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Unilateral moyamoya disease (MMD) represents a distinct subtype characterised by occlusive changes in the circle of Willis and abnormal vascular network formation. However, the aetiology and pathogenesis of unilateral MMD remain unclear. In this study, genetic screening of a family with unilateral MMD using whole-genome sequencing helped identify the c.1205 C > A variant of FOXM1, which encodes the transcription factor FOXM1 and plays a crucial role in angiogenesis and cell proliferation, as a susceptibility gene mutation. We demonstrated that this mutation significantly attenuated the proangiogenic effects of FOXM1 in human brain endothelial cells, leading to reduced proliferation, migration, and tube formation. Furthermore, FOXM1 c.1205 C > A results in increased apoptosis of human brain endothelial cells, mediated by the downregulation of the transcription of the apoptosis-inhibiting protein BCL2. These results suggest a potential role for the FOXM1 c.1205 C > A mutation in the pathogenesis of unilateral MMD and may contribute to the understanding and treatment of this condition., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background and Purpose: Although chronic ischemia is known to induce myelin and axonal damage in animal models, knowledge regarding patients with Moyamoya disease is limited. We aimed to investigate the presence of myelin and axonal damage in Moyamoya disease and their relationship with cognitive performance., Materials and Methods: Eighteen patients with Moyamoya disease (16-55 years of age) and 18 age- and sex-matched healthy controls were evaluated with myelin-sensitive MR imaging based on magnetization transfer saturation imaging and 2-shell diffusion MR imaging. The myelin volume fraction, which reflects the amount of myelin sheath; the g-ratio, which represents the ratio of the inner (axon) to the outer (axon plus myelin) diameter of the fiber; and the axon volume fraction, which reflects axonal components, were calculated and compared between the patients and controls. In the patients with Moyamoya disease, the relationship between these parameters and cognitive task-measuring performance speed was also evaluated., Results: Compared with the healthy controls, the patients with Moyamoya disease showed a significant decrease in the myelin and axon volume fractions ( P < .05) in many WM regions, while the increases in the g-ratio values were not statistically significant. Correlations with cognitive performance were most frequently observed with the axon volume fraction ( r = 0.52-0.54; P < .03 in the right middle and posterior cerebral artery areas) and were the strongest with the g-ratio values in the right posterior cerebral artery region ( r = 0.64; P = .004)., Conclusions: Myelin-sensitive MR imaging and diffusion MR imaging revealed that myelin and axonal damage exist in patients with Moyamoya disease. The relationship with cognitive performance might be stronger with axonal damage than with myelin damage., (© 2020 by American Journal of Neuroradiology.)

Objective: Unilateral movement disorder associated with moyamoya disease is a rare finding and the mechanism remains to be fully elucidated. Theories postulated include contralateral cerebral ischemic or hemorrhagic lesions, and/or hypoperfusion. However, few studies have reported such patients without contralateral lesions nor hypoperfusion. This study aimed to explore the potential mechanism of those who had neither contralateral cerebral lesions nor hypoperfusion., Methods: Neuroradiological features of lenticulostriate arteries in three cases with unilateral movement disorder associated with moyamoya disease who had neither contralateral lesions nor hypoperfusion were mainly analyzed., Results: Angiography and 3 T black-blood T1-weighted intracranial vessel wall imaging both demonstrated a significant asymmetry between bilateral lenticulostriate arteries qualitatively and quantitatively on admission. After one-year follow-up, two patients' vessel wall imaging indicated that the asymmetry diminished, and the symptoms spontaneously resolved., Conclusion: This report demonstrated that patients with moyamoya disease with unilateral movement disorder who had neither contralateral lesions nor hypoperfusion may be related to the asymmetry between bilateral lenticulostriate arteries through basal ganglia.

Purpose/Aim: Acute movement disorder is an uncommon presenting symptom in patients with diabetes mellitus. We report a 20-year-old lady with poorly controlled type 1 diabetes, who presented with acute hemichorea and was found to have two rare diabetes-related central nervous complications of diabetic striatopathy and severe moyamoya disease (MMD). Materials and methods: She was treated with aggressive glycemic control; clonazepam and tetrabenazine as well as aspirin stroke prophylaxis for her MMD with resolution of her chorea 3 months later. She subsequently underwent cerebral revascularization surgery for her MMD. Results: This case highlights the possible differentials of acute chorea in diabetic patients and explores the pathophysiological mechanisms that may underlie both conditions in patients with type 1 diabetes. Conclusion: We recommend performing both magnetic resonance imaging (MRI) and magnetic resonance angiogram (MRA) brain for comprehensive evaluation of diabetic patients with new onset chorea. Prompt and accurate diagnosis is crucial as it guides prognostication and treatment strategies.

Background: Moyamoya disease often leads to ischemic strokes visible on diffusion-weighted imaging (DWI) and T2-weighted magnetic resonance imaging (MRI) with subsequent cognitive impairment. In adults with moyamoya, apparent diffusion coefficient (ADC) is correlated with regions of steal phenomenon and executive dysfunction prior to white matter changes., Objective: To investigate quantitative global diffusion changes in pediatric moyamoya patients prior to explicit structural ischemic damage., Methods: We retrospectively reviewed children (<20 yr old) with moyamoya disease and syndrome who underwent bypass surgery at our institution. We identified 29 children with normal structural preoperative MRI and without findings of cortical infarction or chronic white matter ischemic changes. DWI datasets were used to calculate ADC maps for each subject as well as for 60 age-matched healthy controls. Using an atlas-based approach, the cerebral white matter, cerebral cortex, thalamus, caudate, putamen, pallidum, hippocampus, amygdala, nucleus accumbens, and brainstem were segmented in each DWI dataset and used to calculate regional volumes and ADC values., Results: Multivariate analysis of covariance using the regional ADC and volume values as dependent variables and age and gender as covariates revealed a significant difference between the groups (P < .001). Post hoc analysis demonstrated significantly elevated ADC values for children with moyamoya in the cerebral cortex, white matter, caudate, putamen, and nucleus accumbens. No significant volume differences were found., Conclusion: Prior to having bypass surgery, and in the absence of imaging evidence of ischemic stroke, children with moyamoya exhibit cerebral diffusion changes. These findings could reflect microstructural changes stemming from exhaustion of cerebrovascular reserve., (Copyright © 2019 by the Congress of Neurological Surgeons.)

Background and Purpose- Predicting the risk of stroke and determining intervention indications are highly important for patients with Moyamoya disease (MMD). Here, we evaluated a novel MMD grading system based on collateral circulation and Suzuki stage to evaluate symptoms and predict prognosis. Methods- In total, 301 idiopathic MMD patients were retrospectively analyzed between 2014 and 2016. A collateral circulation grading system with scores ranging from 1 to 12 was established: the anatomic extent of pial collateral blood flow from posterior cerebral artery to middle cerebral artery and anterior cerebral artery was scored from 1 to 6; perforator collateral and internal cerebral artery flow were scored as 6 to 1, which corresponded to Suzuki stages 1 to 6. Dynamic susceptibility contrast-magnetic resonance imaging was used to evaluate hemodynamic status. We assessed the association between the grading system and clinical characteristics. Results- We analyzed 364 symptomatic hemispheres of 301 patients (146 males, 28±16 years). Ischemic patients who presented with infarction were more likely to score <8 points ( P <0.001), whereas those with ischemia symptoms (transient ischemic attack and headache) were more likely to score >8 points. Hemorrhagic patients who presented with intraparenchymal hemorrhage were more likely to score <8 points, whereas those who presented with intraventricular hemorrhage were more likely to score >8 points ( P <0.001). According to dynamic susceptibility contrast-magnetic resonance imaging, lower scores were correlated with more severe time to peak delay ( P <0.001) and worse relative cerebral blood volume ratio ( P =0.016) and cerebral flow ratio ( P =0.002). Encephaloduroarteriosynangiosis was performed in 348 symptomatic hemispheres. Patients who had collateral scores <4 points were more likely to have a postoperative stroke and a worse prognosis during the follow-up. Conclusions- This new MMD collateral grading system correlated well with clinical symptoms, hemodynamic status, and therapeutic prognosis and may facilitate risk stratification and prognosis predictions in patients with MMD.

Background: Arterial spin labeling (ASL) perfusion magnetic resonance imaging (MRI) may be used to determine brain regions at risk for ischemia in patients with moyamoya vasculopathy and to identify patients who may benefit from surgical revascularization. We aimed to investigate whether 1) the severity of moyamoya is related to the presence of leptomeningeal collaterals and cerebrovascular reactivity (CVR), 2) the presence of collaterals and ivy sign reflects disturbed CVR, and 3) arterial transit artefacts (ATAs) and ivy sign reflect the presence of collaterals., Methods: We determined severity of moyamoya on digital subtraction angiography (DSA) according to the modified Suzuki classification in 20 brain regions and scored regional tissue revascularization using a 4-point scale. Regional CVR and ATAs were assessed on ASL perfusion MRI, ivy sign on fluid attenuation inversion recovery MRI., Results: In 11 patients (median age 36 years; 91% female), we studied 203 regions. ATAs were associated with the presence of collaterals on DSA (P < 0.01). Of all regions with clearly visible collateral vessels on DSA, however, only 24% had ATAs. Ivy sign was not related to the presence or absence of collaterals nor to CVR. In 10% of regions with good vascularization on DSA, CVR was poor or showed steal., Conclusions: ATAs were associated with the presence of collaterals on DSA. Although DSA vascularization scores correlated with CVR, 10% of regions with good vascularization on DSA had absent CVR or steal on ASL-MRI. DSA and ivy sign did not provide adequate information on the hemodynamic status of brain tissue in patients with moyamoya vasculopathy., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background and Purpose: Chronic ischemia may induce brain microstructural damage and lead to neurocognitive dysfunction in patients with Moyamoya disease (MMD). We applied neurite orientation dispersion and density imaging (NODDI) and 15 O-gas positron emission tomography (PET) to elucidate the specific ischemic brain microstructural damage of MMD in the cortex and the white matter., Materials and Methods: Thirty-one patients (16-63years old, 9 males) and 20 age- and sex-matched normal controls were enrolled in this study. NODDI evaluates quantitative parameters reflecting neurite and axonal density, network complexity and the interstitial fluid in all participants. Of 31 patients, 12 newly diagnosed patients were evaluated with PET, also. We evaluated correlations between the microstructural parameters of NODDI and the hemodynamic and metabolic parameters of PET, the relationship between NODDI and clinical severity of each hemisphere (Normal, Asymtpomatic, Symptomatic, and Infarcted) as well as neurocognitive performance., Results: All NODDI parameters significantly correlated with PET parameters (absolute r = 0.46-0.83, P ≤ .048) and clinical severity (P < .001), suggesting that neurite and axonal density and network complexity decreased, and the interstitial fluid increased, as the ischemic burden became severe. NODDI parameters reflecting neurite and axonal density and network complexity significantly correlated with neurocognitive profiles (r = 0.36-0.64, P ≤ .048), but the interstitial fluid component did not., Conclusions: Chronic ischemia in patients with MMD may induce decreased neurite and axonal density, simplified network complexity, and may lead to neurocognitive dysfunction. The increased interstitial fluid accompanying hemodynamic impairment may not be identical to the decreased neurite density and might be driven by another mechanism., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background/aims: To enable the diagnosis of moyamoya disease (MMD), detection of distal internal carotid artery stenosis and hazy network of basal collaterals (BCs) are required. This study aimed at evaluating the factors that could determine the degree of BCs in patients with angiographically confirmed MMD., Methods: We analyzed 146 consecutive patients with MMD (age 26.2 ± 19.6, range 1-75). The degree of BCs (%) was measured based on conventional angiography. Factors associated with the degree of BCs, including clinico-radiological and genetic factors (p.Arg4810Lys variant), were analyzed., Results: The degree of BCs varied among MMD patients and significantly decreased with an increase in the age of diagnosis of MMD (coefficient -1.55; p < 0.001). Although the degree of BC development depends on the MMD stage (Suzuki stage), it is less prominent in adult-onset (>18 years) MMD compared to childhood MMD. The presence of p.Arg4810Lys variant, types of MMD (bilateral vs. unilateral) and stroke (ischemic, hemorrhagic, or asymptomatic), shrinkage (outer diameter) of intracranial vessels, external carotid collateral status, and cortical neovascularization were not associated with the degree of BCs., Conclusion: Although prominent BCs are required for diagnosis of MMD, BCs are decreased with aging, suggesting that angiogenic capacity is altered in adult onset MMD compared to childhood MMD., (© 2016 S. Karger AG, Basel.)

Moyamoya disease (MMD) is a chronic, occlusive cerebrovascular disease with an unknown etiology. Recent genome-wide and locus-specific association studies identified the RNF213 gene (RNF213) as an important susceptibility gene of MMD among East Asian populations; however, the mechanism by which an abnormality in RNF213 leads to MMD has not yet been elucidated. Therefore, we herein generated Rnf213-knock-in mice (RNF213-KI) expressing a missense mutation in mouse Rnf213, p. R4828K, on Exon 61, corresponding to human RNF213, p. R4859K, on Exon 60, in MMD patients, and investigated whether they developed MMD. We assessed the temporal profile of intracranial arteries by 9.4-T magnetic resonance angiography (MRA) continuously in the same mouse up to 64 weeks of age. The ratios of the outer diameter of the internal carotid artery (ICA)/basilar artery (BA) and middle cerebral artery (MCA)/BA were evaluated histopathologically. The common carotid arteries (CCA) were sectioned and arterial wall thickness/thinness was evaluated by Elastica-Masson staining before and after CCA ligation, which selectively induced vascular hyperplasia. The results obtained showed that RNF213-KI grew normally, with no significant difference being observed in MRA findings or the anatomy of the circle of Willis between homozygous RNF213-KI and wild-type (Wt) littermates. Furthermore, no significant difference was noted in the diameter of the intracranial vasculature (ICA/BA; p=0.82, MCA/BA; p=0.27) or in vascular remodeling after CCA ligation. Therefore, RNF213-KI did not spontaneously develop MMD. Multiple secondary insults such as environmental factors may contribute to the onset of MMD in addition to genetic factors., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Purpose: Leptomeningeal collateral, in moyamoya disease (MMD), appears as an ivy sign on fluid-attenuated inversion-recovery (FLAIR) images. There has been little investigation into the relationship between presentation of ivy signs and old brain lesions. We aimed to evaluate clinical significance of ivy signs and whether they correlate with old brain lesions and the severity of clinical symptoms in patients with MMD., Materials and Methods: FLAIR images of 83 patients were reviewed. Each cerebral hemisphere was divided into 4 regions and each region was scored based on the prominence of the ivy sign. Total ivy score (TIS) was defined as the sum of the scores from the eight regions and dominant hemispheric ivy sign (DHI) was determined by comparing the ivy scores from each hemisphere. According to the degree of ischemic symptoms, patients were classified into four subgroups: 1) nonspecific symptoms without motor weakness, 2) single transient ischemic attack (TIA), 3) recurrent TIA, or 4) complete stroke., Results: TIS was significantly different as follows: 4.86±2.55 in patients with nonspecific symptoms, 5.89±3.10 in patients with single TIA, 9.60±3.98 in patients with recurrent TIA and 8.37±3.39 in patients with complete stroke (p=0.003). TIS associated with old lesions was significantly higher than those not associated with old lesions (9.35±4.22 vs. 7.49±3.37, p=0.032). We found a significant correlation between DHI and motor symptoms (p=0.001)., Conclusion: Because TIS has a strong tendency with severity of ischemic motor symptom and the presence of old lesions, the ivy sign may be useful in predicting severity of disease progression.

Purpose: The purpose of this study was to compare clinical outcomes and surgical results after encephaloduroarteriosynangiosis (EDAS) in pediatric patients with Moyamoya disease that manifested as either ischemia or epileptic seizures., Methods: We treated 23 children who underwent EDAS; we divided the patients into either ischemic or epileptic groups according to the individuals' clinical presentation. Group Ia included those who mainly presented with cerebral ischemia in the form of preoperative transient ischemic attacks (TIA), while Group Ib presented with ischemia in the form of irreversible neurologic deficits or proven cerebral infarcts. Group II included those who presented with epileptic seizures rather than cerebral ischemia. We compared the clinical outcomes and surgical results following EDAS in the three groups., Results: We grouped the patients into three groups according to their main preoperative clinical symptoms (Group Ia n = 10, Group Ib n = 6, and Group II n = 7). Group II, the epileptic manifestation group, tended to show more favorable clinical outcomes compared to the ischemic manifestation group, especially the severe ischemic group. However, there were no significant differences in postoperative neuroimaging and hemodynamic assessments between the groups., Conclusions: EDAS is a safe and effective surgical technique that prevents epileptic seizures and shows more favorable clinical outcomes when used in patients with Moyamoya disease presenting with epileptic seizures compared to cerebral ischemia.

Background: Moyamoya disease is characterized by progressive cerebrovascular stenosis with recurrent cerebral ischemic events. Transient ischemic attacks are often associated with hyperventilation in children with moyamoya, suggesting hypoperfusion rather than thrombotic vaso-occlusion as a prominent mechanism. The patterns of ischemia and severity of steno-occlusive disease in such children may elucidate these mechanisms., Methods: Children, 1 month to 18 years, with moyamoya, observed over 11 years were analyzed. A study neuroradiologist reviewed all presurgical neuroimaging. Ischemic injury was categorized into cortical, subcortical, and watershed infarction. Angiographic findings were staged using a standardized method., Results: Twenty children, 15 girls, median age 6.4 years, were included. All children had magnetic resonance imaging and angiography, and in 16, conventional angiography was available. All 40 hemispheres, in 20 children, were evaluated. The initial clinical presentation included neurological deficits in 17, recurrent transient ischemic attacks in 7, headache in 8, seizures in 8, and alteration in consciousness in 4 children. Infarcts were bilateral in 13 (65%) children (ischemia alone in 14, ischemic stroke with hemorrhagic transformation in two, and primary hemorrhage in two). Infarcts were cortical and/or subcortical in 13 (65%), both deep and cortical watershed in 11 (55%), and cortical watershed alone in 5 (25%) children. The predominant vascular territory involved was the middle cerebral artery. The internal carotid arterial system was involved in all, with stage IV being the most frequent angiographic stage., Conclusions: Ischemic injury in deep watershed zones is common in childhood moyamoya and may reflect non-vaso-occlusive ischemic mechanisms. Location and severity of vascular involvement may correlate with various patterns of ischemic infarction in moyamoya disease and requires further study., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Epilepsy cannot always be recognized in patients with moyamoya disease. In this report, the clinical features of patients with epilepsy were evaluated for assessing the predictive factors of epilepsy in moyamoya disease., Methods: A total of 64 consecutive patients with moyamoya disease were included in this study. During their follow-up periods, 7 patients were diagnosed with epilepsy. Then, the patients with epilepsy were compared with the patients without epilepsy regarding their clinical features., Results: Analysis of patient background characteristics revealed a significantly higher incidence of epilepsy in patients with high modified Rankin Scale (mRS) scores, high cerebrovascular attack scores, onset age of 3 years or less, early seizures, cortical involvement, stroke subtype, and diffuse brain atrophy. A logistic analysis of epilepsy data revealed significant differences between the 2 groups in mRS score, cerebrovascular attack score, onset age 3 years or less, early seizure, cortical involvement, stroke subtype, and diffuse brain atrophy. Of these, significant differences were noted in 3 items (mRS score, early seizure, and diffuse brain atrophy) on multivariate analysis. These 3 items were selected as the basis of our new moyamoya disease epilepsy risk scale (MDERS), which we then evaluated. The cutoff value estimated by the receiver operating characteristic curve was set at 1 (sensitivity, .857; specificity, .825) or 2 (sensitivity, .571; specificity, 1.000)., Conclusions: Epilepsy in moyamoya disease is associated with clinical factors and is not an independent category. For prediction of epilepsy in moyamoya disease, MDERS is a simple and convenient assessment scale., (Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Background and Purpose: A promising method for identifying hemodynamic impairment that may serve as a biomarker for stroke risk in patients with intracranial stenosis is cerebrovascular reactivity (CVR) mapping using noninvasive MRI. Here, abilities to measure CVR safely in the clinic using hypercarbic hyperoxic (carbogen) gas challenges, which increase oxygen delivery to tissue, are investigated., Methods: In sequence with structural and angiographic imaging, blood oxygenation level-dependent carbogen-induced CVR scans were performed in patients with symptomatic intracranial stenosis (n=92) and control (n=10) volunteers, with a subgroup of patients (n=57) undergoing cerebral blood flow-weighted pseudocontinuous arterial spin labeling CVR. Subjects were stratified for 4 substudies to evaluate relationships between (1) carbogen and hypercarbic normoxic CVR in healthy tissue (n=10), (2) carbogen cerebral blood flow CVR and blood oxygenation level-dependent CVR in intracranial stenosis patients (n=57), (3) carbogen CVR and clinical measures of disease in patients with asymmetrical intracranial atherosclerotic (n=31) and moyamoya (n=29) disease, and (4) the CVR scan and immediate and longer-term complications (n=92)., Results: Noninvasive blood oxygenation level-dependent carbogen-induced CVR values correlate with (1) lobar hypercarbic normoxic gas stimuli in healthy tissue (R=0.92; P<0.001), (2) carbogen-induced cerebral blood flow CVR in patients with intracranial stenosis (R=0.30-0.33; P<0.012), and (3) angiographic measures of disease severity both in atherosclerotic and moyamoya patients after appropriate processing. No immediate stroke-related complications were reported in response to carbogen administration; longer-term neurological events fell within the range for expected events in this patient population., Conclusions: Carbogen-induced CVR elicited no added adverse events and provided a surrogate marker of cerebrovascular reserve consistent with intracranial vasculopathy., (© 2014 American Heart Association, Inc.)

Background and Purpose: Diagnosis of Moyamoya disease (MMD) is based on the characteristic angiographic findings. However, differentiating MMD from intracranial atherosclerotic disease (ICAD) is difficult. We compared vessel wall imaging findings on high-resolution magnetic resonance imaging between MMD and ICAD., Methods: High-resolution magnetic resonance imaging was performed on 32 patients with angiographically proven MMD and 16 patients with acute infarcts because of ICAD. Bilateral internal carotid arteries and steno-occlusive middle cerebral artery were analyzed for wall enhancement and remodeling., Results: Enhancement patterns and distribution were different. Most patients with MMD (90.6%) showed concentric enhancement on distal internal carotid arteries and middle cerebral arteries, whereas focal eccentric enhancement was observed on the symptomatic segment in ICAD. MMD was characterized by middle cerebral artery shrinkage; the remodeling index and wall area were lower in MMD than in ICAD (remodeling index, 0.19±0.11 versus 1.00±0.43; wall area, 0.32±0.22 versus 6.00±2.72; P<0.001)., Conclusions: MMD was characterized by concentric enhancement on bilateral distal internal carotid arteries and shrinkage of middle cerebral artery, regardless of symptoms., (© 2014 American Heart Association, Inc.)

Purpose: To develop a multivariate machine learning classification-based cerebral blood flow (CBF) quantification method for arterial spin labeling (ASL) perfusion MRI., Methods: The label and control images of ASL MRI were separated using a machine-learning algorithm, the support vector machine (SVM). The perfusion-weighted image was subsequently extracted from the multivariate (all voxels) SVM classifier. Using the same pre-processing steps, the proposed method was compared with standard ASL CBF quantification method using synthetic data and in-vivo ASL images., Results: As compared with the conventional univariate approach, the proposed ASL CBF quantification method significantly improved spatial signal-to-noise-ratio (SNR) and image appearance of ASL CBF images., Conclusion: the multivariate machine learning-based classification is useful for ASL CBF quantification., (Copyright © 2014 Wiley Periodicals, Inc.)

Background: Adult moyamoya disease (MMD) is known to have high incidence of cerebral microbleeds (cMBs); however, the clinical significance still remains unclear. We investigated the frequency of cMBs in a large number of patients and analyzed the patterns of MB distribution in association with the location of the hematoma and moyamoya vessels., Methods: We studied 259 consecutive patients with MMD using prospectively collected database. One hundred ninety-one patients were eligible for the present study, and image analysis was performed retrospectively. The presence of cMBs and remains of hemorrhage were determined using gradient-echo T2*-weighted sequence (1.5 T). The development of moyamoya vessels was assessed on source images of time-of-flight magnetic resonance angiography. The analysis consists of descriptive assessment of the spatial relationship between cMB, remains of hemorrhage, and moyamoya vessels. Statistical analysis was performed to calculate relative risk ratio in the presence of cMBs in relation to the remains of hemorrhage (macrohematoma), age of onset, and the presence of concomitant moyamoya vessels., Results: Thirty MBs were observed in 20 adult MMD patients (16.9%). MBs were located predominantly in the periventricular white matter (63.3%) followed by the basal ganglia/thalami (20%). Comparing the patients with cMBs from those without, hematoma was more frequently observed in patients with cMBs (odds ratio [OR] 4.29; 95% confidence interval [CI] 1.58-11.62; P=.0062). Patients with adult onset was more likely to demonstrate cMBs (14.4%) compared with the patients with pediatric onset (4.1%) (OR 3.93; 95% CI 1.11-13.91). Moyamoya vessels appeared in the lateral part of the trigon, and the periventricular white matter was significantly associated with the presence of cMBs (lateral part of the trigon; OR 3.29 [1.59-6.82], P=.0019, periventricle of the body of lateral ventricle; OR 2.40 [1.20-4.79], P=.0214, respectively). cMBs accompanied concomitant arteries in 23 (76.7%) lesions. The subependymal-leptomeningeal artery anastomosis was the most common pattern (n=20, 66.7%)., Conclusions: Spatial relationship was demonstrated between the moyamoya vessels and perivascular hemosiderin deposition particularly around the subependymal-leptomeningeal anastomosis, suggesting the mechanism for the development of cMBs in MMD. Present study further supports previous findings that cMBs potentially serve as a marker for the bleeding-prone microangiopathy in MMD. The significance of the present study lies in selecting optimal surgical candidate for preventing future hemorrhage by the presence of the cMBs, whereas current surgical indication relying on the degree of ischemia frequently fails to detect patients with future hemorrhage., (Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Background: Both basal collaterals (BC) and cortical microvascularization (CM) on angiography have been suggested as moyamoya disease (MMD)-specific findings; however, it is unknown whether the vascular network represents compensatory mechanisms for vascular occlusion or aberrant active neovascularization., Methods: We investigated the grade of antegrade MCA flow, the degree of BC, and the presence of CM on conventional angiography in relation to disease severity in pediatric MMD. CM was defined as enlarged and winding distal cortical arteries and categorized into anterior or posterior CM depending on their sources. Findings from basal and acetazolamide stress brain perfusion SPECT studies were also evaluated., Results: A total of 172 pediatric patients with MMD were enrolled in this study. As the severity of MMD increased, the grade of antegrade MCA flow gradually diminished. While the degree of BC peaked at Suzuki stage 3-4, CM was frequently observed at early MMD stages. About two-thirds of hemispheres with normal antegrade MCA flow on angiography and normal perfusion status on SPECT had anterior and/or posterior CM. Both anterior and posterior CM gradually decreased with the advancement of MMD., Conclusion: Our findings from a large cohort of angiographically confirmed pediatric MMD patients indicate that neovascularization may occur before significant hemodynamic impairment in MMD., (© 2014 S. Karger AG, Basel.)

Moyamoya disease is an idiopathic progressive steno-occlusive disorder of the intracranial arteries located at the base of the brain. It is associated with the development of compensatory extensive network of fine collaterals. Moyamoya disease is considered syndromic when certain genetic or acquired disorders such as polycystic kidney disease, neurofibromatosis, or meningitis are also present. Although the genetic contribution in moyamoya is indisputable, its cause and pathogenesis remain under discussion. Herein, we report a rare occurrence of moyamoya syndrome in two European Caucasian siblings in association with unusual multisystemic malformations (polycystic kidney disease in one, and intestinal duplication cyst in the other). The karyotype was normal. No mutation in the RFN213 gene was found, and none of the HLA types linked to moyamoya disease or described in similar familial cases were identified. By describing these multisystemic associations, polycystic kidney disease for the second time, and intestinal malformation for the first time in the literature, our report expands the phenotypic variability of moyamoya syndrome. The coexistence of disparate malformations among close relatives suggests an underlying common genetic background predisposing to structural or physiological abnormalities in different tissues and organs., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: Moyamoya disease (MM) is a rare disorder of the cerebral arterial circulation, whereas multiple sclerosis (MS) is a relatively common immune-mediated attack on central myelin. Despite the differences in pathogenesis, the 2 disorders share some clinical features which can lead to diagnostic confusion: both can affect young adults, cause intermittent neurological symptoms, and show multifocal abnormalities on brain imaging., Objective: To emphasize the need for early consideration of MM in the differential diagnosis of MS-spectrum disorders., Methods: Chart reviews and individual case analyses., Results: We present detailed descriptions of 3 patients with MM, and summary data on 8 additional cases, in which there was diagnostic confusion with MS, with delays in treatment ranging from 2 months to 19 years (median=4 y)., Conclusions: MM can be misdiagnosed as MS, leading to delay in correct treatment. We highlight the clinical and radiologic features which allow differentiation of these conditions early in the course, when treatment can have maximum benefit.

Background: Moyamoya disease (MMD) is a chronic occlusive cerebrovascular disorder. Patients diagnosed asymptomatic MMD should have no prior ischemic or hemorrhagic episode and no history of neurologic diseases. The incidence of asymptomatic MMD has turned out to be higher than previously thought due to better diagnosis with the increasing availability of magnetic resonance imaging or magnetic resonance angiography technology. However, the clinical symptoms of asymptomatic MMDs are still obscure., Clinical Case: This report presents an asymptomatic MMD patient, who was a previously healthy 42-year-old-woman. The patient suffered from burst coma and started vomiting 3 hours before hospitalization. The patient died of the rupture of hemorrhage located on the right temporal lobe near the cortex. Autopsy revealed that the vascular networks were increased at the right postcentral gyrus and on the surface of the occipital lobe., Conclusions: As a small number of asymptomatic MMD patients have clinical symptoms, we must be aware of the possibility of MMD. The clinical symptoms of transient ischemic attack, ischemic stroke, or/and intracranial bleeding maybe the manifestation of this disease. Early recognition, accurate diagnosis and prompt treatment are vital to the survival of the patients with asymptomatic MMD.

Background and Purpose: An ivy sign is considered to represent diffuse leptomeningeal collaterals found on fluid-attenuated inversion recovery (FLAIR) images of patients with Moyamoya disease. We evaluated the correlation between unilateral ivy proliferation in a hemisphere and cerebrovascular hemodynamic status to learn the clinical significance of the ivy sign., Materials and Methods: A total of 35 patients with Moyamoya disease were included. Correlation between ivy dominance on FLAIR images and hemodynamic status with use of iodine 123 N-isopropyl-p-iodoamphetamine ((123)I-IMP) single-photon emission CT (SPECT) was evaluated., Results: Distributional differences of ivy signs between both hemispheres were observed in 22 (64.7%) of 34 patients with a positive ivy sign, all of whom showed decreased vascular reserve/reactivity in the ivy-dominant hemisphere (IDH). The proportion of the stage II (misery perfusion) area to IDH was higher than that in the ivy less-dominant hemisphere (ILDH) in the quantitative analysis. The mean vascular reserve was lower in IDH than ILDH. There were 15 of 22 patients who had bypass surgery on IDH because of transient ischemic attack from ischemia of IDH. Patients with symmetric ivy distributions showed a variety of hemodynamic status. MR angiography (MRA) stage of IDH (2.95 +/- 0.39) was higher compared with ILDH (2.60 +/- 0.50; P < .05). Regional arteriocapillary circulation time ratio in IDH was longer compared with ILDH (P < .05). Ivy proliferation decreased in 10 (55.6%) of 18 patients who underwent bypass surgery during the follow-up period., Conclusions: Unilateral hemispheric ivy proliferation correlated highly with the existence of an ipsilateral decreased vascular reserve associated with the development of leptomeningeal collaterals in patients with Moyamoya disease.

Moyamoya phenomenon occurs in response to an occlusive vasculopathy affecting the distal internal carotid artery and its proximal branches. The nature of the occlusive vasculopathy is unknown in most patients. We present a patient in whom 3T magnetic resonance imaging was used to examine the arterial wall at the site of occlusion in a patient with unilateral moyamoya phenomenon. Signal characteristics were consistent with atherosclerotic disease. 3T magnetic resonance imaging may be useful for distinguishing the underlying etiology of moyamoya phenomenon in some patients.

Moyamoya disease (MMD) is a progressive, occlusive disease of the distal internal carotid arteries associated with secondary stenosis of the circle of Willis. Symptoms include ischemic infarcts in children and hemorrhages in adults. Bypass of the stenotic vessel(s) is the primary surgical treatment modality for MMD. Superficial temporal artery-to-middle cerebral artery bypass is the most common direct bypass method. Indirect techniques rely on the approximation of vascularized tissue to the cerebral cortex to promote neoangiogenesis. This tissue may be in the form of muscle, pericranium, dura, or even omentum. This review highlights the surgical options available for the treatment of MMD.

Background: Several authors have reported temporary neurologic deterioration after revascularization surgery in some patients with moyamoya disease. The present study examined the incidence and mechanisms of PONDs in adult patients with moyamoya disease., Methods: Postoperative neurological deficits were retrospectively evaluated 1 month or less postoperatively on 32 hemispheric sides of 17 symptomatic adult patients with moyamoya disease treated surgically with direct and/or indirect revascularization., Results: Various PONDs were observed in 9 sides (28%) from 7 patients 1 month or less after surgery. Symptoms were recognized in 7 (39%) of 18 sides with ischemic onset, and 2 (14%) of 14 sides with hemorrhagic onset. Postoperative neurological deficits were usually observed 1 week or less after surgery, and resolved within 2 weeks. Postoperative neurological deficits were divided into 3 groups based on duration of symptoms: single transient neurologic deficits in 3 sides; repeated transient neurologic deficits in 3 sides; and continuous neurologic deficits in 3 sides. Radiologic examinations demonstrated no ischemic changes in any patients, and subsequent focal hyperemia after surgery on 3 sides. Postoperative neurological deficits occurred more frequently in younger patients or those with poor vascular response before surgery., Conclusions: Postoperative neurological deficits frequently occur in patients with moyamoya disease, but are temporary. These deficits appear to result from focal hyperperfusion after surgery, rather than from ischemic changes.

In the normal adult brain, blood vessel formation is tightly down-regulated. However, pathologic processes such as brain tumors can increase the proportion of endothelial cells involved in angiogenesis. When this process is initiated, a complex series of timed events result in new vessel formation. In this review, we will describe the process of angiogenesis in the central nervous system. We will discuss the roles of Vascular Endothelial Growth Factor (VEGF), Fibroblast Growth Factor (FGF), Angiopoietins, Platelet Derived Growth Factor (PDGF), and integrins in angiogenesis. We will also look into their significance in disease processes such as neoplasms, arteriovenous malformations (AVM), and Moyamoya disease.

Background: Cerebrovascular reconstruction procedures run the risk of changing the balance between oxygen supply and consumption during surgery. We assessed the value of visual light spectroscopy for detecting changes in cerebral blood oxygenation (CBO) during superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis., Methods: We developed a VLS monitoring system which permits continuous monitoring of CBO changes during surgery. Using the VLS, we evaluated the CBO changes in the MCA territory on the lesion side in 18 patients who underwent STA-MCA anastomosis., Results: Temporary occlusion of the MCA (M4 portion) did not change the CBO in 17 patients. However, in the patient with dissecting aneurysm, it caused decreases of oxyhemoglobin and cortical oxygen saturation (CoSo(2)) associated with an increase of deoxyhemoglobin, although these CBO changes were normalized by STA blood flow. In 5 patients, STA blood flow increased the oxyhemoglobin and CoSo(2) and decreased the deoxyhemoglobin, indicating that cortical blood flow (CoBF) was increased. The CoSo(2) before anastomosis was significantly low in the patients who showed an increase of CoSo(2) by STA blood flow (63.0% +/- 2.5%) as compared with those who did not (72.0 +/- 6.1%, P = .024)., Conclusion: Temporary occlusion of a cortical artery during bypass surgery did not affect the CBO in patients who had chronic cerebral ischemia, but caused acute ischemia in the patient who did not. STA blood flow increased the CoBF during surgery more frequently in patients who showed a low perfusion pressure. The VLS monitoring system is considered useful for evaluating bypass function and facilitates safe and accurate bypass surgery.

Case Report: We describe a 15-year-old girl with moyamoya disease whose initial manifestation was chorea-like involuntary movements. T2-weighted magnetic resonance imaging showed high signal intensity lesions in the left frontal lobe, right parieto-occipital lobes, and frontal subcortical white matter. Single-photon emission computed tomography (SPECT) showed diffuse hypoperfusion of the whole brain. Bilateral direct and indirect cerebrovascular bypass surgeries were performed. Chorea disappeared 2 days after the surgery. Follow-up SPECT demonstrated increased cerebral perfusion in the bilateral frontal, temporal, and parietal regions., Conclusions: Chorea accompanied with moyamoya disease can be properly managed by revascularization surgery. Moyamoya disease should be remembered as being one of the differential diagnoses of chorea, which is treatable by surgery.

Background and Purpose: We evaluated whether basal/acetazolamide stress brain perfusion SPECT performed after revascularization surgery can predict the further clinical outcome of patients with pediatric moyamoya disease., Methods: A total of 77 (31 males, 46 females, age 6.6+/-3.2 years) patients with postoperative pediatric moyamoya disease who underwent basal/acetazolamide stress brain perfusion SPECT 6 to 12 months after revascularization surgery and who were followed-up >12 months after SPECT were included. Mean follow-up period after SPECT was 36+/-19 months. Sixty-two patients underwent bilateral ribbon encephaloduroarteriosynangiosis (EDAS), 14 bilateral EDAS, and 1 unilateral EDAS. Ordinal logistic regression analysis using 5 independent variables (infarction on preoperative MRI, age at the first operation, highest Suzuki stage on cerebral angiography, and regional cerebrovascular reserve on postoperative SPECT) against postoperative clinical outcomes was performed., Results: Fifty-one patients had preserved reserve on postoperative SPECT and their clinical outcomes were excellent (30), good (15), fair (4), and poor (2); 26 patients had decreased reserve (excellent, 1; good, 7; fair, 14; poor, 4). On ordinal logistic regression analysis, age at the first operation (P=0.033) and reserve on postoperative SPECT (P<0.001) were statistically significant., Conclusions: Basal/acetazolamide stress brain perfusion SPECT performed at 6 to 12 months after the indirect bypass operation could predict the further clinical outcome of pediatric patients with moyamoya disease. Patients with decreased cerebrovascular reserve will have remaining neurological deficit and ischemic attacks on follow-up.

Background: The optimum management of patients with moyamoya disease remains controversial., Objectives: To examine retrospectively the correlation between the degree of haemodynamic stress and the clinical presentation by measuring cerebral haemodynamics and metabolism using positron emission tomography (PET)., Methods: 57 patients with moyamoya disease (mean age 32 years, range 12 to 64), classified into five groups according to clinical manifestations, underwent PET measurement of cerebral blood flow (CBF), cerebral blood volume (CBV), cerebral metabolic rate for oxygen (CMR(O2)), and oxygen extraction fraction (OEF) using (15)O labelled gases. The regional values in patient groups were compared with a normal group., Results: CBF in non-symptomatic patients, patients presenting with transient ischaemic attacks (TIA), and patients with haemorrhagic onset (H) was not significantly lower than in normal controls in any region. CBV in the TIA group and in patients with infarction associated with TIA (I/TIA) was significantly higher than in the controls in most regions. OEF in the frontal, parietal, and temporal cortex was significantly higher in the I/TIA group than in the controls. Patients in the H group and those with a permanent deficit with infarction (PD group) had decreased metabolism with normal OEF. Multivariate analysis to test the distribution of the three dimensional vector (CBF, CBV, OEF) showed significant differences between every possible pair among the six groups except NS v H and H v PD in the frontal cortex., Conclusions: The haemodynamic status of moyamoya disease is not uniform, and severe haemodynamic stress occurs in selected subgroups of patients.

A previously healthy 24-day-old boy presented with a 2-day history of fever and had a convulsion on the day of admission. MRI showed abnormal signal in the thalami, caudate nuclei and central white matter. Acute necrotising encephalopathy was diagnosed, other causes having been excluded after biochemical and haematological analysis of blood, urine and CSF. He recovered, but with spastic quadriparesis. At the age of 28 months, he suffered sudden deterioration of consciousness and motor weakness of his right limbs. MRI was consistent with an acute cerebrovascular accident. Angiography showed bilateral middle cerebral artery stenosis or frank occlusion with numerous lenticulostriate collateral vessels consistent with moyamoya disease.

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., (Copyright RSNA, 2002)

A 3-year-old male patient with hereditary spherocytosis who developed moyamoya syndrome, presenting hemiplegia, and slurred speech is reported. Transient ischemic attacks occurred repeatedly with hemolytic crises. Magnetic resonance imaging and angiography revealed bilateral occlusion of the internal carotid and middle cerebral arteries with the formation of moyamoya vessels and multiple infarctions in the basal ganglia. Although splenectomy can increase the risk of stroke, no stroke occurred after splenectomy. On aspirin and dipyridamole therapy the patient has been free of neurologic deficits and progression of the vasculopathy for 5 years. This rare observation suggests that anemic hypoxia more greatly contributes to the progression of moyamoya syndrome than postsplenectomy thrombocytosis or reduced deformability of spherocytes.

Early diagnosis and treatment of moyamoya disease in children is essential to minimize residual mental and physiologic deficits. Current treatment of childhood moyamoya disease in Japan, preoperative evaluation of perfusion reserve as a surgical indication, and the role of noninvasive follow-up by magnetic resonance angiography are reported. Approximately 20% of children with definite moyamoya disease were observed or treated medically. Among surgical procedures, single indirect bypass surgery was used in approximately 30% of all patients; combinations of direct and indirect bypass surgery, 20%; and multiple-indirect bypass surgery, 18%. Both adequate understanding of the primary condition and determination of optimal treatment, including specific operative procedures, required evaluation of cerebral circulation and metabolism. Surgical indications included reduced perfusion reserve in affected brain by positron emission tomography or single photon emission tomography with administration of acetazolamide or a CO2 load. Postoperative improvements of cerebral perfusion reserve show better correlation with disappearance of ischemic attacks than does angiographically demonstrated collateral formation. Follow-up evaluation with magnetic resonance angiography has advantages over conventional angiography because it is noninvasive and avoids general anesthesia.

A diagnosis of moyamoya disease was made in three children aged five, eight and 13 years (including two Turkish sisters). Clinical presentation was recurrent episodes of cerebral ischemia and stroke. CT scans and MRI showed infarcts in various distributions. Angiography revealed anterior bilateral stenosis of the circle of Willis and development of Moyamoya collateral pathways. In one case there was coagulopathy with protein C deficiency. To increase transdural collateral flow, revascularisation with encephalo-duro-arterio-synangiosis was attempted in all three children. Outcome was clinically and angiographically satisfactory and none of the children developed further neurological complications. The current state of study on Moyamoya disease is also presented.

Background: Central benzodiazepine (BZD) receptor imaging is effective to evaluate neuron density in the pathological brain cortex. This study used BZD receptor imaging to evaluate neuronal damage in adult ischemic moyamoya disease., Methods: Single photon emission computed tomography and a novel tracer, 123I-iomazenil, were used to measure BZD receptor density in the brain. Evaluation of early and late images was performed in three asymptomatic, unoperated patients, and six mildly symptomatic, operated patients., Results: Uptakes in the frontal, parietal, and occipital lobes of symptomatic patients were significantly lower (p<0.05) than those of asymptomatic patients. The late image/ early image count ratios (L/E ratios) of asymptomatic patients were relatively constant (mean, 0.571; range, 0.550-0.581) in all regions of interest. In contrast, the L/E ratios of symptomatic patients were not uniform., Conclusions: The neuron density was preserved in adult asymptomatic patients despite harboring moyamoya disease. In contrast, the neuronal density was decreased in symptomatic patients even though their symptoms were mild and they had undergone revascularization.

We describe the findings in a six-year-old female with typical clinical symptoms of Moyamoya phenomena, but with an unusual angiographic appearance. The vertebral artery showed segmented occlusion in the upper cervical region, with reconstitution via collateral circulation through muscular branches. The carotid circulation showed involvement of the external carotid artery (ECA) branches and marked narrowing of the internal carotid arteries (ICA) bilaterally, suggesting that this disease is systemic in nature.

We report a case of moyamoya disease associated with Down syndrome and congenital heart malformations. Findings of cranial MR imaging indicated cortical laminar necrosis along with cerebral infarction. To explain the development of these findings, we hypothesized that hypoxic brain damage manifesting cortical laminar necrosis was caused by hypoperfusion of the brain due to occlusive changes to the cerebral vessels in moyamoya disease, in addition to a state of general hypoxemia secondary to congenital heart malformations.

We evaluated the cerebral hemodynamics and metabolism in Moyamoya patients who did not demonstrate either cerebral infarct or hemorrhage on MRI. The subjects consisted of 5 patients with Moyamoya disease (4 females and one male, aged from 15 to 40 years). The CBF, OEF and CMRO2 of the Moyamoya patients did not differ from those of the normal control subjects. The CBV did increase significantly in the cerebral cortices and striatum, but not in the cerebellum. The TT was also significantly prolonged in the frontal and parietal regions. The cerebrovascular CO2 response was markedly impaired in the frontal, temporal and parietal cortices. However, it was relatively preserved in the occipital cortex, thalamus and cerebellum. Thus, the cerebral hemodynamic reserve capacity decreased even in the Moyamoya patients not demonstrating either cerebral infarct or hemorrhage on MRI, and it should be considered in the management of these patients.

The incidence, clinical manifestations, diagnosis, and management of cerebral hemorrhage from amyloid angiopathy and moyamoya disease are reviewed. Particular attention is given to pathophysiologic mechanisms producing cerebral hemorrhage in these conditions, the diagnosis based on characteristic CT and angiographic appearances, and the role of surgery in comprehensive management.

An autopsy case of severely progressed "Moya Moya" disease was presented. A 38-year-old male was admitted because of unconsciousness. On examination, he showed spider-like extremities, suggesting Marfan's syndrome. In the past history, he experienced acute rt. hemiparesis at 6 years old and generalized convulsion, lt. hemiparesis and aphasia at 7 years old. After these episodes, he spent an uneventful life until 38 years old, when he was found unconscious in his room by the family. Lt. CAG showed severe stenosis at the siphon of lt. ICA and fine vascular networks in the basal ganglia and many transdural collateral arteries. Three days later, he died and an autopsy was performed. On histological examination, proliferation of the intima, elongated elastica interna and lost of the media were identified in the stenotic arteries. In the vessels of other organs, especially of the heart, proliferated intima and lost of the media were also noticed. From these findings, "Moya Moya" disease was thought to be one of the manifestations of the systemic vascular diseases. The autopsy cases of "Moya Moya" disease in Japan were reviewed. According to the review, most of these autopsy cases died from intracerebral bleeding attack. Recently, EC-IC bypass operations have been performed in order to improve ischemic condition of "Moya Moya" disease. According to the finding of the review, however, the financial efficiency of such by-pass operations for "Moya Moya" disease must be elucidated after long-term follow-up study.