Encephaloduroarteriosynangiosis Research Articles

Direct Bypass Surgery Vs. Combined Bypass Surgery for Hemorrhagic Moyamoya Disease: A Comparison of Angiographic Outcomes.

Objective: Extracranial-intracranial bypass is currently recognized as the optimal treatment for hemorrhagic-type moyamoya disease (MMD) which reduces incidence of rebleeding. Recent studies have reported the advantage of combined bypass over direct bypass for the general MMD patients. However, the effect of direct bypass and combined bypass surgery specifically for hemorrhagic-type MMD had not been investigated yet.Methods: Hemorrhagic-type MMD patients who underwent direct and combined bypass surgery with complete clinical and radiological documentation from a multicenter cohort between 2009 and 2017 were retrospectively included. Surgical methods included superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis (direct bypass), combined STA-MCA bypass with encephalodurosynangiosis (EDS), and combined STA-MCA bypass with encephaloduroarteriosynangiosis (EDAS). Matsushima standard on follow-up catheter angiography was used to assess surgical outcome. Modified Rankin Scale, incidence of rebleeding and ischemia during follow-up were recorded. Rebleeding-free survival rates between direct and combined bypass were compared by Kaplan-Meier analysis.Results: Sixty eight hemorrhagic-onset MMD patients were included in this study, among which 71 hemispheres were treated with surgery (direct bypass: 17; bypass+EDS: 24; bypass+EDAS: 30). Forty six (64.8%) hemispheres had satisfactory revascularization (Matsushima level 2–3) and 26 (36.6%) had poor neoangiogenesis. Matsushima level was not significantly different between surgical groups (P = 0.258). Good neoangiogenesis from dural grafts was achieved in 26 (36.6%) hemispheres, and good neoangiogenesis from STA grafts was only seen in 4 (out of 30, 12.5%) hemispheres. Multivariate analysis showed bypass patency [P < 0.001, OR (95%CI): 13.41 (3.28–54.80)] and dural neoangiogenesis [P < 0.001, OR (95%CI): 13.18 (3.26–53.36)] both independently contributed to good angiographic outcome. During follow-up, incidences of rebleeding or ischemic events, and re-bleeding free survival rate were not significantly different between surgical groups (P = 0.433, P = 0.559, and P = 0.997). However, patients who underwent combined bypass surgery had significantly lower mRS at follow-up comparing to patients who underwent direct bypass (P = 0.006).Conclusion: Combined bypass surgery and direct bypass surgery offered similar revascularization for hemorrhagic MMD. Bypass patency and dural angiogenesis both contributed to revascularization independently. The potential of indirect bypass to grow new vessels in hemorrhagic-MMD patients was generally limited, but dural leaflets offered better neoangiogenesis than STA grafts and was therefore recommended for surgical revascularization of hemorrhagic MMD.

Preservation of the Arachnoid Membrane During Encephaloduroarteriosynangiosis (EDAS) Reduces Post-Operative Complications Without Undermining the Surgical Outcome in Paediatric Moyamoya Disease

Background: Encephaloduroarteriosynangiosis (EDAS) is a commonly used indirect revascularization operation method to treat pediatric Moyamoya disease (MMD) patients. Arachnoid dissection has been frequently performed during the EDAS operation in an effort to promote better revascularization. However, no studies have yet proven its surgical benefits. In this study, we investigated the impact of arachnoid preservation on the surgical outcome and post-operative complication by comparing pediatric MMD patients who had the arachnoid membrane preserved during EDAS operation with those who had the arachnoid membrane dissected. Methods: This was a retrospective cohort study based on a single institution, single surgeon's experience. A total of 206 pediatric MMD patients who underwent EDAS operation at Seoul National University Children's Hospital were recruited for the study. We compared the surgical outcomes of these two groups, as well as, post-operation complication rate. Furthermore, risk factors for post-operative complication were analyzed. Findings: The overall clinical outcome (p = 0.342) and the extent of revascularization of MCA territories (p = 0.736) were not different between the arachnoid dissection group and the arachnoid preservation group. However, post-operative infarction/hemorrhage rate was significantly higher in the arachnoid dissection group (p = 0.005). Arachnoid dissection (p = 0.011) and young age (less than 3 years old, less than 3 years, p = 0.012) were significantly associated with increased risk of post-operative complication. Interpretation: Arachnoid preservation may help to reduce post-operative complication without decreasing the surgical outcomes of EDAS operation. Furthermore, patient factors such as the patient's age should be taken into account when treating pediatric MMD patients. Funding Statement: This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI12C0066). Declaration of Interests: The authors state: There are no conflicts of interests. Ethics Approval Statement: The present study was a retrospective cohort study which was approved by the Seoul National University Hospital Institutional Review Board.

Comparison of Therapeutic Efficacy Between Isolated Encephaloduroarteriosynangiosis and Medical Treatment in Patients with Atherosclerotic Middle Cerebral Artery Occlusion

Encephaloduroarteriosynangiosis (EDAS) as a form of indirect revascularization has been recently proposed as a potentially promising alternative for patients with intracranial atherosclerotic disease (ICAD). The object of this study was to compare the prognostic roles between isolated EDAS and medical therapy in patients with atherosclerotic middle cerebral artery occlusion (MCAO). From January 2014 to June 2017, 125 patients with atherosclerotic MCAO were enrolled in this prospective nonrandomized controlled cohort study. Patients who underwent EDAS (n= 60) were compared with those treated medically (n= 65). Early and late adverse events and functional outcomes including memory ability were compared between groups. During 23.7 months of mean follow-up, rates of adverse events, including ischemic events in the territory of the qualifying middle cerebral artery, and death from any causes, were not significantly different in patients treated with EDAS and with medical therapy (6.7% vs. 12.3%; P=0.285). Landmark analyses showed that at initial 6-month follow-up, there was no significant difference for adverse event rates, whereas the opposite finding was shown for the subsequent period (EDAS 1/57 [1.7%] vs. medical management 7/64 [10.9%]; P= 0.024). The P value for the interaction between time (first 6 months vs. subsequent period) was 0.044. No significant differences were found with respect to neural function status and cognitive ability. In the long-term, isolated EDAS can be considered effective and safe for patients with atherosclerotic MCAO, whereas it may need additional medical therapy support in the short-term.

Encephaloduroarteriosynangiosis for pediatric moyamoya disease: long-term follow-up of 100 cases at a single center.

OBJECTIVE The object of this study was to summarize the long-term effect of encephaloduroarteriosynangiosis (EDAS) for the treatment of pediatric moyamoya disease (MMD) and to investigate factors influencing the clinical outcomes of EDAS. METHODS Clinical features, angiographic findings, and clinical outcomes were analyzed among MMD patients younger than 18 years who had been treated with EDAS between 2002 and 2007 at the authors' institution. The Kaplan-Meier method was used to estimate stroke risk after EDAS. Predictors of neurological outcome were assessed. RESULTS One hundred fifteen patients were identified. The mean age at symptom onset was 7.3 ± 4.0 years. The incidence of familial MMD was 11.3%. The female/male ratio was 1:1.16. A total of 232 EDAS procedures were performed, and the incidence of postoperative complications was 3%. Postoperative digital subtraction angiography was performed in 54% of the patients, and about 80% of the hemispheres showed good or excellent results. Neovascularization showed significant correlations with delay time (from symptom onset to first operation), Suzuki stage, and preoperative stroke (all p < 0.05). Clinical follow-up was available in 100 patients with a mean follow-up of 124.4 ± 10.5 months. Ten-year cumulative survival was 96.5% after surgery, and the risk of stroke was 0.33%/person-year. An independent life with no significant disability was reported by 92% of the patients. A good outcome correlated with a low Suzuki stage (p = 0.001). Older children and those without preoperative stroke had better clinical outcomes (p < 0.05). CONCLUSIONS On the basis of long-term follow-up data, the authors concluded that EDAS is a safe and effective treatment for pediatric MMD, can reduce the risk of subsequent neurological events, and can improve quality of life. The risk of ischemia-related complications was higher in younger patients, and older children showed better outcomes. Compensation was greater with more prominent cerebral ischemia. The long-term clinical outcome largely depended on the presence and extent of preoperative stroke.

Encephaloduroarteriosynangiosis for hemorrhagic moyamoya disease: long-term outcome of a consecutive series of 95 adult patients from a single center.

The objective of this study was to investigate long-term outcomes after encephaloduroarteriosynangiosis (EDAS) for the treatment of hemorrhagic moyamoya disease (MMD) and identify the risk factors for recurrent hemorrhages. The authors retrospectively reviewed 95 patients with hemorrhagic MMD who were treated with EDAS at 307th Hospital PLA. Clinical features, angiographic findings, and clinical outcomes were investigated. Rebleeding incidences were compared between anterior or posterior hemorrhagic sites. Kaplan-Meier survival analysis and Cox proportional hazards regression models were used to estimate rebleeding risks after EDAS. The average age at symptom onset was 37.1 years (range 20-54 years) for adult patients. The ratio of female to male patients was 1.16:1. In 61 of 95 hemorrhagic hemispheres (64.2%), the anterior choroidal artery (AChA) or posterior communicating artery (PCoA) was extremely dilated, with extensive branches beyond the choroidal fissure, which only occurred in 28 of 86 nonhemorrhagic hemispheres (32.6%). Fifty-seven incidences were classified as anterior hemorrhages and 38 as posterior. Sixteen of 95 patients (16.8%) suffered cerebral rebleeding after a median follow-up duration of 8.5 years. The annual rebleeding rate was 2.2% per person per year. The incidence rate was higher for the posterior group than for the anterior group, but this difference was not statistically significant (p > 0.05). Cox regression analysis revealed that the age of symptom onset (OR 1.075, 95% CI 1.008-1.147, p = 0.028) was a predictor of rebleeding strokes. Through long-term follow up, EDAS proved beneficial for patients with hemorrhagic MMD. Dilation of the AChA-PCoA is associated with the initial hemorrhage of MMD, and rebleeding is age-related. Patients with hemorrhagic MMD should undergo follow-up over the course of their lives, even when neurological status is excellent.

Long-term Outcomes After Encephaloduroarteriosynangiosis in Adult Patients with Moyamoya Disease Presenting with Ischemia

In adult Moyamoya disease (MMD), there remains controversy about the effectiveness of revascularization surgeries because randomized studies have not been performed to compare the efficacy of surgical techniques. This study was conducted to assess the most appropriate surgical treatment for adult patients with MMD. Encephaloduroarteriosynangiosis (EDAS) was performed on 247 hemispheres in 145 patients. The clinical and demographic characteristics of patients were obtained via retrospective chart review. Clinical and angiographic states were evaluated retrospectively using quantitative methods. The mean duration of clinical follow up was 141.4 ± 19.5 months. A total of 247 EDAS procedures were performed in 145 patients, including 15 EDAS performed using the occipital artery as the donor vessel. The mortality rate was 0%, and the permanent morbidity rates were 1.2% per operation and 2.0% per person. The mean modified Rankin Scale score was 1.21 ± 1.31 postoperatively and 1.01 ± 1.39 at the last follow-up. Of the 109 hemispheres studied, 45% were classified as grade A, 34% as grade B, and 21% as grade C collateral circulation. The annual rates of stroke were calculated to be 0.73% per person-year. Overall, the 1-,5-, and 10-year actuarial stroke rates were 2.1±1.2%, 6.8±2.1%, and 8.9±2.4%, respectively. Bilateral involvement was a common significant factor in any, hemorrhagic, and ischemic strokes. Hypertension was a risk factor for ischemic strokes during follow-up. EDAS is an effective procedure in a Chinese cohort of patients with MMD. EDAS resulted in satisfactory long-term improvement of clinical states and prevention of recurrent strokes.

Neuropsychological impacts of indirect revascularization for pediatric moyamoya disease.

Moyamoya disease (MMD) commonly leads to neurocognitive impairment. This study was carried out to show that temporal encephaloduroarteriosynangiosis (EDAS) has a positive neuropsychological impact on pediatric MMD patients. Fifty-five participants diagnosed with MMD from 2008 to 2014 were included in this retrospective study. The mean age at the preoperative evaluation was 9.5years and the mean age at postoperative evaluation was 10.4. The average interval of initial and follow-up test was 10months. K-WISC-III, Rey-Kim memory test, Children's Color Trails test (CCTT), Wisconsin Card Sorting Test (WCST), and Advanced Test of Attention (ATA) were used to evaluate patient's neurocognitive profile. In this study, preoperative and postoperative neuropsychological fields were compared. Prior operation, pediatric MMD patients showed 54.2% deficit of inattention but only around 2.5% deficit in verbal memory recall function. There was a significant increase of performance IQ and PO score component of PIQ improved almost 10 scores after surgery. For memorial function, there was an improvement of approximately 10 scores in MQ after the surgery. This study also showed parietal activation following surgical treatment which enhanced the ability to interpret visual materials, to register and to retrieve visual information. Interestingly, despite the parietal cover surgery, there was a significant improvement of performance on WCST and CCTT measuring the prefrontal executive function. Concerning failure to maintain set, no significant postoperative improvements were made. However, simple and selective visual attention on ATA was significantly improved postoperatively. The results from neuropsychological field comparison testifies the effectiveness of temporal EDAS in pediatric MMD patients. The surgery not only enhances the blood flow in operative regions, but it also improves the broad cerebral function including frontoparietal domains. Such alteration leads to overall advancement in cognitive function which are impaired due to MMD.

Acceleration of blood flow as an indicator of improved hemodynamics after indirect bypass surgery in Moyamoya disease

Objective: The ultrasonography findings in the superficial temporal artery (STA) in Moyamoya disease patients treated with indirect bypass remain unclear. We evaluated the time-related changes in ultrasonography findings of the STA main trunk and branches in patients with Moyamoya disease who underwent encephalo-duro-arterio-synangiosis (EDAS). Patients and methodsPatients (n=21, 30 sides) with Moyamoya disease who underwent EDAS at Fukuoka University Hospital were prospectively registered between 2008 and 2015. EDAS using the frontal and parietal branches of the STA was adopted in an indirect bypass procedure. Mean velocity (MV) and resistance index (RI) were used as ultrasonography markers, and their changes over time in the STA main trunk and branches were assessed. ResultsThere was a significant increase in MV in both the STA main trunk (p=0.001) and branches (frontal: p=0.005, parietal: p=0.003) at 3 months after EDAS, whereas there was a decrease in RI at 14days after EDAS (main trunk: p <0.001, frontal: p <0.001, parietal: p=0.014). In subgroup analysis of patients divided by EDAS outcome, compared with before EDAS, there were significant differences at 3 months after EDAS in MV (responders: main trunk: p=0.002, frontal: p=0.001, parietal: p=0.001; non-responders: main trunk: p=0.093, frontal: p=0.24, parietal: p=0.96) and RI (responders: main trunk: p<0.001, frontal: p<0.001, parietal: p=0.006; non-responders: main trunk: p=0.17, frontal: p=0.12, parietal: p=0.17). ConclusionsMeasurement of MV may be useful for predicting outcome at 3 months after EDAS.

Encephaloduroarteriosynangiosis (EDAS) in young patients with cerebrovascular complications of sickle cell disease: Single-institution experience

ABSTRACTMoyamoya syndrome occurs in sickle cell disease (SCD) as a secondary complication of large-artery stenosis. Moyamoya increases the risk of stroke, but its optimal management in SCD is not established. Encephaloduroarteriosynangiosis (EDAS) is a neurosurgical revascularization procedure for moyamoya whose use has been reported in SCD patients. We report the outcomes of 11 patients with SCD systematically evaluated for EDAS by a multidisciplinary team and compare the rate of stroke in patients who received EDAS to those who did not. Moyamoya syndrome was diagnosed by flow abnormalities on magnetic resonance angiography at median age of 8.2 years. Four patients deferred surgery. Seven patients underwent EDAS at median age of 19 years. There were no intraoperative complications, perioperative strokes, or deaths. Transient postoperative complications occurred in six cases (86%). On follow-up, three patients (43%) had no evidence of flow in their EDAS grafts, and one later developed a hemorrhagic stroke. Five EDAS patients (71%) had radiographically stable vasculopathy. Compared to the four patients who deferred surgery, the incidence of stroke in EDAS group was no different. The optimal use of EDAS in patients with SCD-associated moyamoya syndrome requires further investigation by a prospective, controlled clinical trial.

Clinical features and surgical treatment of hemorrhagic type moyamoya disease

Objective To investigate the clinical characteristics of hemorrhagic type moyamoya disease and its outcomes after revascularization. Methods The data of 46 patients with hemorrhagic moyamoya disease, including clinical features and surgical outcomes, were retrospectively reviewed. Among them, 42 cases were treated at Beijing Tiantan Hospital from August 2007 to November 2011. The other 4 cases were managed at the People's Liberation Army (PLA) 174 Hospital from August 2011 to June 2014. In this series of 46 patients, the operation of revascularization was performed in 50 hemispheres. Among them, direct superficial temporal artery to middle cerebral artery (STA-MCA)bypass surgery was conducted in 28 hemispheres, the encephalo-duro-arterio-synangiosis (EDAS) was performed in 10 hemispheres, and 12 hemispheres underwent a combination of STA-MCA bypass surgery and EDAS. Results The mean follow-up period was 52.5±6.5 months with a range of 18 ~ 87 months. Among the 19 cases with preoperative neurological deficiency, the symptoms were improved in 11cases, remained unchanged in 6 cases and became worse in 2 cases due to rebleeding. Among the preoperatively asymptomatic 27 cases, good outcomes were observed in 24 cases and rebleeding occurred in the non-surgical hemispheres of the remaining 3 cases. Follow-up CT Perfusion (CTP) and/or SPECT were performed in 25 cases and demonstrated significant improvement of cerebral blood perfusion in 20 cases and no remarkable change in 5 cases. Follow-up (at least 3 months post operation) DSA in the 15 patients who underwent STA-MCA bypass showed complete patency of the anastomosis and diminishing of the moyamoya vessels. In addition, 2 concurrent microaneurysms was found to have disappeared after the direct bypass surgery. Rebleeding developed in 2 (4%) hemispheres (post EDAS) in the surgical group and 3 (7%) hemispheres in the nonsurgical group. There was no statistical difference in the rate of rebleeding rate between the 2 groups(P>0.05). Conclusion The surgery of revascularization could improve the symptoms and cerebral perfusion for the patients with hemorrhagic moyamoya disease. Key words: Moyamoya disease; Hemorrhage; Cerebral revascularization; Treatment outcome

Characteristics of infarction after encephaloduroarteriosynangiosis in young patients with moyamoya disease.

OBJECTIVE Young patients with moyamoya disease can exhibit infarction after revascularization surgery. This analysis of the characteristics of infarction after encephaloduroarteriosynangiosis (EDAS) in young patients with moyamoya disease was undertaken in an effort to elucidate the infarction mechanism. METHODS The authors retrospectively collected clinical information and reviewed pre- and postoperative MRI studies from cases involving patients younger than 18 years who underwent EDAS for the treatment of moyamoya disease between January 2012 and February 2015. Infarction patterns were categorized into watershed, territorial, or mixed pattern. The Wilcoxon rank sum test, chi-square test, and Fisher exact test were used to compare the clinical and imaging variables between patient groups. The characteristics of patients with and without postoperative infarction were compared using univariate and multivariate analysis. The cumulative proportion of patients without postoperative infarction according to operation stage was calculated using the Kaplan-Meier method and the resulting curves were compared using the log-rank test. RESULTS In 100 patients, 171 EDAS procedures had been performed. There were 38 cases of preoperative infarction in 35 patients and 20 cases of postoperative infarction in 13 patients. Territorial infarction was more frequent in the postoperative infarction group than in the preoperative infarction group (55.0% vs 37.8%, p = 0.037). Infarction was more common on the bilateral or contralateral side of the operation after first-stage EDAS (9 [75.0%] of 12 infarctions) than in the second-stage operation (2 [25.0%] of 8 infarctions), but the difference was not statistically significant (p = 0.068). The frequency of postoperative infarction was not significantly different depending on the stage of the operation (p = 0.694). CONCLUSIONS An acute infarction pattern after EDAS was more frequently territorial, suggesting an underlying occlusive mechanism. Operation stage did not affect the rate of postoperative infarction occurrence.

Ultrasonographic Changes after Indirect Revascularization Surgery in Pediatric Patients with Moyamoya Disease

The marked cerebral hypoperfusion of moyamoya disease (MMD) can be treated with encephaloduroarteriosynangiosis (EDAS), an indirect revascularization surgery. Collateral establishment after the surgery is a gradual process; thus, easy access to serial assessment is of great importance. We prospectively recruited 15 pediatric moyamoya patients who underwent EDAS surgeries on a total of 19 hemispheres. Ultrasonography of extracranial and intracranial arteries was performed pre-operatively and post-operatively at 1, 3 and 6 mo. Among the extracranial arteries, the superficial temporal artery had the most pronounced increase in flow velocity and decrease in flow resistance from 1 mo post-surgery (p < 0.01). Among the large intracranial arteries, a significant increase in peak systolic velocity was observed in the anterior cerebral artery from 3 mo post-surgery (p < 0.05). These findings indicate significant hemodynamic changes on ultrasonography in pediatric moyamoya patients after indirect revascularization surgery.

Intracranial Aneurysms Associated with Moyamoya Disease in Children: Clinical Features and Long-Term Surgical Outcome

Moyamoya disease (MMD) in children was rarely associated with intracranial aneurysms. The purpose of this study was to report the clinical characteristics and long-term surgical outcomes of pediatric intracranial aneurysms accompanied with MMD. Between October 2002 and October 2013, our department treated 9 pediatric MMD patients (aged ≤17 years) with intracranial aneurysms. Clinical and angiographic features, treatment selection, as well as follow-up information were obtained and analyzed. The efficacy of vascularization and the changes of intracranial aneurysms were evaluated with digital subtraction angiography (DSA). We also collected 7 previously published reports to analyze the characteristics of this rare condition. In our series of 9 patients, 7 were male. The mean age was 11 ± 3.4 years (range 5-16). Seven patients presented with intracranial hemorrhage as the initial manifestation, while 2 patients suffered transient ischemic attacks. The most common aneurysm location was the posterior choroidal artery (4, 44.4%). One anterior choroidal artery aneurysm was completely embolized with Onyx (ev3, Irvine, California, USA). One posterior choroidal artery aneurysm failed due to inaccessibility to the parent artery. Bilateral encephalo-duro-arterio-synangiosis (EDAS) surgery was performed for all the children. During the follow-up period of 6.4 ± 2.2 years (range 3-11), spontaneous occlusion of aneurysm was observed in 4 children, including 1 child with middle cerebral artery aneurysm, 1 with lenticulostriate artery aneurysm, and 2 with posterior choroidal artery aneurysm. Good or fair vascularization was observed in all the 9 children with DSA follow-up. No patients suffered intracranial hemorrhage during the follow-up period. The long-term survey showed EDAS surgery could effectively increase the cerebral blood flow and maintain good outcomes in children, which may further result in the disappearance of the intracranial aneurysms and decrease the incidence of recurrent hemorrhage.

Indirect Revascularization for Non–Moyamoya Disease Anterior Circulation Arterial Steno-occlusion: Clinical Features, Surgical Treatment, and Medium-Term Outcomes in Adults

Symptomatic anterior arterial steno-occlusion is often associated with neurofunctional deficits or a high risk of recurrent stroke or both. Although both medical and endovascular treatments are useful and suitable, few studies have investigated the continued use of indirect encephaloduroarteriosynangiosis (EDAS) bypass in patients with non-moyamoya disease ischemia. We retrospectively investigated clinical features, surgical treatments, and medium-term outcomes of indirect revascularization for patients with non-moyamoya disease anterior circulation arterial steno-occlusion in China. EDAS without burr holes was performed in 51 adult patients with cerebral ischemic events and diagnosed nonmoyamoya anterior circulation arterial steno-occlusion. Preoperative, postoperative, and follow-up neurologic status was evaluated using the National Institutes of Health Stroke Scale; changes on angiography and perfusion-weighted magnetic resonance imaging were evaluated. Unilateral EDAS was performed in 48 patients, and bilateral EDAS was performed in 3 patients. Four patients experienced complications before hospital discharge; only 23 patients underwent follow-up angiograms. Of the 51 patients, 44 (86.3%) exhibited improved muscle strength; 21 of 23 patients (91.3%) with follow-up angiography data exhibited evidence of new visible branches from the superficial temporal artery or middle meningeal artery or both. Preoperative and postoperative perfusion-weighted magnetic resonance imaging was performed for 5 patients. Despite clinical improvement in all patients, only 2 exhibited hemodynamic improvement. Indirect revascularization may be safe and effective for improving blood flow to the ischemic region following nonmoyamoya anterior circulation arterial steno-occlusion, especially in patients with residual postinfarction neurologic deficits. Our study demonstrates that improvements in ischemic symptoms after EDAS correspond to neovascularization from the superficial temporal artery or middle meningeal artery in ischemic brain areas.

Abstract WP138: Effects of Intensive Medical Management (IMM) and Encephaloduroarteriosynangiosis (EDAS) On VEGFA165a/b Ratios in Patients With Intracranial Atherosclerosis (ICASi

Objective: VEGFA isoforms 165a and 165b are pro and antiangiogenic, respectively. We aimed to evaluate the effects of IMM and EDAS in the VEGFA165a/b ratio in patients with ICAS. Methods: This is a prospective observational study of VEGFA165a and b in patients with stenosis greater than 70% due to ICAS. All patients received IMM. Patients with persistent symptoms underwent EDAS while maintaining IMM. Serum samples were collected at baseline, 1 week, 1, 3, and 6 months. VEGFA isoforms were quantified using multiplex sandwich ELISA. All samples were run in duplicate and accepted as valid if the intersample variability was less than 20%. A mixed model was built for the outcome variable VEGFA165a/b ratio using the predictor variables timepoint, treatment, and the interaction of time and treatment. The restricted maximum likelihood method was used to fit the model with random effects to account for the repeated measurements and intersubject variability. Results: A total of 72 patients were enrolled, of which 58 had IMM alone and 14 had EDAS. Mean age was 61.8 ± 12.3, 53% were females. The regression model demonstrated that there were no significant differences in the VEGFA165a/b ratio at baseline and 1 month after enrollment. Significant differences in VEGFA165a/b ratio were found at one week with higher levels in the surgical group (EDAS: 0.46 ± 0.22, IMM: 0.24 ± 0.07, p=0.03) and at 3 and 6 months with higher levels in the IMM group (3m: EDAS: 0.29 ± 0.14, IMM: 0.45 ± 0.20, p=0.03, 6m: EDAS:0.19 ± 0.11, IMM 0.37 ± 0.19 p=0.01). Conclusion: While the surgical event may well explain the early elevation of the VEGFA165a/b ratio one week after surgery, the elevation of a proangiogenic profile by the 3rd and 6th month in the IMM group is relevant. None of the patients in the IMM or EDAS groups had strokes at the last 6 months follow-up, and the peak (early for EDAS and at 3 and 6 months for IMM) of the VEGFA165a/b ratio may indicate a protective effect, averting stroke.

Abstract 32: Radiographic and Clinical Outcomes Demonstrate Long-term Efficacy of Indirect Revascularization 20 Years After Surgery for Pediatric Moyamoya

Introduction: Pediatric moyamoya patients have little long-term data to inform them about what to expect after revascularization beyond a 5-year window. Here we present a series of pediatric patients treated with indirect revascularization with long-term clinical and radiographic follow-up. Hypothesis: We assessed the hypothesis that indirect revascularization, such as pial synangiosis, provides durable clinical and radiographic protection from stroke in pediatric moyamoya patients. Methods: Retrospective case series. Records of all children with moyamoya surgically revascularized by the senior author prior to 1996 (20 years ago) were analyzed. Results: 37 patients (27F/12M) were identified, all diagnosed under age 22 years. Most common presentations included ischemic symptoms and 30 patients (81%) had a radiographic stroke prior to surgery. Bilateral disease existed in 36 patients; 1 unilateral. Average age at surgery was 8 years (range=1-22 yr.). Surgery consisted of 25 EDAS (encephalo-duro-arterio-synangiosis) and 48 pial synangiosis. Average follow-up=16 years (range=5.5-31.8 years). Only one stroke occurred during this period (2.7% of patients). Two deaths occurred, 1 from a malignant meningioma at age 27 and the other from aneurysmal hemorrhage after intracranial radiation for tumor at age 40. In all other patients, mRS scores were stable or improved at most recent follow-up. Descriptive data less amenable to analysis but subjectively helpful to patients includes information on patient life experiences. A total of 91% completed high school, 90% are employed, 56% completed college and 3 patients have graduate degrees. Four of the female patients had successful vaginal child births. Conclusions: Revascularization confers durable protection from stroke for pediatric patients on long-term follow up. These data suggest that pediatric patients do very well after treatment and support the use of interventions such as pial synangiosis.

Encephaloduroarteriosynangiosis for adult intracranial arterial steno-occlusive disease: long-term single-center experience with 107 operations.

Encephaloduroarteriosynangiosis (EDAS) is a form of revascularization that has shown promising early results in the treatment of adult patients with moyamoya disease (MMD) and more recently in patients with intracranial atherosclerotic steno-occlusive disease (ICASD). Herein the authors present the long-term results of a single-center experience with EDAS for adult MMD and ICASD. Patients with ischemic symptoms despite intensive medical therapy were considered for EDAS. All patients undergoing EDAS were included. Clinical data, including recurrence of transient ischemic attack (TIA) and/or stroke, functional status, and death, were collected from a retrospective data set and a prospective cohort. Perren revascularization and American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology (ASITN/SIR) collateral grades were recorded from angiograms. A total of 107 EDAS procedures were performed in 82 adults (36 with ICASD and 46 with MMD). During a median follow-up of 22 months, 2 (2.4%) patients had strokes; both patients were in the ICASD group. TIA-free survival and stroke-free survival analyses were performed using the product limit estimator (Kaplan-Meier) method. The probability of stroke-free survival at 2 years in the ICASD group was 94.3% (95% CI 80%-98.6%). No patient in the MMD group suffered a stroke. The probability of TIA-free survival at 2 years was 89.4% (95% CI 74.7%-96%) in ICASD and 99.7% (95% CI 87.5%-99.9%) in MMD. There were no hemorrhages or stroke-related deaths. Angiograms in 85.7% of ICASD and 92% of MMD patients demonstrated Perren Grade 3 and improvement in ASITN/SIR grade in all cases. EDAS is well tolerated in adults with MMD and ICASD and improves collateral circulation to territories at risk. The rates of stroke after EDAS are lower than those reported with other treatments, including intensive medical therapy in patients with ICASD.

Encephaloduroarteriosynangiosis and encephalomyoarteriosynangiosis for treatment of moyamoya syndrome in pediatric patients with sickle cell disease.

OBJECT Pediatric patients with sickle cell disease (SCD) and moyamoya syndrome (MMS) are at significant risk for cerebrovascular accidents despite chronic transfusion therapy. Encephaloduroarteriosynangiosis (EDAS) and encephalomyoarteriosynangiosis (EMAS) are additional therapeutic options for these patients. To date, the incidence of complications after and efficacy of EDAS and EMAS in stroke prevention in this population have been described in several institutional case series reports, but no randomized prospective trials have been reported. METHODS The authors retrospectively reviewed the cases of all pediatric patients at the University of Alabama at Birmingham with a history of homozygous hemoglobin S (HbS) and sickle cell/β-thalassemia (SB0 thalassemia) and on chronic transfusion therapy, including 14 patients with MMS who underwent EDAS or EMAS. RESULTS Sixty-two patients with SCD and on chronic transfusion therapy were identified. After exclusion of patients on chronic transfusion therapy for indications other than stroke prevention, 48 patients (77.4%) remained. Of those patients, 14 (29.1%) underwent EDAS or EMAS. Nine (18.8%) and 25 (52.1%) patients were on chronic transfusion therapy for primary or secondary stroke prevention, respectively, but did not undergo EDAS or EMAS. The 14 patients with SCD and radiological evidence of MMS and on chronic transfusion therapy for primary or secondary stroke prevention underwent 21 EDAS or EMAS procedures for progressive vascular disease (92.9% of patients), stroke (71.4%), and/or seizure (7.1%). The mean (± SD) time from initiation of chronic transfusion therapy to EDAS or EMAS was 76.8 ± 58.8 months. Complications included 1 perioperative stroke, 1 symptomatic subdural hygroma, 1 postoperative seizure, and 1 case of intraoperative cerebral edema that required subsequent cranioplasty. Before EDAS or EMAS, the stroke rate was calculated to be 1 stroke per 7.8 patient-years. One additional stroke occurred during the follow-up period (mean follow-up time 33.7 ± 19.6 months), resulting in a post-EDAS/EMAS stroke rate of 1 stroke per 39.3 patient-years, a 5-fold reduction compared with that in the pre-EDAS/EMAS period. The patients' mean pre-EDAS/EMAS HbS level of 29.5% ± 6.4% was comparable to the mean post-EDAS/EMAS HbS level of 25.5% ± 6.1% (p = 0.104). CONCLUSIONS The results of this retrospective case series in a large cohort of pediatric patients with SCD and MMS suggest that EDAS/EMAS provides a stroke-prevention benefit with an acceptably low morbidity rate. Given the combined experience with EDAS and EMAS for this indication at this and other institutions, a prospective clinical trial to assess their efficacy compared with that of chronic transfusion therapy alone is warranted.

Differential clinical outcomes following encephaloduroarteriosynangiosis in pediatric moyamoya disease presenting with epilepsy or ischemia.

The purpose of this study was to compare clinical outcomes and surgical results after encephaloduroarteriosynangiosis (EDAS) in pediatric patients with Moyamoya disease that manifested as either ischemia or epileptic seizures. We treated 23 children who underwent EDAS; we divided the patients into either ischemic or epileptic groups according to the individuals' clinical presentation. Group Ia included those who mainly presented with cerebral ischemia in the form of preoperative transient ischemic attacks (TIA), while Group Ib presented with ischemia in the form of irreversible neurologic deficits or proven cerebral infarcts. Group II included those who presented with epileptic seizures rather than cerebral ischemia. We compared the clinical outcomes and surgical results following EDAS in the three groups. We grouped the patients into three groups according to their main preoperative clinical symptoms (Group Ia n = 10, Group Ib n = 6, and Group II n = 7). Group II, the epileptic manifestation group, tended to show more favorable clinical outcomes compared to the ischemic manifestation group, especially the severe ischemic group. However, there were no significant differences in postoperative neuroimaging and hemodynamic assessments between the groups. EDAS is a safe and effective surgical technique that prevents epileptic seizures and shows more favorable clinical outcomes when used in patients with Moyamoya disease presenting with epileptic seizures compared to cerebral ischemia.

The Importance of Encephalo-Myo-Synangiosis in Surgical Revascularization Strategies for Moyamoya Disease in Children and Adults

The optimal surgical procedure (direct, indirect, or combined anastomosis) for management of moyamoya disease is still debated. We evaluated the outcome of our broad area revascularization protocol, the Tokyo Daigaku (The University of Tokyo) (TODAI) protocol, analyzing the relative importance of direct, indirect, and combination revascularization strategies to identify the optimal surgical protocol. The TODAI protocol was used to treat 65 patients with moyamoya disease (91 hemispheres, including 48 in 29 childhood cases collected during 1996-2012). The TODAI protocol combined direct superficial temporal artery (STA)-middle cerebral artery (MCA) anastomosis with indirect revascularization using encephalo-myo-synangiosis (EMS) forpatients ≥10 years old or indirect revascularization using encephalo-duro-arterio-synangiosis (EDAS) with EMS for patients ≤9 years old. Clinical outcome was evaluated retrospectively. Digital subtraction angiography was performed for postoperative evaluation of revascularization in 47 patients (62 hemispheres; 27 adults and 35 children). Based on the relative contribution of additional flow from each revascularization path, 4 revascularization patterns were established. The mean follow-up period was 90 months in children and 72 months in adults. Perioperative complications were seen in 4 of 48 operations in children and 1 of 43 operations in adults. Except for 1 child with recurrent transient ischemic attacks and 1 adult with intracerebral hemorrhage, the patients showed excellent clinical outcomes. Postoperative digital subtraction angiography evaluation showed that in STA-MCA anastomosis+ EMS cases (34 hemispheres; 25 adults and 9 children), STA-MCA anastomosis provided greater revascularization than EMS (STA-MCA anastomosis > EMS) in 7 hemispheres, the opposite was true (STA-MCA anastomosis < EMS) in 14 hemispheres, an equivalent contribution to revascularization (STA-MCA anastomosis ≈ EMS) was present in 12 hemispheres, and no functioning anastomosis was present in 1 hemisphere. In cases of EDAS+ EMS (28 hemispheres; 2 adults and 26 children), all hemispheres showed revascularization: EDAS was dominant to EMS (EDAS > EMS) in 1 hemisphere, the opposite (EMS > EDAS) was true in 14 hemispheres, and EDAS was equivalent to EMS (EDAS ≈ EMS) in 13 hemispheres. EMS plus direct or indirect anastomosis is an effective surgical procedure in adults and children. The TODAI protocol provided efficient revascularization and yielded excellent results in preventing strokes in patients with moyamoya disease with very few complications. EMS had a main role in revascularization in each of the combined techniques.