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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Radiological diagnosis of inflammatory ulcerative diseases of small bowel

AIMS To analyze the radiological features of the ul- cerative diseases of the small bowel. METHODS Thirty-five patients (20 men,15 women) with inflammatory ulcerative bowel diseases were stud- ied radiographically (barium meal and/or double con- trast study),including:11 cases of tuberculosis,13 Crohn disease,7 bowel Behcet disease,2 simple ulcer and 2 ischemic bowel disease. Diagnosis was estab- lished pathologically in 33 cases and by clinical obser- vation after therapy in 2 cases. RESULTS The lesions were located in ileum,in 9 of 11 cases of TB;in 10 of 13 cases of Crohn disease;in 5 of 7 cases of bowel Behcet disease;in 1 of 2 cases of simple ulcer and in 2 cases of ischemic bowel disease. Ulceration was always present with variable appearances. Longitudinal ulcers,and fissures were noted in Crohn disease only. There were 5 cases of large and deep ulcer and 3 occurred in bowel Behcet disease,10 of 13 cases of superficial and irregular ul- cers were tuberculous,2 cases of transverse ulcer were also tuberculous. CONCLUSIONS The morphologic appearances of the ulcer,surrounding mucosal alterations and bowel deformation were the basis for the radiologic diagnosis. Correct diagnosis was dependent on optimal X-ray ex- amination technique and proper interpretation of the morphologic changes.

Diagnostic Value of Dental Pulp Stones in the Early Diagnosis of Ischemic Heart Diseases

Background: Pulp stones are calcified masses formed in the primary and permanent dentitions. The ischemic cardiovascular disorders (CVD) can be the first health problem of the world. It seems that there is a relationship between pulp stones and cardiovascular diseases to determine the diagnostic value of panoramic dental radiographs as non-invasive test for the early detection of CVD. Methods and Materials: The subjects of the study came from patients presenting to Dental Radiology Department of Dental School in Yazd who aged 30 - 64 years, had 8 natural teeth. They were referred to the Cardiovascular Center of Afshar Hospital in Yazd for cardiovascular evaluation. To set the cut-off point, the ratio of teeth with pulp stones to the total number of teeth for each person was calculated and also ABI for diagnosing IHD via ROC curve was used. Results: Only 3.8% of patients without pulp stone were affected by ischemic heart disease (IHD). About Sixty seven percent (67.3%) of individuals had at least one tooth with pulp stone. In individuals without IHD, 5% of the teeth showed pulp stone while this rate was 45% (9 times) in CVD patients. The number of patients for whom the ratio of teeth with pulp stone to total number of teeth was 0.2 or more, was 138.7 times greater than the other. Conclusion: The dentists, who order panoramic radiographs for the treatment of patients, exactly study those teeth for the presence of pulp stones. The ratio of teeth with pulp stone to total teeth equal 0.2 or more was a good tool for early detection of CVD.

Idiopathic steno-occlusive disease with bilateral internal carotid artery occlusion:A Case Report

BACKGROUND Moyamoya disease(MMD)is a rare cause of acute stroke and transient ischemic attacks in children.We described clinical,diagnostic features and follow-ups of a young child with acute stroke.CASE SUMMARY We report a 4-year-old girl with left hemiparesis after an acute ischemic stroke.Her history was also significant for repeated left or right focal motor seizures,generalized tonic-clonic convulsions and transient ischemic attacks.Her magnetic resonance imaging and computed tomography(CT)of the brain and magnetic resonance angiography,CT angiography and venography on the cerebral vessels revealed evidence of bilateral fronto-parietal ischemic infarctions,occlusion of the right and left internal carotid arteries started at its bifurcation and non-visualization of right and left anterior and middle cerebral arteries.There was evidence of progression in angiography manifested as development of collaterals from the basal perforating vessels,increase in the extent of large intracranial arterial stenosis/occlusion and extensive collateral circulation with predominance from the posterior circulation.Physical and neurological evaluation and comprehensive laboratory investigations excluded an obvious comorbid disease or risk factor for the child’s condition.The diagnosis of MMD was highly suggested as a cause of the child’s steno-occlusive condition.She was treated symptomatically with levetiracetam,an antiepileptic medication.Aspirin was prescribed for secondary prevention.Her clinical manifestations were improved during the three years of follow-up.Revascularization surgery was postponed.CONCLUSION Up to our knowledge,this is the first report for MMD in a child in our country.The clinical improvement and the stabilization of the child’s condition over the 3 years of follow-up could be attributed to the rapid and extensive recruitment of collaterals and absence of risk factors or comorbidities.Revascularization surgery is highly recommended.

Moyamoya病侧支途径的DSA评价及其与临床的关系

目的 应用 DSA分析 Moyamoya病的侧支途径 ,探讨侧支循环建立情况与临床、CT表现之间的关系。材料与方法 回顾分析 30例经脑血管造影确诊的 Moyamoya病患者的血管造影表现、CT结果及临床资料。结果 所有病例均出现颈内动脉或其分支不同程度狭窄或闭塞和颅底异常血管网 (MMD血管 ) ;7例可见后组 MMD血管 ;2 0例由 Willis环提供侧支血流 ;14例眼动脉增粗 ;17例软脑膜吻合支明显增粗 ;1例脉络膜前动脉增粗。 30例中头颅 CT显示有脑梗塞灶 4例 ,正常表现 3例 ,脑出血 2 3例。结论 DSA是诊断 Moyamoya病的金标准 ,对其侧支途径的研究提供了可靠方法。 Moyamoya病的侧支循环建立情况与临床密切相关。明确 Moyamoya病的侧支循环情况 ,可为临床治疗和预后判断提供可靠依据。

出血型Moyamoya病临床分析

目的 回顾性分析首都医科大学附属北京天坛医院神经外科15年来收治的82例出血型烟雾病(Moyamoya)患者的临床资料,以提高对出血型Moyamoya病的进一步认识.方法 全部患者均经脑血管造影检查确诊为Moyamoya病.根据CT检查及脑血管造影将其分为3组.A组:10例(12%),脑血管造影显示合并有动脉瘤.B组:38例(46%),CT显示为脑内出血(ICH),脑血管造影无动脉瘤.C组:34例(42%),CT显示为脑室出血(IVH),无动脉瘤或ICH.手术治疗49例患者,保守治疗33例.回顾性分析患者的临床及影像学资料并对其恢复情况做随访调查.结果 共随访64例患者,其中手术治疗者42例,保守治疗者22例.疗效优良者46例,良好者9例,1例恢复差,8例死亡.有10例患者在随访期间在初次出血后0.3～8年间发生再出血,再出血率为12%,82例患者中有2例死于初次出血,死亡率为2.4%,6例患者死于再出血,死亡率为60%.结论 出血是Moyamoya患者的重要死亡原因,再出血是出血型Moyamoya病的主要死亡原因. 其预后主要取决于颅内出血部位、出血量和有无再次出血及治疗时机等.

Moyamoya病的MRI和MRA诊断(附15例报告)

目的：探讨ＭＲＩ和ＭＲＡ对Ｍｏｙａｍｏｙａ病的诊断价值。材料与方法：１５例Ｍｏｙａｍｏｙａ病患者中男６例，女９例。年龄４～４９岁，２０岁以下者１１例。应用Ｓｉｅｍｅｎｓ１．０Ｔ超导型ＭＲ系统（Ｉｍｐａｃｔ）行ＳＥ序列ＭＲＩ和三维时间飞跃法（３ＤＴＯＦ）ＭＲＡ。均有ＳＥ序列Ｔ１ＷＩ和Ｔ２ＷＩ，１４例有３ＤＴＯＦＭＲＡ，１例有ＤＳＡ，６例有平扫ＣＴ。选择２０例ＭＲＩ和ＭＲＡ正常者作为对照组。结果：ＭＲＩ均见丘脑基底节区（单侧３例，双侧１２例）有扩张的流空血管（Ｍｏｙａｍｏｙａ血管），其中１０例Ｔ２ＷＩ鞍上池有明确的异常血管网。１４例ＭＲＡ和１例ＤＳＡ均见颈内动脉（ＩＣＡ）上段或大脑中动脉（ＭＣＡ）、大脑前动脉（ＡＣＡ）近端闭塞以及丘脑基底节区的Ｍｏｙａｍｏｙａ血管，这些病理血管分布与ＳＥ序列ＭＲＩ所见一致。对照组ＭＲＩ和ＭＲＡ均见不到丘脑基底节区正常细小的穿支血管。６例有ＣＴ者仅２例可疑有Ｍｏｙａｍｏｙａ血管。结论：ＭＲＩ和ＭＲＡ是诊断Ｍｏｙａｍｏｙａ病的有效非创伤性方法。ＭＲＡ尚适用于随诊Ｍｏｙａｍｏｙａ病的演变、血管旁路术后血管再通情况以及高危人群普查。ＭＲＩ诊断Ｍｏｙａｍｏｙａ病优于平扫ＣＴ。