Adult Moyamoya Disease Research Articles

Macrovascular blood flow and microvascular cerebrovascular reactivity are regionally coupled in adolescence.

Cerebrovascular imaging assessments are particularly challenging in adolescent cohorts, where not all modalities are appropriate, and rapid brain maturation alters hemodynamics at both macro- and microvascular scales. In a preliminary sample of healthy adolescents (n = 12, 8-25 years), we investigated relationships between 4D flow MRI-derived blood velocity and blood flow in bilateral anterior, middle, and posterior cerebral arteries and BOLD cerebrovascular reactivity (CVR) in associated vascular territories. As hypothesized, higher velocities in large arteries are associated with an earlier response to a vasodilatory stimulus (cerebrovascular reactivity delay) in the downstream territory. Higher blood flow through these arteries is associated with a larger BOLD response to a vasodilatory stimulus (cerebrovascular reactivity amplitude) in the associated territory. These trends are consistent in a case study of adult moyamoya disease. In our small adolescent cohort, macrovascular-microvascular relationships for velocity/delay and flow/CVR change with age, though underlying mechanisms are unclear. Our work emphasizes the need to better characterize this key stage of human brain development, when cerebrovascular hemodynamics are changing, and standard imaging methods offer limited insight into these processes. We provide important normative data for future comparisons in pathology, where combining macro- and microvascular assessments may better help us prevent, stratify, and treat cerebrovascular disease.

Autoregulatory dysfunction in adult Moyamoya disease with cerebral hyperperfusion syndrome after bypass surgery

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

Clinical Characteristics and Multi-Model Imaging Analysis of Moyamoya Disease: An Observational Study.

Previous studies have lacked a comprehensive analysis of imaging modalities for diagnosing Moyamoya disease (MMD). This study aims to bridge this gap by utilizing multi-modal imaging to provide a more detailed understanding of the clinical and imaging characteristics of MMD. A retrospective analysis was conducted on seventy-eight adult MMD patients enrolled from March 2018 to March 2021. The study focused on clinical features, imaging findings, and treatment outcomes, with a particular emphasis on the comparative efficacy of different imaging modalities. In this series, clinical manifestations varied depending on the type of MMD, with intracerebral hemorrhage (ICH) being the most common (69.2%), followed by cerebral infarction (25.6%). Imaging techniques provided critical diagnostic insights: magnetic resonance imaging (MRI) demonstrated superior sensitivity over computed tomography (CT) in detecting hemorrhages, whereas computed tomography angiography (CTA) and digital subtraction angiography (DSA) identified intricate vascular lesions, including moyamoya vessels and aneurysms. Notably, cerebral perfusion imaging (CTP) highlighted significant differences in cerebral blood flow and volume between infarction and hemorrhage cases. This comprehensive imaging approach guided varied therapeutic strategies, including bypass surgery in 57 patients and interventional embolization for aneurysms in 14 patients. The authors' findings underscore the critical role of early diagnosis using DSA, whereas highlighting CTA and MRA as valuable noninvasive tools for screening and follow-up. The integration of multi-modal imaging provides a detailed vascular assessment crucial for individualized patient management, facilitating timely interventions and significantly improving clinical outcomes.

Impact of Surgical Revascularization on Regression of Enlarged Perivascular Spaces in Adult Moyamoya Disease.

Previous studies have suggested that enlarged perivascular spaces (EPVSs) are potential radiological markers of cerebral ischemia in moyamoya disease (MMD). However, serial changes in EPVSs after surgical revascularization have not yet been clarified. We aimed to elucidate the postoperative changes in EPVSs in adult patients with MMD, clinical and radiological factors affecting the number of EPVSs, and the degree of postoperative changes. We counted the EPVSs in the centrum semiovale in each hemisphere on a T2-weighted MRI performed before surgery. EPVSs were quantified 3months and 2years after combined bypass surgery in surgically treated patients and compared with the number of EPVSs before surgery. We performed multivariate logistic regression analysis to identify the clinical and radiological factors associated with the number of EPVSs. This study included 120 hemispheres of 65 adults with MMD. Older age (P < 0.01), posterior cerebral artery (PCA) involvement (P < 0.01), and cerebral blood flow (CBF) impairment (P = 0.02) were significantly associated with a large number of EPVSs. The number of EPVSs markedly decreased at 3months and 2years after surgery compared with that before surgery (P < 0.01). PCA involvement (P = 0.04) and CBF impairment (P = 0.02) were independent predictors of the regression of EPVSs after surgery. The number of EPVSs in the centrum semiovale was closely associated with age, PCA involvement, and CBF impairment in adult patients with MMD, which remarkably regressed after surgical revascularization, especially in the hemispheres with PCA involvement and CBF impairment. EPVSs are reversible radiological markers reflecting impaired cerebral hemodynamics in adult patients with MMD.

Macrovascular blood flow and microvascular cerebrovascular reactivity are regionally coupled in adolescence.

Cerebrovascular imaging assessments are particularly challenging in adolescent cohorts, where not all modalities are appropriate, and rapid brain maturation alters hemodynamics at both macro- and microvascular scales. In a preliminary sample of healthy adolescents (n=12, 8-25 years), we investigated relationships between 4D flow MRI-derived blood velocity and blood flow in bilateral anterior, middle, and posterior cerebral arteries and BOLD cerebrovascular reactivity in associated vascular territories. As hypothesized, higher velocities in large arteries are associated with an earlier response to a vasodilatory stimulus (cerebrovascular reactivity delay) in the downstream territory. Higher blood flow through these arteries is associated with a larger BOLD response to a vasodilatory stimulus (cerebrovascular reactivity amplitude) in the associated territory. These trends are consistent in a case study of adult moyamoya disease. In our small adolescent cohort, macrovascular-microvascular relationships for velocity/delay and flow/CVR change with age, though underlying mechanisms are unclear. Our work emphasizes the need to better characterize this key stage of human brain development, when cerebrovascular hemodynamics are changing, and standard imaging methods offer limited insight into these processes. We provide important normative data for future comparisons in pathology, where combining macro- and microvascular assessments may better help us prevent, stratify, and treat cerebrovascular disease.

Association between angiographic and clinical outcomes after STA-MCA bypass in adult moyamoya disease.

As an angiographic outcome, postoperative collateral formation (PCF) is commonly used to evaluate the effect of STA-MCA bypass in moyamoya disease (MMD), but whether it can reliably reflect clinical outcomes is still unclear. We investigated the association between PCF and clinical outcomes in adult MMD. All STA-MCA bypass procedures performed from January 2013 to December 2019 were screened in this prospective cohort study. Patients who acquired presurgical and follow-up catheter angiography were included. The clinical outcomes consisted of symptom improvement and recurrent cerebrovascular events. Logistic and Cox regression and Kaplan-Meier analyses were performed to explore the association between PCF and clinical outcomes. Of 165 included symptomatic hemispheres of 154 patients, 104 (63.0%) and 61 (37.0%) had good and poor PCF, respectively. The hemispheres with good PCF were younger (p = 0.004) and had a higher incidence of hemodynamic dysfunction on admission (p < 0.001) than those with poor PCF. Multivariate logistic regression analysis showed that the good PCF (odd ratio, 28.96; 95% confidence interval (CI), 9.12-91.98; p < 0.001) was associated with a higher incidence of symptom improvement. Multivariate Cox regression analysis showed that the poor PCF (hazard ratio, 3.77; 95% CI, 1.31-10.84; p = 0.014) was associated with a higher incidence of recurrent cerebrovascular events. In the hemorrhagic-onset hemispheres, good PCF group had a higher incidence of symptom improvement (p < 0.001) and a longer hemorrhage-free time (p = 0.031). In the ischemic-onset hemispheres, good PCF group also had a higher incidence of symptom improvement (p < 0.001) and a longer ischemia-free time (p = 0.028). As a angiographic outcome, collateral formation is a qualified surrogate measure for clinical outcomes after STA-MCA bypass in adult MMD.

Comprehensive Serum Proteomic and Metabolomic Profiles of Pediatric Patients with Moyamoya Disease Reveal Core Pathways.

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

Superficial Temporal Artery Size Changes After Encephaloduroarteriosynangiosis for the Treatment of Moyamoya Disease

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

Update on the anesthesia management in adult patients with moyamoya disease.

The anesthetic management of patients with Moyamoya disease (MMD) is challenging and continues to evolve. The goal of this review is to provide updated recommendations on the anesthetic management of adult MMD patients based on the relevant existing literature. Key findings include the importance of aggressive hydration preoperatively to sustain cerebral perfusion. Hypertension induced intraoperatively may prevent cerebral hypoperfusion. Vigilance against cerebral hyperperfusion after revascularization is necessary, with specific blood pressure targets recommended. Fluid management should aim for normovolemia to mild hypervolemia. Maintaining body temperature helps prevent cerebral vasospasm induced by hypothermia. Maintaining adequate oxygen supply during surgery is crucial. In cases of ischemic stroke, managing hematocrit and oxygen carrying capacity is essential to prevent further ischemia. Extubation decisions should consider baseline neurological function, while postoperative normocapnia helps prevent cerebral hyperperfusion and hypertension. In intensive care, cautious blood pressure management is crucial to prevent secondary complications. Strategies in the preoperative, intraoperative, and postoperative anesthetic management of MMD patients should aim to maintain adequate cerebral perfusion to prevent cerebral ischemia.

Prediction of cerebral infarction after bypass surgery in adult moyamoya disease: using pulsatility index on TCD

BackgroundAt present, the most effective treatment for symptomatic moyamoya disease (MMD) is surgery. However, the high incidence of postoperative complications is a serious problem plaguing the surgical treatment of MMD, especially the acute cerebral infarction. Decreased cerebrovascular reserve is an independent risk factor for ischemic infarction, and the pulsatility index (PI) of transcranial Doppler (TCD) is a common intuitive index for evaluating intracranial vascular compliance. However, the relationship between PI and the occurrence of ischemic stroke after operation is unclear.ObjectiveTo explore whether the PI in the middle cerebral artery (MCA) could serve as a potential predictor for the occurrence of ischemic infarction after bypass surgery in MMD.MethodsWe performed a retrospective analysis of data from 71 patients who underwent combined revascularization surgery, including superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis and encephalo-duro-myo-synangiosis (EDMS). The patients were divided into two groups according to the median of ipsilateral MCA-PI before operation, low PI group (MCA-PI < 0.614) and high PI group (MCA-PI ≥ 0.614). Univariate and multivariate regression analysis were used to explore risk factors affecting the occurrence of postoperative cerebral infarction.ResultsAmong the 71 patients with moyamoya disease, 11 patients had cerebral infarction within one week after revascularization. Among them, 10 patients’ ipsilateral MCA-PI were less than 0.614, and another one’s MCA- PI is higher than 0.614. Univariate analysis showed that the lower ipsilateral MCA-PI (0.448 ± 0.109 vs. 0.637 ± 0.124; P = 0.001) and higher Suzuki stage (P = 0.025) were linked to postoperative cerebral infarction. Multivariate analysis revealed that lower ipsilateral MCA-PI was an independent risk factor for predicting postoperative cerebral infarction (adjusted OR = 14.063; 95% CI = 6.265 ~ 37.308; P = 0.009).ConclusionsA lower PI in the ipsilateral MCA may predict the cerebral infarction after combined revascularization surgery with high specificity. And combined revascularization appears to be safer for the moyamoya patients in early stages.

Association of Cognitive Reserve and Preoperative Cognitive Function in Patients with Adult Moyamoya Disease: A Preliminary Study.

Many patients with moyamoya disease (MMD) exhibit cognitive decline; however, the link between cognitive reserve (CR) and cognitive function in those who have not undergone revascularization remains unexplored. We aimed to evaluate preoperative cognitive impairment in such patients and to explore the relationship between CR, measured using the Cognitive Reserve Index questionnaire (CRIq), and cognitive abilities across different domains, determined using neuropsychological tests. Demographic, clinical, CRIq, and neuropsychological assessment data were gathered from patients with MMD who underwent preoperative cognitive functional assessments at our center during 2021-2023. These patients were categorized according to their Montreal Cognitive Assessment score. Multivariable linear regression was performed to analyze the association between CRIq score and cognitive performance, both globally and in specific domains. In the MMD cohort of 53 patients, 49% (n = 26) of the patients exhibited a decrease in overall cognitive performance. Individuals with cognitive dysfunction had significantly lower composite CRIq scores than those with intact cognition. Although no association between overall cognitive ability and CR was observed, independent associations emerged between CR and specific cognitive functions - language (β = 0.56, p = 0.002), verbal memory (β = 0.45, p = 0.001), and executive function (β = 0.35, p = 0.03). This preliminary study revealed that expressive language, verbal memory, and executive function are linked to CR in presurgical patients with MMD, highlighting the role of CR in predicting cognitive outcomes. Further research is warranted to elucidate the combined effects of CR and other risk factors on the cognitive function of patients with MMD.

Neuropsychological Test Performance Differentiates Subgroups of Individuals With Adult Moyamoya Disease: A Cross-Sectional Clinical Study.

Moyamoya disease (MMD) is a rare noninflammatory disorder involving progressive intracranial vasculopathy and impaired cerebral blood flow in the anterior circulation, resulting in stroke and cognitive impairment. We aimed to characterize cognitive impairment and the possible predictive value of sociodemographic and clinical characteristics of adults with MMD. This cross-sectional study examined neurocognitive performance in a group of 42 consecutive adult patients (mean age = 40.52 years; 69% female) referred for a presurgical neuropsychological evaluation. Neuropsychological functioning was assessed with a comprehensive battery, and cognitive dysfunction was defined as 1.5 SDs below the mean. Neurocognitive performance correlated with clinical/demographic characteristics and disease markers. Most patients (91%) had a history of stroke, and 45% had cognitive deficits, most notably on measures of attention/speed (48%), executive functioning (47%), visuoconstruction (41%), and memory (31%-54%). Only higher educational attainment and poor collateral blood flow in the right hemisphere differentiated cognitively impaired (n = 19) and intact groups (n = 23), and MMD-related characteristics (eg, disease duration, stroke history) did not differentiate the 2 groups. Consistent with previous work, frontal-subcortical cognitive deficits (eg, deficits in mental speed, attention, executive functioning) were found in nearly half of patients with MMD and better cognitive performance was associated with factors related to cognitive reserve. Angiographic metrics of disease burden (eg, Suzuki rating, collateral flow) and hemodynamic reserve were not consistently associated with poorer cognitive outcomes, suggesting that cognition is a crucial independent factor to assess in MMD and has relevance for treatment planning and functional status.

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.

Vascular risk profile and changes of arterial hypertension after surgical revascularization in adult Moyamoya patients

Moyamoya disease (MMD) is a rare stenoocclusive cerebral vasculopathy often treated by neurosurgical revascularization using extracranial-intracranial bypasses to prevent ischemic or hemorrhagic events. Little is known about the vascular risk profile of adult MMD patients compared to the general population. We therefore analyzed 133 adult MMD patients and compared them with data from more than 22,000 patients from the German Health Update database. Patients with MMD showed an age- and sex-adjusted increased prevalence of arterial hypertension, especially in women between 30 and 44 years and in patients of both sexes between 45 and 64 years. Diabetes mellitus was diagnosed significantly more frequently in MMD patients with increasing age, whereas the vascular risk profile in terms of obesity, nicotine and alcohol consumption was similar to that of the general population. Antihypertensive medication was changed one year after surgical revascularization in 67.5% of patients with a tendency towards dose reduction in 43.2% of all patients. After revascularization, physicians need to be aware of a high likelihood of changes in arterial hypertension and should adjust all other modifiable systemic vascular risk factors to achieve the best treatment possible.

Predictive value of the hemispheric magnetic resonance angiography score on the development of indirect pial synangiosis after combined revascularization surgery for adult moyamoya disease.

It is difficult to precisely predict indirect bypass development in the context of combined bypass procedures in moyamoya disease (MMD). We aimed to investigate the predictive value of magnetic resonance angiography (MRA) signal intensity in the peripheral portion of the major cerebral arteries for indirect bypass development in adult patients with MMD. We studied 93 hemispheres from 62 adult patients who underwent combined direct and indirect revascularization between 2005 and 2019 and genetic analysis for RNF213 p.R4810K. The signal intensity of the peripheral portion of the major intracranial arteries during preoperative MRA was graded as a hemispheric MRA score (0-3 in the middle cerebral artery and 0-2 in the anterior cerebral and posterior cerebral arteries, with a high score representing low visibility) according to each vessel's visibility. Postoperative bypass development was qualitatively evaluated using MRA, and we evaluated the correlation between preoperative factors, including the hemispheric MRA score and bypass development, using univariate and multivariate analyses. A good indirect bypass was observed in 70% of the hemispheres. Hemispheric MRA scores were significantly higher in hemispheres with good indirect bypass development than in those with poor indirect bypass development (median: 3 vs. 1; p < 0.0001). Multiple logistic regression analysis revealed hemispheric MRA score as an independent predictor of good indirect bypass development (odds ratio, 2.1; 95% confidence interval, 1.3-3.6; p < 0.01). The low hemispheric MRA score (< 2) and wild-type RNF213 predicted poor indirect bypass development with a specificity of 0.92. Hemispheric MRA score was a predictive factor for indirect bypass development in adult patients who underwent a combined bypass procedure for MMD. Predicting poor indirect bypass development may lead to future tailored bypass surgeries for MMD.

Natural course of hemodynamically stable hemispheres contralateral to operated hemispheres in adult patients with ischemic moyamoya diseases

The necessity of bilateral bypass in adult moyamoya disease (MMD) remains unclear despite its recommendation for pediatric and hemorrhagic cases. We aimed to investigate the natural course of hemodynamically stable unoperated hemispheres after bypass surgery for symptomatic and hemodynamically unstable hemispheres in adult patients with ischemic MMD. Among 288 patients, the mean age at the first operation of the unstable hemispheres was 40.8 ± 12.2 years. The mean follow-up period was 62.9 ± 46.5 months. 45 patients (15.6%) experienced stroke events in the unoperated hemisphere, consisting of hemorrhagic stroke in 8 (2.8%) and ischemic stroke in 37 (12.8%), including progressive transient ischemic attack in 25 (8.7%) and infarction in 12 (4.2%). Among them, 39 patients (13.5%) underwent bypass surgery. The annual risk of total stroke is 3.0%/patient-year, with 2.5% for ischemic stroke and 0.5% for hemorrhagic stroke. The 5- and 10-year cumulative risks of ischemic stroke were 13.4% and 18.3%, respectively, and those of hemorrhagic stroke were each 3.2%. The natural course of hemodynamically stable hemispheres contralateral to the operated ones appeared fairly good. Additional bypass surgery on the unoperated hemispheres should be considered for symptomatic and hemodynamically unstable hemispheres in adult patients with ischemic MMD during the follow-up.

Decreased diffusivity along the perivascular space and cerebral hemodynamic disturbance in adult moyamoya disease

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

Prediction of postoperative cerebral infarction after combined bypass surgery in adult moyamoya disease: combining quantitative parameters on RAPID perfusion CT with clinically related factors.

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. 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. 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). 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.

106 Characteristics of Cognitive Impairment in Moyamoya Disease

INTRODUCTION: Cognitive impairment in adult moyamoya disease (MMD) is thought to be the result of ischemic stroke; however, the presence and extent of cognitive decline in asymptomatic patients remain largely unknown. METHODS: After classification using T2-weighted fluid attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI), a total of 19 MMD patients with a history of cerebral infarction, 21 asymptomatic MMD patients, and 20 healthy controls matched for age, sex, and years of education were prospectively included in this study. A detailed neuropsychological evaluation of two moyamoya subgroups and normal controls was conducted. In addition, participants underwent arterial spin labeling and resting state fMRI sequences. RESULTS: Asymptomatic patients showed varying degrees of decline in intelligence (Raven’s Standard Progressive Matrices, P = 0.001), spatial imagination (mental rotation, P = 0.014), working memory (verbal working memory-backward digit span, P = 0.011), and computational ability (simple subtraction, P = 0.014; complex subtraction, P &lt; 0.001) compared with normal controls. MMD patients with cerebral infarction had more severe impairment in complex arithmetic (P = 0.027) and word short-term memory (P = 0.01) than those without symptoms. The asymptomatic MMD group also showed decreased CBF in the left anterior central and left inferior frontal gyri of the island fap with multiple node abnormalities in the brain network and reduced network connectivity. There was a significant association of these changes with cognitive decline in the MMD group. CONCLUSIONS: In asymptomatic MMD patients, a variety of cognitive impairments precedes the onset of clinical symptoms such as cerebral infarction, which may be a long-term complication of conservative treatment. Besides, disturbance of CBF and impaired brain network connections may be important causes of cognitive decline.

309 High Glutamine Associated With the Risk of Stroke by Inducing Endothelial to Mesenchymal Transition Through ITGB4 MAPK-ERK Smad in Moyamoya Disease

INTRODUCTION: Previous studies have suggested potential association between glutamine and stroke. The role of glutamine in moyamoya disease (MMD) manifestation and pathological process remains unknown. METHODS: A prospective cohort of 360 adult MMD patients between September 2020 to December 2021 was established. Human brain microvascular endothelial cells (HBMECs) were utilized for rt-qPCR, western blot, immunofluorescence, and functional assays including CCK8, Edu for proliferation and wound healing for migration. HBMECs were transfected with ITGB4 adenovirus, ITGB4 siRNA or Smad4 siRNA to explore the downstream alterations. Atorvastatin was used to treat HBMECs and the mechanism was explored. Finally, the expression of ITGB4 was validated in databases and immunofluorescence staining of superficial temporal artery in MMD patients. RESULTS: After fully adjusted, the risk of stroke increased with each increment of glutamine level (OR = 1.599, 95% CI = 1.071 – 2.387, p = 0.022). Consistently, compared with patients in the lower tertiles of serum glutamine levels, a significantly higher risk of complete stroke was found in those in highest glutamine tertile (OR = 2.752, 95% CI = 1.556 – 4.868, p = 0.001). After treated with glutamine, HBMECs showed increased proliferation, migration, and endothelial-mesenchymal transition (EndMT) which was reversed by ITGB4 knockdown. In ITGB4-transfected HBMECs, MAPK-ERK-TGF-β/BMP pathway was activated and Smad4 knockdown could reverse the EndMT. Atorvastatin alleviated the EndMT by inhibiting Smad2/3 phosphorylation in ITGB4-transfected HBMECs. The upregulated ITGB4 expression was validated in the superficial temporal artery of MMD patients. CONCLUSIONS: High glutamine was independently associated with the risk of stroke in MMD. Glutamine promotes the proliferation, migration, and EndMT by ITGB4 through MAPK-ERK-TGFβ/BMP-Smad pathway. Atorvastatin could alleviate the EndMT by inhibiting Smad2/3 phosphorylation and promoting Smad4 ubiquitination and thus may be a potential drug for MMD patients.