age of presentation occurs with the first peak in the first decade of life and the second during the fourth decade. There is a slight female predominance (female to male ratio of 1.8:1). The western population presents at a later age. The mean age was 17 years in the Indiana series (206) and 32 years in the Houston series (22), and the median age was 42 years in the St. Louis series (44).

Ischemic symptoms predominate in the young, with transient ischemic attacks occurring in approximately 40% and ischemic stroke in approximately 30%. Those with unilateral moyamoya appear to have a lower risk for infarction (150). The transient ischemic attacks are usually motor related and may remain unilateral or may alternate sides. Transient ischemic attacks may be precipitated by fever, crying, coughing, or hyperventilation during exercise or while playing wind instruments. Cerebral hypoperfusion can result in movement disorders such as hemidystonia, hemichoreoathetosis, paroxysmal exercise-induced dyskinesia, and “limb-shaking TIAs” (127; 126; 26). However, clinical presentation with a movement disorder is rare, particularly in the pediatric population. In the Stanford series, four children out of 118 presented with movement disorders, and in all four patients the movement disorder resolved after surgical revascularization (154). Progressive pseudobulbar palsy has also been described. It is not uncommon in pediatric patients to experience signs of orthostatic intolerance, such as headache, vertigo/dizziness on standing, fatigue, and difficulty with getting out of bed (190).

Other symptoms include intellectual dysfunction ranging from mental slowness to profound retardation from underlying strokes, transient sensory deficits, dysarthria, headaches, and seizures (177; 22). In Karasawa's series of 104 patients who were treated surgically, 36% of patients diagnosed before three years of age had subnormal IQs (below 82); all patients had underlying strokes. Subnormal IQs were noted in 18% of patients between three and seven years of age. Those who developed symptoms after seven years of age had a normal or borderline IQ (72). In adults, executive functioning appears to be more impaired than memory and perception; however, their overall level of cognitive dysfunction is less severe than in children (73). Cognitive impairment may precede the occurrence of clinical symptoms such as strokes (49). Evaluation of patients with asymptomatic moyamoya disease have demonstrated decline in computational ability and short-term memory associated with cerebral blood flow disturbances and impaired brain network connections (50). Epilepsy is reported in about 25% of pediatric cases and in 5% of adult cases. Gelastic attacks have been reported in a child with moyamoya disease (176).

Patients with moyamoya phenomenon might manifest signs and symptoms of the associated condition, for example neurofibromatosis, sickle cell anemia, and Down syndrome. Ocular abnormalities such as morning glory disc anomaly and choroidal coloboma have been associated with Moyamoya disease (130; 12; 98; 116; 19).

Hemorrhagic symptoms (typically an altered level of consciousness) predominate in older patients, with a frequency of approximately 60% (47). However, in the Western literature, the incidence of hemorrhage appears to be lower, approximately 12% to 14% (22; 206). As compared to primary intracerebral hemorrhage, moyamoya disease patients have higher rates of rebleeding and infarction, and hemorrhages are often intraventricular in location (145). Microbleeds on susceptibility weighted MRI are found in over 40% of patients, can accumulate over time, and higher numbers of microbleeds appear to predict future symptomatic brain hemorrhage (78; 79; 141; 108).

There are at least three different sources for hemorrhages in moyamoya disease. A major source is weakened dilated moyamoya vessels. In addition, a number of cases of angiographically identified aneurysms forming on collateral vessels have been reported, including aneurysms on the anterior choroidal, posterior choroidal, and penetrating arteries (181). Some might be pseudoaneurysms, as follow-up angiograms have documented the disappearance of aneurysms (91; 193; 45). Patients with ruptured choroidal collateral artery aneurysms usually have a poor prognosis (41% deceased or permanently disabled) and a high risk of re-rupture (40%), especially within the first 35 days (198). Another source of hemorrhage is the rupture of aneurysms that have formed on those vessels that are providing collateral flow. The basilar artery is an important source for the leptomeningeal collateral flow and is subject to increased hemodynamic stress, which is assumed to contribute to the formation of the basilar aneurysms (91; 63; 95). Furuse noted that of 44 cases of aneurysms found with moyamoya, there were 24 adults and three children with aneurysms of the moyamoya vessels (38). Seventeen patients had aneurysms independent of the moyamoya vessels; the locations were basilar artery (8), anterior communicating artery (3), middle cerebral arteries (2), internal carotid artery (3), and posterior communicating artery (1). Aneurysms can form on the transdural collateral vessels; rupture of one of these lesions can produce an acute subdural hematoma (110; 153). Morioka and colleagues analyzed angiographic findings in a series of 107 patients and concluded that angiographic dilatation and branch extension of the anterior choroidal and posterior communicating arteries are predictors of hemorrhage (143). Abnormal periventricular collaterals have been associated with hemorrhagic presentations (37).

The risk of recurrent hemorrhage is high, and rebleeding can occur as late as 20 years after the initial bleed. Aoki reported that rebleeding occurred in 17% to 33% of cases during a follow-up period of up to 18 years (09). Morioka and colleagues reported a rebleeding rate of 61% during a mean follow-up period of 12.7 years in a series of 36 patients who were not surgically treated (143). Kobayashi and colleagues reported similarly high rates of rebleeding and emphasized that the type and side of hemorrhage can vary (89). Lateral posterior choroidal artery anastomosis and smoking have been independently associated with recurrent hemorrhage (71; 194).

Prognosis and complications

Limited data on prognosis are available. Prognosis appears to be related to the age of onset and the type of symptoms. Patients who present at less than five years of age appear to have a worse outcome. A pediatric study showed a stroke rate of 14% among patients with nonischemic presentations and radiographic progression of 36% over 5.6 years (39). Patients who have repetitive transient ischemic attacks, without stroke have a benign outcome. Patients who present with hemorrhage have a high mortality and high risk of recurrent hemorrhages and infarctions (145).

Stenosis progression rates may differ depending on the underlying etiology. An observational study found a higher incidence of cerebrovascular events in patients with moyamoya disease when compared to patients with atherosclerosis associated moyamoya syndrome over a mean follow-up of 46 months (14% vs. 7%) (124).

Biological basis

Etiology and pathogenesis

The pathophysiology of cerebral arterial narrowing in patients with moyamoya disease and moyamoya phenomenon is not known. Moyamoya disease appears to be distinct from moyamoya phenomenon on the basis of the absence of associated diseases such as neurofibromatosis, craniopharyngioma, optic glioma, distal internal carotid artery compression by tumor, Down syndrome, chronic meningitis, leptospiral infections, atherosclerosis, sickle cell disease, antiphospholipid syndrome or lupus anticoagulant, Alagille syndrome, osteogenesis imperfecta, Costello syndrome, Graves disease, use of vasoconstrictive drugs such as cocaine, use of birth control pills (possibly in combination with cigarettes), essential thrombocythemia, and thrombotic thrombocytopenic purpura (169).

Although most cases of moyamoya disease appear to be sporadic, 7% to 15% occur as familial cases where the mode of inheritance is probably autosomal dominant with incomplete penetrance (137) or X-linked recessive (51). A number of possible triggering events have been proposed, including infectious and inflammatory processes and mechanical trauma (185; 200). Histological, genetic, proteomic, and molecular studies have started providing insights into the pathogenesis of moyamoya disease (02).

A role for angiogenesis and vascular remodeling is suggested by studies showing a higher number of circulating endothelial progenitor cells, higher levels of growth factors, and increased matrix metalloproteinase (MMP) expression (32; 158; 70; 119). Studies have examined the role of growth factors, including vascular endothelial growth factor, angiopoietins, platelet-derived growth factor, integrins, basic fibroblast growth factor, transforming growth factor-beta1, and hepatocyte growth factor (209; 53; 147; 120). Several groups have evaluated the possible role of basic fibroblast growth factor, a potent mitogen of smooth muscle cells and vascular endothelial cells. High levels of this growth factor have been found in endothelial and smooth muscle cells of superficial temporal arteries of patients with moyamoya disease (55). Cerebrospinal fluid samples from patients with moyamoya disease demonstrate significantly elevated levels of basic fibroblast growth factor over controls but not over other abnormal vascular disorders of the central nervous system (129). The dura of the moyamoya patients also demonstrated strong staining for basic fibroblast growth factor of the meningeal and vascular cells. Basic fibroblast growth factor is required for the movement of vascular cells during neovascularization, suggesting this may be the messenger involved in the neovascularity that occurs in moyamoya disease.

Genome-wide association studies have identified the c.14576G>A variant in the ring finger protein 213 (RNF213) as the first susceptibility gene for moyamoya disease with high risk for various phenotypes of moyamoya disease (68; 140). The homozygous variant is associated with early onset and more severe phenotype (80). A study found a high frequency of this genetic marker in Asian patients with presumed atherosclerotic intracranial disease, suggesting that they may actually have moyamoya disease (13). A Chinese study has showed a higher carrying rate of RNF213 p.R4810K in patients with moyamoya disease, associated with earlier onset age and more severe posterior cerebral artery involvement (196). Patients with mutant type of RNF213 have a more common age at onset under 18 years, familial moyamoya disease, cerebral ischemic stroke, and posterior cerebral artery involvement compared with wild type (66). Genetic linkage studies of moyamoya disease have shown that susceptibility loci are located on chromosome 3p (58), 6q (61), 17q (205), 17q25.3 (136), 8q, and 12p (166). Interestingly, genes encoding tissue inhibitor of metalloproteinase [TIMP] 2 and TIMP 4 span chromosomes 3p and 17q, and a study of familial moyamoya disease found single nucleotide polymorphisms of these genes (69). A metanalysis evaluating 4711 patients with moyamoya disease found RNF213 rs112735431 and rs148731719 positively associated, and TIMP-2 rs8179090, MMP-2 rs243865, and MMP-3 rs3025058 inversely associated with moyamoya disease (195). An X-linked moyamoya syndrome characterized by moyamoya angiopathy, short stature, facial dysmorphism, hypogonadism, hypertension, and dilated cardiomyopathy has been shown to result from Xq28 deletions (138). Genetic studies have found an association between moyamoya disease and mutations in the NF-1 gene and the smooth muscle alpha-actin gene ACTA-2, which promotes smooth muscle proliferation, suggesting a role for hyperplastic vasculopathy (42; 135).

A study has suggested modifiable risk factors for moyamoya disease. Increased body mass index and homocysteine levels were independently associated with a higher risk of the disease (40).

Sera from patients with moyamoya disease have a higher incidence of anti-alpha-fodrin autoantibodies, suggesting a role for chronic endothelial cell apoptosis (151). Immunohistochemistry studies on middle cerebral artery specimens from moyamoya patients have shown evidence for caspase-3-dependent apoptosis (180). Finally, case-control studies have found a higher prevalence of elevated thyroid autoantibodies and other autoantibody mediated conditions in patients with moyamoya disease (83; 118; 17), which extends previous observations of moyamoya disease in patients with Graves disease (60; 57; 171).

Moyamoya disease results from slowly progressive occlusion of the distal internal carotid artery, which permits the development of the unique small anastomotic collateral pathways. Factors that trigger the opening of these collateral pathways or the development of new collateral pathways are not well defined but may be related to chronic hypoperfusion and release of angiogenic growth factors. Pathological examination of the distal internal carotid artery reveals intimal thickening from smooth muscle cell proliferation and reduplication of the elastic lamina. The medial fibrosis and attenuation of the wall thickness with occasional regions of discontinuity of the elastic lamina of the penetrating vessels predispose to rupture from the hemodynamic stress of increased volume flow (152). Lipid deposition is minimal or absent (131). Intimal thickening may be the result of smooth muscle cell proliferation and conversion from a contractile state to a secretory state. Some authors have suggested local thrombosis contributes to both progressive stenosis and ischemic events (203; 204). A prospective study found evidence for prothrombotic disorders such as protein S deficiency and lupus anticoagulant and anticardiolipin antibodies in four of 10 consecutive children with moyamoya disease (16). Potential predictors of disease progression include lower age, family history, and presence of contralateral abnormality (21).

Differential diagnosis

Numerous conditions have been associated with moyamoya “phenomenon” and should be investigated with appropriate tests. A detailed history and clinical examination must be obtained to identify features of Down syndrome, sickle cell disease, brain radiation therapy, neurofibromatosis, antiphospholipid syndrome or lupus anticoagulant, Alagille syndrome, osteogenesis imperfecta, Costello syndrome, Graves disease, use of vasoconstrictive drugs such as cocaine, use of birth control pills (possibly in combination with cigarettes), essential thrombocythemia, and thrombotic thrombocytopenic purpura (169). In patients with a history of brain radiation, the incidence of moyamoya syndrome after receiving proton beam therapy is almost double that of photon-induced moyamoya syndrome (30). Pediatric patients with neurofibromatosis and moyamoya syndrome present with stroke in 46% of cases, mostly those with less than four years of age and bilateral disease (20).

Confusing conditions

Moyamoya is an angiographic diagnosis. The differential diagnosis is determined by the mode of onset. In young patients with transient ischemic attacks, alternative diagnoses include hypoglycemia, cardiac source emboli, hypercoagulable states, or seizures. Moyamoya disease is progressive, and serial vascular imaging can help distinguish it from reversible arteriopathies such as childhood transient cerebral arteriopathy (18). Primary CNS angiitis rarely manifests with similar angiographic changes and can be distinguished with examination of the cerebrospinal fluid and MRI findings, (eg, infarct topography) (96). Another important differential in the acute setting, especially if the initial presentation includes headaches, and hemorrhagic and ischemic lesions, is reversible cerebral vasoconstriction syndrome (28). The RCVS2 score and clinical approach can be a tool to help differentiate these patients in the acute setting (162). Moyamoya disease should be considered in children with alternating hemiparesis or transient ischemic attacks induced by hyperventilation. Seizures may be a manifestation of the cerebral ischemia in 25% of pediatric cases, and moyamoya should be in the differential for young patients, especially in cases of focal seizures.

Atherosclerotic intracranial disease is an important differential diagnosis of moyamoya disease. A study with artificial intelligence has assisted in distinguishing these two diseases. A deep learning-based approach evaluating two axial continuous slices of T2-weighted MRI at the level of the basal cistern, basal ganglia, and centrum semiovale has shown high accuracies for distinguishing between patients with moyamoya disease, atherosclerotic disease, or controls (92.8, 84.8, and 87.8%, respectively) (05).

In the older patients who present with intracerebral hemorrhage or intraventricular hemorrhage, moyamoya should be included in the list of potential causes.

Diagnostic workup

The diagnosis rests on the identification of the angiographic changes. Abnormalities detected by CT or MRI depend on the stage of development of the moyamoya, as well as the adequacy of collateral flow.

Moyamoya disease brain imaging

The figure shows brain imaging in a patient with Moyamoya disease. Narrowing of the terminal internal carotid artery and severe stenosis of the bilateral middle cerebral arteries are seen on the CT-angiogram (A) and MR-angiogram (...

Magnetic resonance studies of unilateral moyamoya disease have shown that endothelial shear stress on the intact side seen in time-of-flight sequences predicts contralateral progression of the disease (113).

Noncontrast CT performed in patients with ischemic syndromes can be normal or show nonspecific abnormalities such as sulcal or ventricular dilatation. Infarctions in the borderzone territories between the anterior cerebral, middle cerebral, and posterior cerebral arteries are common. Infarctions may be located in the cerebral cortex or the centrum semiovale, which is supplied by medullary arteries arising from the cortical branches. Deep infarctions in regions of the penetrating arteries are also common. The actual distribution of the infarction is dependent on the collateral vessels and the pattern of supply. In general, infarctions in the posterior cerebral artery territory are rare. Patients with cortical infarctions, and those with posteriorly distributed lesions, tend to have more advanced stages of disease (84). In patients with brain hemorrhage, the location of the bleed can be intraparenchymal (basal ganglia), with or without intraventricular extension, or primarily intraventricular. Subdural hematomas and subarachnoid hemorrhages are not uncommon.

MRI detects the same pattern of infarctions as seen with CT. In addition, MRI may detect the presence of moyamoya vessels (dilated, tortuous signal void regions in the basal ganglia) or the severe stenosis and occlusion of the distal internal carotid artery. Asymptomatic microbleeds can be identified using T2*-weighted gradient-echo MRI or susceptibility-weighted MRI in over 40% of patients, accumulate over time, and higher numbers predict a higher risk for symptomatic brain hemorrhage (78; 79; 141; 108). Leptomeningeal contrast enhancement (the "ivy sign"), believed to represent the fine vascular network over the pial surface, can be seen in up to one third of patients on contrast-enhanced T1-weighted images and FLAIR images (93; 207). The ivy sign indicates severe hypoperfusion and reduced cerebrovascular reserve (76; 142; 192) and can improve after bypass surgery (75). Following contrast administration, there may be a diffuse enhancement of the basal ganglia in the region of the moyamoya vessels. Medullary streaks, believed to represent dilated medullary vessels due to chronic hypoperfusion, can be seen on high-resolution T2 images (48). Ongoing research is investigating the utility of 3T and even 7T MRI in distinguishing the various intracranial arteriopathies, such as moyamoya, atherosclerosis, and vasculitis (179; 163; 04; 210). Preliminary high-resolution MRI studies show that the cerebral arteries in patients with moyamoya disease rarely enhance and show smaller, concentric occlusion as compared to patients with symptomatic intracranial atherosclerosis (87).

Transcranial Doppler ultrasound imaging may be a useful noninvasive test to follow the progression of intracranial vascular stenosis over time (156). In addition, transcranial Doppler ultrasound findings could be used in conjunction with invasive and noninvasive angiographic tests to determine the severity or stage of moyamoya (114). Relatively noninvasive angiographic techniques are gaining favor in diagnosing moyamoya. 3-D CT angiography might have value in the evaluation of surgical bypass patency and in following the disease progression (77). Magnetic resonance angiography appears sensitive to detect the local cerebral arterial stenoses and collateral circulation (33; 182; 164; 201). However, transfemoral contrast cerebral angiography remains the gold standard for diagnosis. The complication rate of cerebral angiography is not higher in the moyamoya population (161).

Suzuki's 1969 description remains the best overall reference for the six sequential stages of angiographic progression of the disease (177). In stage 1, the distal internal carotid artery narrows, virtually always distal to the origin of the ophthalmic artery and usually distal to the posterior communicating artery (both potential anastomotic sources). In stage 2, the moyamoya begins, accompanied by resistance-lowering dilation of the large intracerebral arteries. There is slight moyamoya formation from dilation of the penetrating arteries, primarily in the basal ganglia. Although no external carotid to intracranial vessel anastomoses are present at this stage, vertebral angiography can demonstrate leptomeningeal collaterals. In stage 3, the moyamoya formation intensifies, and filling of the middle cerebral and anterior cerebral artery trunks and branches is progressively lost although maintaining the posterior communicating artery. In stage 4, the moyamoya abates, the terminal internal carotid artery is occluded, and the posterior communicating artery usually becomes occluded. The middle cerebral and anterior cerebral artery branches are filled via the moyamoya vessels, and collateral flow comes from the external carotid artery to the intracranial internal carotid artery territory through transdural collaterals via the orbit into the infraorbital branches and via the meningeal branches to the cortical branches. In stage 5, the moyamoya continues to abate, and the moyamoya vessels begin to involute. There is a progressive increase in the extracranial carotid artery collaterals. In stage 6, the moyamoya disappears; the siphon of the internal carotid artery is occluded. Only the extracranial carotid artery collaterals are visualized on carotid arteriography. The cerebral circulation is maintained only by the route of the external carotid or the vertebral artery. Yamashita, reporting on 22 autopsied cases, noted that both the density and extent of the vascular network were conspicuous in children and adolescents (202). In the older patients, the network was usually restricted to a small area of the base of the brain, whereas transdural collaterals were more conspicuous. These findings support the sequence of changes proposed by Suzuki.

A collateral grading system has been proposed ranging from 1 to 12, according to the extent of pial collateral blood flow from posterior cerebral artery to middle cerebral artery and anterior cerebral artery, perforator collateral and internal cerebral artery flow, as well as Suzuki grading. Patients with scores less than four points were more likely to have a postoperative stroke and a worse prognosis during the follow-up (123).

Because the internal carotid artery stenosis occurs distal to the origin of the posterior communicating and ophthalmic arteries and often involves the proximal anterior cerebral artery, the circle of Willis is unable to provide collateral flow. Matsushima and Inaba have described three collateral pathways: (1) leptomeningeal collaterals from the posterior cerebral artery to the distal middle cerebral and anterior cerebral artery; (2) dilated penetrating arteries between the distal internal carotid artery, the proximal anterior cerebral artery, the middle cerebral artery, and the choroidal system; and (3) transdural collateral from the external carotid system to the intracranial carotid system (132).

Cerebral blood flow may be normal or decreased depending on the adequacy of collaterals. Patients with symptomatic moyamoya have decreased vasoreactivity in response to hypercarbia or acetazolamide consistent with exhausted reserve or maximal dilation of the autoregulatory arterioles (186; 62; 178). PET and SPECT scanning have demonstrated similar findings (183; 59; 144).

Electroencephalography may be useful in the evaluation of these patients. Typically, there is a normal to slow background. Focal slow activity may be noted. With hyperventilation there may be bursts of high-amplitude delta. Following cessation of hyperventilation, the delta activity can resolve and spontaneously recur. Suzuki has referred to this as the "re-build up phenomenon." This appears to be much more frequent in advanced cases and in children (90; 106). The utility of EEG as an adjunctive diagnostic and follow-up modality to assess hemodynamic status was shown in a study of 127 patients where 80% showed abnormal EEG findings before revascularization surgery. The typical rebuild-up phenomenon was observed in 65%, and localized build-up in 25%, without any significant clinical ischemic events during and after hyperventilation. Rebuild-up was more frequent in individuals younger than 13 years or with advanced disease, and its location correlated with SPECT and perfusion-MRI abnormalities. Persistent rebuild-up in postoperative follow-up was associated with poorer clinical outcomes (23).

The 2023 European Stroke Organisation (ESO) Guidelines on moyamoya angiopathy state that all patients should perform hemodynamic assessment during the diagnostic workup to help decision-making. The preferred method of assessment (CT, MRI, SPECT, PET, or ultrasound) should be the most familiar and available depending on individual institutions. The guideline also recommends assessment of posterior circulation involvement, especially in children below five years of age, to identify patients at higher risk of stroke and cognitive impairment (14).

Although some may suggest RNF213 polymorphism screening to evaluate patients younger than 18 years old with ischemic moyamoya disease for early detection and treatment (66), the European guidelines do not recommend systematic variant screening of RNF213 (14).

Management

Guidelines on the management of moyamoya disease have been published (34; 173; 14). Because ischemic stroke is common and can occur from emboli as well as thrombus formation, antiplatelet (aspirin) therapy is considered beneficial (168; 160; 14). A meta-analysis with 16,186 patients showed that antiplatelet therapy was associated with a reduced risk of hemorrhagic stroke but did not reduce the risk of ischemic stroke or decrease morbidity (121). Another meta-analysis evaluating 28,925 patients with moyamoya disease showed that antiplatelets reduced mortality in hemorrhagic cases and reduced stroke risk during follow-up (125). Warfarin is contraindicated because of the risk for spontaneous bleeding from abnormal moyamoya vessels. Indeed, multicenter data from the International Pediatric Stroke Study Group show that patients with moyamoya disease are typically treated with antiplatelet agents rather than warfarin (41). However, some patients with associated hypercoagulable states such as factor V Leiden mutation can be treated with warfarin to prevent arterial thrombosis (64). Steroids have been successfully used in a few cases of movement disorders (155). Anecdotal reports have suggested benefit with calcium channel blockers (133; 54). However, none of the medications can reverse or slow disease progression. In the acute setting, intravenous thrombolysis and intraarterial thrombectomy have been reported; however, the evidence concerning safety and efficacy remains insufficient (92). In a meta-summary of 10 case reports, all patients treated with thrombolysis and/or thrombectomy survived, and some experienced symptomatic and/or functional improvement. No patient experienced symptomatic intracranial hemorrhage (92).

Historically, there has been ambiguity about the choice of surgical procedure, its timing, and long-term benefit (159; 168; 197). Literature accumulated over the past few years indicates that early surgical revascularization procedures result in improved intellectual outcome (109) and a significantly lower risk for recurrent subsequent strokes and transient ischemic attacks (85; 170). Analysis of surgical revascularization procedures in 329 consecutive patients (233 adults, 96 children) from Stanford University, showed that the cumulative risk for perioperative or subsequent stroke or death over five years was low (5.5%), and the cohort had a significant improvement in the quality of life (43). Similarly encouraging results have been documented in a study of 43 adult patients treated with the EDAS procedure at Columbia University (174). Careful patient selection using techniques, such as positron emission tomography (214), perfusion-CT with acetazolamide challenge (07), or BOLD-MRI (52), which help to assess the risk for cerebral ischemia, may further improve outcomes after surgery. Acute stroke in the preoperative period and reduced cerebrovascular reserve are associated with poor surgical outcome (08). Surgical revascularization, including direct, indirect, and a combination of both, was shown to significantly reduce rebleeding, ischemic events, and mortality in hemorrhagic moyamoya disease (211). The European guideline suggest that revascularization surgery be considered in patients with ischemic presentation in case of clinical symptoms or hemodynamic impairment on neuroimaging. In adult asymptomatic patients, the treatment of choice is conservative except in patients with both cerebral hemodynamic impairment and silent ischemic lesions in the same brain region (14).

A number of surgical interventions have been designed to improve collateral flow to the cortical surface using the external carotid circulation as a donor supply, including extracranial to intracranial anastomoses and superficial temporal artery to middle cerebral artery bypass. Several techniques that do not require direct anastomoses have been developed and involve placement of the extracranial arteries on the cortical brain surface (pial synangiosis). These techniques rely on the spontaneous development of collateral connections due to the particularly high levels of endogenous growth factors in patients with moyamoya. Encephalomyosynangiosis (EMS) involves placement of the temporalis muscle directly onto the brain surface. Encephalo-duro-angio-synangiosis (EDAS) involves the attachment of scalp artery in a strip of galea that is freed from the pericranium and fascia. A linear dural slit is made to allow suturing of the galea to the dura, and the artery and galea are laid on the arachnid membrane. In encephalo-arterio-synangiosis, the superficial temporal artery is stripped along its course, and the artery with the strip of galea is laid on the arachnoid membrane. Encephalo-duro-arterio-myo-synangiosis involves a combination of the above techniques (88; 208). These procedures are sometimes done in combination with a superficial temporal artery to middle cerebral artery bypass. Angiography following these indirect revascularization procedures demonstrates anastomoses that can be detected as early as two weeks after surgery but are usually seen by three months postoperatively. Perfusion MRI and arterial spin-labeled MRI have been used to evaluate the adequacy of collateral development (15). Guidelines issued by the American Heart Association Stroke Council recommend indirect revascularization techniques for younger children, whose small caliber vessels make direct anastomosis difficult, and direct bypass techniques in older individuals (160). The European guideline suggests direct/combined revascularization in adults and combined revascularization whenever technically possible instead of indirect strategies in pediatric patients (14). A meta-analysis with 2460 pediatric moyamoya patients showed that indirect, direct, and combined bypasses were relatively effective and safe, although direct and combined methods were associated with better long-term revascularization outcomes that did not translate into better stroke and mortality rates (112). Indications for surgery include progressive ischemic symptoms or evidence for tissue “at risk” for ischemia, eg, poor cerebrovascular reserve (07; 27). Early surgical intervention (eg, encephalo-duro-arterio-synangiosis) before the establishment of irreversible hemodynamic change has shown benefit in preventing stroke in children and adults, as well as in delaying cognitive decline and improving performance in activities of daily living (44; 43; 82; 212). In adults, surgical revascularization procedures have been shown to improve cerebral metabolism and hemodynamics, clinical function, cognition, and prevent strokes (24; 29; 107; 139; 15; 115; 165). Metanalyses have indicated a superiority of direct and combined bypasses on future stroke risk as compared to indirect bypass (65; 117; 148). Another metanalysis showed a lower rate of long-term hemorrhages in patients with direct bypass as compared to indirect bypass, despite a higher rate of perioperative hemorrhage (175). Clinical trials are needed to indicate which method is superior. Revascularization surgery also appears effective in reducing stroke risk in addition to medial therapy in patients with sickle cell disease and moyamoya syndrome (06). A large single-center study evaluating 769 patients submitted to bypass surgery (1118 direct bypasses, 132 indirect bypasses) showed a major stroke rate of 4.2% per-bypass-procedure (6.8% per patient) 30 days after the procedure and a 0.6% per-patient-year long-term stroke risk (188).

Kashiwazaki and colleagues have suggested a score entitled the Berlin Grading System based on MRI, DSA, and SPECT imaging for stratification of clinical severity and prediction of postoperative neurologic morbidity and new ischemic lesions on MRI (74; 189). A meta-analysis evaluating 22 studies identified high-risk patients for postoperative ischemic stroke. Among pediatric patients, age less than three years was a risk factor for stroke, whereas among adults, diabetes, a Suzuki grade greater than 3, mean intraoperative systolic blood pressure, mean intraoperative diastolic blood pressure, and revascularization in the left hemisphere were risk factors (157). Aspirin may be indicated after revascularization, as it showed a trend to less mid- and long-term strokes postoperatively (213; 157). The European guideline indicates that continuation of antiplatelet treatment as monotherapy during bypass surgery (aspirin) is safe. In case of discontinuation, the suggestion is to restart antiplatelet therapy 1 to 7 days after surgery, depending on the post-surgery CT scan. In case of dual antiplatelet therapy, the suggestion is to stop clopidogrel, or the other second antiplatelet therapy, for seven days before surgery (14).

The treatment of aneurysms associated with moyamoya disease is still a matter of debate. Endovascular treatment with coils or liquid embolic agents has shown good results in selected cases (56); however, the use of open microsurgery in these patients is challenging (111). Revascularization surgery seems to indirectly treat peripheral intracranial aneurysms (111). A systematic review evaluating 72 patients with ruptured choroidal collateral system aneurysms showed that conservative treatment was associated with a high bleeding recurrence rate (40%). Endovascular treatment was mainly performed with parent vessel sacrifice, and although it appeared to be safe, rates of treatment failure reached 21% due to inadequate access. Open surgery was effective but with a high complication rate (25%). These results favored aneurysm treatment over conservative management (198).

Special considerations

Pregnancy

Several case reports describe the occurrence of strokes (usually hemorrhagic strokes) around the time of pregnancy (94; 199; 146; 86). At least three studies have shown a relatively low risk of complications (mostly transient ischemic attacks or seizures with full recovery) during pregnancy and delivery (35; 67; 31). Vaginal delivery appears safe (184). In a Chinese study, the risk of hemorrhagic stroke was approximately three percent during pregnancy or puerperium, which was not significantly different from the risk in nonpregnant women (122). Care should be taken to avoid hypocapnia, hypotension, or hypertension. A study showed high rates of hypertensive disorders of pregnancy (19.2%), many of them requiring and emergency cesarean sections (10). Whether cesarean section lowers the risk for complications is unknown (94). A combined spinal and epidural technique has been advocated because it allows better analgesia than epidural anesthesia and more hemodynamic stability than either general or spinal anesthesia (01). Spinal anesthesia has been associated with lower mean arterial pressure during cesarean delivery and better control of postoperative pain in moyamoya patients (81).

Anesthesia

Anesthetic risks for moyamoya are particularly high for any surgical procedure, and anesthesia can precipitate symptoms for the first time. Hyperventilation should be avoided because this may decrease cerebral blood flow secondary to cerebral vasoconstriction. Carbon dioxide levels should be normal to slightly elevated during anesthesia. Normovolemia should be maintained and blood pressure controlled carefully so as to avoid hypotension and hypertension. Intraoperative EEG may be helpful. Intravenous anesthesia may be superior to inhalational anesthesia secondary to decreased intracerebral steal (167). However, a retrospective analysis of 72 moyamoya patients undergoing surgical revascularization showed that there was no significant difference in the incidence of postoperative complications occurring within two weeks with use of either intravenous or inhalation anesthesia (03).

References

01: Abouleish E, Wiggins M, Ali V. Combined spinal and epidural anesthesia for cesarean section in a parturient with moyamoya disease. Acta Anaesthesiol Scand 1998;42:1120-3. PMID 9809100
02: Achrol AS, Guzman R, Lee M, Steinberg GK. Pathophysiology and genetic factors in moyamoya disease. Neurosurg Focus 2009;26(4):E4. PMID 19335130
03: Adachi K, Yamamoto Y, Kameyama E, Suzuki H, Horinouchi T. Early postoperative complications in patients with Moyamoya disease--a comparison of inhaled anesthesia with total intravenous anesthesia (TIVA). Masui 2005;54:653-7. PMID 15966384
04: Ahn SH, Lee J, Kim YJ, et al. Isolated MCA disease in patients without significant atherosclerotic risk factors: a high-resolution magnetic resonance imaging study. Stroke 2015;46(3):697-703. PMID 25628303
05: Akiyama Y, Mikami T, Mikuni N. Deep learning-based approach for the diagnosis of Moyamoya disease. J Stroke Cerebrovasc Dis 2020;29(12):105322. PMID 32992181
06: Aldana PR, Hanel RA, Piatt J, et al. Cerebral revascularization surgery reduces cerebrovascular events in children with sickle cell disease and moyamoya syndrome: Results of the stroke in sickle cell revascularization surgery retrospective study. Pediatr Blood Cancer 2023;70(7):e30336. PMID 37057741
07: Andaluz N, Choutka O, Vagal A, Strunk R, Zuccarello M. Patient selection for revascularization procedures in adult Moyamoya disease based on dynamic perfusion computerized tomography with acetazolamide challenge (PCTA). Neurosurg Rev 2010;33(2):225-32; discussion 232-3. PMID 20140634
08: Antonucci MU, Burns TC, Pulling TM, et al. Acute preoperative infarcts and poor cerebrovascular reserve are independent risk factors for severe ischemic complications following direct extracranial-intracranial bypass for moyamoya disease. AJNR Am J Neuroradiol 2016;37(2):228-35. PMID 26564435
09: Aoki N. Cerebrovascular bypass surgery for the treatment of moyamoya disease: unsatisfactory outcome in the patients presenting with intracranial hemorrhage. Surg Neurol 1993;40:372-7. PMID 8211652
10: Aoyama J, Nariai T, Moriyama K, et al. Clinical characteristics of the pregnancies and deliveries of patients with moyamoya disease: a single-center analysis over three decades. Int J Stroke 2020;16(5):526-33. PMID 33040699
11: Baba T, Houkin K, Kuroda S. Novel epidemiological features of moyamoya disease. J Neurol Neurosurg Psychiatry 2008;79(8):900-4. PMID 18077479
12: Bakri SJ, Siker D, Masaryk T, Luciano MG, Traboulsi EI. Ocular malformations, moyamoya disease, and midline cranial defects: a distinct syndrome. Am J Ophthalmol 1999;127:356-7. PMID 10088755
13: Bang OY, Ryoo S, Kim SJ, et al. Adult moyamoya disease: a burden of intracranial stenosis in east Asians? PLoS One 2015;10(6):e0130663. PMID 26125557
14: Bersano A, Khan N, Fuentes B, et al. European Stroke Organisation (ESO) Guidelines on Moyamoya angiopathy endorsed by Vascular European Reference Network (VASCERN). Eur Stroke J 2023;8(1):55-84. PMID 37021176
15: Blauwblomme T, Lemaitre H, Naggara O, et al. Cerebral blood flow improvement after indirect revascularization for pediatric moyamoya disease: a statistical analysis of arterial spin-labeling MRI. AJNR Am J Neuroradiol 2016;37(4):706-12. PMID 26585258
16: Bonduel M, Hepner M, Sciuccati G, Torres AF, Tenembaum S. Prothrombotic disorders in children with moyamoya syndrome. Stroke 2001;32(8):1786-92. PMID 11486106
17: Bower RS, Mallory GW, Nwojo M, Kudva YC, Flemming KD, Meyer FB. Moyamoya disease in a primarily white, midwestern US population: increased prevalence of autoimmune disease. Stroke 2013;44(7):1997-9. PMID 23652271
18: Braun KP, Bulder MM, Chabrier S, et al. The course and outcome of unilateral intracranial arteriopathy in 79 children with ischaemic stroke. Brain 2009;132(Pt 2):544-57. PMID 19039009
19: Brodsky MC, Parsa CF. The moyamoya optic disc. JAMA Ophthalmol 2015;133(2):164. PMID 25521249
20: Brosius SN, Vossough A, Fisher MJ, et al. Characteristics of Moyamoya syndrome in pediatric patients with neurofibromatosis type 1. Pediatr Neurol 2022;134:85-92. PMID 35849956
21: Cao J, Xing Z, Dai L, et al. Potential predictors for progression of moyamoya disease: A systematic review and meta-analysis. Front Neurol 2023;14:1128338. PMID 36937514
22: Chiu D, Shedden P, Bratina P, Grotta JC. Clinical features of moyamoya disease in the United States. Stroke 1998;29:1347-51. PMID 9660385
23: Cho A, Chae JH, Kim HM, et al. Electroencephalography in pediatric moyamoya disease: reappraisal of clinical value. Childs Nerv Syst 2014a;30(3):449-59. PMID 23943190
24: Cho WS, Kim JE, Kim CH, et al. Long-term outcomes after combined revascularization surgery in adult moyamoya disease. Stroke 2014b;45(10):3025-31. PMID 25184359
25: Choi HY, Lee JE, Jung YH, Cho HJ, Kim DJ, Heo JH. Progression of isolated middle cerebral artery stenosis into moyamoya disease. Neurology 2007;68(12):954. PMID 17372134
26: Chung SJ, Lee HS, Yoo HS, et al. A case of isolated middle cerebral artery stenosis with hemichorea and moyamoya pattern collateralization. J Mov Disord 2013;6(1):13-6. PMID 24868419
27: Conklin J, Fierstra J, Crawley AP, et al. Impaired cerebrovascular reactivity with steal phenomenon is associated with increased diffusion in white matter of patients with Moyamoya disease. Stroke 2010;41(8):1610-6. PMID 20576954
28: Das AS, Lerner DP, Mason XL, et al. Clinical reasoning: Moyamoya disease masquerading as acute refractory cerebral vasospasm. Neurology 2018;91(6):e594-8. PMID 30082446
29: Derdeyn CP. Direct bypass reduces the risk of recurrent hemorrhage in moyamoya syndrome, but effect on functional outcome is less certain. Stroke 2014;45(5):1245-6. PMID 24668205
30: Elkatatny A, Ismail M, Ibrahim KMM, Aly MH, Fouda MA. The incidence of radiation-induced moyamoya among pediatric brain tumor patients who received photon radiation versus those who received proton beam therapy: a systematic review. Neurosurg Rev 2023;46(1):146. PMID 37354243
31: Fluss R, Ligas BA, Chan AW, et al. Moyamoya-related stroke risk during pregnancy: an evidence-based reappraisal. World Neurosurg 2019;129:e582-5. PMID 31176061
32: Fujimura M, Watanabe M, Narisawa A, Shimizu H, Tominaga T. Increased expression of serum matrix metalloproteinase-9 in patients with moyamoya disease. Surg Neurol 2009;72(5):476-80; discussion 80. PMID 19147196
33: Fujisawa I, Asato R, Nishimura K, et al. Moyamoya disease: MR imaging. Radiology 1987;164:103-5. PMID 3588894
34: Fukui M. Guidelines for the diagnosis and treatment of spontaneous occlusion of the circle of Willis ('moyamoya' disease). Research Committee on Spontaneous Occlusion of the Circle of Willis (Moyamoya Disease) of the Ministry of Health and Welfare, Japan. Clin Neurol Neurosurg 1997;99(Suppl 2):S238-40. PMID 9409446
35: Fukushima K, Yumoto Y, Kondo Y, et al. A retrospective chart review of the perinatal period in 22 pregnancies of 16 women with Moyamoya disease. J Clin Neurosci 2012;19(10):1358-62. PMID 22917762
36: Fullerton HJ, Wintermark M, Hills NK, et al. Risk of recurrent arterial ischemic stroke in childhood: a prospective international study. Stroke 2016;47(1):53-9. PMID 26556824
37: Funaki T, Takahashi JC, Yoshida K, et al. Periventricular anastomosis in moyamoya disease: detecting fragile collateral vessels with MR angiography. J Neurosurg 2016;124(6):1766-72. PMID 26613176
38: Furuse S, Matsumoto S, Tanaka Y, et al. Moyamoya disease associated with a false aneurysm: case report and review of the literature. No Shinkei Geka 1982;10:1005-12. PMID 7177326
39: Gatti JR, Sun LR. Nonischemic presentations of pediatric moyamoya arteriopathy: a natural history study. Stroke 2022;53(6):e219-20. PMID 35502663
40: Ge P, Zhang Q, Ye X, et al. Modifiable risk factors associated with Moyamoya disease: a case-control study. Stroke 2020;51(8):2472-9. PMID 32640948
41: Goldenberg NA, Bernard TJ, Fullerton HJ, Gordon A, deVeber G. Antithrombotic treatments, outcomes, and prognostic factors in acute childhood-onset arterial ischaemic stroke: a multicentre, observational, cohort study. Lancet Neurol 2009;8(12):1120-7. PMID 19801204
42: Guo DC, Papke CL, Tran-Fadulu V, et al. Mutations in smooth muscle alpha-actin (ACTA2) cause coronary artery disease, stroke, and Moyamoya disease, along with thoracic aortic disease. Am J Hum Genet 2009;84(5):617-27. PMID 19409525
43: Guzman R, Lee M, Achrol A, et al. Clinical outcome after 450 revascularization procedures for moyamoya disease clinical article. J Neurosurg 2009;111(5):927-35. PMID 19463046
44: Hallemeier CL, Rick KM, Grubb RL Jr, et al. Clinical features and outcome in North American adults with moyamoya phenomenon. Stroke 2006;37:1490-6. PMID 16645133
45: Hamada J, Hashimoto N, Tsukahara T. Moyamoya disease with repeated intraventricular hemorrhage due to aneurysm rupture. Report of two cases. J Neurosurg 1994;80:328-31. PMID 8283274
46: Han C, Feng H, Han YQ, et al. Prospective screening of family members with moyamoya disease patients. PLoS One 2014;9(2):e88765. PMID 24586386
47: Han DH, Kwon OK, Byun BJ, et al. A co-operative study: clinical characteristics of 334 Korean patients with moyamoya disease treated at neurosurgical institutes (1976-1994). The Korean Society for Cerebrovascular Disease. Acta Neurochir (Wien) 2000;142(11):1263-73. PMID 11201642
48: Harada A, Fujii Y, Yoneoka Y, Takeuchi S, Tanaka R, Nakada T. High-field magnetic resonance imaging in patients with moyamoya disease. J Neurosurg 2001;94(2):233-7. PMID 11213959
49: He S, Duan R, Liu Z, et al. Characteristics of cognitive impairment in adult asymptomatic moyamoya disease. BMC Neurol 2020;20(1):322. PMID 32867701
50: He S, Liu Z, Wei Y, et al. Impairments in brain perfusion, executive control network, topological characteristics, and neurocognition in adult patients with asymptomatic Moyamoya disease. BMC Neurosci 2021;22(1):35. PMID 33980154
51: Herve D, Touraine P, Verloes A, et al. A hereditary moyamoya syndrome with multisystemic manifestations. Neurology 2010;75(3):259-64. PMID 20644152
52: Heyn C, Poublanc J, Crawley A, et al. Quantification of cerebrovascular reactivity by blood oxygen level-dependent MR imaging and correlation with conventional angiography in patients with moyamoya disease. AJNR Am J Neuroradiol 2010;31(5):862-7. PMID 20075092
53: Hojo M, Hoshimaru M, Miyamoto S, et al. Role of transforming growth factor-beta1 in the pathogenesis of moyamoya disease. J Neurosurg 1998;89:623-9. PMID 9761057
54: Hosain SA, Hughes JT, Forem SL, Wisoff J, Fish I. Use of a calcium channel blocker (nicardipine HCl) in the treatment of childhood moyamoya disease. J Child Neurol 1994;9:378-80. PMID 7822727
55: Hoshimaru M, Takahashi JA, Kikuchi H, Nagata I, Hatanaka M. Possible roles of basic fibroblast growth factor in the pathogenesis of moyamoya disease: an immunohistochemical study. J Neurosurg 1991;75:267-70. PMID 2072165
56: Hou K, Li G, Luan T, Xu K, Yu J. The prospects and pitfalls in the endovascular treatment of moyamoya disease-associated intracranial aneurysms. Neurosurg Rev 2021;44(1):261-71. PMID 32052219
57: Hsu SW, Chaloupka JC, Fattal D. Rapidly progressive fatal bihemispheric infarction secondary to Moyamoya syndrome in association with Graves thyrotoxicosis. AJNR Am J Neuroradiol 2006;27:643-7. PMID 16552009
58: 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 1999;64:533-7. PMID 9973290
59: Ikezaki K, Matsushima T, Kuwabara Y, Suzuki SO, Nomura T, Fukui M. Cerebral circulation and oxygen metabolism in childhood moyamoya disease: a perioperative positron emission tomography study. J Neurosurg 1994;81:843-50. PMID 7965114
60: Im SH, Oh CW, Kwon OK, Kin JE, Han DH. Moyamoya disease associated with Graves disease: special considerations regarding clinical significance and management. J Neurosurg 2005;102:1013-7. PMID 16028759
61: Inoue TK, Ikezaki K, Sasazuki T, Matsushima T, Fukui M. Linkage analysis of moyamoya disease on chromosome 6. J Child Neurol 2000;15(3):179-82. PMID 10757474
62: Inoue Y, Momose T, Machida K, Honda N, Tsutsumi K. Cerebral vasodilatory capacity mapping using technetium-99m-DTPA-HSA SPECT and acetazolamide in moyamoya disease. J Nucl Med 1993;34:1984-6. PMID 8229245
63: Izawa M, Sentoh S. A case of cerebrovascular moyamoya disease associated with basilar aneurysm. Neurol Surg 1981;9:365-70.
64: Jabbour R, Taher A, Shamseddine A, Atweh SF. Moyamoya syndrome with intraventricular hemorrhage in an adult with factor v leiden mutation. Arch Neurol 2005;62:1144-6. PMID 16009774
65: Jeon JP, Kim JE, Cho WS, Bang JS, Son YJ, Oh CW. Meta-analysis of the surgical outcomes of symptomatic moyamoya disease in adults. J Neurosurg 2018;128(3):793-9. PMID 28474994
66: Jiang X, Liu L, Sijin A, et al. Meta-analysis of the association between RNF213 polymorphisms and clinical features of moyamoya disease in Asian population. Clin Neurol Neurosurg 2023;231:107801. PMID 37267801
67: Jung YJ, Kim MA, Kwon JY, et al. Pregnancy outcomes in women with moyamoya disease: experiences at a single center in Korea. Yonsei Med J 2015;56(3):793-7. PMID 25837187
68: Kamada F, Aoki Y, Narisawa A, et al. A genome-wide association study identifies RNF213 as the first Moyamoya disease gene. J Hum Genet 2011;56(1):34-40. PMID 21048783
69: Kang HS, Kim SK, Cho BK, Kim YY, Hwang YS, Wang KC. Single nucleotide polymorphisms of tissue inhibitor of metalloproteinase genes in familial moyamoya disease. Neurosurgery 2006;58:1074-80. PMID 16723886
70: Kang HS, Kim JH, Phi JH, et al. Plasma matrix metalloproteinases, cytokines, and angiogenic factors in moyamoya disease. J Neurol Neurosurg Psychiatry 2010;81(6):673-8. PMID 19965844
71: Kang S, Liu X, Zhang D, et al. Natural course of Moyamoya disease in patients with prior hemorrhagic stroke. Stroke 2019;50(5):1060-6. PMID 30909836
72: Karasawa J, Touho H, Ohnishi H, Miyamoto S, Kikuchi H. Long-term follow-up study after extracranial-intracranial bypass surgery for anterior circulation ischemia in childhood moyamoya disease. J Neurosurg 1992;77:84-9. PMID 1607976
73: Karzmark P, Zeifert PD, Tan S, Dorfman LJ, Bell-Stephens TE, Steinberg GK. Effect of moyamoya disease on neuropsychological functioning in adults. Neurosurgery 2008;62(5):1048-52. PMID 18580802
74: Kashiwazaki D, Akioka N, Kuwayama N, et al. Berlin Grading System can stratify the onset and predict perioperative complications in adult moyamoya disease. Neurosurgery 2017;81(6):986-91. PMID 28605471
75: Kawashima M, Noguchi T, Takase Y, Nakahara Y, Matsushima T. Decrease in leptomeningeal ivy sign on fluid-attenuated inversion recovery images after cerebral revascularization in patients with Moyamoya disease. AJNR Am J Neuroradiol 2010;31(9):1713-8. PMID 20466798
76: Kawashima M, Noguchi T, Takase Y, Ootsuka T, Kido N, Matsushima T. Unilateral hemispheric proliferation of ivy sign on fluid-attenuated inversion recovery images in moyamoya disease correlates highly with ipsilateral hemispheric decrease of cerebrovascular reserve. AJNR Am J Neuroradiol 2009;30(9):1709-16. PMID 19713323
77: Kikuchi M, Asato M, Sugahara S, et al. Evaluation of surgically formed collateral circulation in moyamoya disease with 3D-CT angiography: comparison with MR angiography and X-ray angiography. Neuropediatrics 1996;27:45-9. PMID 8677026
78: Kikuta K, Takagi Y, Nozaki K, et al. Asymptomatic microbleeds in moyamoya disease: T2-weighted gradient-echo magnetic resonance imaging study. J Neurosurg 2005;102:470-5. PMID 15796381
79: Kikuta K, Takagi Y, Nozaki K, Sawamoto N, Fukuyama H, Hashimoto N. The presence of multiple microbleeds as a predictor of subsequent cerebral hemorrhage in patients with moyamoya disease. Neurosurgery 2008;62(1):104-11, discussion 111-2. PMID 18300897
80: Kim EH, Yum MS, Ra YS, et al. Importance of RNF213 polymorphism on clinical features and long-term outcome in moyamoya disease. J Neurosurg 2016;124(5):1221-7. PMID 26430847
81: Kim HJ, Choi SH, Kwon H, et al. Spinal versus general anesthesia for cesarean delivery in pregnant women with Moyamoya disease: a retrospective observational study. Anesth Analg 2022;135(3):617-24. PMID 35089266
82: Kim SK, Cho BK, Phi JH, et al. Pediatric moyamoya disease: An analysis of 410 consecutive cases. Ann Neurol 2010a;68(1):92-101. PMID 20582955
83: Kim SJ, Heo KG, Shin HY, et al. Association of thyroid autoantibodies with moyamoya-type cerebrovascular disease: a prospective study. Stroke 2010b;41(1):173-6. PMID 19926842
84: Kim JM, Lee SH, Roh JK. Changing ischemic lesion patterns in adult moyamoya disease. J Neurol Neurosurg Psychiatry 2009;80(1):36-40. PMID 18450791
85: Kim SK, Seol HJ, Cho BK, Hwang YS, Lee DS, Wang KC. Moyamoya disease among young patients: its aggressive clinical course and the role of active surgical treatment. Neurosurgery 2004a;54(4):840-4; discussion 844-6. PMID 15046649
86: Kim TS, Lee JH, Kim IY, et al. Moyamoya disease with repeated intracranial haemorrhage in two consecutive pregnancies. J Clin Neurosci 2004b;11(5):525-7. PMID 15177400
87: Kim YJ, Lee DH, Kwon JY, et al. High resolution MRI difference between moyamoya disease and intracranial atherosclerosis. Eur J Neurol 2013;20(9):1311-8. PMID 23789981
88: Kinugasa K, Mandai S, Kamata I, Sugiu K, Ohmoto T. Surgical treatment of moyamoya disease: operative technique for encephalo-duro-arterio-myo-synangiosis, its follow-up, clinical results, and angiograms. Neurosurgery 1993;32:527-31. PMID 8474642
89: Kobayashi E, Saeki N, Oishi H, Hirai S, Yamaura A. Long-term natural history of hemorrhagic moyamoya disease in 42 patients. J Neurosurg 2000;93(6):976-80. PMID 11117870
90: Kodama N, Aoki Y, Hiraga H, Wada T, Suzuki J. Electroencephalographic findings in children with moyamoya disease. Arch Neurol 1979;36:16-9. PMID 420596
91: Kodama N, Suzuki J. Moyamoya disease associated with aneurysm. J Neurosurg 1978;48:565-9. PMID 632880
92: Koh MY, Toh KZ, Ho JS, et al. Intravenous thrombolysis and endovascular thrombectomy for acute ischaemic stroke in patients with Moyamoya disease - a systematic review and meta-summary of case reports. J Thromb Thrombolysis 2022;54(2):339-49. PMID 35699873
93: Komiyama M, Nakajima H, Nishikawa M, Yasui T, Kitano S, Sakamoto H. Leptomeningeal contrast enhancement in moyamoya: its potential role in postoperative assessment of circulation through the bypass. Neuroradiology 2001;43(1):17-23. PMID 11214642
94: Komiyama M, Yasui T, Kitano S, Sakamoto H, Fujitani K, Matsuo S. Moyamoya disease and pregnancy: case report and review of the literature. Neurosurgery 1998;43(2):360-9. PMID 9696092
95: Konishi Y, Kadowaki C, Hara M, Takeuchi K. Aneurysms associated with moyamoya disease. Neurosurg 1985;16:484-91. PMID 3990927
96: Kraemer M, Berlit P. Primary central nervous system vasculitis and moyamoya disease: similarities and differences. J Neurol 2010;257(5):816-9. PMID 20037765
97: Kraemer M, Heienbrok W, Berlit P. Moyamoya disease in Europeans. Stroke 2008;39(12):3193-200. PMID 18787200
98: Krishnan C, Roy A, Traboulsi E. Morning glory disk anomaly, choroidal coloboma, and congenital constrictive malformations of the internal carotid arteries (moyamoya disease). Ophthalmic Genet 2000;21(1):21-4. PMID 10779846
99: Kudo T. A disease with abnormal intracranial vascular networks. Spontaneous occlusion of the circle of Willis. Tokyo: Igaku Shoin, 1967.
100: Kudo T. Spontaneous occlusion of the circle of Willis. A disease apparently confined to the Japanese. Neurology 1968;18:485-96. PMID 5691175
101: Kuriyama S, Kusaka Y, Fujimura M, et al. Prevalence and clinicoepidemiological features of moyamoya disease in Japan: findings from a nationwide epidemiological survey. Stroke 2008;39(1):42-7. PMID 18048855
102: Kuroda S, AMORE Study Group. Asymptomatic moyamoya disease: literature review and ongoing AMORE study. Neurol Med Chir (Tokyo) 2015;55(3):194-8. PMID 25739434
103: Kuroda S, Fujimura M, Takahashi J, et al. Diagnostic criteria for Moyamoya disease - 2021 revised version. Neurol Med Chir (Tokyo) 2022;62(7):307-12. PMID 35613882
104: Kuroda S, Hashimoto N, Yoshimoto T, Iwasaki Y; Research Committee on Moyamoya Disease in Japan. Radiological findings, clinical course, and outcome in asymptomatic moyamoya disease: results of multicenter survey in Japan. Stroke 2007;38(5):1430-5. PMID 17395863
105: Kuroda S, Houkin K. Moyamoya disease: current concepts and future perspectives. Lancet Neurol 2008;7(11):1056-66. PMID 18940695
106: Kurlemann G, Fahrendorf G, Krings W, Sciuk J, Palm D. Characteristic EEG findings in childhood moyamoya syndrome. Neurosurg Rev 1992;15:57-60. PMID 1584439
107: Kuroda S, Kashiwazaki D, Hirata K, Shiga T, Houkin K, Tamaki N. Effects of surgical revascularization on cerebral oxygen metabolism in patients with Moyamoya disease: an 15O-gas positron emission tomographic study. Stroke 2014;45(9):2717-21. PMID 25116870
108: Kuroda S, Kashiwazaki D, Ishikawa T, Nakayama N, Houkin K. Incidence, locations, and longitudinal course of silent microbleeds in moyamoya disease: a prospective T2-weighted MRI study. Stroke 2013;44(2):516-8. PMID 23223508
109: Kuroda S, Houkin K, Ishikawa T, et al. Determinants of intellectual outcome after surgical revascularization in pediatric moyamoya disease: a multivariate analysis. Childs Nerv Syst 2004;20:302-8. PMID 15045517
110: Kwak R, Kadoya S. Moyamoya disease associated with persistent trigeminal artery. Report of two cases. J Neurosurg 1983;59:166-71. PMID 6864274
111: Larson A, Rinaldo L, Brinjikji W, Meyer F, Lanzino G. Intracranial aneurysms in white patients with Moyamoya disease: A U.S. single-center case series and review. World Neurosurg 2020;138:e749-58. PMID 32201292
112: Lee KS, Zhang JJY, Bhate S, et al. Surgical revascularizations for pediatric moyamoya: a systematic review, meta-analysis, and meta-regression analysis. Childs Nerv Syst 2023;39(5):1225-43. PMID 36752913
113: Lee WJ, Jeong SK, Han KS, et al. Impact of endothelial shear stress on the bilateral progression of unilateral Moyamoya disease. Stroke 2020;51(3):775-83. PMID 31856692
114: Lee YS, Jung KH, Roh J. Diagnosis of moyamoya disease with transcranial Doppler sonography: correlation study with magnetic resonance angiography. J Neuroimaging 2004;4:319-23. PMID 15358951
115: Lei Y, Li YJ, Guo QH, et al. Postoperative executive function in adult moyamoya disease: a preliminary study of its functional anatomy and behavioral correlates. J Neurosurg 2017;126(2):527-36. PMID 27058195
116: Lenhart PD, Lambert SR, Newman NJ, et al. Intracranial vascular anomalies in patients with morning glory disk anomaly. Am J Ophthalmol 2006;142(4):644-50. PMID 17011858
117: Li Q, Gao Y, Xin W, et al. Meta-analysis of prognosis of different treatments for symptomatic Moyamoya disease. World Neurosurg 2019;127:354-61. PMID 30995556
118: Li H, Zhang ZS, Dong ZN, et al. Increased thyroid function and elevated thyroid autoantibodies in pediatric patients with moyamoya disease: a case-control study. Stroke 2011;42(4):1138-9. PMID 21350209
119: Li H, Zhang ZS, Liu W, et al. Association of a functional polymorphism in the MMP-3 gene with Moyamoya Disease in the Chinese Han population. Cerebrovasc Dis 2010;30(6):618-25. PMID 20948207
120: Lim M, Cheshier S, Steinberg GK. New vessel formation in the central nervous system during tumor growth, vascular malformations, and Moyamoya. Curr Neurovasc Res 2006;3:237-45. PMID 16918387
121: Liu T, Qin M, Xiong X, et al. Benefits and risks of antiplatelet therapy for moyamoya disease: a systematic review and meta-analysis. Front Neurol 2023;14:1132339. PMID 37409015
122: Liu XJ, Zhang D, Wang S, et al. Intracranial hemorrhage from moyamoya disease during pregnancy and puerperium. Int J Gynaecol Obstet 2014;125(2):150-3. PMID 24552854
123: Liu ZW, Han C, Zhao F, et al. Collateral circulation in Moyamoya disease: a new grading system. Stroke 2019;50(10):2708-15. PMID 31409266
124: Lu M, Zhang H, Liu S, et al. Long-term outcomes of moyamoya disease versus atherosclerosis-associated moyamoya vasculopathy using high-resolution MR vessel wall imaging. J Neurol Neurosurg Psychiatry 2023;94(7):567-74. PMID 36868848
125: Luo Y, Cao Z, Ye H, Wu S, Sun X. Antiplatelet therapy may improve the prognosis of patients with moyamoya disease: a 12-year retrospective study. J Neurol 2023;270(8):3876-84. PMID 37106259
126: Lyoo CH, Kim DJ, Chang H, Lee MS. Moyamoya disease presenting with paroxysmal exercise-induced dyskinesia. Parkinsonism Relat Disord 2007;13(7):446-8. PMID 16952479
127: Lyoo CH, Oh SH, Joo JY, Chung TS, Lee MS. Hemidystonia and hemichoreoathetosis as an initial manifestation of moyamoya disease. Arch Neurol 2000;57:1510-2. PMID 11030805
128: Maki Y, Nakata Y. Autopsy of a case with an analogous hemangioma of the internal carotid at the skull base. Brain Nerve (Tokyo) 1965;17:764.
129: Malek AM, Connors S, Robertson RL, Folkman J, Scott RM. Elevation of cerebrospinal fluid levels of basic fibroblast growth factor in moyamoya and central nervous system disorders. Pediatr Neurosurg 1997;27:182-9. PMID 9577971
130: Massaro M, Thorarensen O, Liu GT, Maguire AM, Zimmerman RA, Brodsky MC. Morning glory disc anomaly and moyamoya vessels. Arch Ophthalmol 1998;116:253-4. PMID 9488287
131: Masuda J, Ogata J, Yutani C. Smooth muscle cell proliferation and localization of macrophages and T cells in the occlusive major arteries in moyamoya disease. Stroke 1993;24:1960-7. PMID 7902623
132: Matsushima Y, Inaba Y. The specificity of the collaterals to the brain through the study and surgical treatment of moyamoya disease. Stroke 1986;17:117-22. PMID 3945975
133: McLean MJ, Gebarski SS, van der Spek AF, Goldstein GW. Treatment of acute deficits of moyamoya disease with verapamil. Ann Acad Med Singapore 1985;14:65-70. PMID 4004130
134: Miao W, Zhao PL, Zhang YS, et al. Epidemiological and clinical features of Moyamoya disease in Nanjing, China. Clin Neurol Neurosurg 2010;112(3):199-203. PMID 20004511
135: Milewicz DM, Kwartler CS, Papke CL, Regalado ES, Cao J, Reid AJ. Genetic variants promoting smooth muscle cell proliferation can result in diffuse and diverse vascular diseases: evidence for a hyperplastic vasculomyopathy. Genet Med 2010;12(4):196-203. PMID 20130469
136: Mineharu Y, Liu W, Inoue K, et al. Autosomal dominant moyamoya disease maps to chromosome 17q25.3. Neurology 2008;70:2357-63. PMID 18463369
137: Mineharu Y, Takenaka K, Yamakawa H, et al. Inheritance pattern of familial moyamoya disease: autosomal dominant mode and genomic imprinting. J Neurol Neurosurg Psychiatry 2006;77:1025-9. PMID 16788009
138: Miskinyte S, Butler MG, Herve D, et al. Loss of BRCC3 Deubiquitinating Enzyme Leads to Abnormal Angiogenesis and Is Associated with Syndromic Moyamoya. Am J Hum Genet 2011;88(6):718-28. PMID 21596366
139: Miyamoto S, Yoshimoto T, Hashimoto N, et al. Effects of extracranial-intracranial bypass for patients with hemorrhagic moyamoya disease: results of the Japan Adult Moyamoya Trial. Stroke 2014;45(5):1415-21. PMID 24668203
140: Miyawaki S, Imai H, Takayanagi S, Mukasa A, Nakatomi H, Saito N. Identification of a genetic variant common to moyamoya disease and intracranial major artery stenosis/occlusion. Stroke 2012;43(12):3371-4. PMID 23010677
141: Mori N, Miki Y, Kikuta K, et al. Microbleeds in moyamoya disease: susceptibility-weighted imaging versus T2-weighted imaging at 3 Tesla. Invest Radiol 2008;43(8):574-9. PMID 18648257
142: Mori N, Mugikura S, Higano S, et al. The leptomeningeal "ivy sign" on fluid-attenuated inversion recovery MR imaging in Moyamoya disease: a sign of decreased cerebral vascular reserve. AJNR Am J Neuroradiol 2009;30(5):930-5. PMID 19246527
143: Morioka M, Hamada J, Kawano T, et al. Angiographic dilatation and branch extension of the anterior choroidal and posterior communicating arteries are predictors of hemorrhage in adult moyamoya patients. Stroke 2003;34(1):90-5. PMID 12511756
144: Muroi C, Yonekawa Y, Khan N, Pangalu A, Keller E. Metabolic changes after H(2) 15O-positron emission tomography with acetazolamide in a patient with moyamoya disease: case report and review of previous cases. J Neurosurg Anesthesiol 2003;15(2):131-9. PMID 12657999
145: Nah HW, Kwon SU, Kang DW, Ahn JS, Kwun BD, Kim JS. Moyamoya disease-related versus primary intracerebral hemorrhage: [corrected] location and outcomes are different. Stroke 2012;43(7):1947-50. PMID 22693130
146: Nakai Y, Hyodo A, Yanaka K, Nose T. Fatal cerebral infarction after intraventricular hemorrhage in a pregnant patient with moyamoya disease. J Clin Neurosci 2002;9(4):456-8. PMID 12217680
147: Nanba R, Kuroda S, Ishikawa T, Houkin K, Iwasaki Y. Increased expression of hepatocyte growth factor in cerebrospinal fluid and intracranial artery in moyamoya disease. Stroke 2004;35:2837-42. PMID 15528455
148: Nguyen VN, Motiwala M, Elarjani T, et al. Direct, indirect, and combined extracranial-to-intracranial bypass for adult Moyamoya disease: an updated systematic review and meta-analysis. Stroke 2022;53(12):3572-82. PMID 36134563
149: Nishimoto A, Takeuchi S. Abnormal cerebrovascular network related to the internal carotid arteries. J Neurosurg 1968;29:255-60. PMID 5684407
150: Ogata T, Yasaka M, Inoue T, et al. The clinical features of adult unilateral moyamoya disease: does it have the same clinical characteristics as typical moyamoya disease. Cerebrovasc Dis 2008;26(3):244-9. PMID 18648196
151: Ogawa K, Nagahiro S, Arakaki R, Ishimaru N, Kobayashi M, Hayashi Y. Anti-alpha-fodrin autoantibodies in Moyamoya disease. Stroke 2003;34(12):e244-6. PMID 14657555
152: Oka K, Yamashita M, Sadoshima S, Tanaka K. Cerebral hemorrhage in moyamoya disease at autopsy. Virchows Arch (Pathol Anat) 1981;392:247-61. PMID 7269227
153: Oppenheim JS, Gennuso R, Sacher M, Hollis P. Acute atraumatic subdural hematoma associated with moyamoya disease in an African American. Neurosurgery 1991;28:616-8. PMID 1812845
154: Pandey P, Bell-Stephens T, Steinberg GK. Patients with moyamoya disease presenting with movement disorder. J Neurosurg Pediatr 2010;6(6):559-66. PMID 21121731
155: Pavlakis SG, Schneider S, Black K, Gould RJ. Steroid responsive chorea in moyamoya disease. Mov Disord 1991;6:163-4. PMID 1758454
156: Perren F, Meairs S, Schmiedek P, Hennerici M, Horn P. Power Doppler evaluation of revascularization in childhood moyamoya. Neurology 2005;64:558-60. PMID 15699398
157: Pettersson SD, Olofsson HKL, Ali S, Szarek D, Miękisiak G, Ogilvy CS. Risk factors for ischemic stroke after revascularization surgery in patients with Moyamoya disease: an age-stratified comparative meta-analysis. World Nuerosurg 2023;173:146-57.e14. PMID 36716854
158: Rafat N, Beck G, Pena-Tapia PG, Schmiedek P, Vajkoczy P. Increased levels of circulating endothelial progenitor cells in patients with Moyamoya disease. Stroke 2009;40(2):432-8. PMID 19095988
159: Roach ES. Immediate surgery for moyamoya syndrome. Not necessarily. Arch Neurol 2001;58(1):130-1. PMID 11176948
160: Roach ES, Golomb MR, Adams R, et al. Management of stroke in infants and children: a scientific statement from a Special Writing Group of the American Heart Association Stroke Council and the Council on Cardiovascular Disease in the Young. Stroke 2008;39(9):2644-91. PMID 18635845
161: Robertson RL, Chavali RV, Robson CD, et al. Neurologic complications of cerebral angiography in childhood moyamoya syndrome. Pediatr Radiol 1998;28(11):824-9. PMID 9799310
162: Rocha EA, Topcuoglu MA, Silva GS, Singhal AB. RCVS2 score and diagnostic approach for reversible cerebral vasoconstriction syndrome. Neurology 2019;92(7):e639-47. PMID 30635475
163: Ryoo S, Cha J, Kim SJ, et al. High-resolution magnetic resonance wall imaging findings of Moyamoya disease. Stroke 2014;45(8):2457-60. PMID 24947295
164: Saeki N, Silva MN, Kubota M, et al. Comparative performance of magnetic resonance angiography and conventional angiography in moyamoya disease. J Clin Neurosci 2000;7(2):112-5. PMID 10844793
165: Sakamoto Y, Okamoto S, Maesawa S, et al. Default mode network changes in moyamoya disease before and after bypass surgery: preliminary report. World Neurosurg 2018;112:e652-61. PMID 29374613
166: Sakurai K, Horiuchi Y, Ikeda H, et al. A novel susceptibility locus for moyamoya disease on chromosome 8q23. J Hum Genet 2004;49(5):278-81. PMID 15362573
167: Sato K, Shirane R, Kato M, Yoshimoto T. Effect of inhalational anesthesia on cerebral circulation. J Neurosurg Anesthesiol 1999;11(1):25-30. PMID 9890382
168: Scott RM. Surgery for moyamoya syndrome. Yes. Arch Neurol 2001;58:128-9. PMID 11176947
169: Scott RM, Smith ER. Moyamoya disease and moyamoya syndrome. N Engl J Med 2009;360(12):1226-37. PMID 19297575
170: Scott RM, Smith JL, Robertson RL, Madsen JR, Soriano SG, Rockoff MA. Long-term outcome in children with moyamoya syndrome after cranial revascularization by pial synangiosis. J Neurosurg 2004;100:142-9. PMID 14758941
171: Shen AL, Ryu SJ, Lin SK. Concurrent moyamoya disease and Graves’ thyrotoxicosis: case report and literature review. Acta Neurol Taiwan 2006;15:114-9. PMID 16871899
172: Shimizu K, Takeuchi K. Hypoplasia of the bilateral internal carotid arteries. Brain Nerve (Tokyo) 1957;9:37-43.
173: Smith ER, Scott RM. Spontaneous occlusion of the circle of Willis in children: pediatric moyamoya summary with proposed evidence-based practice guidelines. a review. J Neurosurg Pediatr 2012;9(4):353-60. PMID 22462697
174: Starke RM, Komotar RJ, Hickman ZL, et al. Clinical features, surgical treatment, and long-term outcome in adult patients with moyamoya disease: clinical article. J Neurosurg 2009;111(5):936-42. PMID 19374496
175: Sun H, Wilson C, Ozpinar A, et al. Perioperative complications and long-term outcomes after bypasses in adults with moyamoya disease: a systematic review and meta-analysis.World Neurosurg. 2016;92:179-88. PMID 27150649
176: Suzuki H, Mikami T, Enatsu R, Kanno A, Takahashi Y, Mikuni N. Gelastic attack in a child with moyamoya disease. Neurology 2018;91(3):141-2. PMID 30012654
177: Suzuki J, Takaku A. Cerebrovascular "moyamoya" disease; disease showing abnormal net-like vessels in base of brain. Arch Neurol 1969;20:288-99. PMID 5775283
178: Suzuki R, Nariai T, Matsushima Y, Hirakawa K. Xe-CT in cerebrovascular disease and moyamoya disease. Acta Neurol Scand Suppl 1996;166:69-71. PMID 8686446
179: Swartz RH, Bhuta SS, Farb RI, et al. Intracranial arterial wall imaging using high-resolution 3-tesla contrast-enhanced MRI. Neurology 2009;72(7):627-34. PMID 19221296
180: Takagi Y, Kikuta K, Sadamasa N, Nozaki K, Hashimoto N. Caspase-3-dependent apoptosis in middle cerebral arteries in patients with moyamoya disease. Neurosurgery 2006;59:894-900; discussion 900-1. PMID 17038954
181: Takahashi M. Magnification angiography in moyamoya disease: new observations on collateral vessels. Radiology 1980;136:379-86. PMID 7403514
182: Takanashi JI, Sugita K, Niimi H. Evaluation of magnetic resonance angiography with selective maximum intensity projection in patients with childhood moyamoya disease. Eur J Paediatr Neurol 1998;2:83-9. PMID 10724101
183: Taki W, Yonekawa Y, Kobayashi A, et al. Cerebral circulation and metabolism in adults moyamoya disease-PET study. Acta Neurochir 1989;100:150-4. PMID 2589122
184: Tanaka H, Katsuragi S, Tanaka K, et al. Vaginal delivery in pregnancy with Moyamoya disease: experience at a single institute. J Obstet Gynaecol Res 2015;41(4):517-22. PMID 25345600
185: 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 1997;99(Suppl 2):S225-8. PMID 9409443
186: Tatemichi TK, Prohovnik I, Mohr JP, Correll JW, Quest DO, Jarvis L. Reduced hypercapnic vasoreactivity in moyamoya disease. Neurology 1988;3:1575-81. PMID 3419602
187: Tavares JM. Multiple progressive intracranial arterial occlusion: a syndrome of children and young adults. AJR Am J Roentgenol 1969;106:235-68.
188: Teo M, Abhinav K, Bell-Stephens TE, et al. Short- and long-term outcomes of moyamoya patients post-revascularization. J Neurosurg 2022;138(5):1374-84. PMID 36272120
189: Teo M, Furtado S, Kaneko OF, et al. Validation and application for the Berlin grading system of Moyamoya disease in adult patients. Neurosurgery 2020;86(2):203-12. PMID 30864668
190: Uchino H, Kazumata K, Ito M, Nakayama N, Houkin K. Novel insights into symptomatology of moyamoya disease in pediatric patients: survey of symptoms suggestive of orthostatic intolerance. J Neurosurg Pediatr 2017;20(5):485-8. PMID 28862519
191: Uchino K, Johnston SC, Becker KJ, Tirschwell DL. Moyamoya disease in Washington State and California. Neurology 2005;65(6):956-8. PMID 16186547
192: Vuignier S, Ito M, Kurisu K, et al. Ivy sign, misery perfusion, and asymptomatic moyamoya disease: FLAIR imaging and (15)O-gas positron emission tomography. Acta Neurochir (Wien) 2013;155(11):2097-104. PMID 24036671
193: Waga S, Tochio H. Intracranial aneurysm associated with moyamoya disease in childhood. Surg Neurol 1985;23:237-43. PMID 3975804
194: Wang J, Yang Y, Li X, et al. Lateral posterior choroidal collateral anastomosis predicts recurrent ipsilateral hemorrhage in adult patients with Moyamoya disease. AJNR Am J Neuroradiol 2019;40(10):1665-71. PMID 31537520
195: Wang X, Wang Y, Nie F, et al. Association of genetic variants with Moyamoya disease in 13 000 individuals: a meta-analysis. Stroke 2020a;51(6):1647-55. PMID 32390555
196: Wang Y, Zhang Z, Wei L, et al. Predictive role of heterozygous p.R4810K of RNF213 in the phenotype of Chinese moyamoya disease. Neurology 2020b;94(7):e678-86. PMID 31949090
197: Whitaker J. Management of moyamoya syndrome. Arch Neurol 2001;58:132. PMID 11176949
198: Wiedmann MKH, Davidoff C, Presti AL, et al. Treatment of ruptured aneurysms of the choroidal collateral system in moyamoya disease: a systematic review and data analysis. J Neurosurg 2021;136(3):637-46. PMID 34450582
199: Williams DL, Martin IL, Gully RM. Intracerebral hemorrhage and Moyamoya disease in pregnancy. Can J Anaesth 2000;47:996-1000. PMID 11032277
200: Yamada H, Deguchi K, Tanigawara T, et al. The relationship between moyamoya disease and bacterial infection. Clin Neurol Neurosurg 1997;99(Suppl 2):S221-4. PMID 9409442
201: Yamada I, Nakagawa T, Matsushima Y, Shibuya H. High-resolution turbo magnetic resonance angiography for diagnosis of Moyamoya disease. Stroke 2001;32:1825-31. PMID 11486112
202: Yamashita M, Oka K, Tanaka K. Histopathology of the brain vascular network in moyamoya disease. Stroke 1983;14:50-8. PMID 6823686
203: Yamashita M, Oka K, Tanaka K. Cervico-cephalic arterial thrombi and thromboembolic in moyamoya disease: possible correlation with progressive intimal thickening in the intracranial major arteries. Stroke 1984a;15:264-70. PMID 6701935
204: Yamashita M, Tanaka K, Kishikawa T, Yokota K. Moyamoya disease associated with renovascular hypertension. Hum Pathol 1984b;15:191-3. PMID 6698536
205: Yamauchi T, Tada M, Houkin K, et al. Linkage of familial moyamoya disease (spontaneous occlusion of the circle of Willis) to chromosome 17q25. Stroke 2000;31:930-5. PMID 10754001
206: Yilmaz EY, Pritz MB, Bruno A, Lopez-Yunez A, Biller J. Moyamoya: Indiana University Medical Center experience. Arch Neurol 2001;58:1274-8. PMID 11493168
207: Yoon HK, Shin HJ, Chang YW. "Ivy sign" in childhood moyamoya disease: depiction on FLAIR and contrast-enhanced T1-weighted MR images. Radiology 2002;223:384-9. PMID 11997541
208: Yoshida Y, Shirane R, Yoshimoto T. Non-anastomotic bypass surgery for childhood moyamoya disease using dural pedicle insertion over the brain surface combined with encephalogaleomyosynangiosis. Surg Neurol 1999b;51:404-11. PMID 10199294
209: Yoshimoto T, Houkin K, Takahashi A, Abe H. Angiogenic factors in moyamoya disease. Stroke 1996;27:2160-5. PMID 8969773
210: Zhang C, Shi J. 7T MRI for intracranial vessel wall lesions and its associated neurological disorders: a systematic review. Brain Sci 2022;12(5):528. PMID 35624915
211: Zhang XH, He JH, Zhang XS, et al. Comparison of revascularization and conservative treatment for hemorrhagic moyamoya disease in East Asian Countries: a single-center case series and a systematic review with meta-analysis. Front Neurol 2023;14:1169440. PMID 37332987
212: Zhang Y, Bao XY, Duan L, et al. Encephaloduroarteriosynangiosis for pediatric moyamoya disease: long-term follow-up of 100 cases at a single center. J Neurosurg Pediatr 2018;22(2):173-80. PMID 29856299
213: Zhao Y, Zhang Q, Zhang D, Zhao Y. The effect of aspirin in the postoperative management of adult ischemic moyamoya disease. World Neurosurg 2017;105:728-31. PMID 28625901
214: Zipfel GJ, Sagar J, Miller JP, et al. Cerebral hemodynamics as a predictor of stroke in adult patients with moyamoya disease: a prospective observational study. Neurosurg Focus 2009;26(4):E6. PMID 19335132

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Moyamoya disease

Associated Disorders

Acute hemiplegia in childhood
Alagille syndrome
Antiphospholipid syndrome
Atherosclerosis
Brain trauma
- Chronic meningitis
- Cocaine abuse
- Cranial irradiation for brain tumor
- Down syndrome
- Leptospiral meningitis
- Morning glory optic disc abnormality
- Neurofibromatosis
- Osteogenesis imperfecta
- Peripheral arterial disease
- Sickle cell disease
- Stroke in young adults

Differential Diagnosis

hypoglycemia
cardiac source emboli
hypercoagulable states
seizures
childhood transient cerebral arteriopathy
- alternating hemiparesis induced by hyperventilation
- transient ischemic attacks induced by hyperventilation
- cerebral ischemia
- focal seizures
- intracerebral hematoma
- intraventricular hemorrhage

Also Relevant

Acute hemiplegia in childhood
Cerebral arteriopathies
Ischemic stroke
Stroke associated with sickle cell disease
Stroke in young adults

Moyamoya disease …

Moyamoya disease

Introduction

Overview

Key points

Historical note and terminology

Clinical manifestations

Presentation and course

Prognosis and complications

Biological basis

Etiology and pathogenesis

Epidemiology

Prevention

Differential diagnosis

Confusing conditions

Diagnostic workup

Management

Special considerations

Pregnancy

Anesthesia

Media

References

Contributors

Authors

Editor

Former Authors

Patient Profile

ICD & OMIM codes

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Also in This Category

Infant botulism

Neonatal intraventricular hemorrhage

Congenital heart disease: neurologic complications

Parenteral nutrition in infants and children

Atypical teratoid/rhabdoid tumors

Rostral brainstem and thalamic infarctions

Sleep-related rhythmic movement disorder

Myelomeningocele

Moyamoya disease

Introduction

Overview

Key points

Historical note and terminology

Clinical manifestations

Presentation and course

Prognosis and complications

Biological basis

Etiology and pathogenesis

Epidemiology

Prevention

Differential diagnosis

Confusing conditions

Diagnostic workup

Management

Special considerations

Pregnancy

Anesthesia

Media

References

Contributors

Authors

Editor

Former Authors

Patient Profile

ICD & OMIM codes

This is an article preview. Start a Free Account to access the full version.

Questions or Comment?

Also in This Category

Infant botulism

Neonatal intraventricular hemorrhage

Congenital heart disease: neurologic complications

Parenteral nutrition in infants and children

Atypical teratoid/rhabdoid tumors

Rostral brainstem and thalamic infarctions

Sleep-related rhythmic movement disorder

Myelomeningocele

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