Aneurysmal formation of periventricular anastomosis is associated with collateral development of Moyamoya disease and its rupture portends poor prognosis: detailed analysis by multivariate statistical and machine learning approaches.
Neurosurgical review
Periventricular anastomosis (PA) is the characteristic collateral network in Moyamoya disease (MMD). However, PA aneurysms are rare, resulting in limited knowledge of their clinical significance. We aimed to elucidate the associated factors and clinical outcomes of PA aneurysms. We reviewed MMD patients who underwent digital subtraction angiography in our institution between December 2001 and March 2023. Genetic analysis was conducted in several cases, and PA aneurysm-positive patients were identified. PA score was defined as the grades of development of periventricular anastomosis. Multivariate analysis and machine learning approaches were used to investigate the significance of the disease and factors associated with PA aneurysm positivity. A total of 301 hemispheres (171 patients) were included. PA aneurysm occurred in 8 hemispheres of MMD (2.7%). PA aneurysm was associated with higher initial modified Rankin scale (mRS) scores (OR, 2.61; 95% CI, 1.45-4.70) and higher PA scores (OR, 1.60; 95% CI, 1.06-2.40). This predisposition was corroborated by gradient boosting and random forest algorithms. Further analysis revealed that PA aneurysm was a risk factor for future hemorrhagic stroke events (HR, 8.29; 95% CI, 1.44-47.7). Among patients in the hemorrhagic-onset group (33 cases), PA aneurysm was a risk factor for worse outcomes (P = 0.008). Principal component analysis also revealed distinct characteristics of hemorrhagic onset aneurysms compared to other MMD cases. Higher PA scores were associated with the presence of aneurysm. PA aneurysm suggests a higher risk of future hemorrhagic strokes, and its rupture portends a worse prognosis.
10.1007/s10143-024-03097-2
Nomogram to Predict Good Neoangiogenesis After Indirect Revascularization Surgery in Patients with Moyamoya Disease: a Case-control Study.
Translational stroke research
Indirect bypass surgery is an effective treatment for moyamoya disease (MMD), but the success of the surgery depends on the formation of spontaneous collateral vessels, which cannot be accurately predicted before surgery. Developing a prediction nomogram model for neoangiogenesis in patients after indirect revascularization surgery can aid surgeons in identifying suitable candidates for indirect revascularization surgery. This retrospective observational study enrolled patients with MMD who underwent indirect bypass surgery from a multicenter cohort between December 2010 and December 2018. Data including potential clinical and radiological predictors were obtained from hospital records. A nomogram was generated based on a multivariate logistic regression analysis identifying potential predictors of good neoangiogenesis. A total of 263 hemispheres of 241 patients (mean ± SD age 24.38 ± 15.78 years, range 1-61 years) were reviewed, including 168 (63.9%) hemispheres with good postoperative collateral formation and 95 (36.1%) with poor postoperative collateral formation. Based on multivariate analysis, a nomogram was formulated incorporating four predictors, including age at operation, abundance of ICA moyamoya vessels, onset type, and Suzuki stage. The C-index for this nomogram was 0.80. Calibration curve and decision-making analysis validated the fitness and clinical application value of this nomogram. The nomogram developed in this study exhibits high accuracy in predicting good neoangiogenesis after indirect revascularization surgery in MMD patients. This model can be very helpful for clinicians when making decisions about surgical strategies for MMD patients in clinical practice.
10.1007/s12975-023-01177-x
Evaluation of deep learning algorithms in detecting moyamoya disease: a systematic review and single-arm meta-analysis.
Neurosurgical review
The diagnosis of Moyamoya disease (MMD) relies heavily on imaging, which could benefit from standardized machine learning tools. This study aims to evaluate the diagnostic efficacy of deep learning (DL) algorithms for MMD by analyzing sensitivity, specificity, and the area under the curve (AUC) compared to expert consensus. We conducted a systematic search of PubMed, Embase, and Web of Science for articles published from inception to February 2024. Eligible studies were required to report diagnostic accuracy metrics such as sensitivity, specificity, and AUC, excluding those not in English or using traditional machine learning methods. Seven studies were included, comprising a sample of 4,416 patients, of whom 1,358 had MMD. The pooled sensitivity for common and random effects models was 0.89 (95% CI: 0.85 to 0.92) and 0.92 (95% CI: 0.85 to 0.96), respectively. The pooled specificity was 0.89 (95% CI: 0.86 to 0.91) in the common effects model and 0.91 (95% CI: 0.75 to 0.97) in the random effects model. Two studies reported the AUC alongside their confidence intervals. A meta-analysis synthesizing these findings aggregated a mean AUC of 0.94 (95% CI: 0.92 to 0.96) for common effects and 0.89 (95% CI: 0.76 to 1.02) for random effects models. Deep learning models significantly enhance the diagnosis of MMD by efficiently extracting and identifying complex image patterns with high sensitivity and specificity. Trial registration: CRD42024524998 https://www.crd.york.ac.uk/prospero/displayrecord.php?RecordID=524998.
10.1007/s10143-024-02537-3
Diagnosis and management of adult Moyamoya angiopathy: An overview of guideline recommendations and identification of future research directions.
International journal of stroke : official journal of the International Stroke Society
Despite the progress made in understanding the management and outcomes of Moyamoya angiopathy (MMA), several aspects of the disease remain largely unknown. In particular, evidence on the disease history and management of MMA is lacking, mainly due to methodological and selection biases in the available studies and the lack of large, randomized prospective studies. Therefore, the care of MMA patients remains limited to a few expert centers worldwide, and management is often based on local expertise and available resources. Over the years, recommendations or expert opinions have been written to provide guidance to physicians in the treatment of this condition with the goal of reducing the risk of stroke recurrence and long-term disability. However, there is no complete agreement between the available guidelines and recommendations due to differences in the articles addressed, methodologies, expertise, and validated approaches to literature review. This lack of consensus on the management of MMA may confuse clinicians and highlight some important issues and points. The aim of this comprehensive review article is to critically examine three recent guidelines and recommendations on MMA, discussing their differences and similarities and highlighting gaps in MMA care that need to be covered.
10.1177/17474930241297031
Moyamoya Disease: Advances in Diagnosis, Treatment, and Surgical Interventions.
Cureus
Moyamoya disease (MMD) is a rare cerebrovascular disorder characterized by progressive narrowing of the brain's arteries, leading to an increased risk of stroke. The primary susceptibility gene, RNF213, has been identified in individuals of East Asian descent, contributing to ongoing research into potential therapeutic targets. The distinction between idiopathic MMD and secondary forms, such as Moyamoya syndrome (MMS), is discussed, focusing on associated conditions and risk factors. Surgical revascularization emerges as the mainstay of treatment, with direct, indirect, and combination bypass procedures explored. The review delves into advancements in imaging technology for diagnosis and treatment planning, emphasizing non-invasive magnetic resonance examination's role in identifying asymptomatic patients. Additionally, insights into anesthetic care and therapeutic approaches underscore the evolving understanding of this complex disease. The presented information aims to contribute to the ongoing dialogue surrounding MMD, providing a valuable resource for clinicians and researchers.
10.7759/cureus.59826
[Genetic Analysis of Cerebrovascular Diseases].
No shinkei geka. Neurological surgery
With advances in genetic analysis technology, the genetic and molecular backgrounds of cerebrovascular diseases have become clearer. In moyamoya disease and intracranial artery stenosis, p.Arg4810Lys has been identified as a disease susceptibility gene variant(germline variant), and various analyses have been conducted. mutations have been identified as characteristic somatic variants in cerebral aneurysms and are attracting attention. In addition, and mutaions have been identified in cerebral cavernous malformations as somatic variants. Moreover, and mutations have been identified in arteriovenous malformations as somatic variants, respectively. Further studies are in progress. We reviewed the results of recent genetic analyses of cerebrovascular diseases, focusing particularly on genetic mutations.
10.11477/mf.1436205016
Management of moyamoya disease: a review of current and future therapeutic strategies.
Journal of neurosurgery
Moyamoya disease (MMD) is characterized by idiopathic, progressive stenosis of the circle of Willis and the terminal portion of the internal carotid arteries with the development of prominent small collateral vessels and a characteristic moyamoya or puff-of-smoke radiographic appearance. The incidence and prevalence of MMD varies by region, age, and sex, with higher rates in Asian and East Asian populations compared to North American or European populations. There is a bimodal distribution of patients diagnosed with MMD. Pediatric patients are more commonly diagnosed within the 1st decade of life, whereas adult patients present in the 5th or 6th decade of life. Overall, there is a nearly 2:1 female-to-male ratio. Ischemic symptoms are the most common presentation in pediatric and adult populations, but adult patients are nearly twice as likely to present with intracranial hemorrhage compared to their pediatric counterparts. Surgical revascularization is indicated in symptomatic cases, and antiplatelet therapy may be a useful adjunct to prevent recurrent symptoms. Direct and combined bypass procedures seem to be more effective in adults, whereas children respond well to indirect bypass. The identification of key genetic, molecular, and environmental factors including RNF213 and GUCY1A3 loss-of-function mutations, angiogenic growth factors, autoantibodies, CNS infections, and radiation exposure suggest multiple pathways for the development of moyamoya arteriopathy. Further research is needed to better understand the heterogeneity of pathogenetic mechanisms that lead to moyamoya and to identify novel therapeutic targets to prevent, stabilize, and treat MMD.
10.3171/2024.1.JNS221977
Remote ischemic conditioning after stroke: Research progress in clinical study.
CNS neuroscience & therapeutics
BACKGROUND AND PURPOSE:Stroke is a leading cause of global morbidity and mortality, indicating the necessity and urgency of effective prevention and treatment. Remote ischemic conditioning (RIC) is a convenient, simple, non-intrusive, and effective method that can be easily added to the treatment regime of stroke patients. Animal experiments and clinical trials have proved the neuroprotective effects of RIC on brain injury including (examples of neuroprotective effects). This neuroprotection is achieved by raising brain tolerance to ischemia, increasing local cerebral blood perfusion, promoting collateral circulations, neural regeneration, and reducing the incidence of hematomas in brain tissue. This current paper will summarize the studies within the last 2 years for the comprehensive understanding of the use of RIC in the treatment of stroke. METHODS:This paper summarizes the clinical research progress of RIC on stroke (ischemic stroke and hemorrhagic stroke (HS)). This paper is a systematic review of research published on registered clinical trials using RIC in stroke from inception through November 2022. Four major databases (PUBMED, WEB OF SCIENCE, EMBASE, and ClinicalTrials.gov) were searched. RESULTS:Forty-eight studies were identified meeting our criteria. Of these studies, 14 were in patients with acute ischemic stroke with onset times ranging from 6 h to 14 days, seven were in patients with intravenous thrombolysis or endovascular thrombectomy, 10 were in patients with intracranial atherosclerotic stenosis, six on patients with vascular cognitive impairment, three on patients with moyamoya disease, and eight on patients with HS. Of the 48 studies, 42 were completed and six are ongoing. CONCLUSIONS:RIC is safe, feasible, and effective in the treatment of stroke. Large-scale research is still required to explore the optimal treatment options and mechanisms of RIC in the future to develop a breakthrough in stroke prevention and treatment.
10.1111/cns.14507
Ubiquitous regulation of cerebrovascular diseases by ubiquitin-modifying enzymes.
Clinical and translational medicine
Cerebrovascular diseases (CVDs) are a major threat to global health. Elucidation of the molecular mechanisms underlying the pathology of CVDs is critical for the development of efficacious preventative and therapeutic approaches. Accumulating studies have highlighted the significance of ubiquitin-modifying enzymes (UMEs) in the regulation of CVDs. UMEs are a group of enzymes that orchestrate ubiquitination, a post-translational modification tightly involved in CVDs. Functionally, UMEs regulate multiple pathological processes in ischemic and hemorrhagic stroke, moyamoya disease, and atherosclerosis. Considering the important roles of UMEs in CVDs, they may become novel druggable targets for these diseases. Besides, techniques applying UMEs, such as proteolysis-targeting chimera and deubiquitinase-targeting chimera, may also revolutionize the therapy of CVDs in the future.
10.1002/ctm2.1719
Factors Influencing Collateral Circulation Formation After Indirect Revascularization for Moyamoya Disease: a Narrative Review.
Translational stroke research
Indirect revascularization is one of the main techniques for the treatment of Moyamoya disease. The formation of good collateral circulation is a key measure to improve cerebral blood perfusion and reduce the risk of secondary stroke, and is the main method for evaluating the effect of indirect revascularization. Therefore, how to predict and promote the formation of collateral circulation before and after surgery is important for improving the success rate of indirect revascularization in Moyamoya disease. Previous studies have shown that vascular endothelial growth factor, endothelial progenitor cells, Caveolin-1, and other factors observed in patients with Moyamoya disease may play a key role in the generation of collateral vessels after indirect revascularization through endothelial hyperplasia and smooth muscle migration. In addition, mutations in the genetic factor RNF213 have also been associated with this process. This study summarizes the factors and mechanisms influencing collateral circulation formation after indirect revascularization in Moyamoya disease.
10.1007/s12975-023-01185-x
Ruptured Peripheral Cerebral Aneurysms Associated With Moyamoya Disease: A Systematic Review.
Journal of stroke
BACKGROUND AND PURPOSE:A ruptured peripheral cerebral aneurysm (PPCA) associated with moyamoya disease (MMD) is a rare but potentially life-threatening condition with controversial management strategies. We aim to summarize the clinical characteristics, treatment strategies, and prognostic factors of PPCAs in MMD. METHODS:We reviewed studies published in PubMed between 1980 and 2023 and used logistic regression analysis to identify the risk factors for adverse outcomes. RESULTS:Of 425 identified studies, 48 eligible studies involving 121 participants were included in the current study. The mean age at diagnosis was 40.8±15.1 years, with a peak age of onset between 41 and 50 years. Among the identified participants, 59.6% were female, and 55.9% presented with impaired consciousness. Aneurysms were present in the posterior (35.5%) or anterior (30.6%) choroidal arteries in 66.1% of the cases, and 71.1% of the patients presented with intraventricular hemorrhage (IVH) with or without intracerebral hematoma (ICH). The treatment strategies were embolization (28.9%), direct surgery (21.5%), revascularization (22.3%), and conservation (27.3%). Favorable outcomes were achieved in 86.8% of all cases, with 97.1% for embolization, 65.4% for direct surgery, 96.3% for revascularization, and 84.8% for conservative treatment. Aneurysm rebleeding occurred in 11 (26.8%) of 41 patients managed conservatively, leading to worse outcomes in 7 patients (63.6%). Impaired consciousness (odds ratio [OR], 8.61; 95% confidence interval [CI], 2.06-36.00) and aneurysm rebleeding (OR, 16.54; 95% CI, 3.08-88.90) independently predicted poor outcomes. CONCLUSION:PPCA should be considered in patients with hemorrhagic MMD, particularly those with IVH with or without ICH. Endovascular and bypass treatments are recommended as first-line options, with direct open surgery as an alternative in urgent hematoma evacuation cases. Detailed preoperative planning and intraoperative technical assistance are necessary to reduce procedure-related complications. Conservative management should be selected with caution because of the high risk of rebleeding and poor outcomes. Impaired consciousness and aneurysm rebleeding appeared to be independent risk factors for adverse prognoses. We emphasize that treatment selection should be personalized, and the potential benefits should be weighed against the associated risks.
10.5853/jos.2024.02061
Moyamoya Vasculopathy and Moyamoya-Related Systemic Vasculopathy: A Review With Histopathological and Genetic Viewpoints.
Stroke
Systemic vasculopathy has occasionally been reported in cases of moyamoya disease (MMD). Since the pathological relationship between moyamoya vasculopathy (MMV) and moyamoya-related systemic vasculopathy (MMRSV) remains unclear, it was examined herein by a review of histopathologic studies in consideration of clinicopathological and genetic viewpoints. Although luminal stenosis was a common finding in MMV and MMRSV, histopathologic findings of vascular remodeling markedly differed. MMV showed intimal hyperplasia, marked medial atrophy, and redundant tortuosity of the internal elastic lamina, with outer diameter narrowing called negative remodeling. MMRSV showed hyperplasia, mainly in the intima and sometimes in the media, with disrupted stratification of the internal elastic lamina. Systemic vasculopathy has also been observed in patients with non-MMD carrying the RNF213 (ring finger protein 213) mutation, leading to the concept of RNF213 vasculopathy. RNF213 vasculopathy in patients with non-MMD was histopathologically similar to MMRSV. Cases of MMRSV have sometimes been diagnosed with fibromuscular dysplasia. Fibromuscular dysplasia is similar to MMD not only in the histopathologic findings of MMRSV but also from clinicopathological and genetic viewpoints. The significant histopathologic difference between MMV and MMRSV may be attributed to a difference in the original vascular wall structure and its resistance to pathological stress between the intracranial and systemic arteries. To understand the pathogeneses of MMD and MMRSV, a broader perspective that includes RNF213 vasculopathy and fibromuscular dysplasia as well as an examination of the 2- or multiple-hit theory consisting of genetic factors, vascular structural conditions, and vascular environmental factors, such as blood immune cells and hemodynamics, are needed.
10.1161/STROKEAHA.124.046999
Association of cognitive function and hypoperfusion in Moyamoya disease patients without stroke.
Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
The influence of hypoperfusion on cognition in patients with Moyamoya disease (MMD) is unclear. This study investigated cognitive function changes in MMD patients without stroke and illustrated the relationship between cognitive impairment and hypoperfusion. We prospectively performed a structured battery of seven neurocognitive tests on 115 adult MMD patients without stroke and 82 healthy controls. Hemodynamic assessment was performed using dynamic susceptibility contrast-enhanced MRI. The best subset regression (BSR) strategy was used to identify risk factors. Global cognition (MoCA), speed of information processing (TMT-A), executive function (TMT-B), visuospatial function (CDT), and verbal memory (CAVLT) were significantly poorer in MMD patients without stroke than in healthy controls. The TMT-B score significantly correlated with cerebral blood flow (CBF) in the bilateral lateral frontal lobes, centrum semiovale, and temporal lobes. The TMT-A and CAVLT scores significantly correlated with CBF in the left centrum semiovale (L-CSO) and temporal lobes. According to the BSR results, age, education, white matter lesions, and hypoperfusion of the L-CSO were risk factors for cognitive impairment. Hypoperfusion leads to multiple cognitive impairments in MMD patients without stroke. The perfusion of particular areas may help evaluate the cognitive function of MMD patients and guide therapeutic strategies.
10.1177/0271678X221140349
Rare variants in ANO1, encoding a calcium-activated chloride channel, predispose to moyamoya disease.
Brain : a journal of neurology
Moyamoya disease, a cerebrovascular disease leading to strokes in children and young adults, is characterized by progressive occlusion of the distal internal carotid arteries and the formation of collateral vessels. Altered genes play a prominent role in the aetiology of moyamoya disease, but a causative gene is not identified in the majority of cases. Exome sequencing data from 151 individuals from 84 unsolved families were analysed to identify further genes for moyamoya disease, then candidate genes assessed in additional cases (150 probands). Two families had the same rare variant in ANO1, which encodes a calcium-activated chloride channel, anoctamin-1. Haplotype analyses found the families were related, and ANO1 p.Met658Val segregated with moyamoya disease in the family with an LOD score of 3.3. Six additional ANO1 rare variants were identified in moyamoya disease families. The ANO1 rare variants were assessed using patch-clamp recordings, and the majority of variants, including ANO1 p.Met658Val, displayed increased sensitivity to intracellular Ca2+. Patients harbouring these gain-of-function ANO1 variants had classic features of moyamoya disease, but also had aneurysm, stenosis and/or occlusion in the posterior circulation. Our studies support that ANO1 gain-of-function pathogenic variants predispose to moyamoya disease and are associated with unique involvement of the posterior circulation.
10.1093/brain/awad172
Endothelial Cell-Derived Let-7c-Induced TLR7 Activation on Smooth Muscle Cell Mediate Vascular Wall Remodeling in Moyamoya Disease.
Translational stroke research
Moyamoya disease (MMD) is characterized by frequent migration and phenotypic transformation of vascular smooth muscle cells (VSMCs) in the intima layer of blood vessels. However, the underlying mechanism is unclear. Toll-like receptor (TLR) 7 is abundantly expressed in smooth muscle cells (SMCs) in multiple vascular diseases, which might be linked to the disease-associated vascular remodeling. In the present study, the expression of TLR7 in MMD vessels was examined using the superficial temporal artery (STA) and middle cerebral artery (MCA) from MMD patients. Furthermore, the effect of TLR7 activation on the VSMC phenotype switch in vitro and vascular remodeling in vivo was assessed using a 9.4Tesla MRI. Our results demonstrated that the TLR7 and microRNA Let-7c expression are upregulated in VSMCs and the plasma of MMD patients, respectively. Additionally, TLR7 stimulation by Let-7c or Imiquimod induces a synthetic phenotype switch in VSMCs. Mechanistic studies revealed that Akt/mTOR signaling is responsible for this TLR-induced VSMC phenotypic switch. The Let-7c or Imiquimod treatment also resulted in reduced blood flow of internal carotid arteries (ICAs) in an in vivo model, while TLR7 inhibition attenuated the ICA stenosis. Besides, Let-7c was also found to be elevated in the hypoxic endothelial cells. Taken together, our study demonstrates that Let-7c released by endothelial cells under hypoxic conditions may activate TLR7 on VSMCs, ultimately leading to the phenotype switch and vascular wall remodeling. These findings thus elucidate the putative mechanisms underlying progressive stenosis of blood vessels in MMD and provide prospective therapeutic targets for further exploration.
10.1007/s12975-022-01088-3
Long-term outcomes of moyamoya disease versus atherosclerosis-associated moyamoya vasculopathy using high-resolution MR vessel wall imaging.
Journal of neurology, neurosurgery, and psychiatry
OBJECTIVES:We aimed to compare the long-term outcomes and surgical benefits between moyamoya disease (MMD) and atherosclerosis-associated moyamoya vasculopathy (AS-MMV) using high-resolution MRI (HRMRI). METHODS:MMV patients were retrospectively included and divided into the MMD and AS-MMV groups according to vessel wall features on HRMRI. Kaplan-Meier survival and Cox regression were performed to compare the incidence of cerebrovascular events and prognosis of encephaloduroarteriosynangiosis (EDAS) treatment between MMD and AS-MMV. RESULTS:Of the 1173 patients (mean age: 42.4±11.0 years; male: 51.0%) included in the study, 881 were classified into the MMD group and 292 into the AS-MMV group. During the average follow-up of 46.0±24.7 months, the incidence of cerebrovascular events in the MMD group was higher compared with that in the AS-MMV group before (13.7% vs 7.2%; HR 1.86; 95% CI 1.17 to 2.96; p=0.008) and after propensity score matching (6.1% vs 7.3%; HR 2.24; 95% CI 1.34 to 3.76; p=0.002). Additionally, patients treated with EDAS had a lower incidence of events than those not treated with EDAS, regardless of whether they were in the MMD (HR 0.65; 95% CI 0.42 to 0.97; p=0.043) or AS-MMV group (HR 0.49; 95% CI 0.51 to 0.98; p=0.048). CONCLUSIONS:Patients with MMD had a higher risk of ischaemic stroke than those with AS-MMV, and patients with both MMD and AS-MMV could benefit from EDAS. Our findings suggest that HRMRI could be used to identify those who are at a higher risk of future cerebrovascular events.
10.1136/jnnp-2022-330542
Vessel wall enhancement as a predictor of arterial stenosis progression and poor outcomes in moyamoya disease.
European radiology
OBJECTIVES:This study aimed to determine the association between vessel wall enhancement and progression of arterial stenosis and clinical outcomes in patients with moyamoya (MMD) using high-resolution magnetic resonance (HRMR) vessel wall imaging. METHODS:Consecutive participants diagnosed with MMD were prospectively recruited and underwent HRMR at baseline and during follow-up, which had an interval period of ≥ 6 months and were clinically followed up for ≤ 24 months to record the occurrence of ischemic stroke. The relationship between vessel wall enhancement and arterial stenosis progression and stroke occurrence was evaluated. RESULTS:HRMR vessel wall imaging was used to identify 309 stenotic lesions at the internal carotid artery (ICA) in 170 participants (mean age: 37.7 ± 11.3 years old, male: 44.1%). The baseline presence (adjusted odds ratio [aOR] = 3.57, 95% CI = 1.97-6.44, p < 0.001) and progression (aOR = 2.96, 95% CI = 1.29-6.80, p = 0.010) of vessel wall enhancement and middle cerebral artery (MCA) involvement (aOR = 4.98, 95% CI = 1.50-16.52, p = 0.009) were significantly associated with rapid progression of arterial stenosis. Furthermore, vessel wall enhancement (adjusted HR = 3.59, 95% CI = 1.33-9.70, p = 0.011) and rapid progression of arterial stenosis (adjusted HR = 4.52, 95% CI = 1.48-13.81, p = 0.008) were correlated with future stroke occurrence. CONCLUSION:The baseline presence of vessel wall enhancement was associated with rapid progression of arterial stenosis and increased risk for stroke in MMD patients. Our findings suggest that vessel wall enhancement may serve as a predictor of disease progression and poor outcomes in MMD. KEY POINTS:• The baseline presence of vessel wall enhancement was significantly associated with the rapid progression of arterial stenosis. • The baseline presence of vessel wall enhancement and rapid progression of arterial stenosis were both correlated with increased risk for future occurrence of stroke. • Our findings suggest that vessel wall enhancement may serve as a predictor of rapid progression of arterial stenosis and poor outcomes in MMD patients.
10.1007/s00330-022-09223-2
The diagnostic performance of high-resolution magnetic resonance-vessel wall imaging in differentiating atherosclerosis-associated moyamoya vasculopathy from moyamoya disease.
European radiology
OBJECTIVES:To evaluate the diagnostic performance of high-resolution magnetic resonance-vessel wall imaging (HRMR-VWI) in differentiating moyamoya disease (MMD) from atherosclerosis-associated moyamoya vasculopathy (AS-MMV) and investigate an accurate approach for the differential diagnosis. METHODS:Adult patients who were diagnosed as MMD or AS-MMV and underwent HRMR-VWI were retrospectively included. The three vessel wall features (outer diameter (OD), remodeling index (RI), and pattern of vessel wall thickening) of middle cerebral artery (MCA) in identifying MMD from AS-MMV were assessed and compared. Furthermore, subgroup analysis stratified by degree of luminal stenosis was performed and the cutoff values of different vessel wall features in differentiating MMD from AS-MMV were also calculated. RESULTS:A total of 265 patients (160 cases of MMD and 105 AS-MMV) were included. Patients with AS-MMV had greater OD and RI and were more likely to exhibit eccentric thickening of vessel wall compared to those with MMD (all p < 0.001). The ROC analysis showed that the AUC value of OD was greater than that of RI (0.912 vs. 0.889, p = 0.007) in differentiating MMD from AS-MMV, and their corresponding cutoff values were 1.77 mm and 0.27, respectively. And the AUC value of pattern of vessel wall thickening was 0.786 in non-occluded patients. With the increase of lumen stenosis, the discrimination power of the three indicators enhanced correspondingly. CONCLUSIONS:HRMR-VWI is valuable in distinguishing MMD from AS-MMV. The OD of MCA has better diagnostic performance in differentiating AS-MMV from MMD compared to RI and pattern of vessel wall thickening. CLINICAL RELEVANCE STATEMENT:The outer diameter of the involved artery proved to be both accurate and convenient in distinguishing atherosclerosis-associated moyamoya vasculopathy from moyamoya disease and may provide a quantitative reference for clinical diagnosis. KEY POINTS:High-resolution magnetic resonance-vessel wall imaging is valuable in distinguishing atherosclerosis-associated moyamoya vasculopathy from moyamoya disease. Compared to remodeling index and pattern of vessel wall thickening, outer diameter is more accurate in differentiating atherosclerosis-associated moyamoya vasculopathy from moyamoya disease. With the increase of lumen stenosis, the discrimination power of outer diameter, remodeling index, and pattern of vessel wall thickening enhanced correspondingly.
10.1007/s00330-023-09951-z
The ivy sign as a radiological marker for follow-up of postoperative cerebral perfusion status in adult moyamoya disease.
Journal of neurosurgery
OBJECTIVE:Little is known about the relationship between postoperative changes in cerebral perfusion and the ivy sign representing leptomeningeal collateral burden in moyamoya disease (MMD). This study aimed to investigate the usefulness of the ivy sign in evaluating cerebral perfusion status following bypass surgery in patients with adult MMD. METHODS:Two hundred thirty-three hemispheres in 192 patients with adult MMD undergoing combined bypass between 2010 and 2018 were retrospectively enrolled. The ivy sign was represented as the ivy score on FLAIR MRI in each territory of the anterior, middle, and posterior cerebral arteries. Ivy scores, as well as clinical and hemodynamic states on SPECT, were semiquantitatively compared both preoperatively and at 6 months after surgery. RESULTS:Clinical status improved at 6 months after surgery (p < 0.01). On average, ivy scores in whole and individual territories were decreased at 6 months (all p values < 0.01). Cerebral blood flow (CBF) postoperatively improved in three individual vascular territories (all p values ≤ 0.03) except for the posterior cerebral artery territory (PCAt), and cerebrovascular reserve (CVR) improved in those areas (all p values ≤ 0.04) except for the PCAt. Postoperative changes in ivy scores and CBF were inversely correlated in all territories (p ≤ 0.02), except for the PCAt. Furthermore, changes in ivy scores and CVR were only correlated in the posterior half of the middle cerebral artery territory (p = 0.01). CONCLUSIONS:The ivy sign was significantly decreased after bypass surgery, which was well correlated with postoperative hemodynamic improvement in the anterior circulation territories. The ivy sign is believed to be a useful radiological marker for postoperative follow-up of cerebral perfusion status.
10.3171/2023.4.JNS23294
Association between DIAPH1 variant and posterior circulation involvement with Moyamoya disease.
Scientific reports
Moyamoya disease (MMD) is a chronic and progressive cerebrovascular stenosis or occlusive disease that occurs near Willis blood vessels. The aim of this study was to investigate the mutation of DIAPH1 in Asian population, and to compare the angiographic features of MMD patients with and without the mutation of the DIAPH1 gene. Blood samples of 50 patients with MMD were collected, and DIAPH1 gene mutation was detected. The angiographic involvement of the posterior cerebral artery was compared between the mutant group and the non-mutant group. The independent risk factors of posterior cerebral artery involvement were determined by multivariate logistic regression analysis. DIAPH1 gene mutation was detected in 9 (18%) of 50 patients, including 7 synonymous mutations and 2 missense mutations. However, the incidence of posterior cerebral artery involvement in mutation positive group was very higher than that in mutation negative group (77.8% versus 12%; p = 0.001). There is an association between DIAPH1 mutation and PCA involvement (odds ratio 29.483, 95% confidence interval 3.920-221.736; p = 0.001). DIAPH1 gene mutation is not a major genetic risk gene for Asian patients with moyamoya disease but may play an important role in the involvement of posterior cerebral artery.
10.1038/s41598-023-37665-1
The value of indocyanine green-FLOW800 in microvasculature for predicting cerebral hyperperfusion syndrome in moyamoya disease patients.
Scientific reports
Among the notable complications of direct hemodynamic reconstruction for moyamoya disease (MMD) is cerebral hyperperfusion syndrome (CHS). In this study, we evaluated hemodynamic changes in small regional microvasculature (SRMV) around the anastomosis site by using indocyanine green (ICG)-FLOW800 video angiography and verified that it better predicted the onset of CHS. Intraoperative ICG-FLOW800 analysis was performed on 31 patients (36 cerebral hemispheres) with MMD who underwent superficial temporal artery-middle cerebral artery (MCA) bypass grafting at our institution. The regions of interest were established in the SRMV and thicker MCA around the anastomosis. Calculations were made for half-peak to time (TTP), cerebral blood volume (CBV), and cerebral blood flow (CBF). According to the presence or absence of CHS after surgery, CHS and non-CHS groups of patients were separated. The results showed that ΔCBV and ΔCBF were substantially greater in SRMV than in MCA (p < 0.001). Compared with the non-CHS group, ΔCBF and ΔCBV of SRMV and MCA were considerably greater in the CHS group (p < 0.001). ΔCBF and ΔCBV on the ROC curve for both SRMV and MCA had high sensitivity and specificity (SRMV: ΔCBF, AUC = 0.8586; ΔCBV, AUC = 0.8158. MCA: ΔCBF, AUC = 0.7993; ΔCBV, AUC = 0.8684). ICG-FLOW800 video angiography verified the differential hemodynamic changes in the peri-anastomotic MCA and SRMV before and after bypass surgery in patients with MMD.
10.1038/s41598-023-45676-1
Adult Moyamoya Disease and Syndrome: Current Perspectives and Future Directions: A Scientific Statement From the American Heart Association/American Stroke Association.
Stroke
Adult moyamoya disease and syndrome are rare disorders with significant morbidity and mortality. A writing group of experts was selected to conduct a literature search, summarize the current knowledge on the topic, and provide a road map for future investigation. The document presents an update in the definitions of moyamoya disease and syndrome, modern methods for diagnosis, and updated information on pathophysiology, epidemiology, and both medical and surgical treatment. Despite recent advancements, there are still many unresolved questions about moyamoya disease and syndrome, including lack of unified diagnostic criteria, reliable biomarkers, better understanding of the underlying pathophysiology, and stronger evidence for treatment guidelines. To advance progress in this area, it is crucial to acknowledge the limitations and weaknesses of current studies and explore new approaches, which are outlined in this scientific statement for future research strategies.
10.1161/STR.0000000000000443
Surgical outcomes following encephaloduroarteriosynangiosis in adult moyamoya disease associated with Type 2 diabetes.
Ren Bin,Zhang Zheng-Shan,Liu Wei-Wei,Bao Xiang-Yang,Li De-Sheng,Han Cong,Xian Peng,Zhao Feng,Wang Hui,Wang Hai,Duan Lian
Journal of neurosurgery
OBJECTIVE Debate exists regarding the merits and shortcomings of an indirect bypass procedure for treating adult patients with moyamoya disease (MMD). Considerable variation in neovascularization occurs among different organs in patients with diabetes mellitus. Here, the effect of encephaloduroarteriosynangiosis on MMD associated with Type 2 diabetes mellitus (T2DM) is evaluated. METHODS A retrospective and 1:2 matched case-control study was conducted in moyamoya patients with or without T2DM (n = 180). Postoperative collateral formations were graded according to the Modified Collateral Grading System that originated from the Matsushima Angiographic Stage Classification. Neurological function outcomes before and after the operation were evaluated according to the modified Rankin Scale. Univariate and multivariate logistic regression analyses were performed to determine the risk factors for clinical outcome. RESULTS There was no statistically significant difference in the constituent ratios of initial symptom and preoperative Suzuki stage between patients with and without T2DM. Progression of angiopathy around the circle of Willis was postoperatively observed in bilateral internal carotid arteries in both groups. Patients with T2DM had a higher postoperative Suzuki stage (p < 0.01) and more frequent development of collateral angiogenesis germinating from the external carotid after indirect revascularization procedures in the surgical cerebral hemisphere (82.7% vs 72.2%; p < 0.05). The extent of postoperative collateral formation in patients with diabetes mellitus was significantly higher (p < 0.01). Postoperative clinical improvement in the diabetes group was more common after revascularization procedures (p < 0.05), and the diabetes group had lower modified Rankin Scale scores (p < 0.05) in comparison with the nondiabetes group. Late postoperative stroke and posterior cerebral artery involvement were identified as predictors of unfavorable clinical outcome in both groups, while T2DM was associated with a favorable clinical outcome. CONCLUSIONS Encephaloduroarteriosynangiosis is an efficacious treatment for adult patients with MMD. Patients with T2DM could achieve better collateral circulation and clinical improvement following surgery.
10.3171/2015.7.JNS15218
Proteome Profiling of the Dura Mater in Patients with Moyamoya Angiopathy.
International journal of molecular sciences
Moyamoya angiopathy (MMA) is an uncommon cerebrovascular disease characterized by a progressive steno-occlusive lesion of the internal carotid artery and the compensatory development of an unstable network of collateral vessels. These vascular hallmarks are responsible for recurrent ischemic/hemorrhagic strokes. Surgical treatment represents the preferred procedure for MMA patients, and indirect revascularization may induce a spontaneous angiogenesis between the brain surface and dura mater (DM), whose function remains rather unknown. A better understanding of MMA pathogenesis is expected from the molecular characterization of DM. We performed a comprehensive, label-free, quantitative mass spectrometry-based proteomic characterization of DM. The 30 most abundant identified proteins were located in the extracellular region or exosomes and were involved in extracellular matrix organization. Gene ontology analysis revealed that most proteins were involved in binding functions and hydrolase activity. Among the 30 most abundant proteins, Filamin A is particularly relevant because considering its well-known biochemical functions and molecular features, it could be a possible second hit gene with a potential role in MMA pathogenesis. The current explorative study could pave the way for further analyses aimed at better understanding such uncommon and disabling intracranial vasculopathy.
10.3390/ijms241311194