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Background and Objective: 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., Methods: 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., Results: 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., Conclusions: 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., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: Although asymmetrical vascular involvement between hemispheres is common in pediatric patients with bilateral moyamoya disease, whether hemispheres with mild vascular changes and hemodynamic impairment require immediate surgical revascularization or whether they can be observed until disease progression remains unclear. The authors evaluated the long-term outcomes of their strategy to initially perform unilateral surgery and withhold surgery to the contralateral hemispheres with mild vascular changes and hemodynamic impairment., Methods: The authors retrospectively evaluated Japanese pediatric patients (onset age ≤ 15 years) diagnosed with bilateral sporadic moyamoya disease who underwent unilateral revascularization. The authors investigated whether the patient underwent additional collateral surgery and the incidence of ischemic events during follow-up. They also compared visual assessments of arterial spin labeling (ASL) images obtained before initial surgery, before additional contralateral surgery, and at last follow-up., Results: Overall, 30/47 patients (63.8%) experienced progression of hemodynamic impairment in the contralateral hemisphere and underwent additional surgery. The age at initial surgery of the patients who needed additional contralateral surgery was significantly younger than that of the patients who did not require contralateral surgery (mean [SD] 7.0 [3.0] years vs 9.8 [2.6] years, p = 0.002). One patient (age 4 years) developed ischemic stroke before admission for preoperative evaluation 2 months after novel symptom onset, and another patient (age 6 years) experienced ischemic stroke in the contralateral hemisphere while discontinuing antiplatelet agents before surgery; both patients fully recovered from the neurological deficits. In contralateral hemispheres that required additional surgery, the ASL visual assessment scores significantly decreased before the additional contralateral surgery compared to those obtained before the initial surgery (p = 0.008)., Conclusions: In pediatric patients with bilateral moyamoya disease, withholding surgery for hemispheres with mild vascular changes and hemodynamic impairment is generally safe. Younger patients were more likely to experience contralateral progression and require additional surgery, so close follow-up is needed. ASL imaging is useful for detecting and following the progression of hemodynamic impairment in conservatively treated hemispheres.

Objective: A superficial temporal artery-middle cerebral artery (STA-MCA) bypass is classically considered a low-flow bypass. It is known that the flow in the flow augmentation STA-MCA bypass is influenced by flow demand of the revascularized territory and can reach significantly higher values. The authors report their intraoperative flow measurement data in a consecutive series of 100 STA-MCA bypasses performed at their institution. Moreover, in a subanalysis, they show the postoperative bypass flow measured with quantitative MR angiography (qMRA) noninvasive optimal vessel analysis (NOVA)., Methods: Between January 2013 and October 2023, 100 patients with acute, subacute, or chronic large-vessel occlusion (LVO) or moyamoya disease underwent a flow augmentation STA-MCA bypass revascularization at the authors' department with intraoperative bypass flow measurement. Patients with atherosclerotic LVO who underwent bypass surgery within a 6-week period following the onset of ischemic stroke symptoms were categorized into the acute bypass group, encompassing both acute and subacute LVO cases. Conversely, those who underwent bypass surgery > 6 weeks after the last occurrence of ischemic stroke were classified as the chronic group. Since May 2019, a consecutive subgroup of 37 patients received a postoperative (before discharge) bypass flow measurement with the qMRA-NOVA imaging tool., Results: The mean ± SD intraoperative bypass flow in this consecutive series of 100 STA-MCA bypasses was 53.5 ± 28.8 ml/min (range 14-145 ml/min). In the subanalysis, there was no difference in the intraoperative flow capacity between the acute and chronic groups and between the moyamoya and acute groups. Patients in the moyamoya group showed a significantly higher flow rate in the STA-MCA bypass compared with the chronic group (63.0 ± 30.2 ml/min vs 48.4 ± 26.5 ml/min, p = 0.03). In a consecutive subanalysis of 37 STA-MCA bypass cases, postoperative flow measurements were also performed using qMRA-NOVA, showing a significant increase in the flow of STA-MCA bypasses after surgery compared with intraoperative flow measurements (mean intraoperative bypass flow rate vs qMRA-NOVA postoperative bypass flow rate: 73.4 ± 29.9 ml/min vs 111.3 ± 51.4 ml/min, p = 0.005)., Conclusions: Using intraoperative and postoperative quantitative flow measurements of the STA, the data confirm that the flow in the flow augmentation STA-MCA bypass is influenced by the flow demand of the revascularized territory and can reach high values if needed. Moreover, the significant flow increase in the postoperative flow measurement using qMRA-NOVA demonstrates that the bypass can increase its flow over time.

Objective: Cerebral revascularization surgery (CRS) has been used to prevent stroke in children with sickle cell disease (SCD) and cerebral vasculopathy (e.g., moyamoya syndrome). While results suggest that it may be an effective treatment, surgical indications have not been well defined. This study sought to determine indications for offering revascularization surgery in centers with established sickle cell programs in the US., Methods: Three sequential surveys utilizing the Delphi methodology were administered to neurosurgeons participating in the Stroke in Sickle Cell Revascularization Surgery study. Respondents were presented with clinical scenarios of patients with SCD and varying degrees of ischemic presentation and vasculopathy, and the group's agreement to offer surgical revascularization was measured. Consensus was defined as ≥ 75% similar responses., Results: The response rate to all 3 surveys was 100%. Seventeen neurosurgeons from 16 different centers participated. The presence of moyamoya collaterals (MMCs) and arterial stenosis matching an ischemic distribution yielded the strongest recommendations to offer surgery. There was consensus to offer revascularization in the presence of MMCs and at least 50% arterial stenosis matching an ischemic distribution. In contrast, there was no consensus to offer revascularization with 50%-70% stenosis not matching an ischemic presentation in the absence of MMCs. The presence of the ivy sign in the distribution of the stenotic artery also contributed to the consensus to offer surgery in certain scenarios., Conclusions: There were several clinical scenarios that attained consensus to offer surgery; the strongest was moderate to severe arterial stenosis that matched the distribution of ischemic presentation in the presence of MMCs. Radiological findings of decreased cerebral flow or perfusion also facilitated attaining consensus to offer surgery. The findings of this study reflect expert opinion about questions that deserve prospective clinical research. Determination of indications for CRS can guide clinical practice and aid the design of prospective studies.

Objective: Diabetes is often linked to poorer outcomes in patients with moyamoya disease (MMD). However, experience has shown that certain individuals with diabetes have favorable outcomes after encephaloduroarteriosynangiosis (EDAS). The authors aimed to develop a nomogram to predict good neoangiogenesis in patients with MMD and type 2 diabetes mellitus (T2DM) to aid neurosurgeons in the identification of suitable candidates for EDAS., Methods: Adults with MMD and T2DM who underwent EDAS between June 2004 and December 2018 were included in the analysis. In total, 126 patients (213 hemispheres) with MMD and T2DM from the Fifth Medical Centre of the Chinese PLA General Hospital were included and randomly divided into training (152 hemispheres) and internal validation (61 hemispheres) cohorts at a ratio of 7:3. Univariate logistic and least absolute shrinkage and selection operator regression analyses were used to identify the significant factors associated with good neoangiogenesis, which were used to develop a nomogram. The discrimination, calibration, and clinical utility were assessed., Results: A total of 213 hemispheres in 126 patients were reviewed, including 152 (71.36%) hemispheres with good postoperative collateral formation and 61 (28.64%) with poor postoperative collateral formation. The authors selected 4 predictors (FGD5 rs11128722, VEGFA rs9472135, Suzuki stage, and internal carotid artery [ICA] moyamoya vessels) for nomogram development. The C-indices of the nomogram in the training and internal validation cohorts were 0.873 and 0.841, respectively. The nomogram exhibited a sensitivity of 84.5% and specificity of 81.0%. The positive and negative predictive values were 92.1% and 66.7%, respectively. The calibration curves indicated high predictive accuracy, and receiver operating characteristic curve analysis showed the superiority of the nomogram. The decision-making analysis validated the fitness and clinical application value of this nomogram. Then a web-based calculator to facilitate clinical application was generated., Conclusions: The nomogram developed in this study accurately predicted neoangiogenesis in patients with MMD and T2DM after EDAS and may assist neurosurgeons in identifying suitable candidates for indirect revascularization surgery.

Objective: The aim of this study was to develop and validate a predictive nomogram model for long-term rebleeding events in patients with hemorrhagic moyamoya disease (HMMD)., Methods: In total, 554 patients with HMMD from the Fifth Medical Center of the Chinese PLA General Hospital (5-PLAGH cohort) were included and randomly divided into training (390 patients) and internal validation (164 patients) sets. An independent cohort from the First Medical Center and Eighth Medical Center of Chinese PLA General Hospital (the 1-PLAGH and 8-PLAGH cohort) was used for external validation (133 patients). Univariate Cox regression analysis and least absolute shrinkage and selection operator (LASSO) regression algorithm were used to identify significant factors associated with rebleeding, which were used to develop a nomogram for predicting 5- and 10-year rebleeding., Results: Intraventricular hemorrhage was the most common type of cerebral hemorrhage (39.0% of patients in the 5-PLAGH cohort and 42.9% of the 1-PLAGH and 8-PLAGH cohort). During the mean ± SD follow-up period of 10.4 ± 2.9 years, 91 (16.4%) patients had rebleeding events in the 5-PLAGH cohort. The rebleeding rates were 12.3% (68 patients) at 5 years and 14.8% (82 patients) at 10 years. Rebleeding events were observed in 72 patients (14.3%) in the encephaloduroarteriosynangiosis (EDAS) surgery group, whereas 19 patients (37.3%) experienced rebleeding events in the conservative treatment group. This difference was statistically significant (p < 0.001). We selected 4 predictors (age at onset, number of episodes of bleeding, posterior circulation involvement, and EDAS surgery) for nomogram development. The concordance index (C-index) values of the nomograms of the training cohort, internal validation cohort, and the external validation cohort were 0.767 (95% CI 0.704-0.830), 0.814 (95% CI 0.694-0.934), and 0.718 (95% CI 0.661-0.775), respectively. The nomogram at 5 years exhibited a sensitivity of 48.1% and specificity of 87.5%. The positive and negative predictive values were 38.2% and 91.3%, respectively. The nomogram at 10 years exhibited a sensitivity of 47.1% and specificity of 89.1%. The positive and negative predictive values were 48.5% and 88.5%, respectively., Conclusions: EDAS may prevent rebleeding events and improve long-term clinical outcomes in patients with HMMD. The nomogram accurately predicted rebleeding events and assisted clinicians in identifying high-risk patients and devising individual treatments. Simultaneously, comprehensive and ongoing monitoring should be implemented for specific patients with HMMD throughout their entire lifespan.

Objective: Moyamoya arteriopathy can develop in patients with brain tumors, particularly when associated with neurofibromatosis type 1 (NF1) or cranial irradiation. The present study aimed to analyze the clinical outcomes of moyamoya after brain tumor treatment and elucidate the effect of revascularization on brain tumors., Methods: The authors retrospectively reviewed clinical and radiographic findings in 27 patients with brain tumors who developed moyamoya requiring revascularization surgery between January 1985 and June 2017 at a single institution. The long-term clinical and neuroimaging-based outcomes were analyzed., Results: Among 27 patients, 22 patients underwent radiotherapy, and 12 patients had NF1. The mean ages at diagnosis of brain tumors and moyamoya were 4.4 years and 10.3 years, respectively. The mean interval between radiotherapy and moyamoya diagnosis was 4.0 years. The mean follow-up period after revascularization surgery was 8.5 years. Among 46 affected hemispheres in 27 patients, the patients who underwent radiotherapy (30 hemispheres in 22 patients) had a higher incidence of Suzuki stage 5 or 6 (20% [6/30] vs 0% [0/8]) and infarction (63.6% [14/22] vs 0% [0/5]) compared with patients without radiotherapy (8 hemispheres in 5 patients). After revascularization, stroke occurred in 4 patients, and 6 hemispheres showed Matsushima grade C, all of which occurred in patients with a history of radiotherapy. The residual brain tumors progressed in 4 of 21 patients (19%) after revascularization, comparable to the progression rates of brain tumors without revascularization in previous literature., Conclusions: Patients with brain tumors can develop moyamoya that exhibits characteristic clinical and radiographic features of idiopathic MMD. Moyamoya associated with cranial irradiation has a higher incidence of stroke with less capacity for revascularization, requiring thorough evaluations and timely treatment. Revascularization does not appear to have any effect on the progression of existing brain tumors.

Moyamoya disease (MMD) is characterized by idiopathic, progressive stenosis of the circle of Willis and the terminal portion of the internal carotid arteries with the development of prominent small collateral vessels and a characteristic moyamoya or puff-of-smoke radiographic appearance. The incidence and prevalence of MMD varies by region, age, and sex, with higher rates in Asian and East Asian populations compared to North American or European populations. There is a bimodal distribution of patients diagnosed with MMD. Pediatric patients are more commonly diagnosed within the 1st decade of life, whereas adult patients present in the 5th or 6th decade of life. Overall, there is a nearly 2:1 female-to-male ratio. Ischemic symptoms are the most common presentation in pediatric and adult populations, but adult patients are nearly twice as likely to present with intracranial hemorrhage compared to their pediatric counterparts. Surgical revascularization is indicated in symptomatic cases, and antiplatelet therapy may be a useful adjunct to prevent recurrent symptoms. Direct and combined bypass procedures seem to be more effective in adults, whereas children respond well to indirect bypass. The identification of key genetic, molecular, and environmental factors including RNF213 and GUCY1A3 loss-of-function mutations, angiogenic growth factors, autoantibodies, CNS infections, and radiation exposure suggest multiple pathways for the development of moyamoya arteriopathy. Further research is needed to better understand the heterogeneity of pathogenetic mechanisms that lead to moyamoya and to identify novel therapeutic targets to prevent, stabilize, and treat MMD.

Objective: The aim of this study was to identify predictive factors of postoperative cerebral infarction (PostCI) following combined bypass (CB) surgery in adult patients with moyamoya disease (MMD) using quantitative parameters from the rapid processing of perfusion and diffusion (RAPID) perfusion CT (PCT) software., Methods: The authors retrospectively reviewed 276 total hemispheres in patients with MMD who underwent CB. Preoperative volumes of time-to-maximum (Tmax) > 4 sec and > 6 sec were obtained from the RAPID analysis of PCT. These quantitative parameters, along with other clinical and angiographic factors, were statistically analyzed to determine the significant predictors for PostCI following CB., Results: PostCI occurred in 17 hemispheres (6.16%). PCA involvement (p = 0.016), and the volume of Tmax > 6 sec (p < 0.001) and Tmax > 4 sec (p < 0.001), were identified as variables related to PostCI in the univariable analysis. In the multivariable analysis, the volume of Tmax > 6 sec (OR 1.013, 95% confidence interval 1.007-1.019, p < 0.001) was determined to be an independent predictive factor significantly associated with PostCI after CB in adult patients with MMD. In the receiver operating characteristic (ROC) curve, the cutoff value of the preoperative volume of Tmax > 6 sec was determined to be 59.5 ml (sensitivity 82.4%, specificity 71.9%, area under the ROC curve 0.811)., Conclusions: For adult patients with MMD and a large volume of Tmax > 6 sec over 59.5 ml, more caution is required when deciding to undergo bypass surgery and in postoperative management.

Objective: Indirect revascularization is a common and effective treatment for pediatric moyamoya disease. However, in several cases postoperative angiogenesis is not sufficient. It is not fully understood which factors are involved in the development of postoperative collateral circulation. In this study, the authors aimed to elucidate the factors related to postoperative angiogenesis in indirect revascularization., Methods: Among the patients who underwent indirect revascularization for moyamoya disease from January 2015 to December 2022, those whose angiogenesis was evaluated using angiography were included. Age, onset symptoms, comorbidities, preoperative imaging findings, surgical details, perioperative complications, postoperative imaging findings, and modified Rankin Scale (mRS) score at the last outpatient visit were retrospectively examined., Results: Ninety cases (53 patients; 37 bilateral, 16 unilateral) were included. Sixty-eight cases (75.6%) were symptomatic. The mean age at surgery was 7.9 years, and the mean postoperative follow-up duration was 48.5 months. Frontotemporal encephalo-duro-arterio-synangiosis (EDAS) was performed in all cases, and simultaneous frontal encephalo-galeo-synangiosis (EGS) was performed in 34 cases. Postoperative angiography revealed insufficient angiogenesis in 14 of 90 cases (15.6%) after frontotemporal EDAS and in 8 of 34 cases (23.5%) after frontal EGS. A high degree of ivy sign depicted on preoperative MRI was found to be significantly correlated with good angiogenesis after both surgical procedures (p = 0.00030 for EDAS and p = 0.0039 for frontal EGS). In addition, an advanced preoperative Suzuki stage was significantly correlated with good postoperative angiogenesis after EDAS (p = 0.00040). Good angiogenesis was significantly correlated with postoperative improvement of the ivy sign in both procedures (p = 0.0005 in EDAS and p = 0.030 in frontal EGS) as well as correlated with a better mRS score at long-term follow-up after EDAS (p = 0.018)., Conclusions: Preoperative ivy sign and Suzuki classification are related to the degree of angiogenesis achieved after indirect revascularization for pediatric moyamoya disease.

Objective: Cerebral infarction is a common complication in patients undergoing revascularization surgery for moyamoya disease (MMD). Although previous statistical evaluations have identified several risk factors for postoperative brain ischemia, the ability to predict its occurrence based on these limited predictors remains inadequately explored. This study aimed to assess the feasibility of machine learning algorithms for predicting cerebral infarction after revascularization surgery in patients with MMD., Methods: This retrospective study was conducted across two centers and harnessed data from 512 patients with MMD who had undergone revascularization surgery. The patient cohort was partitioned into internal and external datasets. Using perioperative clinical data from the internal cohort, three distinct machine learning algorithms-namely the support vector machine, random forest, and light gradient-boosting machine models-were trained and cross-validated to predict the occurrence of postoperative cerebral infarction. Predictive performance validity was subsequently assessed using an external dataset. Shapley additive explanations (SHAP) analysis was conducted to augment the prediction model's transparency and to quantify the impact of each input variable on shaping both the aggregate and individual patient predictions., Results: In the cohort of 512 patients, 33 (6.4%) experienced postrevascularization cerebral infarction. The cross-validation outcomes revealed that, among the three models, the support vector machine model achieved the largest area under the receiver operating characteristic curve (ROC-AUC) at mean ± SD 0.785 ± 0.052. Notably, during external validation, the light gradient-boosting machine model exhibited the highest accuracy at 0.903 and the largest ROC-AUC at 0.710. The top-performing prediction model utilized five input variables: postoperative serum gamma-glutamyl transpeptidase value, positive posterior cerebral artery (PCA) involvement on preoperative MRA, infarction as the rationale for surgery, presence of an infarction scar on preoperative MRI, and preoperative modified Rankin Scale score. Furthermore, the SHAP analysis identified presence of PCA involvement, infarction as the rationale for surgery, and presence of an infarction scar on preoperative MRI as positive influences on postoperative cerebral infarction., Conclusions: This study indicates the usefulness of employing machine learning techniques with routine perioperative data to predict the occurrence of cerebral infarction after revascularization procedures in patients with MMD.

Objective: This study aimed to investigate whether high homocysteine (Hcy) levels associated with the MTHFR gene influence the formation of the collateral vascular network in patients with moyamoya disease (MMD) after encephaloduroarteriosynangiosis (EDAS) by influencing the number of endothelial progenitor cells (EPCs) in peripheral blood., Methods: A total of 118 Chinese patients with bilateral primary MMD were prospectively included. Blood samples were collected from the anterior cubital vein before surgery, and MTHFR rs9651118 was genotyped using high-throughput mass spectrometry to determine the genotype of the test specimen. Serum Hcy and EPC levels were measured, the latter with flow cytometry. Digital subtraction angiography was performed 6 months after EDAS, and the formation of collateral circulation was evaluated using the Matsushima grade system. The correlations between MTHFR rs9651118 genotype, Hcy and EPC levels, and Matsushima grade were compared., Results: Among the 118 patients, 53 had the TT genotype (wild type) of MTHFR rs9651118, 33 TC genotype (heterozygous mutation), and 32 CC genotype (homozygous mutation). The mean ± SD Hcy level was 13.4 ± 9.5 μmol/L in TT patients, 9.8 ± 3.2 μmol/L in TC patients, and 8.9 ± 2.9 μmol/L in CC patients (p < 0.001). The level of EPCs in the venous blood of TT patients was 0.039% ± 0.016%, that of TC patients 0.088% ± 0.061%, and that of CC patients 0.103% ± 0.062% (p < 0.001). When the rs9651118 gene locus was mutated, Matsushima grade was better (p < 0.001) but there was no difference between heterozygous and homozygous mutations., Conclusions: The results suggest that the MTHFR rs9651118 polymorphism is a good biomarker for collateral vascular network formation after EDAS in MMD patients.

Objective: Intellectual function declines in about 30% of children with moyamoya disease (MMD). Memory function underpins higher order brain function, but the relationship between intellectual function and memory in pediatric MMD patients has not been well studied. This study aimed to investigate correlations between scores on the Wechsler Intelligence Scale for Children (WISC) and the Benton Visual Retention Test (BVRT), a visual memory test that can be administered to children, in children with MMD. Relationships between intellectual function or memory and regional cerebral blood flow (rCBF) have also not been well clarified in pediatric MMD patients. The authors also investigated associations between WISC or BVRT scores and rCBF in various brain regions., Methods: WISC and BVRT scores and rCBF were assessed in 17 children with ischemic-onset MMD before revascularization. Single-photon emission CT with 123I-iodoamphetamine was used to measure rCBF. Relationships between WISC and BVRT scores were evaluated using Spearman's correlation coefficient and multivariate linear regression analysis. Cutoff values were identified for BVRT scores. Sensitivity and specificity were calculated to predict full-scale intelligence quotient (FSIQ) > 85 or ≤ 85. Associations between rCBF and WISC or BVRT scores were evaluated using linear regression analysis., Results: BVRT scores were significantly correlated with FSIQ and scores on the Working Memory Index (WMI), Processing Speed Index, and Verbal Comprehension Index (VCI)/Verbal Intelligence Quotient (VIQ) of WISC. Multivariate linear regression revealed that number correct score and number of errors score of BVRT were associated with FSIQ. As cutoff values, a number correct score of 5 and a number of errors score of 8 offered the most reliable predictors of FSIQ > 85 and ≤ 85, respectively. FSIQ correlated positively with rCBF in the right and left hemispheres, right and left ganglia, right and left thalamus, right and left cerebellum, right middle cerebral artery (MCA) territory, pons, and vermis. WMI score was positively associated with rCBF in the right hemisphere, right anterior cerebral artery territory, right MCA territory, right basal ganglia, right and left thalamus, right and left cerebellum, pons, and vermis., Conclusions: BVRT score correlated well with WISC index scores, suggesting that BVRT may be helpful in screening for intellectual impairments in children with MMD. In the MCA territory, basal ganglia, thalamus, cerebellum, pons, and vermis, rCBF associated well with WISC index scores, suggesting that reduced rCBF in relevant brain regions may influence intellectual function.

Objective: The objective of this retrospective study was to establish a novel system for evaluating collateralization of the external carotid artery in patients with moyamoya disease (MMD) following direct and indirect revascularization surgeries., Methods: The authors conducted a retrospective analysis of 456 patients diagnosed with MMD who underwent direct and indirect revascularization procedures at Beijing Tiantan Hospital, Capital Medical University, between January 2015 and May 2023. Using a newly proposed digital subtraction angiography (DSA)-based evaluation system, the authors assessed collateralization angiogenesis objectively and in a standardized manner., Results: The authors' findings indicated that there was no significant difference in collateralization angiogenesis between patients undergoing direct or indirect cerebral revascularization (p = 0.702). However, after cerebral revascularization, patients with ischemic MMD exhibited significantly higher collateralization angiogenesis compared with those with hemorrhagic MMD (p = 0.007). Children with MMD demonstrated higher angiogenesis levels than adults (p < 0.001), but subgroup analysis showed age-specific variations. In adults, collateralization angiogenesis was significantly greater in those with ischemic MMD (p = 0.006), whereas in children, no significant difference was noted between ischemic and hemorrhagic MMD (p = 0.962). Furthermore, regardless of MMD type, direct and indirect revascularization methods yielded similar collateralization angiogenesis (p = 0.962 and p = 0.963, respectively). Importantly, the Matsushima grading system revealed significant differences in angiogenesis in patients with ischemic MMD (p < 0.001)., Conclusions: The newly introduced DSA-based evaluation system offers an objective and standardized method for assessing collateralization angiogenesis in MMD. This study supports the efficacy of both direct and indirect revascularization surgical procedures and highlights distinct pathophysiological processes of ischemic and hemorrhagic disease subtypes. These findings contribute to a better understanding of surgical outcomes and aid in the selection of appropriate treatment strategies for patients with MMD.

Objective: Perioperative stroke is a major complication of revascularization surgery in patients with moyamoya. Vomiting is common after neurosurgical procedures and may result in acute changes in intracranial pressure and cerebral blood flow. The authors instituted a standardized perioperative nausea and vomiting protocol for children with moyamoya undergoing indirect bypass surgery at their institution and analyzed its association with perioperative stroke. They hypothesized that instituting a standardized perioperative nausea and vomiting protocol would be associated with reduction in the number of perioperative strokes in children with moyamoya undergoing indirect bypass surgery., Methods: The authors retrospectively reviewed consecutive cases of children and young adults with moyamoya who underwent indirect bypass surgery before and after implementation of a new perioperative nausea and vomiting protocol at a single institution. They compared the rate of strokes in the perioperative period (postoperative days 0 and 1) in the 31 months following implementation to 31 months prior to implementation using Fisher's exact test., Results: The median ages pre- and postimplementation were 8.5 (IQR 4-12) years and 8.3 (IQR 5-15) years, respectively. There were no significant differences between the cohorts in disease severity or other potentially confounding factors. In the 31 months prior to initiation of the perioperative nausea and vomiting protocol, there were 5 strokes in 137 surgically treated hemispheres (3.6%). After initiation of the protocol, there were no strokes in 114 surgically treated hemispheres (p = 0.065)., Conclusions: Instituting a standardized perioperative nausea and vomiting protocol was associated with reduction in perioperative strokes in children with moyamoya treated with indirect bypass surgery.

Objective: Transient neurological events (TNEs) are among the most important events after revascularization surgery in pediatric patients with moyamoya disease (MMD). Although hemodynamic changes and crying are representative factors of TNEs, brain compression by encephalomyosynangiosis (EMS) is another important cause of TNEs. Therefore, the authors assumed that making the EMS as thin as possible reduces the frequency of TNEs. However, thin-split EMS can lead to insufficient development of collateral vessels. This study aimed to evaluate the effects of thin-split EMS in combined revascularization surgery on postoperative outcomes in pediatric patients with MMD., Methods: The authors retrospectively included 56 consecutive combined revascularization surgeries in the anterior cerebral circulation in pediatric patients with MMD. These surgeries were classified into the former group and thin-split EMS group. The temporal muscle was halved in the former EMS group and split as thinly as possible in the thin-split EMS group. The authors performed between-group comparisons of postoperative stroke events and TNEs during the acute period and the development of collateral flow and stroke events during the chronic period., Results: Former and thin-split EMS procedures were performed in 37 and 19 patients, respectively. TNEs without crying or hemodynamic changes were observed significantly less frequently in the thin-split EMS group than in the former EMS group (0 [0.0%] in the thin-split EMS group vs 9 [24.3%] in the former EMS group, p = 0.021). There were no significant between-group differences in the development of indirect bypass during the chronic period (good: 34 [91.9%] and poor: 3 [8.1%] in the former EMS group vs good: 16 [84.2%] and poor: 3 [15.8%] in the thin-split EMS group; p = 0.397). Additionally, there were no significant between-group differences in the incidence of chronic clinical events, including death or stroke., Conclusions: Thin-split EMS can reduce TNEs that do not accompany crying or hemodynamic changes. Furthermore, the procedure has sufficient prevention effects against stroke events during the chronic postoperative period in pediatric patients with MMD.

Objective: The aim of this study was to evaluate whether indirect revascularization in pediatric patients with moyamoya disease leads to periventricular anastomosis (PVA) regression, which is markedly developed in moyamoya vessels and is regarded as a risk factor for hemorrhage., Methods: Pediatric patients with moyamoya disease treated with indirect revascularization from 2011 to 2021 were included in this study. Magnetic resonance angiography and arterial spin labeling images acquired before and 1 year after surgery were assessed to obtain a visual scale of postoperative collateral artery formation, moyamoya vessels, PVA, and quantitative values of cerebral blood flow (CBF). The relationship between background information (age, sex, RNF213 p.R4810K variant status, and preoperative CBF) and postoperative collateral artery formation, as well as postoperative CBF improvement and regression of moyamoya vessels and PVA, was evaluated., Results: Of 89 hemispheres in 58 patients (34 females; mean [SD] patient age 8.0 [3.4] years), 74.2% showed good postoperative collateral artery formation and a significant increase in CBF (p < 0.001). Postoperative PVA showed significant regression (postoperative score 1.46 [1.06] vs 2.02 [1.69], p = 0.001), especially in those arising from choroidal arteries (postoperative score 0.28 [0.50] vs 0.72 [0.67], p < 0.001). Compared with hemispheres without good collateral artery formation, those with good collateral artery formation were more likely to show a higher increase in CBF (9.74 [12.44] ml/min/100 g vs -4.86 [9.68] ml/min/100 g, p < 0.001) and regression of PVA (54.5% [36/66] vs 30.4% [7/23], p = 0.015). Although not statistically significant, patients with postoperative PVA progression were younger than those with regression (6.75 [3.03] years vs 8.18 [3.17] years, p = 0.188), and patients with the RNF213 p.R4810K variant were more likely to show regression (28/57 [49.1%] hemispheres vs 5/13 [38.5%] hemispheres, p = 0.069)., Conclusions: Indirect revascularization in pediatric patients with moyamoya disease resulted in good collateral extracranial artery formation and an increase in CBF and PVA regression, especially of vessels arising from choroidal arteries. With good postoperative collateral artery development, patients were more likely to show improved CBF and regression of moyamoya vessels, including PVA. Whether postoperative PVA changes reduce future hemorrhage risk requires further investigation.

Objective: This study aimed to explore the clinical features of moyamoya disease (MMD) and the efficacy of encephaloduroarteriosynangiosis (EDAS) in elderly patients with MMD and to identify the risk factors for long-term stroke events., Methods: Clinical data were retrospectively collected on elderly patients with MMD (age ≥ 60 years) who had been treated at the authors' center from May 2007 to December 2017. Clinical features, angiographic findings, and long-term outcomes (> 5-year follow-up) were analyzed. Cox regression analysis was performed to determine the risk factors for postoperative stroke events. Long-term stroke events were analyzed using Kaplan-Meier curves., Results: The mean age at symptom onset was 62.9 ± 3.0 years among 111 elderly patients with MMD. Vascular comorbidities were present in 80 (72.1%) patients. The ratio of female to male patients was 1:1.2. Familial MMD was found in 7 (6.3%) patients. Cerebral ischemia was the most common clinical manifestation observed in 82 (73.9%) patients. Most patients (59.5%) presented with Suzuki stages 5 and 6 MMD, and 29 (26.1%) patients presented with stenosis or occlusion of the posterior circulation. Unilateral MMD was present in 17 (15.3%) patients. Among the 58 (52.3%) patients who underwent EDAS, 28 (48.3%) and 30 (51.7%) underwent bilateral and unilateral surgeries, respectively. Overall, 53 (47.7%) patients were treated conservatively using internal medicine. After a median follow-up duration of 8.2 years, stroke incidence in the EDAS and conservative treatment groups was respectively 17.2% (7 and 3 cases of cerebral infarction and hemorrhage, respectively) and 49.1% (22 and 4 cases of cerebral infarction and hemorrhage, respectively). The stroke incidence rate was higher in the conservative group than in the EDAS group, with a statistically significant difference (p = 0.001) according to results of the Kaplan-Meier analysis. The identified predictor of postoperative stroke events was initial hemorrhage in the EDAS group and advanced age, aneurysm, and initial ischemia in the conservative treatment group., Conclusions: The postoperative long-term stroke rate among elderly patients with MMD was lower in the EDAS group than in the conservative treatment group. Long-term stroke events were associated with advanced age, aneurysm, and initial ischemia after conservative treatment and only initial hemorrhage after EDAS.

Objective: Choroidal anastomosis (ChA) has been implicated as the main indicator of an increased hemorrhagic risk in adult moyamoya disease. In this retrospective study, the authors aimed to identify the potential risk factors that can influence the rupture of ChA., Methods: The authors evaluated the clinical and radiological data on brain hemispheres positive for ChA from September 2019 to March 2023. The rupture status of the ChA was determined using previously described methods. Two independent raters quantitatively investigated the lumen diameter (LD) and lumen area (LA) of the ChA using high-resolution vessel wall imaging (VWI). Multivariate logistic regression analysis was conducted to identify the risk factors for ruptured ChA., Results: Ruptured and unruptured ChAs were identified in 16 and 60 hemispheres, respectively. Univariate analysis showed that the mean values of the LD (1.251 ± 0.241 vs 0.967 ± 0.214 mm, p < 0.001) and LA (1.607 ± 0.445 vs 0.945 ± 0.372 mm2, p < 0.001) of ChAs were significantly greater in the ruptured group than in the unruptured group. A periventricular anastomosis (PA) score of 1, indicating the angiographic presence of ChA alone, was more prevalent in the ruptured group than in the unruptured group (43.8% vs 11.7%, p = 0.003). Multivariate analysis demonstrated that a larger LA of the ChA (OR 37.01, 95% CI 5.787-236.7, p < 0.001) and PA score 1 (OR 6.661, 95% CI 1.260-35.21, p = 0.026) were independently associated with ruptured ChA hemispheres. Receiver operating characteristic curve analysis revealed that the optimal cutoff point for the LA was 1.285 mm2 (sensitivity 81.3%, specificity 86.7%)., Conclusions: A larger LA (> 1.285 mm2) of the ChA and the angiographic presence of ChA alone are independent risk factors for a ruptured ChA. Revascularization surgery for the prevention of future hemorrhage may be indicated for hemispheres with a high-risk unruptured ChA. These characteristics may help to determine treatment strategies for patients with an unruptured ChA.

Objective: Direct cerebral revascularization is considered as one of the most technically challenging operations in neurosurgery. Technical errors are often not identified during the case, but only after the recirculation stage, making management crucial at that time of the procedure. In this study, the authors sought to describe troubleshooting of the technical errors encountered in initially failed bypass cases., Methods: A retrospective analysis describing a single-surgeon, single-institution experience between 2014 and 2021 was performed, based on operative reports and videos, including a 30-day follow-up period. Initially failed bypass was defined if the bypass was not patent or had a significant leak after recirculation, irrespective of the final result., Results: One hundred thirty-eight bypass cases were reviewed for complex aneurysms (n = 49), moyamoya disease (n = 59), and atherosclerosis (n = 30). Fifty-one initially failed anastomoses were identified; 43 of these were the result of a technical error. Etiologies of these failed anastomoses included a clot (n = 14), vessel kinking (n = 4), spasm (n = 5), suture-related cause (n = 5), inappropriate donor or recipient (n = 3), or lack of demand (n = 8). A major leak was attributed to an uncoagulated side branch (n = 4), vessel injury due to suture/clip placement (n = 1), or inadequate suture line coverage (n = 7). Thirty-seven (86%) of 43 cases were troubleshot successfully, as salvage maneuvers included papaverine vessel massage, donor repositioning, re-anastomosis for occlusion in select cases, local hemostatic agents, and suturing or coagulating side branches in a leak. Thirty-day follow-up revealed similar rates of patency between successfully troubleshot patients (35/37) and the rest of the cases (80/87, p = 0.6)., Conclusions: Three major patterns of a noncompatible bypass were found: a major leak, an acute occlusion, or a delayed occlusion. Based on the authors' experience, salvage strategies proved successful, showing an eventual high patency rate. The authors suggest a gradual, structured algorithm to address this stage in surgery that may contribute specifically to cerebrovascular neurosurgeons at the beginning of their careers.

Objective: The optimal surgical approach for hemorrhagic moyamoya disease (hMMD) continues to be a topic of debate. The authors' prior research demonstrated that both combined and indirect revascularization were efficacious. However, questions remain regarding the long-term prognosis consistency between these two treatments. Therefore, the objective of this study was to evaluate and compare the enduring effects of these surgical modalities on adult hMMD, extending the findings of the authors' previous studies., Methods: The authors recruited patients diagnosed with hMMD between 2010 and 2015. The patients were categorized into two groups: those who underwent combined revascularization (superficial temporal artery-middle cerebral artery bypass alongside dural reverse application) and those who underwent indirect revascularization (encephaloduroarteriosynangiosis [EDAS]). The primary and secondary endpoints of this study were instances of rebleeding, confirmed with CT scan, and death resulting from rebleeding, respectively. The authors estimated rebleeding-free and death-free survival rates by utilizing the Kaplan-Meier survival method. They used Cox regression to adjust for confounders and to evaluate the effects of the varying surgical modalities on the endpoints., Results: After an average follow-up period of 114 months, 35 patients (28.6%) experienced 40 rebleeding events, yielding an average annual incidence of 3.5%. Of the 79 patients who received combined revascularization, 17 (21.5%) experienced rebleeding events. Similarly, of 43 patients who underwent EDAS, 18 (41.9%) experienced rebleeding events (p = 0.018). Most rebleeding instances occurred 61-120 months after surgery (21 patients [60%]), followed by 12-60 months (11 patients [31.4%]). Multivariate survival analysis highlighted significant differences in surgical outcomes (HR 0.33, 95% CI 0.15-0.74, p = 0.007). The authors observed that 8 patients (10.1%) died of rebleeding events in the combined group, as well as 10 patients (23.3%) in the EDAS group. Despite the lack of a statistically significant difference in mortality (p = 0.051), multivariable survival analysis found a significant difference (HR 0.31, 95% CI 0.10-0.97, p = 0.044)., Conclusions: High rebleeding rates persist in adult hMMD patients, even after revascularization. Combined revascularization proved superior to EDAS in preventing long-term rebleeding. In contrast, EDAS alone did not display a clear effect on reducing long-term rebleeding rates.

Objective: Moyamoya disease (MMD) is a chronic steno-occlusive cerebrovascular disease and features the formation of hazy collateral vessels at the base of the brain. Angiopoietin (Ang)-1 and -2, their receptor Tie-2, and vascular endothelial growth factor (VEGF) that regulate angiogenesis might be important in MMD pathophysiology and postoperative collateral formation. The goal of this study was to determine whether levels of these angiogenic factors could predict collateralization in patients with MMD., Methods: A total of 196 patients with MMD and 57 with atherosclerotic cerebrovascular disease serving as controls were enrolled. Ang-1, Ang-2, Tie-2, and VEGF mRNA levels were analyzed in middle cerebral artery (MCA) arterial wall specimens by using real-time quantitative polymerase chain reaction. MCA and peripheral plasma concentrations of Ang-1, Ang-2, soluble Tie-2 (sTie-2), and VEGF were examined by enzyme-linked immunosorbent assay. Cerebral arteriography was performed 6 months after bypass surgery to assess the postoperative collateralization., Results: In MCA specimens, patients with MMD exhibited higher expression levels of Ang-1 and Ang-2 but lowered VEGF expression. The patients with MMD had significantly higher concentrations of Ang-1 and Ang-2 but lower levels of VEGF in MCA plasma. Peripheral plasma concentrations of these growth factors were not changed. MCA and peripheral plasma sTie-2 levels were both reduced in patients with MMD. The 6-month follow-up showed that patients with good collateral formation had lower sTie-2 levels in both MCA and peripheral plasma. Furthermore, the Suzuki stage and peripheral plasma sTie-2 level were significantly correlated with good postoperative collateral formation on multivariate analysis., Conclusions: Ang-1, Ang-2, Tie-2, and VEGF are involved in MMD pathogenesis. The peripheral plasma level of sTie-2 can differentiate MMD from atherosclerotic cerebrovascular disease and serve as a novel biomarker to predict postoperative collateral formation.

Objective: Little is known about the relationship between postoperative changes in cerebral perfusion and the ivy sign representing leptomeningeal collateral burden in moyamoya disease (MMD). This study aimed to investigate the usefulness of the ivy sign in evaluating cerebral perfusion status following bypass surgery in patients with adult MMD., Methods: Two hundred thirty-three hemispheres in 192 patients with adult MMD undergoing combined bypass between 2010 and 2018 were retrospectively enrolled. The ivy sign was represented as the ivy score on FLAIR MRI in each territory of the anterior, middle, and posterior cerebral arteries. Ivy scores, as well as clinical and hemodynamic states on SPECT, were semiquantitatively compared both preoperatively and at 6 months after surgery., Results: Clinical status improved at 6 months after surgery (p < 0.01). On average, ivy scores in whole and individual territories were decreased at 6 months (all p values < 0.01). Cerebral blood flow (CBF) postoperatively improved in three individual vascular territories (all p values ≤ 0.03) except for the posterior cerebral artery territory (PCAt), and cerebrovascular reserve (CVR) improved in those areas (all p values ≤ 0.04) except for the PCAt. Postoperative changes in ivy scores and CBF were inversely correlated in all territories (p ≤ 0.02), except for the PCAt. Furthermore, changes in ivy scores and CVR were only correlated in the posterior half of the middle cerebral artery territory (p = 0.01)., Conclusions: The ivy sign was significantly decreased after bypass surgery, which was well correlated with postoperative hemodynamic improvement in the anterior circulation territories. The ivy sign is believed to be a useful radiological marker for postoperative follow-up of cerebral perfusion status.

Objective: In moyamoya disease (MMD), blood flow to the internal carotid artery (ICA) system is supplied via the basal fine vascular network, leptomeningeal anastomoses, and transdural collateral vessels from the external carotid artery (ECA). After revascularization, there is a dramatic change in cerebral perfusion to the ECA system. Understanding this shift in blood supply is important for evaluating treatment efficacy and elucidating the postoperative pathophysiology. However, anatomical and quantitative methods for doing so have not yet been established. In the present study, selective intraarterial injection CT angiography (iaCTA) was performed in patients with MMD, and blood supply changes in each arterial system before and after revascularization surgery were evaluated., Methods: This study included 10 hemispheres in 10 patients who underwent combined revascularization surgery for adult MMD. Digital subtraction angiography was performed before and 3 months after surgery, and selective iaCTA was performed from the ICA, ECA, and vertebral artery (VA) at the same times in a hybrid CT/digital subtraction angiography suite. The anatomical distribution of each vessel was determined and perfusion volume was measured quantitatively on contrast-enhanced axial CT images., Results: Selective iaCTA clearly depicted the anatomical distribution of perfusion for each vessel. Conversion of blood supply from the ICA and VA to the ECA system was observed in the cerebral cortices and insulae but not in the basal ganglia. The mean volume of perfusion territories of the ECA (preoperative 0.9 cm3, postoperative 98.8 cm3); ICA (preoperative 225.7 cm3, postoperative 159.3 cm3); and VA (preoperative 244.0 cm3, postoperative 163.6 cm3) in the cerebral hemispheres changed significantly after revascularization. There was a correlation between increase in the ECA territory volume and decrease in the VA territory volume due to revascularization (R = -0.84, p < 0.005)., Conclusions: Selective iaCTA enabled clear visualization of anatomical changes in each vascular perfusion territory and quantitative measurement of each perfusion volume. Perfusion conversion to the ECA system after bypass surgery was observed in the cortical regions and in the insulae on the bypass operation sides, but not in the basal ganglia. Combined revascularization promoted the development of ECA-perfused territory, which correlated with a decrease in hemodynamic burden of the posterior cerebral artery.

Objective: This study aimed to explore the long-term course of posterior circulation changes and predictors in patients with moyamoya disease (MMD)., Methods: The authors retrospectively enrolled patients who were diagnosed with MMD and underwent encephaloduroarteriosynangiosis (EDAS) surgery at the authors' department from December 2002 to September 2011. A comparative study between short-term (6-12 months) and long-term (≥ 9 years) follow-up angiography was conducted. The progression of lesions was defined from lower to higher stages of the posterior cerebral artery (PCA)., Results: Eighty-eight patients who received indirect EDAS were enrolled in the study. The mean age at first surgery was 28.1 ± 15.0 years. Among these 88 patients with MMD, 39 (44.3%) exhibited transient ischemic attack and 27 (30.7%) exhibited infarction, comprising 5 with occipital lobe infarction, 14 (15.9%) with hemorrhagic symptoms, and 8 (9.1%) with atypical symptoms as the initial symptoms. Heterozygous mutations occurred significantly more frequently in the cases that presented with PCA involvement. During follow-up, stage progression of PCA was observed in 21 patients (28 hemispheres). At short-term follow-up, 21/176 (11.9%) hemispheres had progression of steno-occlusive lesions in the PCA. At long-term follow-up, 7 (4.0%) hemispheres had progression of steno-occlusive lesions in the PCA. At short-term follow-up, the progression of steno-occlusive lesions in the PCA was associated with progression of the internal carotid artery. Stage progression of PCA occurred significantly more frequently in the cases with PCA involvement on preoperative angiography. Nine strokes (10.2%) occurred in 88 patients during long-term follow-up. Four patients (4.5%) presented with ischemic stroke, including 2 with occipital lobe infarctions., Conclusions: Progression of PCA stenosis is common in patients with MMD, even if the PCA is normal initially. Mutations of RNF213 p.R4810K may predict PCA involvement or progression. Follow-up of the PCA in MMD patients should be conducted, and timely surgical revascularization is needed.

Objective: Proton beam therapy (PBT) is an increasingly used treatment modality for pediatric patients with brain tumors. Moyamoya syndrome (MMS) is well recognized as a complication of traditional photon radiotherapy, however its association with PBT is less well described. The authors discuss their initial experience with the neurosurgical management of MMS secondary to PBT in a large-volume pediatric neurovascular service., Methods: The authors performed a retrospective case review of consecutive children referred for neurosurgical management of MMS after PBT between 2009 and 2022. Patient demographic characteristics, oncological history and treatment, interval between PBT and MMS diagnosis, and MMS management were recorded. Clinical outcome at last review was classified as good if the modified Rankin Scale (mRS) score was ≤ 2 and/or the patient attended mainstream education without additional assistance. Poor outcome was defined as mRS score ≥ 3 and/or the patient received additional educational support. The recorded radiological outcomes included angiographic analysis of stenosis, evidence of brain ischemia/infarction on MRI, and postsurgical angiographic revascularization., Results: Ten patients were identified. Oncological diagnosis included craniopharyngioma (n = 6), optic pathway glioma (1), ependymoma (1), Ewing sarcoma (1), and rhabdosarcoma (1). The median (interquartile range [IQR]) age at PBT was 5.1 (2.7-7.9) years. The median (IQR) age at MMS diagnosis was 7.8 (5.7-9.3) years. The median time between PBT and diagnosis of MMS was 20 (15-41) months. Six patients had poor functional status after initial oncological treatment and prior to diagnosis of MMS. All 10 patients had endocrine dysfunction, 8 had visual impairment, and 4 had behavioral issues prior to MMS diagnosis. Four patients had a perioperative ischemic event: 2 after tumor surgery, 1 after MMS surgical revascularization, and 1 after receiving a general anesthetic for an MRI scan during oncological surveillance. Seven children were treated with surgical revascularization, whereas 3 were managed medically. The incidence of ischemic events per cerebral hemisphere was reduced after surgical revascularization: only 1 patient of 7 had an ischemic event during the follow-up period after surgery. No children moved from good to poor functional status after MMS diagnosis., Conclusions: MMS can occur after PBT. Magnetic resonance angiography sequences should be included in surveillance MRI scans to screen for MMS, and families should be counseled about this complication. Management at a high-volume pediatric neurovascular center, including selective use of revascularization surgery, appears to maintain functional status in these children.

Recent next-generation DNA and RNA sequencing studies of congenital and pediatric cerebrovascular anomalies such as moyamoya disease, arteriovenous malformations, vein of Galen malformations, and cavernous malformations have shed new insight into the genetic regulation of human cerebrovascular development by implicating multiple novel disease genes and signaling pathways in the pathogenesis of these disorders. These diseases are now beginning to be categorized by molecular disruptions in canonical signaling pathways that impact the differentiation and proliferation of specific venous, capillary, or arterial cells during the hierarchical development of the cerebrovascular system. Here, the authors discuss how the continued study of these and other congenital cerebrovascular conditions has the potential to replace the current antiquated, anatomically based disease classification systems with a molecular taxonomy that has the potential to increase precision in genetic counseling, prognostication, and neurosurgical and endovascular treatment stratification. Importantly, the authors also discuss how molecular genetic data are already informing clinical trials and catalyzing the development of targeted therapies for these conditions historically considered as exclusively neurosurgical lesions.

Objective: Patients sometimes experience transient neurological events (TNEs) during the early postoperative period after revascularization surgery for childhood moyamoya disease. The clinical background and pathophysiology of TNEs remain unclear. This study aimed to evaluate the incidence rate of TNEs and discuss the factors associated with pediatric moyamoya disease., Methods: The authors retrospectively reviewed 110 cerebral hemispheres of 61 pediatric patients younger than 15 years who were treated from 2011 to 2020. All children underwent either simple double-direct or combined revascularization surgery. Of these 61 patients, 52 underwent bilateral surgery and 9 underwent unilateral surgery. The authors calculated the incidence of TNEs in accordance with a previously reported TNE definition. Cerebral blood flow (CBF) was evaluated in all eligible cases with xenon CT immediately after revascularization surgery., Results: The incidence rate of TNEs in patients with childhood moyamoya disease was 26.4%. TNEs occurred after an average (range) of 6.26 (2-12) days postoperatively without triggers, and all identified TNEs spontaneously resolved within 2 weeks. The most common symptoms were dysarthria, facial palsy, and numbness around the mouth, followed by sensory disturbance of the upper extremities. The presence of focal hyperperfusion on xenon CT performed immediately after revascularization surgery was strongly correlated with the incidence of TNEs (p = 0.0001). Focal hyperperfusion was observed in 43 of 110 operative sides (39.1%). Notably, only 25.6% of patients with focal hyperperfusion showed numerical global hyperperfusion. In addition, a decrease in CBF compared with the thalamic region in the contralateral side was observed in TNE-affected cases (p = 0.0443)., Conclusions: TNEs occurred more frequently in childhood moyamoya disease patients than expected. The clinical background, including symptoms, timing, and duration, was almost identical to TNEs in adults. Focal hyperperfusion, rather than numerical global hyperperfusion, was strongly correlated with the incidence of TNEs. Furthermore, the authors advocate the notion that a clinical course where symptoms occur without triggers may be a unique characteristic of TNEs, especially in childhood moyamoya disease.

Objective: The post-bypass stroke risk factors and long-term outcomes of moyamoya patients are not well documented. Therefore, the authors studied 30-day stroke risks and patients' long-term physical, functional, and social well-being., Methods: This was a single-institution combined moyamoya disease (MMD) database interrogation and questionnaire study. From 1991 to 2014, 1250 revascularization procedures (1118 direct bypasses, 132 indirect bypasses) were performed in 769 patients. Completed questionnaires were received from and available for analysis on 391 patients, and 6-month follow-up data were available for 96.4% (741/769) of the patients., Results: The patients consisted of 548 females and 221 males, with a mean age of 32 years (range 1-69 years). Three hundred fifty-eight bypasses were performed in 205 pediatric patients (73% direct bypasses), and 892 revascularizations were performed in 564 adults (96% direct bypasses). Fifty-two patients (6.8%) developed major strokes with a worsening modified Rankin Scale (mRS) score within 30 days postoperatively. The 30-day major stroke risk was 5.3% (41/769) and 2.6% (12/467) after the first and second bypasses, respectively. Logistic regression analysis revealed that older age, modified MRI (mMRI) score, and hemodynamic reserve (HDR) score are clearly associated with higher postoperative stroke risks. Over a mean follow-up of 7.3 years (range 0.5-26 years), the long-term stroke risk among 741 patients was 0.6% per patient-year; 75% of these patients had excellent outcomes (mRS score 0-1). The long-term outcome questionnaire study showed that 84% (234/277) of patients reported resolution or improvement in their preoperative headache, 83% (325/391) remained employed or in school, and 87% (303/348) were self-caring., Conclusions: In this large, single-center surgical series, most of the adult and pediatric patients had direct revascularization, with a 4.2% per-bypass-procedure (6.8% per patient) 30-day major stroke risk and a 0.6% per-patient-year long-term stroke risk. The authors identified various risk factors that are highly correlated with postoperative morbidity (age, mMRI score, and HDR score) and are involved in ongoing work to develop the predictive modeling for future patient selection and treatment.

Objective: Side-to-side (S-S) superficial temporal artery-middle cerebral artery (STA-MCA) bypass was reportedly used to treat a special moyamoya disease (MMD) patient with collaterals arising from the donor STA. However, the S-S technique is not routinely performed to date, and its benefits are still unknown for adult MMD. The purpose of this study was to investigate the possibility of routine use of the S-S technique for adult MMD., Methods: The authors retrospectively analyzed the clinical data of 50 adult patients (65 hemispheres, including 30 in the end-to-side [E-S] group and 35 in the S-S group) with MMD who underwent STA-MCA bypass. The patient demographic characteristics, clinical courses, technical details, intraoperative blood flow data, postoperative and preoperative relative cerebral blood flow (rCBF) values, modified Rankin Scale (mRS) scores, and short-term revascularization results were compared between the 2 groups., Results: There were no significant differences observed in terms of the baseline characteristics, bypass patency rates, postoperative/preoperative rCBF values, incidence of cerebral hyperperfusion syndrome (CHS), mRS scores, and short-term revascularization results between the 2 groups (all p > 0.05). Intraoperative blood flow analysis showed that the increase of STA flow in the E-S group was significantly higher than that of proximal STA flow in the S-S group (p = 0.008). Although the increases of proximal and distal recipient flow in the E-S group seemed greater than those in the S-S group, the results were not statistically significant (p = 0.086 for proximal flow and p = 0.076 for distal flow). CHS symptoms in the S-S group were milder and with much shorter duration. The follow-up angiographic data of the representative case demonstrated that both frontal and parietal STA branches and the occipital artery participated in postoperative collateralization., Conclusions: S-S anastomosis can achieve comparable clinical effects to standard E-S construction. S-S anastomosis used in adult MMD demonstrated mild CHS symptoms with short duration and had the potential to arouse all scalp arteries as donor sources for revascularization through the intact distal STA branch via flow self-regulation.

Objective: Cerebral angiography is the gold standard for diagnosing moyamoya disease (MMD), whereas magnetic resonance (MR) imaging/angiography is becoming more popular in the field of cerebrovascular disease due to its low invasiveness. Although there are concerns about using only MR imaging/angiography for preoperative analysis of MMD, considering the underestimation of pre-existing transdural collateral circulations and dangerous collaterals related to the risk of hemorrhage, we retrospectively reviewed our 10-year experience of MR imaging-first diagnosis and analyzed the perioperative outcomes., Methods: We analyzed 160 consecutive direct/indirect combined revascularization procedures for MMD preoperatively assessed using MR imaging/angiography alone. Perioperative complications were assessed for up to 2 weeks after surgery. Locations of the lesions responsible for complications were further classified into the surgical field, the ipsilateral hemisphere outside the surgical field, and the contralateral hemisphere., Results: Sixty-four revascularization procedures were performed in 38 children, and 96 procedures were performed in 68 adults. There was no difference in the incidence of perioperative ischemic complications between adults (6.3%) and pediatric patients (4.7%), but hemorrhagic complications were more frequently observed in adults (7.3%) than in children (0%) (P < 0.05). There was no specific lesion deviation for ischemic complications; however, hemorrhagic complications predominantly occurred in the surgical field., Conclusions: Direct/indirect combined revascularization surgery based on our preoperative diagnostic protocol with the MR-first strategy resulted in favorable outcomes in pediatric MMD patients with relatively low complication rates. However, the validity of the MR-first diagnostic protocol should be further evaluated in adult patients with MMD., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: Moyamoya disease (MMD) is a rare cerebrovascular disease characterized by progressive stenosis of the internal carotid artery (ICA) and secondary formation of collateral vessels. Revascularization surgery is performed in patients with MMD to prevent stroke; however, the pathogenesis of MMD remains unknown. Recently, long noncoding RNAs (lncRNAs) have been found to play a key role in gene regulation and are implicated in various vascular diseases. However, the lncRNA expression profile in MMD lesions has not been investigated. In this study the authors aimed to determine the characteristics of lncRNA expression in MMD lesions., Methods: The authors collected microsamples of the middle cerebral artery (MCA) from patients with MMD (n = 21) and patients with control conditions (n = 11) who underwent neurosurgical treatment. Using microarray experiments, the authors compared the profiles of lncRNA expression in the MCAs of the MMD and control patient groups and identified differentially expressed lncRNAs (fold change > 2, q < 0.05). In addition, the neighboring coding genes, whose transcription can be regulated in cis by the identified differentially expressed lncRNAs, were investigated and Gene Ontology (GO) analysis was applied to predict associated biological functions., Results: The authors detected 308 differentially expressed lncRNAs (fold change > 2, q < 0.05), including 306 upregulated and 2 downregulated lncRNAs in the MCA from patients with MMD. Regarding the prediction of biological function, GO analyses with possible coding genes whose transcription was regulated in cis by the identified differentially expressed lncRNAs suggested involvement in the antibacterial humoral response, T-cell receptor signaling pathway, positive regulation of cytokine production, and branching involved in blood vessel morphogenesis., Conclusions: The profile of lncRNA expression in MMD lesions was different from that in the normal cerebral artery, and differentially expressed lncRNAs were identified. This study provides new insights into the pathophysiology of MMD.

Objective: The aim of this study was to identify predictive factors for hemorrhagic cerebral hyperperfusion syndrome (hCHS) after direct bypass surgery in adult nonhemorrhagic moyamoya disease (non-hMMD) using quantitative parameters on rapid processing of perfusion and diffusion (RAPID) perfusion CT software., Methods: A total of 277 hemispheres in 223 patients with non-hMMD who underwent combined bypass were retrospectively reviewed. Preoperative volumes of time to maximum (Tmax) > 4 seconds and > 6 seconds were obtained from RAPID analysis of perfusion CT. These quantitative parameters, along with other clinical and angiographic factors, were statistically analyzed to determine the significant predictors for hCHS after bypass surgery., Results: Intra- or postoperative hCHS occurred in 13 hemispheres (4.7%). In 7 hemispheres, subarachnoid hemorrhage occurred intraoperatively, and in 6 hemispheres, intracerebral hemorrhage was detected postoperatively. All hCHS occurred within the 4 days after bypass. Advanced age (OR 1.096, 95% CI 1.039-1.163, p = 0.001) and a large volume of Tmax > 6 seconds (OR 1.011, 95% CI 1.004-1.018, p = 0.002) were statistically significant factors in predicting the risk of hCHS after surgery. The cutoff values of patient age and volume of Tmax > 6 seconds were 43.5 years old (area under the curve [AUC] 0.761) and 80.5 ml (AUC 0.762), respectively., Conclusions: In adult patients with non-hMMD older than 43.5 years or with a large volume of Tmax > 6 seconds over 80.5 ml, more prudence is required in the decision to undergo bypass surgery and in postoperative management.

Direct superficial temporal artery (STA) to middle cerebral artery (MCA) anastomosis combined with indirect pial synangiosis provides favorable surgical collaterals for Moyamoya disease (MMD), especially in adults; however, factors leading to the development of each direct and indirect collateral are not well documented.We aimed to investigate the association between RNF213 founder polymorphism (p.R4810K) and each direct and indirect collateral development. By qualitative and quantitative evaluations of direct and indirect surgical collaterals using time-of-flight MR angiography, postoperative development of each type of bypass was evaluated independently into two categories. Multivariate logistic regression analysis was performed to study the contributing factors for the development of each surgical collateral. Excellent development of postoperative direct and indirect bypass was observed in 65 hemispheres (70%) by qualitative evaluation, which was confirmed by quantitative evaluation. Multivariate logistic regression analysis of excellent indirect bypass development revealed a significant positive correlation with the p.R4810K (odds ratio, OR4.0; 95%-confidence interval, CI 1.2-16), advanced MR angiographic stage (OR9.5; 95%CI 1.7-73), and preoperative middle meningeal artery caliber (OR6.8; 95%CI 1.8-35), but a significant negative correlation was found with the excellent direct bypass development (OR0.17; 95%CI 0.03-0.75). No significant correlation was observed between excellent direct bypass development and the p.R4810K (OR0.95; 95%CI 0.37-2.4).In conclusion, excellent development of indirect collaterals after STA-MCA anastomosis combined with indirect pial synangiosis occurs more frequently in adult MMD with the RNF213 founder polymorphism, suggesting a role of the p.R4810K variant for marked in-growth of indirect collaterals and the utility of preoperative genetic analysis., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: Patients with moyamoya vasculopathy often experience cognitive impairments. In this prospective single-center study, the authors investigated the profile of neurocognitive impairment and its relation with the severity of ischemic brain lesions and hemodynamic compromise., Methods: Patients treated in a Dutch tertiary referral center were prospectively included. All patients underwent standardized neuropsychological evaluation, MRI, digital subtraction angiography, and [15O]H2O-PET (to measure cerebrovascular reactivity [CVR]). The authors determined z-scores for 7 cognitive domains and the proportion of patients with cognitive impairment (z-score < -1.5 SD in at least one domain). The authors explored associations between patient characteristics, imaging and CVR findings, and cognitive scores per domain by using multivariable linear regression and Bayesian regression analysis., Results: A total of 40 patients (22 children; 75% females) were included. The median age for children was 9 years (range 1-16 years); for adults it was 39 years (range 19-53 years). Thirty patients (75%) had an infarction, and 31 patients (78%) had impaired CVR (steal phenomenon). Six of 7 cognitive domains scored below the population norm. Twenty-nine patients (73%) had cognitive impairment. Adults performed better than children in the cognitive domain visuospatial functioning (p = 0.033, Bayes factor = 4.0), and children performed better in processing speed (p = 0.041, Bayes factor = 3.5). The authors did not find an association between infarction, white matter disease, or CVR and cognitive domains., Conclusions: In this Western cohort, cognitive functioning in patients with moyamoya vasculopathy was below the population norm, and 73% had cognitive impairment in at least one domain. The cognitive profile differed between adults and children. The authors could not find an association with imaging findings.

Objective: Obtaining operative experience for the treatment of rare conditions in children represents a challenge for pediatric neurosurgeons. Starting in November 2017, a surgeon was mentored in surgical revascularization (SR) for pediatric moyamoya with a view to service development and sustainability. The aim of this audit was to evaluate early outcomes of SR for pediatric moyamoya during and following a surgical mentorship., Methods: A retrospective cohort study with chart/database review of consecutive moyamoya surgeries performed by a new attending surgeon (between November 2017 and March 2020) was compared to a previously published cohort from the authors' institution in terms of clinical and angiographic outcomes, complications, operating time, and length of stay. A standardized technique of encephaloduroarteriomyosynangiosis with the superficial temporal artery was used., Results: Twenty-two children underwent 36 indirect SRs during the study period. Patient demographics were similar between cohorts. The first group of 6 patients had 11 SRs performed jointly by the new attending surgeon mentored by an established senior surgeon (group A), followed by 10 patients with 16 SRs performed independently by the new attending surgeon (group B). The last 6 patients had 9 SRs with the new attending surgeon mentoring a senior fellow (group C) in performing SR. Good angiographic collateralization (Matsushima grades A and B) was observed in 80% of patients, with similar proportions across all 3 groups. A total of 18/19 symptomatic patients (95%) derived symptomatic benefit. There was no perioperative death and, compared to the historical cohort, a similar proportion had a recurrent arterial ischemic event (i.e., acute ischemic stroke) necessitating a second SR (1/22 vs 3/73). Operative times were longest in group C, with no difference in length of hospital stay among the 3 groups., Conclusions: Early outcomes demonstrate the feasibility of mentorship for safely incorporating new neurosurgeons in sustaining and developing a tertiary-level surgical service.

Objective: Twig-like middle cerebral artery (T-MCA) is a rare congenital anomaly that is difficult to distinguish from moyamoya angiopathy (MMA), given the similarity of the angioarchitectures. The aim of this study was to gain insights into the radiological and clinical features of T-MCA and to distinguish this condition from MMA., Methods: A multicenter retrospective study was conducted in 29 patients with T-MCA and 57 patients with MMA. Demographic, radiological, and clinical data were compared between the patients with T-MCA and those with MMA., Results: The T-MCA group tended to be older than the MMA group (mean age 47 ± 18 vs 39 ± 22 years). Twenty patients with T-MCA (69%) were initially diagnosed with MMA. All T-MCA cases had twig-like networks and steno-occlusive changes involving the MCA. The T-MCA group had a higher incidence of intracranial aneurysms (35% vs 11%) and coexisting arterial anomalies (48% vs 12%). T-MCA and MMA cases had significant differences in involvement of the internal carotid artery terminus (0% vs 100%) and posterior cerebral artery (0% vs 23%), and in transdural anastomosis (0% vs 51%). T-MCA cases were less likely to present with stroke (59% vs 86%) and more likely to be asymptomatic (28% vs 12%). Of the patients with stroke, those with T-MCA had more hemorrhagic strokes (41% vs 29%) and fewer ischemic strokes (59% vs 71%) compared to those with MMA., Conclusions: This study suggests that T-MCA is a different disease entity from MMA based on significant differences in the radiological and clinical features. Neurosurgeons should recognize this anomaly and understand the key features that differentiate T-MCA from MMA.

Objective: Healthcare disparities are widely described in adults, but barriers affecting access to care for pediatric patients with moyamoya disease (MMD) are unknown. Understanding socioeconomic factors impacting hospital access and outcomes is necessary to address pediatric healthcare disparities., Methods: In this cross-sectional observational study, the Kids' Inpatient Database was used to identify patients admitted with a primary diagnosis of MMD from 2003 to 2016. Patients ≤ 18 years with a primary diagnosis of MMD based on International Classification of Diseases (ICD) codes were included. Hospital admissions were queried for use of cerebral revascularization based on ICD procedure codes., Results: Query of the KID yielded 1449 MMD hospitalizations. After multivariable regression, Hispanic ethnicity (OR 0.52 [95% CI 0.33-0.81], p = 0.004) was associated with lack of surgical revascularization. Private insurance (OR 1.56 [95% CI 1.15-2.13], p = 0.004), admissions at medium- and high-volume centers (OR 2.01 [95% CI 1.42-2.83], p < 0.001 and OR 2.84 [95% CI 1.95-4.14], p < 0.001, respectively), and elective hospitalization (OR 3.37 [95% CI 2.46-4.64], p < 0.001) were positively associated with revascularization. Compared with Caucasian race, Hispanic ethnicity was associated with increased mean (± SEM) length of stay by 2.01 ± 0.70 days (p = 0.004) and increased hospital charges by $24,333.61 ± $7918.20 (p = 0.002), despite the decreased utilization of surgical revascularization. Private insurance was associated with elective admission (OR 1.50 [95% CI 1.10-2.05], p = 0.01) and admission to high-volume centers (OR 1.90 [95% CI 1.26-2.88], p = 0.002). African American race was associated with the development of in-hospital complications (OR 2.52 [95% CI 1.38-4.59], p = 0.003)., Conclusions: Among pediatric MMD hospitalizations, multiple socioeconomic factors were associated with access to care, whether surgical treatment is provided, and whether in-hospital complications occur. These results suggest that socioeconomic factors are important drivers of healthcare disparities in children with MMD and warrant further study.

Objective: Ivy sign is a radiographic finding on FLAIR MRI sequences and is associated with slow cortical blood flow in moyamoya. Limited data exist on the utility of the ivy sign as a diagnostic and prognostic tool in pediatric patients, particularly outside of Asian populations. The authors aimed to investigate a modified grading scale with which to characterize the prevalence and extent of the ivy sign in children with moyamoya and evaluate its efficacy as a biomarker in predicting postoperative outcomes, including stroke risk., Methods: Pre- and postoperative clinical and radiographic data of all pediatric patients (21 years of age or younger) who underwent surgery for moyamoya disease or moyamoya syndrome at two major tertiary referral centers in the US and Israel, between July 2009 and August 2019, were retrospectively reviewed. Ivy sign scores were correlated to Suzuki stage, Matsushima grade, and postoperative stroke rate to quantify the diagnostic and prognostic utility of ivy sign., Results: A total of 171 hemispheres in 107 patients were included. The median age at the time of surgery was 9 years (range 3 months-21 years). The ivy sign was most frequently encountered in association with Suzuki stage III or IV disease in all vascular territories, including the anterior cerebral artery (53.7%), middle cerebral artery (56.3%), and posterior cerebral artery (47.5%) territories. Following surgical revascularization, 85% of hemispheres with Matsushima grade A demonstrated a concomitant, statistically significant reduction in ivy sign scores (OR 5.3, 95% CI 1.4-20.0; p = 0.013). Postoperatively, revascularized hemispheres that exhibited ivy sign score decreases had significantly lower rates of postoperative stroke (3.4%) compared with hemispheres that demonstrated no reversal of the ivy sign (16.1%) (OR 5.5, 95% CI 1.5-21.0; p = 0.008)., Conclusions: This is the largest study to date that focuses on the role of the ivy sign in pediatric moyamoya. These data demonstrate that the ivy sign was present in approximately half the pediatric patients with moyamoya with Suzuki stage III or IV disease, when blood flow was most unstable. The authors found that reversal of the ivy sign provided both radiographic and clinical utility as a prognostic biomarker postoperatively, given the statistically significant association with both better Matsushima grades and a fivefold reduction in postoperative stroke rates. These findings can help inform clinical decision-making, and they have particular value in the pediatric population, as the ability to minimize additional radiographic evaluations and tailor radiographic surveillance is requisite.

Objective: The authors' objective was to investigate the influence of the RNF213 p.R4810K variant on the clinical presentation and outcomes of Japanese pediatric patients with moyamoya disease., Methods: A total of 129 Japanese patients with pediatric-onset moyamoya disease (onset age ≤ 15 years) who visited the authors' department from 2012 to 2020 participated in this study. After RNF213 p.R4810K genotyping of each patient was performed, the relationship between genotype and clinical presentation or outcomes, including onset age, initial presentation, surgical outcomes, and subsequent cerebrovascular events, was evaluated. Patients without the p.R4810K variant were tested for RNF213 variants other than p.R4810K. The authors especially focused on the results of patients who presented with moyamoya disease at younger than 1 year of age (infantile onset)., Results: Compared with the patients with heterozygous variants, patients without the p.R4810K variant were younger at onset (7.1 ± 3.7 vs 4.4 ± 0.9 years), and all 4 patients with infantile onset lacked the p.R4810K variant. A greater proportion of patients without the p.R4810K variant presented with infarction than patients with the heterozygous variant (24.0% vs 7.6%) and a decreased proportion presented with transient ischemic attack (36.0% vs 71.7%). No significant correlation was observed between p.R4810K genotype and clinical outcomes, including surgical outcomes and subsequent cerebrovascular events; however, a decreased proportion of patients without the p.R4810K variant had good surgical outcomes compared with that of patients with the heterozygous variant (76.5% vs 92.2%). Among the 25 patients without the p.R4810K variant, 8 rare variants other than p.R4810K were identified. Three of 4 patients with infantile onset had RNF213 variants other than p.R4810K, which had a more severe functional effect on this gene than p.R4810K., Conclusions: Absence of the RNF213 p.R4810K variant may be a novel biomarker for identification of a severe form of pediatric moyamoya disease.

Objective: Digital subtraction angiography (DSA) is commonly performed after pial synangiosis surgery for pediatric moyamoya disease to assess the degree of neovascularization. However, angiography is invasive, and the risk of ionizing radiation is a concern in children. In this study, the authors aimed to identify whether arterial spin labeling (ASL) can predict postoperative angiogram grading. In addition, they sought to determine whether patients who underwent ASL imaging without DSA had similar postoperative outcomes when compared with patients who received ASL imaging and postoperative DSA., Methods: The medical records of pediatric patients who underwent pial synangiosis for moyamoya disease at a quaternary children's hospital were reviewed during a 10-year period. ASL-only and ASL+DSA cohorts were analyzed. The frequency of preoperative and postoperative symptoms was analyzed within each cohort. Three neuroradiologists assigned a visual ASL grade for each patient indicating the change from the preoperative to postoperative ASL perfusion sequences. A postoperative neovascularization grade was also assigned for patients who underwent DSA., Results: Overall, 21 hemispheres of 14 patients with ASL only and 14 hemispheres of 8 patients with ASL+DSA were analyzed. The groups had similar rates of MRI evidence of acute or chronic stroke preoperatively (61.9% in the ASL-only group and 64.3% in the ASL+DSA group). In the entire cohort, transient ischemic attack (TIA) (p = 0.027), TIA composite (TIA or unexplained neurological symptoms; p = 0.0006), chronic headaches (p = 0.035), aphasia (p = 0.019), and weakness (p = 0.001) all had decreased frequency after intervention. The authors found a positive association between revascularization observed on DSA and the visual ASL grading (p = 0.048). The visual ASL grades in patients with an angiogram indicating robust neovascularization demonstrated improved perfusion when compared with the ASL grades of patients with a poor neovascularization., Conclusions: Noninvasive ASL perfusion imaging had an association with postoperative DSA neoangiogenesis following pial synangiosis surgery in children. There were no significant postoperative stroke differences between the ASL-only and ASL+DSA cohorts. Both cohorts demonstrated significant improvement in preoperative symptoms after surgery. Further study in larger cohorts is necessary to determine whether the results of this study are validated in order to circumvent the invasive catheter angiogram.

Objective: Although many studies have analyzed risk factors for contralateral progression in unilateral moyamoya disease, they have not been fully elucidated. The aim of this study was to examine whether genetic factors as well as nongenetic factors are involved in the contralateral progression., Methods: The authors performed a multicenter cohort study in which 93 cases with unilateral moyamoya disease were retrospectively reviewed. The demographic features, RNF213 R4810K mutation, lifestyle factors such as smoking and drinking, past medical history, and angiographic findings were analyzed. A Cox proportional hazards model was used to find risk factors for contralateral progression., Results: Contralateral progression was observed in 24.7% of cases during a mean follow-up period of 72.2 months. Clinical characteristics were not significantly different between 67 patients with the R4810K mutation and those without it. Cox regression analysis showed that the R4810K mutation (hazard ratio [HR] 4.64, p = 0.044), childhood onset (HR 7.21, p < 0.001), male sex (HR 2.85, p = 0.023), and daily alcohol drinking (HR 4.25, p = 0.034) were independent risk factors for contralateral progression., Conclusions: These results indicate that both genetic and nongenetic factors are associated with contralateral progression of unilateral moyamoya disease. The findings would serve to help us better understand the pathophysiology of moyamoya disease and to manage patients more appropriately.

Moyamoya disease is a rare disorder of the cerebrovascular system affecting individuals in a bimodal age distribution and is characterized by progressive vascular stenosis of the bilateral supraclinoid internal carotid arteries with compensatory formation of collateral vessels at the base of the brain. Despite the disease's initial description in the literature in 1957, little progress has been made in the development of medical and surgical therapeutics due to, in no small part, the lack of effective experimental animal models. Currently, there is a poor understanding of the pathophysiological mechanisms behind the development of the moyamoya vasculopathies. Since the description of a genetic association between moyamoya disease, few studies have investigated the impact of genetic manipulation on the development of an animal model for experimentation. To date, no one model recapitulates the precise phenotype of the moyamoya vasculopathies, although development of an appropriate model would allow for an in-depth investigation into the pathological mechanisms underlying the disease. In this review, the authors discuss the immunological, mechanical, and genetic methods used to develop moyamoya experimental models, as well as future perspectives.

Objective: Quasi-moyamoya disease (QMMD) is moyamoya disease (MMD) associated with additional underlying diseases. Although the ring finger protein 213 (RNF213) c.14576G>A mutation is highly correlated with MMD in the Asian population, its relationship to QMMD is unclear. Therefore, in this study the authors sought to investigate the RNF213 c.14576G>A mutation in the genetic diagnosis and classification of QMMD., Methods: This case-control study was conducted among four core hospitals. A screening system for the RNF213 c.14576G>A mutation based on high-resolution melting curve analysis was designed. The prevalence of RNF213 c.14576G>A was investigated in 76 patients with MMD and 10 patients with QMMD., Results: There were no significant differences in age, sex, family history, and mode of onset between the two groups. Underlying diseases presenting in patients with QMMD were hyperthyroidism (n = 6), neurofibromatosis type 1 (n = 2), Sjögren's syndrome (n = 1), and meningitis (n =1). The RNF213 c.14576G>A mutation was found in 64 patients (84.2%) with MMD and 8 patients (80%) with QMMD; no significant difference in mutation frequency was observed between cohorts., Conclusions: There are two forms of QMMD, one in which the vascular abnormality is associated with an underlying disease, and the other in which MMD is coincidentally complicated by an unrelated underlying disease. It has been suggested that the presence or absence of the RNF213 c.14576G>A mutation may be useful in distinguishing between these disease types.

Objective: Moyamoya disease (MMD) is a chronic, progressive steno-occlusive condition of the distal internal carotid arteries of unknown etiology. Collateral arterial networks typically develop in MMD, bypassing the steno-occlusion. Aneurysms arising on the collateral networks are a known source of hemorrhage. The choroidal collateral system is the most common location for collateral pathway aneurysms in MMD and associated hemorrhage. The authors performed data collection and analysis to further elucidate the best treatment approaches for ruptured aneurysms of the choroidal collateral system in MMD, which as yet remain unclear., Methods: A comprehensive data collection and analysis of case reports and case series with ruptured choroidal collateral artery aneurysms (CCAAs) was performed. PRISMA guidelines for systematic reviews were followed and the Medline, Embase, and Scopus databases were searched for relevant studies. A database was created including patients with ruptured CCAA in MMD. Original data from case series were included whenever possible. A previously unreported case of a ruptured choroidal artery aneurysm in MMD treated by the authors was also included., Results: The database comprised 72 patients with ruptured CCAA in MMD. The most common clinical symptoms were headache, nausea, and vomiting (39%). Initially, a conservative treatment approach was chosen in 29% of cases but led to rehemorrhage in 40% of cases; 63% of these rehemorrhages occurred during the first 35 days. Endovascular treatment seemed a safe option for aneurysm exclusion, mainly through parent vessel sacrifice, but had a treatment failure rate of 21%, due to inadequate access. Aneurysm treatment with revascularization as the initial treatment strategy led to aneurysm regression in 82% with no reported rehemorrhage. Aneurysm exclusion through open surgery was effective but was associated with a relatively high complication rate (25%). Outcome after rupture of CCAA was poor, with 41% of patients deceased or permanently disabled. Overall, patient outcomes were better in the endovascular and revascularization treatment group than in the conservative treatment group., Conclusions: Rupture of CCAA in MMD is associated with high morbidity and rerupture rate requiring urgent treatment.

Objective: Cerebral extracranial-intracranial (EC-IC) direct bypass is a commonly used procedure for ischemic vasculopathy. A previously described variation of this technique is to utilize one donor artery to supply two recipient arteries, which the authors designate as 1D2R. The purpose of this study is to present a single surgeon's series of 1D2R direct bypasses for moyamoya and ischemia using detailed clinical, angiographic, and intraoperative blood flow measurement data. To the authors' knowledge, this is the largest series reported to date., Methods: Hospital, office, and radiographic imaging records for all patients who underwent cerebral revascularization using a 1D2R bypass by the senior author were reviewed. The patients' demographic information, clinical presentation, associated medical conditions, intraoperative information, and postoperative course were obtained from reviewing the medical records., Results: A total of 21 1D2R bypasses were performed in 19 patients during the study period. Immediate bypass patency was 100% and was 90% on delayed follow-up. The mean initial cut flow index (CFI(i)) was 0.64 ± 0.33 prior to the second anastomosis and the mean final value (CFI(f)) was 0.94 ± 0.38 after the second anastomosis (p < 0.001). The overall bypass flow increased on average by 50% (mean 17.9 ml/min, range -10 to 40 ml/min) with the addition of the second anastomosis. There was no significant difference in the overall flow measurements when the end-to-side anastomosis or side-to-side anastomosis was performed first. There was a statistically significant difference in the proportion of patients with a modified Rankin Scale (mRS) score of 0 or 1 postoperatively compared to preoperatively (p < 0.01). Through the application of Poiseuille's law, the authors analyzed flow dynamics, deduced the component vascular resistances based on an analogy to electrical circuits and Ohm's law, and introduced the new concepts of "second anastomosis relative augmentation" and "second anastomosis sink index" in the evaluation of 1D2R bypasses., Conclusions: The application of the 1D2R technique in a series of 19 consecutive patients undergoing direct EC-IC bypass for flow augmentation demonstrated high patency rates, statistically significantly higher CFIs compared to 1D1R, and improved mRS scores at last clinical follow-up. Additionally, the technique allows a shorter dissection time and preserves blood flow to the scalp. The routine utilization of intraoperative volumetric flow measurements in such surgeries allows a deeper understanding of the hemodynamic impact on individual patients.

Objective: Patients with pediatric moyamoya disease (PMMD) showing recurrent symptoms or decreased cerebral blood flow after initial revascularization therapy may require additional revascularization to improve their clinical condition. The authors evaluated the clinical and hemodynamic benefits of an occipital artery (OA)-middle cerebral artery (MCA) bypass for patients with PMMD who have undergone an initial revascularization procedure., Methods: The authors retrospectively identified 9 patients with PMMD who had undergone OA-MCA bypass between March 2013 and December 2017, and who had received a previous superficial temporal artery-MCA bypass. The following clinical data were collected: initial revascularization procedure, symptoms (presence or recurrence), pre- and postoperative cerebral blood flow and cerebrovascular reactivity (CVR) changes, posterior cerebral artery (PCA) stenosis, PCA-related and nonrelated symptoms, and latest follow-up., Results: Preoperatively, all patients (n = 9) suffered non-PCA-related recurrent symptoms, and 4 had PCA-related symptoms. At 1-year follow-up, all patients with PCA-related symptoms showed complete recovery. Additionally, 8 (89%) patients with non-PCA symptoms experienced improvement. Only 1 (11%) patient showed no improvement after the surgical procedure. The mean pre- and postoperative CVR values of the MCA territory were 14.8% and 31.3%, respectively, whereas the respective mean CVR values of the PCA territory were 22.8% and 40.0%., Conclusions: The OA-MCA bypass is an effective rescue therapy to improve the clinical condition and hemodynamic changes caused by PMMD in patients who experience recurrent symptoms after initial revascularization.

Moyamoya is an uncommon disease that presents with stenoocclusion of the major vasculature at the base of the brain and associated collateral vessel formation. Many pediatric patients with moyamoya present with transient ischemic attacks or complete occlusions. The authors report the case of a 9-year-old girl who presented with posterior fossa hemorrhage and was treated with an emergency suboccipital craniotomy for evacuation. After emergency surgery, an angiogram was performed, and the patient was diagnosed with moyamoya disease. Six months later, the patient was treated for moyamoya using direct and indirect revascularization; after surgery there was excellent vascularization in both regions of the bypass and no further progression of moyamoya changes. This case illustrates a rare example of intracerebral hemorrhage associated with moyamoya changes in the posterior vascularization in a pediatric patient and subsequent use of direct and indirect revascularization to reduce the risk of future hemorrhage and moyamoya progression.

Moyamoya is a progressive cerebrovascular arteriopathy that affects children of any age. The goal of this study was to determine imaging and clinical outcomes as well as complication rates in a pediatric cohort undergoing either a combined direct/indirect or indirect-only revascularization approach. Patients with moyamoya disease or syndrome ≤ 18 years of age at the time of initial surgery were identified, and clinical data were collected retrospectively. Over a 12-year period, 26 patients underwent revascularization procedures on 49 hemispheres with a median follow-up of 2.6 years from surgery. Median age at surgery was 7.3 years (range 1.4-18.0 years). Thirty-three hemispheres (67.3%) underwent combined revascularization with a direct bypass and encephalomyosynangiosis, and sixteen hemispheres (32.7%) underwent indirect-only revascularization. The rate of 30-day perioperative complication was 10.2%, and the rate of postoperative clinical stroke by end of follow-up was 10.2% by hemisphere. There was a 5.7% rate of intraoperative bypass failure requiring conversion to an indirect revascularization approach. On follow-up imaging, 96.9% of direct bypasses remained patent. On multivariate analysis, higher preoperative Pediatric Stroke Outcome Measure (PSOM) scores were associated with lower rates of good clinical outcome on follow-up (unit OR 0.03; p = 0.03). Patients with age < 5.4 years had lower rates of good clinical outcome on follow-up. In this North American cohort, both combined direct/indirect and indirect only revascularization techniques were feasible. However, younger children < 5.4 years of age have worse outcomes than older children, similar to east Asian cohorts., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objective: The only effective treatment for ischemic moyamoya disease (iMMD) is cerebral revascularization by an extracranial to intracranial bypass. The preferred revascularization method remains controversial: direct versus indirect bypass. The purpose of this study was to test the hypothesis that method choice should be personalized based on angiographic, hemodynamic, and clinical characteristics to balance the risk of perioperative major stroke against treatment efficacy., Methods: Patients with iMMD were identified retrospectively from a prospectively maintained database. Those with mild to moderate internal carotid artery or M1 segment stenosis, preserved cerebrovascular reserve, intraoperative M4 segment anterograde flow ≥ 8 ml/min, or the absence of frequent and severe transient ischemic attacks (TIAs) or stroke had been assigned to indirect bypass. The criteria for direct bypass were severe ICA or M1 segment stenosis or occlusion, impaired cerebrovascular reserve or steal phenomenon, intraoperative M4 segment retrograde flow or anterograde flow < 8 ml/min, and the presence of frequent and severe TIAs or clinical strokes. The primary study endpoint was MRI-confirmed symptomatic stroke ≤ 7 days postoperatively resulting in a decline in the modified Rankin Scale (mRS) score from preoperatively to 6 months postoperatively. As a secondary endpoint, the authors assessed 6-month postoperative DSA-demonstrated revascularization, which was classified as < 1/3, 1/3-2/3, or > 2/3 of the middle cerebral artery territory., Results: One hundred thirty-eight patients with iMMD affecting 195 hemispheres revascularized in the period from March 2016 to June 2018 were included in this analysis. One hundred thirty-three hemispheres were revascularized with direct bypass and 62 with indirect bypass. The perioperative stroke rate was 4.7% and 6.8% in the direct and indirect groups, respectively (p = 0.36). Degree of revascularization was higher in the direct bypass group (p = 0.03). The proportion of patients improving to an mRS score 0-1 (from preoperatively to 6 months postoperatively) tended to be higher in the direct bypass group, although the difference between the two bypass groups was not statistically significant (p = 0.27)., Conclusions: The selective use of an indirect bypass procedure for iMMD did not decrease the perioperative stroke rate. Direct bypass provided a significantly higher degree of revascularization. The authors conclude that direct bypass is the treatment of choice for iMMD.