Is medical management useful in Moyamoya disease?

Moyamoya disease(MMD),characterized by progressive internal carotid artery stenosis and collateral vessel formation,prompts cerebral perfusion complications and is stratified into idiopathic and Moyamoya syndrome subtypes.A multifa-ceted approach toward MMD management addresses cerebral infarctions through revascularization surgery and adjunctive medical therapy,while also navigating risks such as intracranial hemorrhage and cerebral infarction resulting from arte-rial stenosis and fragile collateral vessels.Addressing antithrombotic management reveals a potential role for treatments like antiplatelet agents and anticoagulants,despite the ambiguous contribution of thrombosis to MMD-related infarctions and the critical balance between preventing ischemic events and averting hemo-rrhagic complications.Transcranial doppler has proven useful in thromboembolic detection,despite persisting challenges concerning the efficacy and safety of an-tithrombotic treatments.Furthermore,antihypertensive interventions aim to ma-nage blood pressure meticulously,especially during intracerebral hemorrhage,with recommendations and protocols varying based on the patient’s hypertension status.Additionally,lipid-lowering therapeutic strategies,particularly employing statins,are appraised for their possible beneficial role in MMD management,even as comprehensive data from disease-specific clinical trials remains elusive.Com-prehensive guidelines and protocols to navigate the multifaceted therapeutic ave-nues for MMD,while maintaining a delicate balance between efficacy and safety,warrant further meticulous research and development.This protocol manuscript seeks to elucidate the various aspects and challenges imbued in managing and navigating through the complex landscape of MMD treatment.

Recent Advances for Global Perspectives on Etiology, Pathophysiology, Clinical Presentations, and Management of Moyamoya Disease

Moyamoya disease (MMD) is a condition characterized by the gradual narrowing and blockage of blood vessels in the brain, specifically those in the circle of Willis and the arteries that supply it. This results in reduced blood flow and oxygen to the brain, leading to progressive symptoms and potential complications. The underlying pathophysiological mechanism remains elucidated. However, recent studies have highlighted numerous etiologic factors: abnormal immune complex responses, susceptibility genes, branched-chain amino acids, antibodies, heritable diseases, and acquired diseases, which may be the great potential triggers for the development of moyamoya disease. Its clinical presentation has varying degrees from transient asymptomatic events to significant neurological deficits. Moyamoya disease (MMD) shows different patterns in children and adults. Children with MMD are more susceptible to ischemic events due to decreased blood flow to the brain. Conversely, adults with MMD are more prone to hemorrhagic events involving brain bleeding. Children with MMD may experience a range of symptoms including motor impairments, sensory issues, seizures, headaches, dizziness, cognitive delays, or ongoing neurological problems. Although adults may present with similar clinical symptoms as children, they are more prone to experiencing sudden onset intraventricular, subarachnoid, or intracerebral hemorrhages. One of the challenges in moyamoya disease is the potential for misdiagnosis or delayed diagnosis, particularly when physicians fail to consider MMD as a possible cause in stroke patients. This review aims to provide a comprehensive overview of recent global studies on the pathophysiology of MMD, along with advancements in its management. Additionally, the review will delve into various surgical treatment options for MMD, as well as its rare occurrence alongside atrioventricular malformations. Exciting prospects include the use of autologous bone marrow transplant and the potential role of Connexin 43 protein treatment in the development of moyamoya disease.

Analysis of the Effect of the Comprehensive Nursing Model on Patients with Moyamoya Disease Undergoing Intracranial and Extracranial Revascularization Surgery

Objective:To explore the effect of a comprehensive nursing model on patients with Moyamoya disease who underwent intracranial and extracranial revascularization surgery.Methods:110 cases were divided into control and observation groups with 55 cases each.The control group received routine perioperative care,and the observation group received perioperative care along with comprehensive nursing care.The two groups’disease cognition levels,anxiety,symptoms,daily living ability scores,and postoperative complication rates were compared.Results:The anxiety score and total postoperative complications of the observation group upon discharge were lower than that of the control group,and the disease cognition level and daily living ability upon discharge were higher than that of the control group(P<0.05).Conclusion:Applying the comprehensive nursing model in conjunction with perioperative care for patients undergoing surgery can effectively improve their anxiety,strengthen activities of daily living,and reduce the risk of postoperative complications.

Anesthetic and Obstetric Considerations of Moyamoya Disease in Pregnancy after Intracranial Bypass Grafting: A Case Report and Literature Review

Moyamoya disease (MD) is a chronic idiopathic vasculopathy characterized by bilateral stenosis of the distal internal carotid arteries (ICA’s) with subsequent formation of abnormal collateral vessels. The underlying etiology is unknown [1]. Patients with MD are predisposed to intracranial hemorrhage or cerebral ischemia given the fragile nature of the collateral circulation. Although there is no curative treatment for MD, there are surgical palliative procedures that can augment cerebral blood flow to areas of impaired perfusion and circumvent the abnormal collateral circulation. Medical management exists for patients who are not surgical candidates. Because the incidence of MD peaks during the second and third decades of life, it can potentially affect women of childbearing age [2]. However, the optimal anesthetic and obstetric management of the parturient with MD remains controversial. We present a case of a primigravida with a history of MD who underwent intracranial bypass grafting prior to conception and subsequently had a successful cesarean delivery that was complicated by transient ischemic attacks (TIA) in the postpartum period.

Enhancement Expression of bFGF in Chinese Patients with Moyamoya Disease

Objective To detect the content of the basic fibroblast growth factor in blood samples of patients with Moyamoya disease, and investigate the relationship between Moyamoya disease and the basic fibroblast growth factor. Methods This tissue microarray study included 24 cases of superficial temporal artery samples, 15 cases of Moyamoya disease, and 9 cases of normal arteries as control, and bFGF immunofluorescence assay was applied to test the samples. The number of positive cells and total cells of the muscular layer and the endothelium layer were counted separately in every picture, the positive rates were calculated, and the experimental data were analyzed statistically. Results The bFGF immunofluorescence staining of smooth muscular layer cells, intima cells and endothelial cells from the moyamoya disease group were obviously stronger than that from the control group （P0.01）. Conclusion The enhancement expression of bFGF in the Moyamaya disease group implicates that bFGF plays an important part in the pathogenesis of Moyamoya disease.

Recognition of moyamoya disease and its hemorrhagic risk using deep learning algorithms:sourced from retrospective studies

Although intracranial hemorrhage in moyamoya disease can occur repeatedly,predicting the disease is difficult.Deep learning algorithms developed in recent years provide a new angle for identifying hidden risk factors,evaluating the weight of different factors,and quantitatively evaluating the risk of intracranial hemorrhage in moyamoya disease.To investigate whether convolutional neural network algorithms can be used to recognize moyamoya disease and predict hemorrhagic episodes,we retrospectively selected 460 adult unilateral hemispheres with moyamoya vasculopathy as positive samples for diagnosis modeling,including 418 hemispheres with moyamoya disease and 42 hemispheres with moyamoya syndromes.Another 500 hemispheres with normal vessel appearance were selected as negative samples.We used deep residual neural network(ResNet-152)algorithms to extract features from raw data obtained from digital subtraction angiography of the internal carotid artery,then trained and validated the model.The accuracy,sensitivity,and specificity of the model in identifying unilateral moyamoya vasculopathy were 97.64±0.87%,96.55±3.44%,and 98.29±0.98%,respectively.The area under the receiver operating characteristic curve was 0.990.We used a combined multi-view conventional neural network algorithm to integrate age,sex,and hemorrhagic factors with features of the digital subtraction angiography.The accuracy of the model in predicting unilateral hemorrhagic risk was 90.69±1.58%and the sensitivity and specificity were 94.12±2.75%and 89.86±3.64%,respectively.The deep learning algorithms we proposed were valuable and might assist in the automatic diagnosis of moyamoya disease and timely recognition of the risk for re-hemorrhage.This study was approved by the Institutional Review Board of Huashan Hospital,Fudan University,China(approved No.2014-278)on January 12,2015.

Acute recurrent cerebral infarction caused by moyamoya disease complicated with adenomyosis:A case report

BACKGROUND Moyamoya disease is essentially an ischemic cerebrovascular disease.Here,we describe a case of acute recurrent cerebral infarction caused by moyamoya disease with concurrent adenomyosis which,to our knowledge,is the first in the literature.A literature review is also presented.CASE SUMMARY A 38-year-old female presented to the Research and Treatment Center of Moyamoya Disease in our hospital with"left limb weakness"as the main symptom.She was diagnosed with acute cerebral infarction and moyamoya disease through magnetic resonance imaging and digital subtraction angiography.Prior to this,she had experienced a prolonged menstrual period of one-month duration.This was investigated and adenomyosis was diagnosed.After passing the acute cerebral infarction phase,the patient underwent surgery for adenomyosis followed by combined cerebral revascularization.During the postoperative follow-up,improvements of the perfusion imaging stage and modified Rankin Scale were observed.A review of the literature showed only 16 reported cases of gynecological diseases complicated with stroke.The clinical characteristics,pathogenesis,therapeutic effects,and long-term prognosis of these cases have been studied and discussed.CONCLUSION In patients with moyamoya disease,early management of gynecological-related bleeding disorders is essential to prevent the complications of cerebral events.

Significance of Cyclooxygenase-2 Elevation in Middle Cerebral Artery for Patients with Hemorrhagic Moyamoya Disease

The etiology and pathogenesis of moyamoya disease（MMD） remain elusive. Some inflammatory proteins, such as cyclooxygenase（COX）-2, are believed to be implicated in the development of MMD. So far, the relationship between COX-2 and MMD is poorly understood and reports on the intracranial vessels of MMD patients are scanty. In this study, tiny pieces of middle cerebral artery（MCA） and superficial temporal artery（STA） from 13 MMD patients were surgically harvested. The MCA and STA samples from 5 control patients were also collected by using the same technique. The expression of COX-2 was immunohistochemically detected and the average absorbance（A） of positively-stained areas was measured. High-level COX-2 expression was found in all layers of the MCA samples from all 5 hemorrhagic MMD patients, while positive but weak expression of COX-2 was observed only in the endothelial layer of the MCA samples from most ischemic MMD patients（6/8, 75%）. The average A values of COX-2 in the hemorrhagic MMD patients were substantially higher than those in their ischemic counterparts（t=4.632, P=0.001）. There was no significant difference in the COX-2 expression among the ＂gender＂ groups, or ＂radiographic grade＂ groups, or ＂lesion location＂ groups（P0.05 for all）. The COX-2 expression was detected neither in the MCA samples from the controls nor in all STA specimens. Our results suggested that COX-2 was up-regulated in the MCA of MMD patients, especially in hemorrhagic MMD patients. We are led to speculate that COX-2 may be involved in the pathogenesis of MMD and even contribute to the hemorrhagic stroke of MMD patients.

Histopathological Features of Middle Cerebral Artery and Superficial Temporal Artery from Patients with Moyamoya Disease and Enlightenments on Clinical Treatment

The histopathological features of the middle cerebral artery（MCA） and superficial temporal artery（STA） from moyamoya disease（MMD） and their relationships with gender,age,angiography stage were explored.The causes and the clinical significance of vasculopathy of STA were also discussed.The clinical data and specimens of MCA and STA from 30 MMD patients were collected.Twelve samples of MCA and STA from non-MMD patients served as control group.Histopathological examination was then performed by measuring the thickness of intima and media,and statistical analysis was conducted.The MCA and STA specimens from MMD group had apparently thicker intima and thinner media than those from the control group.There was no significant pathological difference between the hemorrhage group and non-hemorrhage group,and between the males and females in MMD patients.Neither the age nor the digital subtraction angiography（DSA） stage was correlated with the thickness of intima in MCA and STA.MMD is a systemic vascular disease involving both intracranial and extracranial vessels.Preoperative external carotid arteriography,especially super-selective arteriography of the STA,benefits the selection of donor vessel.

Clinical manifestations and cerebral angiographic findings of moyamoya disease

Objective To study the clinical features and angiographic findings of moyamoya disease (MMD) as well as their relationship. Methods A total of 22 MMD patients received routine digital substraction angiography (DSA). The clinical manifestations and angiographic findings were analyzed. Results Clinical manifestations varied and each patient often had multiple symptoms,including cerebral infarction in 9 patients with an average age of 23.6 (13-39 years) and cerebral hemorrhage in 7 patients with an average age of 31.2 (28-46 years). Angiographic examination found that all the diseased sides showed MMD blood vessels. The patients who received encephalo-myo-arterio-synangiosis (EMAS) had better prognosis than those without receiving the treatment. Conclusion Cerebral infarction is frequent in children and adolescents with MMD,whereas cerebral hemorrhage is common in adults. DSA is a golden criterion for diagnosing MMD. Surgical treatment,EMAS blood supply reconstruction in particular,should be prescribed.

Microstructural damage pattern of vascular cognitive impairment: a comparison between moyamoya disease and cerebrovascular atherosclerotic disease

Moyamoya disease and cerebrovascular atherosclerotic disease are both chronic ischemic diseases with similar presentations of vascular cognitive impairment. The aim of the present study was to investigate the patterns of microstructural damage associated with vascular cognitive impairment in the two diseases. The study recruited 34 patients with moyamoya disease(age 43.9 ± 9.2 years; 20 men and 14 women, 27 patients with cerebrovascular atherosclerotic disease(age: 44.6 ± 7.6 years; 17 men and 10 women), and 31 normal controls(age 43.6 ± 7.3 years; 18 men and 13 women) from Huashan Hospital of Fudan University in China. Cognitive function was assessed using the Mini-Mental State Examination, long-term delayed recall of Auditory Verbal Learning Test, Trail Making Test Part B, and the Symbol Digit Modalities Test. Single-photon emission-computed tomography was used to examine cerebral perfusion. Voxel-based morphometry and tract-based spatial statistics were performed to identify regions of gray matter atrophy and white matter deterioration in patients and normal controls. The results demonstrated that the severity of cognitive impairment was similar between the two diseases in all tested domains. Patients with moyamoya disease and those with cerebrovascular atherosclerotic disease suffered from disturbed supratentorial hemodynamics. Gray matter atrophy in bilateral middle cingulate cortex and parts of the frontal gyrus was prominent in both diseases, but in general, was more severe and more diffuse in those with moyamoya disease. White matter deterioration was significant for both diseases in the genu and body of corpus callosum, in the anterior and superior corona radiation, and in the posterior thalamic radiation, but in moyamoya disease, it was more diffuse and more severe. Vascular cognitive impairment was associated with regional microstructural damage, with a potential link between, gray and white matter damage. Overall, these results provide insight into the pathophysiological nature of vascular cognitive impairment. This study was approved by the Institutional Review Board in Huashan Hospital, China(approval No. 2014-278). This study was registered with ClinicalTrials.gov on December 2, 2014 with the identifier NCT02305407.

On-pump coronary artery bypass in moyamoya disease: A case report

A 54-year-old female with pre-existing idiopathic moyamoya disease developed chest pain with acute myocardial infarction. Coronary angiography detected occluded and stenotic lesions in the coronary arteries. Right coronary artery stenosis was treated by balloon angioplasty and stenting. Because of the restenosis, on-pump cardiopulmonary bypass was performed. The operation was uneventful and no perioperative cerebral ischemic episode occurred. The conclusion is that on-pump cardiopulmonary bypass preserving intraoperative hemodynamic parameters at an optimal level is a safe procedure in a patient with moyamoya disease.

Involuntary Movements Induced and Remitted by Indirect Bypass Surgery in a Patient with Moyamoya Disease

Involuntary movement is an uncommon manifestation of moyamoya disease. We describe a 12-year-old boy who suffered from involuntary movement after the first surgery but it improved dramatically after the second surgery. Initially, the patient underwent an encephalo-duro-arterio-myosynangiosis on the right side and encephalo-duro-periostealsynangiosis on the bifrontal side, which ameliorated his motor weakness in his left upper extremity. However, involuntary movement appeared in his right upper extremity. Secondly, the patient underwent encephalo-duro-arterio-myo-periostealsynangiosis on the left side. Thereafter, the patient’s involuntary movement completely resolved. The involuntary movement might occur due to the unequal distribution of the blood flow in the basal ganglia.

GM-CSF Promotes the Development of Dysfunctional Vascular Networks in Moyamoya Disease

Moyamoya disease(MMD)is a chronic occlusive cerebrovascular disease with the development of a network of abnormal vessels.Immune inflammation is associated with the occurrence and development of MMD.However,the mechanisms underlying the formation of the abnormal vascular network remain unclear.Twenty-eight patients with MMD,26 ischemic stroke patients,and 26 unrelated healthy volunteers were enrolled in this study The data showed that the levels of granulocyte-macrophage colony-stimulating factor(GM-CSF)were higher in MMD patients than in healthy controls(P<0.01),and GM-CSF was mainly from Th1 and Th17 cells in MMD.We found that increased GM-CSF drove monocytes to secrete a series of cytokines associated with angiogenesis,inflammation,and chemotaxis.In summary,our findings demonstrate for the first time the important involvement of GM-CSF in MMD and that GM-CSF is an important factor in the formation of abnormal vascular networks in MMD.

Classification and treatment strategy for Moyamoya disease-related aneurysms

Background Moyamoya disease(MMD)is a cerebrovascular disorder characterized by progressive unilateral or bilateral stenosis of the distal internal carotid artery.As hemodynamic features in MMD patients alter,the comorbidity of intracranial aneurysm(IA)is sometimes observed clinically.We aim to investigate clinical characteristics and therapeutic strategies for the comorbidity of Moyamoya disease with intracranial aneurysms(MMD-IA).Methods A total of 13 MMD-IA patients were recruited in this study and were manifested to be intracranial hemorrhage.We reviewed the surgical technique notes for all patients.Results According to the locations of an aneurysm,MMD-IA could be divided into several categories:(1)MMD-IA at a circle of Willis—aneurysms usually located at the trunk of Willis circle;(2)MMD-IA at collateral anastomosis—aneurysms located at the distal end of collateral anastomosis;and(3)MMA-IA at basal ganglia region.In this report,aneurysms in 10 patients located at Willis circle,2 at the pericallosal artery,and 1 at the basal ganglia region.Among them,endovascular embolism was performed among 5 patients.Aneurysm clipping was conducted among 7 patients.A patient with an aneurysm at the basal ganglia region just accepted revascularization treatment.All the treatments were successful.Follow-up studies,ranging from 6 to 24 months,demonstrated all patients received satisfactory curative effects.Conclusion Diverse clinical presentations could be observed among MMD-IA patients.Individualized neurosurgical treatments should be chosen according to the locations of the aneurysm.

Remote ischemic conditioning prevents ischemic cerebrovascular events in children with moyamoya disease:a randomized controlled trial

Background Moyamoya disease(MMD)is a significant cause of childhood stroke and transient ischemic attacks(TIAs).This study aimed to assess the safety and efficacy of remote ischemic conditioning(RIC)in children with MMD.Methods In a single-center pilot study,46 MMD patients aged 4 to 14 years,with no history of reconstructive surgery,were randomly assigned to receive either RIC or sham RIC treatment twice daily for a year.The primary outcome measured was the cumulative incidence of major adverse cerebrovascular events(MACEs).Secondary outcomes included ischemic stroke,recurrent TIA,hemorrhagic stroke,revascularization rates,and clinical improvement assessed using the patient global impression of change(PGIC)scale during follow-up.RIC-related adverse events were also recorded,and cerebral hemodynamics were evaluated using transcranial Doppler.Results All 46 patients completed the final follow-up(23 each in the RIC and sham RIC groups).No severe adverse events associated with RIC were observed.Kaplan-Meier analysis indicated a significant reduction in MACEs frequency after RIC treatment[log-rank test(Mantel-Cox),P=0.021].At 3-year follow-up,two(4.35%)patients had an ischemic stroke,four(8.70%)experienced TIAs,and two(4.35%)underwent revascularization as the qualifying MACEs.The clinical improvement rate in the RIC group was higher than the sham RIC group on the PGIC scale(65.2%vs.26.1%,P<0.01).No statistical difference in cerebral hemodynamics post-treatment was observed.Conclusions RIC is a safe and effective adjunct therapy for asymptomatic children with MMD.This was largely due to the reduced incidence of ischemic cerebrovascular events.

Risk factors of postoperative cerebral hyperperfusion syndrome and its relationship with clinical prognosis in adult patients with moyamoya disease

Background To investigate the incidence,risk factors,and clinical prognosis of cerebral hyperperfusion syndrome(CHS)after superficial temporal artery-middle cerebral artery anastomosis combined with encephalo-duro-arterio-synangiosis(STA-MCA/EDAS)in adult patients with moyamoya disease(MMD).Methods The clinical data of 160 adult patients with MMD treated by STA-MCA/EDAS from January 2016 to January 2017 were retrospectively analyzed.According to CHS diagnosis,MMD patients were divided into CHS and non-CHS group.Univariate and multivariate analysis of risk factors and Kaplan-Meier curve of stroke-free survival for CHS were performed.Results A total of 12 patients(7.5%)developed postoperative CHS,of which 4 patients(2.5%)presented with cerebral hemorrhage.Univariate and multivariate analysis showed moyamoya vessel on the surgical hemisphere(OR=3.04,95%CI=1.02-9.03,P=0.046)and left operated hemisphere(OR=5.16,95%CI=1.09-21.34,P=0.041)were independent risk factors for CHS.The other variables,such as age,gender,presentation,hypertension,diabetes,smoking,mean mRS score on admission,modified Suzuki stage and pre-infarction stage on surgical hemisphere,and bypass patency,had no association with postoperative CHS(P>0.05).At final follow-up with average 38 months,there were 18 out of 133 patients(13.5%,4.91%per person year)presented with newly developed complications.There was no significant difference between newly developed complications,mean mRS scores,and Kaplan-Meier curve of stroke-free survival in patients with and without CHS(P>0.05).Conclusion The concentration of moyamoya vessels and left operated hemisphere was independent risk factors for CHS,which could not affect the clinical prognosis if treated timely and properly.The current study offers a new perspective of moyamoya vessels and supporting data for choosing MMD candidates on cerebral revascularization.

Clinical and experimental pathology of Moyamoya disease

Objective To investigate the etiology, pathology, and mechanism of pathogenesis of Moyamoya disease. Methods A total of 15 human autopsies were analyzed. In addition, in order to create an animal model of the disease, 21 Japanese rabbits were divided randomly into two groups and subjected to injections of horse serum either intravenously or locally in the area of the sympathetic ganglia. Pathological and immunohistochemical characteristics were observed. Results The pathological features of the autopsies and the animal models both involved intima hyperplasia and stenosis or even occlusion of the lumen in the terminal ends of the internal carotid artery and the anterior and middle cerebral arteries. Disconnections or even breakages of the inner layer of the lumen were also observed, without an obvious inflammatory response. Hyperplasic smooth muscle cells of the medial membrane had extended inward through broken portions of the internal elastic lamina, with intima cell hyperplasia resulting in lumen stenosis. The hyperplastic vascular walls were positive for IgG and IgM.Conclusions The etiology of Moyamoya disease may involve allergic angiitis. A possible mechanism is that proximal portions of the circle of Willis first develop chronic stenosis or occlusion, leading to compensatory small vessel proliferation, which perforates into the cerebral parenchyma.

Superficial temporal artery-middle cerebral artery bypass combined with encephalo-duro-myo-synangiosis in treating moyamoya disease： surgical techniques, indications and midterm follow-up results

Background Surgical interventions for moyamoya disease include direct and indirect revascularizations. This study aimed to evaluate the therapeutic effect of superficial temporal artery-middle cerebral artery bypass combined with an indirect revascularization procedure, encephalo-duro-myo-synangiosis, in the treatment of moyamoya disease. Methods From October 2005 to November 2009, we performed this combined revascularization procedure in 111 patients with different types and stages of moyamoya disease. The superficial temporal artery, middle meningeal artery and the deep temporal artery were evaluated for individualized surgical planning in these cases. The integrity of the deep temporal artery and the middle meningeal artery network, and the pre-existing spontaneous anastomoses of the distal branches of the external carotid artery with the cortical arteries were well preserved. The mean follow-up time was 72.5 months, all clinical and radiological data were retrospectively reviewed. Results A total of 198 stomas were performed in 122 hemispheres, all remaining patent until the last follow-up. The encephalo-duro-myo-synangiosis resulted in extensive anastomoses of the deep temporal artery （100%）, the middle meningeal artery （90.9%）, and the sphenopalatine artery （39.8%） with the cortical arteries, respectitvely. The superficial temporal artery, deep temporal artery, and the middle meningeal artery were significantly thickened in 88 patients as determined by digital subtraction angiography at follow-up. The relative cerebral blood flow increased significantly within one week after the operation. At 6 months post the operation, the relative cerebral blood flow was further increased by 15.5% from the gradual formation of anastomoses as a result of indirect revascularization. Transient ischemic attacks were effectively reduced or totally arrested. The neurological deficits significantly improved in 37 patients, with the National Institutes of Health Stroke Scale scores lowered by 2-8. There was no rehemorrhage in hemorrhagic moyamoya disease patients. Conclusion This study showed that the superficial temporal artery-middle cerebral artery bypass combined with encephalo-duro-myo-synangiosis can achieve good therapeutic effect in the treatment of moyamoya disease.

Role of Ring Finger Protein 213 in Moyamoya Disease

Objective：The aim of this study was to help people comprehensively understand the research advances related to ring finger protein 213 （RNF213） in moyamoya disease （MMD） and to understand the disease at the molecular level to provide a new perspective of the diagnosis of the disease.Data Sources：This review was based on data in articles published between 2005 and 2015 that were retrieved from the PubMed database.The search terms included RNF213,MMD,intracranial major artery stenosis/occlusion （ICASO）,genotype,phenotype,mutant and variants,and the combinations of these terms.Study Selection：Articles related to MMD and RNF213 were selected for review,and we also reviewed publications related to ICASO.Results：RNF213 is not only associated with MMD but also associated with intracranial major artery stenosis.In addition,RNF213 variants exhibit apparent ethnic diversity;specifically,the c.14576G〉A variant is mainly detected in Korean,Chinese,and Japanese populations,particularly the latter population.The genotypes of RNF213 correlate with the phenotypes of MMD;for example,the homozygous c.14576G〉A variant is associated with early-onset,severe symptoms,and an unfavorable prognosis.Furthermore,the RNF213 c.14576G〉A variant should be considered during the diagnosis of MMD because no patients with quasi-MMD have been reported to carry the RNF213 c.14576G〉A variant whereas 66 of 78 patients with definite MMD have been found to carry this variant.Conclusions：The growing literature demonstrates that MMD is primarily caused by the synergy of genetic and environmental factors,and unknown genetic modifiers might play roles in the etiology of MMD.Further research should be conducted to clarify the pathogenic mechanism of MMD.