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BACKGROUND: Surgical revascularization decreases the long-term risk of stroke in children with moyamoya arteriopathy but can be associated with an increased risk of stroke during the perioperative period. Evidence-based approaches to optimize perioperative management are limited and practice varies widely. Using a modified Delphi process, we sought to establish expert consensus on key components of the perioperative care of children with moyamoya undergoing indirect revascularization surgery and identify areas of equipoise to define future research priorities. METHODS: Thirty neurologists, neurosurgeons, and intensivists practicing in North America with expertise in the management of pediatric moyamoya were invited to participate in a three-round, modified Delphi process consisting of a 138-item practice patterns survey, anonymous electronic evaluation of 88 consensus statements on a 5-point Likert scale, and a virtual group meeting during which statements were discussed, revised, and reassessed. Consensus was defined as ≥ 80% agreement or disagreement. RESULTS: Thirty-nine statements regarding perioperative pediatric moyamoya care for indirect revascularization surgery reached consensus. Salient areas of consensus included the following: (1) children at a high risk for stroke and those with sickle cell disease should be preadmitted prior to indirect revascularization; (2) intravenous isotonic fluids should be administered in all patients for at least 4 h before and 24 h after surgery; (3) aspirin should not be discontinued in the immediate preoperative and postoperative periods; (4) arterial lines for blood pressure monitoring should be continued for at least 24 h after surgery and until active interventions to achieve blood pressure goals are not needed; (5) postoperative care should include hourly vital signs for at least 24 h, hourly neurologic assessments for at least 12 h, adequate pain control, maintaining normoxia and normothermia, and avoiding hypotension; and (6) intravenous fluid bolus administration should be considered the first-line intervention for new focal neurologic deficits following indirect revascularization surgery. CONCLUSIONS: In the absence of data supporting specific care practices before and after indirect revascularization surgery in children with moyamoya, this Delphi process defined areas of consensus among neurosurgeons, neurologists, and intensivists with moyamoya expertise. Research priorities identified include determining the role of continuous electroencephalography in postoperative moyamoya care, optimal perioperative blood pressure and hemoglobin targets, and the role of supplemental oxygen for treatment of suspected postoperative ischemia.

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. [ABSTRACT FROM AUTHOR]

To explore the relationship between morphological and hemodynamic parameters, baseline characteristics, and long-term outcomes in patients with moyamoya disease (MMD) using a computational fluid dynamics model. We retrospectively reviewed 129 patients at Beijing Tiantan hospital between July 2020 and December 2021. Perioperative clinical variables and Suzuki stage were recorded. Logistic regression analysis was employed to identify the risk factors for unfavorable long-term outcomes. The association between morphological, CT perfusion parameters, hemodynamic parameters and the Suzuki stage, clinical variables of MMD was also analyzed. Patients with high relative Wall Shear Stress (rWSS) were older and had more cases with higher Suzuki stage and worse follow-up mRS scores (p < 0.05). High rWSS at the terminal ICA and diabetes mellitus were identified as independent predictors of unfavorable long-term outcomes [OR = 3.039(1.191–7.754), p = 0.020; OR = 3.164(1.141–8.723), p = 0.027, respectively]. ROC analysis demonstrated that predictive models incorporating rWSS improved AUC values, with the highest AUC in Model 2 (AUC = 0.889). High rWSS was significantly associated with future TIA and stroke events (p = 0.032). We speculated that high rWSS and diabetes mellitus were independent risk factors for unfavorable long-term outcomes in patients with MMD. rWSS and morphological parameters are crucial for predicting MMD progression and understanding its pathogenesis. [ABSTRACT FROM AUTHOR]

The effects of RNF213, which leads to moyamoya disease susceptibility, on radiation-induced moyamoya syndrome (MMS) remain unknown. We report a case of MMS after proton beam therapy (PBT) was deployed to treat a brain tumor in a patient with an RNF213 polymorphism. An 8-year-old boy underwent whole ventricular and local PBT for a pineal germ cell tumor and was diagnosed with radiation-induced MMS 9 months later. He underwent right and left revascularization surgeries for cerebral hemodynamic compromise at 17- and 18-years of age, respectively. Genetic analysis revealed a heterozygous germline polymorphism RNF213 p.R4810K. This is the first report to suggest an association between RNF213 polymorphism and radiation-induced MMS. [ABSTRACT FROM AUTHOR]

Cerebral hyperperfusion syndrome (CHS) is a serious complication after bypass surgery in Moyamoya disease (MMD), with autoregulatory dysfunction being a major pathogenesis. This study investigated the change of perioperative autoregulation and preoperative prognostic potentials in MMD with postoperative CHS. Among 26 hemispheres in 24 patients with adult MMD undergoing combined bypass, 13 hemispheres experienced postoperative CHS. Arterial blood pressure and cerebral blood flow velocity were perioperatively measured with transcranial Doppler ultrasound during resting and the Valsalva maneuver (VM). Autoregulation profiles were discovered in both the CHS and non-CHS groups using mean flow index (Mxa), VM Autoregulatory Index (VMAI), and a new metric termed VM Overshooting Index (VMOI). The CHS group had inferior autoregulation than the non-CHS group as indicated by VMOI on preoperative day 1 and postoperative 3rd day. Deteriorated autoregulation was observed via Mxa in the CHS group than in the non-CHS group on the postoperative 3rd and discharge days. Postoperative longitudinal autoregulation recovery in the CHS group was found in a logistic regression model with diminished group differences over the time course. This work represents a step forward in utilizing autoregulation indices derived from physiological signals, to predict the postoperative CHS in adult MMD. [ABSTRACT FROM AUTHOR]

Recurrent stroke after revascularization surgeries predicts poor outcome in patients with moyamoya disease (MMD). Early identification of patients with stroke risk paves the way for rescue intervention. This study aimed to investigate the role of ultrasound in identifying patients at risk of post-operative ischemic events (PIEs). This prospective study enrolled patients with symptomatic MMD who underwent indirect revascularization surgeries. Ultrasound examinations were performed preoperatively and at 3 mo post-operatively to evaluate the hemodynamic changes in extracranial and intracranial arteries on the operated side. PIE was defined as ischemic stroke or transient ischemic attack in the operated hemisphere within 1 y. The areas under receiver operating characteristic curves were compared between models for prediction of PIE. A total of 56 operated hemispheres from 36 patients (mean age, 23.0 ± 18.5 y) were enrolled in this study, and 27% developed PIE. In multivariate logistic regression models, PIE was associated with lower end-diastolic velocity and flow volume (FV) of the ipsilateral external carotid artery (ECA), and lower FV of ipsilateral superficial temporal artery and occipital artery at 3 mo post-operatively (all p < 0.05). Moreover, the post-operative FV of the ipsilateral ECA was the only one factor that significantly increased the areas under receiver operating characteristic curves from 0.727 to 0.932 when adding to a clinical–angiographic model for prediction of PIE (p = 0.017). This parameter was significantly lower in hemispheres with PIE, both in adult and pediatric patients. After indirect revascularization, surgeries in patients with symptomatic MMD, FV of ipsilateral ECA at 3 mo helps clinicians to identify patients at risk of PIE. [ABSTRACT FROM AUTHOR]

The safety and efficacy of coronavirus disease 2019 (COVID-19) vaccination in patients diagnosed with Moyamoya disease (MMD) have not been established. Using National Health Insurance Service data, this study analyzed the occurrence of stroke-related events and mortality following COVID-19 vaccination among patients diagnosed with MMD from 2008 to 2020. Among 10,297 MMD patients, 296 (2.9%) experienced events and 175 (1.7%) died in 2021. Significant risk factors for events included ages 50–59 (Odds Ratio [OR] 3.29; P = 0.022) and 60 or above (OR 5.20; P = 0.001) (reference group: age in 20s), low BMI (OR 2.00; P = 0.011), previous stroke (OR 1.96; P < 0.001), and COVID-19 infection (OR 2.28; P = 0.034). Female (OR 0.64 [95% CI 0.50–0.82]; p = 0.011), revascularization surgery (RS) (OR 0.38 [95% CI 0.21–0.70]; p < 0.001), and vaccination (OR 0.17 [95% CI 0.13–0.22]; p < 0.001) were associated with reduced odds of stroke-related events. For mortality, significant risks were age over 60 (OR 7.09; P = 0.008), low BMI (OR 3.87; P = 0.001), and prior stroke (OR 1.74; p = 0.004), while being female, RS (OR 0.41; P = 0.022), and vaccination (OR 0.12; P < 0.001) were associated with a lower frequency of mortality. mRNA vaccines were associated with a significantly lower incidence of events, mortality, and COVID-19 infections compared to vector vaccines. COVID-19 vaccination is linked to reduced stroke-related events and mortality in MMD patients, with mRNA vaccines showing a significantly lower incidence compared to vector vaccines. COVID-19 infection raises the risk of events, underscoring the benefit of vaccination. [ABSTRACT FROM AUTHOR]

Changes in local cerebral blood flow (CBF) are a major cause of transient neurological events (TNEs) after revascularization for moyamoya disease (MMD); however, the influence of preoperative collateral pathway development on TNEs has not yet been investigated. This study included 28 hemispheres from 28 consecutive patients with MMD who underwent surgical revascularization, including a superficial temporal artery (STA) to middle cerebral artery (MCA) bypass, between January 2014 and March 2022. The collateralization pathways included the anterior communicating artery (AcomA) collaterals, posterior communicating artery (PcomA) collaterals, transdural collaterals, posterior pericallosal anastomosis, lenticulostriate anastomosis, thalamic anastomosis, and choroidal anastomosis. These collateral pathways were analyzed to identify predictive factors significantly associated with TNEs. TNEs were observed in 11 (39.3%) hemispheres. The development of posterior pericallosal anastomosis and choroidal anastomosis was a significant independent predictor of the occurrence of TNEs after bypass surgery for MMD (P = 0.01, OR 26.9, 95% CI 1.50–480.0; P = 0.002, OR 47.6, 95% CI 2.65–856.6). The development of choroidal and posterior pericallosal anastomosis could be reliable preoperative predictors of TNEs after bypass surgery for MMD. Our results provide useful information for future studies aimed at clarifying the mechanisms underlying TNEs. [ABSTRACT FROM AUTHOR]

Moyamoya vasculopathy secondary to various genetic disorders is classified as moyamoya syndrome (MMS). Recent studies indicate MMS occurs due to a combination of genetic modifiers and causative mutations for the primary genetic disorders. We performed whole-exome sequencing (WES) in 13 patients with various genetic disorders who developed MMS. WES successfully revealed the genetic diagnoses of neurofibromatosis type 1 (NF-1), Down syndrome, multisystemic smooth muscle dysfunction syndrome, Noonan syndrome, and alpha thalassemia. The previously reported modifier genes, RNF213 and MRVI1, were confirmed in the NF-1 and Down syndrome cases. Further analysis revealed rare hypomorphic variants in the causative genes of the primary disorders underlying MMS, such as Alagille syndrome and Rasopathies, conferred susceptibility to MMS. Genes involved in the development of pulmonary arterial hypertension (PAH), such as ABCC8 and BMPR2, were also identified as potential modifiers. The rare variants in the MMS and PAH genes were significantly enriched in the eight Japanese patients with MMS compared with the 104 Japanese individuals from the 1000 Genomes Project. Disease genes associated with the arterial occlusive conditions represented by those of Rasopathies and PAH may provide novel diagnostic markers and future therapeutic targets for MMS as well as moyamoya disease with an unknown cause. [ABSTRACT FROM AUTHOR]

Moyamoya disease (MMD) is closely associated with the Ring Finger Protein 213 (RNF213), a susceptibility gene for MMD. However, its biological function remains unclear. We aimed to elucidate the role of RNF213 in the damage incurred by human endothelial cells under oxygen-glucose deprivation (OGD). We analyzed autophagy in peripheral blood mononuclear cells (PBMCs) derived from patients carrying either RNF213 wildtype (WT) or variant (p.R4810K). Subsequently, human umbilical vein endothelial cells (HUVECs) were transfected with RNF213 WT (HUVECWT) or p.R4810K (HUVECR4810K) and exposed to OGD for 2 h. Immunoblotting was used to analyze autophagy marker proteins, and endothelial function was analyzed by tube formation assay. Autophagic vesicles were observed using transmission electron microscopy. Post-OGD exposure, we administered rapamycin and cilostazol as potential autophagy inducers. The RNF213 variant group during post-OGD exposure (vs. pre-OGD) showed autophagy inhibition, increased protein expression of SQSTM1/p62 (p < 0.0001) and LC3-II (p = 0.0039), and impaired endothelial function (p = 0.0252). HUVECR4810K during post-OGD exposure (versus pre-OGD) showed a remarkable increase in autophagic vesicles. Administration of rapamycin and cilostazol notably restored the function of HUVECR4810K and autophagy. Our findings support the pivotal role of autophagy impaired by the RNF213 variant in MMD-induced endothelial cell dysfunction. [ABSTRACT FROM AUTHOR]

Moyamoya disease (MMD) causes cerebral arterial stenosis and hemodynamic disturbance, the latter of which may disrupt glymphatic system activity, the waste clearance system. We evaluated 46 adult patients with MMD and 33 age- and sex-matched controls using diffusivity along the perivascular space (ALPS) measured with diffusion tensor imaging (ALPS index), which may partly reflect glymphatic system activity, and multishell diffusion MRI to generate freewater maps. Twenty-three patients were also evaluated via 15O-gas positron emission tomography (PET), and all patients underwent cognitive tests. Compared to controls, patients (38.4 (13.2) years old, 35 females) had lower ALPS indices in the left and right hemispheres (1.94 (0.27) vs. 1.65 (0.25) and 1.94 (0.22) vs. 1.65 (0.19), P < 0.001). While the right ALPS index showed no correlation, the left ALPS index was correlated with parenchymal freewater (ρ = −0.47, P < 0.001); perfusion measured with PET (cerebral blood flow, ρ = 0.70, P < 0.001; mean transit time, ρ = −0.60, P = 0.003; and oxygen extraction fraction, ρ = −0.52, P = 0.003); and cognitive tests (trail making test part B for executive function; ρ = −0.37, P = 0.01). Adult patients with MMD may exhibit decreased glymphatic system activity, which is correlated with the degree of hemodynamic disturbance, increased interstitial freewater, and cognitive dysfunction, but further investigation is needed. [ABSTRACT FROM AUTHOR]

Hemorrhagic moyamoya disease (HMMD) can result in poor outcomes. Serum biomarkers may play a significant role in predicting HMMD outcomes. This study retrospectively analyzed the correlation between serum biomarkers at the time of admission and outcomes for patients with HMMD. We evaluated 270 patients with HMMD admitted to Yijishan Hopital of Wannan Medical College between July 2017 and April 2023. The patients were categorized into 2 groups according to their modified Rankin Scale scores at 3 months after discharge. Univariate and multivariate analyses were used to identify the associations between biomarkers and clinical outcomes. Receiver operating characteristic curves were obtained to investigate the potential of the biomarkers for predicting prognosis. Of the 270 patients analyzed, 96 (35.6%) had unfavorable outcomes. The potential predictors were identified using the univariate analysis. The subsequent multivariate logistic regression analysis showed that the systemic inflammatory response index (SIRI) (odds ratio 0.86, 95% confidence interval 0.75–0.98, P = 0.028] and serum glucose to potassium ratio (GPR) (odds ratio 0.53, 95% confidence interval 0.38–0.76, P < 0.001) were independent risk factors of poor outcomes. The receiver operating characteristic analysis indicated that patients with a higher SIRI (≥2.12) and GPR (≥1.75) levels were more likely to have unfavorable outcomes. An elevated GPR and SIRI at admission were associated with a poor clinical outcome at the 3-month follow-up for patients with HMMD. Therefore, these biomarkers could be considered in future management decisions for these patients. [ABSTRACT FROM AUTHOR]

Surgery is the mainstay of stroke prevention in patients with symptomatic moyamoya disease (MMD). We present the results of a single-center retrospective study of indirect revascularization surgery for adult MMD, emphasizing angiographic outcomes, including dilation of the superficial temporal artery and formation of new collaterals. A prospectively maintained database of procedures performed for MMD was reviewed. Adult patients treated with indirect revascularization and with long-term angiographic follow-up were included. Preoperative and postoperative angiographic images and baseline and procedural characteristics were analyzed. A Wilcoxon signed-rank test was used to test the hypothesis that the superficial temporal artery increases in diameter postoperatively. We identified 40 hemispheres in 27 patients, of which 35 had a sufficient angiographic follow-up. Bilateral procedures were performed on 16 patients. Most patients were female (72.5%), with a median age of 43 years old. The most common clinical presentation was ischemic stroke in 59.3% of cases. All patients underwent an encephaloduroarteriosynangiosis for treatment. A follow-up angiogram was performed at a median of 13.8 months postoperatively, showing superficial temporal artery (STA)-derived collaterals in 71.4% and collateral ingrowth via the burr holes in 61.8% of cases. Disease progression was evident in 34.3% of hemispheres. The normalized STA diameter was significantly increased postoperatively (2.4 to 3 mm; P < 0.05). A univariate analysis revealed that transdural collaterals and hyperlipidemia may affect collateral ingrowth from the STA, and no other patient- or procedure-related factors, including replacement of the bone flap, impacted on this. A significant increase in STA diameter on follow-up angiography after encephaloduroarteriosynangiosis was found; however, this was not directly associated with STA collateral development. Rates of postoperative transient ischemic attacks were low, and no patients had a new ischemic or hemorrhagic stroke at last follow-up. The presence of transdural collaterals and the absence of hyperlipidemia were associated with STA collateral development on follow-up angiography, but the causality of this finding is unclear. [ABSTRACT FROM AUTHOR]

Background: We report a case of 39-year-old male patient with an unruptured middle cerebral artery aneurysm associated with moyamoya disease (MMD) treated by surgical clipping combined with encephalo-duro-myo-synangiosis surgery. Case description: A 39-year-old male patient with a history of intraventricular hemorrhage was admitted to our hospital. Preoperative digital subtraction angiography (DSA) showed the aneurysm, arising from a collateral branch of the right middle cerebral artery (RMCA), had an extremely thin neck. Also present were an occlusion of the RMCA main trunk, and moyamoya vessels. Microsurgical aneurysm clipping was performed for the aneurysm, while encephalo-duro-myo-synangiosis was performed for ipsilateral MMD. At the 4-month follow-up, the patient had recovered well and DSA indicated improved cerebral perfusion with no de novo aneurysms. Conclusions: For ipsilateral moyamoya disease accompanied with intracranial aneurysm (IA), simultaneous surgery combining microsurgical clipping and encephalo-duro-myo-synangiosis can be a good treatment option. [ABSTRACT FROM AUTHOR]

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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. [ABSTRACT FROM AUTHOR]

Background: Systemic Lupus Erythematosus (SLE) is acknowledged for its significant influence on systemic health. This study sought to explore potential crosstalk genes, pathways, and immune cells in the relationship between SLE and moyamoya disease (MMD). Methods: We obtained data on SLE and MMD from the Gene Expression Omnibus (GEO) database. Differential expression analysis and weighted gene co-expression network analysis (WGCNA) were conducted to identify common genes. Subsequently, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed on these shared genes. Hub genes were further selected through the least absolute shrinkage and selection operator (LASSO) regression, and a receiver operating characteristic (ROC) curve was generated based on the results of this selection. Finally, singlesample Gene Set Enrichment Analysis (ssGSEA) was utilized to assess the infiltration levels of 28 immune cells in the expression profile and their association with the identified hub genes. Results: By intersecting the important module genes from WGCNA with the DEGs, the study highlighted CAMP, CFD, MYO1F, CTSS, DEFA3, NLRP12, MAN2B1, NMI, QPCT, KCNJ2, JAML, MPZL3, NDC80, FRAT2, THEMIS2, CCL4, FCER1A, EVI2B, CD74, HLA-DRB5, TOR4A, GAPT, CXCR1, LAG3, CD68, NCKAP1L, TMEM33, and S100P as key crosstalk genes linking SLE and MMD. GO analysis indicated that these shared genes were predominantly enriched in immune system process and immune response. LASSO analysis identified MPZL3 as the optimal shared diagnostic biomarkers for both SLE and MMD. Additionally, the analysis of immune cell infiltration revealed the significant involvement of activation of T and monocytes cells in the pathogenesis of SLE and MMD. Conclusion: This study is pioneering in its use of bioinformatics tools to explore the close genetic relationship between MMD and SLE. The genes CAMP, CFD, MYO1F, CTSS, DEFA3, NLRP12, MAN2B1, NMI, QPCT, KCNJ2, JAML, MPZL3, NDC80, FRAT2, THEMIS2, CCL4, FCER1A, EVI2B, CD74, HLA-DRB5, TOR4A, GAPT, CXCR1, LAG3, CD68, NCKAP1L, TMEM33, and S100P have been identified as key crosstalk genes that connect MMD and SLE. Activation of T and monocytes cells-mediated immune responses are proposed to play a significant role in the association between MMD and SLE. [ABSTRACT FROM AUTHOR]

Background: Systemic immune-inflammatory markers combine various individual inflammatory cell parameters to comprehensively explore their relationship with the development and long-term outcomes of cardiovascular, cerebrovascular, and oncological disorders. The systemic immune-inflammatory marker index has not been extensively studied in terms of its impact on the long-term prognosis following cerebral revascularization in MMD patients. Our research aims to address this gap and improve the prediction of long-term outcomes for these patients. Methods: We included 851 patients with Moyamoya disease who underwent cerebral revascularization at our medical center from 2009 to 2021. Systemic immune-inflammatory markers were calculated based on routine blood test results at admission, and follow-up was conducted for over 6 months after surgery. During monitoring and upon release, we evaluated patient neurological condition by utilizing the modified Rankin Scale (mRS). We examined the correlation between alterations in mRS ratings and systemic immuneinflammatory markers. Results: Comparing the unfavorable long-term prognosis group to the favorable long-term prognosis group, it was found that the NLR level was markedly higher (p = 0.037), while the LMR was lower in the unfavorable long-term prognosis group (p = 0.004). Results from logistic regression analysis revealed that the high-level LMR group had a lower risk of unfavorable long-term prognosis compared to the low-level group (T3: OR = 0.433, 95% CI [0.204-0.859], p = 0.026). The AUC of the model was 0.750 (95% CI [0.693-0.806]). Conclusion: Lymphocyte-to-monocyte ratio levels are independently linked to an increased risk of unfavorable long-term prognosis, highlighting LMR as a new and effective predictor for postoperative Moyamoya patients. [ABSTRACT FROM AUTHOR]

Background: Moyamoya disease (MMD) is a rare cerebrovascular disorder characterized by progressive steno-occlusive changes in the internal carotid arteries, leading to an abnormal vascular network. Hypertension is prevalent among MMD patients, raising concerns about its impact on disease outcomes. This study aims to compare the clinical characteristics and outcomes of MMD patients with and without hypertension. Methods: We conducted a multicenter, retrospective study involving 598 MMD patients who underwent surgical revascularization across 13 academic institutions in North America. Patients were categorized into hypertensive (n=292) and non-hypertensive (n=306) cohorts. Propensity score matching (PSM) was performed to adjust for baseline differences. Results: The mean age was higher in the hypertension group (46 years vs. 36.8 years, p < 0.001). Hypertensive patients had higher rates of diabetes mellitus (45.2% vs. 10.7%, p < 0.001) and smoking (48.8% vs. 27.1%, p < 0.001). Symptomatic stroke rates were higher in the hypertension group (16% vs. 7.1%; OR: 2.48; 95% CI: 1.39-4.40, p = 0.002) before matching. After PSM, there were no significant differences in symptomatic stroke rates (11.1% vs. 7.7%; OR: 1.5; CI: 0.64-3.47, p = 0.34), perioperative strokes (6.2% vs. 2.1%; OR 3.13; 95% CI: 0.83-11.82, p = 0.09), or good functional outcomes at discharge (93% vs. 92.3%; OR 1.1; 95% CI: 0.45-2.69, p = 0.82). Conclusion: No significant differences in symptomatic stroke rates, perioperative strokes, or functional outcomes were observed between hypertensive and non-hypertensive Moyamoya patients. Appropriate management can lead to similar outcomes in both groups. Further prospective studies are required to validate these findings. [ABSTRACT FROM AUTHOR]

Moyamoya disease (MMD) is a chronic, rare cerebrovascular disorder of unknown cause featured by extensive narrowing of the terminal internal carotid artery (ICA) and its main branches. As a compensatory mechanism, perforators dilate forming fragile collateral vessels that appear as an abnormal vascular network resembling 'puff of smoke drifting in the air' observed via angiography around stenotic area in the brain. Patients and methods: The database of the current hospital was retrospectively studied. All patients with ischemic strokes owing to MMD treated with surgical revascularization between January 2015 and December 2022 were included. MMD was identified on catheter-based digital subtraction angiography (DSA) by the presence of stenosis at the terminal portions of both internal carotid arteries and the development of abnormal collateral "moyamoya vessels" around the base of the brain. Clinical, radiological and follow-up data were retrospectively analyzed. Results: During the mentioned time window, nine patients were diagnosed with moyamoya disease among all pediatric patients with established diagnosis of ischemic stroke in our institute; six of them underwent surgery. Unilateral EDMS was performed in 5 cases (83.3%), while one patient (16.67%) underwent staged bilateral surgeries with no added neurological deficit. Conclusion: Indirect revascularization surgery for pediatric moyamoya-related stroke patients has high rates of reperfusion and promising outcomes. [ABSTRACT FROM AUTHOR]

Moyamoya disease, characterized by basal cerebral artery obstruction, was studied for differential protein expression to elucidate its pathogenesis. Proteomic analysis of cerebrospinal fluid from 10 patients, categorized by postoperative angiography into good and poor prognosis groups, revealed 46 differentially expressed proteins. Notably, cadherin 18 (CDH18) was the most significantly upregulated in the good prognosis group. In addition, the expression of cadherin 18 (CDH18) and phenotypic transformation-related proteins were measured by qRT-PCR and western blot. The effects of CDH18 in vascular smooth muscle cells were detected by CCK-8, EdU, transwell and wound healing assays. The overexpression of CDH18 in vascular smooth muscle cells (VSMCs) was found to inhibit proliferation, migration, and phenotypic transformation. These findings suggest CDH18 as a potential therapeutic target in moyamoya disease. [ABSTRACT FROM AUTHOR]

Background and Purpose: High‐resolution magnetic resonance imaging (HR‐MRI) can provide valuable insights into the histopathological characteristics of moyamoya disease (MMD). However, the patterns of vessel wall contrast enhancement have not been well established. We aimed to identify the contrast enhancement patterns of the vessel walls associated with acute cerebral infarction using HR‐MRI in MMD. Methods: In this retrospective study, we conducted genetic tests for Ring Finger Protein 213 (RNF 213) and performed HR‐MRI on patients suspected of having MMD. We analyzed wall enhancement patterns including concentric, eccentric, or mixed enhancement types, and the occurrence of acute cerebral infarction in patients who simultaneously tested positive for RNF 213 and exhibited definite features of MMD on HR‐MRI. Results: Among 306 patients who underwent RNF 213 tests for the evaluation of MMD, 56 showed positive RNF 213, and HR‐MRI was performed on 32 of them. Among the patients with acute cerebral infarction, the incidence rate was significantly higher in the group with concentric wall enhancement compared to patients without acute cerebral infarction (73.3% vs. 17.0%, p <.002). Furthermore, the incidence was notably elevated, even in patients with pure concentric wall enhancement (40.0% vs. 5.9%, p =.033). The area under the curve (AUC) for the group with any concentric wall enhancement showed a significant result of.78 (95% confidence interval [CI]:.61‐.95, p =.007), whereas the predictive ability for pure concentric wall enhancement did not reach significance (AUC =.67, 95% CI:.48‐.86, p =.100). Conclusions: Concentric wall enhancement was a significant predictor of acute cerebral infarction in patients with MMD. [ABSTRACT FROM AUTHOR]

Background Moyamoya vasculopathy is a rare neurological disease characterized by the progressive constriction of major intracranial vessels and secondary collateral formation. In the past decade, the popularity of combined bypass surgery has increased. They take advantage of the quick perfusion of direct bypass and collaterals ingrowth from indirect bypass. Objective This study aimed to describe a single-center experience with surgical management of moyamoya disease (MMD) and moyamoya syndrome (MMS) over 7 years. Materials and Methods In this retrospective medical records review, we enrolled patients diagnosed with MMD and MMS who were treated with combined surgical revascularization at the Hamad Medical Corporation center between 2015 and 2022. SPSS 26.0 was used to analyze the data. Results A total of 20 patients were included, with 15% having MMS. The mean age was 37.4 ± 10.26 years, and 60% of them were males. The mean follow-up period was 13.6 months. The modified Rankin score was significantly decreased by 1.9 ± 2.1, p = 0.0001. Following surgery, no deficits were observed in 16 cases, whereas three were not improved, and one died. Following up on the stroke status, one patient developed a hemorrhagic stroke, and another showed right-side numbness. The postoperative status was substantially linked with the initial clinical presentation (p = 0.004). Conclusion Combined direct and indirect surgical revascularization procedures have favorable outcomes in MMD and MMS patients. Additional rigorous, prospective, controlled, high-quality trials with large-sample are needed to support our results. [ABSTRACT FROM AUTHOR]

Background: Moyamoya disease (MMD) signifies a cerebrovascular disorder with obscure origin and a more rapid and severe progression in children than adults. This investigation aims to uncover age-associated distinctions through proteomic and metabolomic profiling to gain insights into the underlying mechanisms of MMD. Methods: Twelve MMD patients—six children and six adults—along with six healthy controls (HC), participated, each providing a 10 mL blood sample. Serum proteomic and metabolomic analyses were conducted using ultra-performance liquid chromatography and high-resolution mass spectrometry, complemented by bioinformatics to identify differential biomolecules and their interactions. Pathway implications were ascertained using GO and KEGG enrichment analysis. Results: Notable proteomic and metabolomic discrepancies were observed between pediatric and adult MMD subjects. A total of 235 and 216 proteins varied in adult and pediatric cases compared to HCs, with 73 proteins shared. In addition, 129 and 74 anionic, plus 96 and 104 cationic metabolites, were differentially expressed in the pediatric and adult groups, respectively, with 34 anionic and 28 cationic metabolites in common. Age-specific biomolecules further characterized these distinctions. Enrichment analysis pinpointed immunity and inflammation pathways, with vitamin digestion and absorption highlighted as pivotal in pediatric MMD. Conclusion: This study unveils distinct metabolic and proteomic patterns within pediatric and adult MMD patients. The critical role of the vitamin digestion and absorption pathway in the pathogenesis of pediatric MMD offers novel insight into disease mechanisms. [ABSTRACT FROM AUTHOR]

The pathogenesis and development of Moyamoya disease are still unclear. This study aimed to investigate the effect of desmoglein-2 (DSG2) on Moyamoya disease and determine the inhibitory effect of DSG2 in vascular remodeling in Moyamoya disease. RNA sequencing, immunohistochemistry (IHC), and western blotting were used to detect the expression of DSG2 in the superficial temporal artery (STA) tissues of Moyamoya disease. The association between DSG2 and endothelial cells' biological activities was investigated by cell counting kit-8 (CCK-8), migration assay, tube formation assay, flow cytometry with Annexin V-FITC/PI staining, and TUNEL apoptotic cell detection kit. Pathways affected by overexpression or knockdown of DSG2 were identified in endothelial cells. The expression of DSG2 in the STA tissues of Moyamoya disease was lower than that in normal controls. Overexpression of DSG2 inhibits the proliferation and migration but promotes apoptosis in endothelial cells, and low DSG2 levels result in impaired angiogenesis. In addition, there was an interaction between DSG2 and MMP-9, and DSG2 acted through the PI3K signaling in endothelial cells. Our results indicate that DSG2 affects PI3K signaling in vascular endothelial cells, and MMP-9 is involved in DSG2-mediated vascular changes in Moyamoya disease. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Using two case reports of adult women with moyamoya disease presenting with intracranial hemorrhage from ruptured aneurysms on moyamoya collateral vessels, we aim to demonstrate the potential for effective endovascular treatment navigated by CT angiography, digital subtraction angiography, and flat panel CT. Case 1 Presentation: A 45-year-old female patient with sudden onset of headache, followed by somnolency. CT scan showed a four-ventricle hematocephalus caused by a 27 × 31 × 17 mm hematoma located in the left basal ganglia. Angiography revealed a 3 mm aneurysm on hypertrophic lenticulostriate artery bridging the M1 occlusion. Selective catheterization and distal embolisation with acrylic glue was done. Case 2 Presentation: A 47-year-old woman was admitted for a sudden onset of severe headache, CT scan showed four-ventricle hematocephalus. A 4 mm aneurysm on the collateral vessel–anterior chorioidal artery bridging the closure of the terminal segment of the internal carotid artery was diagnosed as the source of bleeding. Selective catheterization and distal embolisation with acrylic glue was done. Conclusions: Selective embolisation of ruptured aneurysms on moya moya collaterals is a simple, effective, and safe procedure when relevant microcatheters are used with imaging software navigation such as 3D DSA, 3D road map and flat-panel CT. [ABSTRACT FROM AUTHOR]

This case report demonstrates a rare finding of a pediatric patient with Morning Glory anomaly and Moyamoya Disease with a palatal meningeal hamartoma discovered as a mass within a previously repaired incomplete cleft of the alveolus. Oral meningeal hamartomas are exceedingly rare with only two palatal cases described and none within a cleft palate or alveolus. These findings prompt a review of oral hamartomas with meningeal subclassification. Further discussion describes the relationship of the proposed origins of meningeal hamartomas within the setting of cleft palate development. [ABSTRACT FROM AUTHOR]

Abstract To explore the relationship between morphological and hemodynamic parameters, baseline characteristics, and long-term outcomes in patients with moyamoya disease (MMD) using a computational fluid dynamics model. We retrospectively reviewed 129 patients at Beijing Tiantan hospital between July 2020 and December 2021. Perioperative clinical variables and Suzuki stage were recorded. Logistic regression analysis was employed to identify the risk factors for unfavorable long-term outcomes. The association between morphological, CT perfusion parameters, hemodynamic parameters and the Suzuki stage, clinical variables of MMD was also analyzed. Patients with high relative Wall Shear Stress (rWSS) were older and had more cases with higher Suzuki stage and worse follow-up mRS scores (p

Abstract Cerebral hyperperfusion syndrome (CHS) is a serious complication after bypass surgery in Moyamoya disease (MMD), with autoregulatory dysfunction being a major pathogenesis. This study investigated the change of perioperative autoregulation and preoperative prognostic potentials in MMD with postoperative CHS. Among 26 hemispheres in 24 patients with adult MMD undergoing combined bypass, 13 hemispheres experienced postoperative CHS. Arterial blood pressure and cerebral blood flow velocity were perioperatively measured with transcranial Doppler ultrasound during resting and the Valsalva maneuver (VM). Autoregulation profiles were discovered in both the CHS and non-CHS groups using mean flow index (Mxa), VM Autoregulatory Index (VMAI), and a new metric termed VM Overshooting Index (VMOI). The CHS group had inferior autoregulation than the non-CHS group as indicated by VMOI on preoperative day 1 and postoperative 3rd day. Deteriorated autoregulation was observed via Mxa in the CHS group than in the non-CHS group on the postoperative 3rd and discharge days. Postoperative longitudinal autoregulation recovery in the CHS group was found in a logistic regression model with diminished group differences over the time course. This work represents a step forward in utilizing autoregulation indices derived from physiological signals, to predict the postoperative CHS in adult MMD.

Recent cohort studies on hemorrhagic and asymptomatic moyamoya disease have revealed that choroidal anastomosis, a type of fragile periventricular collateral pathway (periventricular anastomosis) typical of the disease, is an independent predictor of hemorrhagic stroke. However, treatment strategies for less-symptomatic nonhemorrhagic patients with choroidal anastomosis remain unclear. The Moyamoya Periventricular Choroidal Collateral (P-ChoC) Registry is an ongoing multicentered observational study that will test the hypothesis that extracranial-intracranial bypass prevents de novo hemorrhagic stroke in less symptomatic, nonhemorrhagic patients with choroidal anastomosis and may thus contribute to improving the prognosis of moyamoya disease. In this study, we report the study protocol of the moyamoya P-ChoC Registry and review the literature on choroidal anastomosis as a fragile collateral pathway.

Abstract Moyamoya disease (MMD) suffers from impaired cerebrovascular hemodynamics and high perioperative complications occurrence. This study aims to propose and evaluate the relationship between intraoperative hemodynamics and perioperative complications, and propose a potential compensatory self-recirculation network in MMD. We prospectively enrolled 63 MMD patients undergone combined revascularization, and patients were divided into decreased and increased group according to decreased and increased microvascular transit time (MVTT), respectively. Mean age of all patients was 45.9 ± 9.4 years. The post-bypass hyperperfusion syndrome occurrence was significantly higher in the decreased MVTT group, and the cerebral infarction occurrence was significantly higher in the increased MVTT group. For the hemodynamics of the recipient artery around anastomosis, the parameters of distal site demonstrated a significant higher intensity and shorter time in the decreased MVTT group, while the parameters of the proximal site demonstrated a significant higher intensity and shorter time in the increased MVTT group. Pre-bypass and post-bypass collision of blood flow in artery and vein were firstly observed and illustrated. Intraoperative hemodynamics showed close relationship with perioperative complications. The blood flow of MMD seems to develop a unique compensatory self-recirculation system and contribute to the clinical complications, providing a new insight to the clinical management the pathology of the disease.

Abstract The safety and efficacy of coronavirus disease 2019 (COVID-19) vaccination in patients diagnosed with Moyamoya disease (MMD) have not been established. Using National Health Insurance Service data, this study analyzed the occurrence of stroke-related events and mortality following COVID-19 vaccination among patients diagnosed with MMD from 2008 to 2020. Among 10,297 MMD patients, 296 (2.9%) experienced events and 175 (1.7%) died in 2021. Significant risk factors for events included ages 50–59 (Odds Ratio [OR] 3.29; P = 0.022) and 60 or above (OR 5.20; P = 0.001) (reference group: age in 20s), low BMI (OR 2.00; P = 0.011), previous stroke (OR 1.96; P

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.

Abstract Moyamoya disease, characterized by basal cerebral artery obstruction, was studied for differential protein expression to elucidate its pathogenesis. Proteomic analysis of cerebrospinal fluid from 10 patients, categorized by postoperative angiography into good and poor prognosis groups, revealed 46 differentially expressed proteins. Notably, cadherin 18 (CDH18) was the most significantly upregulated in the good prognosis group. In addition, the expression of cadherin 18 (CDH18) and phenotypic transformation-related proteins were measured by qRT-PCR and western blot. The effects of CDH18 in vascular smooth muscle cells were detected by CCK-8, EdU, transwell and wound healing assays. The overexpression of CDH18 in vascular smooth muscle cells (VSMCs) was found to inhibit proliferation, migration, and phenotypic transformation. These findings suggest CDH18 as a potential therapeutic target in moyamoya disease.

Primitive proatlantal intersegmental artery (PPIA) is rare and can be divided into types I and II. PPIAs can be associated with some anatomical variations and vascular diseases. However, no case of PPIA combined with moyamoya disease (MMD) has been reported. Here, we reported such a case. A 54-year-old man experienced headache for 1 month. The results of the neurological examinations were unremarkable. Magnetic resonance angiography and digital subtraction angiography revealed a right type I PPIA with MMD. The PPIA serves as an important collateral path for MMD patients. Because the patient only experienced headache, he was discharged and underwent follow-up observation. This case indicates that, rarely, PPIA can be associated with MMD and serve as a collateral vessel for MMD patients.

Purpose: The primary purpose of this study was to develop and implement a novel Hemispheric Surgical Score to guide the treatment of pediatric patients with Moyamoya disease (MMD). Additionally, we aimed to describe a comprehensive flowchart for the evaluation, treatment, and follow-up of these patients and to share our experience with the interdisciplinary management of a large pediatric cohort at a referral pediatric hospital. Methods: We conducted a retrospective observational study using medical records of patients diagnosed with MMD at the Pediatric Hospital "Prof. Dr. Juan P. Garrahan" in Buenos Aires, Argentina, from July 2013 to July 2023. From July 2016 onward, data were analyzed prospectively following the implementation of the Hemispheric Surgical Score and the flowchart. Evaluations included clinical, MRI, and angiographic criteria, and patients were managed by an interdisciplinary team. Demographic, clinical, and neuroimaging data were collected and analyzed. Results: Eighty hemispheres from 40 patients were analyzed, with cerebral revascularization performed on 72 hemispheres from 37 patients. The Hemispheric Surgical Score and flowchart standardized treatment decisions, and reduced the need for invasive studies like angiographies for follow-up. The majority of patients (79.1%) had favorable outcomes, with complete disease progression arrest and no worsening of imaging nor clinical scores during a median follow-up of 35.8 months. Conclusion: The Hemispheric Surgical Score and the comprehensive flowchart have improved the management of MMD in pediatric patients by standardizing treatment and reducing unnecessary invasive procedures. This interdisciplinary approach has led to better patient outcomes, highlighting the need for further validation in larger studies and comparisons of different revascularization techniques through randomized clinical trials. [ABSTRACT FROM AUTHOR]

Moyamoya disease (MMD) is a rare progressive condition of unknown etiology that affects the blood vessels in the brain and is characterized by narrowing or stenosis of the distal parts of the internal carotid and major intracranial arteries, leading to the development of fragile collateral supplies. This makes it a significant causative factor for both ischemic strokes as well as intracerebral hemorrhages. As per the recommendations by the Research Committee on Moyamoya disease in 2021, the diagnostic criteria for MMD are essentially based on indicative radiological findings on cerebral angiography or MRI Brain and MRA, after excluding possible differentials. In this case report, we present the case of a 45-year-old Asian lady who presented with sudden-onset headaches and right-sided weakness. Her admission non-contrast CT brain scan was undiagnostic. MRI brain and MRA scans revealed bilateral anterior circulation watershed infarcts of variable age along with supra-clinoid stenosis. She was initially treated with steroids for vasculitis after discussions with a multidisciplinary team involving neurologists, stroke physicians and neuro-radiologists; however, further imaging revealed a diagnosis of MMD, and she was subsequently referred for revascularization surgery. Given the limited number of similarly documented cases, we hope this report will contribute to the knowledge base. [ABSTRACT FROM AUTHOR]

Background and purpose: The penetrance of the RNF213 p.R4810K, a founder mutation of moyamoya disease (MMD), is estimated to be only 1/150–1/300. However, the factors affecting its penetrance remain unclear. Therefore, our study aims to identify modifier genes associated with the incomplete penetrance of this founder mutation. Methods: Whole‐exome sequencing (WES) was performed on 36 participants, including 22 MMD patients and 14 non‐MMD controls with RNF213 p.R4810K mutation. Fisher's exact test was used to assess the presence of genetic variants that differed significantly between MMD patients and non‐MMD controls. In order to exclude false‐positive results, another 55 carriers were included to perform Fisher's exact test for the selected sites in the WES discovery stage. Subsequently, human brain microvascular endothelial cells were transfected with wild‐type and mutant HAPLN3 for tube formation assays and western blotting to explore the impact of candidate genes on angiogenesis. Results: Analysis of variants from WES data revealed a total of 12 non‐synonymous variants. Through bioinformatics analysis, the focus was on the HAPLN3 p.T34A variant with a significant p value of 0.00731 in Fisher's exact test. Validation through Sanger sequencing confirmed the presence of this variant in the WES data. In vitro experiments revealed that silencing HAPLN3 and transfecting HAPLN3 p.T34A significantly enhanced tube formation and increased the relative protein expression of vascular endothelial growth factor in endothelial cells. Conclusions: These results suggest that HAPLN3 may function as a modifier gene of RNF213 p.R4810K, promoting the development of MMD and contributing to the incomplete penetrance of MMD founder mutations. [ABSTRACT FROM AUTHOR]

Objective Despite revascularization has been proven to be the optimal choice of moyamoya disease (MMD), many complications may occur in this context.. This study aimed to analyse the risk factors for new or expanded symptomatic infarctions of patients with MMD after revascularization. Methods Patients with MMD who received revascularization in our department were retrospectively enrolled, new or expanded cerebral infarction within a month after revascularization was the main concern. Basic and clinical information, and intraoperative conditions were evaluated. Univariate and multivariate analyses were performed to evaluate the risk factors. Receiver operating characteristic curve analysis was conducted to evaluate the efficiency of the risk factors. Results: Eventually, 108 consecutive patients received 174 surgeries were enrolled, experienced new or expanded infarction occured in 13 (7.47%) surgeries, which showed higher Suzuki stage on the non-operative side, more posterior cerebral artery (PCA) involvement, and more intraoperative hypotension compared to those without infarction(p < .05). The Suzuki stage on the non-operative side had the highest area under the curve (AUC) of 0.737, with a sensitivity of 0.692 and specificity of 0.783. Combination of the three factors showed better efficiency, with an AUC of 0.762, a sensitivity of 0.692, and a specificity of 0.907. Conclusions: Revascularization was a safe option for patients with MMD, higher Suzuki stage on the non-operative side, PCA involvement, and intraoperative hypotension might be the risk factors for new or expanded infarction after revascularization in patients with MMD. [ABSTRACT FROM AUTHOR]

It is unclear how rare RNF213 variants, other than the p.R4810K founder variant, affect the clinical phenotype or the function of RNF213 in moyamoya disease (MMD). This study included 151 Japanese patients with MMD. After performing targeted resequencing for all coding exons in RNF213, we investigated the clinical phenotype and statistically analyzed the genotype–phenotype correlation. We mapped RNF213 variants on a three-dimensional (3D) model of human RNF213 and analyzed the structural changes due to variants. The RNF213 p.R4810K homozygous variant, p.R4810K heterozygous variant, and wild type were detected in 10 (6.6%), 111 (73.5%), and 30 (19.9%) MMD patients, respectively. In addition, 15 rare variants were detected in 16 (10.6%) patients. In addition to the influence of the p.R4810K homozygous variant, the frequency of cerebral infarction at disease onset was higher in pediatric patients with other rare variants (3/6, 50.0%, P = 0.006) than in those with only the p.R4810K heterozygous variant or with no variants (2/51, 3.9%). Furthermore, on 3D modelling of RNF213, the majority of rare variants found in pediatric patients were located in the E3 module and associated with salt bridge loss, contrary to the results for adult patients. The clinical phenotype of rare RNF213 variants, mapped mutation position, and their predicted structural change differed between pediatric and adult patients with MMD. Rare RNF213 variants, in addition to the founder p.R4810K homozygous variant, can influence MMD clinical phenotypes or structural change which may contribute to the destabilization of RNF213. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Dan Li,1 Fang Lv,2 Chenyuan Ding,3 Zhaohan Zhuang,3 Shijun Wang1 1Department of Obstetrics & Gynecology, Xuanwu Hospital Capital Medical University, Beijing, 100053, People’s Republic of China; 2Department of Medical Record Statistics, Xuanwu Hospital Capital Medical University, Beijing, 100053, People’s Republic of China; 3Education Section, Xuanwu Hospital Capital Medical University, Beijing, 100053, People’s Republic of ChinaCorrespondence: Shijun Wang, Department of Obstetrics & Gynaecology, Xuanwu Hospital Capital Medical University, No. 45 Changchun Street, Xicheng District, Beijing, 100053, People’s Republic of China, Tel +86-13601222289, Email wangshijun20158866@126.comPurpose: This case report aimed to summarize the risk factors, clinical characteristics, imaging changes, and maternal and fetal prognosis associated with Moyamoya disease in pregnant women and to explore effective management strategies and a comprehensive delivery plan.Case Presentation: The clinical data of four pregnant women who were diagnosed with Moyamoya disease and admitted to our hospital between January 2010 and January 2019 were retrospectively analyzed. Their diagnosis, treatment, delivery, and postpartum management during the pregnancy were analyzed. Among the four pregnant women, three were primipara and one was multipara. The age ranged from 27 to 41 years old. The gestational week of termination of pregnancy ranged between 8 and 39 weeks. During pregnancy, one case died in utero; one case was complicated with postpartum hemorrhage; one case was complicated with chronic hypertension, multiple cerebral artery stenosis and occlusion, bilateral middle cerebral artery occlusion, bilateral internal carotid artery occlusion, and Hashimoto’s thyroiditis. Under epidural anesthesia, two cases underwent a lower segment cesarean section; one case underwent artificial abortion; and one case underwent induced labor during late pregnancy. Two newborns survived.Conclusion: Moyamoya disease is a rare and serious complication of pregnancy. Pregnancy and childbirth may exacerbate the progression of this disease or induce cerebrovascular accidents, with a high mortality and disability rate, which seriously threatens the safety of mother and infant lives; however, with the close collaboration of a multidisciplinary team, it is possible to maximize a good pregnancy outcome.Keywords: pregnancy, cerebrovascular lesions, moyamoya disease

Introduction: Moyamoya disease (MMD) and non-MMD intracranial cerebral artery stenosis (ICAS) have been linked to the RNF213 rs112735431 gene in Korean and Japanese populations. This cross-sectional study investigates the prevalence of the RNF213 rs112735431 gene in non-cardioembolic ischemic stroke (NCIS) among Thai patients. Methods: A cross-sectional investigation was conducted on patients aged 18 years or older admitted to King Chulalongkorn Memorial Hospital between June 2015 and March 2016 with acute NCIS. ICAS and extracranial carotid artery stenosis (ECAS) were assessed through computer tomography angiography or magnetic resonance angiography. Blood samples were collected, and Sanger sequencing was performed. Results: Among 234 acute NCIS cases, 113 exhibited ICAS, 12 had ECAS, 20 had both, and 89 had neither. The RNF213 rs112735431 gene variant was detected in 2 patients, both heterozygous A/G. The frequency of the RNF213 rs112735431 variant was 0.9% (2/234; 95% CI: 0–2.1%) in acute NCIS patients and 1.8% (2/113; 95% CI: 0–4.2%) in ICAS. All individuals with the RNF213 variant were males with hypertension, diabetes mellitus, dyslipidemia, and ICAS, without a family history of ischemic stroke. Conclusion: This study reveals that the RNF213 rs112735431 gene variant is uncommon among Thai NCIS patients, suggesting a discrepancy in the prevalence of this genetic variation between Thai and other Eastern Asian populations.

Introduction: Revascularization surgery is recommended for all pediatric patients with moyamoya disease (MMD) with ischemic symptoms because the brains of such patients are still developing. By contrast, no clear guidelines for selective revascularization surgery in adult patients (30 years or more) with ischemic presentation have been established. Regarding the age of initial onset of ischemic MMD, patients in their 20s are at the bottom of the distribution and this age group may share features with both adult and pediatric patients. The present prospective study aimed to clarify the clinical features and treatment outcomes of patients in their 20s (younger patients) with ischemic MMD compared with patients aged 30–60 years (older patients). Methods: While patients with misery perfusion in the symptomatic cerebral hemisphere on 15O-positron emission tomography underwent combined surgery including direct and indirect revascularizations in the first study period and indirect revascularization alone in the second study period, patients without misery perfusion in that hemisphere received pharmacotherapy alone through the two study periods. Cerebral angiography via arterial catheterization and neuropsychological testing were performed before and after surgery. Results: During 12 years, 12 younger patients were included and comprised 6% of all adult patients (194 patients). The incidence of misery perfusion in the affected hemisphere was significantly higher in younger (12/12 [100%]) than in older patients (57/182 [31%]) (p < 0.0001). No difference in the incidence of cerebral hyperperfusion syndrome and postoperatively declined cognition was seen between younger (2/5 [40%] and 2/5 [40%], respectively) and older (11/36 [31%] and 15/36 [42%], respectively) cerebral hemispheres undergoing combined revascularization surgery. No difference in the incidence of postoperatively formed collateral flows feeding more than one-third of the middle cerebral artery cortical territory on angiograms and postoperatively improved cognition was seen between younger (9/10 [90%] and 6/10 [60%], respectively) and older (18/22 [83%] and 14/22 [64%], respectively) cerebral hemispheres undergoing indirect revascularization surgery alone. Conclusion: Patients in their 20s with ischemic MMD always exhibit misery perfusion in the affected hemisphere, unlike older patients, and sometimes develop cerebral hyperperfusion syndrome after combined revascularization surgery, leading to cognitive decline, similar to older patients. Moreover, indirect revascularization surgery alone forms sufficient collateral circulation and restores cognitive function in patients in their 20s, similar to older patients.

烟雾病是一种病因不明的慢性进展性脑血管疾病，高发于东亚人群的儿童和青壮年。近20年来，烟雾病的基础和临床研究飞速发展，取得了以易感基因研究为代表的一系列突破性进展。然而，在取得进步的同时也面临着诸多问题与挑战：基因检测是否必要？儿童和成人烟雾病的差异在哪里？无症状患者是真的无症状吗？烟雾病和烟雾综合征是否能明确区分？出血型烟雾病患者能否从手术中获益?一系列问题依旧给临床上带来困惑。未来研究者需要通过开展一系列高质量的基础和临床研究来驱散烟雾病诊疗中的“迷雾”。 Abstract: Moyamoya disease is a chronic progressive cerebrovascular disease of unknown etiology, which is most prevalent in children and young adults in East Asia. Over the past two decades, there have been rapid advancements in basic and clinical research on Moyamoya disease, leading to groundbreaking developments, particularly in susceptible gene studies. However, while progress has been made, there are still many problems and challenges. Is genetic testing necessary? What are the differences between Moyamoya disease in children and adults? Are asymptomatic patients truly asymptomatic? Can Moyamoya disease be clearly distinguished from Moyamoya syndrome? Can patients with hemorrhagic Moyamoya disease benefit from surgery? A series of questions continue to perplex clinicians in the field. In the future, researchers need to conduct high-quality basic and clinical research to dispel the “fog” surrounding the diagnosis and treatment of Moyamoya disease.

目的 探讨烟雾病患者CT灌注和DSA侧支代偿之间的相关性以及影响其大脑半球灌注的危险因素。 方法 研究纳入115例成年烟雾病患者，共230个大脑半球，收集其DSA和CT灌注数据。ASPECTS分区用于划分大脑区域，对达峰时间（time to peak，TTP）、平均通过时间（mean transit time，MTT）、脑血流量（cerebral blood flow，CBF）和脑血容量（cerebral blood volume，CBV）这4项灌注血流动力学指标进行评分，并对DSA显示的脑血管侧支代偿进行评分。对4项CT灌注血流动力学指标和DSA侧支代偿评分进行Spearman相关分析和多元线性回归分析。 结果 在115例烟雾病患者中，MTT评分（r=0.41，P

目的 探讨颞浅动脉-大脑中动脉端侧吻合术中不同临时阻断技术的效果及可靠性。 方法 回顾性分析2015年1月—2023年4月南方医科大学南方医院神经外科收治的接受直接搭桥术治疗的烟雾病患者资料，根据临时阻断策略的不同将患者分为3组：①有垫片、多阻断夹阻断组（multi-clips+rubber pad group，M+R组）；②无垫片、多阻断夹阻断组（multi-clips group，M组）；③无垫片、单阻断夹阻断组（single-clip group，S组）。比较组间临时阻断时间、受体动脉切开后有无渗血、术中穿支血管损伤以及术后新发脑梗死情况。 结果 共355例患者、360个大脑半球纳入分析，按大脑半球统计患者360例，其中男性188例，女性172例，平均年龄为（43.8±0.7）岁。其中M+R组45例，M组191例，S组124例。3组平均阻断时间：M+R组为（37.9±9.8）min，M组为（20.9±9.0）min，S组为（11.0±3.5）min，组间差异有统计学意义（P＜0.001）。阻断后受体动脉管腔内渗血以及术中穿支血管损伤发生率：M+R组为8.89%（阻断后受体动脉渗血4例），M组为14.66%（阻断后受体动脉渗血19例，术中穿支血管损伤8例，临时阻断部位有血栓形成1例），S组为5.65%（阻断后受体动脉渗血7例），组间差异无统计学意义（P>0.05）。术后新发脑梗死发生率差异无统计学意义（P>0.05）。 结论 单阻断夹阻断策略安全、有效，能显著缩短临时阻断时间，可以优先考虑作为颞浅动脉-大脑中动脉端侧吻合过程中的临时阻断策略。 Abstract: Objective To investigate the effects and reliability of different temporary occlusion techniques in end-to-side anastomosis of the superficial temporal artery-middle cerebral artery. Methods A retrospective analysis was conducted on the data of patients with Moyamoya disease who underwent direct bypass surgery in the Department of Neurosurgery, Nanfang Hospital, Southern Medical University, from January 2015 to April 2023. The patients were divided into three groups according to the different temporary occlusion strategies: ①multi-clips+rubber pad group (M+R group); ②multi-clips group (M group); and ③single-clip group (S group). Temporary occlusion time, presence of errhysis after recipient artery incision, intraoperative perforator vessel injury, and postoperative novel cerebral infarction were compared among the three groups. Results A total of 355 patients and 360 cerebral hemispheres were included in the analysis, and 360 patients were counted according to the number of cerebral hemispheres, including 188 males and 172 females, with an average age of (43.8±0.7) years. There were 45 cases in the M+R group, 191 cases in the M group, and 124 cases in the S group. The average occlusion time were (37.9±9.8) minutes in the M+R group, (20.9±9.0) minutes in the M group, and (11.0±3.5) minutes in the S group, with significant differences between the groups (P0.05). There was no significant difference in the incidence of novel cerebral infarctions postoperatively (P>0.05). Conclusions The single-clip occlusion strategy is safe and effective, which significantly shortens the temporary occlusion time, and should be prioritized as the temporary occlusion technique in end-to-side anastomosis of the superficial temporal artery-middle cerebral artery.

目的 评估成人烟雾病患者的认知水平及其在长期随访中的变化，并探讨成人烟雾病患者认知功能下降的影响因素。 方法 采用前瞻性队列研究设计，连续纳入2015年1月—2016年6月海军军医大学第一附属医院脑血管病中心收治的成人烟雾病患者64例，其中42例接受血流重建术（联合血流重建术16例、间接血流重建术26例）治疗，22例未接受手术治疗。收集所有患者的基线资料，并使用MoCA评估患者基线、短期[（6±1）个月]随访、长期[（10±1）年]随访时的认知功能，采用9条目患者健康问卷（patient health questionnaire-9，PHQ-9）和7条目广泛性焦虑障碍（generalized anxiety disorder-7-item，GAD-7）量表评估患者的情绪状态。分析所有患者以及接受不同治疗患者在短期随访和长期随访中的认知功能和情绪状态变化。采用可靠变化指数（reliable change index，RCI）判断是否存在功能下降，计算公式为RCIMoCA=（X2-X1）/标准差（standard deviation，SD），将RCIMoCA＜-1定义为认知功能下降。采用二元logistic回归模型探讨成人烟雾病患者长期认知功能下降的独立影响因素。 结果 共53例患者完成长期随访，其中接受联合血流重建术治疗患者13例，接受间接血流重建术治疗患者22例，未接受手术者18例。整体人群3个随访时期MoCA评分趋于稳定（P=0.694）：接受联合血流重建术[21（18～25）分 vs. 19（17～24）分，P=0.035]和间接血流重建术[20（17～22）分 vs. 19（16～22）分，P=0.047]治疗的患者短期随访MoCA评分有改善，但长期随访相对基线趋于稳定；未手术患者短期随访MoCA评分无明显下降，长期随访较基线有下降[（15（11～24）分 vs. 18（14～26）分，P=0.039]。随着时间的延长，成人烟雾病患者的认知功能恶化有加重趋势，而焦虑、抑郁状态有好转趋势。长期随访认知功能下降组与未下降组之间的手术治疗比例差异有统计学意义（P=0.037），但logistic回归分析未发现手术治疗是其独立影响因素（P＞0.05）。 结论 在长期随访中，成人烟雾病患者认知功能大致保持稳定，焦虑、抑郁状态趋于好转。血流重建术可能对维持长期认知稳定有积极作用，但仍需扩大样本量进一步明确。 Abstract: Objective To assess the cognitive function of adult patients with Moyamoya disease (MMD) and the changes during long-term follow-up, and to explore the influencing factors of cognitive decline in adult patients with MMD. Methods A prospective cohort study was used to continuously include 64 adult patients with MMD admitted to the First Affiliated Hospital of Naval Medical University from January 2015 to June 2016, of whom 42 patients underwent revascularization (16 patients underwent combined revascularization and 26 patients underwent indirect revascularization), and 22 patients did not receive surgical treatment. Baseline characteristics of all patients were collected, and cognitive function was assessed by the MoCA at baseline, short-term [(6±1) months] follow-up, and long-term [(10±1) years] follow-up. Emotional status was assessed by patient health questionnaire-9 (PHQ-9) and generalized anxiety disorder-7-item (GAD-7). The changes in cognitive function and emotional status were analyzed in all patients, as well as in patients receiving different treatment approaches, during short- and long-term follow-ups. The reliable change index (RCI) was used to determine whether there was a decline in function with the following formula: RCIMoCA= (X2-X1) /standard deviation (SD). It was defined as cognitive decline when RCIMoCA＜-1. The binary logistic regression model was used to explore the independent influencing factors of long-term cognitive decline in adult patients with MMD. Results A total of 53 patients completed the long-term follow-up, including 13 patients who underwent combined revascularization, 22 patients who underwent indirect revascularization, and 18 patients who did not undergo surgery. The MoCA scores of the overall population tended to stabilize during the long-term follow-up period (P=0.694). Patients who underwent combined revascularization [21 (18-25) points vs. 19 (17-24) points, P=0.035] and indirect revascularization [20 (17-22) points vs. 19 (16-22) points, P=0.047] showed improvement in MoCA scores at short-term follow-up, but tended to stabilize relative to baseline at long-term follow-up. There was no significant decrease in MoCA scores in patients who did not undergo surgery at short-term follow-up, but there was a decrease in MoCA scores compared with baseline at long-term follow-up [15 (11-24) points vs. 18 (14-26) points, P=0.039]. Over time, the cognitive function of adult patients with MMD tended to worsen, while the anxiety and depression status tended to improve. There was a significant difference in the proportion of surgical treatment between the two groups with and without cognitive decline during the long-term follow-up (P=0.037), but logistic regression did not find it as an independent influencing factor (P>0.05). Conclusions During long-term follow-up, the cognitive function of adult patients with MMD generally remain stable, and the anxiety and depression status tends to improve. Revascularization may have a positive effect on maintaining long-term cognitive stability, and future studies with larger sample sizes are needed.