Encephaloduroarteriosynangiosis Research Articles

Factors affecting the collateral ingrowth from the superficial temporal artery after Encephalo-Duro-Arterio-Synangiosis in adult patients with Moyamoya disease

BackgroundMultiple factors have been proposed to affect the vessel ingrowth from the superficial temporal artery (STA) after Encephalo-Duro-Arterio-Synangiosis (EDAS). MethodsThis retrospective single-center analyses included patients with Moyamoya Disease (MMD) undergoing EDAS from January 1st, 2013, to December 31st, 2023. Evaluated variables included demographic characteristics, clinical presentation, technical details, modified Rankin Scale (mRS) scores, and radiographic outcomes. Univariate and multivariate analysis was performed to identify factors favoring the ingrowth of collaterals from the STA. ResultsForty adult patients with MMD, most commonly females (77.5 %) with a median age of 48, underwent 56 EDAS. The most common initial presentations were ischemic events (75.0 %), followed by hemorrhagic events (27.5 %) and seizures (7.5 %). Digital angiography performed at a median of 13.7 months post-procedure revealed collateral growth from the STA in 78.6 % of cases, with a Matsushima grade A identified in 35.7 % of the revascularized hemispheres. Univariate analysis showed more collaterals in patients with a larger preoperative STA diameter (p=0.035), higher Suzuki grades (p=0.021) and longer angiographic follow-ups (p=0.048). Patients with occlusion of the internal carotid artery (ICA; p<0.01), middle cerebral artery (MCA; p<0.01), or anterior cerebral artery (ACA; p<0.01) also had more collateral ingrowth. Multivariate analysis revealed that ICA occlusion (OR=6.54; 95 % CI=1.03–41.48) and ACA occlusion (OR=6.52; 95 % CI=1.02–41.67) as predictors of collateral ingrowth from the STA. ConclusionICA and ACA occlusion were associated with success after EDAS. Longer follow-ups and larger STA demonstrated significant association on univariate analysis, but lost significance after adjusting for other procedural characteristics.

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.

Development and validation of a novel nomogram for predicting good neoangiogenesis after encephaloduroarteriosynangiosis in patients with moyamoya disease and type 2 diabetes mellitus: a case-control study.

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

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.

Axial Magnetic Resonance Angiography in Evaluating Revascularization after Indirect Bypass Surgery for Moyamoya Axial Magnetic Resonance Angiography after Indirect Bypass

Introduction: At our institution, revascularization after indirect moyamoya surgery is routinely evaluated using magnetic resonance angiography (MRA) rather than catheter angiography. In this paper, we review how revascularization can be visualized on axial MRA and compare its visualization on MRA to that on catheter angiography. We also compare clinical outcomes of patients followed with routine postoperative MRA with outcomes of patients followed with routine catheter angiography. Methods: We retrospectively reviewed the records of all patients treated at our institution who underwent unilateral encephaloduroarteriosynangiosis (EDAS) and/or pial synangiosis between the ages of 1 and 21 years and between December 31, 2003, and May 1, 2021. We included patients who underwent EDAS/pial synangiosis at other hospitals as long as they met all inclusion criteria. Inclusion criteria included having a preoperative MRA within 18 months of surgery and a postoperative MRA 3−30 months after surgery. Clinical outcomes included development of postoperative stroke and transient ischemic attacks (TIAs) and changes in symptoms (improved, unchanged, or worsened), including seizures, balance issues, and headaches. Clinical outcomes were compared between patients who had routine postoperative MRA only versus those who had routine postoperative angiograms, with or without routine MRA. For each surgery, we determined the ratios of the diameters and areas of the donor vessel and the contralateral corresponding vessel, as well as the relative signal intensities of these two vessels, on preoperative and 3- to 30-month postoperative MRA. We did the same for the middle meningeal artery (MMA) ipsilateral to the donor artery and the contralateral MMA. We assessed changes from pre- to post-operation in diameter ratios, area ratios, relative signal intensity, ivy sign, and in brain perfusion on arterial spin labeled (ASL) imaging. MRI and MRA measures of revascularization and flow were compared to Matsushima grades in patients who had postoperative catheter angiograms. Results: Fifty-one operations for 42 unique patients were included. There were no significant differences in the rates of postoperative strokes, postoperative TIAs, changes in symptoms, or new symptoms after surgeries evaluated by routine postoperative MRA versus catheter angiogram (p = 0.282, 1, 0.664, and 0.727, respectively). There were significant associations between greater collateralization on postoperative MRA and greater median increases in preoperative-to-postoperative ratios of donor-vessel-over-contralateral-vessel diameter (p = 0.0461), ipsilateral-MMA-over-contralateral-MMA diameter (p = 0.0135), and the summed donor and ipsilateral MMA diameters over the summed contralateral vessel diameters (p < 0.001). The median increase in the ratio of the donor vessel and contralateral corresponding vessel diameters was significantly higher for Matsushima grade A versus B (p = 0.036). The median increase in the ratio of the sum of donor and ipsilateral MMA diameters over the sum of the contralateral vessel diameters was significantly higher for improved-versus-unchanged perfusion on ASL imaging (p = 0.0074). There was a nonsignificant association between greater postoperative collateralization on MRA and Matsushima grade (p = 0.1160). Conclusion: Cerebral revascularization after EDAS and pial synangiosis can be evaluated on axial MRA by comparing the diameter and/or signal intensity of the donor vessel and corresponding contralateral vessel, as well as the ipsilateral and contralateral MMA, on postoperative-versus-preoperative MRA. The use of routine postoperative MRA rather than catheter angiography does not appear to negatively affect outcomes.

The Association of Heterozygous p.R4810K of RNF213 and Long-Term Unfavorable Outcomes after Encephaloduroarteriosynangiosis in Chinese Pediatric Patients with Moyamoya Disease

Background. Previous studies have established that heterozygous mutation for the p.R4810K variant can influence the severity of the clinical phenotype in patients with moyamoya disease (MMD) at disease onset. However, the relationship between the p.R4810K variant and the clinical phenotype of long-term unfavorable outcomes in Chinese pediatric patients remains unclear. Objectives. The primary aim of this study was to examine the association of heterozygous p.R4810K of RNF213 and long-term unfavorable outcomes after encephaloduroarteriosynangiosis (EDAS) in Chinese pediatric patients with MMD. Method. In this retrospective cohort study, we included 259 pediatric patients with MMD who possessed the known p.R4810K genotype. These individuals underwent EDAS along with genotyping analysis for p.R4810K via a TaqMan probe and the QuantStudio 6 Flex Real-Time PCR System. Subsequently, we evaluated their long-term outcomes. The variables we assessed were age at diagnosis, gender, p.R4810K genotypes, initial modified Rankin scale (mRS), clinical manifestations (such as hemorrhage and ischemia), posterior cerebral artery (PCA) involvement combined with angiographic stage, and their history of risk factors like hyperlipidemia and hyperhomocysteinemia. Furthermore, we scrutinized long-term unfavorable outcomes using both univariate analyses and multivariate logistic regression to identify independent predictive factors. Results. This study enrolled 259 Chinese pediatric patients with MMD, which included both newly and previously diagnosed cases, who underwent EDAS. The cohort comprised 130 male participants (50.19%) and 129 female participants (49.81%), with a median onset age of 8 years (median, IQR: 6-12 years). Among these patients, homozygous mutations were exceptionally rare, identified in only 4 individuals (1.54%), while the prevalence of heterozygous mutations was relatively higher, observed in 85 children (32.82%). The multivariate logistic regression showed that several factors were significantly associated with long-term unfavorable outcomes: older age at diagnosis (OR, 0.82 [95% CI, 0.7-0.96], P=0.014), onset with hematoma (OR, 12.76 [95% CI, 1.52-106.89], P=0.019), initial mRS (OR, 24.53 [95% CI, 6.51-92.41], P&lt;0.001), perioperative infarction (OR, 22.16 [95% CI, 1.45-337.96], P=0.026), and infarction during follow-up (OR, 14.5 [95% CI, 2.04-103.12], P=0.008). Furthermore, the cumulative incidence of initial infarction suggested that pediatric patients with homozygous or heterozygous mutations typically present at a younger age and exhibit a higher incidence of initial infarction compared to those carrying wild-type genotypes. Conclusions. The study suggests that the p.R4810K variant is associated with the onset age of MMD in Chinese pediatric patients, potentially impacting long-term outcomes. Surprisingly low recurrent stroke rates were observed across all genotypes, including homozygous individuals for the pathogenic variant, indicating that nongenetic factors may also play a role in the course and outcomes of MMD in this population.

Indirect revascularization for pediatric moyamoya disease.

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

Association between polymorphism in the MTHFR gene and encephaloduroarteriosynangiosis-induced collateral circulation formation.

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

Long-term outcomes after conservative and EDAS treatment for 111 elderly patients with moyamoya disease: longitudinal and cross-sectional study.

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

Clinical and genetic factors associated with contralateral progression in unilateral moyamoya disease: Longitudinal and Cross-Sectional Study

ObjectiveThis study aimed to explore the long-term outcome of unilateral moyamoya disease and predict the clinical and genetic factors associated with contralateral progression in unilateral moyamoya disease. MethodsWe retrospectively recruited unilateral moyamoya disease patients with available genetic data who underwent encephaloduroarteriosynangiosis (EDAS) surgery at our institution from January 2009 to November 2017. Long-term follow-up data, including clinical outcomes, angiographic features, and genetic information, were analyzed. ResultsA total of 83 unilateral moyamoya disease patients with available genetic data were enrolled in our study. The mean duration of clinical follow-up was 7.9 ± 2.0 years. Among all patients, 19 patients demonstrated contralateral progression to bilateral disease. Heterozygous Ring Finger Protein 213 p.R4810K mutations occurred significantly more frequently in unilateral moyamoya disease patients with contralateral progression. Furthermore, patients with contralateral progression typically demonstrated an earlier age of onset than those with non-progressing unilateral moyamoya disease. In the contralateral progression group, posterior circulation involvement was observed in 11 (11/19, 57.9%) patients compared to 12 (12/64, 18.8%) in the non-contralateral progression group (P = 0.001). The time to peak of cerebral perfusion and neurological status showed significant postoperative improvement. ConclusionLong-term follow-up revealed that the EDAS procedure might provide benefits for unilateral moyamoya disease patients. Ring Finger Protein 213 p.R4810K mutations, younger age, and posterior circulation involvement might predict the contralateral progression of unilateral moyamoya disease.

Abstract 17474: Factors Affecting Cognitive Status in Patients With Intracranial Atherosclerosis After Surgical Revascularization: A Post Hoc Analysis of ERSIAS Phase-2 Performance Criterion (PC) Trial

Introduction: Cognitive decline affects a large proportion of patients with ischemic stroke. Intracranial atherosclerotic disease (ICAD) is a common stroke etiology associated with a high and prolonged risk of recurrence. In the ERSIAS phase-II trial, patients with symptomatic ICAD received revascularization with encephaloduroarteriosynangiosis (EDAS) plus intensive medical management (IMM) of stroke risk factors. We present a subgroup analysis of features affecting cognitive outcomes. Hypothesis: To evaluate the factors contributing to cognitive decline in patients who underwent revascularization for symptomatic ICAD. Methods: ERSIAS patients without aphasia that completed at least one year of follow-up were included. Cognitive status was evaluated using MoCA at baseline and each follow-up and classified as improved/preserved vs. worsened. Classification and Regression Tree Analysis (CART) was used to identify factors associated with changes in cognitive function. Factors considered were age, sex, stenosis vs. occlusion, baseline-mRS, good collateralization and compliance with diabetes (DM) hypertension (HTN), and hyperlipidemia (HLD) treatments. Results: In ERSIAS, the mean MoCA at baseline was 22.4 (SD 4.9), and 23.9 (SD 4.9) at one-year follow-up in the complete population. Thirty-nine patients were included in this analysis. Median age was 46 (IQR 37.0-56.0), and 27 (69.2%) were female. MoCA improved or remained stable in 33 (84.6%) patients and declined in 6 (15.4%). CART analysis revealed that the most relevant factors for improved MoCA were compliance with DM treatment (94.5%(yes) vs.74.2%(no) p=0.02) HLD treatment (83.3% (yes) 60.5%(no) p=0.2) and stenosis 99.1% vs. occlusion 80.9%, p=0.6 Other factors where not found to be contributory. Conclusions: Compliance with DM treatment is a significant predictor of cognitive preservation in symptomatic ICAD patients. Our findings emphasize the importance of IMM of stroke risk factors in patients with intracranial atherosclerosis, even after surgical revascularization.

Evaluation of surgical revascularization procedure outcomes for adult Moyamoya disease: a computed tomography perfusion-based study

BackgroundThe effectiveness of surgical interventions, whether direct or indirect, for Moyamoya disease (MMD) remains controversial. This study aims to investigate CT perfusion (CTP) as an objective method to evaluate the outcomes of different surgical modalities for adult MMD.MethodsThe clinical and imaging data of 41 patients who underwent superficial temporal artery-middle cerebral artery (STA-MCA) bypass and 43 who received encephaloduroarteriosynangiosis (EDAS) were retrospectively analyzed. Intra- and intergroup differences in the Modified Rankin Scale (mRS) score, the change in clinical symptoms, collateral grade, and CTP parameters pre- and postoperatively were compared.ResultsThe overall level of the change in clinical symptoms in the STA-MCA group was higher than in the EDAS group (p < 0.05). In the operative area, the relative cerebral blood flow (rCBF) was significantly higher whereas the relative time to peak (rTTP) and the relative mean transit time (rMTT) were significantly lower in the STA-MCA and EDAS groups postoperatively than preoperatively (all p < 0.05). In the ipsilateral frontal lobe and basal ganglia, the postoperative rCBF was significantly higher, and the rTTP was significantly lower than the preoperative in the STA-MCA group (all p < 0.05). The postoperative rCBF improvement was higher in each brain area for STA-MCA than in the EDAS group (all p < 0.05).ConclusionHighlighting the utility of CTP, this study demonstrates its effectiveness in assessing postoperative cerebral hemodynamic changes in adult MMD patients. STA-MCA yielded a larger postoperative perfusion area and greater improvement compared to EDAS, suggesting CTP’s potential to elucidate symptom variation between two surgical revascularization procedures.Critical relevance statementWe analyzed computed tomography perfusion parameters in pre- and postoperative adult Moyamoya disease patients undergoing superficial temporal artery-middle cerebral artery bypass and encephaloduroarteriosynangiosis. Our findings suggest computed tomography perfusion’s potential in objectively elucidating symptom variations between these surgical revascularization approaches for MMD.Key points• Postoperative perfusion improvement is only confined to the operative area after EDAS.• Besides the operative area, postoperative perfusion in the ipsilateral frontal lobe and basal ganglia was also improved after STA-MCA.• The degree of perfusion improvement in each brain area in the STA-MCA group was generally greater than that in the EDAS group.Graphical

Abstract 110: Autoangiogenesis Secondary to Chronic Cocaine Use Mimicking Moya‐Moya

Introduction We present the case of a young male presenting with syncope who was found to have incidental hypodensities on computed tomography (CT) of his head, with magnetic resonance imaging (MRI) concerning for Moya‐Moya related occlusion of the right internal carotid artery, but with digital subtraction angiography (DSA) showing extensive autoangiogenesis and collateralization from all other intracranial vascular territories, without Moya‐Moya related changes. This presumably developed as reactive changes to severe chronic cocaine use. Methods We present a case from a tertiary care center in the borough of Manhattan, New York City, USA. All information is deidentified and exempt from IRB approval. Results A 36‐year‐old man with history significant for asthma, active smoker status, and active cocaine use, presented for loss of consciousness. The patient reported 3 days of upper respiratory symptoms and decreased oral intake with subsequent loss of consciousness immediately preceded by lightheadedness and nausea, and without any post‐event confusion, lacerations, or incontinence. Neurologic history is significant for right upper extremity weakness from 9/2022‐12/2022 that self‐resolved and was believed to be a peripheral nerve pathology. Admission exam without focal deficits. Admission CT of his head showed multifocal confluent hypodensities in the subcortical right frontal lobe. CT Angiogram of head and neck showed severe narrowing at right Internal Carotid Artery (ICA) terminus and right M1 segment with lenticulostriate arterial collateralization, severe bilateral A1 stenosis with distal Anterior Cerebral Artery (ACA) flow suggestive of chronic collateralization, and significant right Posterior Cerebral Artery (PCA) collateralization. Given concern for Moya‐Moya disease, MRI of the brain was obtained and despite no acute infarct, MRI was significant for multifocal white matter T2/FLAIR hyperintensities with the largest in the right frontal lobe. The patient subsequently underwent digital subtraction angiography (DSA) to assess collaterals and stratify for possible need for future encephaloduroarteriosynangiosis (EDAS). DSA showed significant auto‐angiogenesis between numerous vascular territories, including recruitment of right Posterior Cerebral Artery and External Carotid Artery branches to perfuse the territory of the severe right ICA terminus steno‐occlusive disease. With minimal anterograde flow into the right Anterior Choroidal Artery and none to the right Middle Cerebral Artery (MCA), the characteristic Moya‐Moya appearance was not appreciated on DSA given minimal anigogenesis around the right ICA occlusion site. Rather, distal perfusion of the R ICA territory was dependent on collaterals from the right PCA, right ACA via the Anterior Communicating Artery, angiogenesis between the right Anterior Falcine Artery and R ACA, and angiogenesis between the right MCA and ACA/MCA cortical branches. These proliferative changes involved all cranial vascular territories, including those without steno‐occlusive disease. Conclusion Acute cocaine use is associated with increased risk of acute ischemic stroke[1], due in part to its sympathomimetic effects causing vasospasm and to its arrhythmic properties[2]. Neuroadaptation after chronic cocaine use is less well understood though rat models suggest that as cerebral ischemia develops from chronic cocaine use, the HIF‐VEGF pathway is activated to promote angiogenesis to restore local blood flow[3]. We present this case as evidence of a similar angiogenic physiologic response in humans to minimize the microvascular ischemic injury from chronic cocaine use.

A long-term study of posterior circulation changes after revascularization in patients with moyamoya disease.

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

Role of human dural fibroblasts in the angiogenic responses of human endothelial cells: An in vitro dural model and the application of lab-on-a-chip for EDAS.

Encephaloduroarteriosynangiosis (EDAS), an indirect anastomosis procedure, is widely accepted as a primary treatment for moyamoya disease (MMD) to improve collateral blood flow. During surgical intervention, dural fibroblasts (DuF) are thought to produce various proteins that create an angiogenic microenvironment. However, the biophysiological evidence supporting the angiogenic properties of this surgical technique has not been thoroughly elucidated. The purpose of these studies was to determine whether DuF releases pro-angiogenic factors and chemokines and promotes angiogenic properties in human endothelial cells (ECs) under IL-1β-mediated wound conditions, which are expected to occur during the process of neo-vascularization within the dura mater. Furthermore, a microfluidic chemotaxis platform was implemented to investigate the angiogenic activity of ECs in response to a reconstituted dura model. Transcriptome sequencing revealed that IL-1β stimulation on DuF induced a significant upregulation of various pro-angiogenic genes, including IL-6, IL-8, CCL-2, CCL-5, SMOC-1, and SCG-2 (p < 0.05). Moreover, compared to ECs cultured in naïve media or naïve DuF media, those exposed to IL-1β-DuF conditioned media expressed higher mRNA and protein levels of these pro-angiogenic factors (p < 0.001). ECs co-cultured with IL-1β-DuF also exhibited considerable migration on the microfluidic chemotaxis platform. Furthermore, the chemotactic effects on the ECs were reduced upon neutralization of IL-8 or inhibition of NF-κB signaling. Our findings demonstrate that IL-1β-DuFs release factors that activate and enhance the angiogenic properties of ECs. These results suggest a potential interaction between DuF and ECs following EDAS for MMD, and these components could be targeted for the development of therapeutic biomarkers.

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.

To explore the effectiveness of atorvastatin in the postoperative formation of collateral blood vessels after encephaloduroarteriosynangiosis in patients with moyamoya disease: a prospective double-blind randomized controlled study.

The aim of this large, prospective, double-blind randomized controlled trial is to investigate the effect of atorvastatin on the formation of collateral blood vessels in patients after encephaloduroarteriosynangiosis (EDAS) and to provide a theoretical basis for clinical drug intervention. Specifically, we will determine whether atorvastatin has an effect on the development of collateral vascularization and on cerebral blood perfusion after revasculoplasty in patients with moyamoya disease (MMD). Overall, 180 patients with moyamoya disease will be recruited and randomly assigned to the atorvastatin treatment group or the placebo control group in a 1:1 ratio. Before revascularization surgery, magnetic resonance imaging (MRI) scanning and digital subangiography (DSA) examination will be routinely performed on the enrolled patients. All patients will receive intervention via EDAS. According to the randomization results, patients in the experimental group will be treated with atorvastatin (20 mg/day, once a day, for 8 weeks) and patients in the control group will be treated with placebo (20 mg/day, once a day, for 8 weeks). All participants will return to the hospital for MRI scan and DSA examination 6 months after EDAS surgery. The primary outcome of this trial will be the difference in the formation of collateral blood vessels revealed by DSA examination at 6 months after EDAS surgery between the two groups. The secondary outcome will be an improvement in the dynamic susceptibility contrast sequence cerebral perfusion on MRI at 6 months after EDAS, compared to the preoperative baseline. This study was approved by the Ethics Committee of the First Medical Center of the PLA General Hospital. All participates will voluntary provide written informed consent before participating in the trial. ClinicalTrials.gov, ChiCTR2200064976.

5613251 RAPIDLY PROGRESSING MOYAMOYA SYNDROME IN SICKLE CELL DISEASE -- CASE REPORT

Introduction: Moyamoya syndrome (MMS) is an uncommon cerebrovascular complication of Sickle Cell Disease (SCD) characterized by progressive narrowing of large intracranial vessels and development of small-vessel collaterals. This association leads to a significant risk of ischemic stroke and poor neurologic outcomes. Case description: We present a case of a 5-year-old female child, with irregular follow-up at Pediatric Hematology Consultation due to Sickle Cell Disease, who presented to our hospital with a first ischemic stroke. The magnetic resonance angiography (MRA) showed narrowing of the terminal portions of the right internal carotid artery, the proximal segments of the right middle and anterior cerebral arteries and the A1 segment of left anterior cerebral artery, with multiple collaterals, aspects highly suggestive of MMS. She initiated hydroxycarbamide, acetylsalicylic acid and chronic red blood cell exchange (RBCX) aiming HbS<30% and 3 months later she presented with a new transient ischemic stroke. She was submitted to right encephaloduroarteriosynangiosis (EDAS) and was stable, without new ischemic events, until 1 year later when she presented with a new transient ischemic stroke of the left cerebral territory. Since then, she had multiple recurrent ischemic events with total recovery of neurologic deficits. MRA and Computed tomography (CT) showed multiple diffuse areas of cerebral infarction and bilateral severe segmental stenosis of internal carotid, middle and anterior cerebral arteries. Discussion/Conclusion: The literature review suggests that early detection and surgical revascularization in addition to RBCX could significantly reduce stroke recurrence and improve neurocognitive outcome. However, in this case, despite the recommended treatment, it was not possible to prevent the rapid progression of MMS, revealing the complexity of the approach to these patients.

Long-term outcomes of moyamoya disease versus atherosclerosis-associated moyamoya vasculopathy using high-resolution MR vessel wall imaging

ObjectivesWe aimed to compare the long-term outcomes and surgical benefits between moyamoya disease (MMD) and atherosclerosis-associated moyamoya vasculopathy (AS-MMV) using high-resolution MRI (HRMRI).MethodsMMV patients were retrospectively included and divided into...

Abstract Number ‐ 216: Limb‐Shaking Transient Ischemic Attack in the Setting of Moyamoya Disease

Introduction Moyamoya disease (MMD) is a cerebrovascular disorder characterized by progressive narrowing of the large intracranial arteries, primarily the internal carotid artery (ICA) and its branches, with secondary development of prominent small‐vessel collaterals. Limb shaking is a rare manifestation of transient ischemic attack (TIA) that is characterized by brief, irregular, involuntary jerking of the arms or legs and momentary disorientation without complete loss of consciousness. It is mainly associated with high grade carotid stenosis. In rare cases, limb‐shaking TIA can occur in the setting of MMD. Methods The patient was identified in routine clinical practice. Results A woman in her 50s presented with a six‐year history of progressive weakness below the neck when standing and initiating movement. These episodes were followed by violent shaking of her arms and legs that lasted several seconds to minutes. She reported transient confusion after the events, but no seizure activity was seen on multiple EEGs, and anti‐epileptic drugs (AEDs) failed to alleviate her symptoms. Further neurological workup included a MR angiogram of the brain that was suggestive of MMD. Catheter angiography confirmed bilateral occlusion of the M1 segments of the middle cerebral arteries (MCAs) and the A1 segment of the left anterior cerebral artery (ACA). There was neovascularization in the same territories with significant collateral flow from the posterior circulation. She was diagnosed with bilateral limb‐shaking TIA in the setting of MMD. She recently underwent two revascularization procedures, a left superficial temporal artery (STA) to middle cerebral artery (MCA) bypass and a right sided encephaloduroarteriosynangiosis (EDAS). Conclusions Limb‐shaking TIA is predominantly associated with severe atherosclerotic extracranial carotid artery stenosis. In rare cases, the limb‐shaking episodes are caused by cerebral hypoperfusion secondary to severe stenosis of the ICAs, and their branches, in the setting of moyamoya disease. Treatment of limb‐shaking TIA to prevent further brain ischemia includes adjustment of fluid intake, careful blood pressure management to avoid episodes of relative brain hypoperfusion, and revascularization procedures. Revascularization is also the most effective method of treating MMD and patients will often experience improvement of their symptoms within one year. Early recognition of limb‐shaking TIA in MMD is critical to avoid unnecessary and potentially harmful treatments (e.g. AEDs), provide patients with accurate explanations of their symptoms, and ensure timely administration of the appropriate treatments.