Moyamoya Disease

Background

Moyamoya disease (MMD) is a rare disorder of the blood vessels of the brain. It is characterized by a progressive occlusive disease of the cerebral vasculature with particular involvement of the circle of Willis and the feeding arteries. The name Moyamoya is Japanese for "puff of smoke". This distinctive name describes the angiographic appearance of the abnormal vascular collateral networks that develop adjacent to the stenotic vessels. The changes may affect the major blood vessels of the brain including the anterior, middle, and posterior cerebral arteries.

The symptoms and clinical course vary widely and depend upon the location and severity of the hemorrhage or damage. Thus signs and symptoms may range from asymptomatic to transient events to severe neurologic deficits.

ADULTS CHILDREN

Hemorrhage (intraventricular, subarachnoid, or intracerebral hemorrhage) more common Cerebral ischemic events more common
Hemiparesis, monoparesis, sensory impairment, involuntary movements, headaches, dizziness, or seizures
Mental retardation or persistent neurologic deficits

The exact etiology of MMD is unknown but several familial cases have been reported. Several other diseases have been associated with the disease.

OUTLINE

Epidemiology

Disease Associations

Pathogenesis

Laboratory/Radiologic/Other Diagnostic Testing

Gross Appearance and Clinical Variants

Histopathological Features and Variants

Special Stains/Immunohistochemistry/Electron Microscopy

Differential Diagnosis

Prognosis

Treatment

Commonly Used Terms

Internet Links

EPIDEMIOLOGY CHARACTERIZATION

INCIDENCE/PREVALENCE Very rare

AGE 6 months to 67 years, with the highest peak in the first decade and smaller peaks in the third and fourth decades

SEX Female-to-male ratio is 1.8:1

EPIDEMIOLOGIC ASSOCIATIONS Primarily in Asians
Less common in Caucasians, African Americans, Haitians, and Hispanics

GREECE

Familial moyamoya disease in a Greek family.

Zafeiriou DI, Ikeda H, Anastasiou A, Vargiami E, Vougiouklis N, Katzos G, Gombakis N, Gioula G, Matsushima Y, Kirkham FJ.

1st Paediatric Klinic, Aristotle University, Thessaloniki, Greece

Brain Dev. 2003 Jun;25(4):288-90. Abstract quote
Moyamoya disease (M-M) is characterized by progressive obstruction of the supraclinoid portion of internal carotid arteries and the proximal middle, anterior and posterior cerebral arteries, associated with the formation of a characteristic net of collateral vessels in the basal ganglia region.

Clinical manifestations in childhood include transient ischaemic attacks, seizures and multiple infarcts. Approximately 7% of M-M cases are familial.

We report two affected Greek siblings with typical clinical and neuroradiological findings of M-M. Linkage analysis of the whole family was consistent with linkage to the region 3p24-26, as previously reported in other familial Japanese M-M cases

KOREA

Epidemiological survey of moyamoya disease in Korea.

Ikezaki K, Han DH, Kawano T, Inamura T, Fukui M.

Department of Neurosurgery, Kyushu University Faculty of Medicine, Fukuoka, Japan.
Clin Neurol Neurosurg. 1997 Oct;99 Suppl 2:S6-10. Abstract quote
To both clarify the current clinico-epidemiological features of Moyamoya disease in Korea as well as compare these cases with Japanese patients, 451 cases were collected from 26 Korean major neurosurgical institutes and 296 definite cases were analyzed statistically.

Although the Korean age distribution patterns of Moyamoya disease showed two peaks, similar to Japanese patients, the Korean pattern was shifted to the right thus indicating Korean adult population to be 20% higher than that of Japanese patients. The female/male ratio was 1:3, which was slightly less than that for Japanese. The family occurrence rate in Koreans was 1.8%.

The incidence of cerebral infarction and bleeding in Koreans was higher while transient ischemic attack (TIA) and seizure were less than that of Japanese. The incidence of infarction in children and of hemorrhage in children and adults were also statistically higher in Koreans. The incidence of hemorrhage was higher in females than in males. Both the age at onset and sex affected the disease type. Single encephalo-duro-arterio-synangiosis (EDAS) was performed on 87.6% of all surgical cases. Although the incidence of bleeding was higher in Korea, the outcomes of the patients were similar to that of the Japanese patients.

Although Korean Moyamoya disease showed a relatively higher incidence of hemorrhage and adult onset, the overall clinical background was similar to that of Japanese patients.

DISEASE ASSOCIATIONS CHARACTERIZATION

ATHEROSCLEROSIS

CARDIO-FACIO-CUTANEOUS SYNDROME

Cardio-facio-cutaneous syndrome and moyamoya syndrome.

Ishiguro Y, Kubota T, Takenaka J, Maruyama K, Okumura A, Negoro T, Watanabe K.

Department of Pediatrics, Nagoya University School of Medicine, 65 Tsurumai-cho, Showa-ku, Aichi 466-8550, Japan.
Brain Dev. 2002 Jun;24(4):245-9. Abstract quote
We reported a patient with cardio-facio-cutaneous (CFC) syndrome associated with moyamoya syndrome. The patient was referred at 6 years 5 months with left hemiplegia and right-sided eye deviation. He had an apparently short stature, macrocephaly, left ptosis and atopic skin, and was odd looking. He exhibited an incomplete right bundle branch block on electrocardiogram and an atrial septal defect on ultrasound cardiography.

He was diagnosed as having CFC syndrome. Head magnetic resonance imaging showed a flow void in the bilateral basal ganglia, but did not show any ischemic changes. Magnetic resonance angiography showed bilateral stenosis with an internal carotid artery at the Willis artery ring level and bilateral moyamoya. Contrast angiography demonstrated occlusion of both middle cerebral arteries. Cerebrovascular anomalies have not previously been reported in CFC syndrome.

This is the first case of CFC syndrome associated with moyamoya syndrome.

DOWN SYNDROME

Moyamoya disease and Down syndrome: case report and review of the literature.

de Borchgrave V, Saussu F, Depre A, de Barsy T.

Centre Neurologique William Lennox, Cliniques Universitaires Saint-Luc, Universite Catholique de Louvain, 1200 Brussels.

Acta Neurol Belg. 2002 Jun;102(2):63-6. Abstract quote
We present the case of a 29-year-old woman with Down syndrome who developed bilateral frontal ischemic stroke. Cerebral angiography demonstrated an occlusion of the both supraclinoid internal carotid arteries associated with dilated collateral vessels, consistent with moyamoya disease.

We review the clinical and radiological features of moyamoya disease associated with Down syndrome and discuss a few major physiopathologic hypotheses to explain this association.

Moyamoya disease (syndrome) and the Down syndrome.

Fukuyama Y, Osawa M, Kanai N.

Department of Pediatrics, Tokyo Women's Medical College, Japan.
Brain Dev. 1992 Jul;14(4):254-6.

HEMATOLOGIC DISORDERS Aplastic anemia, Fanconi anemia, sickle cell anemia, and lupus anticoagulant

INFECTIONS
Leptospirosis and tuberculosis

LIVEDO RETICULARIS

Livedo reticularis in a child with moyamoya disease.

Richards KA, Paller AS.

Departments of Dermatology and Pediatrics, Children's Memorial Hospital, Northwestern University Medical School, Chicago, Illinois
Pediatr Dermatol. 2003 Mar-Apr;20(2):124-7. Abstract quote
Moyamoya disease is a rare, chronic cerebrovascular occlusive disease of unknown etiology. It is characterized by progressive stenosis of the arteries of the circle of Willis leading to an abnormal capillary network and resultant ischemic strokes or cerebral hemorrhages.

The association of moyamoya disease with livedo reticularis has been described in a previously reported patient with a factor V Leiden mutation, leading to hypercoagulation.

We describe a girl with livedo reticularis and moyamoya disease with extensive cardiovascular malformations, but without a primary coagulopathy.

NEPHROTIC SYNDROME

Moyamoya disease complicated with renal artery stenosis and nephrotic syndrome: reversal of nephrotic syndrome after nephrectomy.
Kuwayama F, Hamasaki Y, Shinagawa T, Kubota C, Ichikawa I, Kato Y, Oi S, Shinohara O.

Department of Pediatrics, Tokai University School of Medicine, Kanagawa, Japan.

Pediatr. 2001 Mar;138(3):418-20. Abstract quote
A 7-year-old boy with moyamoya disease developed sustained hypertension, nephrotic syndrome, hyperreninemia, and occlusion of the right renal artery. After right nephrectomy, hyperreninemia and hypertension improved.

Proteinuria was resolved after nephrectomy, in parallel with the decrease in plasma renin activity.

Moyamoya disease can cause nephrotic-range proteinuria, which is caused hemodynamically by hyperreninemia.

RADIATION

Moyamoya phenomenon after radiation for optic glioma.

Kestle JR, Hoffman HJ, Mock AR.

Division of Neurosurgery, Hospital for Sick Children, Toronto, Ontario, Canada.

J Neurosurg. 1993 Jul;79(1):32-5. Abstract quote
The role of radiotherapy in the management of patients with optic pathway glioma is controversial.

In a series of patients with optic pathway glioma treated at The Hospital for Sick Children in Toronto, five children were encountered who developed moyamoya phenomenon after radiotherapy.

A retrospective review of the medical records was undertaken in order to assess the relationship between optic pathway glioma, neurofibromatosis type 1 (NF1), radiation therapy, and moyamoya disease.

Forty-seven patients with optic pathway glioma were operated on at The Hospital for Sick Children between 1971 and 1990. The moyamoya phenomenon did not occur in any of the 19 patients not receiving radiotherapy. Among the 28 patients who received radiotherapy, five developed moyamoya disease (two of 23 without NF1 and three of five with NF1). There was a statistically significant relationship between radiotherapy and moyamoya disease when the analysis was stratified according to the presence of NF1 (Mantel-Haensel chi-squared test 15.23, p < 0.01).

The high incidence of moyamoya disease (three of five cases, or 60%) in patients with NF1 who have undergone radiotherapy suggests a synergistic relationship that should be considered when formulating a treatment plan for NF1 patients with optic pathway glioma.

RENOVASCULAR HYPERTENSION

Moyamoya disease associated with renovascular hypertension.

Yamashita M, Tanaka K, Kishikawa T, Yokota K.
Hum Pathol. 1984 Feb;15(2):191-3. Abstract quote
Findings at the autopsy of a 7-year-old Japanese girl with moyamoya disease associated with renovascular hypertension are reported. There was disruption of a saccular aneurysm located at the junction of the left posterior cerebral and the posterior communicating arteries.

Intimal thickening of carotid, coronary, and renal arteries, similar to findings in cases of intimal hyperplasia of fibromuscular dysplasia, was observed.

These findings indicate that moyamoya disease may actually be an intracranial manifestation in a systemic arterial disorder.

SICKLE CELL DISEASE

Moyamoya syndrome in childhood sickle cell disease: a predictive factor for recurrent cerebrovascular events.

Dobson SR, Holden KR, Nietert PJ, Cure JK, Laver JH, Disco D, Abboud MR.

Department of Neurology, Medical University of South Carolina, Charleston, SC 29425, USA.
Blood. 2002 May 1;99(9):3144-50 Abstract quote
We conducted a retrospective study to determine whether the presence of moyamoya collaterals influenced the risk of recurrence of cerebrovascular events (CVEs: stroke or transient ischemic attack) in patients with sickle cell disease placed on chronic transfusions after a stroke. Forty-three patients with homozygous sickle cell anemia (HbSS) and 1 with HbSO(Arab) (16 females, 28 males) who had suffered strokes while under the age of 18 were studied.

All patients had been on transfusions aimed at maintaining the sickle hemoglobin (HbS) level below 30%. They were followed for a mean of 6.6 years (2.2 to 20.4 years). The presence of collaterals was diagnosed based on either magnetic resonance angiography or conventional angiography. Eighteen (41%) of the 44 patients suffered recurrent CVEs. Nineteen (43%) (6 females, 13 males) patients had moyamoya collaterals. Eleven (58%) of these 19 experienced 21 total recurrent CVEs, including 4 strokes in 4 patients (21%). In comparison, 7 (28%) of 25 patients without moyamoya collaterals experienced 9 recurrent CVEs (P <.05) with only 1 recurrent stroke (4%). Moyamoya patients were also more likely to have 2 recurrent CVEs (42% vs 8%, P <.05) as well as poorer neuropsychological testing results. A proportional hazards regression analysis indicated that patients with moyamoya were more than twice as likely to incur a subsequent CVE (hazard ratio, 2.40; 95% confidence interval, 0.85, 6.75).

We conclude that up to 41% of patients with sickle cell disease experience recurrent CVEs after an initial stroke despite chronic transfusions and that the risk of recurrence is significantly higher for those who have moyamoya collaterals.

PATHOGENESIS CHARACTERIZATION

PROTEIN C DEFICIENCY

Are the strokes in moyamoya syndrome associated with Down syndrome due to protein C deficiency?

Gururaj A, Hardy D, Al-Gazali LI, Sztriha L, Roos A, Nork M.

Department of Paediatrics, Faculty of Medicine, UAE University and Tawam Hospital, Al Ain, United Arab Emirates
Brain Dev. 2002 Oct;24(7):719-22. Abstract quote
Moyamoya syndrome has occasionally been seen in association with Down syndrome.

We report a child with moyamoya syndrome and Down syndrome who was admitted with repeated episodes of strokes; his magnetic resonance imaging and magnetic resonance angiography findings confirmed the presence of occlusive cerebrovascular disease with basal collateral vessels. His protein C levels were significantly decreased during the stroke. Complete clinical recovery was seen during follow-up.

This raises the possibility of a link between protein C deficiency and Down syndrome with moyamoya syndrome.

LABORATORY/RADIOLOGIC/
OTHER TESTS
CHARACTERIZATION

RADIOLOGIC

Neoangiogenesis in association with moyamoya syndrome shown by estimation of relative recirculation based on dynamic contrast-enhanced MR images.

Kassner A, Zhu XP, Li KL, Jackson A.

Philips Medical Systems, London, England.
AJNR Am J Neuroradiol. 2003 May;24(5):810-8. Abstract quote
BACKGROUND AND PURPOSE: This study examined abnormalities of the recirculation phase of the contrast medium concentration time course curve in patients with moyamoya disease by using the relative recirculation (rR) parameter. Our aims were to increase understanding of the rR parameter and to assess its possible value in the investigation of moyamoya disease.

METHODS: Six patients with confirmed moyamoya disease and five normal participants were examined by using dynamic T2*-weighted MR perfusion imaging. Parametric maps of relative cerebral blood volume, time to peak (TTP), and rR were calculated. The width of the normal distribution of TTP and the normal upper limit for rR were derived from the normal participants by identification of the 97.5% confidence limits for the distributions. Major vessels were identified by selection of pixels with relative cerebral blood volume >0.5. Areas of abnormally prolonged TTP and of increased rR were then identified in patients, and the relationship between these parameters and major vessels was examined.

RESULTS: The combination of cerebral blood volume >50%, elevated TTP, and elevated rR values accurately identified areas of moyamoya vessel formation seen on angiograms. Larger well-developed meningeal and basal collaterals did not show abnormalities of rR. Areas of prolonged TTP were also observed to occur in the brain distal to arterial occlusion in all cases. In three of these, abnormal elevation of rR was observed in the center of regions of prolonged TTP.

CONCLUSION: These findings support those of our previous work, which suggested that rR can act as an indicator of regional microvascular abnormality, such as that seen in areas of angiogenic activity. They also suggest that measurement of rR may provide valuable additional information regarding patients with moyamoya disease.

Evaluation of cerebral hemodynamics with perfusion MRI in childhood moyamoya disease.

Kim SK, Wang KC, Oh CW, Kim IO, Lee DS, Song IC, Cho BK.

Department of Neurosurgery, Seoul National University Hospital, Seoul, Korea.
Pediatr Neurosurg. 2003 Feb;38(2):68-75 Abstract quote
The purpose of our study was to evaluate the role of perfusion MRI and to compare the findings with those of conventional imaging in childhood moyamoya disease (MMD).

Perfusion MRI was performed preoperatively on 13 cases of childhood MMD. Based on the perfusion MRI findings, patients were classified into four groups: those with normal regional cerebral blood volume (rCBV) and time to peak (TTP) (group 1, n = 2); those with normal rCBV and delayed TTP (group 2, n = 1); those with increased rCBV and delayed TTP (group 3, n = 5), and those with decreased rCBV and delayed TTP (group 4, n = 5). Lesion volume as determined using the rCBV map was compared with that on MRI and single photon emission computerized tomography (SPECT).

The characteristics of groups 1, 2 and 3 were a high frequency of transient ischemic attacks, normal finding on MRI, early angiographic stages, decreased reserve on SPECT and favorable operative outcome. In group 3, angiography revealed abundant collateral channels. In group 4, all cases had infarction on MRI and abnormal perfusion on SPECT. Angiographic stages tended to have progressed, and operative outcome was less favorable. Perfusion MRI documented hemodynamic asymmetries in the five cases with normal MRI. Perfusion MRI is suggested to have a sensitivity intermediate between rest and acetazolamide SPECTs.

We conclude that perfusion MRI may be a valuable tool for characterizing and monitoring ischemia in MMD. Perfusion MRI provides additional functional information not available from conventional MRI and has a potential role comparable to SPECT in the evaluation of MMD.

"Ivy sign" in childhood moyamoya disease: depiction on FLAIR and contrast-enhanced T1-weighted MR images.

Yoon HK, Shin HJ, Chang YW.

Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Kangnam-gu, Seoul 135-710, Korea.
Radiology. 2002 May;223(2):384-9. Abstract quote
PURPOSE: To compare contrast material-enhanced T1-weighted and fluid-attenuated inversion recovery (FLAIR) magnetic resonance (MR) images with or without gadolinium in depicting the leptomeningeal ivy sign in children with moyamoya disease.

MATERIALS AND METHODS: Twenty-nine sets of FLAIR and postcontrast T1-weighted MR images were available in 19 consecutive children with primary moyamoya disease confirmed with conventional and MR angiography. Contrast-enhanced FLAIR MR images also were available in 15 sets. Two pediatric radiologists reviewed FLAIR and postcontrast T1-weighted images in separate sessions for the leptomeningeal ivy sign and assigned a rating of "present," "absent," or "equivocal" by consensus. Unenhanced and contrast-enhanced FLAIR MR images were compared side by side to determine which better depicted leptomeningeal high signal intensities.

RESULTS: Postcontrast T1-weighted MR images revealed the leptomeningeal ivy sign in 40 hemispheres (frequency of visualization, 71% [40 of 56 hemispheres]), whereas unenhanced FLAIR MR images depicted it in 26 hemispheres (frequency of visualization, 46% [26 of 56 hemispheres]). An equivocal rating was given in 21 hemispheres versus in 11 on FLAIR and postcontrast T1-weighted images, respectively. FLAIR and postcontrast T1-weighted images agreed in 40 hemispheres. There was no case with a positive rating on FLAIR images when postcontrast T1-weighted images were negative. Unenhanced FLAIR MR imaging was superior to contrast-enhanced FLAIR imaging in seven hemispheres, whereas enhanced FLAIR was better in four of 28 hemispheres. In the remaining 17, findings with each sequence were similar.

CONCLUSION: Contrast-enhanced T1-weighted images are better than FLAIR images for depicting the leptomeningeal ivy sign in moyamoya disease.

Moyamoya disease: comparison of assessment with MR angiography and MR imaging versus conventional angiography.

Yamada I, Suzuki S, Matsushima Y.

Department of Radiology, Faculty of Medicine, Tokyo Medical and Dental University, Japan.

Radiology. 1995 Jul;196(1):211-8. Abstract quote
PURPOSE: To evaluate magnetic resonance (MR) angiography and MR imaging in assessment of moyamoya disease.

MATERIALS AND METHODS: The cases of 26 patients with moyamoya disease were evaluated prospectively. After three-dimensional time-of-flight 1.5-T MR angiography and MR imaging, images were evaluated in blinded separate interpretation.

RESULTS: MR angiography and MR imaging accurately depicted 217 (82%) and 184 (70%) of 264 arteries, respectively, but the degree of stenosis was overestimated in the other arteries. Basal cerebral moyamoya vessels were depicted in all 52 hemispheres with conventional angiography and in 42 (81%) and 48 (92%) hemispheres with MR angiography and MR imaging, respectively. The respective sensitivity and specificity for diagnosis of moyamoya disease were 73% and 100% for MR angiography, 92% and 100% for MR imaging, and 92% and 100% for MR angiography plus MR imaging.

CONCLUSION: Assessment of moyamoya disease is most thorough with MR angiography and MR imaging.

PET SCAN

Metabolic changes after H(2) 15O-positron emission tomography with acetazolamide in a patient with moyamoya disease: case report and review of previous cases.

Muroi C, Yonekawa Y, Khan N, Pangalu A, Keller E.

Department of Neurosurgery, University Hospital Zurich, Zurich, Switzerland

J Neurosurg Anesthesiol. 2003 Apr;15(2):131-9. Abstract quote
Perioperative ischemic complications not directly related to surgery require special attention in patients with moyamoya disease; positron emission tomography (H(2) 15O-PET) and single-photon emission computed tomography have been considered indispensable for evaluating pre- and postsurgical cerebral hemodynamics.

The clinical records of 14 patients with moyamoya disease who underwent 26 extracranial-intracranial bypass operations were reviewed with special reference to perisurgical complications. One patient developed multiple postoperative ischemic infarctions and died of ischemic brain edema. The history of this patient with prolonged acidosis is analyzed, and the role of metabolic changes induced by H(2) 15O-PET with acetazolamide challenge is reviewed. Seven (77.8%) of nine patients operated on within 48 hours after H(2) 15O-PET with acetazolamide (group 1) developed metabolic acidosis, whereas only three (17.6%) of 17 patients operated on >48 hours (group 2) after the examination had intraoperative pH of <7.35. In group 1, the mean intraoperative pH was 7.328, which was significantly lower than the mean pH of 7.393 (P <.0001) in group 2. After H(2) 15O-PET with acetazolamide challenge, patients must be carefully observed concerning acidosis and volume state.

We recommend at least 48 hours between examination and surgery for patients with moyamoya disease so that their conditions can stabilize. Furthermore, special care should be taken to avoid additional perioperative risk factors such as hypotension, hypocapnia, hypercapnia, and hypovolemia.

GROSS APPEARANCE/
CLINICAL VARIANTS CHARACTERIZATION

GENERAL

Moyamoya disease: an elusive diagnosis.

Asumal KB, Akhtar N, Syed NA, Shafqat S, Baig SM.

Section of Neurology, Department of Medicine, The Aga Khan University Hospital Karachi.

J Pak Med Assoc. 2003 Apr;53(4):160-2 Abstract quote
OBJECTIVE AND BACKGROUND: Moyamoya disease is an idiopathic vasculopathy of circle of Willis. Stroke is a common presentation. We describe clinical and radiological features of moyamoya disease in four patients.

SETTING: Tertiary care center in a metropolitan city.

MATERIALS AND METHODS: Patients with moyamoya disease were identified by ICD-9 coding system of the hospital medical records. Demographic characteristics, clinical features/presentation, laboratory investigations and radiological investigations were recorded and analyzed.

RESULTS: Four patients (three children and one adult) presented with hemiparesis. One patient expired during hospital stay. Two patients underwent surgery (synangiosis). EEGs of three patients showed focal abnormalities. Neuroimaging showed ischemic infarctions in all patients. Findings on four vessel digital substraction angiography and/or magnetic resonance angiography were compatible with moyamoya disease.

CONCLUSION: Moyamoya disease should be considered in all young patients, especially children, presenting with stroke.

Moyamoya: Indiana University Medical Center experience.

Yilmaz EY, Pritz MB, Bruno A, Lopez-Yunez A, Biller J.

Department of Neurology, Indiana University School of Medicine, 545 Barnhill Dr, Emerson Hall 125, Indianapolis, IN 46202, USA
Arch Neurol. 2001 Aug;58(8):1274-8. Abstract quote
BACKGROUND: Moyamoya usually presents with cerebral ischemia in children and intracranial hemorrhage in adults. Treatment remains controversial.

DESIGN AND OBJECTIVE: We reviewed our experience from June 1995 to August 1999 of 20 adult and pediatric angiographically diagnosed patients with moyamoya to report their clinical presentation, radiological findings, management, and clinical outcomes.

RESULTS: The mean age of patients at symptom onset was 17 years (range, 2-54 years). Patients were divided into 2 age groups (group 1, <18 years; group 2, > or =18 years). There were 13 patients in group 1 and 7 patients in group 2. Ischemic strokes or transient ischemic attacks were the predominant initial presentations in both groups. One patient in group 2 had an intraparenchymal brain hemorrhage. Five patients received medical treatment, and 15 had surgical revascularization. The mean time from symptom onset to surgical procedure was significantly longer for patients in group 1 than for those in group 2 (P =.03). The mean follow-up time was 36 months. One patient in group 1 had an ischemic stroke. There was no difference in stroke recurrence, mortality, or modified Rankin scale score among medically or surgically treated patients.

CONCLUSIONS: Moyamoya disease may have a different presentation and more benign natural history in our population than in Asian populations. Our findings emphasize the need to better understand the natural history of patients with moyamoya as well as the clinical benefit of different treatment modalities. Structured multicenter randomized clinical trials are needed to further assess the best treatment modalities for patients with moyamoya in the United States.

VARIANTS

FAMILIAL

Moyamoya disease in monovular twins: case report.

Yamada H, Nakamura S, Kageyama N.
J Neurosurg. 1980 Jul;53(1):109-12. Abstract quote
The first reported instance of identical twins with moyamoya disease is presented. The involved portions of the main intracranial arteries were similar, but the formation of the moyamoya vessels was somewhat different.

The cause of obstructive changes in large intracranial arteries remains obscure, but the frequent familial occurrence suggests that the initial stages of this disease and the formation of the moyamoya vessels occur in the prenatal period.

Familial occurrence of bilateral intracranial occlusion of the internal carotid arteries (Moya Moya).

Sogaard I, Jorgensen J.
Acta Neurochir (Wien). 1975;31(3-4):245-52. Abstract quote
In a family of 14 brothers and sisters, 3 cases of occlusive disease of the large intracranial vessels (Moya Moya) were found. Each of the three had one or more cerebrovascular attacks and a typical cerebral angiogram.

Eight other members of the family had severe headaches. Angiography was carried out in three of these with normal findings.

HEMICHOREA

Hemichorea as an initial manifestation of moyamoya disease: reversible striatal hypoperfusion demonstrated on single photon emission computed tomography.

Hong YH, Ahn TB, Oh CW, Jeon BS.

Department of Neurology, Clinical Research Institute, Seoul National University Hospital, SNUMRC, College of Medicine, Seoul National University, Seoul, South Korea.
Mov Disord. 2002 Nov;17(6):1380-3. Abstract quote
We describe a case with unilateral moyamoya disease that showed progressive hemichorea as an initial manifestation. Single photon emission computed tomography showed perfusion defect in the contralateral basal ganglia although magnetic resonance imaging was unremarkable.

Hemichorea improved along with normalization of perfusion after bypass surgery, suggestive of striatal hypoperfusion as the cause of hemichorea.

PEDIATRIC

Moyamoya syndrome in young children: MR comparison with adult onset.

Takanashi J, Sugita K, Ishii M, Tanabe Y, Ito C, Date H, Niimi H.

Department of Pediatrics, School of Medicine, Chiba University, Japan.
AJNR Am J Neuroradiol. 1993 Sep-Oct;14(5):1139-43. Abstract quote
PURPOSE: To clarify whether there were any differences in MR appearance between the childhood and the adult moyamoya syndromes.

METHOD: We compared the cranial MR findings in four children under the age of 6 who had moyamoya syndrome with previously documented adult cases.

RESULTS: Moyamoya syndrome in younger children exhibited a significant increase in cortical and subcortical infarction, and a decreased incidence of deep white matter infarction in the centrum semiovale and basal ganglia, in contrast to adult cases. There were no remarkable differences between these two groups of moyamoya cases with regard to the occlusive changes of the internal carotid and middle cerebral arteries, or to the flow void sign on MR.

CONCLUSION: These differences in the sites and frequencies of infarctions between the childhood and the adult moyamoya syndromes observed on MR might reflect differences in the cerebral circulation.

HISTOLOGICAL TYPES CHARACTERIZATION

GENERAL
Intimal thickening in the walls of the terminal portions of the internal carotid vessels bilaterally

Proliferating intima may contain lipid deposits.

DIFFERENTIAL DIAGNOSIS KEY DIFFERENTIATING FEATURES

RADIATION

Radiation-induced arteritis: thickened wall with prominent enhancement on cranial MR images report of five cases and comparison with 18 cases of Moyamoya disease.

Aoki S, Hayashi N, Abe O, Shirouzu I, Ishigame K, Okubo T, Nakagawa K, Ohtomo K, Araki T.

Department of Radiology, University of Tokyo Hospital, 7-3-1 Hongo, Bunkyoku, Tokyo 113-8655, Japan.

Radiology. 2002 Jun;223(3):683-8. Abstract quote
PURPOSE: To evaluate magnetic resonance (MR) imaging findings of radiation-induced cranial arteritis regarding arterial wall thickening and degree of enhancement, as well as to compare the findings with those of idiopathic moyamoya disease.

MATERIALS AND METHODS: We reviewed cerebral MR images in five patients with radiation-induced large cerebral arteritis. All patients had undergone irradiation 2-25 years prior to this study. Conventional nonenhanced MR, MR angiographic, and contrast material-enhanced MR images were evaluated. Special attention was paid to wall enhancement of the affected arteries (distal internal carotid artery). Wall enhancement was staged in three levels by two neuroradiologists. We also reviewed MR images in 18 patients with primary moyamoya disease for comparison and analyzed them statistically (Fisher exact test).

RESULTS: Wall thickening and prominent ring enhancement of the wall of the affected large cerebral arteries were observed in all (five of five) patients with radiation-induced arteritis. In contrast, wall thickening and prominent ring enhancement of the wall of the occluded arteries either were not seen (13 of 18 patients) or were faint (five of 18 patients) in patients with moyamoya disease. Contrast enhancement of the arterial walls in patients with radiation-induced arteritis was significantly more prominent than in patients with moyamoya disease (P =.003).

CONCLUSION: MR images of wall thickening and prominent ring enhancement of the wall of affected large cerebral arteries may be a diagnostic clue in differentiating radiation-induced arteritis from moyamoya disease.

PROGNOSIS CHARACTERIZATION

GENERAL
Mortality rates are approximately 10% in adults and 4.3% in children

Death is usually from hemorrhage

About 50-60% of affected individuals experience a gradual deterioration of cognitive function possibly secondary to recurrent strokes

A co-operative study: clinical characteristics of 334 Korean patients with moyamoya disease treated at neurosurgical institutes (1976-1994). The Korean Society for Cerebrovascular Disease.

Han DH, Kwon OK, Byun BJ, Choi BY, Choi CW, Choi JU, Choi SG, Doh JO, Han JW, Jung S, Kang SD, Kim DJ, Kim HI, Kim HD, Kim MC, Kim SC, Kim SC, Kim Y, Kwun BD, Lee BG, Lim YJ, Moon JG, Park HS, Shin MS, Song JH, Suk JS, Yim MB; Korean Society for Cerebrovascular Disease.

Department of Neurosurgery, Seoul National University Hospital, Chongno-gu, Korea.

Acta Neurochir (Wien). 2000;142(11):1263-73 Abstract quote
A co-operative study was conducted to determine the clinical characteristics of patients with moyamoya disease who were diagnosed and treated at neurosurgical institutes in Korea before 1995. Twenty-six hospitals contributed 505 cases and among them, the clinical characteristics of 334 patients with definite moyamoya disease were evaluated. The number of patients began to increase from the late 1980s, and after that approximately 20 patients were treated each year. There were two age peaks: from six to 15 and from 31 to 40 years of age. Haemorrhagic manifestations occurred in approximately 43% of the patients.

The major clinical manifestations were haemorrhage in adults (62.4%) and ischaemia in children (61.2%). Overall 54.5% of the patients experienced decreased consciousness levels, mainly due to intracranial haemorrhage or cerebral infarction. In the patients with ischemic manifestations, the adult patients were more likely to have cerebral infarction than the pediatric patients (80% vs. 39%) and the pediatric patients were more likely to have TIA (61% vs. 25%). Thirty eight percent of the patients underwent bypass surgery and 53% of these procedures were performed bilaterally.

Treatment policies, including indications for bypass surgery and commonly used drugs, were somewhat different according to the institution. Overall favorable outcome was 73%, and the most significant factor affecting poor outcome was haemorrhagic manifestation. This article describes the characteristics of 334 patients with moyamoya disease, who were diagnosed and treated at neurosurgical institutes in Korea before 1995.

Long-term outcomes of pediatric moyamoya disease monitored to adulthood.

Imaizumi T, Hayashi K, Saito K, Osawa M, Fukuyama Y.

Imaizumi Pediatric Clinic, Gunma, Japan.
Pediatr Neurol. 1998 Apr;18(4):321-5. Abstract quote
The long-term outcomes of 25 patients with childhood moyamoya disease (18 with the transient ischemic attack [TIA] type and seven with the non-TIA type), who were monitored to adulthood (older than 20 years of age), were evaluated in terms of residual clinical symptoms, intellectual development, and activities of daily living.

Surgical treatment was performed in ten patients, encephaloduroarteriosynangiosis in nine, and superficial temporal artery to middle cerebral artery anastomosis plus encephalomyosynangiosis in one. Only seven with the TIA type (three surgically and four medically treated) demonstrated good activities of daily living without TIA or headache and normal IQ. Two patients with the TIA type and three with the non-TIA type demonstrated poor outcomes. Three of these patients with poor outcomes had renal artery stenosis. Surgery was effective in nine.

Since the long-term outcomes of patients with childhood moyamoya disease are generally poor, surgical treatment is believed to be an effective procedure for preventing the progression of clinical symptoms.

Long-term follow-up study after extracranial-intracranial bypass surgery for anterior circulation ischemia in childhood moyamoya disease.

Karasawa J, Touho H, Ohnishi H, Miyamoto S, Kikuchi H.

Department of Neurosurgery, Osaka Neurological Institute, Japan.
J Neurosurg. 1992 Jul;77(1):84-9. Abstract quote
Between May, 1974, and March, 1991, 104 patients with moyamoya disease, all under 16 years old at the time of first surgery, underwent superficial temporal-to-middle cerebral artery anastomosis and/or encephalomyosynangiosis.

The mean follow-up period was 9.6 years (range 4.8 to 16.0 years). Hemiplegia was the most frequent symptom before the first operation. Transient ischemic attacks (TIA's) were noted in 57 patients and minor stroke with hemiplegia in 44. The most frequent type of cortical dysfunction was aphasia (21 cases). Postoperatively, the incidence of TIA's and/or completed stroke with motor weakness of the extremities was markedly decreased, but visual disturbance progressed and major or minor stroke with visual disturbance was found in two cases. In patients under the age of 3 years, a major stroke prior to surgery resulted in a poor outcome in 36% of cases.

Preoperative major stroke in patients between the ages of 3 and 7 years was less frequent, and poor outcomes were seen in 17% of this group. There were no major preoperative strokes in patients with surgery after the age of 7 years, and no poor outcomes were recorded in this group.

A major preoperative stroke prior to surgery had adverse impact on the ultimate patient intelligence quotient (IQ) following surgery. All patients operated on after the age of 7 years had a normal or borderline IQ at follow-up examination.

HEMORRHAGE

High-risk age for rebleeding in patients with hemorrhagic moyamoya disease: long-term follow-up study.

Morioka M, Hamada J, Todaka T, Yano S, Kai Y, Ushio Y.

Department of Neurosurgery, Kumamoto University School of Medicine, Kumamoto, Japan.

Neurosurgery. 2003 May;52(5):1049-54 Abstract quote
OBJECTIVE: The prevention of rebleeding is one of the most important issues in the successful treatment of moyamoya disease with hemorrhagic onset. However, the natural course of hemorrhagic moyamoya disease and the characteristics of rebleeding remain unclear.

METHODS: To study the natural course of the disease in conservatively treated patients, we analyzed long-term follow-up reports on 36 patients (12 male and 24 female) treated without bypass surgery at our hospitals before 1994 (mean follow-up, 12.7 +/- 7.1 yr; range, 2.9-27.0 yr).

RESULTS: Of our 36 patients, 22 (61.1%) experienced rebleeding; there were 29 rebleeding episodes. The outcomes in patients with rebleeding were worse than in patients who did not rebleed (P < 0.05); in most cases, unsatisfactory results were attributable to rebleeding. Kaplan-Meier and multivariate analysis of rebleeding-free survival showed that age at onset (>36 yr) was a statistically significant risk factor; sex, hypertension, type of intracranial bleeding, and outcome after the first bleeding episode were not. Although the intervals between the first and subsequent episodes varied, both the rebleeding rate and the number of rebleeding episodes were highest in patients 46 to 55 years old.

CONCLUSION: Rebleeding is the most important factor in unsatisfactory outcomes of patients with hemorrhagic moyamoya disease. Rebleeding seems to be age-related; rebleeding occurs at an increased rate when patients reach the age range of 46 to 55 years. Patients with hemorrhagic moyamoya must be followed up throughout their lives, even if their neurological status is excellent.

RADIOGRAPHIC FINDINGS

Angiographic dilatation and branch extension of the anterior choroidal and posterior communicating arteries are predictors of hemorrhage in adult moyamoya patients.

Morioka M, Hamada J, Kawano T, Todaka T, Yano S, Kai Y, Ushio Y.

Department of Neurosurgery, Kumamoto University, School of Medicine, Kumamoto, Japan
Stroke. 2003 Jan;34(1):90-5. Abstract quote
BACKGROUND AND PURPOSE: The cause of intracranial bleeding in moyamoya disease patients is still unknown. To identify factors that contribute to bleeding, we assessed the angiographic findings of moyamoya disease patients.

METHODS: We examined angiograms obtained from 107 moyamoya patients; 70 manifested ischemic and 37 had hemorrhagic lesions. Patients with intracerebral aneurysms or both hemorrhagic and ischemic lesions in the same cerebral hemisphere were not included. Patients were divided into those <20 years of age (n=47) and those > or =20 years of age (n=60). The right and left hemispheres in each patient were individually classified as hemorrhagic, ischemic, or asymptomatic. Each hemisphere was assessed for dilatation and branch extension of the anterior choroidal artery (AChA) and posterior communicating artery (P-CoM) and for the degree of proliferation of basal moyamoya vessels. These data were then statistically analyzed for correlation with intracranial bleeding events.

RESULTS: The degree of proliferation of basal moyamoya vessels was not statistically correlated with hemorrhagic events. On the other hand, there was a correlation between hemorrhage and dilatation and abnormal branching of the AChA. In 27 of 37 hemorrhagic hemispheres (73.0%), this artery was dilated, and its abnormal branches served as collateral supply vessels to other regions. This phenomenon was observed in 4 of 5 hemorrhagic hemispheres from young patients; it was noted in fewer than one third of ischemic and asymptomatic hemispheres from this age group. Similarly, 71.9% of hemorrhagic hemispheres from adult patients manifested AChA dilatation and branching, and the difference between hemorrhagic hemispheres and those that were ischemic or asymptomatic was statistically significant (P<0.01). Although the incidence of dilatation and abnormal branching of the P-CoM was relatively low in hemorrhagic hemispheres from adult patients (18.8%), it was significantly higher than in the ischemic and asymptomatic hemispheres from this age group. Using dilatation and abnormal branching of the AChA and/or P-CoM as assessment criteria, we obtained high specificity (86.4%) and sensitivity (84.4%) for hemorrhagic events in adult moyamoya patients.

CONCLUSIONS: In adult moyamoya patients, dilatation and abnormal branching of the AChA and/or P-CoM are strong predictors of hemorrhagic events.

MR perfusion imaging in Moyamoya Syndrome: potential implications for clinical evaluation of occlusive cerebrovascular disease.

Calamante F, Ganesan V, Kirkham FJ, Jan W, Chong WK, Gadian DG, Connelly A.

Radiology and Physics Units, Institute of Child Health, University College London, UK.
Stroke. 2001 Dec 1;32(12):2810-6. Abstract quote
BACKGROUND AND PURPOSE: Ischemic symptoms in patients with moyamoya syndrome (MMS) are usually due to hemodynamically mediated perfusion failure, and identification of abnormal tissue perfusion in these patients is therefore clinically important. Although dynamic susceptibility contrast (DSC) MRI can be used to study tissue perfusion, there are potential technical problems in MMS. This study investigates the scope and limitations of perfusion MRI in the clinical evaluation of such patients.

METHODS: Thirteen patients with bilateral MMS were studied with the use of structural, diffusion, and perfusion MRI. The DSC MRI data were analyzed both visually and by a quantitative regional analysis, and the relationship between perfusion status and clinical symptoms was investigated.

RESULTS: Extensive bilateral DSC MRI abnormalities were observed in all the patients. There was a very heterogeneous distribution of bolus arrival time. The areas of abnormality included the major arterial border zones in all cases, although these usually appeared normal on structural and diffusion MRI. Only the most clinically unstable patients had peak width (defined as time to peak minus bolus arrival time) >5 seconds on the quantitative regional analysis. Several technical limitations of perfusion quantification in MMS are described, as well as the implications of these limitations in patients with other forms of occlusive large-vessel disease.

CONCLUSIONS: The technical limitations of DSC MRI described in this study are important for the accurate interpretation of perfusion MRI in MMS. Despite these limitations, these preliminary findings suggest that the use of quantitative regional analysis of summary parameters may provide clinically useful information in patients with MMS.

TREATMENT CHARACTERIZATION

GENERAL

OMENTAL TRANSPLANTATION

Cerebral revascularization using omental transplantation for childhood moyamoya disease.

Karasawa J, Touho H, Ohnishi H, Miyamoto S, Kikuchi H.

Department of Neurosurgery, Osaka Neurological Institute, Japan.

J Neurosurg. 1993 Aug;79(2):192-6. Abstract quote
Between January, 1986, and October, 1990, 30 children with moyamoya disease, aged from 2 to 17 years, underwent omental transplantation to either the anterior or the posterior cerebral artery territory.

The mean follow-up period was 3.8 years, ranging from 1.6 to 6.4 years. Seventeen patients had symptoms of monoparesis, paraparesis, and/or urinary incontinence and were treated using unilateral or bilateral omental transplantation to the anterior cerebral artery territory. Eleven patients had visual symptoms and were treated with unilateral or bilateral omental transplantation to the posterior cerebral artery territory. Two patients had symptoms associated with both the anterior and the posterior cerebral arteries, and were treated with dual omental transplantations.

All 19 patients treated with omental transplantation to the anterior cerebral artery and 11 (84.6%) of the 13 treated with omental transplantation to the posterior cerebral artery showed improvement in their neurological state.

Patients with more collateral vessels via the omentum had more rapid and complete improvement in their neurological state. Patients with severe preoperative neurological deficits associated with the posterior cerebral artery had persistence of their symptoms.

SURGERY

Surgical treatment of moyamoya disease: operative technique for encephalo-duro-arterio-myo-synangiosis, its follow-up, clinical results, and angiograms.

Kinugasa K, Mandai S, Kamata I, Sugiu K, Ohmoto T.

Department of Neurological Surgery, Okayama University Medical School, Japan.

Neurosurgery. 1993 Apr;32(4):527-31. Abstract quote
Moyamoya syndrome is defined as the development of collateral anastomosis pathways at the base of the brain, associated with chronic progressive stenosis of the carotid fork. Both reconstructive vascular surgery and conservative strategies are used to treat this syndrome, but the latter cannot prevent the disease from progressing.

We describe the procedure of encephalo-duro-arterio-myo-synangiosis (EDAMS), and report the results in 17 patients (28 sides) who underwent EDAMS. The clinical symptoms of moyamoya disease include transient ischemic attacks, reversible ischemic neurological deficits, stroke, seizures, Gerstmann's syndrome, involuntary movements, or mental retardation resulting from the lack of cerebral blood flow. The clinical results of EDAMS were poor in one patient, fair in two, good in five, excellent in eight, and fair on one side and excellent on the other side in one patient.

Postoperative angiograms showed widespread collateral circulation on the ischemic brain surface in patients undergoing EDAMS.

Moyamoya disease in children and its surgical treatment. Introduction of a new surgical procedure and its follow-up angiograms.

Matsushima Y, Inaba Y.
Childs Brain. 1984;11(3):155-70. Abstract quote
Moyamoya disease is an unusual form of chronic cerebrovascular occlusive disease characterized usually by bilateral stenosis of distal internal carotid arteries and their vicinity, by a hazy network of collateral circulation at the base of the brain called moyamoya vessels and clinically by recurring hemispheric ischemic attacks in children.

This disease was first reported by a Japanese neurosurgeon and many reports and studies on this disease have been published in Japan.

We report here the recent progress in the diagnosis of the disease and introduce a newly developed operative procedure which we think is an ideal surgical method for treating this disease in children.

Henry JB. Clinical Diagnosis and Management by Laboratory Methods. Twentieth Edition. WB Saunders. 2001.
Rosai J. Ackerman's Surgical Pathology. Eight Edition. Mosby 1996.
Sternberg S. Diagnostic Surgical Pathology. Third Edition. Lipincott Williams and Wilkins 1999.
Robbins Pathologic Basis of Disease. Sixth Edition. WB Saunders 1999.
DeMay RM. The Art and Science of Cytopathology. Volume 1 and 2. ASCP Press. 1996.
Weedon D. Weedon's Skin Pathology Second Edition. Churchill Livingstone. 2002
Fitzpatrick's Dermatology in General Medicine. 5th Edition. McGraw-Hill. 1999.
Weiss SW and Goldblum JR. Enzinger and Weiss's Soft Tissue Tumors. Fourth Edition. Mosby 2001.

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LABORATORY/RADIOLOGIC/ OTHER TESTS	CHARACTERIZATION
RADIOLOGIC
Neoangiogenesis in association with moyamoya syndrome shown by estimation of relative recirculation based on dynamic contrast-enhanced MR images. Kassner A, Zhu XP, Li KL, Jackson A. Philips Medical Systems, London, England.	AJNR Am J Neuroradiol. 2003 May;24(5):810-8. Abstract quote BACKGROUND AND PURPOSE: This study examined abnormalities of the recirculation phase of the contrast medium concentration time course curve in patients with moyamoya disease by using the relative recirculation (rR) parameter. Our aims were to increase understanding of the rR parameter and to assess its possible value in the investigation of moyamoya disease. METHODS: Six patients with confirmed moyamoya disease and five normal participants were examined by using dynamic T2*-weighted MR perfusion imaging. Parametric maps of relative cerebral blood volume, time to peak (TTP), and rR were calculated. The width of the normal distribution of TTP and the normal upper limit for rR were derived from the normal participants by identification of the 97.5% confidence limits for the distributions. Major vessels were identified by selection of pixels with relative cerebral blood volume >0.5. Areas of abnormally prolonged TTP and of increased rR were then identified in patients, and the relationship between these parameters and major vessels was examined. RESULTS: The combination of cerebral blood volume >50%, elevated TTP, and elevated rR values accurately identified areas of moyamoya vessel formation seen on angiograms. Larger well-developed meningeal and basal collaterals did not show abnormalities of rR. Areas of prolonged TTP were also observed to occur in the brain distal to arterial occlusion in all cases. In three of these, abnormal elevation of rR was observed in the center of regions of prolonged TTP. CONCLUSION: These findings support those of our previous work, which suggested that rR can act as an indicator of regional microvascular abnormality, such as that seen in areas of angiogenic activity. They also suggest that measurement of rR may provide valuable additional information regarding patients with moyamoya disease.
Evaluation of cerebral hemodynamics with perfusion MRI in childhood moyamoya disease. Kim SK, Wang KC, Oh CW, Kim IO, Lee DS, Song IC, Cho BK. Department of Neurosurgery, Seoul National University Hospital, Seoul, Korea.	Pediatr Neurosurg. 2003 Feb;38(2):68-75 Abstract quote The purpose of our study was to evaluate the role of perfusion MRI and to compare the findings with those of conventional imaging in childhood moyamoya disease (MMD). Perfusion MRI was performed preoperatively on 13 cases of childhood MMD. Based on the perfusion MRI findings, patients were classified into four groups: those with normal regional cerebral blood volume (rCBV) and time to peak (TTP) (group 1, n = 2); those with normal rCBV and delayed TTP (group 2, n = 1); those with increased rCBV and delayed TTP (group 3, n = 5), and those with decreased rCBV and delayed TTP (group 4, n = 5). Lesion volume as determined using the rCBV map was compared with that on MRI and single photon emission computerized tomography (SPECT). The characteristics of groups 1, 2 and 3 were a high frequency of transient ischemic attacks, normal finding on MRI, early angiographic stages, decreased reserve on SPECT and favorable operative outcome. In group 3, angiography revealed abundant collateral channels. In group 4, all cases had infarction on MRI and abnormal perfusion on SPECT. Angiographic stages tended to have progressed, and operative outcome was less favorable. Perfusion MRI documented hemodynamic asymmetries in the five cases with normal MRI. Perfusion MRI is suggested to have a sensitivity intermediate between rest and acetazolamide SPECTs. We conclude that perfusion MRI may be a valuable tool for characterizing and monitoring ischemia in MMD. Perfusion MRI provides additional functional information not available from conventional MRI and has a potential role comparable to SPECT in the evaluation of MMD.
"Ivy sign" in childhood moyamoya disease: depiction on FLAIR and contrast-enhanced T1-weighted MR images. Yoon HK, Shin HJ, Chang YW. Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Kangnam-gu, Seoul 135-710, Korea.	Radiology. 2002 May;223(2):384-9. Abstract quote PURPOSE: To compare contrast material-enhanced T1-weighted and fluid-attenuated inversion recovery (FLAIR) magnetic resonance (MR) images with or without gadolinium in depicting the leptomeningeal ivy sign in children with moyamoya disease. MATERIALS AND METHODS: Twenty-nine sets of FLAIR and postcontrast T1-weighted MR images were available in 19 consecutive children with primary moyamoya disease confirmed with conventional and MR angiography. Contrast-enhanced FLAIR MR images also were available in 15 sets. Two pediatric radiologists reviewed FLAIR and postcontrast T1-weighted images in separate sessions for the leptomeningeal ivy sign and assigned a rating of "present," "absent," or "equivocal" by consensus. Unenhanced and contrast-enhanced FLAIR MR images were compared side by side to determine which better depicted leptomeningeal high signal intensities. RESULTS: Postcontrast T1-weighted MR images revealed the leptomeningeal ivy sign in 40 hemispheres (frequency of visualization, 71% [40 of 56 hemispheres]), whereas unenhanced FLAIR MR images depicted it in 26 hemispheres (frequency of visualization, 46% [26 of 56 hemispheres]). An equivocal rating was given in 21 hemispheres versus in 11 on FLAIR and postcontrast T1-weighted images, respectively. FLAIR and postcontrast T1-weighted images agreed in 40 hemispheres. There was no case with a positive rating on FLAIR images when postcontrast T1-weighted images were negative. Unenhanced FLAIR MR imaging was superior to contrast-enhanced FLAIR imaging in seven hemispheres, whereas enhanced FLAIR was better in four of 28 hemispheres. In the remaining 17, findings with each sequence were similar. CONCLUSION: Contrast-enhanced T1-weighted images are better than FLAIR images for depicting the leptomeningeal ivy sign in moyamoya disease.
Moyamoya disease: comparison of assessment with MR angiography and MR imaging versus conventional angiography. Yamada I, Suzuki S, Matsushima Y. Department of Radiology, Faculty of Medicine, Tokyo Medical and Dental University, Japan.	Radiology. 1995 Jul;196(1):211-8. Abstract quote PURPOSE: To evaluate magnetic resonance (MR) angiography and MR imaging in assessment of moyamoya disease. MATERIALS AND METHODS: The cases of 26 patients with moyamoya disease were evaluated prospectively. After three-dimensional time-of-flight 1.5-T MR angiography and MR imaging, images were evaluated in blinded separate interpretation. RESULTS: MR angiography and MR imaging accurately depicted 217 (82%) and 184 (70%) of 264 arteries, respectively, but the degree of stenosis was overestimated in the other arteries. Basal cerebral moyamoya vessels were depicted in all 52 hemispheres with conventional angiography and in 42 (81%) and 48 (92%) hemispheres with MR angiography and MR imaging, respectively. The respective sensitivity and specificity for diagnosis of moyamoya disease were 73% and 100% for MR angiography, 92% and 100% for MR imaging, and 92% and 100% for MR angiography plus MR imaging. CONCLUSION: Assessment of moyamoya disease is most thorough with MR angiography and MR imaging.
PET SCAN
Metabolic changes after H(2) 15O-positron emission tomography with acetazolamide in a patient with moyamoya disease: case report and review of previous cases. Muroi C, Yonekawa Y, Khan N, Pangalu A, Keller E. Department of Neurosurgery, University Hospital Zurich, Zurich, Switzerland	J Neurosurg Anesthesiol. 2003 Apr;15(2):131-9. Abstract quote Perioperative ischemic complications not directly related to surgery require special attention in patients with moyamoya disease; positron emission tomography (H(2) 15O-PET) and single-photon emission computed tomography have been considered indispensable for evaluating pre- and postsurgical cerebral hemodynamics. The clinical records of 14 patients with moyamoya disease who underwent 26 extracranial-intracranial bypass operations were reviewed with special reference to perisurgical complications. One patient developed multiple postoperative ischemic infarctions and died of ischemic brain edema. The history of this patient with prolonged acidosis is analyzed, and the role of metabolic changes induced by H(2) 15O-PET with acetazolamide challenge is reviewed. Seven (77.8%) of nine patients operated on within 48 hours after H(2) 15O-PET with acetazolamide (group 1) developed metabolic acidosis, whereas only three (17.6%) of 17 patients operated on >48 hours (group 2) after the examination had intraoperative pH of <7.35. In group 1, the mean intraoperative pH was 7.328, which was significantly lower than the mean pH of 7.393 (P <.0001) in group 2. After H(2) 15O-PET with acetazolamide challenge, patients must be carefully observed concerning acidosis and volume state. We recommend at least 48 hours between examination and surgery for patients with moyamoya disease so that their conditions can stabilize. Furthermore, special care should be taken to avoid additional perioperative risk factors such as hypotension, hypocapnia, hypercapnia, and hypovolemia.

GROSS APPEARANCE/ CLINICAL VARIANTS	CHARACTERIZATION
GENERAL
Moyamoya disease: an elusive diagnosis. Asumal KB, Akhtar N, Syed NA, Shafqat S, Baig SM. Section of Neurology, Department of Medicine, The Aga Khan University Hospital Karachi.	J Pak Med Assoc. 2003 Apr;53(4):160-2 Abstract quote OBJECTIVE AND BACKGROUND: Moyamoya disease is an idiopathic vasculopathy of circle of Willis. Stroke is a common presentation. We describe clinical and radiological features of moyamoya disease in four patients. SETTING: Tertiary care center in a metropolitan city. MATERIALS AND METHODS: Patients with moyamoya disease were identified by ICD-9 coding system of the hospital medical records. Demographic characteristics, clinical features/presentation, laboratory investigations and radiological investigations were recorded and analyzed. RESULTS: Four patients (three children and one adult) presented with hemiparesis. One patient expired during hospital stay. Two patients underwent surgery (synangiosis). EEGs of three patients showed focal abnormalities. Neuroimaging showed ischemic infarctions in all patients. Findings on four vessel digital substraction angiography and/or magnetic resonance angiography were compatible with moyamoya disease. CONCLUSION: Moyamoya disease should be considered in all young patients, especially children, presenting with stroke.
Moyamoya: Indiana University Medical Center experience. Yilmaz EY, Pritz MB, Bruno A, Lopez-Yunez A, Biller J. Department of Neurology, Indiana University School of Medicine, 545 Barnhill Dr, Emerson Hall 125, Indianapolis, IN 46202, USA	Arch Neurol. 2001 Aug;58(8):1274-8. Abstract quote BACKGROUND: Moyamoya usually presents with cerebral ischemia in children and intracranial hemorrhage in adults. Treatment remains controversial. DESIGN AND OBJECTIVE: We reviewed our experience from June 1995 to August 1999 of 20 adult and pediatric angiographically diagnosed patients with moyamoya to report their clinical presentation, radiological findings, management, and clinical outcomes. RESULTS: The mean age of patients at symptom onset was 17 years (range, 2-54 years). Patients were divided into 2 age groups (group 1, <18 years; group 2, > or =18 years). There were 13 patients in group 1 and 7 patients in group 2. Ischemic strokes or transient ischemic attacks were the predominant initial presentations in both groups. One patient in group 2 had an intraparenchymal brain hemorrhage. Five patients received medical treatment, and 15 had surgical revascularization. The mean time from symptom onset to surgical procedure was significantly longer for patients in group 1 than for those in group 2 (P =.03). The mean follow-up time was 36 months. One patient in group 1 had an ischemic stroke. There was no difference in stroke recurrence, mortality, or modified Rankin scale score among medically or surgically treated patients. CONCLUSIONS: Moyamoya disease may have a different presentation and more benign natural history in our population than in Asian populations. Our findings emphasize the need to better understand the natural history of patients with moyamoya as well as the clinical benefit of different treatment modalities. Structured multicenter randomized clinical trials are needed to further assess the best treatment modalities for patients with moyamoya in the United States.
VARIANTS
FAMILIAL
Moyamoya disease in monovular twins: case report. Yamada H, Nakamura S, Kageyama N.	J Neurosurg. 1980 Jul;53(1):109-12. Abstract quote The first reported instance of identical twins with moyamoya disease is presented. The involved portions of the main intracranial arteries were similar, but the formation of the moyamoya vessels was somewhat different. The cause of obstructive changes in large intracranial arteries remains obscure, but the frequent familial occurrence suggests that the initial stages of this disease and the formation of the moyamoya vessels occur in the prenatal period.
Familial occurrence of bilateral intracranial occlusion of the internal carotid arteries (Moya Moya). Sogaard I, Jorgensen J.	Acta Neurochir (Wien). 1975;31(3-4):245-52. Abstract quote In a family of 14 brothers and sisters, 3 cases of occlusive disease of the large intracranial vessels (Moya Moya) were found. Each of the three had one or more cerebrovascular attacks and a typical cerebral angiogram. Eight other members of the family had severe headaches. Angiography was carried out in three of these with normal findings.
HEMICHOREA
Hemichorea as an initial manifestation of moyamoya disease: reversible striatal hypoperfusion demonstrated on single photon emission computed tomography. Hong YH, Ahn TB, Oh CW, Jeon BS. Department of Neurology, Clinical Research Institute, Seoul National University Hospital, SNUMRC, College of Medicine, Seoul National University, Seoul, South Korea.	Mov Disord. 2002 Nov;17(6):1380-3. Abstract quote We describe a case with unilateral moyamoya disease that showed progressive hemichorea as an initial manifestation. Single photon emission computed tomography showed perfusion defect in the contralateral basal ganglia although magnetic resonance imaging was unremarkable. Hemichorea improved along with normalization of perfusion after bypass surgery, suggestive of striatal hypoperfusion as the cause of hemichorea.
PEDIATRIC
Moyamoya syndrome in young children: MR comparison with adult onset. Takanashi J, Sugita K, Ishii M, Tanabe Y, Ito C, Date H, Niimi H. Department of Pediatrics, School of Medicine, Chiba University, Japan.	AJNR Am J Neuroradiol. 1993 Sep-Oct;14(5):1139-43. Abstract quote PURPOSE: To clarify whether there were any differences in MR appearance between the childhood and the adult moyamoya syndromes. METHOD: We compared the cranial MR findings in four children under the age of 6 who had moyamoya syndrome with previously documented adult cases. RESULTS: Moyamoya syndrome in younger children exhibited a significant increase in cortical and subcortical infarction, and a decreased incidence of deep white matter infarction in the centrum semiovale and basal ganglia, in contrast to adult cases. There were no remarkable differences between these two groups of moyamoya cases with regard to the occlusive changes of the internal carotid and middle cerebral arteries, or to the flow void sign on MR. CONCLUSION: These differences in the sites and frequencies of infarctions between the childhood and the adult moyamoya syndromes observed on MR might reflect differences in the cerebral circulation.

PROGNOSIS	CHARACTERIZATION
GENERAL	Mortality rates are approximately 10% in adults and 4.3% in children Death is usually from hemorrhage About 50-60% of affected individuals experience a gradual deterioration of cognitive function possibly secondary to recurrent strokes
A co-operative study: clinical characteristics of 334 Korean patients with moyamoya disease treated at neurosurgical institutes (1976-1994). The Korean Society for Cerebrovascular Disease. Han DH, Kwon OK, Byun BJ, Choi BY, Choi CW, Choi JU, Choi SG, Doh JO, Han JW, Jung S, Kang SD, Kim DJ, Kim HI, Kim HD, Kim MC, Kim SC, Kim SC, Kim Y, Kwun BD, Lee BG, Lim YJ, Moon JG, Park HS, Shin MS, Song JH, Suk JS, Yim MB; Korean Society for Cerebrovascular Disease. Department of Neurosurgery, Seoul National University Hospital, Chongno-gu, Korea.	Acta Neurochir (Wien). 2000;142(11):1263-73 Abstract quote A co-operative study was conducted to determine the clinical characteristics of patients with moyamoya disease who were diagnosed and treated at neurosurgical institutes in Korea before 1995. Twenty-six hospitals contributed 505 cases and among them, the clinical characteristics of 334 patients with definite moyamoya disease were evaluated. The number of patients began to increase from the late 1980s, and after that approximately 20 patients were treated each year. There were two age peaks: from six to 15 and from 31 to 40 years of age. Haemorrhagic manifestations occurred in approximately 43% of the patients. The major clinical manifestations were haemorrhage in adults (62.4%) and ischaemia in children (61.2%). Overall 54.5% of the patients experienced decreased consciousness levels, mainly due to intracranial haemorrhage or cerebral infarction. In the patients with ischemic manifestations, the adult patients were more likely to have cerebral infarction than the pediatric patients (80% vs. 39%) and the pediatric patients were more likely to have TIA (61% vs. 25%). Thirty eight percent of the patients underwent bypass surgery and 53% of these procedures were performed bilaterally. Treatment policies, including indications for bypass surgery and commonly used drugs, were somewhat different according to the institution. Overall favorable outcome was 73%, and the most significant factor affecting poor outcome was haemorrhagic manifestation. This article describes the characteristics of 334 patients with moyamoya disease, who were diagnosed and treated at neurosurgical institutes in Korea before 1995.
Long-term outcomes of pediatric moyamoya disease monitored to adulthood. Imaizumi T, Hayashi K, Saito K, Osawa M, Fukuyama Y. Imaizumi Pediatric Clinic, Gunma, Japan.	Pediatr Neurol. 1998 Apr;18(4):321-5. Abstract quote The long-term outcomes of 25 patients with childhood moyamoya disease (18 with the transient ischemic attack [TIA] type and seven with the non-TIA type), who were monitored to adulthood (older than 20 years of age), were evaluated in terms of residual clinical symptoms, intellectual development, and activities of daily living. Surgical treatment was performed in ten patients, encephaloduroarteriosynangiosis in nine, and superficial temporal artery to middle cerebral artery anastomosis plus encephalomyosynangiosis in one. Only seven with the TIA type (three surgically and four medically treated) demonstrated good activities of daily living without TIA or headache and normal IQ. Two patients with the TIA type and three with the non-TIA type demonstrated poor outcomes. Three of these patients with poor outcomes had renal artery stenosis. Surgery was effective in nine. Since the long-term outcomes of patients with childhood moyamoya disease are generally poor, surgical treatment is believed to be an effective procedure for preventing the progression of clinical symptoms.
Long-term follow-up study after extracranial-intracranial bypass surgery for anterior circulation ischemia in childhood moyamoya disease. Karasawa J, Touho H, Ohnishi H, Miyamoto S, Kikuchi H. Department of Neurosurgery, Osaka Neurological Institute, Japan.	J Neurosurg. 1992 Jul;77(1):84-9. Abstract quote Between May, 1974, and March, 1991, 104 patients with moyamoya disease, all under 16 years old at the time of first surgery, underwent superficial temporal-to-middle cerebral artery anastomosis and/or encephalomyosynangiosis. The mean follow-up period was 9.6 years (range 4.8 to 16.0 years). Hemiplegia was the most frequent symptom before the first operation. Transient ischemic attacks (TIA's) were noted in 57 patients and minor stroke with hemiplegia in 44. The most frequent type of cortical dysfunction was aphasia (21 cases). Postoperatively, the incidence of TIA's and/or completed stroke with motor weakness of the extremities was markedly decreased, but visual disturbance progressed and major or minor stroke with visual disturbance was found in two cases. In patients under the age of 3 years, a major stroke prior to surgery resulted in a poor outcome in 36% of cases. Preoperative major stroke in patients between the ages of 3 and 7 years was less frequent, and poor outcomes were seen in 17% of this group. There were no major preoperative strokes in patients with surgery after the age of 7 years, and no poor outcomes were recorded in this group. A major preoperative stroke prior to surgery had adverse impact on the ultimate patient intelligence quotient (IQ) following surgery. All patients operated on after the age of 7 years had a normal or borderline IQ at follow-up examination.
HEMORRHAGE
High-risk age for rebleeding in patients with hemorrhagic moyamoya disease: long-term follow-up study. Morioka M, Hamada J, Todaka T, Yano S, Kai Y, Ushio Y. Department of Neurosurgery, Kumamoto University School of Medicine, Kumamoto, Japan.	Neurosurgery. 2003 May;52(5):1049-54 Abstract quote OBJECTIVE: The prevention of rebleeding is one of the most important issues in the successful treatment of moyamoya disease with hemorrhagic onset. However, the natural course of hemorrhagic moyamoya disease and the characteristics of rebleeding remain unclear. METHODS: To study the natural course of the disease in conservatively treated patients, we analyzed long-term follow-up reports on 36 patients (12 male and 24 female) treated without bypass surgery at our hospitals before 1994 (mean follow-up, 12.7 +/- 7.1 yr; range, 2.9-27.0 yr). RESULTS: Of our 36 patients, 22 (61.1%) experienced rebleeding; there were 29 rebleeding episodes. The outcomes in patients with rebleeding were worse than in patients who did not rebleed (P < 0.05); in most cases, unsatisfactory results were attributable to rebleeding. Kaplan-Meier and multivariate analysis of rebleeding-free survival showed that age at onset (>36 yr) was a statistically significant risk factor; sex, hypertension, type of intracranial bleeding, and outcome after the first bleeding episode were not. Although the intervals between the first and subsequent episodes varied, both the rebleeding rate and the number of rebleeding episodes were highest in patients 46 to 55 years old. CONCLUSION: Rebleeding is the most important factor in unsatisfactory outcomes of patients with hemorrhagic moyamoya disease. Rebleeding seems to be age-related; rebleeding occurs at an increased rate when patients reach the age range of 46 to 55 years. Patients with hemorrhagic moyamoya must be followed up throughout their lives, even if their neurological status is excellent.
RADIOGRAPHIC FINDINGS
Angiographic dilatation and branch extension of the anterior choroidal and posterior communicating arteries are predictors of hemorrhage in adult moyamoya patients. Morioka M, Hamada J, Kawano T, Todaka T, Yano S, Kai Y, Ushio Y. Department of Neurosurgery, Kumamoto University, School of Medicine, Kumamoto, Japan	Stroke. 2003 Jan;34(1):90-5. Abstract quote BACKGROUND AND PURPOSE: The cause of intracranial bleeding in moyamoya disease patients is still unknown. To identify factors that contribute to bleeding, we assessed the angiographic findings of moyamoya disease patients. METHODS: We examined angiograms obtained from 107 moyamoya patients; 70 manifested ischemic and 37 had hemorrhagic lesions. Patients with intracerebral aneurysms or both hemorrhagic and ischemic lesions in the same cerebral hemisphere were not included. Patients were divided into those <20 years of age (n=47) and those > or =20 years of age (n=60). The right and left hemispheres in each patient were individually classified as hemorrhagic, ischemic, or asymptomatic. Each hemisphere was assessed for dilatation and branch extension of the anterior choroidal artery (AChA) and posterior communicating artery (P-CoM) and for the degree of proliferation of basal moyamoya vessels. These data were then statistically analyzed for correlation with intracranial bleeding events. RESULTS: The degree of proliferation of basal moyamoya vessels was not statistically correlated with hemorrhagic events. On the other hand, there was a correlation between hemorrhage and dilatation and abnormal branching of the AChA. In 27 of 37 hemorrhagic hemispheres (73.0%), this artery was dilated, and its abnormal branches served as collateral supply vessels to other regions. This phenomenon was observed in 4 of 5 hemorrhagic hemispheres from young patients; it was noted in fewer than one third of ischemic and asymptomatic hemispheres from this age group. Similarly, 71.9% of hemorrhagic hemispheres from adult patients manifested AChA dilatation and branching, and the difference between hemorrhagic hemispheres and those that were ischemic or asymptomatic was statistically significant (P<0.01). Although the incidence of dilatation and abnormal branching of the P-CoM was relatively low in hemorrhagic hemispheres from adult patients (18.8%), it was significantly higher than in the ischemic and asymptomatic hemispheres from this age group. Using dilatation and abnormal branching of the AChA and/or P-CoM as assessment criteria, we obtained high specificity (86.4%) and sensitivity (84.4%) for hemorrhagic events in adult moyamoya patients. CONCLUSIONS: In adult moyamoya patients, dilatation and abnormal branching of the AChA and/or P-CoM are strong predictors of hemorrhagic events.
MR perfusion imaging in Moyamoya Syndrome: potential implications for clinical evaluation of occlusive cerebrovascular disease. Calamante F, Ganesan V, Kirkham FJ, Jan W, Chong WK, Gadian DG, Connelly A. Radiology and Physics Units, Institute of Child Health, University College London, UK.	Stroke. 2001 Dec 1;32(12):2810-6. Abstract quote BACKGROUND AND PURPOSE: Ischemic symptoms in patients with moyamoya syndrome (MMS) are usually due to hemodynamically mediated perfusion failure, and identification of abnormal tissue perfusion in these patients is therefore clinically important. Although dynamic susceptibility contrast (DSC) MRI can be used to study tissue perfusion, there are potential technical problems in MMS. This study investigates the scope and limitations of perfusion MRI in the clinical evaluation of such patients. METHODS: Thirteen patients with bilateral MMS were studied with the use of structural, diffusion, and perfusion MRI. The DSC MRI data were analyzed both visually and by a quantitative regional analysis, and the relationship between perfusion status and clinical symptoms was investigated. RESULTS: Extensive bilateral DSC MRI abnormalities were observed in all the patients. There was a very heterogeneous distribution of bolus arrival time. The areas of abnormality included the major arterial border zones in all cases, although these usually appeared normal on structural and diffusion MRI. Only the most clinically unstable patients had peak width (defined as time to peak minus bolus arrival time) >5 seconds on the quantitative regional analysis. Several technical limitations of perfusion quantification in MMS are described, as well as the implications of these limitations in patients with other forms of occlusive large-vessel disease. CONCLUSIONS: The technical limitations of DSC MRI described in this study are important for the accurate interpretation of perfusion MRI in MMS. Despite these limitations, these preliminary findings suggest that the use of quantitative regional analysis of summary parameters may provide clinically useful information in patients with MMS.

TREATMENT	CHARACTERIZATION
GENERAL
OMENTAL TRANSPLANTATION
Cerebral revascularization using omental transplantation for childhood moyamoya disease. Karasawa J, Touho H, Ohnishi H, Miyamoto S, Kikuchi H. Department of Neurosurgery, Osaka Neurological Institute, Japan.	J Neurosurg. 1993 Aug;79(2):192-6. Abstract quote Between January, 1986, and October, 1990, 30 children with moyamoya disease, aged from 2 to 17 years, underwent omental transplantation to either the anterior or the posterior cerebral artery territory. The mean follow-up period was 3.8 years, ranging from 1.6 to 6.4 years. Seventeen patients had symptoms of monoparesis, paraparesis, and/or urinary incontinence and were treated using unilateral or bilateral omental transplantation to the anterior cerebral artery territory. Eleven patients had visual symptoms and were treated with unilateral or bilateral omental transplantation to the posterior cerebral artery territory. Two patients had symptoms associated with both the anterior and the posterior cerebral arteries, and were treated with dual omental transplantations. All 19 patients treated with omental transplantation to the anterior cerebral artery and 11 (84.6%) of the 13 treated with omental transplantation to the posterior cerebral artery showed improvement in their neurological state. Patients with more collateral vessels via the omentum had more rapid and complete improvement in their neurological state. Patients with severe preoperative neurological deficits associated with the posterior cerebral artery had persistence of their symptoms.
SURGERY
Surgical treatment of moyamoya disease: operative technique for encephalo-duro-arterio-myo-synangiosis, its follow-up, clinical results, and angiograms. Kinugasa K, Mandai S, Kamata I, Sugiu K, Ohmoto T. Department of Neurological Surgery, Okayama University Medical School, Japan.	Neurosurgery. 1993 Apr;32(4):527-31. Abstract quote Moyamoya syndrome is defined as the development of collateral anastomosis pathways at the base of the brain, associated with chronic progressive stenosis of the carotid fork. Both reconstructive vascular surgery and conservative strategies are used to treat this syndrome, but the latter cannot prevent the disease from progressing. We describe the procedure of encephalo-duro-arterio-myo-synangiosis (EDAMS), and report the results in 17 patients (28 sides) who underwent EDAMS. The clinical symptoms of moyamoya disease include transient ischemic attacks, reversible ischemic neurological deficits, stroke, seizures, Gerstmann's syndrome, involuntary movements, or mental retardation resulting from the lack of cerebral blood flow. The clinical results of EDAMS were poor in one patient, fair in two, good in five, excellent in eight, and fair on one side and excellent on the other side in one patient. Postoperative angiograms showed widespread collateral circulation on the ischemic brain surface in patients undergoing EDAMS.
Moyamoya disease in children and its surgical treatment. Introduction of a new surgical procedure and its follow-up angiograms. Matsushima Y, Inaba Y.	Childs Brain. 1984;11(3):155-70. Abstract quote Moyamoya disease is an unusual form of chronic cerebrovascular occlusive disease characterized usually by bilateral stenosis of distal internal carotid arteries and their vicinity, by a hazy network of collateral circulation at the base of the brain called moyamoya vessels and clinically by recurring hemispheric ischemic attacks in children. This disease was first reported by a Japanese neurosurgeon and many reports and studies on this disease have been published in Japan. We report here the recent progress in the diagnosis of the disease and introduce a newly developed operative procedure which we think is an ideal surgical method for treating this disease in children.

ADULTS	CHILDREN
Hemorrhage (intraventricular, subarachnoid, or intracerebral hemorrhage) more common	Cerebral ischemic events more common Hemiparesis, monoparesis, sensory impairment, involuntary movements, headaches, dizziness, or seizures Mental retardation or persistent neurologic deficits

Epidemiology
Disease Associations
Pathogenesis
Laboratory/Radiologic/Other Diagnostic Testing
Gross Appearance and Clinical Variants
Histopathological Features and Variants
Special Stains/Immunohistochemistry/Electron Microscopy
Differential Diagnosis
Prognosis
Treatment
Commonly Used Terms
Internet Links

EPIDEMIOLOGY	CHARACTERIZATION
INCIDENCE/PREVALENCE	Very rare
AGE	6 months to 67 years, with the highest peak in the first decade and smaller peaks in the third and fourth decades
SEX	Female-to-male ratio is 1.8:1
EPIDEMIOLOGIC ASSOCIATIONS	Primarily in Asians Less common in Caucasians, African Americans, Haitians, and Hispanics
GREECE
Familial moyamoya disease in a Greek family. Zafeiriou DI, Ikeda H, Anastasiou A, Vargiami E, Vougiouklis N, Katzos G, Gombakis N, Gioula G, Matsushima Y, Kirkham FJ. 1st Paediatric Klinic, Aristotle University, Thessaloniki, Greece	Brain Dev. 2003 Jun;25(4):288-90. Abstract quote Moyamoya disease (M-M) is characterized by progressive obstruction of the supraclinoid portion of internal carotid arteries and the proximal middle, anterior and posterior cerebral arteries, associated with the formation of a characteristic net of collateral vessels in the basal ganglia region. Clinical manifestations in childhood include transient ischaemic attacks, seizures and multiple infarcts. Approximately 7% of M-M cases are familial. We report two affected Greek siblings with typical clinical and neuroradiological findings of M-M. Linkage analysis of the whole family was consistent with linkage to the region 3p24-26, as previously reported in other familial Japanese M-M cases
KOREA
Epidemiological survey of moyamoya disease in Korea. Ikezaki K, Han DH, Kawano T, Inamura T, Fukui M. Department of Neurosurgery, Kyushu University Faculty of Medicine, Fukuoka, Japan.	Clin Neurol Neurosurg. 1997 Oct;99 Suppl 2:S6-10. Abstract quote To both clarify the current clinico-epidemiological features of Moyamoya disease in Korea as well as compare these cases with Japanese patients, 451 cases were collected from 26 Korean major neurosurgical institutes and 296 definite cases were analyzed statistically. Although the Korean age distribution patterns of Moyamoya disease showed two peaks, similar to Japanese patients, the Korean pattern was shifted to the right thus indicating Korean adult population to be 20% higher than that of Japanese patients. The female/male ratio was 1:3, which was slightly less than that for Japanese. The family occurrence rate in Koreans was 1.8%. The incidence of cerebral infarction and bleeding in Koreans was higher while transient ischemic attack (TIA) and seizure were less than that of Japanese. The incidence of infarction in children and of hemorrhage in children and adults were also statistically higher in Koreans. The incidence of hemorrhage was higher in females than in males. Both the age at onset and sex affected the disease type. Single encephalo-duro-arterio-synangiosis (EDAS) was performed on 87.6% of all surgical cases. Although the incidence of bleeding was higher in Korea, the outcomes of the patients were similar to that of the Japanese patients. Although Korean Moyamoya disease showed a relatively higher incidence of hemorrhage and adult onset, the overall clinical background was similar to that of Japanese patients.

DISEASE ASSOCIATIONS	CHARACTERIZATION
ATHEROSCLEROSIS
CARDIO-FACIO-CUTANEOUS SYNDROME
Cardio-facio-cutaneous syndrome and moyamoya syndrome. Ishiguro Y, Kubota T, Takenaka J, Maruyama K, Okumura A, Negoro T, Watanabe K. Department of Pediatrics, Nagoya University School of Medicine, 65 Tsurumai-cho, Showa-ku, Aichi 466-8550, Japan.	Brain Dev. 2002 Jun;24(4):245-9. Abstract quote We reported a patient with cardio-facio-cutaneous (CFC) syndrome associated with moyamoya syndrome. The patient was referred at 6 years 5 months with left hemiplegia and right-sided eye deviation. He had an apparently short stature, macrocephaly, left ptosis and atopic skin, and was odd looking. He exhibited an incomplete right bundle branch block on electrocardiogram and an atrial septal defect on ultrasound cardiography. He was diagnosed as having CFC syndrome. Head magnetic resonance imaging showed a flow void in the bilateral basal ganglia, but did not show any ischemic changes. Magnetic resonance angiography showed bilateral stenosis with an internal carotid artery at the Willis artery ring level and bilateral moyamoya. Contrast angiography demonstrated occlusion of both middle cerebral arteries. Cerebrovascular anomalies have not previously been reported in CFC syndrome. This is the first case of CFC syndrome associated with moyamoya syndrome.
DOWN SYNDROME
Moyamoya disease and Down syndrome: case report and review of the literature. de Borchgrave V, Saussu F, Depre A, de Barsy T. Centre Neurologique William Lennox, Cliniques Universitaires Saint-Luc, Universite Catholique de Louvain, 1200 Brussels.	Acta Neurol Belg. 2002 Jun;102(2):63-6. Abstract quote We present the case of a 29-year-old woman with Down syndrome who developed bilateral frontal ischemic stroke. Cerebral angiography demonstrated an occlusion of the both supraclinoid internal carotid arteries associated with dilated collateral vessels, consistent with moyamoya disease. We review the clinical and radiological features of moyamoya disease associated with Down syndrome and discuss a few major physiopathologic hypotheses to explain this association.
Moyamoya disease (syndrome) and the Down syndrome. Fukuyama Y, Osawa M, Kanai N. Department of Pediatrics, Tokyo Women's Medical College, Japan.	Brain Dev. 1992 Jul;14(4):254-6.
HEMATOLOGIC DISORDERS	Aplastic anemia, Fanconi anemia, sickle cell anemia, and lupus anticoagulant
INFECTIONS	Leptospirosis and tuberculosis
LIVEDO RETICULARIS
Livedo reticularis in a child with moyamoya disease. Richards KA, Paller AS. Departments of Dermatology and Pediatrics, Children's Memorial Hospital, Northwestern University Medical School, Chicago, Illinois	Pediatr Dermatol. 2003 Mar-Apr;20(2):124-7. Abstract quote Moyamoya disease is a rare, chronic cerebrovascular occlusive disease of unknown etiology. It is characterized by progressive stenosis of the arteries of the circle of Willis leading to an abnormal capillary network and resultant ischemic strokes or cerebral hemorrhages. The association of moyamoya disease with livedo reticularis has been described in a previously reported patient with a factor V Leiden mutation, leading to hypercoagulation. We describe a girl with livedo reticularis and moyamoya disease with extensive cardiovascular malformations, but without a primary coagulopathy.
NEPHROTIC SYNDROME
Moyamoya disease complicated with renal artery stenosis and nephrotic syndrome: reversal of nephrotic syndrome after nephrectomy. Kuwayama F, Hamasaki Y, Shinagawa T, Kubota C, Ichikawa I, Kato Y, Oi S, Shinohara O. Department of Pediatrics, Tokai University School of Medicine, Kanagawa, Japan.	Pediatr. 2001 Mar;138(3):418-20. Abstract quote A 7-year-old boy with moyamoya disease developed sustained hypertension, nephrotic syndrome, hyperreninemia, and occlusion of the right renal artery. After right nephrectomy, hyperreninemia and hypertension improved. Proteinuria was resolved after nephrectomy, in parallel with the decrease in plasma renin activity. Moyamoya disease can cause nephrotic-range proteinuria, which is caused hemodynamically by hyperreninemia.
RADIATION
Moyamoya phenomenon after radiation for optic glioma. Kestle JR, Hoffman HJ, Mock AR. Division of Neurosurgery, Hospital for Sick Children, Toronto, Ontario, Canada.	J Neurosurg. 1993 Jul;79(1):32-5. Abstract quote The role of radiotherapy in the management of patients with optic pathway glioma is controversial. In a series of patients with optic pathway glioma treated at The Hospital for Sick Children in Toronto, five children were encountered who developed moyamoya phenomenon after radiotherapy. A retrospective review of the medical records was undertaken in order to assess the relationship between optic pathway glioma, neurofibromatosis type 1 (NF1), radiation therapy, and moyamoya disease. Forty-seven patients with optic pathway glioma were operated on at The Hospital for Sick Children between 1971 and 1990. The moyamoya phenomenon did not occur in any of the 19 patients not receiving radiotherapy. Among the 28 patients who received radiotherapy, five developed moyamoya disease (two of 23 without NF1 and three of five with NF1). There was a statistically significant relationship between radiotherapy and moyamoya disease when the analysis was stratified according to the presence of NF1 (Mantel-Haensel chi-squared test 15.23, p < 0.01). The high incidence of moyamoya disease (three of five cases, or 60%) in patients with NF1 who have undergone radiotherapy suggests a synergistic relationship that should be considered when formulating a treatment plan for NF1 patients with optic pathway glioma.
RENOVASCULAR HYPERTENSION
Moyamoya disease associated with renovascular hypertension. Yamashita M, Tanaka K, Kishikawa T, Yokota K.	Hum Pathol. 1984 Feb;15(2):191-3. Abstract quote Findings at the autopsy of a 7-year-old Japanese girl with moyamoya disease associated with renovascular hypertension are reported. There was disruption of a saccular aneurysm located at the junction of the left posterior cerebral and the posterior communicating arteries. Intimal thickening of carotid, coronary, and renal arteries, similar to findings in cases of intimal hyperplasia of fibromuscular dysplasia, was observed. These findings indicate that moyamoya disease may actually be an intracranial manifestation in a systemic arterial disorder.
SICKLE CELL DISEASE
Moyamoya syndrome in childhood sickle cell disease: a predictive factor for recurrent cerebrovascular events. Dobson SR, Holden KR, Nietert PJ, Cure JK, Laver JH, Disco D, Abboud MR. Department of Neurology, Medical University of South Carolina, Charleston, SC 29425, USA.	Blood. 2002 May 1;99(9):3144-50 Abstract quote We conducted a retrospective study to determine whether the presence of moyamoya collaterals influenced the risk of recurrence of cerebrovascular events (CVEs: stroke or transient ischemic attack) in patients with sickle cell disease placed on chronic transfusions after a stroke. Forty-three patients with homozygous sickle cell anemia (HbSS) and 1 with HbSO(Arab) (16 females, 28 males) who had suffered strokes while under the age of 18 were studied. All patients had been on transfusions aimed at maintaining the sickle hemoglobin (HbS) level below 30%. They were followed for a mean of 6.6 years (2.2 to 20.4 years). The presence of collaterals was diagnosed based on either magnetic resonance angiography or conventional angiography. Eighteen (41%) of the 44 patients suffered recurrent CVEs. Nineteen (43%) (6 females, 13 males) patients had moyamoya collaterals. Eleven (58%) of these 19 experienced 21 total recurrent CVEs, including 4 strokes in 4 patients (21%). In comparison, 7 (28%) of 25 patients without moyamoya collaterals experienced 9 recurrent CVEs (P <.05) with only 1 recurrent stroke (4%). Moyamoya patients were also more likely to have 2 recurrent CVEs (42% vs 8%, P <.05) as well as poorer neuropsychological testing results. A proportional hazards regression analysis indicated that patients with moyamoya were more than twice as likely to incur a subsequent CVE (hazard ratio, 2.40; 95% confidence interval, 0.85, 6.75). We conclude that up to 41% of patients with sickle cell disease experience recurrent CVEs after an initial stroke despite chronic transfusions and that the risk of recurrence is significantly higher for those who have moyamoya collaterals.