Version July 2025
INTRODUCTION —
Moyamoya is an uncommon cerebrovascular condition characterized by the progressive narrowing of large intracranial arteries around the circle of Willis and the secondary development of prominent small-vessel collaterals. These collateral vessels produce a characteristic “smoky” appearance on digital subtraction angiography (DSA), which was first called "moyamoya," a Japanese word meaning puffy, obscure, or hazy like a puff of smoke in the air. The progressive vascular changes in moyamoya may lead to ischemic stroke or intracranial hemorrhage in children and adults [1,2].
This topic will review the etiologies, clinical features, and diagnosis of moyamoya. The prognosis and treatment of moyamoya are discussed separately. (See "Moyamoya disease and moyamoya syndrome: Treatment and prognosis".)
TERMINOLOGY
●The term "moyamoya" refers to the specific angiographic findings of unilateral or bilateral stenosis or occlusion of the arteries around the circle of Willis with prominent arterial collateral circulation (image 1).
●Moyamoya disease (MMD) is a condition characterized by the occurrence of moyamoya angiographic findings along with associated genetic susceptibilities but no underlying contributing medical conditions. MMD may also be called primary or idiopathic moyamoya as well and may also be referred to descriptively as the "spontaneous occlusion of the circle of Willis" [3,4].
●Moyamoya syndrome (MMS) is a condition characterized by the occurrence of moyamoya angiographic findings along with an associated medical condition implicated in the development of vascular changes. (See 'Associated conditions' below.)
Moyamoya associated with an underlying medical condition has also been called "moyamoya phenomenon," "angiographic moyamoya," or "quasi-moyamoya disease" [3,5-7].
PATHOPHYSIOLOGY
Pathogenesis — The pathophysiologic processes leading to arterial stenosis and subsequent small vessel collateralization involve vessel wall thickening and angiogenesis. A genetic susceptibility may be implicated in MMD, while underlying associated conditions trigger the development of MMS. (See 'Etiology' below.)
Vascular stenosis and collateral formation in moyamoya may be related to impaired response to inflammation or defects in cellular repair mechanisms [8]. Such changes have been associated with evidence of increased angiogenesis-related factors, including endothelial colony-forming cells, various cytokines, vascular endothelial growth factor, and basic fibroblast growth factor [9-11]. High levels of fibroblast growth factor, which may stimulate arterial growth, have been found in the vascular intima, media, and smooth muscle as well as cerebrospinal fluid among patients with moyamoya [12,13]. Transforming growth factor beta-1, which mediates neovascularization, may also contribute to the pathogenesis [14,15]. Elevated levels of other neovascular factors have also been detected in arterial walls and cerebrospinal fluid of patients with moyamoya, including hepatocyte growth factor, nitric oxide metabolites, platelet derived growth factor, plasminogen activator 1, tumor necrosis factor, and epidermal growth factor [16]. Expression of caspase-3 and hypoxia inducible factor-1 in intracranial vessel walls has been correlated with apoptosis of smooth muscle cells and thickening of vascular intima [2,17-20].
Pathologic findings — Tissue analysis in patients with moyamoya shows evidence of arterial vessel narrowing and secondary vascular proliferation characteristic of the disease as well as tissue damage related to the vascular abnormalities.
●Vascular stenosis – Pathologic vascular lesions appear in the large vessels of the circle of Willis and in the small collateral vessels [21]. The terminal portions of the internal carotid arteries (ICAs) as well as the proximal middle and anterior cerebral arteries are most involved [22]. Some patients may have unilateral stenosis at presentation, although progression to bilateral involvement occurs in approximately one-third of these patients by two- to eight-year follow-up [23-25]. Less frequently, the posterior circulation is affected, especially the posterior cerebral artery [24,26].
In the affected large arteries, variable stenosis or occlusion is associated with intimal fibrocellular thickening, irregular distortion or duplication of the internal elastic lamina, and attenuation of the media [27-30].
●Collateral vessels – Several types of collateral vessels may be found in patients with moyamoya.
•Moyamoya vessels are the hallmark vascular finding in moyamoya, characterized by a collateral meshwork of overgrown and dilated small arteries that branch from the circle of Willis (image 2). These moyamoya, or basal collateral, vessels develop adjacent to areas of vessel stenosis.
•Larger leptomeningeal vessels are another common source of collaterals in moyamoya. As a result of hypoperfusion from intracranial arterial stenosis, leptomeningeal anastomoses may develop between surface vessels and cortical branches of the middle, anterior, or posterior cerebral arteries. These collaterals result from dilatation of preexisting arteries and veins.
•Transdural anastomoses, termed vault moyamoya, may develop as a consequence of intracranial stenosis, providing intracranial perfusion from extracranial arteries such as the middle meningeal and superficial temporal arteries [31].
The pathology of the smaller perforating vessels in moyamoya is variable. Morphometric analysis suggests that some are dilated with relatively thin walls while others are stenotic with thick walls [27]. Dilated vessels, more common in younger patients than in adults, tend to show fibrosis with attenuation of the media and microaneurysm formation.
●Associated aneurysms – Cerebral aneurysms have been associated with moyamoya in several reports [32-36]. Aneurysms commonly develop at vessel branching points in the circle of Willis or along collateral vessels [37,38]. In a review of 111 moyamoya patients with cerebral aneurysm, most presented with intracranial hemorrhage and were found to have a single aneurysm in 86 percent of cases. Aneurysms along the circle of Willis were found in 56 percent, of which almost 60 percent were in the posterior circulation [38].
Aneurysms can also arise from the small collateral moyamoya vessels or other distal collateral arteries [37]. These small-vessel aneurysms are the major cause of intracerebral and intraventricular hemorrhage in moyamoya [39].
Histologic studies of aneurysm autopsy specimens showed the disappearance of internal elastic lamina and media [40]. These findings are similar to those of the berry aneurysms commonly observed in primary subarachnoid hemorrhage.
●Extracranial involvement – While moyamoya is characterized as an intracranial vasculopathy, some patients with MMD and MMS may be found to have stenosis in extracranial and systemic arteries, including the cervical carotid, renal, pulmonary, aortic, and coronary vessels [41-45]. Stenosis may be related to genetic factors in MMD or an underlying associated systemic condition in MMS [46]. Fibrocellular intimal thickening may be found pathologically in some cases [28,47].
Involvement of the renal arteries has been most frequently reported. In one study of 86 patients with MMD, six had renal artery stenosis, two had associated renovascular hypertension, and one had a renal artery aneurysm [48]. Similarly, in a later study of 73 consecutive patients with MMD, four had renal artery stenosis [49].
●Parenchymal injury – Brain tissue of patients with moyamoya usually reveals evidence of prior ischemic or hemorrhagic stroke. Multiple areas of cerebral infarction and focal cortical atrophy are commonly found. Although large-vessel stenosis and occlusion are the hallmarks of this disease, extensive territorial infarction is uncommon. Brain infarcts are generally found in the ICA distribution or at the borderzone between the anterior and middle cerebral artery vascular territories, such as at the basal ganglia, internal capsule, thalamus, centrum semiovale, and subcortical regions [50]. However, the cause of death in most autopsy cases is intracerebral hemorrhage [51].
Hemorrhage is commonly found in the basal ganglia, thalamus, hypothalamus, midbrain, and/or periventricular region. Bleeding into the intraventricular space is frequently observed. The major causes of intracranial bleeding include rupture of microaneurysms or dilated perforating arteries or fibrinoid arterial necrosis in the basal ganglia [39].
ETIOLOGY —
The spectrum of moyamoya encompasses MMD, attributed to genetic susceptibilities, and MMS, attributed to an underlying vascular or systemic condition. The etiology of MMD is unknown, but several genetic associations have been identified. MMS has been associated with multiple conditions, which implicates diverse pathophysiologic processes leading to the characteristic vascular abnormalities.
Genetic associations — The high incidence of MMD among the East Asian population, together with a familial occurrence of approximately 10 to 15 percent of cases, strongly suggests a genetic etiology.
Variants of the RNF213 gene on chromosome 17q25.3 have been identified as susceptibility factors for MMD in populations in several East Asian countries [52-60]. The RNF213 gene variant p.R4810K has been reported in up to 95 percent of familial and 79 percent of sporadic cases of MMD in some reports [61,62]. This variant has also been found to be highly prevalent among East Asian patients with MMD compared with baseline prevalence in the general population, including Japanese (90 versus 3 percent), Korean (79 versus 3 percent), and Chinese (23 versus 1 percent) populations, and is absent among White populations with MMD [63]. Patients with this polymorphism tend to have an earlier disease onset and exhibit a more severe progression of MMD [61].
Several reports have also linked familial MMD to chromosomes 3p24.2, 3p26, 6q25, 8q23, 12p12, and 17q25 [64-67]. Although the mode of inheritance is not established, one study suggested that familial moyamoya is an autosomal dominant disease with incomplete penetrance [68]. The authors proposed that genomic imprinting and epigenetic modification may account for the predominantly maternal transmission and elevated female-to-male incidence ratio. (See 'Epidemiology' below.)
Associated conditions — Several conditions have been associated with MMS. Some of these conditions chiefly cause the development of the moyamoya vasculopathy, while others are characterized by specific clinical syndromes that can include moyamoya. Some conditions associated with MMS include:
●Intracranial conditions
•Radiation vasculopathy [69] (see "Delayed complications of cranial irradiation", section on 'Cerebrovascular effects')
•Cranial trauma [70]
•Brain tumors [71-73]
•Meningitis [74]
●Hematologic conditions
•Sickle cell disease [75-77]
•Beta thalassemia [78]
•Fanconi anemia [79]
•Hereditary spherocytosis [80]
•Homocystinuria and hyperhomocysteinemia [81]
•Factor XII deficiency [82]
•Essential thrombocythemia [83]
•Protein S deficiency [84-86]
•Pyruvate kinase deficiency [87]
•Systemic viral or bacterial infection (eg, Cutibacterium acnes, leptospirosis, human immunodeficiency virus [HIV]) [88-90]
●Vasculitis and autoimmune and multisystem diseases
•Graves disease and thyroiditis [91-94]
•Systemic lupus erythematosus [95]
•Polyarteritis nodosa and postinfectious vasculopathy [96]
•Sneddon syndrome and the antiphospholipid antibody syndrome [97,98]
•Type 1 diabetes mellitus [94]
•Pulmonary sarcoidosis [99,100]
●Other vasculopathies and extracranial cardiovascular diseases
•Coarctation of the aorta [101]
•Congenital heart disease [102]
•Fibromuscular dysplasia [103]
•Renal artery stenosis [48]
●Genetic and developmental disorders
•Alagille syndrome [104,105]
•Down syndrome [106,107]
•Hypomelanosis of Ito [108]
•Marfan syndrome [109]
•Microcephalic osteodysplastic primordial dwarfism type 2 [110]
•Multisystem disorder with short stature, hypergonadotropic hypogonadism, and dysmorphism [111,112]
•Neurofibromatosis type 1 [113-116]
•Noonan syndrome [117-119]
•Phakomatosis pigmentovascularis type IIIb [120]
•Prader-Willi syndrome [121]
•Pseudoxanthoma elasticum [122]
•Sturge-Weber syndrome [123]
•Tuberous sclerosis complex [124]
•Turner syndrome [125]
•Williams syndrome [126]
•Morning glory optic disc anomaly (image 3), usually in conjunction with other craniofacial abnormalities [127-129] (see "Congenital and acquired abnormalities of the optic nerve", section on 'Morning glory disc')
●Metabolic diseases
•Type I glycogenosis [130,131]
•Hyperphosphatasia [132]
•Primary oxalosis [133]
●Kidney disorders
•Polycystic kidney disease [134-136]
•Wilms tumor [21,28,31-37,40,47,48,51,137]
EPIDEMIOLOGY
Incidence and prevalence — The relative prevalence of MMD and MMS varies geographically. MMD is more common in East Asian countries than elsewhere, with the highest prevalence reported in Japan, China, and Korea [22,138,139].
In epidemiologic surveys conducted in Japan, the annual incidence of MMD is 0.35 to 0.94 per 100,000 individuals, while the prevalence of moyamoya is 3.2 to 10.5 per 100,000 [140-143]. There is a female predominance, with a female-to-male ratio of 1.9, and a family history of MMD is reported in up to 12 percent of patients. The incidence of MMS in Japan is approximately 10 times lower than MMD [144,145].
A United States study using hospital admissions data reported an annual incidence of moyamoya of 0.57 per 100,000 individuals [146]. Among ethnic groups in California, the moyamoya incidence rate for Asian Americans was 0.28 per 100,000, similar to that in Japan. The incidence rates were lower for African American, White American, and Hispanic populations (0.13, 0.06, and 0.03 per 100,000, respectively). The female-to-male ratio was 2.6.
Bimodal age distribution — MMD and MMS both occur in children and adults; presentation in infancy is uncommon [147,148]. Data from a nationwide registry in Japan, with 2545 cases of MMD, showed a bimodal distribution in the age of onset, with one higher peak at approximately 5 to 10 years of age and a second broader peak at 30 to 50 years of age [143]. A cohort study of 802 patients with MMD from China also demonstrated a bimodal age distribution, with a major peak at five to nine years of age and another peak at 35 to 39 years of age [149].
CLINICAL FEATURES —
Moyamoya can present with a range of neurologic symptoms and suggestive neuroimaging findings related to the underlying intracranial vasculopathy, but it also may be asymptomatic, found incidentally on neuroimaging pursued for other indications.
Neurologic presentations — Moyamoya most commonly presents with cerebrovascular ischemic or hemorrhagic symptoms but may also present less commonly with seizures or other neurologic symptoms.
Ischemic stroke and transient ischemic attack — Ischemic stroke or transient ischemic attack (TIA) is the most common presentation for adults or children with moyamoya [150-154]. In one retrospective series from the United States, 61 percent of adults with MMD or MMS presented with TIA or stroke symptoms [153]. In another retrospective study from Germany, 21 patients with MMD all presented with ischemic events, most of whom were adults at initial symptom onset [152]. In the International Pediatric Stroke Study (IPS) involving 174 children with moyamoya, ischemic stroke was the initial presentation in 90 percent of children and TIA in 7.5 percent [150].
●Characteristic symptoms – Ischemic symptoms of hemiparesis, hemisensory loss, or speech impairment predominate, reflecting the predilection for stenosis of the anterior cerebral circulation (anterior and middle cerebral artery territories) [150]. Brainstem symptoms such as vertigo and dysphagia at presentation are uncommon [155].
●Recurrent symptoms – TIA and stroke symptoms can frequently be recurrent in moyamoya, reflecting regional cerebral susceptibility due to the fixed underlying stenosis [150,154]. In the IPS study, 20 percent of children had recurrent symptoms in the median 13-month follow-up interval [150]. Multiple recurrent events are common in other studies as well. In one study from Korea of 88 children and adults who were followed for 6 to 216 months, multiple cerebrovascular events occurred in 55 percent [156]. Recurrences were most commonly ischemic.
●TIA triggers – TIA and stroke symptoms may be spontaneous. However, symptomatic episodes of ischemia are frequently triggered by exercise, crying, coughing, straining, fever, or hyperventilation [8,157,158]. Triggers are postulated to lower blood pressure and/or reduce cerebral perfusion from transient hypocapnia [159,160]. In a single-center observational study of 160 consecutive patients with moyamoya, neurologic symptoms were triggered in 41 percent, including fever, emotional stress, and exercise [161]. Triggers were more common in children than adults (52 versus 32 percent).
Intracranial hemorrhage — Hemorrhagic complications of moyamoya are less common than ischemic cerebrovascular presentations of moyamoya, but they represent a significant clinical burden, accounting for 25 to 30 percent of moyamoya presentations, mostly in adults [155,162]. Hemorrhagic susceptibility in moyamoya may be due to elevated pressures at the regions of stenosis and/or fragility of small collateral vessels or to associated aneurysms. Hemorrhagic manifestations include:
●Intracerebral hemorrhage (ICH)
●Subarachnoid hemorrhage
●Intraventricular hemorrhage
ICH is more common in adults than children [154,163]. In a series of adult patients, 10 percent of patients presented with intracranial hemorrhage, while only 2.5 percent of children in the IPS had a hemorrhagic presentation of moyamoya [150,153]. ICH also appears to be a more common presentation among patients in China and Taiwan than those in the United States [151].
Intraventricular hemorrhage may occur with or without ICH [164]. Among adults with moyamoya who present with intraventricular hemorrhage, ruptured aneurysms in the periventricular area may be identified (image 4 and image 5). Patients may also present with subarachnoid hemorrhage [165].
Seizures — Seizures are an uncommon initial presentation of moyamoya, accounting for <10 percent of clinical presentations [166]. Seizures in moyamoya are often attributed to prior or concurrent ischemic stroke [162]. However, epilepsy is a frequent complication of moyamoya, reported in up to 40 percent in some series [163,167].
Specific findings on electroencephalography (EEG) have also been associated with moyamoya.
●Hyperventilation, performed as a part of EEG protocol, induces generalized high-voltage slow waves (the "build-up" phenomenon) that resolve after hyperventilation stops. The reappearance of generalized or localized high-voltage slow waves on EEG 20 to 60 seconds after the end of hyperventilation (the "rebuild-up" phenomenon) is considered pathognomonic for moyamoya and occurs in approximately two-thirds of affected children [168,169].
●Asymmetric posterior alpha activity and centrotemporal slowing have also been described in children with moyamoya. Background abnormalities in children and adults with MMD include nonspecific generalized, asymmetric, or localized slow-wave activity [169,170].
Of note, hyperventilation should be minimized in patients with a diagnosis of moyamoya since it may induce reflex cerebral vasoconstriction [171]. While EEG with hyperventilation was reported to be safe in one series of 127 children [169], rare reports link hyperventilation to limb-shaking TIA and episodes of chorea and dystonia [172-174].
Other manifestations — While the underlying vasculopathy of moyamoya most commonly leads to acute cerebrovascular ischemic or hemorrhagic presentations, some patients may present with other neurologic symptoms. Such symptoms may be due to chronic cerebral hypoperfusion and ischemia or previously asymptomatic cortical or subcortical infarction.
Case reports describe patients with moyamoya who develop dystonia, chorea, or dyskinesia, but these appear to be rare presenting manifestations, representing approximately 3 to 6 percent of cases [175-177]. Headache is common in patients with moyamoya, perhaps due to the activation of intracranial arterial nociceptors within dilated cortical vessels [178]. However, the causal relationship between these headache syndromes and moyamoya is uncertain, and the high prevalence of headache in the population suggests it may be incidental to moyamoya in some patients. Migraine is the most common headache phenotype, but tension-type headache and cluster headache have also been reported [179,180].
Cognitive impairment may result from recurrent ischemic insults, presenting as poor scholastic performance in children with moyamoya. Adults with moyamoya may have neurocognitive impairment even in the absence of clinically apparent prior stroke symptoms [181].
Initial neuroimaging findings — Neuroimaging performed as part of the routine initial assessment of neurologic symptoms or for unrelated indications such as head trauma or screening imaging for cerebral aneurysm may show specific features suggestive of moyamoya [182,183]. A nationwide study in Japan using a questionnaire in 1994 identified 33 asymptomatic cases (1.5 percent) out of a total of 2193 patients [184].
These imaging features may guide additional diagnostic imaging or, in some cases, may be used to establish the diagnosis. (See 'Vascular imaging evaluation' below.)
●Brain imaging
•Patterns of cerebrovascular injury – Cerebral infarction often involves cortical and subcortical regions (image 6). Superficial and deep border-zone regions distal to the stenotic or occluded moyamoya vessel are most susceptible to hypoperfusion [153,185]. In a retrospective series of 32 adults with first-ever ischemic stroke, patients with early-stage MMD had ischemic lesions involving only deep subcortical structures, while those with advanced stage had predominantly cortical lesions [186].
ICH typically occurs in deep structures such as the basal ganglia, thalamus, and/or ventricular system, due to the proximity of associated small collateral vessels (image 5). Bleeding in the cortical and subcortical regions has been reported with lower frequency [187,188]. However, asymptomatic cerebral microbleeds were present on T2*-weighted gradient-echo magnetic resonance imaging (MRI) in 30 percent or more of adult patients with MMD [189-191]. One study of 50 patients with moyamoya found that the presence of multiple microbleeds was an independent risk factor for subsequent ICH (hazard ratio [HR] 2.89, 95% CI 1.001-13.24) [190].
•Evidence of vasculopathy on brain imaging – Brain parenchymal imaging studies may also show evidence of vasculopathy suggestive of moyamoya. These findings include:
-The "ivy sign" refers to focal, tubular, or serpentine hyperintensities on T2-weighted fluid-attenuated inversion recovery (T2-FLAIR) or contrast-enhanced T1 images in the subarachnoid spaces (image 7) [192-194]. These hyperintensities represent slow, retrograde collateral flow through engorged pial vessels via leptomeningeal anastomoses. However, this sign is not specific for moyamoya and has been reported in association with large-vessel stenosis or occlusions, where it is referred to as T2-FLAIR vascular hyperintensities or the hyperintense vessel sign [195].
-The "brush sign" refers to prominent hypointensity on susceptibility-weighted imaging typically found in medullary veins draining areas of impaired cerebral perfusion (image 8). The brush sign may be more prominent in those with impaired cerebrovascular reserve and symptomatic patients with TIA and infarction [196]. Like the ivy sign, the brush sign is not specific for moyamoya and has been identified in patients with subacute stroke from many causes [197].
-Multiple punctate or serpentine flow voids (hypointense on T2-weighted MRI) in the basal ganglia or thalamus, a finding that is considered virtually diagnostic of moyamoya (image 9) [198].
●Vascular imaging – Noninvasive vascular imaging pursued as part of the assessment of symptoms such as ischemic stroke or ICH or performed as a screening evaluation for cerebral aneurysms can demonstrate characteristic vascular findings in moyamoya. These include the stenotic or occlusive lesions in the distal internal carotid arteries (ICAs) and/or the proximal arteries around the circle of Willis (image 10) as well as collateral "moyamoya vessels" in the basal ganglia (image 11) [199-201]. (See 'Vascular imaging evaluation' below.)
DIAGNOSIS —
The diagnosis of moyamoya is made by identifying the characteristic angiographic appearance of bilateral stenoses affecting the distal internal carotid arteries (ICAs) (or other proximal circle of Willis vessels) along with the presence of prominent collateral vessels (image 6) after excluding alternative conditions.
MMD is diagnosed in patients who have characteristic angiographic features with or without a genetic susceptibility or family history of moyamoya and not due to an associated underlying condition. MMS is diagnosed by identifying characteristic angiographic features in the setting of an associated condition. (See 'Associated conditions' above.)
When to suspect moyamoya — The possibility of moyamoya should be suspected in the following clinical scenarios:
●Children or young adults with recurring transient symptoms suspicious for transient ischemic attacks due to low perfusion in the same arterial territory. (See 'Ischemic stroke and transient ischemic attack' above.)
●Individuals with intracerebral hemorrhage (ICH) involving brain regions supplied by small vessels that branch from the circle of Willis (eg, caudate, thalamus, or intraventricular hemorrhage within the lateral ventricles) who do not have hypertension or other typical ICH risk factors. (See 'Intracranial hemorrhage' above.)
●Children with seizures who have the reappearance of generalized or localized high-voltage slow waves on electroencephalography (EEG) 20 to 60 seconds after the end of hyperventilation. (See 'Seizures' above.)
●Individuals with brain MRI findings such as dilated collateral vessels in the basal ganglia or thalamus, the "ivy sign," the "brush sign," or enhancement of the arterial wall. (See 'Initial neuroimaging findings' above.)
Vascular imaging evaluation — Cerebrovascular evaluation is required for the diagnosis of moyamoya to identify characteristic vasculopathy and exclude alternative conditions. (See 'Differential diagnosis' below.)
Study selection — Vasculopathic features of moyamoya can be identified by noninvasive computed tomography angiography (CTA), magnetic resonance angiography (MRA), or conventional digital subtraction angiography (DSA).
●Noninvasive vascular imaging – CTA or MRA are noninvasive cerebrovascular imaging modalities that may be used for the diagnosis in many patients. Revised diagnostic criteria permit diagnosis of moyamoya with high-quality noninvasive imaging studies that show characteristic findings involving bilateral carotid and middle cerebral arteries (see 'Diagnostic criteria' below). CTA and MRA have supplanted conventional DSA in many centers as the initial imaging modality to evaluate moyamoya [198,201]. MRA is the preferred initial study for children with suspected moyamoya to avoid radiation and contrast exposure associated with other modalities [202]. CTA is frequently performed as part of the initial imaging evaluation of patients with acute stroke symptoms.
Noninvasive vascular studies may identify vasculopathy characteristic for moyamoya and may also help with surgical planning by showing the relationship between intracranial moyamoya vasculopathy and potential extracranial donor vessels. However, they have limitations in assessing collateral circulation involving very small vessels and may not accurately detect early-stage moyamoya changes.
●DSA – DSA is regarded as the gold standard for the diagnosis of moyamoya due to its superior spatial resolution and is required for patients with nondiagnostic or unilateral findings on noninvasive imaging studies (see 'Diagnostic criteria' below) [203]. It is also typically required for patients undergoing surgical treatment planning because it provides anatomical information regarding potential donor vessels like the superficial temporal or occipital arteries in the affected hemisphere [202]. However, DSA is an invasive study that requires arterial puncture and has been associated with uncommon procedural complications including puncture site hematoma, infection, and risk of vascular injury including dissection and stroke. Neurologic complications occur in approximately 3 per 1000 DSA procedures [204].
●Other testing for selected patients – Advanced vessel wall imaging may be performed for selected patients with nondiagnostic DSA to help characterize the etiology of arterial stenosis. The presence of “negative remodeling of blood vessels” may help differentiate MMD from atherosclerosis by showing a reduced outer diameter of the terminal portion of ICA or proximal middle cerebral artery (MCA) in moyamoya, a characteristic absent in atherosclerosis. In the early stage, intimal thickening leads to supraclinoid carotid stenosis and a reduction in outer diameter. As moyamoya progresses, medial thinning and alterations in the elastic lamina further contribute to arterial shrinkage, advancing alongside luminal stenosis [205,206].
Concentric postcontrast enhancement within the distal internal carotid arterial walls may be seen on high-resolution brain MRI in patients with moyamoya, whereas patients with intracranial atherosclerotic disease generally have focal and eccentric enhancement of the symptomatic arterial segment [207,208].
Characteristic findings — Characteristic angiographic findings include stenosis or occlusion at the distal ICA and the origin of the anterior cerebral artery (ACA) and MCA on both sides, as well as abnormal vascular networks at the basal ganglia or moyamoya vessels (image 1).
●Proximal arterial stenosis – Noninvasive imaging (CTA and MRA) can demonstrate stenotic or occlusive lesions in the distal ICAs (image 10) and the arteries around the circle of Willis [199-201]. Anterior circulation vessels (ICA, MCA, and ACA) are most commonly involved; however, some patients with bilateral or advanced involvement may have posterior circulation involvement. In a review of 120 adult and pediatric patients with moyamoya, posterior cerebral artery stenosis was found in 29 percent [209].
●Abnormal collateral vessels – Although less sensitive than DSA for smaller vessels, noninvasive testing can also visualize the collateral "moyamoya vessels" in the basal ganglia (image 11).
Cerebral aneurysms may also be found adjacent to areas of stenosis or collateral vessels [165]. Ruptured aneurysms can cause subarachnoid and/or intraventricular hemorrhagic presentations.
Because the vascular changes and associated risks of ischemia or hemorrhage sequelae in MMD and MMS are often progressive, characterizing the degree of vascular abnormality is important. Angiographic severity staging systems can help monitor disease progression. The Suzuki classification of angiographic progression in moyamoya is widely used [155,210]. Findings on DSA include:
●Stage I – Narrowing of the intracranial internal carotid bifurcation
●Stage II – Narrowing of the distal intracranial ICA plus dilation of the ACA and MCA, initial moyamoya blush in striatocapsular collaterals
●Stage III – Loss of opacification of the proximal ACA and MCA, development of leptomeningeal collateralization from the posterior cerebral arteries, and increased prominence of moyamoya blush
●Stage IV – Progressive occlusion of the ICA up to the origin of the posterior cerebral artery (PCA) and reduction of moyamoya blush
●Stage V – Complete loss of opacification of the ICA, ACA, and MCA, development of intracranial collateral supply from the external carotid artery (ECA), and further reduction of moyamoya blush
●Stage VI – Loss of intracranial opacification/blood supply from the ICA; blood supply exclusively from the ECA
Several other scoring systems have been established for assessing severity of moyamoya. The Berlin grading system uses a combination of information from DSA, brain MRI, and cerebral perfusion studies [211,212]. The Angiographic Outcome Score uses DSA calculating vascular severity based on findings at major intracranial vessels, basal collaterals, leptomeningeal collaterals, transdural collaterals, and regional perfusion [213].
The role of perfusion studies to assess cerebrovascular reserve is discussed in greater detail separately. (See "Moyamoya disease and moyamoya syndrome: Treatment and prognosis", section on 'Neuroimaging'.)
Differential diagnosis — Alternative conditions that may mimic vascular findings of moyamoya include other intracranial vasculopathies. These are identified by specific vascular features and/or by other associated clinical findings and may include:
●Intracranial atherosclerosis – Patients with intracranial atherosclerotic stenosis often have atherosclerotic risk factors such as hypertension, hyperlipidemia, type 2 diabetes mellitus, chronic kidney disease, and/or a history of tobacco use, as well as older age. Vessel imaging in atherosclerosis typically reveals luminal narrowing but does not show a reduction in the outer vessel diameter, which often helps differentiate it from moyamoya. In addition, collateral vessel formation in the lenticulostriate region, characteristic of moyamoya vasculopathy, is mild or absent in intracranial atherosclerosis. (See "Intracranial large artery atherosclerosis: Epidemiology, clinical manifestations, and diagnosis".)
●Arterial dissection – Intracranial arterial dissection may occur at the terminal portion of the ICA or MCA, typical locations of vascular stenosis in moyamoya. However, clinical features associated with dissection are typically monophasic and spontaneous rather than recurrent over weeks to months or triggered by episodes of laughing or crying. High-resolution vessel wall imaging can help discriminate between these conditions by showing the vessel lining tear and intramural thrombus in dissection cases or stenosis involving the outside diameter of the vessel and prominent collateral vessels in moyamoya cases. (See "Cerebral and cervical artery dissection: Clinical features and diagnosis".)
●Reversible cerebral vasoconstriction syndrome – Reversible cerebral vasoconstriction syndrome (RCVS) is a group of conditions characterized by multifocal narrowing of the cerebral arteries, including distal ICA and MCA. It is clinically characterized by abrupt-onset severe (thunderclap) headache that may be recurrent over several days. Prominent collaterals are not found in RCVS, and apparent vasoconstriction resolves if follow-up imaging is performed. (See "Reversible cerebral vasoconstriction syndrome".)
●Focal cerebral arteriopathy – Focal cerebral arteriopathy (FCA) is a term that describes a unilateral focal arterial stenosis found in children with ischemic stroke. It may be due to dissection or focal inflammation. FCA may be found in the distal ICA, proximal MCA, and/or ACA, but prominent collateral vessels are not associated with this condition. Unlike moyamoya, FCA is usually a nonprogressive condition [214]. (See "Ischemic stroke in children and young adults: Epidemiology, etiology, and risk factors", section on 'Focal cerebral arteriopathy'.)
●Vasculitis – Imaging findings in vasculitis may mimic the stenotic findings characteristic of moyamoya. However, prominent collateral vessels are not characteristic of vasculitis. In addition, angiitis of the central nervous system is more commonly associated with indolent clinical systems such as headache or cognitive impairment, and systemic vasculitis with cerebrovascular involvement may be associated with musculoskeletal, dermatologic, or other symptoms associated with the underlying vasculitis. (See "Vasculitis in children: Incidence and classification" and "Overview of and approach to the vasculitides in adults", section on 'Major categories of vasculitis'.)
Diagnostic criteria — Diagnostic criteria for moyamoya, updated in 2021 by the Research Committee on MMD of the Ministry of Health, Labor and Welfare, Japan, require either invasive or noninvasive cerebrovascular imaging, using either DSA or brain MRI and MRA, respectively.
Diagnostic findings for moyamoya include the following [215]:
●DSA – Cerebrovascular angiography with DSA is the gold standard imaging modality for moyamoya due to superior resolution over noninvasive options. Diagnostic findings of moyamoya on DSA include:
•Stenosis or occlusion centered at the terminal portion of one or both intracranial ICAs AND
•Moyamoya vessels (abnormal vascular networks) near the occlusive or stenotic lesions in the arterial phase.
Both bilateral and unilateral findings on DSA can be diagnosed as moyamoya.
●Noninvasive vascular imaging – Moyamoya can be diagnosed on MRA when the following signs are present:
•Stenosis or occlusion of the terminal portion of both intracranial ICAs, AND
•Narrowing of the outer diameters of both the terminal portion of both ICAs and both proximal MCAs, AND
•Moyamoya collateral vessels (abnormal vascular networks) in the basal ganglia and/or periventricular white matter.
Abnormal vascular networks typically identified on MRA may also be identified on brain MRI that shows reticular flow voids in the basal ganglia (image 9), the “ivy” sign (image 7), or both.
CTA may also be performed to identify moyamoya findings, although it was not specified in the diagnostic criteria. CTA is noninvasive like MRA but is typically quicker to perform and routinely used as a part of the initial evaluation of patients with acute stroke. (See 'Study selection' above.)
For unilateral findings or stenotic lesions without apparent narrowing of the outer diameter of the vessel wall on noninvasive imaging, DSA is required to exclude atherosclerosis and other vasculopathies.
For the diagnosis of MMD, underlying associated conditions (suggestive instead of MMS) are excluded. (See 'Further evaluation' below.)
Further evaluation
●Assess for underlying cause – For individuals with a known genetic predisposition to MMD, we refer for genetic counseling and testing. (See 'Genetic associations' above and "Genetic counseling: Family history interpretation and risk assessment".)
In the absence of a known genetic predisposition to MMD, patients with moyamoya should be evaluated for underlying conditions to institute the most appropriate secondary prevention strategy. We perform a comprehensive history and clinical examination to assess for conditions associated with MMS. (See 'Associated conditions' above.)
Specific testing varies depending on the clinical circumstances such as patient age and the presence of clinical features suggestive of a systemic condition (eg, vasculitis) [215].
•For children and adults with unilateral vascular findings, we typically assess for associated thyroid disease and autoimmune conditions (eg, systemic lupus erythematosus, polyarteritis nodosa, Sjögren syndrome). (See "Primary angiitis of the central nervous system in adults", section on 'Laboratory testing to exclude alternative diagnoses'.)
•For children and adults with mild or unilateral vascular findings who present with ischemic stroke, we obtain laboratory testing to assess for hypercoagulable conditions. In addition, we obtain herpes simplex virus and varicella zoster virus antibodies, as these infections have been implicated in cases of vasculopathy due to focal cerebral arteriopathy. (See "Arterial ischemic stroke in children and adolescents: Clinical presentation and evaluation", section on 'Hypercoagulable evaluation' and "Arterial ischemic stroke in children and adolescents: Clinical presentation and evaluation", section on 'Focal cerebral arteriopathy'.)
•For adults who present with ischemic stroke or ICH, we assess for atherosclerotic risk factors (eg, diabetes mellitus, dyslipidemia, tobacco use, hyperhomocysteinemia) to identify alternative sources of large-vessel vasculopathy. (See "Intracranial large artery atherosclerosis: Epidemiology, clinical manifestations, and diagnosis", section on 'Identifying other causes of intracranial stenosis'.)
Referral for genetic counseling and testing may also be appropriate for selected patients with moyamoya who have no known genetic predisposition to MMD when evaluation for underlying conditions associated with MMS is unrevealing.
●Determine cerebrovascular reserve – Hemodynamic perfusion studies are used to assess and monitor cerebrovascular reserve, to assess disease severity, and to determine the risk of ischemic morbidity. These modalities are discussed in greater detail separately. (See "Moyamoya disease and moyamoya syndrome: Treatment and prognosis", section on 'Neuroimaging'.)
THE ROLE OF SCREENING IMAGING —
In general, we do not screen asymptomatic individuals for moyamoya; however, screening with a noninvasive angiographic modality may be reasonable in those with a family history of MMD, particularly individuals from or with families from Eastern Asia.
A 2019 scientific statement from the American Heart Association indicates that there is insufficient evidence to recommend screening studies in asymptomatic individuals or in relatives of patients with moyamoya in the absence of a strong family history of MMD or medical conditions that predispose to MMS [202].
Even in individuals with a strong family history of MMD or those with medical conditions that predispose to MMS, the utility of angiographic screening is unclear, particularly since available medical and surgical treatment of asymptomatic MMD is of uncertain benefit. In addition, normal results on a single screening imaging study, particularly in younger individuals, do not exclude the possibility that moyamoya vasculopathy will develop later.
SOCIETY GUIDELINE LINKS —
Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Stroke in adults" and "Society guideline links: Stroke in children".)
SUMMARY AND RECOMMENDATIONS
●Definitions – Moyamoya is a cerebrovascular condition characterized by the progressive narrowing of large intracranial arteries around the circle of Willis and the secondary development of prominent small-vessel collateral vessels (image 1 and image 11). (See 'Terminology' above.)
•Moyamoya disease (MMD) is a condition characterized by the occurrence of moyamoya angiographic findings along with associated genetic susceptibilities but no underlying contributing medical conditions. (See 'Genetic associations' above.)
•Moyamoya syndrome (MMS) is a condition characterized by the occurrence of moyamoya angiographic findings along with an associated medical condition implicated in the development of vascular changes. (See 'Associated conditions' above.)
●Epidemiology – MMD and MMS are rare with annual incidence rates ranging from 0.35 to 0.94 per 100,000 individuals and prevalence rates ranging from 3.2 to 10.5 per 100,000. MMD is more common in Japan, China, and Korea than elsewhere. There is a bimodal distribution in the age of onset, with one peak at 5 to 10 years of age and a second, broader peak at 30 to 50 years of age. (See 'Epidemiology' above.)
●Initial presentations – Moyamoya can present with a range of neurologic symptoms and suggestive neuroimaging findings related to the underlying intracranial vasculopathy, but it also may be asymptomatic, found incidentally on neuroimaging pursued for other indications. (See 'Clinical features' above.)
•Neurologic features – Moyamoya most commonly presents with cerebrovascular ischemic or hemorrhagic symptoms but may also present less commonly with seizures or other neurologic symptoms. Ischemic stroke or transient ischemic attack (TIA) symptoms may be spontaneous or triggered (eg, by exercising or with episodes of crying or laughing) and recurrent, reflecting an underlying fixed vascular stenosis.
•Neuroimaging findings – Cerebral infarction often involves cortical and subcortical regions (image 6). Superficial and deep border-zone regions distal to the stenotic or occluded moyamoya vessel are most susceptible to hypoperfusion. Intracerebral hemorrhage (ICH) typically occurs in deep structures such as the basal ganglia, thalamus, and/or ventricular system due to the proximity of associated small collateral vessels (image 5). (See 'Initial neuroimaging findings' above.)
Evidence of vasculopathy may be found on brain imaging including the “ivy sign” (image 7), the “brush sign” (image 8), and multiple punctate or serpentine flow voids (hypointense on T2-weighted MRI) in the basal ganglia or thalamus (image 9). Noninvasive vascular imaging may demonstrate characteristic stenotic or occlusive lesions in the distal internal carotid arteries (ICAs) and/or the proximal arteries around the circle of Willis (image 10) as well as collateral "moyamoya vessels" in the basal ganglia (image 11).
●Diagnosis – The diagnosis of moyamoya is made by identifying the characteristic angiographic appearance of bilateral stenoses affecting the distal ICAs (or other proximal circle of Willis vessels) along with the presence of prominent collateral vessels (image 6) after excluding alternative conditions. (See 'Diagnosis' above.)
•Cerebrovascular imaging – Cerebrovascular evaluation is required for the diagnosis of moyamoya to identify characteristic vasculopathy and exclude alternative conditions. Noninvasive brain MRI and MR angiogram or CT angiogram may be used for diagnosis in patients with characteristic findings involving bilateral carotid and middle cerebral arteries (MCAs). Digital subtraction angiography (DSA) is regarded as the gold standard for diagnosis due to its superior spatial resolution and is required for patients with unilateral findings on noninvasive imaging studies. (See 'Vascular imaging evaluation' above.)
•Differential diagnosis – Alternative conditions that may mimic vascular findings of moyamoya include other intracranial vasculopathies. These are identified by specific vascular features and/or by other associated clinical findings and may include intracranial atherosclerosis, arterial dissection, reversible cerebral vasoconstriction syndrome, focal cerebral arteriopathy of childhood, and cerebral vasculitis. (See 'Differential diagnosis' above.)
•Additional evaluation – For individuals with a known genetic predisposition to MMD, we refer for genetic counseling and testing. For other patients with moyamoya, we perform a comprehensive history and clinical examination to assess for conditions associated with MMS. Specific testing varies depending on the clinical circumstances such as patient age and the presence of clinical features suggestive of a systemic condition (eg, vasculitis). (See 'Associated conditions' above.)
