Hemorrhagic Moyamoya Disease Research Articles

Ruptured Peripheral Cerebral Aneurysms Associated With Moyamoya Disease: A Systematic Review.

A ruptured peripheral cerebral aneurysm (PPCA) associated with moyamoya disease (MMD) is a rare but potentially life-threatening condition with controversial management strategies. We aim to summarize the clinical characteristics, treatment strategies, and prognostic factors of PPCAs in MMD. We reviewed studies published in PubMed between 1980 and 2023 and used logistic regression analysis to identify the risk factors for adverse outcomes. Of 425 identified studies, 48 eligible studies involving 121 participants were included in the current study. The mean age at diagnosis was 40.8±15.1 years, with a peak age of onset between 41 and 50 years. Among the identified participants, 59.6% were female, and 55.9% presented with impaired consciousness. Aneurysms were present in the posterior (35.5%) or anterior (30.6%) choroidal arteries in 66.1% of the cases, and 71.1% of the patients presented with intraventricular hemorrhage (IVH) with or without intracerebral hematoma (ICH). The treatment strategies were embolization (28.9%), direct surgery (21.5%), revascularization (22.3%), and conservation (27.3%). Favorable outcomes were achieved in 86.8% of all cases, with 97.1% for embolization, 65.4% for direct surgery, 96.3% for revascularization, and 84.8% for conservative treatment. Aneurysm rebleeding occurred in 11 (26.8%) of 41 patients managed conservatively, leading to worse outcomes in 7 patients (63.6%). Impaired consciousness (odds ratio [OR], 8.61; 95% confidence interval [CI], 2.06-36.00) and aneurysm rebleeding (OR, 16.54; 95% CI, 3.08-88.90) independently predicted poor outcomes. PPCA should be considered in patients with hemorrhagic MMD, particularly those with IVH with or without ICH. Endovascular and bypass treatments are recommended as first-line options, with direct open surgery as an alternative in urgent hematoma evacuation cases. Detailed preoperative planning and intraoperative technical assistance are necessary to reduce procedure-related complications. Conservative management should be selected with caution because of the high risk of rebleeding and poor outcomes. Impaired consciousness and aneurysm rebleeding appeared to be independent risk factors for adverse prognoses. We emphasize that treatment selection should be personalized, and the potential benefits should be weighed against the associated risks.

Superior Cerebellar Artery Aneurysm in a Case of Moyamoya Disease: A Rare Entity

AbstractMoyamoya disease is a rare condition characterized by progressive narrowing and occlusion of internal carotid artery and other major arteries of the brain with formation of multiple collaterals. The incidence of aneurysm in moyamoya disease is higher than normal population. Treating the simultaneous pathology of aneurysm and moyamoya disease in an individual is a rare entity. A 35-year-old male presented with headache, loss of consciousness, and generalized tonic-clonic seizure with subarachnoid hemorrhage. Digital Subtraction angiography showed moyamoya disease with left superior cerebellar artery aneurysm. Rupture of aneurysm was suspected to be the source of subarachnoid hemorrhage. Patient underwent clipping of the left superior cerebellar artery aneurysm with encephalo-duro-arterio-myo-synangiosis. Patient survived the procedures. All patients with subarachnoid hemorrhage in moyamoya disease should undergo angiogram and aneurysm should be looked for carefully. The site of aneurysm and the risk for damaging the collaterals should be kept in mind while planning the surgery in such cases.

Glymphatic System Impairment in the Advanced Stage of Moyamoya Disease.

Assessing the glymphatic system activity using diffusion tensor imaging analysis along with the perivascular space (DTI-ALPS) may be helpful to understand the pathophysiology of moyamoya disease (MMD). 63 adult patients with MMD and 20 healthy controls (HCs) were included for T1-weighted images, T2-FLAIR, pseudocontinuous arterial spin labeling, and DTI. 60 patients had digital subtraction angiography more than 6 months after combined revascularization. The Suzuki stage, postoperative Matsushima grade, periventricular anastomoses (PA), enlarged perivascular spaces (EPVS), deep and subcortical white matter hyperintensities (DSWMH), DTI-ALPS, cerebral blood flow (CBF), and cognitive scales of MMD patients were assessed. MMD patients were divided into early and advanced stage based on the Suzuki stage. We detected lower DTI-ALPS in patients with advanced stage relative to HCs (p = 0.046) and patients with early stage (p = 0.004), hemorrhagic MMD compared with ischemic MMD (p = 0.048), and PA Grade 2 compared with Grade 0 (p = 0.010). DTI-ALPS was correlated with the EPVS in basal ganglia (r = -0.686, p < 0.001), Suzuki stage (r = -0.465, p < 0.001), DSWMH (r = -0.423, p = 0.001), and global CBF (r = 0.300, p = 0.017) and cognitive scores (r = 0.343, p = 0.018). The DTI-ALPS of patients with good postoperative collateral formation was higher compared to those with poor postoperative collateral formation (p = 0.038). In conclusion, the glymphatic system was impaired in advanced MMD patients and may affected cognitive function and postoperative neoangiogenesis.

System Inflammation Response Index and Serum Glucose-Potassium Ratio as Prognostic Indicators for Hemorrhagic Moyamoya Disease

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

Worse outcome in hemorrhagic moyamoya disease of anterior circulation type compared to posterior circulation type

ObjectiveDespite the known poor outcomes of patients with hemorrhagic moyamoya disease (MMD), previous studies have not explored the entire population of hemorrhagic MMD, often excluding severely impaired patients due to the lack of imaging studies demonstrating cerebral angioarchitecture. Herein, we investigate the prevalence, location of intracerebral hematoma (ICH), and outcomes in patients with hemorrhagic MMD, including severely impaired individuals who underwent emergency computed tomography (CT) angiography (CTA) to identify secondary ICHs. MethodsWe conducted a retrospective analysis of 2092 patients admitted to our hospital within 3 days of ICH onset from January 2010 to December 2022. CTA was performed for all patients with ICH, principally. ResultsCTA was performed in 1645 (78.6%) patients. We diagnosed MMD in 40 patients (2.5%), making it the third leading cause of secondary ICH. Twenty patients had anterior-type hematomas, while the remaining twenty had posterior-type hematomas. At 90 days after onset, 19 patients (95%) with anterior-type hematomas had unfavorable outcomes (modified Rankin scale [mRS] scores of 3–6), compared to 11 patients (55%) with posterior-type hematomas. The number of unfavorable outcomes was significantly higher in the anterior-type group compared to the posterior-type group (p = 0.008). ConclusionThis comprehensive study highlights that the majority of MMD cases with ICH result in unfavorable outcomes, especially when the ICH is located in the anterior circulation. While recent studies have focused on preventing bleeding from choroidal anastomosis in the posterior circulation, overall outcome improvement of hemorrhagic MMD necessitates a greater emphasis on addressing anterior circulation ICHs.

Outcomes of Bypass Surgery in Adult Moyamoya Disease by Onset Type

Moyamoya disease (MMD) is a rare chronic cerebrovascular disease, and the outcomes of bypass management in adult patients remain controversial. To categorize adult MMD based on asymptomatic, ischemic, and hemorrhagic onset and compare the outcomes (death, hemorrhagic stroke [HS], and ischemic stroke [IS]) of bypass surgery (direct or indirect) with those of conservative management. This retrospective, nationwide, population-based longitudinal cohort study used Korean National Health Insurance Research data to identify adults (aged ≥15 years) with MMD who were diagnosed between January 1, 2008, and December 31, 2020, and followed up until December 31, 2021 (median follow-up, 5.74 [IQR, 2.95-9.42] years). A total of 19 700 participants (3194 with hemorrhagic, 517 with ischemic, and 15 989 with asymptomatic MMD) were included. Data were analyzed from January 2 to April 1, 2023. Bypass surgery and conservative management. Death constituted the primary outcome; secondary outcomes consisted of HS or IS. Kaplan-Meier survival curve and Cox proportional hazards regression analysis were applied. The propensity score-matching and stratified analyses were performed to control covariate effects. A total of 19 700 patients (mean [SD] age, 45.43 [14.98] years; 12 766 [64.8%] female) were included. Compared with conservative management, bypass was associated with a reduced risk of death (adjusted hazard ratio [AHR], 0.50 [95% CI, 0.41-0.61]; P < .001) and HS (AHR, 0.36 [0.30-0.40]; P < .001) in hemorrhagic MMD; reduced risk of IS (AHR, 0.55 [95% CI, 0.37-0.81]; P = .002) in ischemic MMD; and reduced risk of death (AHR, 0.74 [95% CI, 0.66-0.84]; P < .001) in asymptomatic MMD. However, bypass was associated with an increased risk of HS (AHR, 1.76 [95% CI, 1.56-2.00]; P < .001) in asymptomatic MMD. Both direct and indirect bypass demonstrated similar effects in hemorrhagic and asymptomatic MMD, except only direct bypass was associated with a reduced risk of IS (AHR, 0.52 [95% CI, 0.33- 0.83]; P = .01) in ischemic MMD. After stratification, bypass was associated with a reduced risk of death in patients younger than 55 years with ischemic (AHR, 0.34 [95% CI, 0.13- 0.88]; P = .03) and asymptomatic (AHR, 0.69 [95% CI, 0.60-0.79]; P < .001) MMD, but an increased risk of HS in patients 55 years or older with ischemic MMD (AHR, 2.13 [95% CI, 1.1-4.16]; P = .03). The findings of this cohort study of bypass outcomes for patients with MMD emphasize the importance of tailoring management strategies in adult patients based on onset types.

Development and validation of a novel nomogram for predicting long-term rebleeding risk among patients with hemorrhagic moyamoya disease: a 10-year multicenter retrospective cohort study.

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). 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. 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. 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.

Combination of neuroendoscopic hematoma evacuation and endovascular coil embolization for a ruptured anterior choroidal artery aneurysm in patients with moyamoya disease: illustrative cases.

The treatment strategy for hemorrhagic moyamoya disease (MMD) due to a ruptured aneurysm at the distal portion of the anterior choroidal artery remains controversial. The authors successfully treated the ruptured aneurysm with neuroendoscopic hematoma evacuation, followed by endovascular coil embolization. The authors encountered two patients with massive hemorrhagic MMD whose MMD had already been diagnosed and who had a periventricular anastomosis due to a ruptured aneurysm of the distal portion of the anterior choroidal artery involving the periventricular anastomosis. In both cases, neuroendoscopic hematoma evacuation was performed for hemorrhagic MMD in the acute phase, followed by endovascular coil embolization of the ruptured aneurysm in the chronic phase. In both endovascular treatments, the patient's condition was stabilized by hematoma evacuation, allowing a detailed preoperative evaluation of the anatomical findings of the vessel and functional findings of intraoperative neurophysiological monitoring using continuous monitoring of motor evoked potentials to preserve motor function. Combination therapy can be useful for hemorrhagic MMD in patients with diagnosed MMD with a periventricular anastomosis. Additionally, a preoperative understanding of the vascular construction and intraoperative neurophysiological monitoring will aid in the successful coil embolization of aneurysms at the distal portion of the anterior choroidal artery with hemorrhagic MMD.

Effectiveness of indirect revascularization for adult hemorrhagic moyamoya disease: a 10-year follow-up study.

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. 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. 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). 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.

Ultrasonography monitoring with Superb Microvascular Imaging during cerebrovascular surgery

IntroductionUltrasonography (US) is used as a real-time dynamic imaging modality during neurosurgery. A novel Doppler US technique, Superb Microvascular Imaging (SMI), can be used to visualize low-velocity flow of small vessels at high resolution with high frame rates. We visualized vessel flow using this US SMI technique and contrast agent during cerebrovascular surgery. MethodsForty-three patients with an unruptured cerebral aneurysm (control), ischemic and hemorrhagic moyamoya disease, carotid artery stenosis, hemangioblastoma, severe stenosis of the middle cerebral artery, venous angioma, and intracerebral hemorrhage (ICH) underwent neurosurgery with US SMI monitoring using a contrast agent. The diameter, length, and number of penetrating vessels were analyzed in patients with an unruptured cerebral aneurysm (control), moyamoya disease, and ICH. ResultsDiameter and length of cerebral penetrating vessels were significantly increased in patients with moyamoya disease and ICH compared to control patients. The number of penetrating vessels was increased in moyamoya disease patients compared to control and ICH patients. In hemorrhagic moyamoya disease, flow in the penetrating vessels originated from a deep periventricular point and extended to the cerebral surface. Pulsatile cerebral aneurysms during clipping surgery and carotid artery stenosis during carotid endarterectomy were easily identified by SMI. Drastically increased vessel flow in patients with a hemangioblastoma or a venous angioma was observed. ConclusionUsing the US SMI technique and contrast agent, we obtained useful flow information of the vascular disease structure and intracerebral deep small vessels during cerebrovascular surgery. Further quantitative analysis will be informative and helpful for cerebrovascular surgery.

A novel system for evaluating collateralization of the external carotid artery after cerebral revascularization in moyamoya disease.

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. 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. 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). 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.

“Transcallosal” periventricular anastomosis in moyamoya disease: the fourth periventricular anastomosis and a potential predictor of hemorrhage

ObjectivesChoroidal anastomosis is a risk factor for hemorrhage in moyamoya disease. One variant of choroidal anastomosis, “transcallosal anastomosis,” originates from the medial posterior choroidal artery, and penetrates the corpus callosum to reconstruct the pericallosal artery. We aimed to investigate the prevalence and the bleeding rate of transcallosal anastomosis using sliding thin-slab maximum intensity projection reformatted from magnetic resonance angiography (MRA). Materials and MethodsThis study included 222 patients. We defined transcallosal anastomosis grades (0-2) and the stenosis of the anterior (ACA, 0-2), middle (MCA, 1-3), and posterior cerebral artery (PCA, 0-2) by MRA scores, independently by two coauthors. ResultsGrade-2 transcallosal anastomosis was detected in 21 patients (9.5 %). There were no correlations of the incidence of transcallosal anastomosis with previous bypass surgery (P = 0.23). Multivariate analysis revealed a significantly higher incidence in hemorrhagic onset and younger age (odds ratio [OR] 3.77, and 0.97). Transcallosal anastomosis had statistically significant correlation with ACA and PCA scores (P = 0.01 and 0.03), but not with MCA scores (P = 0.1). In multivariate analysis, ACA scores 1 and 2 were significantly higher (OR, 15.44 and 11.17), and PCA score 1 was also higher (OR, 3.07), but PCA score 2 was not. Interrater agreement for judgment of transcallosal anastomosis grade was strong (κ = 0.89). Two patients with Grade-2 transcallosal anastomosis had late hemorrhage in the corpus callosum (bleeding rate: 2.5 % per year). ConclusionsTranscallosal anastomosis may be associated with both advanced ACA and moderate PCA stenosis, and cause hemorrhage at the corpus callosum.

Three-Dimensional Arterial Spin Labeling for the Evaluation of the Cerebral Hemodynamics in Ischemic and Hemorrhagic Moyamoya Disease

Introduction: Moyamoya disease (MMD) is a vascular disease with significant risk of mortality due to ischemia or hemorrhage in the brain. The goal of the study was to explore three-dimensional arterial spin labeling (3D-ASL) to improve evaluation of cerebral hemodynamics in patients with MMD. Methods: Our study included 54 cases of ischemic MMD and 42 cases of hemorrhagic MMD. Dynamic susceptibility contrast-enhanced perfusion-weighted imaging (DSC-PWI) and 3D-ASL were performed at 3.0 T. Based on these scans, cerebral blood flow (CBF), mean transit time (MTT), and time to peak (TTP) were calculated and compared between patients with different disease subtypes. Receiver operating characteristics analysis was used to assess the diagnostic sensitivity and specificity of different imaging procedures and parameters. Results: Our data suggested that CBF in the lesion area was more severely reduced in patients with hemorrhagic MMD than in those with ischemic MMD. The CBF parameter in 3D-ASL diagnosed hemorrhagic and ischemic MMD with a significant sensitivity and specificity of 80.59% and 57.41%, respectively, with an area under the curve (AUC) of 0.75. We also found that the relative CBF of 3D-ASL was more pronounced decreased and the relative MTT and TTP of DSC-PWI were significantly increased in patients with hemorrhagic MMD than those with ischemic MMD. Specificity and sensitivity and AUC of 3D-ASL were better than the comparison of absolute values from DSC-PWI scans. Conclusion: Our study indicated that 3D-ASL is powerful in differentiating patients with cerebral ischemic or hemorrhagic MMD, providing another diagnostic tool that could potentially improve precision medicine to monitoring MMD patients.

Autophagy and mitophagy-related extracellular mitochondrial dysfunction of cerebrospinal fluid cells in patients with hemorrhagic moyamoya disease

We aimed to investigate whether mitochondrial dysfunction in extracellular cerebrospinal fluid (CSF), which is associated with autophagy and mitophagy, might be involved in neurological outcomes in adult patients with hemorrhagic moyamoya disease (MMD) whose pathogenesis related to poor outcomes is not well-known. CSF samples were collected from 43 adult MMD patients and analyzed according to outcomes at 3 months. Fluorescence-activated cell sorter analysis (FACS) and the JC-1 red/green ratio were used to assess mitochondrial cells and intact mitochondrial membrane potential (MMP). We performed quantitative real-time polymerase chain reaction and Western blotting analyses of autophagy and mitophagy-related markers, including HIF1α, ATG5, pBECN1, BECN1, BAX, BNIP3L, DAPK1, and PINK1. Finally, FACS analysis with specific fluorescence-conjugated antibodies was performed to evaluate the potential cellular origin of CSF mitochondrial cells. Twenty-seven females (62.8%) with a mean age of 47.4 ± 9.7 years were included in the study. Among 43 patients with hemorrhagic MMD, 23 (53.5%) had poor outcomes. The difference in MMP was evident between the two groups (2.4 ± 0.2 in patients with poor outcome vs. 3.5 ± 0.4 in patients with good outcome; p = 0.02). A significantly higher expression (2–ΔCt) of HIF1α, ATG5, DAPK1 followed by BAX and BNIP3L mRNA and protein was also observed in poor-outcome patients compared to those with good outcomes. Higher percentage of vWF-positive mitochondria, suggesting endothelial cell origins, was observed in patients with good outcome compared with those with poor outcome (25.0 ± 1.4% in patients with good outcome vs. 17.5 ± 1.5% in those with poor outcome; p < 0.01). We observed the association between increased mitochondrial dysfunction concomitant with autophagy and mitophagy in CSF cells and neurological outcomes in adult patients with hemorrhagic MMD. Further prospective multicenter studies are needed to determine whether it has a diagnostic value for risk prediction.

Bypass Surgery for Adult-Onset Hemorrhagic Moyamoya Disease: Analysis Classified by Site of Initial Bleeding

Prevention of rebleeding events is crucial for patients with hemorrhagic moyamoya disease (MMD), as these increase the risk of mortality. Bypass surgery is effective in preventing subsequent hemorrhage, particularly in patients with posterior hemorrhage, but its efficacy in those with anterior hemorrhage remains unclear. We analyzed the effects of surgical intervention, stroke risk factors, and radiological features on rebleeding events. Patients with hemorrhagic-onset MMD who were followed at our institution between 2000 and 2022 were included (41 adult patients, 45 hemispheres). Baseline characteristics and radiological features (anterior or posterior hemorrhagic site, Suzuki grade, posterior cerebral artery involvement, and periventricular anastomosis) were thoroughly reviewed. Of the 45 hemispheres, hemorrhage developed in 9 (20%) hemispheres, with a median duration until rebleeding of 38 (range: 1-44) months. Rebleeding rates were significantly lower in the surgical group than in the nonsurgical group (odds ratio: 0.09; 95% confidence interval [CI]: 0.01-0.79; P= 0.011), and Kaplan-Meier analysis revealed a significantly longer interval between bleeding events in the surgical group (1.3%/y vs. 5.3%/y; P= 0.002), especially in the anterior hemorrhage group (1.3%/y vs. 5.1%/y; P= 0.019). The hazard ratio of surgical intervention for rebleeding with initial anterior hemorrhage was 0.11 (95% CI: 0.01-0.98; P= 0.048). In the nonsurgical group, the presence of hypertension shortened the time to subsequent hemorrhage (P= 0.004). Surgical intervention may decrease the risk of rebleeding in hemorrhagic onset MMD patients, even in those presenting with anterior hemorrhage. Hypertension was a significant risk factor for rebleeding in nonsurgical patients.

Transdural Collateral Circulation Indicates Cerebral Ischemia in Moyamoya Disease

Moyamoya disease (MMD) is an idiopathic occlusive cerebrovascular disorder. The development of collateral circulation originates from the dural and pial collaterals. Currently, the clinical significance of transdural collateral in MMD has not been established. We sought to study the relationship between transdural collateral circulation and the side of relative cerebral ischemia in MMD. Data from MMD patients were collected at Xiangya Hospital from January 2016 to April 2022. A collateral circulation grading system with scores was established, the dominant side of transdural collateral with a higher point. Cerebral perfusion was used to identify the side of relative cerebral ischemia. A total of 102 patients were recruited. Results of digital subtraction angiography showed that 74 (72.5%) patients had transdural collaterals. The transdural collaterals were more common in patients with infarctions than in those with headaches or transient ischemic attacks (P= 0.0074). The dominant side for the formation of transdural collateral circulation was more easily found at the side of relative cerebral ischemia (P < 0.0001). Additionally, the side of the brain with a higher score of transdural collaterals was more likely to experience relative cerebral ischemia (P < 0.0001). There was no significant difference in the formation of transdural collateral circulation between ischemic and hemorrhagic MMD patients. Transdural collateral circulation was common in MMD patients. The transdural collaterals were associated with the occurrence of infarction. Transdural collaterals were well established on the cerebral ischemic side, which indicated higher ischemic levels in the ipsilateral than contralateral side.

Analysis of Prognostic Factors in Patients with Hemorrhagic Moyamoya Disease

Background: Hemorrhagic Moyamoya disease (MMD) is a common subtype of MMD in adult patients, especially in East Asian countries. To our knowledge, current studies regarding factors affecting the prognosis in patients with hemorrhagic MMD is lacking. This study aimed to determine the potential prognostic factors for hemorrhagic MMD.Methods: This retrospective study reviewed patients with hemorrhagic MMD diagnosed at our hospital between June 2011 and June 2021. Patient outcome was measured at discharge using the extended Glasgow outcome scale (GOSE). Prognostic factors were assessed by multivariate logistic regression analysis.Results: Patients discharged with worst outcomes (GOSE 1 and 2) had significantly lower initial Glasgow coma scale (GCS) scores (5.9 ± 3.1 vs. 10.3 ± 3.7; P = 0.002) and were associated with more severe intraventricular hemorrhage (IVH) (P = 0.007), and IVH-related hydrocephalus requiring extraventricular drain (EVD) insertion was more common (n = 12 vs. n = 7; P = 0.001). The multivariate analysis showed that IVH-related hydrocephalus requiring EVD placement (OR 8.256, 95% CI 0.996–68.450; P = 0.016) and low initial GCS scores (OR 0.644; 95% CI 0.465–0.892; P = 0.008) were independent risk factors for unfavorable outcomes (GOSE 1–4) in patients with hemorrhagic MMD.Conclusion: This study analyzed several potential prognostic factors for patients with hemorrhagic MMD. Low initial GCS scores and IVH-related hydrocephalus requiring EVD insertion were related to unfavorable outcomes.

Antiplatelet therapy may improve the prognosis of patients with moyamoya disease: a 12-year retrospective study.

The clinical value of antiplatelet therapy (APT) for moyamoya disease (MMD) remains controversial. Our study attempts to clarify the value of APT in this disease. We collected basic information, treatment strategies, and prognostic information on patients with MMD from 2010 to 2022 at our center. The data were divided into two groups, depending on whether APT was used or not, and compared by Pearson Chi-Square, Fisher's exact test, or Wilcoxon rank-sum test. We used propensity scores or inverse probability of treatment weighting to balance the covariates. Following this, we performed a meta-analysis of APT use in MMD. 177 patients were enrolled, with a median follow-up of 41.1months. APT did not affect the prognosis of patients with perioperative MMD, ischemic MMD, or asymptomatic MMD (P > 0.05), without increasing cerebral hemorrhagic risk. In contrast, APT was found to reduce mortality among patients with hemorrhagic MMD (P = 0.019), without affecting functional status, increasing stroke risk, or causing intracerebral hemorrhage (P > 0.05). But the small group cannot show the effect of APT. Our meta-analysis included nine articles involving 28,925 patients with MMD. It showed that APT could reduce stroke risk (odds ratio, OR = 0.57, 95% CI 0.49 to 0.65) and the Modified Rankin Scale (mRS) (weighted mean difference, WMD = - 0.07, 95% CI 0.14-0.00) during follow-up. The cohort study has limited weight (1.97% and 19.29%) in the meta-analysis. Although the limited number of included documents, APT could be beneficial to the prognosis of MMD.

Clinical and Genetic Characteristics of Patients with Moyamoya Disease who Experienced Both Ischemic and Hemorrhagic Events.

Cerebrovascular events in moyamoya disease are mainly classified into ischemic or hemorrhagic onset. It is rare for one patient to develop both ischemia and hemorrhage in moyamoya disease; detailed clinical course and genetic characteristics of such patients have not been elucidated. We aimed to clarify the clinical features of patients with both ischemic and hemorrhagic cerebrovascular events. We analyzed the background factors, radiological features, and genotype of ring finger protein 213 c.14429G>A (p.Arg4810Lys) of patients with moyamoya disease who visited our hospital between 1996 and 2020, and experienced both ischemic and hemorrhagic cerebrovascular events. Additionally, we analyzed factors that caused subsequent hemorrhage in adult-onset ischemic moyamoya disease. Of 262 patients, 12 presented with both ischemia and hemorrhage, of which, 4 exhibited pediatric onset and 8 had adult onset. In pediatric-onset subjects, ischemia was the initial event in all cases. Hemorrhagic events occurred at a median of 24.7years postoperatively in patients who had undergone bypass surgery. In adult-onset subjects, ischemia preceded hemorrhage in 7 patients. In males, the interval to subsequent hemorrhage was significantly shorter for adult-onset ischemic moyamoya disease, and the hazard ratio for hemorrhagic events was 5.45. The ring finger protein 213 p.Arg4810Lys heterozygous variant was present in 9 patients. A majority of patients with moyamoya disease with both ischemia and hemorrhage experience an ischemic event first. Patients who developed ischemia in childhood may develop subsequent hemorrhage in approximately 20-25years after bypass surgery. Male sex is a risk factor for a subsequent hemorrhagic event in adult-onset ischemic moyamoya disease.

Chinese expert consensus on the treatment of MMD

Moyamoya disease (MMD), also known as spontaneous occlusion of the circle of Willis, is defined by progressive stenosis or occlusion of the internal carotid arteries, and it can progress to the anterior, middle, and posterior cerebral arteries. As these arteries are gradually stenosed, a collateral network of capillaries develops at the base of the brain, producing the characteristic reticulate appearance (“puff of smoke”) on angiography. Therefore, it was named by Suzuki and Takaku in 1969 after the Japanese term “moyamoya” (Suzuki and Takaku, Arch Neurol 20:288–299, 1969). MMD is most common in East Asian countries such as Japan and Korea, and it shows a slight female predominance. MMD is mainly characterized by ischemia and hemorrhage. Hemorrhagic MMD is very rare in children, and most cases occur in adults due to the rupture of the compensatory blood vessels, which often leads to hemorrhagic symptoms (Scott and Smith, N Engl J Med 360:1226–1237, 2009). In recent years, the diagnosis rate has increased with the popularization of imaging techniques. However, the pathogenesis of MMD is still not completely understood, and there is currently no evidence to suggest that drug treatment can delay or even reverse the progression of MMD. The current drug treatment for in MMD only targets its clinical symptoms, including ischemia and hemorrhage. The main choice of treatment for MMD is surgical revascularization. As an increasing number of hospitals have developed surgical treatment for MMD, our compiling group has jointly discussed the formulation of a consensus among Chinese experts on the treatment of MMD.