Adult Moyamoya Disease Research Articles

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.

Safety and efficacy of remote ischemic conditioning in adult moyamoya disease patients undergoing revascularization surgery: a pilot study.

Revascularization surgery for patients with moyamoya disease (MMD) is very complicated and has a high rate of postoperative complications. This pilot study aimed to prove the safety and efficacy of remote ischemic conditioning (RIC) in adult MMD patients undergoing revascularization surgery. A total of 44 patients with MMD were enrolled in this single-center, open-label, prospective, parallel randomized study, including 22 patients assigned to the sham group and 22 patients assigned to the RIC group. The primary outcome was the incidence of major neurologic complications during the perioperative period. Secondary outcomes were the modified Rankin Scale (mRS) score at discharge, at 90 days post-operation, and at 1 year after the operation. The outcome of safety was the incidence of adverse events associated with RIC. Blood samples were obtained to monitor the serum concentrations of cytokines (VEGF, IL-6). No subjects experienced adverse events during RIC intervention, and all patients could tolerate the RIC intervention in the perioperative period. The incidence of major neurologic complications was significantly lower in the RIC group compared with the control group (18.2% vs. 54.5%, P = 0.027). The mRS score at discharge in the RIC group was also lower than the control group (0.86 ± 0.99 vs. 1.18 ± 1.22, P = 0.035). In addition, the serum IL-6 level increased significantly at 7 days after bypass surgery in the control group and the serum level of VEGF at 7 days post-operation in the RIC group. In conclusion, our study demonstrated the neuroprotective effect of RIC by reducing perioperative complications and improving cerebral blood flow in adult MMD patients undergoing revascularization surgery. Thus, RIC seems to be a potential treatment method for MMD. ClinicalTrials.gov, identifier: NCT05860946.

Characteristics and Clinical Implication of White Matter Lesions in Patients With Adult Moyamoya Disease.

Characteristics and Clinical Implication of White Matter Lesions in Patients With Adult Moyamoya Disease.

Surgical outcomes following encephaloduroarteriosynangiosis in moyamoya disease associated with hyperhomocysteinemia.

This study investigated the effect of indirect revascularization surgery in adult patients with moyamoya disease (MMD) complicated with hyperhomocysteinemia (HHcy), and the effect of HHcy on the progression of adult MMD. A retrospective case-control study was conducted in patients with MMD, with or without HHcy (n=123). Postoperative collateral angiogenesis was evaluated using the Matsushima grading system and disease progression using the Suzuki staging system. Cerebral blood flow was evaluated before and after surgery using dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI) and neurological function prognosis using the improved Rankin score (mRS). Univariate and multivariate logistic regression analyses were performed to determine risk factors for the clinical outcomes. There was no significant difference in the Suzuki stage composition ratios between the HHcy group and the non-HHcy group before and after surgery. Non-HHcy patients were more likely to grow new collateral circulating vessels after encephaloduroarteriosynangiosis (EDAS). Moreover, postoperative DSC-MRI indicated that the time to peak significantly improved. HHcy level may be a specific predictor of adverse clinical outcomes after EDAS in patients with MMD and a risk factor for poor collateral circulation and poor prognosis. Patients with MMD complicated with HHcy need to strictly control homocysteine levels before EDAS surgery.

Genome-wide association study identifies novel susceptibilities to adult moyamoya disease.

Genome-wide association study has limited to discover single-nucleotide polymorphisms (SNPs) in several ethnicities. Here, we investigated an initial GWAS to identify genetic modifiers predicting with adult moyamoya disease (MMD) in Koreans. GWAS was performed in 216 patients with MMD and 296 controls using the large-scale Asian-specific Axiom Precision Medicine Research Array. A subsequent fine-mapping analysis was conducted to assess the causal variants associated with adult MMD. A total of 489,966 out of 802,688 SNPs were subjected to quality control analysis. Twenty-one SNPs reached a genome-wide significance threshold (p = 5 × 10-8) after pruning linkage disequilibrium (r2 < 0.8) and mis-clustered SNPs. Among these variants, the 17q25.3 region including TBC1D16, CCDC40, GAA, RNF213, and ENDOV genes was broadly associated with MMD (p = 3.1 × 10-20 to 4.2 × 10-8). Mutations in RNF213 including rs8082521 (Q1133K), rs10782008 (V1195M), rs9913636 (E1272Q), rs8074015 (D1331G), and rs9674961 (S2334N) showed a genome-wide significance (1.9 × 10-8 < p < 4.3 × 10-12) and were also replicated in the East-Asian populations. In subsequent analysis, RNF213 mutations were validated in a fine-mapping outcome (log10BF > 7). Most of the loci associated with MMD including 17q25.3 regions were detected with a statistical power greater than 80%. This study identifies several novel and known variations predicting adult MMD in Koreans. These findings may good biomarkers to evaluate MMD susceptibility and its clinical outcomes.

Integrated analysis of the association between methionine cycle and risk of moyamoya disease.

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

Fetal posterior cerebral artery in pediatric and adult moyamoya disease: A single-center experience of 480 patients

PurposeIn past pediatric and adult cohort studies of moyamoya disease, the fetal posterior cerebral artery has received less attention. Its relationship with the clinical manifestations and collateral circulation of moyamoya disease or ipsilateral cerebral hemispheres remains unclear. MethodWe summarize the clinical features of patients with and without fetal posterior cerebral artery moyamoya disease from consecutive cases.We explored the relationship between fetal posterior cerebral arteries and collateral circulation in the ipsilateral cerebral hemispheres, as well as differences among different subgroups of patients.According to the morphology, the fetal posterior cerebral artery is divided into complete fetal posterior cerebral artery and partial fetal posterior cerebral artery. Clinical features were classified as: infarction,hemorrhage,and non-stroke in unilateral/bilateral cerebral hemispheres. Collateral circulation is divided into extracranial vascular compensation and leptomeningeal collateral circulation. Digital subtraction angiography and CT/MR were used to evaluate the blood flow status and clinical characteristics of patients with moyamoya disease. ResultA total of 960 cerebral hemispheres from 142 pediatric patients and 338 adult patients were included in the study. A total of 273 (56.9%) patients had 399 cerebral hemispheres (41.6%) with fetal posterior cerebral arteries. Adults with fetal posterior cerebral arteries had lower rates of infarction (24.6%vs37.3%, P =0.005) and were less likely to have bilateral stroke (8.4%vs11.5%, P =0.038). Cerebral hemispheres with fetal posterior cerebral artery were more likely to have anterior cerebral artery and middle cerebral artery stenosis and less likely to have occlusion (P =0.002, 0.001), and less likely to involve the posterior circulation (P < 0.001). The cerebral hemispheres of the fetal posterior cerebral artery had higher leptomeningeal collateral circulation scores. There are significant differences in extracranial vascular compensation between cerebral hemispheres with and without fetal posterior cerebral artery. Adult patients with fetal posterior cerebral artery were more advanced in Suzuki stage (P =0.017). ConclusionsOur results suggest that fetal posterior cerebral artery is associated with infarct manifestations in pediatric and adult moyamoya disease. In the cerebral hemispheres, the fetal posterior cerebral artery is associated with ipsilateral hemispheric anterior and posterior circulation artery injury, extracranial vascular compensation, leptomeningeal collateral circulation compensation, and infarction. Adult patients with fetal posterior cerebral artery were more advanced in Suzuki stage.

Analysis of Risk Factors for Epilepsy after Combined Re-Vascularization in Adult Patients with Moyamoya Disease.

Re-vascularization is an effective treatment for moyamoya disease (MMD) patients, including direct re-vascularization, indirect re-vascularization and combined re-vascularization, in which combined re-vascularization is particularly widely used. At present, there are few reports on the analysis of epilepsy after combined re-vascularization surgery. To analysis the risk factors of epilepsy in adult MMD patients after combined re-vascularization. Patients with MMD who underwent combined re-vascularization in the Department of Neurosurgery of the First People's Hospital of Yunnan Province from January 2015 to June 2020 were included. Their pre-operative and post-operative complication-related indicators were collected. Finally, logistic regression was used to analyze the clinical risk factors of epilepsy in MMD patients after operation. The incidence of epilepsy after combined re-vascularization was 15.5%. Univariate analysis showed that pre-operative ischemic or hemorrhagic stroke, pre-operative epilepsy, pre-operative history of diabetes, the location of the bypass recipient artery (frontal or temporal lobe), post-operative new cerebral infarction, hyper-perfusion syndrome, and post-operative intra-cranial hemorrhage were the clinical risk factors of epilepsy in MMD patients (all P < 0.05). Multi-variate logistic regression analysis showed that pre-operative epilepsy, the location of the bypass recipient artery, new cerebral infarction, hyper-perfusion syndrome, and post-operative intra-cranial hemorrhage (all P < 0.05) were independent risk factors for post-operative epilepsy in MMD patients. Pre-operative epilepsy, the location of the bypass recipient artery, new cerebral infarction, hyper-perfusion syndrome, and intra-cranial hemorrhage may have a causal relationship with epilepsy in adult MMD patients. It is suggested that some risk factors could be intervened to reduce the incidence of post-operative epilepsy in MMD patients.

How I do it: combined bypass for adult moyamoya disease with maximal consideration of cosmetic aspects.

Combined bypass, including direct and indirect procedures, has been recognized as the maximal revascularization to prevent further hemorrhagic or ischemic stroke in adult moyamoya disease (MMD). It is also important to consider cosmetic aspects when planning combined bypass for MMD. However, there are few reports that have described the cosmetic considerations in bypass surgery for MMD. We demonstrate our surgical techniques aimed at achieving extended revascularization as well as excellent cosmetic outcomes with figures and video. Our combined bypass procedures which focus on achieving maximal cosmetic results are effective methods that require no special instruments or techniques.

Association of Cerebral Hemodynamics and Cognitive Function in Adult Patients with Moyamoya Disease: A Three-Dimensional Pseudo-Continuous Arterial Spin Labeling Study

Cognitive dysfunction is a serious complication of moyamoya disease (MMD) in adults, and reduced cerebral blood flow (CBF) might be the potential cause. We aimed to explore the correlation between cerebral hemodynamics and cognitive function in adults with MMD by using three-dimensional pseudo-continuous arterial spin labeling (3D-pCASL). A total of 24 MMD patients with a history of cerebral infarction, 25 asymptomatic MMD patients, and 25 healthy controls were prospectively enrolled in this study. All participants were performed 3D-pCASL, and cognitive function was evaluated with the Mini-Mental State Examination (MMSE), the Montreal Cognitive Assessment Scale (MoCA), and the Trail Making Test Part A (TMTA). The correlation between cerebral hemodynamics and cognitive function was explored in the region of interest-based analysis. Compared with healthy controls, both CBF and cognition decreased in adult MMD. In the infarction group, the MMSE and MoCA scores correlated with CBF of the right anterior cerebral artery (P=0.037 and 0.010, respectively) and the left middle cerebral artery (MCA) cortical territories (P=0.002 and 0.001, respectively), and the TMTA time-consuming has a negative correlation with CBF of the right and left MCA cortical territories (P=0.044 and 0.010, respectively); in the asymptomatic group, the MMSE and MoCA scores correlated with CBF of the left MCA cortical territory (P=0.032 and 0.029, respectively). The 3D-pCASL can find the hypoperfusion area of CBF in adults with MMD, and hypoperfusion in specific brain regions may cause cognitive dysfunction even in asymptomatic patients.

Long-term study of the cognitive profile of Moyamoya Disease in adults

Moyamoya Disease (MMD) is a rare cerebrovascular disorder which can have significant cognitive consequences. The aim of the current study was to describe comprehensively the domain-specific cognitive profile of adult patients with MMD and to assess whether this changes in the absence of recurrent stroke over long-term follow-up. Comprehensive neuropsychological assessment covering seven cognitive domains was conducted on 61 adult patients with MMD at baseline and then at up to 3 further time points during follow up (median=2.31, 4.87 and 7.12 years). Although 27 patients had had prior surgical revasculariation, none had surgery between neuropsychological assessments. Cognitive impairment was common. At baseline, impairment in executive functions was most frequent (57%), followed by performance IQ (36%), speed of information processing (31%) and visual memory (30%). We found that the neuropsychological profile remains broadly stable over long-term follow-up with no clear indication of improvement or significant decline. The pattern of impairment also did not differ depending on age of onset or whether there was a history of either prior stroke at presentation or revascularisation surgery at presentation.

Expression of hypoxia-inducing factor-1α and matrix metalloproteinase-9 in the recipient parasylvian cortical arteries with different hemodynamic sources in adult moyamoya disease.

In our latest research, we have demonstrated that the recipient parasylvian cortical arteries (PSCAs) with hemodynamic sources from the middle cerebral artery (M-PSCAs) has a higher risk of postoperative cerebral hyperperfusion (CHP) syndrome than those from non-M-PSCAs in adult moyamoya disease (MMD) patient. However, whether there are differences between M-PSCAs and non-M-PSCAs in vascular specimens characteristics has not been studied. In this study, we further investigate the vascular specimen of recipient PSCAs by histological and immunohistochemical methods. 50 vascular specimens of recipient PSCAs were obtained from 50 adult MMD patients during the combined bypass surgeries in our departments of Zhongnan hospital. 4 recipient PSCAs samples were also obtained in the same way from the middle cerebral artery occlusion patients. The samples were received the pathological sectioning, hematoxylin and eosin staining, and immunohistochemistry, then the vascular wall thickness, matrix metalloproteinase-9 (MMP-9) and hypoxia-inducing factor-1α (HIF-1α) were analyzed. M-PSCAs adult MMD patients had a thinner intima than non-M-PSCAs in the recipient PSCAs specimens. In recipient non-M-PSCAs vascular specimens, the immunoreactivity indicating HIF-1α and matrix metalloproteinase-9 (MMP-9) was significantly higher than M-PSCAs groups. The logistic regression analyses showed that the M-PSCAs was an independent risk factor of postoperative cerebral hyperperfusion (CHP) syndrome (OR 6.235, 95% CI1.018-38.170, P = 0.048) in MMD. Our results indicate that M-PSCAs adult MMD patients had thinner intima than non-MCAs adult MMD patients in the PSCAs. More importantly, HIF-1α and MMP-9 were overexpressed in non-M-PSCAs vascular specimens.

Characteristics and Clinical Implication of White Matter Lesions in Patients With Adult Moyamoya Disease.

White matter hyperintensities (WMHs) are reportedly increased in moyamoya disease (MMD); however, their clinical importance is not well-established owing to their pathophysiologic heterogeneity by distribution. This study aimed to evaluate the burden and pattern of WMHs and its clinical implications in the MMD trajectory. Adult patients with MMD without significant structural lesions were 1:1 propensity score-matched with healthy controls for sex and vascular risk factors. The total, periventricular, and subcortical WMH volumes were segmented and quantified fully automatically. WMH volumes were detrended by age and compared between the 2 groups. MMD severity based on Suzuki stage and future ischemic events were assessed for their association with WMH volumes. A total of 161 pairs of patients with MMD and controls were analyzed. MMD significantly correlated with increased total WMH volume (B [standard error], 0.126 [0.030]; p < 0.001), periventricular WMH volume (0.114 [0.027]; p < 0.001), and periventricular-to-subcortical ratio (0.090 [0.034]; p = 0.009). In the MMD subgroup (n = 187), advanced MMD had an independent association with the total WMH volume (0.120 [0.035]; p < 0.001), periventricular WMH volume (0.110 [0.031]; p < 0.001), and periventricular-to-subcortical ratio (0.139 [0.038]; p < 0.001). Periventricular WMH volume (adjusted hazard ratio [95% confidence interval], 5.12 [1.26-20.79]) and periventricular-to-subcortical ratio (3.80 [1.51-9.56]) were associated with future ischemic events in patients with medically followed up MMD. However, no demonstrable association was found between subcortical WMH volume and MMD, MMD severity, or future ischemic events. Periventricular WMHs, but not subcortical WMHs, may represent the main pathophysiology of MMD. Periventricular WMHs may be used as a marker for ischemic vulnerability in patients with MMD.

Ultrasonic hemodynamic changes of superficial temporal artery graft in different angiogenesis outcomes of Moyamoya disease patients treated with combined revascularization surgery.

Combined bypass is commonly used in adult Moyamoya disease (MMD) for revascularization purposes. The blood flow from the external carotid artery system supplied by the superficial temporal artery (STA), middle meningeal artery (MMA), and deep temporal artery (DTA) can restore the impaired hemodynamics of the ischemic brain. In this study we attempted to evaluate the hemodynamic changes of the STA graft and predict the angiogenesis outcomes in MMD patients after combined bypass surgery by using quantitative ultrasonography. We retrospectively studied Moyamoya patients who were treated by combined bypass between September 2017 and June 2021 in our hospital. We quantitatively measured the STA with ultrasound and recorded the blood flow, diameter, pulsatility index (PI) and resistance index (RI) to assess graft development preoperatively and at 1 day, 7 days, 3 months, and 6 months after surgery. All patients received both pre- and post- operative angiography evaluation. Patients were divided into either well- or poorly-angiogenesis groups according to the transdural collateral formation status on angiography at 6 months after surgery (W group or P group). Patients with matshushima grade A or B were divided into W group. Patients with matshushima grade C were divided into P group, indicating a poor angiogenesis development. A total of 52 patients with 54 operated hemispheres were enrolled, including 25 men and 27 women with an average age of 39 ± 14.3 years. Compared to preoperative values, the average blood flow of an STA graft at day 1 postoperation increased from 16.06 ± 12.47 to 117.47± 73.77 (mL/min), diameter increased from 1.14 ± 0.33 to 1.81 ± 0.30 (mm), PI dropped from 1.77 ± 0.42 to 0.76 ± 0.37, and RI dropped from 1.77 ± 0.42 to 0.50 ± 0.12. According to the Matsushima grade at 6 months after surgery, 30 hemispheres qualified as W group and 24 hemispheres as P group. Statistically significant differences were found between the two groups in diameter (p = 0.010) as well as flow (p = 0.017) at 3 months post-surgery. Flow also remained significantly different at 6 months after surgery (p = 0.014). Based on GEE logistic regression evaluation, the patients with higher levels of flow post-operation were more likely to have poorly-compensated collateral. ROC analysis showed that increased flow of ≥69.5 ml/min (p = 0.003; AUC = 0.74) or a 604% (p = 0.012; AUC = 0.70) increase at 3 months post-surgery compared with the pre-operative value is the cut-off point which had the highest Youden's index for predicting P group. Furthermore, a diameter at 3 months post-surgery that is ≥0.75 mm (p = 0.008; AUC = 0.71) or 52% (p =0.021; AUC = 0.68) wider than pre-operation also indicates a high risk of poor indirect collateral formation. The hemodynamic of the STA graft changed significantly after combined bypass surgery. An increased flow of more than 69.5 ml/min at 3 months was a good predictive factor for poor neoangiogenesis in MMD patients treated with combined bypass surgery.

Association between White Matter Hyperintensities Burden and Cognitive Function in Adult Asymptomatic Moyamoya Disease.

Background and Purpose: White matter hyperintensities (WMH) caused by chronic cerebral hypoperfusion are common in Moyamoya disease (MMD) patients, but WMH burden with comprehensive cognition in adult asymptomatic MMD remains unknown. This study tried to investigate the association between the WMH burden and cognitive function in adult asymptomatic MMD. Methods: Sixty-four adult asymptomatic MMD patients without surgical revascularization were enrolled in this study and underwent a 3T MRI scan and complete cognitive tests from 2021 to 2022. WMH volume was extracted with brain anatomical analysis using the diffeomorphic deformation (BAAD) toolbox, which works on SPM 12 software. Multivariable linear regression analysis was performed to assess the association between WMH burden and cognitive function in asymptomatic MMD. Results: Firstly, our data showed that lower education levels and higher WMH burden were strongly related to global cognitive impairment after adjusting for other variables. Secondly, WMH severity was significantly associated with several domains of neurocognitive function, including memory, semantic memory, and executive function. Finally, when stratified by sex, the female participants with WMH severity had lower cognitive performance in all areas than male participants. Conclusions: These results suggest that WMH burden was highly correlated with global cognition, memory, semantic memory, and executive function in asymptomatic MMD. Especially in female participants, the relationship became more evident.

Abstract WP112: Iodine-123-iomazenil Spect Revealed Recovery Of Neuronal Viability In Association With Improvement Of Cognitive Dysfunction After Revascularization In Moyamoya Disease

Background: Recent studies indicate 123I-iomazenil (123I-IMZ) SPECT could demonstrate a neuronal viability. Although cognitive dysfunction has been recognized as an important issue in adult moyamoya disease (MMD), standard neuroradiological methods to define such condition are not established. Aim: Relationship between cognitive function and 123I-IMZ SPECT before and after revascularization in MMD was firstly examined. Method: Fifteen patients whose cerebrovascular reactivities (CVRs) were decreased only on the treatment sides were studied. Cognitive function was examined using mini-mental scale examination (MMSE, cutoff 27) and frontal assessment battery (FAB, cutoff 16) before and 6 months after surgery. 123I-IMZ and 123I-iodoamphetamine SPECT with acetazolamide challenge were performed at the same timings. Radioreactivities of 123I-IMZ SPECT at the regions with decreased CVR were investigated using affected-to-contralateral side ratio (ACR). Results: Eleven patients showed normal cognitive dysfunction before surgery (MMSE 29.5, FAB 18). In their preoperative 123I-IMZ SPECT, there were no regions with decreased uptakes (ACR 0.97). The cognitive functions and 123I-IMZ SPECT were not worsened after surgery (MMSE 29.9, FAB 18, ACR 0.99). By contrast, preoperative images of four patients with cognitive dysfunction (MMSE 23.8, FAB 14) showed decrease of 123I-IMZ uptakes, and the preoperative ACRs (0.82) were significantly lower than those of the normal group. Cognitive functions and 123I-IMZ uptakes of these four patients tended to ameliorate after revascularization (MMSE 27.5, FAB 15.5, ACR 0.92). Conclusion: Cognitive functions of MMD patients were associated with 123I-IMZ uptakes, and could improve after surgery with recoveries of neuronal viabilities.

Abstract 115: Periventricular But Not Subcortical White Matter Lesions Are Associated With Adult Moyamoya Disease

Introduction: White matter hyperintensities (WMH) are reportedly increased in moyamoya disease (MMD); however, their clinical importance is not well-established owing to their pathophysiological heterogeneity by distribution. This study aimed to evaluate the burden and pattern of WMH and its clinical implications in the MMD trajectory. Methods: Adult MMD patients without significant structural lesions were 1:1 propensity score-matched with healthy controls for sex and vascular risk factors. The total, periventricular, and subcortical WMH volumes were segmented and quantified fully automatically. WMH volumes were detrended by age and compared between the two groups. MMD severity based on Suzuki stage and future ischemic events were assessed for their association with WMH volumes. Results: A total of 190 pairs of patients with MMD and controls were analyzed. MMD significantly correlated with increased total (B, 0.086; standard error [SE], 0.027; p=0.002) and periventricular WMH volumes (B, 0.079; SE, 0.025; p=0.002). In the MMD subgroup, advanced MMD had an independent positive association with the total (B, 0.124; SE, 0.034; p&lt;0.001) and periventricular WMH volumes (B, 0.116; SE, 0.030; p&lt;0.001). Periventricular WMH volume was associated with future ischemic events (adjusted hazard ratio [aHR], 4.96; 95% confidence intervals [CIs], 1.21-20.25) in medically followed-up MMD patients. However, no demonstrable association was found between subcortical WMH volume and MMD (B, 0.007; SE, 0.007; p=0.35), MMD severity (B, 0.010; SE, 0.011; p=0.37), or future ischemic events (aHR, 14.15; 95% CIs, 0.20-1022.96). Conclusions: Periventricular WMH, but not subcortical WMH, may represent the main pathophysiology of MMD. Periventricular WMH may be used as a marker for ischemic vulnerability in patients with MMD.

Computational Modelling of Cerebral Blood Flow Rate at Different Stages of Moyamoya Disease in Adults and Children.

Moyamoya disease is a cerebrovascular disorder which causes a decrease in the cerebral blood flow rate. In this study, a lumped parameter model describing the pressures and flow rates in the heart chambers, circulatory system, and cerebral circulation with the main arteries in the circle of Willis, pial circulation, cerebral capillaries, and veins was used to simulate Moyamoya disease with and without coarctation of the aorta in adults and children. Cerebral blood flow rates were 724 mL/min and 1072 mL/min in the healthy adult and child cardiovascular system models. The cerebral blood flow rates in the adult and child cardiovascular system models simulating Moyamoya disease were 676 mL/min and 1007 mL/min in stage 1, 627 mL/min and 892 mL/min in stage 2, 571 mL/min and 831 in stage 3, and 444 and 537 mL/min in stage 4. The cerebral blood flow rates were 926 mL/min and 1421 mL/min in the adult and child cardiovascular system models simulating coarctation of the aorta. Furthermore, the cerebral blood flow rates in the adult and child cardiovascular system model simulating Moyamoya disease with coarctation of the aorta were 867 mL/min and 1341 mL/min in stage 1, 806 mL/min and 1197 mL/min in stage 2, 735 mL/min and 1121 in stage 3, and 576 and 741 mL/min in stage 4. The numerical model utilised in this study can simulate the advancing stages of Moyamoya disease and evaluate the associated risks with Moyamoya disease.

Analysis of Clinical Characteristic and Risk Factors for Short-Term Prognosis of Moyamoya Disease with Intraventricular Hemorrhage in Adults

Intraventricular hemorrhage (IVH) is the most common type of hemorrhage in moyamoya disease (MMD) with intracerebral hemorrhage (ICH), but the risk factors affecting the short-term prognosis of MMD with IVH in adults are still unclear. We retrospectively analyzed patients of MMD with IVH between January 1, 2018 and January 31, 2020 in the First Affiliated Hospital of Zhengzhou University. According to the modified Rankin Scale (mRS) score at 3 months after discharge, the patients were divided into mRS score ≤2 (good prognosis) group and mRS score >2 (poor prognosis) groups. Univariate and multivariate logistics regression analysis was used to analyze the risk factors affecting the short-term prognosis of adult MMD with IVH. Univariable analyses showed that patients in the poor prognosis group had a significantly older age of onset (48.48 ± 8.34 vs. 43.74 ± 5.44 years; P= 0.002), ahigher percentage of hypertension (57.97% vs. 33.33%; P= 0.014), a higher percentage of tracheotomy (23.19% vs. 2.56%; P= 0.005), a lower Glasgow Coma Scale (GCS) score (7.90 ± 3.58 vs. 11.19 ± 2.56; P= 0.000), a higher Graeb score (7.46 ± 4.04 vs. 5.23 ± 1.93; P= 0.002), and treatment methods (P= 0.000). Multiple logistic regression analysis showed that the lower GCS score (odds ratio [OR],1.761; P= 0.001) and higher Graeb score (OR, 1.767; P= 0.002) were independently associated with the poor prognosis of MMD with IVH, and surgery treatment (OR,0.032; P= 0.000) was independently related to the good prognosis of MMD with IVH. Among patients with MMD with IVH, the lower GCS score and higher Graeb score are independent risk factors for poor prognosis, whereas in patients with MMD with IVH, surgery treatment acts as a protective factor.

Designing a flow-controlled STA-MCA anastomosis based on the Hagen-Poiseuille law for preventing postoperative hyperperfusion in adult moyamoya disease.

Technical improvements for preventing postoperative symptomatic cerebral hyperperfusion (CHP) during superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis for moyamoya disease (MMD) were seldom reported. The aim of this study was to investigate the significance of application of a novel flow-controlled concept which voluntarily reduces the hemodynamic difference between the donor and recipient arteries based on the Hagen-Poiseuille law when performing direct anastomoses of recipient parasylvian cortical arteries (PSCAs) with anterograde hemodynamic sources from the MCA (M-PSCAs) in adult MMD. This was a retrospective observational study. Direct anastomoses of recipient M-PSCAs were performed on 89 symptomatic hemispheres in 82 adult MMD patients in our hospital from January 2020 to June 2021. They were divided into the flow-controlled group (patients who received direct anastomosis under designed flow-controlled principles) and non-flow-controlled group (patients who received conventional direct anastomosis to obtain maximum flow). The patients' basic characteristics and incidence of postoperative CHP were compared between the two groups. Risk factors for occurrence of postoperative CHP were analyzed. Overall, 36 hemispheres were included in the non-flow-controlled group and 53 in flow-controlled group. The incidences of postoperative focal (22.6%) and symptomatic CHP (5.7%) in the flow-controlled group were significantly lower than those (focal, 52.8%; symptomatic, 25.0%) in the non-flow-controlled group (p = 0.003 and 0.009, respectively). Multivariate analysis revealed that the flow-controlled concept was significantly associated with the development of focal (p = 0.005) and symptomatic (p = 0.012) CHP. The flow-controlled STA-MCA anastomosis can significantly decrease the incidence of postoperative CHP during direct anastomoses of recipient M-PSCAs in adult MMD.