Search

Objective: To investigate the angioarchitectural factors associated with postoperative cerebral infarction in ischemic moyamoya disease. Methods: Data on patients who underwent surgery for ischemic MMD from 1 October 2015 to 31 October 2020, at Peking University International Hospital were collected and retrospectively analyzed. General conditions such as patient sex, age, site of surgery, preoperative manifestations such as TIA attack and old cerebral infarction, and seven angioarchitectural factors of the MMD based on DSA were selected and measured. Statistical analysis was performed by the Pearson chi-square statistic, analysis of variance (ANOVA), and multifactor logistic regression analysis. Results: Age (OR, 0.969; 95%CI, 0.939–1.000; p = 0.049), A1stenosis (OR, 5.843; 95%CI, 1.730–19.732; p = 0.004), M1stenosis (OR, 6.206; 95%CI, 2.079–18.526; p = 0.001), PCA anomalies (OR, 4.367; 95%CI, 1.452–13.129; p = 0.049), Unstable compensation (OR, 5.335; 95%CI, 1.427–19.948; p = 0.013), TIA (OR, 4.264; 95%CI, 1.844–9.863; p = 0.001), Old cerebral infarction (OR, 2.972; 95%CI, 1.194–7.397; p = 0.019). The above seven factors can be used in the regression equation to predict the probability of postoperative cerebral infarction. The prediction accuracy is 90.2%. Conclusions: Age, TIA attack, old cerebral infarction, and five angioarchitectural factors of MMD are strongly associated with postoperative cerebral infarction. Seven factors, including age, TIA attack, old infarction, and four angioarchitectural factors, can be taken to quantify the probability of surgical cerebral infarction in MMD. [ABSTRACT FROM AUTHOR]

Objective To elucidate the clinical features, risk factors for contralateral progression, and long-term outcomes of patients with unilateral moyamoya disease (MMD). Methods We retrospectively reviewed 109 patients with unilateral MMD treated at Beijing Tiantan Hospital. Clinical features, radiologic findings, and outcomes were analyzed. Results The mean age at diagnosis was 30.8 ± 14.2 years with a one-peak distribution in the thirties. The ratio of women to men was 1.1:1. Familial occurrence was 5.5%. The primary symptoms at initial presentation were transient ischemic attack (39.4%), infarction (22%), and hemorrhage (26.6%). The distribution of the initial Suzuki stage was as follows: stage 2, n = 33; stage 3, n = 35; stage 4, n = 27; stage 5, n = 11, and stage 6, n = 3. Contralateral abnormality on initial angiography occurred in 19 adult patients (17.4%). Posterior cerebral artery involvement was observed in 28 (25.7%) patients. During the average follow-up of 43.8 ± 21.3 months, contralateral progression was observed in 18 patients (16.5%). Contralateral abnormalities ( P = 0.033) on initial angiography and infarction at initial presentation ( P = 0.041) were significantly associated with contralateral progression in adults and children, respectively. Approximately 91.7% of patients had a modified Rankin Scale score of 0–2 during follow-up. Conclusions A one-peak pattern in age distribution, lower grade of Suzuki stage, fewer familial cases, and posterior cerebral artery involvement were observed in patients with unilateral MMD. Contralateral abnormalities on initial angiography and infarction at onset were risk factors for contralateral progression in adult and pediatric patients, respectively. Good functional outcomes can be anticipated in the vast majority of surgically treated patients. [ABSTRACT FROM AUTHOR]

Background: Moyamoya disease (MMD) stands as a prominent cause of stroke among children and adolescents in East Asian populations. Although a growing body of evidence suggests that dysregulated inflammation and autoimmune responses might contribute to the development of MMD, a comprehensive and detailed understanding of the alterations in circulating immune cells associated with MMD remains elusive. Methods: In this study, we employed a combination of single‐cell RNA sequencing (scRNA‐seq), mass cytometry and RNA‐sequencing techniques to compare immune cell profiles in peripheral blood samples obtained from patients with MMD and age‐matched healthy controls. Results: Our investigation unveiled immune dysfunction in MMD patients, primarily characterized by perturbations in T‐cell (TC) subpopulations, including a reduction in effector TCs and an increase in regulatory TCs (Tregs). Additionally, we observed diminished natural killer cells and dendritic cells alongside heightened B cells and monocytes in MMD patients. Notably, within the MMD group, there was an augmented proportion of fragile Tregs, whereas the stable Treg fraction decreased. MMD was also linked to heightened immune activation, as evidenced by elevated expression levels of HLA‐DR and p‐STAT3. Conclusions: Our findings offer a comprehensive view of the circulating immune cell landscape in MMD patients. Immune dysregulation in patients with MMD was characterized by alterations in T‐cell populations, including a decrease in effector T‐cells and an increase in regulatory T‐cells (Tregs), suggest a potential role for disrupted circulating immunity in the aetiology of MMD. [ABSTRACT FROM AUTHOR]

Background: The study aimed to investigate the association between nonalcoholic fatty liver disease (NAFLD) and ischemic stroke events after revascularization in patients with Moyamoya disease (MMD). Methods: This study prospectively enrolled 275 MMD patients from September 2020 to December 2021. Patients with alcoholism and other liver diseases were excluded. NAFLD was confirmed by CT imaging or abdominal ultrasonography. Stroke events and modified Rankin Scale (mRS) scores at the latest follow-up were compared between the two groups. Results: A total of 275 patients were enrolled in the study, among which 65 were diagnosed with NAFLD. Univariate logistic regression analysis showed that NAFLD (P = 0.029) was related to stroke events. Multivariate logistic regression analysis showed that NAFLD is a predictor of postoperative stroke in MMD patients (OR = 27.145, 95% CI = 2.031–362.81, P = 0.013). Kaplan-Meier analysis showed that compared with MMD patients with NAFLD, patients in the control group had a longer stroke-free time (P = 0.004). Univariate Cox analysis showed that NAFLD (P = 0.016) was associated with ischemic stroke during follow-up in patients with MMD. Multivariate Cox analysis showed that NAFLD was an independent risk factor for stroke in patients with MMD (HR = 10.815, 95% CI = 1.259–92.881, P = 0.030). Furthermore, fewer patients in the NAFLD group had good neurologic status (mRS score ≤ 2) than the control group (P = 0.005). Conclusion: NAFLD was an independent risk factor for stroke in patients with MMD after revascularization and worse neurological function outcomes. [ABSTRACT FROM AUTHOR]

Background: Ischemic events are the most common postoperative complication in bypass surgery for moyamoya disease (MMD), but the risk factors for pediatric MMD remain unclear. The goal of the study was to investigate the risk factors for postoperative ischemic complications in pediatric MMD patients.Methods: We retrospectively reviewed a consecutive series of pediatric MMD cases at Beijing Tiantan Hospital, Capital Medical University from June 2010 through June 2019. Preoperative clinical variables and radiographic findings were recorded, and logistic regression analysis was carried out to identify the risk factors for postoperative ischemic events.Results: A total of 533 operations in 336 patients were included in this study. Postoperative complications occurred after 51 operations (9.6%), including 40/447 indirect bypass procedures, 9/70 direct bypass procedures, and 2/16 combined bypass procedures. Postoperative ischemic events were the most common complication and occurred in 30 patients after 31 procedures (8.9% per patient; 5.8% per operation), including 26/447 indirect bypass procedures, 4/70 direct bypass procedures, and 1/16 combined bypass procedures, and the incidence of these events did not differ significantly between indirect and non-indirect bypass (5.8% vs 5.8%; p = 0.999). Multivariate logistic regression analyses revealed that older age at operation (OR 1.129, 95% CI 1.011-1.260, p = 0.032) and posterior cerebral artery involvement (OR 2.587, 95% CI 1.030-6.496, p = 0.043) were significantly associated with postoperative ischemic events.Conclusion: We speculate that older age at operation and posterior cerebral artery involvement are risk factors for postoperative ischemic events in pediatric MMD patients. [ABSTRACT FROM AUTHOR]

Background and purpose: The prognostic nutrition index (PNI) has been associated with the prognosis of various medical disorders. This study aimed to explore the correlation between PNI and the long-term outcomes of adult patients afflicted with moyamoya disease (MMD). Methods: This prospective study initially employed 138 adult patients diagnosed with MMD. After excluding 15 patients who did not meet the criteria, a total of 123 patients were included. Participants were divided into three groups based on the tertile of change in the PNI score. Statistical analysis compared clinical information and lab tests among the groups. The study was conducted between July 1 and December 31, 2019. Results: After adjusting for multiple variables, patients in the upper two tertiles (tertiles 2–3) exhibited a significantly lower risk of adverse long-term outcomes compared to those in the lowest tertile (tertile 1) (OR, 0.089; 95% CI, 0.009–0.895; P = 0.040). Furthermore, adding PNI tertile to traditional risk factors substantially improved predicting adverse long-term outcomes (net reclassification improvement: 98.03%, P = 0.000; integrated discrimination improvement: 4.65%, P = 0.030). However, there was no statistically significant difference between the first PNI tertile (tertile 1) and the upper two tertiles (tertiles 2–3) in the Kaplan–Meier curve of stroke incidence (log-rank test, P = 0.244). Conclusions: A higher PNI level was significantly associated with a reduced risk of unfavorable long-term outcomes. Nevertheless, the PNI score did not predict stroke recurrence during extended follow-up. This study provides insights into a potential predictor of adverse long-term outcomes after revascularization in MMD patients. Registration number: ChiCTR2000031412 [ABSTRACT FROM AUTHOR]

This article discusses a study on moyamoya disease (MMD), a rare cerebrovascular condition characterized by narrowing of the intracranial internal carotid arteries. The study aims to identify specific metabolomic changes and biomarkers that can distinguish between different subtypes of MMD for clinical diagnosis. The researchers used metabolomics analysis to identify differential metabolite features in patients with MMD compared to healthy controls. They found that LPC 16:1-2, a type of lipid, was significantly lower in patients with ischaemic MMD and could potentially serve as a biomarker for this subtype. Additionally, the study explored the effects of LPC supplementation on cell viability and angiogenesis in MMD. The findings suggest that LPC supplementation may have therapeutic potential for managing MMD. [Extracted from the article]

Objective: The role of methionine (Met) cycle in the pathogenesis and progression of cardiovascular and cerebrovascular diseases has been established, but its association with moyamoya disease (MMD) has rarely been studied. This study aimed to analyze the levels of Met cycle‐related metabolites and constructed a risk model to explore its association with the risk of MMD. Methods: In this prospective study, a total of 302 adult MMD patients and 88 age‐matched healthy individuals were consecutively recruited. The serum levels of Met cycle‐related metabolites were quantified by liquid chromatography‐mass spectrometry (LC–MS). Participants were randomly divided into training set and testing set at a ratio of 1:1. The training set was used to construct the risk score model by LASSO regression. The association between Met cycle‐related risk score and the risk of MMD was analyzed using logistic regression and assessed by ROC curves. The testing set was used for validation. Results: The levels of methionine sulfoxide and homocysteine were significantly increased, while the levels of betaine and choline were significantly decreased in MMD and its subtypes compared to healthy controls (p < 0.05 for all). The training set was used to construct the risk model and the risk score of each participant has been calculated. After adjusting for potential confounders, the risk score was independently associated with the risk of MMD and its subtypes (p < 0.05 for all). We then divided the participants into low‐risk and high‐risk groups, the high‐risk score was significantly associated with the risk of MMD and its subtypes (p < 0.05 for all). The risk scores were further assessed as tertiles, the highest tertile was significantly associated with a higher risk of MMD and its subtypes compared to the lowest (p < 0.05 for all). The results were validated in the testing set. Conclusion: This study has constructed and validated a risk model based on Met cycle‐related metabolites, which was independently associated with the risk of MMD and its subtypes. The findings provided a new perspective on the risk evaluation and prevention of MMD. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The association of exosomal RNA profiling and pathogenesis of moyamoya disease (MMD) and intracranial Atherosclerotic disease (ICAD) is unknown. In this study, we investigated the RNA profiles of sEV (small extracellular vesicles)/exosomes in patients with MMD and ICAD. Whole blood samples were collected from 30 individuals, including 10 patients with MMD, 10 patients with ICAD, and 10 healthy individuals. Whole transcriptome analysis was performed using the GeneChip WT Pico Reagent kit. Transcriptional correlation was verified using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The association between functional dysregulation and candidate RNAs was studied in vitro. In total, 1,486 downregulated and 2,405 upregulated RNAs differed significantly between patients with MMD and healthy controls. Differential expression of six circRNAs was detected using qPCR. Among these significantly differentially expressed RNAs, IPO11 and PRMT1 circRNAs were upregulated, whereas CACNA1F circRNA was downregulated. This is the first study showing that the differential expression of exosomal RNAs associated with MMD pathogenesis, such as overexpression of IPO11 and PRMT1 circRNAs, may be related to angiogenesis in MMD. The downregulation of CACNA1F circRNA may be related to vascular occlusion. These results propose the utility of exosomal RNAs as biological markers in MMD. [ABSTRACT FROM AUTHOR]

N-acetylneuraminic acid (Neu5Ac) is a functional metabolite and has been demonstrated to be a risk factor for cardiovascular diseases. It is not clear whether Neu5Ac is associated with a higher risk of cerebrovascular disorders, especially moyamoya disease (MMD). We sought to elucidate the association between serum Neu5Ac levels and MMD in a case–control study and to create a clinical risk model. In our study, we included 360 MMD patients and 89 matched healthy controls (HCs). We collected the participants' clinical characteristics, laboratory results, and serum Neu5Ac levels. Increased level of serum Neu5Ac was observed in the MMD patients (p = 0.001). After adjusting for traditional confounders, the risk of MMD (odds ratio [OR]: 1.395; 95% confidence interval [CI]: 1.141–1.706) increased with each increment in Neu5Ac level (per μmol/L). The area under the curve (AUC) values of the receiver operating characteristic (ROC) curves of the basic model plus Neu5Ac binary outcomes, Neu5Ac quartiles, and continuous Neu5Ac are 0.869, 0.863, and 0.873, respectively. Furthermore, including Neu5Ac in the model offers a substantial improvement in the risk reclassification and discrimination of MMD and its subtypes. A higher level of Neu5Ac was found to be associated with an increased risk of MMD and its clinical subtypes. [ABSTRACT FROM AUTHOR]

Background and aim. Kynurenine (KYN) and kynurenic acid (KYNA) are key intermediate metabolites associated with inflammation and immune responses in the kynurenine pathway. It remains unknown whether KYN or KYNA is associated with the risk of adult moyamoya disease (MMD). The aim of this study was to prospectively investigate the association between serum KYN or KYNA and the risk of adult MMD. Methods. The study was conducted from July 2020 to December 2021. We measured serum KYN and KYNA levels for 360 adult MMD patients (259 cases of ischemic MMD, 101 cases of hemorrhagic MMD) and 89 age-sex-matched healthy controls. Clinical and laboratory characteristics were collected from the medical record. Results. After multivariate adjustment, decreased serum KYNA (OR, 0.085; 95% CI, 0.035–0.206; p = 0.000) or KYN (OR, 0.430; 95% CI, 0.225–0.820; p = 0.010) levels were associated with increased risk of MMD when upper and lower tertiles were compared. In addition, a higher trend of hemorrhagic MMD was found in MMD patients in KYNA tertile 1 compared with those in tertile 2 to 3 (OR, 0.584; 95% CI, 0.345–0.987; p = 0.044). Addition of serum KYNA (net reclassification improvement: 73.24%, p = 0.000; integrated discrimination improvement: 9.60%, p = 0.000) or KYN (integrated discrimination improvement: 1.70%, p = 0.037) to conventional risk factors significantly improved the risk prediction of MMD. In the exploratory analysis, we observed an interaction between KYN and age (≥40 versus <40 years) or homocysteine levels (≥13.0 versus <13.0 μmol/L) on the risk of MMD. Conclusions. Decreased serum KYNA or KYN levels were associated with an increased risk of adult MMD, suggesting that serum KYNA or KYN may be a valuable predictive biomarker for adult MMD. [ABSTRACT FROM AUTHOR]

Background: Moyamoya disease (MMD) is an uncommon cerebrovascular disease which leads to progressive stenosis and occlusion of the bilateral internal carotid artery and main intracerebral arteries. Concerns are always on how the hemisphere with infarction affects cognitive function, while little attention is paid to the role that the non-infarcted hemisphere plays. Therefore, we aimed to detect cortical indexes, especially cortical complexity in the left or right hemisphere separately in patients with MMD after stroke.Methods: 28 patients with MMD (14 males, 14 females) and 14 healthy controls were included in this study. All participants underwent cognitive tests and magnetic resonance imaging (MRI) scan. The preprocessing of three-dimensional T1 weighted images were performed by standard surface-based morphometry. Surface-based morphometry statistical analysis was carried out with a threshold of False Discovery Rate (FDR) P < 0.05 and fractal dimension (FD) was used to provide a quantitative description of cerebral cortical complexity.Results: Widespread cognitive dysfunctions were found in MMD patient with stroke. Extensive FD reduction in the left hemisphere with right-sided infarction, mainly in the superior temporal, inferior frontal, and insula, while the post central gyrus, superior parietal, and inferior parietal gyrus also showed a wide range of significant differences (FDR corrected P < 0.05). Meanwhile, FD changes in the right hemisphere with left-sided infarction are restricted to the precuneus and cingulate isthmus (FDR corrected P < 0.05).Conclusions: Extensive cognitive impairment was reconfirmed in Moyamoya disease with stroke, while wild and asymmetrical decrease of cortical complexity is observed on both sides. These differences could be relative to unbalanced cognitive dysfunction, and may be the result of a long-term chronic ischemia and compensatory of the contralateral hemisphere to the infarction. [ABSTRACT FROM AUTHOR]

Background and purpose: Standard superficial temporal artery-middle cerebral artery (STA-MCA) bypass surgery is an effective treatment for ischemic cerebrovascular diseases, including moyamoya disease and occlusive cerebrovascular disease. Our purpose in this study was to evaluate the ischemic status based on the imaging modality of computed tomographic perfusion (CTP) before and after STA-MCA bypass in patients with moyamoya disease and occlusive cerebrovascular disease. Methods: CTP was performed on 19 patients, comprising 10 patients with moyamoya disease and nine patients with occlusive cerebrovascular disease, preoperatively and on the third postoperative day. According to the regional cerebral microcirculatory change and modality of CTP, the regional cerebral ischemic status was graded into two stages with four substages (I1, I2, II1, and II2) to indicate the regional cerebral perfusion and ischemic status of the patients. The ischemic status was analyzed in all 19 patients according to those stages preoperatively and postoperatively. Results: Among the 19 patients, nine (47.4%) showed improvement in the regional cerebral ischemic status, six (31.6%) showed no change, and four (21.1%) showed deterioration. Both improvement and no change in the regional cerebral ischemic status were regarded as effective, while deterioration was regarded as ineffective, meaning that 15 (78.9%) patients were effective and four (21.1%) patients were ineffective. The effective rate for moyamoya disease (one of ten, 90.0%) was significantly higher than that for occlusive cerebrovascular disease (three of nine, 66.7%). Postoperatively, only one patient (case N11) exhibited deterioration of symptoms, which presented as right hemiplegia and aphasia, and no obvious changes in symptoms were observed for the other patients in the transient period. Conclusions: This study has shown that STA-MCA bypass is an effective and safe way to improve the regional cerebral perfusion and ischemic status in ischemic cerebrovascular diseases. The stage based on the regional cerebral microcirculatory change and presentation of CTP can directly reflect the pathological mechanism underlying the regional cerebral ischemic status. [ABSTRACT FROM AUTHOR]

Growing evidence has suggested that hyperhomocysteinemia (HHcy) is a risk factor for cerebral infarction. However, the effect of HHcy on postoperative cerebral ischemia is still unclear. We aim to investigate the relationship between HHcy and postoperative ischemia of adult patients with moyamoya disease (MMD). A total of 138 adult patients with MMD were prospectively recruited from July 1 to December 31, 2019. After excluding 14 patients accepting conservative therapy, all 124 patients who underwent surgical treatment were enrolled. Patients were grouped according to postoperative ischemia and HHcy presentation, respectively. Clinical data and laboratory examinations were compared by statistical analyses. Potential risk factors were evaluated by univariate and multivariate logistic regression analysis. Comparing to the normal, patients with postoperative ischemia were higher in serum homocysteine (Hcy) level (P = 0.039) and HHcy ratio (P = 0.035). Furthermore, HHcy was more common in males (P = 0.007) than females. Logistic analysis results showed that HHcy (OR 5.234, 95% CI 1.127–24.315; P = 0.035) was an independent risk factor. HHcy was significantly associated with postoperative ischemia in MMD patients. Our study found that HHcy was correlated to the risk of postoperative ischemia. HHcy can be used as an indicator and a potential therapeutic target for postoperative ischemia in adult patients with MMD. URL: http://www.chictr.org. Unique identifier: ChiCTR2000031412. [ABSTRACT FROM AUTHOR]

Direct bypass surgery improves blood flow in patients with moyamoya disease (MMD) as well as causes local flow relocation and disturbance. This study aimed to describe the characteristics and changes of quantitative blood flow in MMD patients. Sixty-four consecutive MMD patients (67 hemispheres) who underwent STA-MCA anastomosis between August 2013 and September 2017 were included in this study. Intraoperative blood flow of superficial temporal artery and middle cerebral artery was measured with a noninvasive, ultrasound flowprobe, before and after the bypass. All data were collected prospectively. Before the bypass, 67 hemispheres were measured and 45 hemispheres acquired post-bypass measurements. Thirty-three (49.3%) had anterograde flow and 34 (50.7%) had retrograde. Retrograde blood flow was significantly higher than anterograde blood flow in MCA-M4 section (3.71 ± 2.78 ml/min vs 2.39 ± 1.71 ml/min, P = 0.023). Thirty-eight (56.7%) patients had local cerebrovascular reactivity, whereas 29 (43.3%) lost it. After bypass, blood flow was changed into three patterns: anterograde flow (1, 2.2%), retrograde flow (3, 6.7%), and bi-direction flow (41, 91.1%). Flow of M4 was significantly improved in both proximal (13.64 ± 9.16 vs 3.28 ± 2.57, P < 0.001) and distal (7.17 ± 7.21 vs 3.28 ± 2.57, P = 0.002) sides to the bypass. Postoperative infarctions occurred in 4 (8.9%) patients. All postoperative infarctions (n = 4) happened in those patients who did not have change of flow direction in M4 section distal to the bypass (P = 0.040). Direct bypass surgery improves local blood flow after bypass surgery in both sides of the anastomosis. Flow direction was usually changed after the surgery into a bi-direction pattern: anterograde flow in M4 distal to the bypass, and retrograde flow in M4 proximal to the bypass. Proximal side acquired around 5.4 times of flow than the distal side. Patients with change of flow direction in distal M4 were related with lower risks of postoperative infarctions. [ABSTRACT FROM AUTHOR]

Background: Asymptomatic Moyamoya disease (MMD) impairs hemodynamic and cognitive function. The relationship between these changes, cerebral blood flow (CBF), and network connectivity remains largely unknown. The aim of this study was to increase understanding of the relationship between CBF, functional networks, and neurocognition in adults with asymptomatic MMD. We compared CBF and functional status in 26 patients with MMD and 20 healthy controls using arterial spin labeling and resting state functional magnetic resonance imaging sequences. At the same time, a detailed cognitive test was performed in 15 patients with no cerebral or lumen infarction who were selected by magnetic resonance imaging-T2 FLAIR screening.Results: Compared to the controls, the patients showed varying degrees of decline in their computational ability (simple subtraction, p = 0.009; complex subtraction, p = 0.006) and short-term memory (p = 0.042). The asymptomatic MMD group also showed decreased CBF in the left anterior central and left inferior frontal gyri of the island flap with multiple node abnormalities in the brain network and reduced network connectivity. There was a significant association of these changes with cognitive decline in the MMD group.Conclusions: In patients with asymptomatic MMD, disturbance of CBF and impaired brain network connections may be important causes of cognitive decline and appear before clinical symptoms. Clinical trial registration-URL: http://www.chictr.org.cn Unique identifier: ChiCTR1900023610. [ABSTRACT FROM AUTHOR]

Background: Cerebral hyperperfusion syndrome (CHS) is a common complication after direct bypass surgery in patients with Moyamoya disease (MMD). Since preventive measures may be inadequate, we assessed whether the blood flow difference between the superficial temporal artery (STA) and recipient vessels (△BF) and the direct perfusion range (DPR) are related to CHS. Methods: We measured blood flow in the STA and recipient blood vessels before bypass surgery by transit-time probe to calculate △BF. Perfusion changes around the anastomosis before and after bypass were analyzed with FLOW800 to obtain DPR. Multiple factors, such as △BF, DPR, and postoperative CHS, were analyzed using binary logistic regression. Results: Forty-one patients with MMD who underwent direct bypass surgery were included in the study. Postoperative CHS symptoms occurred in 13/41 patients. △BF and DPR significantly differed between the CHS and non-CHS groups. The optimal receiver operating characteristic (ROC) curve cut-off value was 31.4 ml/min for ΔBF, and the area under the ROC curve (AUC) was 0.695 (sensitivity 0.846, specificity 0.500). The optimal cut-off value was 3.5 cm for DPR, and the AUC was 0.702 (sensitivity 0.615, specificity 0.750). Conclusion: Postoperative CHS is caused by multiple factors. △BF is a risk factor for CHS while DPR is a protective factor against CHS. [ABSTRACT FROM AUTHOR]

Few studies focused on the intraoperative blood pressure in Moyamoya disease (MMD) patients. We aimed to clarify whether or not it relates to early cerebral infarction after revascularization. We reviewed a retrospective cohort of Moyamoya disease from 2011 to 2018 in Beijing Tiantan Hospital, and patients with radiologically confirmed early postoperative infarction were included in the analysis. Controls were matched based on age, sex, and revascularization modality at a ratio of 1:5. Perioperative clinical factors and intraoperative blood pressure data were collected and analyzed. A total of 52 patients out of 1497 revascularization surgeries (3.5%) who experienced CT or MRI confirmed early postoperatively cerebral infarction, aged 38.46 ± 11.70; 26 were male (50.0%). Average real variability (ARV)-systolic blood pressure (SBP) (OR 3.29, p = 0.003), ARV-diastolic blood pressure (DBP) (OR 4.10, p = 0.005), ARV-mean arterial pressure (MAP) (OR 4.08, p = 0.004), and the maximum drops of DBP (OR 1.08, p = 0.003) and MAP (OR 1.06, p = 0.004) were associated with early postoperative infarction. In patients who experienced massive cerebral infarction, the maximum drops of DBP (OR 1.11, p = 0.004) and MAP (OR 1.11, p = 0.003) are independent risk factors, whereas ARVs of SBP (OR 3.90, p < 0.001), DBP (OR 4.69, p = 0.008), and MAP (OR 4.72, p = 0.003) are significantly associated with regional infarction. High variance of intraoperative blood pressure and drastic blood pressure decline are independent risk factors for postoperative infarction in MMD patients who underwent revascularization surgery. Maintaining stable intraoperative blood pressure is suggested to prevent early postoperative cerebral infarction in MMD patients. [ABSTRACT FROM AUTHOR]

Background: The research on postoperative collateral formation for hemorrhagic moyamoya disease (MMD) evaluated by using digital subtraction angiography (DSA) is limited. Our study objective was to investigate the postoperative collateral formation after indirect bypass for hemorrhagic MMD.Methods: All consecutive inpatients with hemorrhagic MMD who received indirect bypass at Beijing Tiantan Hospital, Capital Medical University from January 2010 through December 2018 were screened. The site of the hemorrhage was classified as either anterior or posterior. Postoperative collateral formation was evaluated on lateral views using the Matsushima scale. Univariate and multivariate logistic regression analyses were carried out to determine the factors influencing postoperative collateral formation.Results: Six-four patients (64 hemispheres) were included in this study. After a median 8.5 months DSA follow-up, 14 (21.9%) hemispheres had grade A collateral circulation, 13 (20.3%) had grade B, and 37 (57.8%) had grade C. Twenty-seven (42.2%) hemispheres had good postoperative collateral formation and 37 (57.8%) had poor postoperative collateral formation. The univariate logistic regression analyses showed that age at operation (OR, 0.954; 95% CI, 0.908-1.003; p = 0.066), hemorrhagic site (OR, 4.694; 95% CI, 1.582-13.923; p = 0.005), and PCA involvement (OR, 3.474; 95% CI, 0.922-13.086; p = 0.066) may effect postoperative collateral formation. The multivariate logistic regression analyses showed that only anterior hemorrhage (OR, 5.222; 95% CI, 1.605-16.987; p = 0.006) was significantly related to good postoperative collateral formation.Conclusion: Anterior hemorrhage was significantly related to good postoperative collateral formation after indirect bypass. [ABSTRACT FROM AUTHOR]

The ring-finger protein 213 (RNF213) gene is a major susceptibility gene for moyamoya disease. The homozygote of the p.R4810K variant on RNF213 exhibits an early onset age and severe form of moyamoya disease. We report 4 unrelated pediatric moyamoya disease cases with the homozygous p.R4810K variant and the long-term surgical outcomes. Published reports on surgical outcome of moyamoya disease case with the homozygous p.R4810K variant were reviewed. Cerebral angiography revealed classic angiographic findings of moyamoya disease in 7 hemispheres of the 4 children. All patients underwent successful indirect revascularization. Abundant collateral blood flow from the external carotid arteries to the internal carotid arteries was observed in all bypass procedures by angiography. Improvements in symptoms and cerebral blood volume were observed in all patients at long-term follow-up. This report is the first case series in the literature on the surgical management of these patients. These cases highlight the effectiveness of indirect revascularization for moyamoya disease patients with the homozygous p.R4810K variant. Early diagnosis and treatment are crucial to avoid irreversible neurologic deficits in these patients. [ABSTRACT FROM AUTHOR]

Moyamoya disease (MMD) is a cerebrovascular disorder, currently defined as progressive stenosis of intracranial internal carotid artery and its main branches with secondary formation of netlike vessels. Its precise formation mechanism, however, is unknown. We propose that MMD is caused by abnormal embryonic development of the cerebral arteries and also propose a mechanism for MMD formation. The anterior, middle, and posterior cerebral arteries, anterior choroidal arteries (AChoA) and posterior choroidal arteries, and posterior corpus callosum arteries were analyzed separately for each patient with MMD to determine whether the arteries exhibited the following characteristics, which we regarded as remnants of primitive vessels: 1) plexiform arteries rather than normal artery trunks; 2) clustered arteries converging at locations of normal artery trunks; and 3) dilated AChoA. We retrospectively analyzed 39 consecutive patients with MMD, of whom 30 had anterior cerebral arteries, 31 middle cerebral arteries, 10 posterior cerebral arteries, 30 AChoAs, 18 posterior choroidal arteries, and 20 posterior corpus callosum arteries and had the characteristics of primitive vessel remnants. Altogether, 82.05% of the patients had the remnants of primitive vessels. MMD is more likely to be caused by abnormalities of cerebral artery development, which mainly occur in the embryonic period or postnatally. The abnormality developing processes include sprouting angiogenesis, vessel fusion, and pruning, which primarily affect cranial ramus of primitive internal carotid artery, may occasionally affect the caudal ramus of the primitive internal carotid artery, and rarely affect the vertebrobasilar artery system. So-called moyamoya vessels comprise unfused primitive small vessels; to compensate, enlarged AChoAs remain undegenerated but are not dilated. [ABSTRACT FROM AUTHOR]

Recurrent stroke after surgical revascularization is still a big issue for moyamoya disease (MMD). This study aims to identify predictors for postoperative stroke and unfavorable outcome in ischemic-type MMD. We identified a consecutive series of patients with ischemic-type MMD who underwent revascularization between January 2005 and December 2012. Predictors for postoperative stroke and functional outcomes were assessed with logistic and Cox regression analysis. A total of 346 patients underwent 437 revascularization procedures and the mean follow-up period was 4.0 years. The incidence of perioperative stroke was 6.9%. Being adult at onset (odds ratio [OR], 5.033; 95% confidence interval [CI], 1.447–17.506; P = 0.011) and posterior cerebral artery (PCA) stenosis (OR, 3.364; 95% CI, 1.588–7.265; P = 0.002) before surgery were predictors of perioperative stroke. The annual subsequent stroke rate beyond 30 days after surgery was 1.2%. Subsequent stroke events tended to occur throughout the first 5 years after surgery in adults, whereas in children they mainly occurred within the first 2 years after surgery. Age at onset (OR, 1.025; 95% CI, 1.003–1.048; P = 0.023), ischemic stroke or transient ischemic attack at presentation (OR, 2.703; 95% CI, 1.062–6.875; P = 0.037), and PCA involvement (OR, 2.664; 95% CI, 1.462–4.854; P = 0.001) were associated with higher risk of overall postoperative stroke. PCA involvement (OR, 2.62; 95% CI, 1.33–5.15; P = 0.005), internal carotid artery supraclinoid segment occlusion (OR, 2.76; 95% CI, 1.27–6.03; P = 0.011), and older age at onset (OR, 1.03; 95% CI, 1.01–1.05; P = 0.033) were predictive of unfavorable outcome. Patients with ischemic-type MMD at an older age and more severe angiopathy might be at higher risk of recurrent stroke and unfavorable outcome after revascularization. [ABSTRACT FROM AUTHOR]

Object: To investigate the association between p.R4810K variant and postoperative collateral formation (PCF) in patients with moyamoya disease. Methods: The p.R4810K variant was detected in 254 Chinese moyamoya patients. Surgically treated 273 hemispheres with preoperative and postoperative digital subtraction angiography were included. PCF was evaluated on lateral and anteroposterior views using angiography. Univariate and multivariate logistic regression analyses were performed to determine the influence factors for PCF. Results: Among 254 patients, 191 (75.2%) patients carried wild-type p.R4810K variant (GG) and 63 patients (24.8%) carried the heterozygous p.R4810K variant (GA). PCF was better in patients with GA than in patients with GG both on lateral views and anteroposterior views (p < 0.001 and p < 0.001). Over the median 7 months follow-up after discharge, good PCF was observed in 201 hemispheres (73.6%), and poor PCF was observed in 72 hemispheres (26.4%). The univariable logistic regression showed that patients with GA (OR 4.681; 95% CI 1.925–11.383; p = 0.001) was associated with good PCF. On the other hand, the increasing age (OR 0.971; 95% CI 0.952–0.989; p = 0.002) and the presence of hemorrhage (OR 0.189; 95% CI 0.096–0.374; p = 0.000) were associated with poor PCF. Multivariate logistic regression analyses of p.R4810K variant and clinical variables showed that GA (OR 3.671; 95% CI 1.452–9.283; p = 0.006) was associated with a good PCF, while the presence of hemorrhage (OR 0.258; 95% CI 0.065–0.362; p = 0.000) was identified as a predictor of poor PCF. Conclusions: The heterozygous p.R4810K variant was associated with better PCF. [ABSTRACT FROM AUTHOR]

Background: This study aimed to elucidate the clinical features, surgical treatment and long-term outcomes of adolescent patients with moyamoya disease. Methods: We reviewed consecutive patients with moyamoya vasculopathy who were admitted to our hospital from 2009 to 2015 to identify adolescent patients with moyamoya disease. Clinical features, surgical treatment and long-term outcomes were analyzed. Follow-up was performed by face-to-face or structured telephone interviews. Outcome measures were future stroke events. We performed univariate and multivariate time-to-event analyses to identify risk factors associated with future stroke events. Results: A total of 95 adolescent patients with moyamoya disease (age at onset, 13.1 ± 2.3 years) were included in this study. During follow-up, 12 patients (12.6%) had stroke events. We found that the patients who underwent direct/combined bypass had a significantly lower risk of future strokes [hazard ratio (HR), 0.16; 95% confidence interval (CI), 0.03-0.74; P = 0.019] compared to patients who underwent indirect bypass. Conclusions: Our results demonstrate that direct/combined bypass can be more effective in preventing future strokes than indirect bypass in adolescent patients with moyamoya disease. [ABSTRACT FROM AUTHOR]

Moyamoya disease (MMD) is the most common pediatric cerebrovascular disease in Eastern Asian countries but the etiology is not well understood. Circular RNAs (circRNAs) have been implicated in various biological processes, but their role in the development of MMD remains unclear. To address this issue, we carried out a comparative circRNA microarray analysis of blood samples obtained from patients with MMD and healthy subjects and identified 146 circRNAs that were differentially expressed between the two groups. Of these, 29 were upregulated and 117 were downregulated in patients as compared to controls (fold change ≥ 2.0 and P < 0.05). The microarray results were validated by quantitative reverse-transcription PCR. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses revealed that the differentially expressed circRNAs were primarily involved in angiogenesis, metabolism, and immune responses in MMD. In addition, the mitogen-activated protein kinase signaling pathway was found to be the core regulatory pathway associated with disease pathogenesis. These results indicate that specific circRNAs are aberrantly expressed in MMD and are potential therapeutic targets for its treatment. [ABSTRACT FROM AUTHOR]

Objective To elucidate the clinical features of patients with hemorrhagic moyamoya disease (MMD) in China. Methods We retrospectively reviewed 471 patients with hemorrhagic MMD at Beijing Tiantan Hospital. Clinical features and radiologic findings were analyzed. Results The mean age at diagnosis was 35.3 ± 11.5 years, with 1 peak distribution in patients from 35 to 39 years of age. The ratio of women to men was 1.2:1. Familial occurrence was 3.8%. The primary symptoms at initial presentation were intraventricular hemorrhage (42.0%), intracerebral hemorrhage (23.6%), intracerebral hemorrhage with intraventricular hemorrhage (18.3%), and subarachnoid hemorrhage (16.1%). Before the diagnosis, 68 patients experienced a second episode of bleeding. Rebleeding tends to be common within 6 years after the first bleeding (83.8%). The second bleeding episode was characterized by a change in which hemisphere bleeding occurred in 7 patients (10.3%) and by the type of bleeding in 23 patients (33.8%). Most patients presented with Suzuki stage 3 or 4 MMD (61.7%). Posterior cerebral artery involvement was observed in 28 (18.4%) patients. Forty-three intracranial aneurysms were identified in 39 patients (8.3%). Conclusions A 1-peak pattern in age distribution and mild female dominance in sex distribution were observed in patients with hemorrhagic MMD. Rebleeding tends to be common within 6 years after the first bleeding; however, some cases of rebleeding occur after a long period. Furthermore, the second bleeding episode was characterized frequently by a change in hemisphere and the type of bleeding. Early surgical treatment in both hemispheres is recommended. [ABSTRACT FROM AUTHOR]

Background: Despite being the most common presentation in children with moyamoya, transient ischemic attack (TIA) in children has rarely been described. The aim of this study is to describe the clinical characteristics of TIAs in children with moyamoya and explore the risk factors for stroke after TIA.Methods: We reviewed 696 consecutive patients with moyamoya vasculopathy (155 pediatric patients and 541 adults) admitted to our hospital from 2009 to 2015 to identify pediatric patients with moyamoya with an initial presentation of TIA. We defined recurrent TIAs that involve more types of symptoms or symptom extensions as symptom progression. The risk factors for subsequent stroke were analyzed using time-to-event analyses.Results: We identified 60 pediatric patients with moyamoya who had presented with TIA (initial presentation age, 10.0 ± 3.5 years). Motor weakness (n = 51 [85%]) was the most common initial presentation. During follow-up, 55 patients (91.7%) had recurrent TIAs and 14 (23.3%) had subsequent strokes. We identified female gender (hazard ratio, 5.08; 95% confidence interval, 1.40-18.47; P = 0.01), Suzuki grade greater than 3 (hazard ratio, 4.01; 95% confidence interval, 1.16-13.82; P = 0.03), and symptom progression (hazard ratio, 5.31; 95% confidence interval, 1.65-17.14; P = 0.01) as independent predictors of future stroke events.Conclusions: Transient ischemic attacks have a relatively high recurrence rate in children with moyamoya and are associated with subsequent stroke. We identified the female sex, Suzuki grade greater than  3, and symptom progression as independent predictors of future strokes. [ABSTRACT FROM AUTHOR]

X-linked ichthyosis (XLI) is a relatively common, recessive condition caused by mutations in the steroid sulfatase ( STS ) gene. Common loss-of-function mutations in the filaggrin gene ( FLG ) cause ichthyosis vulgaris and predispose individuals to atopic eczema. We report a case of a 6-year-old boy who presented with unusually severe XLI, an increased serum immunoglobulin E level (2120 IU/ml) and moyamoya angiopathy. Whole-exome sequencing identified a gross deletion encompassing the STS in Xp22.31 and the p.K4022X FLG mutation. The deletion is at least 1.6 Mb in size in the proband, based on real-time quantitative polymerase chain reaction results. No other genetic mutations related to ichthyosis, moyamoya or hyper-immunoglobulin E syndrome were detected. Furthermore, his mother's brothers suffered from mild XLI and only had a deletion encompassing the STS . Additionally, his father and older sister suffered from mild ichthyosis vulgaris and had the p.K4022X FLG mutation. We report the first case of XLI with concurrent moyamoya syndrome. Moreover, an IgE-mediated immune response may have triggered the moyamoya signaling cascade in this patient with ichthyosis. Furthermore, our study strengthens the hypothesis that filaggrin defects can synergize with an STS deficiency to exacerbate the ichthyosis phenotype in an ethnically diverse population. [ABSTRACT FROM AUTHOR]

Objective To investigate the long-term outcomes after conservative and direct surgical treatment for patients with moyamoya disease (MMD) at late Suzuki stage. Methods We retrospectively reviewed 82 patients (164 hemispheres) with MMD at late Suzuki stage at Beijing Tiantan Hospital. Clinical features, radiologic findings, and outcomes were analyzed. Results The mean age at diagnosis was 36.4 ± 11.7 years. The distribution of the initial Suzuki stage of MMD was as follows: stage 4, n = 113; stage 5, n = 45; stage 6, n = 6, posterior cerebral artery involvement was observed in 41 hemispheres (25.0%). The incidence of postoperative stroke (<48 hours) was 6.7%. During the average follow-up of 55.1 ± 16.2 months, including postoperative and follow-up strokes, 7 of 75 conservatively treated hemispheres (9.3%) and 9 of 89 surgically treated patients (10.1%) experienced a stroke event; there was no statistical significance in the Kaplan-Meier curve of stroke incidence between the surgical group and conservative group (log-rank test, P = 0.848). However, the rate of perfusion improvement in direct bypass surgically treated patients was higher than in those conservatively treated patients 3 months after discharge ( P < 0.05). Conclusions Although direct bypass surgery was shown to effectively improve the cerebral perfusion in patients with MMD at late Suzuki stage, compared with conservative treatment, it did not reduce the risk of recurrent stroke. Further study is needed to determine whether direct bypass surgery is effective in patients with MMD at late Suzuki stage. [ABSTRACT FROM AUTHOR]

Objective Stroke in young adults is uncommon and rarely described. Moyamoya disease is one of the leading causes of stroke in young adults. We aimed to study the prognostic factors for stroke recurrences and functional outcomes in young stroke patients with moyamoya disease after revascularization. Methods We reviewed 696 consecutive patients with moyamoya disease admitted to our hospital from 2009–2015 and identified patients aged 18–45 years with first-ever stroke. Follow-up was conducted via face-to-face or structured telephone interviews. Outcome measures were recurrent stroke events and unfavorable functional outcomes (modified Rankin Scale >2). Results We included 121 young patients with moyamoya disease suffering from stroke (initial presentation age, 35.4 ± 7.5 years). All patients underwent revascularization after the acute phase of initial stroke events as the secondary prevention for recurrences. During follow-up (median, 40 months), 9 patients (7.4%) experienced recurrent strokes and 8 of them (6.6%) suffered unfavorable functional outcomes. In the multivariate analysis, diabetes was an independent predictor for stroke recurrences (hazard ratio 6.76; 95% confidence interval 1.30–35.11; P = 0.02) and was significantly associated with unfavorable functional outcomes (odds ratio 7.87; 95% confidence interval 1.42–38.74; P = 0.01). Conclusions We identified diabetes as an independent risk factor for recurrent strokes and unfavorable functional outcomes after revascularization in young stroke patients with moyamoya disease. [ABSTRACT FROM AUTHOR]

Objective To elucidate the clinical features, surgical treatment, and long-term outcome in elderly patients with moyamoya disease (MMD). Methods We retrospectively reviewed 87 elderly patients with MMD at Beijing Tiantan Hospital. Clinical features, radiologic findings, and outcomes were analyzed. Results The mean age at diagnosis was 54.0 ± 3.7 years. Familial occurrence was 2.3%. Underlying vascular risk factors was 74.7%. Infarction was the most common symptom in elderly MMD (40.2%). Most patients presented with Suzuki stage 4 or 5 MMD (51.2%). Posterior cerebral artery involvement was observed in 22 (25.3%) patients. The incidence of postoperative infarction or hemorrhages was 6.9%. Diabetes was identified as a predictor of adverse postoperative events. During the average follow-up of 35.5 ± 22.2 months, rebleeding in patients with hemorrhagic MMD was higher than in those with ischemic MMD ( P < 0.05). What's more, the rate of perfusion improvement in surgically treated patients was higher than in conservatively treated patients 3 months after discharge ( P < 0.05). Conclusions Infarction was the most common symptom in elderly MMD. More vascular risk factors, a higher grade of Suzuki stage, fewer familial cases, and posterior cerebral artery involvement were observed in elderly patients with MMD. Diabetes was a risk factor of postoperative events for elderly patients. Hemorrhagic MMD had a higher rate of rebleeding than the ischemic type. Although surgical revascularization procedures can improve cerebral perfusion, further study is needed to determine whether surgical revascularization is effective in elderly patients or with certain techniques. [ABSTRACT FROM AUTHOR]

Background and Purpose Moyamoya disease (MMD) is a chronic cerebrovascular disorder with little known etiology. We aim to propose a new classification system for MMD from the perspective of embryology. Methods MMD patients' digital subtraction angiograms were retrospectively analyzed. Every angiogram was analyzed to find the abnormal vessels and from which part of the posterior cerebral artery (PCA) the lesions begin. Results In 262 MMD cases, 32 pediatric patients had PCA involvement, of which 17 were male and 15 were female; 68 adults had PCA involvement, of which 33 were male and 35 were female. The initially affected part of the PCA was compared between sexes and between pediatric and adult patients, and the findings are not statistically significant ( P = 0.233, P = 0.855, P = 0.343, respectively). However, of the 100 cases with PCA involvement, only 4 had the lesions begin from the first part of the PCA, and all of the 4 cases had the basilar artery lesions. All the other 96 cases had the lesions begin from the second part of the PCA or from the posterior communication artery, which is derived from the caudal ramus of the primitive intracarotid artery, leaving the first part of the PCA and basilar artery excluded from affection. Conclusion MMD should be classified into primitive intracarotid artery system–involved type and primitive vertebral basilar artery system–involved type. The reason that the vertebral basilar artery is so rarely involved in MMD might be because of its late development in the brain. [ABSTRACT FROM AUTHOR]

Background The diagnosis of moyamoya disease (MMD) is often uncertain. Moyamoya syndrome (MMS) is often misdiagnosed as MMD. High-resolution magnetic resonance imaging (HR-MRI) enables vessel wall assessment to obtain more precise diagnoses. The aim of this study was to determine the true etiologies of arterial steno-occlusion in patients with an angiographic diagnosis of MMD or MMS using HR-MRI. Methods HR-MRI was performed in 21 adult patients with angiographically proven MMD or MMS. A definite diagnosis was based on the HR-MRI findings. The diagnoses made via the 2 different imaging technologies were compared, and significant findings were analyzed. Results A total of 21 patients were enrolled, including 7 patients with angiographically proven MMD and 14 patients with angiographically proven MMS. Among the 7 patients with MMD, HR-MRI confirmed the diagnosis of MMD in 6; the remaining patient was considered to have atherosclerosis in the bilateral distal internal carotid arteries (ICAs) and the left middle cerebral artery. Among the 14 patients with MMS, HR-MRI confirmed MMD in 6 patients (including 2 patients with unilateral MMD), atherosclerosis in 5 patients (including 3 patients with bilateral atherosclerosis and 2 with unilateral atherosclerosis), arterial dissection of the left ICA in 1 patient, and MMD in the left cerebral hemisphere with atherosclerosis in the right hemisphere in 2 patients. Conclusions Differentiating MMD from MMS is difficult in certain situations, and HR-MRI may help provide a more in-depth understanding of MMD and MMS, thereby achieving a more reliable diagnosis. [ABSTRACT FROM AUTHOR]

Objective To investigate long noncoding ribonucleic acid (lncRNA) expression patterns in adult moyamoya disease (MMD) patients and explore their possible roles in the pathophysiology of MMD. Methods A healthy control group ( n = 10) and an MMD group ( n = 15) were evaluated. RNA was extracted from peripheral blood samples and hybridized to microarray to get lncRNA expression profiles. Then predicted lncRNA target genes were identified, and bioinformatics analysis was performed to investigate their molecular functions. Results In the MMD group, 3649 lncRNAs exhibited more than 2-fold expression than their counterparts in the healthy control group; of these, 1494 were upregulated, while 2155 were downregulated. Principal component analysis and Hclust analysis produced completely different clusters between the 2 groups. Gene ontology and KEGG pathway enrichment analysis suggested that the differentially expressed lncRNAs regulate multiple signaling pathways that were related with inflammation and vascular disease, and mitogen-activated protein kinase (MAPK) signaling pathway was the core regulatory pathway. Conclusions Long noncoding RNA expression profiles were quite different between MMD and control groups. Multiple signaling pathways that were closely associated with immune response, vasculogenesis, and smooth muscle contraction were indicated to participate in lncRNAs regulatory mechanism; of these, MAPK signaling pathway, which has been well studied for the treatment of many other cardiovascular diseases, was the core of this regulatory network. Our findings could help further understand the pathophysiology of MMD and provide new potential therapeutic targets. [ABSTRACT FROM AUTHOR]

Objective To elucidate the clinical and angiographic features in patients with moyamoya disease (MMD) and the p.R4810K heterozygous variant and present an angiographic grading system to evaluate disease severity. Methods We retrospectively reviewed 87 patients with MMD and the p.R4810K variant treated at Beijing Tiantan Hospital. Clinical features, stroke subtype, and angiographic characteristics were analyzed. Results The median age at diagnosis was 25 years (range, 3–59). The ratio of women to men was 1.2:1. The familial occurrence of MMD was 14.9%. The primary symptom at diagnosis was ischemia, hemorrhage, or other in 67, 16, and 4 patients, respectively. Angiographic features correlating with ischemic stroke or stroke, including Suzuki grade, external carotid artery collaterals, leptomeningeal collaterals, and Mugikura grade, were identified. A binary logistic regression model demonstrated a significant correlation of Suzuki grade ( P = 0.008) and posterior cerebral artery grade ( P = 0.029) with ischemic stroke (142 hemispheres). A modified Suzuki-Mugikura grading system was developed. The areas under the receiver operating characteristic curves used to predict ischemic stroke based on the Suzuki grading, Mugikura grading, and modified Suzuki-Mugikura grading systems were 0.736, 0.69, and 0.741, respectively. Furthermore, the modified Suzuki-Mugikura grades were significantly correlated with infarction in posterior circulation and the number of infarcted regions. Conclusions The clinical and angiographic features of a Chinese MMD population with the p.R4810K variant were similar to those of a Japanese MMD population; they might be a distinct cerebrovascular disease entity and represent a separate subgroup. A modified Suzuki-Mugikura grading system was valuable for predicting stroke and evaluating disease severity. [ABSTRACT FROM AUTHOR]

Objectives: To present a multi-delay pseudo-continuous ASL (pCASL) protocol that offers simultaneous measurements of cerebral blood flow (CBF) and arterial transit time (ATT), and to study correlations between multi-delay pCASL and CT perfusion in moyamoya disease. Methods: A 4 post-labeling delay (PLD) pCASL protocol was applied on 17 patients with moyamoya disease who also underwent CT perfusion imaging. ATT was estimated using the multi-delay protocol and included in the calculation of CBF. ASL and CT perfusion images were rated for lesion severity/conspicuity. Pearson correlation coefficients were calculated across voxels between the two modalities in grey and white matter of each subject respectively and between normalized mean values of ASL and CT perfusion measures in major vascular territories. Results: Significant associations between ASL and CT perfusion were detected using subjective ratings, voxel-wise analysis in grey and white matter and region of interest (ROI)-based analysis of normalized mean perfusion. The correlation between ASL CBF and CT perfusion was improved using the multi-delay pCASL protocol compared to CBF acquired at a single PLD of 2 s ( P < 0.05). Conclusions: There is a correlation between perfusion data from ASL and CT perfusion imaging in patients with moyamoya disease. Multi-delay ASL can improve CBF quantification, which could be a prognostic imaging biomarker in patients with moyamoya disease. Key Points: • Simultaneous measurements of CBF and ATT can be achieved using multi-delay pCASL. • Multi-delay ASL was compared with CT perfusion in patients with moyamoya disease. • Statistical analyses showed significant associations between multi-delay ASL and CT perfusion. • Multi-delay ASL can improve CBF quantification in moyamoya disease. [ABSTRACT FROM AUTHOR]

Delayed anastomotic occlusion occurred in a considerable proportion of hemorrhagic moyamoya disease (MMD) patients undergoing direct revascularization. This study aimed to investigate the predictors and outcomes of delayed anastomotic occlusion in adult hemorrhagic MMD. The authors retrospectively reviewed 87 adult hemorrhagic MMD patients. Univariate and multivariate logistic regression analyses were performed. After an average of 9.1 ± 6.9 months of angiographic follow-up, the long-term graft patency rates were 79.8%. The occluded group had significantly worse angiogenesis than the non-occluded group (p < 0.001). However, the improvement of dilated anterior choroidal artery–posterior communicating artery was similar (p = 0.090). After an average of 4.0 ± 2.5 years of clinical follow-up, the neurological statues and postoperative annualized rupture risk were similar between the occluded and non-occluded groups (p = 0.750; p = 0.679; respectively). In the multivariate logistic regression analysis, collateral circulation Grade III (OR, 4.772; 95% CI, 1.184–19.230; p = 0.028) and preoperative computed tomography perfusion (CTP) Grade I–II (OR, 4.129; 95% CI, 1.294–13.175; p = 0.017) were independent predictors of delayed anastomotic occlusion. Delayed anastomotic occlusion in adult hemorrhagic MMD might be a benign phenomenon. Good collateral circulation (Grade III) and compensable preoperative intracranial perfusion (CTP Grade I–II) are independent predictors for this phenomenon. Moreover, the delayed anastomotic occlusion has no significant correlations with the long-term angiographic and neurological outcomes, except neoangiogenesis. [ABSTRACT FROM AUTHOR]

Background: Cognitive impairment in adult moyamoya disease (MMD) is thought to be the result of ischemic stroke; however, the presence and extent of cognitive decline in asymptomatic patients is unclear.Methods: After classification using T2-weighted fluid attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI), a total of 19 MMD patients with a history of cerebral infarction, 21 asymptomatic MMD patients, and 20 healthy controls matched for age, sex, and years of education were prospectively included in this study. A detailed neuropsychological evaluation of two moyamoya subgroups and normal controls was conducted.Results: Asymptomatic patients showed varying degrees of decline in intelligence (Raven's Standard Progressive Matrices, P = 0.001), spatial imagination (mental rotation, P = 0.014), working memory (verbal working memory-backward digit span, P = 0.011), and computational ability (simple subtraction, P = 0.014; complex subtraction, P < 0.001) compared with normal controls. MMD patients with cerebral infarction had more severe impairment in complex arithmetic (P = 0.027) and word short-term memory (P = 0.01) than those without symptoms.Conclusion: In asymptomatic MMD patients, a variety of cognitive impairment precedes the onset of clinical symptoms such as cerebral infarction, which may be a long-term complication of conservative treatment. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to investigate the hemorrhgic sites and collateral vessels in hemorrhagic MMD with the p.R4810K variant.Methods: Hemorrhage sites were classified as either anterior or posterior. Collateral vessels were classified into three subtypes according to origin: lenticulostriate anastomosis, thalamic anastomosis, and choroidal anastomosis. Hemorrhage sites and collateral vessels were compared between patients with wild-type p.R4810K variant (GG) and patients with heterozygous p.R4810K variant (GA) after 1:1 propensity score matching.Results: A total of 130 hemorrhagic MMD patients were included in present study, 21 pairs (42 hemorrhagic hemispheres) were obtained after 1:1 propensity score. In GA group, 16 hemispheres (76.2%) presented anterior hemorrhage, and 5 hemispheres (23.8%) presented with posterior hemorrhage. In GG group, 13 hemispheres (61.9%) presented anterior hemorrhage, and 8 hemispheres (38.1%) presented with posterior hemorrhage. No significant differences were found in hemorrhagic sites between two matched groups (P > 0.05). Of 21 hemispheres in GA group, 10 (47.6%) exhibited lenticulostriate anastomosis, 6 (28.6%) thalamic anastomosis, and 6 (28.6%) choroidal anastomosis. Of 21 hemispheres in GG group, 3 (14.3%) exhibited lenticulostriate anastomosis, 5 (23.8%) thalamic anastomosis, and 9 (42.9%) choroidal anastomosis. There was significant difference in lenticulostriate anastomosis between two matched groups (P = 0.045). After adjustment the age, sex, and PCA involvement, we found that lenticulostriate anastomosis was associated with p.R4810K variant (OR, 5.995; 95% CI, 1.296-27.737; P = 0.022).Conclusion: Lenticulostriate anastomosis might be associated with p.R4810K variant. Whereas hemorrhagic sites, thalamic anastomosis, and choroidal anastomosis might not be associted withp.R4810K variant. [ABSTRACT FROM AUTHOR]

Background: Ischemic Moyamoya disease is one of the important causes of stroke, which leads to severe impairment in cognitive functions. This cognitive impairment occurs prior to stroke. However, the cognitive functions that are impaired and the mechanisms of these impairments have not been determined.Methods: We analyzed 12 patients with Moyamoya disease and 12 controls. All participants underwent cognitive tests and magnetic resonance imaging (MRI) scans. The diffusion tensor imaging (DTI) data was processed using Tract-Based Spatial Statistics (TBSS). Significantly different white matter areas were correlated with different cognitive functions.Results: There were significant differences in intelligence and subtraction between the patients and controls (p < 0.05). The parameters of DTI such as fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) have different changes in anterior thalamic radiation, inferior fronto-occipital fasciculus (IFO), superior longitudinal fasciculus (SLF), uncinate fasciculus (UF), inferior longitudinal fasciculus, forceps minor, and other regions between the two groups.Conclusion: Left UF and IFO may be the key brain regions affecting arithmetic function, while bilateral IFO has an effect on intelligence. RD and AD may be better indicators for early prediction of chronic white matter damage than FA, while MD tends to have a comprehensive indirect change. There is cognitive impairment in ischemic MMD, which is closely related to white matter impairment.Trial Registration: Clinical Trial Registration, Unique identifier: ChiCTR1900023610 . Registered 4 June 2019 - Prospective study registered. [ABSTRACT FROM AUTHOR]

Background Quasi-moyamoya disease (MMD) is characterized by moyamoya vasculopathy and well-recognized comorbidity. Whether the recently identified MMD susceptibility gene variant, p.R4810K (rs112735431), is associated with quasi-MMD remains unclear. Methods This study was a 2-hospital–based case–control study that was conducted in the neurosurgical departments of Beijing Tiantan Hospital and Peking University International Hospital. A total of 42 patients and 161 controls were enrolled. The p.R4810K polymorphism was assessed with Sanger sequencing. A review of the pertinent literature on the p.R4810K polymorphism and quasi-MMD was performed. Results The mean age of patients at diagnosis was 34.9 ± 16.5 years with a one-peak distribution in the forties; 57.1% of the patients were female. The p.R4810K heterozygous variant was identified in 5 patients, including 3 patients with atherosclerosis, 1 patient with Graves disease, and 1 patient with rheumatoid arthritis; it was also observed in one control. The frequencies of the A allele and the G/A genotype of rs112735431 (p.R4810K) were significantly greater in the patients with quasi-MMD than in the control groups (5.95% vs. 0.31%, odds ratio [OR] 20.316, P = 0.002; 11.9% vs. 0.6%, OR 21.622, P = 0.002, respectively). In the subgroup analysis, the rs112735431 G/A genotype was significantly associated with arteriosclerotic or autoimmune quasi-MMD ( P = 0.006, OR 25.263, confidence interval 2.501–255.175; P = 0.015, OR 29.091, confidence interval 2.444–346.334, respectively). Conclusions The p.R4810K variant was associated with atherosclerotic and autoimmune quasi-MMD in a Chinese population, and a lower prevalence of this variant in patients with quasi-MMD compared with patients with MMD was observed. [ABSTRACT FROM AUTHOR]