Moyamoya disease: Etiology, clinical features, and diagnosis

Author
Nijasri Charnnarong Suwanwela, MD
Section Editors
Jose Biller, MD, FACP, FAAN, FAHA
Douglas R Nordli, Jr, MD
Deputy Editor
John F Dashe, MD, PhD
Disclosures: Nijasri Charnnarong Suwanwela, MD Grant/Research/Clinical Trial Support: AstraZeneca [Acute
ischemic stroke (Ticagrelor)]; Lundbeck [Acute ischemic stroke (Desmoteplase)]. Consultant/Advisory Boards: Bayer AG
[AF and stroke (Rivaroxaban)]; Boehringer Ingelheim [AF and stroke (Dabigatran)]; Pfizer [AF and stroke (Apixaban)].
Speaker's Bureau: Bayer AG [Ischemic stroke (Rivaroxaban)]; Boehringer Ingelheim [Ischemic stroke (Dabigatran)];
Sanofi [Ischemic stroke (Clopidogrel)]. Jose Biller, MD, FACP, FAAN, FAHA Nothing to disclose. Douglas R Nordli,
Jr, MDGrant/Research/Clinical Trial Support: NIH [febrile status, SUDEP]. Consultant/Advisory Boards: Eisai [AED
(zonisamide, perampanel)]. John F Dashe, MD, PhD Nothing to disclose.

Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by
vetting through a multi-level review process, and through requirements for references to be provided to support the
content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of
evidence.

Conflict of interest policy

All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Oct 2015. | This topic last updated: Jul 23, 2015.

INTRODUCTION — Moyamoya disease (MMD) is a unique chronic progressive cerebrovascular

disease characterized by bilateral stenosis or occlusion of the arteries around the circle of Willis with
prominent arterial collateral circulation. "Moyamoya" is a Japanese word meaning puffy, obscure, or
hazy like a puff of smoke in the air. Thus, the term was used to describe the smoky angiographic
appearance of the vascular collateral network [1,2].

Moyamoya disease was first described in Japan in 1957. Many similar cases have subsequently been
reported, mainly in Japan and other Asian countries. The disease is found less frequently in North
America and Europe.

This topic will review the etiology and clinical aspects of moyamoya disease. Prognosis and treatment
are discussed elsewhere. (See "Moyamoya disease: Treatment and prognosis".)

ETIOLOGY — The etiology of MMD is unknown. The high incidence among the Japanese and Asian
population, together with a familial occurrence of approximately 10 to 15 percent of cases, strongly
suggests a genetic etiology.

Accumulating evidence suggests that the RNF213 gene on chromosome 17q25.3 is an important
susceptibility factor for MMD in East Asian populations [3-8].

●A report from Japan found that the c.14576G>A variant of RNF213 was present in 95 percent of
41 patients with familial MMD, 79 percent of 163 patients with sporadic MMD, and 2 percent of
283 normal control subjects [5].
●A study in the Han Chinese population demonstrated that mutations in RNF213 gene were
associated with increased susceptibility to MMD; ischemic MMD was related to the R4810K
mutation, whereas hemorrhagic MMD was associated with the A4399T mutation [9].
●In a report from Korea of 352 subjects with intracranial large artery stenosis, the c.14429G>A
variant of RNF213 was detected in 76 percent of subjects meeting all criteria for MMD (n = 131),
in 35 percent of 221 subjects with intracranial stenosis (n = 221), and in none of the healthy
control subjects (n = 51) [10].
Other reports have linked familial moyamoya disease to chromosomes 3p24.2-p26, 6q25, 8q23, and
12p12 [11-13]. Although the mode of inheritance is not established, one study suggested that familial
moyamoya is an autosomal dominant disease with incomplete penetrance [14]. 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 and "Basic
principles of genetic disease", section on 'Imprinting'.)

Several alleles of class II genes of the human leukocyte antigen (HLA) have been associated with
moyamoya disease [15]. 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 [16,17]. Transforming growth factor beta-1, which mediates
neovascularization, may also contribute to the pathogenesis of the disorder [18,19]. High levels of
hepatocyte growth factor, a strong inducer of angiogenesis, have been detected in the carotid fork and
cerebrospinal fluid in patients with moyamoya disease [20].

An association between upper respiratory tract infection, especially tonsillitis, and moyamoya disease
has been observed, suggesting the possibility of autoimmune disease. However, the absence of
immune complexes on blood vessel walls argues against this hypothesis.

Associated conditions — Classic angiographic findings of moyamoya vessels have been

demonstrated in patients with other medical conditions. This has led some investigators to propose the
term "moyamoya phenomenon" or "moyamoya syndrome" as an entity separate from true idiopathic
moyamoya disease.

Traditionally, patients with the angiographic appearance of moyamoya and no known risk factors are
considered to have moyamoya disease, while those with one of the well recognized associated
conditions (neurofibromatosis type 1, cranial irradiation, Down syndrome, and sickle cell disease) are
classified as having moyamoya syndrome [21].

Some of the conditions associated with moyamoya include:

●Atherosclerosis [22]
●Infectious diseases
•Meningitis [23]
•Other viral or bacterial infection (eg, Propionibacterium acnes, leptospirosis, HIV) [24,25]
●Hematologic conditions
•Sickle cell disease [26-28]
•Beta thalassemia [29]
•Fanconi anemia [30]
•Hereditary spherocytosis [31]
•Homocystinuria and hyperhomocysteinemia [32]
•Factor XII deficiency [33]
•Essential thrombocythemia [34]
●Vasculitis and autoimmune diseases
•Systemic lupus erythematosus [35]
•Polyarteritis nodosa and postinfectious vasculopathy [36]
•Graves disease and thyroiditis [37-40]
•Sneddon syndrome and the antiphospholipid antibody syndrome [41,42]
•Anti-Ro and anti-La antibodies [43]
•Type 1 diabetes mellitus [40]
 ●Connective tissue disorders and neurocutaneous syndromes
•Neurofibromatosis type 1 (NF1) [44-46]
•Tuberous sclerosis [47]
•Sturge-Weber syndrome [48]
•Phakomatosis pigmentovascularis type IIIb [49]
•Hypomelanosis of Ito [50]
•Pseudoxanthoma elasticum [51]
•Marfan syndrome [52]
●Chromosomal disorders
•Down syndrome [53,54]
•Turner syndrome [55]
•Alagille syndrome [56,57]
●Other vasculopathies
•Vasospasm after subarachnoid hemorrhage [58]
•Radiation therapy to the base of the brain (see "Delayed complications of cranial
irradiation", section on 'Cerebrovascular effects') [59]
•Fibromuscular dysplasia [60]
●Other extracranial cardiovascular diseases
•Congenital heart disease [61]
•Williams syndrome [62]
•Coarctation of the aorta [63]
•Renal artery stenosis [64]
●Metabolic diseases
•Type I glycogenosis [65,66]
•Hyperphosphatasia [67]
•Primary oxalosis [68]
●Cranial trauma [69]
●Brain tumors [70-72]
●Cavernous malformation [73]
●Pulmonary sarcoidosis [74,75]
●Hereditary multisystem disorder with short stature, hypergonadotropic hypogonadism, and
dysmorphism [76]
●Polycystic kidney disease [77-79]

EPIDEMIOLOGY — In epidemiologic surveys conducted in Japan, the following observations have

been made [80-82]:

●The annual incidence of moyamoya is 0.35 to 0.94 per 100,000 population

●The prevalence of moyamoya is 3.2 to 10.5 per 100,000 population
●There is a female predominance, with a male-to-female ratio of 1:1.8 to 1:2.2
●A family history of moyamoya disease is present in 10.0 to 15.4 percent of patients

A study that analyzed hospital discharge data from Washington and California in the western United
States found an estimated overall moyamoya incidence (combined idiopathic moyamoya disease and
moyamoya syndrome) of 0.086 per 100,000, lower than in Japan [83]. Among ethnic groups in
California, the moyamoya incidence rate for Asians was 0.28 per 100,000, similar to the incidence in
Japan. The incidence rates were lower for blacks, whites, and Hispanics (0.13, 0.06, and 0.03 per
100,000, respectively).

Age distribution — Moyamoya disease and moyamoya syndrome occur in children and adults of all
ages, although presentation in infancy is rare [84]. Data from Japan regarding the peak age of
moyamoya disease onset are conflicting. A study published in 1995 found a major peak in the 10 to 14
year old age group and a lesser peak in the 40 to 49 year old group [80]. In contrast, a report
published in 2008 found a major peak in the 45 to 49 year old group and a lesser peak in the 5 to 9
year old group [82]. Methodologic differences between studies and improved clinical detection over
time may, at least in part, account for the apparent change in age distribution of moyamoya in Japan.
A cohort study of 802 patients with moyamoya disease from China also demonstrated a bimodal age
distribution, with a major peak in the 5 to 9 year old group and another peak in the 35 to 39 year old
group [85].

CLINICAL FEATURES — The clinical manifestations of moyamoya are variable and include transient
ischemic attack (TIA), ischemic stroke, hemorrhagic stroke, and epilepsy. Although data are
inconsistent, a 2012 systematic review of population-based studies found that the predominant mode
of presentation was ischemia, particularly in children [86]. However, there may be regional and ethnic
differences in the expression of disease by age at the time of diagnosis.

●In the systematic review, intracerebral hemorrhage was the most frequent initial presentation in
China and Taiwan [86]. In an earlier study from Japan not included in the systematic review,
ischemic events were more prevalent than hemorrhagic events in children with moyamoya, while
hemorrhagic stroke (mainly intraparenchymal and intraventricular hemorrhage) was more
common in adults [87]. The rate of epilepsy was also more frequent in children than in adults. A
report from Korea noted that hemorrhagic stroke in moyamoya disease often presented as
intraventricular hemorrhage with or without intraparenchymal hemorrhage [88].
●In contrast, reports from other populations have found that ischemia is more frequent than
hemorrhage in adults with moyamoya disease and moyamoya syndrome [89,90]. As examples,
in a retrospective report from the United States of 31 adults (14 white, 9 Hispanic, 4 black, and 3
Asian) with moyamoya disease or moyamoya syndrome, ischemic symptoms were the
presentation for 19 patients (61 percent), and consisted mainly of a watershed pattern of
infarction in those with stroke [90]. A retrospective study from Germany of 21 white patients with
idiopathic moyamoya disease found that all presented with ischemic events, including 16 who
were adults at symptom onset [89]. Only one hemorrhagic stroke (a subarachnoid hemorrhage)
occurred during a mean follow-up of 3.7 years.

Nevertheless, small patient numbers in studies of moyamoya performed outside of Asian countries
prevent definitive conclusions about regional differences in moyamoya expression.

Among symptomatic patients with moyamoya disease, some have only one or a few events, while
others have multiple recurrences. In a study from Korea with 88 patients (36 of whom had
revascularization surgery) from 1 to 75 years of age at presentation who were followed for 6 to 216
months, the following outcomes were reported [91]:

●A single ischemic or hemorrhagic cerebrovascular episode was noted in 40 patients (45

percent).
●Recurrent ischemic and hemorrhagic cerebrovascular events occurred in 48 patients (55
percent). Recurrences included ischemic events (TIA and/or infarction) in 37 patients, ischemic
and hemorrhagic events in 9, and multiple hemorrhages in 2.
●The most frequent neurologic deficit was hemiparesis in 64 percent of cases. Additional
common sequelae were aphasia, seizure, altered mentation, and visual disturbance.
In children, symptomatic episodes of ischemia may be triggered by exercise, crying, coughing,
straining, fever, or hyperventilation [92,93].

There are case reports of patients with moyamoya who develop dystonia, chorea, or dyskinesia, but
these appear to be uncommon manifestations of moyamoya [94-96]. Rare patients with moyamoya
disease have morning glory optic disc anomaly (picture 1), usually in conjunction with other
craniofacial abnormalities [97-99]. (See "Congenital anomalies and acquired abnormalities of the optic
nerve", section on 'Morning glory disc'.)

The prognosis of moyamoya disease is discussed separately. (See "Moyamoya disease: Treatment
and prognosis", section on 'Natural history and prognosis'.)

Suzuki stages — Suzuki and colleagues followed patients with moyamoya disease and classified the
angiographic progression into six stages [1,2]:

●Stage 1 – Narrowing of carotid fork only

●Stage 2 – Initiation of basal moyamoya with dilatation of all main cerebral arteries
●Stage 3 – Intensification of moyamoya together with reduction of flow in the middle and anterior
cerebral arteries
●Stage 4 – Minimization of moyamoya vessels; the proximal portions of the posterior cerebral
arteries become involved
●Stage 5 – Reduction of moyamoya and absence of all main cerebral arteries
●Stage 6 – Disappearance of moyamoya vessels; the cerebral circulation is supplied only by the
external carotid system

NEUROIMAGING — Head CT and/or brain MRI are important studies for the detection of brain
infarction and hemorrhage in patients with moyamoya. Noninvasive and conventional angiographic
studies can demonstrate stenosis or occlusion of the Circle of Willis vessels. Transcranial Doppler
ultrasonography is a noninvasive way to evaluate intracranial hemodynamics and large artery
stenosis. A number of methods may be useful to estimate resting brain perfusion and blood flow
reserve.

Head CT — On CT scan, infarction may involve cortical and subcortical regions (image 1). Dilatation
of the sulci, accompanied by focal ventricular enlargement indicating volume loss, is usually found in
the chronic phase of disease. In a retrospective series of 32 adults with MMD and first-ever ischemic
stroke, patients with early stage MMD (ie, Suzuki stage 1 or 2) had ischemic lesions on brain MRI
involving only deep subcortical structures, while those with advanced stage MMD (ie, Suzuki stage 3
or higher) had predominantly cortical lesions [100]. (See 'Suzuki stages' above.)

In patients with parenchymal hemorrhage, cranial CT usually shows a high density area indicating
blood in the basal ganglia, thalamus, and/or ventricular system (image 2). Bleeding in the cortical and
subcortical regions has been reported with lower frequency [101,102].

Brain MRI — Brain MRI, particularly diffusion and perfusion MR techniques, is superior to CT scan for
detection of small and/or acute ischemic brain lesions. In one report of 20 children from Canada with
angiographic moyamoya, ischemic injury involving superficial and deep border zone (ie, watershed)
regions, particularly deep border zones, was observed in over one-half of children [103].

In some cases, dilated collateral vessels in the basal ganglia and thalamus can be demonstrated as
multiple punctate flow voids, a finding which is considered virtually diagnostic of moyamoya syndrome
[21]. In prospective studies from Japan, asymptomatic cerebral microbleeds were present on gradient
echo (T2*) MRI sequences in 30 percent or more of adult patients with MMD [104-106]; the presence
of these lesions may predict subsequent intracerebral hemorrhage.
In patients with moyamoya, both fluid-attenuated inversion recovery (FLAIR) images and post contrast
T1 images may show a linear pattern of increased signal in the leptomeninges and perivascular
spaces [107,108]. This pattern has been termed the "ivy sign," since it resembles the appearance of
ivy creeping on stones [107]. The probable cause is slow retrograde collateral flow through engorged
pial vessels via leptomeningeal anastomosis [108,109]. Observational data suggest the ivy sign is
correlated with decreased cerebrovascular reserve [110].

One small study using high resolution MRI vascular wall imaging found that nearly all patients with
MMD demonstrated concentric enhancement of the distal internal carotid arteries, whereas patients
with intracranial atherosclerotic disease generally had focal and eccentric enhancement of the
symptomatic arterial segment [111].

Angiography — Magnetic resonance angiography (MRA) can demonstrate stenotic or occlusive

lesions in the distal internal carotid arteries (image 3) and the arteries around the circle of Willis
[112,113]. In addition, MRA can visualize the collateral "moyamoya vessels" in the basal region (image
4), although it is less sensitive to smaller vessel occlusion than conventional cerebral angiography.
Nevertheless, due to its high diagnostic yield and noninvasive nature, MRA has supplanted
conventional angiography in most centers as the primary imaging modality to evaluate moyamoya
syndrome [21,113]. Computed tomographic angiography (CTA) can also noninvasively demonstrate
the abnormal vessels of moyamoya disease, including the collateral moyamoya vessels in the basal
ganglia [114].

Although now used less frequently than MRA and CTA, conventional cerebral angiography is the gold
standard for the diagnosis of moyamoya disease. Characteristic angiographic findings include stenosis
or occlusion at the distal internal carotid artery and the origin of the anterior cerebral and middle
cerebral arteries on both sides, and abnormal vascular networks at the basal ganglia or moyamoya
vessels (image 1 and image 2).

The Suzuki angiographic stages of moyamoya disease are discussed above. (See 'Suzuki
stages' above.)

In adults who presented with intracerebral or intraventricular hemorrhage, small aneurysms in the
periventricular area have been reported (picture 2).

Hemodynamic studies — Transcranial Doppler ultrasonography (TCD) provides a noninvasive way

to evaluate intracranial hemodynamics by measuring blood flow velocity in large intracranial vessels at
the circle of Willis [21]. Since the mean velocity of blood flow is inversely related to arterial diameter,
TCD can also detect arterial occlusive disease; a focal increase in velocity usually suggests large
artery stenosis.

In patients with suspected moyamoya disease, TCD has been used in the initial evaluation of
moyamoya disease, and serial TCD studies have been used to follow changes in blood flow over time
[21,115,116]. One of the most widespread applications of this method is in patients with sickle cell
disease. (See "Cerebrovascular complications of sickle cell disease", section on 'Predicting risk'.)

Although supporting evidence is limited, additional methods that may be useful to determine the extent
of inadequate resting brain perfusion and blood flow reserve in patients with moyamoya disease prior
to and after treatment include the following [21,117-122]:

●Perfusion CT
●Xenon-enhanced CT
●Perfusion-weighted MRI
●Positron emission tomography (PET)
 ●Single-photon emission CT (SPECT) with acetazolamide challenge

PATHOLOGY — Brain tissue of patients with moyamoya disease usually reveals evidence of prior
stroke. However, the cause of death in most autopsy cases is intracerebral hemorrhage [123]. The
hemorrhage is commonly found in the basal ganglia, thalamus, hypothalamus,
midbrain, and/or periventricular region. Bleeding into the intraventricular space is frequently observed.
Multiple areas of cerebral infarction and focal cortical atrophy are commonly found.

Although large vessel stenosis and occlusion are the hallmark of this disease, extensive territorial
infarction is uncommon. The brain infarcts are generally small and located in the basal ganglia,
internal capsule, thalamus, and subcortical regions [124].

Vascular stenosis — Pathologic vascular lesions appear in the large vessels of the circle of Willis
and in the small collateral vessels [125]. Bilateral concentric stenosis or occlusion is consistently found
in the distal internal carotid arteries and the proximal anterior and middle cerebral arteries. Less
frequently, the posterior circulation is affected, especially the posterior cerebral artery.

In the large arteries, variable stenosis or occlusion is associated with the following microscopic
features [126-128]:

●Fibrocellular thickening of the intima

●Tortuosity and/or duplication or triplication of the internal elastic lamina
●Attenuation of the media

As an example, one study found that specimens of the middle cerebral artery from patients with
moyamoya (n = 25) had significantly thinner media and thicker intima than those from control subjects
(n = 6) [129].

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 [126].
Dilated vessels, more common in younger patients than in adults, tend to show fibrosis with
attenuation of the media, and microaneurysm formation. Stenotic vessels tend to have intimal
thickening and duplication of the elastic lamina.

Collateral vessels — One of the hallmarks of moyamoya disease is the presence of a collateral
meshwork of overgrown and dilated small arteries, the moyamoya vessels, that branch from the circle
of Willis.

Leptomeningeal vessels are another source of collaterals in moyamoya (image 5). As a result of
intracranial internal carotid artery stenosis, leptomeningeal anastomoses may develop among the
three main cerebral arteries (middle, anterior, and posterior). These collaterals result from dilatation of
preexisting arteries and veins. In addition, transdural anastomoses, termed vault moyamoya, may
develop from extracranial arteries such as the middle meningeal and superficial temporal arteries
[130]. Ethmoidal moyamoya is the term applied when the collateral network involves primarily the
frontobasal region, derived from the ophthalmic artery and the posterior and anterior ethmoidal
arteries.

Aneurysms — Cerebral aneurysms have been associated with moyamoya disease in a number of
reports [131-135].

●Large artery aneurysms can develop at vessel branching points in the circle of Willis and cause
subarachnoid hemorrhage when they rupture. In patients with unilateral moyamoya, these
aneurysms are found most commonly in the anterior communicating artery/anterior cerebral
artery complex [136]. In patients with bilateral moyamoya, aneurysms are more often located in
 the basilar artery [136]. Histologic study from autopsy specimens of large artery aneurysms
showed disappearance of internal elastic lamina and media [137]. These findings are similar to
those of the berry aneurysm commonly observed in primary subarachnoid hemorrhage.
●Aneurysms can also arise from the small collateral moyamoya vessels, choroidal arteries, or
other peripheral collateral arteries [136]. These small vessel aneurysms are the major cause of
parenchymal (intracerebral) hemorrhage in moyamoya disease.

Extracranial involvement — In patients with moyamoya disease, stenosis due to fibrocellular intimal
thickening may also affect the extracranial and systemic arteries, including the cervical carotid, renal,
pulmonary, and coronary vessels [127,138]. Involvement of the renal arteries has been most
frequently reported. In one study of 86 patients with moyamoya, six (7 percent) had renal artery
stenosis, two had associated renovascular hypertension, and one had a renal artery aneurysm [64].
Similarly, in a later study of 73 consecutive patients with moyamoya, four (5 percent) had renal artery
stenosis [139].

DIAGNOSIS — The diagnosis of moyamoya disease is based upon the characteristic angiographic
appearance of bilateral stenoses affecting the distal internal carotid arteries and proximal circle of
Willis vessels, along with the presence of prominent basal collateral vessels.

Repeated ischemic attacks resulting from low perfusion in the same arterial
territory, and/or intracerebral hemorrhage in the region of the caudate, or intraventricular hemorrhage
within the lateral ventricles, are patterns suggestive of moyamoya disease. However, some patients
are clinically asymptomatic. Definitive diagnosis requires neurovascular imaging.

Moyamoya disease is one of the differential diagnoses of stroke in children or young adults.
(See "Ischemic stroke in children and young adults: Etiology and clinical features", section on
'Differential diagnosis'.)

Diagnostic criteria — Diagnostic criteria for idiopathic moyamoya disease proposed by a Japanese
research committee include the following major requirements [140]:

●Stenosis or occlusion at the terminal portion of the internal carotid artery and at the proximal
portion of the anterior and middle cerebral arteries on magnetic resonance angiography (MRA)
●Abnormal vascular networks in the basal ganglia on MRA; these networks can also be
diagnosed by the presence of multiple flow voids on brain MRI
●Angiographic findings are present bilaterally; cases with unilateral angiographic findings are
considered probable
●The following conditions should be excluded:
•Arteriosclerosis
•Autoimmune disease
•Brain neoplasm
•A history of cranial irradiation
•Down syndrome
•Head trauma
•Neurofibromatosis
•Meningitis

The diagnostic criteria for conventional cerebral angiography are similar to those for MRA [140].

Screening studies — Indications for angiographic screening studies in family members of patients
with moyamoya are not well defined. The 2008 American Heart Association Stroke Council guidelines
state that there is insufficient evidence to justify screening studies in asymptomatic individuals or in
 relatives of patients with moyamoya syndrome in the absence of a strong family history of moyamoya
disease or medical conditions that predispose to moyamoya syndrome [21].

Even in individuals with a strong family history of moyamoya disease or those with medical conditions
that predispose to moyamoya syndrome, the utility of angiographic screening is unclear, particularly
since available medical and surgical treatment of asymptomatic moyamoya disease is of uncertain
benefit.

SUMMARY AND RECOMMENDATIONS — Moyamoya disease is a unique chronic progressive

cerebrovascular disease characterized by bilateral stenosis or occlusion of the arteries around the
circle of Willis with prominent arterial collateral circulation.

●The etiology of moyamoya disease is unknown. The high incidence among the Japanese and
Asian population, together with a familial occurrence of approximately 10 percent of cases,
strongly suggests a genetic etiology. Accumulating evidence suggests that the RNF213 gene on
chromosome 17q25.3 is an important susceptibility factor for moyamoya disease in East Asian
populations. Patients with the angiographic appearance of moyamoya and no known risk factors
are considered to have moyamoya disease, while those with one of the well recognized
associated conditions (neurofibromatosis type 1, cranial irradiation, Down syndrome, and sickle
cell disease) are classified as having moyamoya syndrome. (See 'Etiology' above.)
●Ischemic cerebrovascular events, either transient ischemic attack or infarction, are more
prevalent than hemorrhagic events in children with moyamoya, while hemorrhagic stroke is more
common in adults. (See 'Clinical features' above.)
●Cranial CT and/or MRI are useful for the detection of brain infarction and hemorrhage in
patients with moyamoya. Vascular imaging with magnetic resonance angiography, Computed
tomographic angiography, or conventional catheter angiography is essential to demonstrate
stenotic or occlusive lesions in the distal internal carotid arteries and the arteries around the
circle of Willis. (See 'Neuroimaging' above.)
●Transcranial Doppler ultrasonography provides a noninvasive way to evaluate intracranial
hemodynamics and large artery stenosis. Perfusion CT, xenon-enhanced CT, perfusion-
weighted MRI, positron emission tomography, and single-photon emission CT
with acetazolamide challenge may be useful to estimate resting brain perfusion and blood flow
reserve. (See 'Hemodynamic studies' above.)
●The pathologic hallmarks of moyamoya are (see 'Pathology' above):
•Concentric stenosis or occlusion in the distal internal carotid arteries and large vessels of
the circle of Willis
•A collateral meshwork of overgrown and dilated small arteries, the moyamoya vessels,
which branch from the circle of Willis
●The diagnosis of moyamoya disease is based upon the characteristic angiographic appearance
of bilateral stenoses affecting the distal internal carotid arteries and proximal circle of Willis
vessels, along with the presence of prominent basal collateral vessels. (See 'Diagnosis' above.)
Use of UpToDate is subject to the Subscription and License Agreement.
REFERENCES

1. Suzuki J, Kodama N. Moyamoya disease--a review. Stroke 1983; 14:104.

2. Suzuki J, Takaku A. Cerebrovascular "moyamoya" disease. Disease showing abnormal net-like
vessels in base of brain. Arch Neurol 1969; 20:288.
3. 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; 56:34.
4. Liu W, Morito D, Takashima S, et al. Identification of RNF213 as a susceptibility gene for moyamoya
disease and its possible role in vascular development. PLoS One 2011; 6:e22542.
5. Miyatake S, Miyake N, Touho H, et al. Homozygous c.14576G>A variant of RNF213 predicts early-
onset and severe form of moyamoya disease. Neurology 2012; 78:803.
6. 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.
7. Mineharu Y, Liu W, Inoue K, et al. Autosomal dominant moyamoya disease maps to chromosome
17q25.3. Neurology 2008; 70:2357.
8. Miyawaki S, Imai H, Takayanagi S, et al. Identification of a genetic variant common to moyamoya
disease and intracranial major artery stenosis/occlusion. Stroke 2012; 43:3371.
9. Wu Z, Jiang H, Zhang L, et al. Molecular analysis of RNF213 gene for moyamoya disease in the
Chinese Han population. PLoS One 2012; 7:e48179.
10. Bang OY, Ryoo S, Kim SJ, et al. Adult Moyamoya Disease: A Burden of Intracranial Stenosis in East
Asians? PLoS One 2015; 10:e0130663.
11. Ikeda H, Sasaki T, Yoshimoto T, et al. Mapping of a familial moyamoya disease gene to chromosome
3p24.2-p26. Am J Hum Genet 1999; 64:533.
12. Inoue TK, Ikezaki K, Sasazuki T, et al. Linkage analysis of moyamoya disease on chromosome 6. J
Child Neurol 2000; 15:179.
13. Sakurai K, Horiuchi Y, Ikeda H, et al. A novel susceptibility locus for moyamoya disease on
chromosome 8q23. J Hum Genet 2004; 49:278.
14. 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.
15. Inoue TK, Ikezaki K, Sasazuki T, et al. Analysis of class II genes of human leukocyte antigen in
patients with moyamoya disease. Clin Neurol Neurosurg 1997; 99 Suppl 2:S234.
16. Suzui H, Hoshimaru M, Takahashi JA, et al. Immunohistochemical reactions for fibroblast growth
factor receptor in arteries of patients with moyamoya disease. Neurosurgery 1994; 35:20.
17. Malek AM, Connors S, Robertson RL, et al. Elevation of cerebrospinal fluid levels of basic fibroblast
growth factor in moyamoya and central nervous system disorders. Pediatr Neurosurg 1997; 27:182.
18. Yamamoto M, Aoyagi M, Tajima S, et al. Increase in elastin gene expression and protein synthesis in
arterial smooth muscle cells derived from patients with Moyamoya disease. Stroke 1997; 28:1733.
19. 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.
20. Nanba R, Kuroda S, Ishikawa T, et al. Increased expression of hepatocyte growth factor in
cerebrospinal fluid and intracranial artery in moyamoya disease. Stroke 2004; 35:2837.
21. 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; 39:2644.
22. Lee SJ, Ahn JY. Stenosis of the proximal external carotid artery in an adult with moyamoya disease:
moyamoya or atherosclerotic change? Neurol Med Chir (Tokyo) 2007; 47:356.
23. Czartoski T, Hallam D, Lacy JM, et al. Postinfectious vasculopathy with evolution to moyamoya
syndrome. J Neurol Neurosurg Psychiatry 2005; 76:256.
24. Yamada H, Deguchi K, Tanigawara T, et al. The relationship between moyamoya disease and
bacterial infection. Clin Neurol Neurosurg 1997; 99 Suppl 2:S221.
25. Sharfstein SR, Ahmed S, Islam MQ, et al. Case of moyamoya disease in a patient with advanced
acquired immunodeficiency syndrome. J Stroke Cerebrovasc Dis 2007; 16:268.
26. Fryer RH, Anderson RC, Chiriboga CA, Feldstein NA. Sickle cell anemia with moyamoya disease:
outcomes after EDAS procedure. Pediatr Neurol 2003; 29:124.
27. Dobson SR, Holden KR, Nietert PJ, et al. Moyamoya syndrome in childhood sickle cell disease: a
predictive factor for recurrent cerebrovascular events. Blood 2002; 99:3144.
28. Kirkham FJ, DeBaun MR. Stroke in Children with Sickle Cell Disease. Curr Treat Options Neurol 2004;
6:357.
29. Marden FA, Putman CM, Grant JM, Greenberg J. Moyamoya disease associated with hemoglobin
Fairfax and beta-thalassemia. Pediatr Neurol 2008; 38:130.
30. Pavlakis SG, Verlander PC, Gould RJ, et al. Fanconi anemia and moyamoya: evidence for an
association. Neurology 1995; 45:998.
31. Tokunaga Y, Ohga S, Suita S, et al. Moyamoya syndrome with spherocytosis: effect of splenectomy
on strokes. Pediatr Neurol 2001; 25:75.
32. Cerrato P, Grasso M, Lentini A, et al. Atherosclerotic adult Moya-Moya disease in a patient with
hyperhomocysteinaemia. Neurol Sci 2007; 28:45.
33. Dhopesh VP, Dunn DP, Schick P. Moyamoya and Hageman factor (Factor XII) deficiency in a black
adult. Arch Neurol 1978; 35:396.
34. Kornblihtt LI, Cocorullo S, Miranda C, et al. Moyamoya syndrome in an adolescent with essential
thrombocythemia: successful intracranial carotid stent placement. Stroke 2005; 36:E71.
35. Wang R, Xu Y, Lv R, Chen J. Systemic lupus erythematosus associated with Moyamoya syndrome: a
case report and literature review. Lupus 2013; 22:629.
36. Kendall B. Cerebral angiography in vasculitis affecting the nervous system. Eur Neurol 1984; 23:400.
37. Sasaki T, Nogawa S, Amano T. Co-morbidity of moyamoya disease with Graves' disease. report of
three cases and a review of the literature. Intern Med 2006; 45:649.
38. Im SH, Oh CW, Kwon OK, et al. Moyamoya disease associated with Graves disease: special
considerations regarding clinical significance and management. J Neurosurg 2005; 102:1013.
39. Kushima K, Satoh Y, Ban Y, et al. Graves' thyrotoxicosis and Moyamoya disease. Can J Neurol Sci
1991; 18:140.
40. Bower RS, Mallory GW, Nwojo M, et al. Moyamoya disease in a primarily white, midwestern US
population: increased prevalence of autoimmune disease. Stroke 2013; 44:1997.
41. Carhuapoma JR, D'Olhaberriague L, Levine SR. Moyamoya syndrome associated with Sneddon's
syndrome and antiphospholipid-protein antibodies. J Stroke Cerebrovasc Dis 1999; 8:51.
42. Bonduel M, Hepner M, Sciuccati G, et al. Prothrombotic disorders in children with moyamoya
syndrome. Stroke 2001; 32:1786.
43. Provost TT, Moses H, Morris EL, et al. Cerebral vasculopathy associated with collateralization
resembling moya moya phenomenon and with anti-Ro/SS-A and anti-La/SS-B antibodies. Arthritis
Rheum 1991; 34:1052.
44. Khan M, Novakovic RL, Rosengart AJ. Intraventricular hemorrhage disclosing neurofibromatosis 1 and
moyamoya phenomena. Arch Neurol 2006; 63:1653.
45. Horikawa M, Utunomiya H, Hirotaka S, et al. Case of von Recklinghausen disease associated with
cerebral infarction. J Child Neurol 1997; 12:144.
46. Rosser TL, Vezina G, Packer RJ. Cerebrovascular abnormalities in a population of children with
neurofibromatosis type 1. Neurology 2005; 64:553.
47. Imaizumi M, Nukada T, Yoneda S, et al. Tuberous sclerosis with moyamoya disease. Case report.
Med J Osaka Univ 1978; 28:345.
48. Garcia JC, Roach ES, McLean WT. Recurrent thrombotic deterioration in the Sturge-Weber syndrome.
Childs Brain 1981; 8:427.
49. Tsuruta D, Fukai K, Seto M, et al. Phakomatosis pigmentovascularis type IIIb associated with
moyamoya disease. Pediatr Dermatol 1999; 16:35.
50. Rafay MF, Al-Futaisi A, Weiss S, Armstrong D. Hypomelanosis of Ito and Moyamoya disease. J Child
Neurol 2005; 20:924.
51. Meyer S, Zanardo L, Kaminski WE, et al. Elastosis perforans serpiginosa-like pseudoxanthoma
elasticum in a child with severe Moya Moya disease. Br J Dermatol 2005; 153:431.
52. Terada T, Yokote H, Tsuura M, et al. Marfan syndrome associated with moyamoya phenomenon and
aortic dissection. Acta Neurochir (Wien) 1999; 141:663.
53. Jea A, Smith ER, Robertson R, Scott RM. Moyamoya syndrome associated with Down syndrome:
outcome after surgical revascularization. Pediatrics 2005; 116:e694.
54. de Borchgrave V, Saussu F, Depre A, de Barsy T. Moyamoya disease and Down syndrome: case
report and review of the literature. Acta Neurol Belg 2002; 102:63.
55. Spengos K, Kosmaidou-Aravidou Z, Tsivgoulis G, et al. Moyamoya syndrome in a Caucasian woman
with Turner's syndrome. Eur J Neurol 2006; 13:e7.
56. Kamath BM, Spinner NB, Emerick KM, et al. Vascular anomalies in Alagille syndrome: a significant
cause of morbidity and mortality. Circulation 2004; 109:1354.
57. Rocha R, Soro I, Leitão A, et al. Moyamoya vascular pattern in Alagille syndrome. Pediatr Neurol
2012; 47:125.
58. Takeuchi K, Hara M, Yokota H, et al. Factors influencing the development of Moyamoya phenomenon.
Acta Neurochir (Wien) 1981; 59:79.
59. Ullrich NJ, Robertson R, Kinnamon DD, et al. Moyamoya following cranial irradiation for primary brain
tumors in children. Neurology 2007; 68:932.
60. de Vries RR, Nikkels PG, van der Laag J, et al. Moyamoya and extracranial vascular involvement:
fibromuscular dysplasia? A report of two children. Neuropediatrics 2003; 34:318.
61. Lutterman J, Scott M, Nass R, Geva T. Moyamoya syndrome associated with congenital heart
disease. Pediatrics 1998; 101:57.
62. Kawai M, Nishikawa T, Tanaka M, et al. An autopsied case of Williams syndrome complicated by
moyamoya disease. Acta Paediatr Jpn 1993; 35:63.
63. Christiaens FJ, Van den Broeck LK, Christophe C, Dan B. Moyamoya disease (moyamoya syndrome)
and coarctation of the aorta. Neuropediatrics 2000; 31:47.
64. Yamada I, Himeno Y, Matsushima Y, Shibuya H. Renal artery lesions in patients with moyamoya
disease: angiographic findings. Stroke 2000; 31:733.
65. Sunder TR. Moyamoya disease in a patient with type I glycogenosis. Arch Neurol 1981; 38:251.
66. Goutières F, Bourgeois M, Trioche P, et al. Moyamoya disease in a child with glycogen storage
disease type Ia. Neuropediatrics 1997; 28:133.
67. Tokuç G, Minareci O, Yavuzer D, et al. Moya Moya syndrome in a child with hyperphosphatasia.
Pediatr Int 1999; 41:399.
68. Lammie GA, Wardlaw J, Dennis M. Thrombo-embolic stroke, moya-moya phenomenon and primary
oxalosis. Cerebrovasc Dis 1998; 8:45.
69. Fernandez-Alvarez E, Pineda M, Royo C, Manzanares R. "Moya-moya' disease caused by cranial
trauma. Brain Dev 1979; 1:133.
70. Kitano S, Sakamoto H, Fujitani K, Kobayashi Y. Moyamoya disease associated with a brain stem
glioma. Childs Nerv Syst 2000; 16:251.
71. Arita K, Uozumi T, Oki S, et al. Moyamoya disease associated with pituitary adenoma--report of two
cases. Neurol Med Chir (Tokyo) 1992; 32:753.
72. Tsuji N, Kuriyama T, Iwamoto M, Shizuki K. Moyamoya disease associated with craniopharyngioma.
Surg Neurol 1984; 21:588.
73. Korematsu K, Yoshioka S, Maruyama T, et al. De novo appearance of cerebellar cavernous
malformation in a patient with moyamoya disease: case report and review of the literature. Clin Neurol
Neurosurg 2007; 109:708.
74. Kim JS, No YJ. Moyamoya-like vascular abnormality in pulmonary sarcoidosis. Cerebrovasc Dis 2006;
22:71.
75. Takenaka K, Ito M, Kumagai M, et al. Moyamoya disease associated with pulmonary sarcoidosis--
case report. Neurol Med Chir (Tokyo) 1998; 38:566.
76. Hervé D, Touraine P, Verloes A, et al. A hereditary moyamoya syndrome with multisystemic
manifestations. Neurology 2010; 75:259.
77. Pracyk JB, Massey JM. Moyamoya disease associated with polycystic kidney disease and eosinophilic
granuloma. Stroke 1989; 20:1092.
78. Nzwalo H, Santos V, Gradil C, et al. Caucasian familial moyamoya syndrome with rare multisystemic
malformations. Pediatr Neurol 2013; 48:240.
79. Peerless SJ. Risk factors of moyamoya disease in Canada and the USA. Clin Neurol Neurosurg 1997;
99 Suppl 2:S45.
80. Wakai K, Tamakoshi A, Ikezaki K, et al. Epidemiological features of moyamoya disease in Japan:
findings from a nationwide survey. Clin Neurol Neurosurg 1997; 99 Suppl 2:S1.
81. 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; 39:42.
82. Baba T, Houkin K, Kuroda S. Novel epidemiological features of moyamoya disease. J Neurol
Neurosurg Psychiatry 2008; 79:900.
83. Uchino K, Johnston SC, Becker KJ, Tirschwell DL. Moyamoya disease in Washington State and
California. Neurology 2005; 65:956.
84. Amlie-Lefond C, Zaidat OO, Lew SM. Moyamoya disease in early infancy: case report and literature
review. Pediatr Neurol 2011; 44:299.
85. Duan L, Bao XY, Yang WZ, et al. Moyamoya disease in China: its clinical features and outcomes.
Stroke 2012; 43:56.
86. Kleinloog R, Regli L, Rinkel GJ, Klijn CJ. Regional differences in incidence and patient characteristics
of moyamoya disease: a systematic review. J Neurol Neurosurg Psychiatry 2012; 83:531.
87. Kitamura, K, Fukui, M, Oka, K, et al. Moyamoya disease. Handbook of Clinical Neurology 1989;
11:293.
88. Nah HW, Kwon SU, Kang DW, et al. Moyamoya disease-related versus primary intracerebral
hemorrhage: [corrected] location and outcomes are different. Stroke 2012; 43:1947.
89. Kraemer M, Heienbrok W, Berlit P. Moyamoya disease in Europeans. Stroke 2008; 39:3193.
90. Zafar SF, Bershad EM, Gildersleeve KL, et al. Adult moyamoya disease in an urban center in the
United States is associated with a high burden of watershed ischemia. J Am Heart Assoc 2014; 3.
91. Choi JU, Kim DS, Kim EY, Lee KC. Natural history of moyamoya disease: comparison of activity of
daily living in surgery and non surgery groups. Clin Neurol Neurosurg 1997; 99 Suppl 2:S11.
92. Hung CC, Tu YK, Su CF, et al. Epidemiological study of moyamoya disease in Taiwan. Clin Neurol
Neurosurg 1997; 99 Suppl 2:S23.
93. Battistella PA, Carollo C. Clinical and neuroradiological findings of moyamoya disease in Italy. Clin
Neurol Neurosurg 1997; 99 Suppl 2:S54.
94. Li JY, Lai PH, Peng NJ. Moyamoya disease presenting with hemichoreoathetosis and hemidystonia.
Mov Disord 2007; 22:1983.
95. Kim YO, Kim TS, Woo YJ, et al. Moyamoya disease-induced hemichorea corrected by indirect bypass
surgery. Pediatr Int 2006; 48:504.
96. Baik JS, Lee MS. Movement disorders associated with moyamoya disease: a report of 4 new cases
and a review of literatures. Mov Disord 2010; 25:1482.
97. Quah BL, Hamilton J, Blaser S, et al. Morning glory disc anomaly, midline cranial defects and
abnormal carotid circulation: an association worth looking for. Pediatr Radiol 2005; 35:525.
98. Komiyama M, Yasui T, Sakamoto H, et al. Basal meningoencephalocele, anomaly of optic disc and
panhypopituitarism in association with moyamoya disease. Pediatr Neurosurg 2000; 33:100.
99. 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; 21:21.
100. Kim JM, Lee SH, Roh JK. Changing ischaemic lesion patterns in adult moyamoya disease. J
Neurol Neurosurg Psychiatry 2009; 80:36.
101. Takahashi M, Miyauchi T, Kowada M. Computed tomography of Moyamoya disease:
demonstration of occluded arteries and collateral vessels as important diagnostic signs. Radiology
1980; 134:671.
102. Handa J, Nakano Y, Okuno T, et al. Computerized tomography in Moyamoya syndrome. Surg
Neurol 1977; 7:315.
103. Rafay MF, Armstrong D, Dirks P, et al. Patterns of cerebral ischemia in children with
moyamoya. Pediatr Neurol 2015; 52:65.
104. 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.
105. Kikuta K, Takagi Y, Nozaki K, et al. The presence of multiple microbleeds as a predictor of
subsequent cerebral hemorrhage in patients with moyamoya disease. Neurosurgery 2008; 62:104.
106. Kuroda S, Kashiwazaki D, Ishikawa T, et al. Incidence, locations, and longitudinal course of
silent microbleeds in moyamoya disease: a prospective T2*-weighted MRI study. Stroke 2013; 44:516.
107. Ohta T, Tanaka H, Kuroiwa T. Diffuse leptomeningeal enhancement, "ivy sign," in magnetic
resonance images of moyamoya disease in childhood: case report. Neurosurgery 1995; 37:1009.
108. Maeda M, Tsuchida C. "Ivy sign" on fluid-attenuated inversion-recovery images in childhood
moyamoya disease. AJNR Am J Neuroradiol 1999; 20:1836.
109. Chung PW, Park KY. Leptomeningeal enhancement in petients with moyamoya disease:
correlation with perfusion imaging. Neurology 2009; 72:1872.
110. 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; 30:930.
111. Ryoo S, Cha J, Kim SJ, et al. High-resolution magnetic resonance wall imaging findings of
Moyamoya disease. Stroke 2014; 45:2457.
112. Hasuo K, Mihara F, Matsushima T. MRI and MR angiography in moyamoya disease. J Magn
Reson Imaging 1998; 8:762.
113. Yamada I, Nakagawa T, Matsushima Y, Shibuya H. High-resolution turbo magnetic resonance
angiography for diagnosis of Moyamoya disease. Stroke 2001; 32:1825.
114. Tsuchiya K, Makita K, Furui S. Moyamoya disease: diagnosis with three-dimensional CT
angiography. Neuroradiology 1994; 36:432.
115. Takase K, Kashihara M, Hashimoto T. Transcranial Doppler ultrasonography in patients with
moyamoya disease. Clin Neurol Neurosurg 1997; 99 Suppl 2:S101.
116. Lee YS, Jung KH, Roh JK. Diagnosis of moyamoya disease with transcranial Doppler
sonography: correlation study with magnetic resonance angiography. J Neuroimaging 2004; 14:319.
117. Takeuchi S, Tanaka R, Ishii R, et al. Cerebral hemodynamics in patients with moyamoya
disease. A study of regional cerebral blood flow by the 133Xe inhalation method. Surg Neurol 1985;
23:468.
118. Ikezaki K, Matsushima T, Kuwabara Y, et al. Cerebral circulation and oxygen metabolism in
childhood moyamoya disease: a perioperative positron emission tomography study. J Neurosurg
1994; 81:843.
119. Nambu K, Suzuki R, Hirakawa K. Cerebral blood flow: measurement with xenon-enhanced
dynamic helical CT. Radiology 1995; 195:53.
120. Shirane R, Yoshida Y, Takahashi T, Yoshimoto T. Assessment of encephalo-galeo-myo-
synangiosis with dural pedicle insertion in childhood moyamoya disease: characteristics of cerebral
blood flow and oxygen metabolism. Clin Neurol Neurosurg 1997; 99 Suppl 2:S79.
121. Khan N, Yonekawa Y. Moyamoya angiopathy in Europe. Acta Neurochir Suppl 2005; 94:149.
122. Tanaka Y, Nariai T, Nagaoka T, et al. Quantitative evaluation of cerebral hemodynamics in
patients with moyamoya disease by dynamic susceptibility contrast magnetic resonance imaging--
comparison with positron emission tomography. J Cereb Blood Flow Metab 2006; 26:291.
123. Oka K, Yamashita M, Sadoshima S, Tanaka K. Cerebral haemorrhage in Moyamoya disease
at autopsy. Virchows Arch A Pathol Anat Histol 1981; 392:247.
124. Morgenlander JC, Goldstein LB. Recurrent transient ischemic attacks and stroke in
association with an internal carotid artery web. Stroke 1991; 22:94.
125. Carlson CB, Harvey FH, Loop J. Progressive alternating hemiplegia in early childhood and
basal arterial stenosis and telangiectasia (moyamoya syndrome). Neurology 1973; 23:734.
126. Yamashita M, Oka K, Tanaka K. Histopathology of the brain vascular network in moyamoya
disease. Stroke 1983; 14:50.
127. Hosoda Y. Pathology of so-called "spontaneous occlusion of the circle of Willis". Pathol Annu
1984; 19 Pt 2:221.
128. Hosoda Y, Ikeda E, Hirose S. Histopathological studies on spontaneous occlusion of the circle
of Willis (cerebrovascular moyamoya disease). Clin Neurol Neurosurg 1997; 99 Suppl 2:S203.
129. Takagi Y, Kikuta K, Nozaki K, Hashimoto N. Histological features of middle cerebral arteries
from patients treated for Moyamoya disease. Neurol Med Chir (Tokyo) 2007; 47:1.
130. Kodama N, Fujiwara S, Horie Y, et al. [Transdural anastomosis in moyamoya disease--vault
moyamoy (author's transl)]. No Shinkei Geka 1980; 8:729.
131. Kodama N, Suzuki J. Moyamoya disease associated with aneurysm. J Neurosurg 1978;
48:565.
132. Adams HP Jr, Kassell NF, Wisoff HS, Drake CG. Intracranial saccular aneurysm and
moyamoya disease. Stroke 1979; 10:174.
133. Nagamine Y, Takahashi S, Sonobe M. Multiple intracranial aneurysms associated with
moyamoya disease. Case report. J Neurosurg 1981; 54:673.
134. Yabumoto M, Funahashi K, Fujii T, et al. Moyamoya disease associated with intracranial
aneurysms. Surg Neurol 1983; 20:20.
135. Konishi Y, Kadowaki C, Hara M, Takeuchi K. Aneurysms associated with moyamoya disease.
Neurosurgery 1985; 16:484.
136. Herreman, F, Nathal, E, Yasui, N, et al. Intracranial aneurysm in moyamoya disease: report of
ten cases and review of the literature. Cerebrovasc Dis 1994; 4:329.
137. Goldstein M, Hanquinet P, Couvreur Y. [A case of fibromuscular dysplasia in an unusual
location]. Acta Chir Belg 1984; 84:345.
138. Ikeda E. Systemic vascular changes in spontaneous occlusion of the circle of Willis. Stroke
1991; 22:1358.
139. Togao O, Mihara F, Yoshiura T, et al. Prevalence of stenoocclusive lesions in the renal and
abdominal arteries in moyamoya disease. AJR Am J Roentgenol 2004; 183:119.
140. 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.

Topic 1131 Version 20.0