Longitudinal angiographic characterization of the efficacy of combined cerebral revascularization using encephalodurosynangiosis in patients with Moyamoya Disease

Longitudinal angiographic characterization of the efficacy of combined cerebral revascularization using encephalodurosynangiosis in patients with Moyamoya Disease | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Longitudinal angiographic characterization of the efficacy of combined cerebral revascularization using encephalodurosynangiosis in patients with Moyamoya Disease Kristin Lucia, Güliz Acker, Friedrich Mrosk, Defne Beyaztas, Peter Vajkoczy This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-1720929/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 7 You are reading this latest preprint version Abstract Background: Moyamoya Vasculopathy (MMV) can be treated using direct, indirect, or combined revascularization procedures. We perform combined revascularization using the STA-MCA bypass and minimally invasive encephalodurosynangiosis (EDS). Due to lack of systematic analyses to date it remains unclear whether and to which extent this limited EDS serves as a growth source for extracerebral blood vessels into the brain. The objective of the current study is to characterize the extent of angiographic filling of EDS and STA-MCA bypass development over time and to determine possible predictors of EDS development in adult MMV patients. Methods: Single-center retrospective analysis of 81 MMV patients (139 hemispheres) treated with a minimally invasive EDS and STA-MCA bypass. Angiographic images, clinical/operative data were reviewed and scored. Uni-/ and multivariate COX-regression analyses identified preoperative predictors of good EDS vascularization. Results: At 3-6 months after surgery EDS showed moderate and high angiographic filling in 40% and 5% of hemispheres, respectively. After 12 months moderate and high filling was in 57% and 4% of hemispheres, respectively. STA-MCA bypass filling was moderate in 47% and high in 7% of hemispheres at 3-6 months and 45% moderate and 9% high after 12 months. High STA-MCA bypass filling on angiography was a negative predictor of EDS development. Conclusions: Minimally invasive EDS is a simple technique and serves as a source of vessel growth into the brain. EDS development lags behind that of STA-MCA bypass and can be recommended as an additive revascularization source when combined with a direct bypass. Moyamoya Encephalodurosynangiosis Bypass Angiogenesis Angiography Figures Figure 1 Figure 2 Figure 3 1. Introduction Moyamoya Vasculopathy (MMV) is a rare stenoocclusive cerebrovascular disease affecting the basal cerebral arteries which leads to the formation of fragile net-like vessels [ 1 ]. As such, patients with MMV can present with intracranial hemorrhage from abnormal vessels as well as ischemic events [ 2 , 3 ]. Surgical revascularization aiming at restoring perfusion and preventing future hemorrhage and ischemia is widely accepted as the primary treatment for MMV [ 4 – 6 ]. Revascularization can be achieved by both direct (anastomosis performed between branches of the internal and external carotid arteries) and indirect techniques which rely on neoangeogenesis between the cortical surface and a pedicled graft [ 7 ] Common indirect revascularization techniques involve the dura mater (encephalodurosynangiosis, EDS), the temporalis muscle (encephalomyosynangiosis, EMS) or further variants thereof such as encephalao-duro-arterio-synangiosis (EDAS) and encephalo-duro-arterio-myo-synangiosis (EDAMS) [ 8 ]. Studies examining the efficacy of combined revascularization procedures have provided evidence of improved angiographic revascularization when EMS [ 9 ], EDAMS [ 10 ] and EDAS [ 11 , 12 ] are used in combination with STA-MCA direct bypass. Radiological studies have also shown increased cortical perfusion in patients treated with indirect revascularization techniques such as EDAS [ 13 ]. To date, the use of EDS as a further indirect revascularization technique in combination with STA-MCA direct bypass has not been angiographically characterized as to whether or not vessel growth occurs, possibly due to the simplicity of the technique as well as the small surface contact between dura and brain surface. In our institution, EDS is performed via a mini-craniotomy which is significantly less invasive than other indirect techniques requiring greater exposure. We therefore aimed to characterize the angiographic bypass development of both minimally invasive indirect EDS and direct STA-MCA bypass over time as well as possible predictors of EDS development. 2. Methods 2.1 Study Design We retrospectively identified all Moyamoya patients who were treated using a minimally invasive EDS as an indirect bypass strategy combined with an STA-MCA direct bypass on at least one hemisphere in our department between January 2007 and December 2019. All patients with unilateral moyamoya and moyamoya syndrome using the ICD code 167.5 (moyamoya) were included. Moyamoya disease (MMD), moyamoya syndrome and unilateral MMV were defined based on the guidelines established by the Research Committee for Moyamoya Disease and patients with possible associated diseases were classified as moyamoya syndrome [ 14 ]. Variables Electronic medical records were used to gather data on patient demographics, time of surgery, follow-up time, angiographic follow-up, history of complications and MRI and hemodynamic diagnostics (obtained either by xenon-computerized tomography or acetazolamide-stimulated single-photon emission computed tomography). Severity of the MMV was classified using the Suzuki and Berlin Gradings [ 1 , 9 ]Preoperative CVRC was included in the calculation of the Berlin Grading. The qualitative assessment of the CVRC was performed as described before [ 15 ]. Briefly, CVRC was assessed qualitatively by visual interpretation with a standardized side-by-side display of anatomically normalized resting and acetazolamide images together with the rCVRC map. Impaired cerebrovascular reserve capacity (CVRC) was defined as a missing signal increase after acetazolamide stimulation. If stimulation with acetazolamide leaded to an increase of the signal, CVRC was considered sustained. Angiographic Evaluation Qualitative angiographic analysis of direct bypass development was performed as previously described by Czabanka et al [ 9 ] with the exception that we implemented a three-grade classification instead of four in which the Czabanka grades 1 and 2 were combined to better allow for uniform comparison of diverse angiographic image sets. Accordingly, angiographic filling of STA-MCA bypasses were classified either as “poor” (no filling of the MCA territory), “moderate” (antegrade filing of one or two MCA branches) or “high” (complete filling of the MCA territory) [ 9 ]. Angiographic filling of EDS was classified in adaptation to previously described methods either as “poor” (no filling), moderate (opacification of cortical vessels) or “high” (any filling of the MCA territory)[ 12 ]. ( Fig. 1 ). In our department, the EDS was performed without changing the exposure strategy for direct revascularization perfomed via a mini-craniotomy of 3 centimeters in diameter [ 16 ]. At the end of the direct revascularization procedure, the dural flap was inverted and pushed beneath the bone ( Fig. 2 ). 2.2 Statistical analysis Quantitative values are presented as median values with range. Univariate Cox regression analysis was performed among all cases of surgically treated MMV using “high” of bypass filling (“poor”, “moderate”, and “high”) as dependent variables. Multivariate analysis was performed on those variables which reached a p-value of 24 months following initial revascularization. P-values of less than 0.05 were considered statistically significant. All analyses were performed in SPSS (version 24; IBM Corp.). 3 Results 3.1 Patient characteristics We analyzed a total of 139 surgically treated hemispheres in 81 MMV patients. All patients were operated in a single institution between 2007 and 2019 by the senior author. Of these patients, 65 (80%) had Moyamoya Disease (MMD), 4 (5%) had unilateral MMD (uMMD) and 12 (15%) had Moyamoya syndrome. The median age at first surgical intervention was 44 years old (range: 6-65 years old and 4 (5%) patients were under 18 years of age. Regarding gender distribution, 58 (72%) of patients were female and 28% were male. The majority of our cohort was of Caucasian background (92%), 6% were of Asian and 2% were of Middle Eastern descent ( Table 1). Table 1: Patient demographics and disease characteristics. Age is reported as median and range. All other parameters as absolute number of patients or hemispheres with percent of total in parentheses. Parameter N (%) Age 44 (6-65) Gender Male 23 (28%) Female 58 (72%) Diagnosis MMD 65 (80%) MMS 12 (15%) uMMD 4 (5%) Onset Ischemic 72 (89%) Hemorrhagic 9 (11%) Suzuki Grade 1 14 (10%) 2 50 (36%) 3 49 (35%) 4 12 (9%) 5 12 (9%) 6 2 (1%) Berlin Grade 1 35 (25%) 2 83 (60%) 3 21 (15%) Follow Up Total 1.6 years (2.5 months-6.7 years) Complications Wound Healing disorder 1 New Ischemia 1 The majority of our cohort (89%) presented with ischemic events leading to diagnosis of MMV with only 9 patients (11%) suffering from hemorrhagic lesions. Berlin grading of all hemispheres revealed 35 (25%) grade 1, 83 (60%) grade 2, 21 (15%) grade 3. Suzuki classification showed 14 stage 1 (10%), 50 stage 2 (36%), 49 stage 3 (35%), 12 stage 4 (9%), 12 stage 5 (9%), 2 stage 6 (1%) hemispheres. 3.2 Angiographic evaluation The median follow-up period for all patients was 1.6 years (range 2.5 months – 6.7 years). For the timepoints 3-6 months postoperative data was available from all 139 hemispheres, at 6-12 months from 78 hemispheres (56%), at 12-24 months for 42 hemispheres (30%) and timepoints beyond 24 months from 14 hemispheres (10%). EDS and STA-MCA bypass filling At 3-6 months following combined revascularization rates of poor bypass filling were seen more frequently (55%) in EDS than STA-MCA (47%). Accordingly, higher rates of moderate bypass filling were 46% of STA-MCA compared to 40% in EDS. The rate of high bypass filling was similar between EDS (5%) and STA-MCA (7%) at this early time point ( Figure 3). At 6-12 months following combined revascularization poor bypass filling rates were stable compared to the first six months following surgery with 47% of STA-MCA and 39% of EDS hemispheres. The rate of moderate bypass filling increased among EDS to 57% (from 40%) of hemispheres with the rate in STA-MCA bypass remaining similar to the earlier time point at 45% (versus 46% at 0-6 months). The rates of high bypass filling rose slightly in STA-MCA from 7% to 9% of hemispheres at this time point while EDS remained similar at 4% (versus 5% at 3-6 months) ( Figure 3). At 12-24 months following combined revascularization poor filling rates remained stable compared to the earlier timepoints among STA-MCA (49%) with EDS at 39% of hemispheres. At this point, an increase in the rate of high bypass filling could be seen in 14% of STA-MCA and EDS cases. Moderate bypass filling remained similar in both groups at 51% (STA-MCA) and 47% (EDS) of hemispheres. ( Figure 3). At time points longer than 24 months following combined revascularization, the rates of poor and moderate bypass filling remained stable for STA-MCA (poor: 42%, moderate: 49% of hemispheres) with lower rates of high bypass filling compared to earlier timepoints of 12-24 months (9% versus 14%). EDS showed a further increase in high bypass filling to 23% from 14% of hemispheres at 12-24 months. months. Accordingly, rates of poor bypass filling decreased by 6% and moderate filling by 3% ( Figure 3). Comparing STA-MCA function over all time points showed that 3% of bypasses showed a regression of function with 52% remaining stable and 45% showing an increase of angiographic illing. In contrast, a higher proportion of EDS showed a regression of bypass filling over time (18%) with 34% remaining stable and 48% improving over time. Bypass occlusion and postoperative complications Four patients (4.9%) experienced a postoperative complication following revascularization surgery. Of these, two were wound healing disorders and two were ischemic events related to surgery. The majority of patients undergoing bypass surgery had no bypass occlusion over the period of observation (90,1%). Four patients in our cohort experienced STA-MCA bypass occlusion of one hemisphere within 1 year of surgery, two cases of bypass occlusion occurred 3.5 years following surgery and two patients experienced bypass occlusion at 5.5 and 6.1 years. Of these, one case of neurological deterioration (recurrent TIAs) was reported resulting in repeat revascularization surgery using a frontal branch of the STA. This case of bypass occlusion occurred within 6 months following initial surgery and the development of EDS filling was rated as “poor”. In the remaining eight hemispheres which demonstrated asymptomatic STA-MCA occlusion, angiographic filling of EDS was rated “moderate” or “high”. Predictors of EDS development Finally, we examined the relationship between several demographic and angiographic factors and the development of EDS function over time. Using univariate cox regression analysis with good EDS outcome defined as a dependent variable, we found that at all time points only the degree of STA-MCA bypass filling was significantly associated with poor EDS bypass filling (Table 2a-d). Multivariate regression analysis performed on the variables preoperative deficit, history of TIA (3-6 months postoperatively), Berlin Grade, STA-MCA grades, Suzuki stage and age (6-12 months postoperatively) revealed no new significant predictors of EDS development, while STA-MCA bypass filling remained significant (Table 2e). Table 2: Model summary of regression analysis. Model summary of regression analysis on moderators analyzed with “good bypass function” being defined as the dependent variable. P<0.05. Tables 2a-2d show univariate regression analysis models. Table 2e displays results of multivariate regression analysis using variables from the univariate analysis which gave a p-value of 24 months, therefore no results are depicted for these times. STA-MCA bypass development was classified as “poor” (no filling of the MCA territory), “moderate” (antegrade filing of one or two MCA branches) or “high” (complete filling of the MCA territory) {Czabanka, 2011 #9. EDS development was classified as “poor” (no filling), moderate (opacification of cortical vessels) or “high” (filling of the MCA territory) [15]. Good leptomeningeal collateralization was determined based on the presence of anastomoses in the watershed zones of the posterior cerebral artery to the anterior and/or to the middle cerebreal artery and poor collateralization was determined in absence of the above anastomoses [16]. Intra-extracranial collateralization was examined based on the presence and degree (none, moderate, extensive) of transdural collaterals arising from the middle meningeal artery [17, 18]. Development of MMV was classified as either absent, faint and localized or abundant [15] as either absent, faint and localized or abundant. a) 3-6 Months Hazard Ratio P CI Berlin Grade -0.165 0.471 -0.222 - 0.104 Suzuki Stage 0.262 0.266 -0.068 - 0.241 Age 0.037 0.787 -0.010 - 0.013 Preoperative Deficit 0.239 0.115 -0.067 - 0.602 History of Stroke -0.031 0.822 -0.331 - 0.264 History of TIA 0.225 0.143 -0.098 - 0.660 History of Hemorrhage -0.025 0.867 -0.557 - 0.470 Leptomeningeal Collaterals 0.057 0.670 -0.493 - 0.761 Intra-Extracranial Collaterals -0.153 0.222 -0.713 - 0.169 STA Bypass 0.334 0.016 0.062 - 0.566 MMV decreased 0.015 0.91 -0.482 - 0.540 b) 6-12 Months Hazard Ratio P CI Berlin Grade 0.422 0.061 -0.009 - 0.370 Suzuki Stage -0.334 0.143 -0.286 - 0.043 Age -0.245 0.139 -0.027 - 0.004 Preoperative Deficit -0.180 0.253 -0.577 - 0.157 History of Stroke 0.073 0.633 -0.273 - 0.442 History of TIA -0.079 0.634 -0.584 - 0.361 History of Hemorrhage -0.056 0.723 -0.766 - 0.537 Leptomeningeal Collaterals -0.220 0.186 -0.614 - 0.124 Intra-Extracranial Collaterals 0.218 0.169 -0.090 - 0.491 STA Bypass 0.491 0.004 0.150 - 0.726 MMV decreased -0.007 0.964 -0.260 - 0.559 c) 12-24 Months Hazard Ratio P CI Berlin Grade -0.034 0.922 -1.371 - 0.906 Suzuki Stage -0.120 0.743 -1.740 - 2.069 Age -0.051 0.850 -0.077 - 0.079 Preoperative Deficit -0.024 0.904 -1.939 - 1.410 History of Stroke 0.021 0.913 -1.986 - 1.853 History of TIA -0.079 0.768 -3.955 - 4.241 History of Hemorrhage -0.297 0.214 -0.141 - 0.702 Leptomeningeal Collaterals -0.249 0.318 -0.619 - 0.838 Intra-Extracranial Collaterals -0.363 0.159 -0.859 - 0.154 STA Bypass 0.481 0.006 0.214 - 0.969 MMV decreased 0.075 0.753 -2.543 - 3.215 d). >24 Months Hazard Ratio P CI Berlin Grade -0.219 0.455 - 0.367 - 0.172 Suzuki Stage 0.075 0.817 -0.222 - 0.277 Age 0.005 0.981 -0.020 - 0.020 Preoperative Deficit 0.135 0.422 -0.251 - 0.571 History of Stroke 0.074 0.675 -0.359 - 0.540 History of TIA -0.058 0.771 -0.814 - 0.614 History of Hemorrhage -0.063 0.740 -1.079 - 0.782 Leptomeningeal Collaterals -0.155 0.442 -0.843 - 0.386 Intra-Extracranial Collaterals -0.339 0.168 -0.989 - 0.187 STA Bypass 0.636 0.002 0.336 - 1.227 MMV decreased -0.095 0.631 -0.741 - 0.462 e). Hazard Ratio P CI 3-6 Months Preoperative Deficit -0.115 0.477 -0.511 - 0.243 History of TIA 0.119 0.396 -0.204 - 0.510 STA Bypass 0.461 0.003 0.151 - 0.673 6-12 Months Berlin Grade 0.439 0.272 -0.218 - 0.662 Suzuki Stage -0.833 0.201 -0.990 - 0.250 Age -0.193 0.204 -0.023 - 0.005 STA-Bypass 0.469 0.022 0.096 - 1.122 12-24 Months - >24 Months - 4 Discussion Although the use of combined bypass strategies in the treatment of both hemorrhagic and ischemic MMV is supported by studies demonstrating positive angiographic, hemodynamic and clinical results [ 6 , 9 , 18-21 ], the use of EDS as a method of indirect revascularization combined with STA-MCA bypass has remained uncharacterized despite its simplicity and ability to perform in a minimally invasive fashion. Several studies on of EDAS [ 13 , 22 ] and EMS [ 9 , 23 ] alone or in combination with STA-MCA bypass have demonstrated increased vessel growth on angiography. However, specific evaluation of EDS has rarely been performed. One study in hemorrhagic-onset MMV patients has analyzed angiographic outcome in a subset of patients (24 hemispheres) receiving combined revascularization using EDS compared to EDAS (30 hemispheres) [ 24 ]. In this series, angiographic development as measured by the Matsushima revascularization level showed no statistically significant difference between the EDS and EDAS groups. As EDS requires less surgical exposure than the above mentioned techniques, these results suggest that its use may allow for comparable angiographic outcome with less invasiveness. Despite initial evidence that EDS may provide angiographic outcome compared to more invasive techniques, our study is to the best of our knowledge, the first to characterize the outcome of EDS in combination with direct bypass in a large cohort of hemorrhagic and ischemic onset MMV. In particular, we describe the use of a minimally invasive EDS via a small craniotomy approximately 3 centimeters in diameter which even further reduces the invasiveness of the overall procedure . Our cohort consisting of 139 hemispheres with 89% ischemic onset and median age of 44 years was representative in comparison to other Caucasian MMV series [ 3, , 25 ]. Here, we did indeed observe that STA-MCA direct bypass showed better angiographic filling at an earlier timepoint than EDS. STA-MCA function was found to be highest at earlier timepoints following initial revascularization and then stagnates at this level after 12 months following surgery. At time points after 12 months following combined revascularization surgery EDS bypass filling began to improve whereas STA-MCA stagnated. These results differ slightly from previous angiographic analysis of an Asian cohort consisting of 25 hemispheres receiving combined bypass surgery using EDAS alone and follow-up at 6 and 12 months [ 26 ]. In these patients maximal neoangiogenesis from indirect bypass was found already at 6 months. This difference to our results may have several reasons, including the use of indirect bypass alone, smaller sample size and follow-up conducted only up to 12 months following surgery in the Asian cohort. A previous analysis from our institution on EMS bypass development alone and in combination with STA-MCA at 6 and 12 months following revascularization demonstrated similar dynamics of bypass function when compared to our results for EDS [ 9 ]. In particular, EDS and EMS both show an increase in the proportion of high bypass filling at later time periods (12 versus 6 months) whereas STA-MCA bypass function shows good function earlier. These findings support the recommendation of aiming for direct revascularization whenever possible in order to provide immediate support for insufficient reserve capacity [ 7 ]. In our study, Cox-regression analysis showed that the grade of STA-MCA bypass development was significantly associated with EDS bypass development, with better STA-MCA bypass filling predicting poor EDS angiographic filling. Functional adaptation of direct anastomoses is hypothesized to rely mainly on pressure gradients from donor to recipient arteries, whereas development of indirect anastomoses involves several precluding steps of angiogenesis and arteriogenesis [ 23 ]. Accordingly, angiographic evidence of bypass perfusion and development of vascular networks may be expected to arise sooner in direct bypasses than indirect [ 7 ], therefore possibly mitigating the angiogenic signals which would otherwise promote EDS development in compensation for insufficient direct bypass function. This question of predictive factors for bypass neoangiogenesis has been addressed in previous studies which have focused on hemorrhagic onset MMV. First, a multicenteric analysis of 231 hemispheres from patients undergoing various indirect revascularization procedures found that hemorrhagic disease onset positively predicts poor neovascularization and that abundant moyamoya vessels were positively associated with good postoperative neovascularization resulting from indirect bypass [ 12 ]. We observed no statistically significant relationship between angiographic grading Suzuki or Berlin grading and the development of EDS, which is concurrent with a recent report on the development of EDAMS in an Indian population [ 27 ]. Secondly, neoangiogenesis and good bypass function have also been previously described to occur more frequently in pediatric than adult patients [ 28 ]. In contrast to this study, our analysis revealed no statistically significant relationship between age and degree of indirect bypass development which may be due to the fact that our pediatric patients in were teenagers closer to 18 years of age rather than younger children. Children also made up only a very small part of our total collective with 4/81 patients being under the age of 18. A further study on a smaller cohort consisting of 64 operated hemispheres found that only the location of initial hemorrhage in the anterior territory was predictive of good postoperative collateral formation [ 29 ]. The use of different grading systems of postoperative neoangiogenesis between these two analyses may have contributed to their varying conclusions. As our study included only a minority of hemorrhagic onset cases a direct comparison of results is challenging. Although angiographic bypass performance is not a guaranteed indicator of clinical stability good angiographic revascularization from indirect bypass (EDAS) has been shown to positively associate with lower incidence of hemorrhage and improvement of neurological symptoms in patients with hemorrhagic onset MMD [ 12 ] In patients undergoing direct STA-MCA revascularization there is also evidence for reduced secondary stroke in cases with good angiographic revascularization [ 30 ]. n our cohort angiographic direct bypass occlusion was found in a total of eight hemispheres, one of which required repeat revascularization using a frontal STA branch due to persisting neurological symptoms. This patient also showed poor EDS development. In the remaining seven hemispheres there was STA-MCA occlusion with good or moderate angiographic filling of EDS. These observations support the hypothesis that combined revascularization with EDS may provide a second line of protection against ischemic insult in case of direct bypass failure similar to EMS [ 9 ]. As the here described EDS does not require any additional invasiveness during the direct revascularization surgery, it can easily be transferred to the clinical routine. The postoperative complication rate was lower than that of EMS reported previously [ 9 ], which could be attributed to the minimally invasive approach via a mini-craniotomy. Nevertheless, due to the relatively small surface of the EDS through the mini craniotomy (performed as a minimally invasive or, MIS-EDS), the hemodynamic functionality in addition to angiographic development should be further assessed in the future. Limitations of the current study include its retrospective design with the majority of adult patients which may skew interpretation of factors affecting bypass development in terms of children versus adults. As this analysis focused on angiographic outcome, data on the development of cerebrovascular reserve capacity over time was not included as this is not regularly performed following surgery in asymptomatic patients, also due to the possible side effects of repetitive acetazolamide and radionuclide application. Thus, the functional contribution of EDS in addition to STA-MCA remains unquantified. Although such analysis may provide more insight into the functional consequences of good or poor bypass development over time, the clinical outcome of patients remains the most important factor in daily neurosurgical practice. As EDS is a procedure which is not performed alone, but only in combination with direct bypass we do not have control group in which only EDS can be compared to. In this regard, a further limitation of our study is that we have no patients which were treated with EDS alone in order to elucidate the development and clinical effect of EDS without the contribution of STA-MCA vascularization. This however lies in the nature of the procedure which is not a stand-alone technique. Nonetheless, EDS merits evaluation as it continues to be implemented in the clinical routine and as our study shows, can be performed in a miminally invasive fashion with angiographic benefit. Conclusion To the best of our knowledge this study represents the largest cohort in which long-term angiographic characterization of combined revascularization with EDS and STA-MCA direct bypass development has been performed. While there are currently no randomized control trials regarding the benefit of different bypass strategies, in our experience EDS is a safe technique of indirect revascularization for MMV and can be used in a standardized fashion through a small craniotomy for both pediatric and adult patients. Despite the use of EDS in clinical practice, until now it has remained unclear whether there is an angiographic benefit. Our results demonstrate that EDS may offer a reasonable option to perform combined revascularization in patients with moyamoya disease and serves as a second line of protection with angiographic evidence of vascularization resulting from EDS. Prospective comparative studies are warranted to address the efficacy of this combined technique in comparison to direct bypass only. Declarations Ethical Approval and Consent to participate This retrospective analysis was approved by the local ethics committee and was conducted in accordance with the Declaration of Helsinki Human and Animal Ethics This retrospective analysis was approved by the local ethics committee and was conducted in accordance with the Declaration of Helsinki Consent for publication All authors consent to publication of this article - Availability of supporting data Available upon reasonable written request - Competing interests The authors declare no competing interests - Funding No funding was received for this work - Authors' contributions K.L wrote the main manuscript text, prepared figures and tables and performed statistical anaylsis. G.A supervised manuscript writing and correction. D.B and F.M aquired data from patient records. P.V, G.A and K.L designed the study. All authors reviewed the manuscript prior to submission. - Acknowledgements The authors thank Kimberly Ohm for her generous contribution of the illustrations in Figure 2. - Authors' information Corresponding author: Prof. Peter Vajkoczy Department of Neurosurgery Charité–Universitätsmedizin Berlin, Germany [email protected] Tel:030450660002 References Suzuki, J. and A. Takaku, Cerebrovascular "moyamoya" disease. Disease showing abnormal net-like vessels in base of brain . Arch Neurol, 1969. 20 (3): p. 288–99. Guidelines for diagnosis and treatment of moyamoya disease (spontaneous occlusion of the circle of Willis) . Neurol Med Chir (Tokyo), 2012. 52 (5): p. 245–66. Acker, G., et al., Distinct clinical and radiographic characteristics of moyamoya disease amongst European Caucasians . Eur J Neurol, 2015. 22 (6): p. 1012–7. Jeon, J.P., et al., Meta-analysis of the surgical outcomes of symptomatic moyamoya disease in adults . J Neurosurg, 2018. 128 (3): p. 793–799. 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Zhao, Y., et al., Time Course of Neoangiogenesis After Indirect Bypass Surgery for Moyamoya Disease: Comparison of Short-term and Long-term Follow-up Angiography . Clin Neuroradiol, 2020. 30 (1): p. 91–99. Furtado, S.V., et al., Surgical Outcome of Encephaloduroarteriomyosynangiosis for Moyamoya Disease . Neurol India, 2021. 69 (5): p. 1259–1264. Liu, Z.W., et al., Clinical characteristics and leptomeningeal collateral status in pediatric and adult patients with ischemic moyamoya disease . CNS Neurosci Ther, 2020. 26 (1): p. 14–20. Ge, P., et al., Postoperative collateral formation after indirect bypass for hemorrhagic moyamoya disease . BMC Neurol, 2020. 20 (1): p. 28. Qian, C., et al., The Efficacy of Surgical Treatment for the Secondary Prevention of Stroke in Symptomatic Moyamoya Disease: A Meta-Analysis . Medicine (Baltimore), 2015. 94 (49): p. e2218. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Major revision 28 Jul, 2022 Reviews received at journal 21 Jun, 2022 Reviewers agreed at journal 16 Jun, 2022 Reviewers invited by journal 16 Jun, 2022 Editor assigned by journal 07 Jun, 2022 Submission checks completed at journal 06 Jun, 2022 First submitted to journal 02 Jun, 2022 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-1720929","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":111307630,"identity":"843eea0e-2114-46fb-a2e7-f235eef29a42","order_by":0,"name":"Kristin Lucia","email":"","orcid":"","institution":"Charité – Universitätsmedizin Berlin corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Kristin","middleName":"","lastName":"Lucia","suffix":""},{"id":111307631,"identity":"96535a9e-0a06-428a-8ee1-a33c59921ed5","order_by":1,"name":"Güliz Acker","email":"","orcid":"","institution":"Charité – Universitätsmedizin Berlin corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Güliz","middleName":"","lastName":"Acker","suffix":""},{"id":111307632,"identity":"e901578e-42e6-4749-8dd0-d877fda914d9","order_by":2,"name":"Friedrich Mrosk","email":"","orcid":"","institution":"Charité – Universitätsmedizin Berlin corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Friedrich","middleName":"","lastName":"Mrosk","suffix":""},{"id":111307633,"identity":"0bb5f9f8-c9d2-4896-ad74-4bbb0f4073f6","order_by":3,"name":"Defne Beyaztas","email":"","orcid":"","institution":"Charité – Universitätsmedizin Berlin corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Defne","middleName":"","lastName":"Beyaztas","suffix":""},{"id":111307634,"identity":"f286534b-726d-4917-aab1-579ed6b20784","order_by":4,"name":"Peter Vajkoczy","email":"data:image/png;base64,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","orcid":"","institution":"Charité – Universitätsmedizin Berlin corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Peter","middleName":"","lastName":"Vajkoczy","suffix":""}],"badges":[],"createdAt":"2022-06-02 23:44:08","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-1720929/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-1720929/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":22412846,"identity":"5d0f856f-b73b-43e3-8858-5c6efc0d16d9","added_by":"auto","created_at":"2022-06-08 15:05:06","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":100525,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eQualitative angiographic grading of EDS and STA bypass development. \u003c/strong\u003eTop Row, single white asterisk: Examples of STA-MCA bypass grading with grade 1 as “poor” (no filling of the MCA territory), grade 2 “moderate” (antegrade filing of one or two MCA branches) or grade 3 “high” (complete filling of the MCA territory). Bottom row, double white asterisk: EDS development was classified either as “poor” (no filling), moderate (opacification of cortical vessels) or “high” (filling of the MCA territory).\u003c/p\u003e\u003cp\u003e\u003cbr\u003e\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-1720929/v1/618ad6a8a9c4c754db664e3c.png"},{"id":22413329,"identity":"2ad0ad06-b664-4255-baf0-592e11d62d31","added_by":"auto","created_at":"2022-06-08 15:10:06","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":127075,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eSchematic illustration of the minimally invasive EDS Technique. \u003c/strong\u003eFor combined revascularization with EDS we use a minimally invasive strategy via a small craniotomy of approximately 3cm diameter which is placed according to a standardized template [\u003ca href=\"about:blank\" rel=\"noopener noreferrer\" target=\"_blank\"\u003e17\u003c/a\u003e]. Following placement of the STA-MCA bypass the dural flap is inverted and laid on top of the cortex and further closure is performed as with any other craniotomy assuring the STA exits through the burr hole.\u003c/p\u003e\u003cp\u003e\u003cbr\u003e\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-1720929/v1/3eb5674136e16b6a08fff7e1.png"},{"id":22412848,"identity":"017149e3-016d-4445-9418-a336c083d4bb","added_by":"auto","created_at":"2022-06-08 15:05:06","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":63076,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eLongitudinal bypass development\u003c/strong\u003e. A) EDS and B) STA-MCA bypass development at the timepoints 3-6 months, 6-12 months, 12-24 months and \u0026gt;24 months following surgery. Percentages represent the number of hemispheres being scored as grade 1 (poor), 2 (moderate) or 3 (high) as a total of all hemispheres undergoing analysis for that particular time period.\u0026nbsp;\u003c/p\u003e\u003cp\u003e\u003cbr\u003e\u003c/p\u003e","description":"","filename":"Figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-1720929/v1/09c5b5327126cec7ec819206.png"},{"id":22413332,"identity":"6729ba15-e850-4780-9aaf-d21bb50758a3","added_by":"auto","created_at":"2022-06-08 15:10:13","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":824638,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-1720929/v1/61531330-5a80-472a-9d2d-131c6dad87ed.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Longitudinal angiographic characterization of the efficacy of combined cerebral revascularization using encephalodurosynangiosis in patients with Moyamoya Disease","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eMoyamoya Vasculopathy (MMV) is a rare stenoocclusive cerebrovascular disease affecting the basal cerebral arteries which leads to the formation of fragile net-like vessels [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. As such, patients with MMV can present with intracranial hemorrhage from abnormal vessels as well as ischemic events [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Surgical revascularization aiming at restoring perfusion and preventing future hemorrhage and ischemia is widely accepted as the primary treatment for MMV [\u003cspan additionalcitationids=\"CR5\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Revascularization can be achieved by both direct (anastomosis performed between branches of the internal and external carotid arteries) and indirect techniques which rely on neoangeogenesis between the cortical surface and a pedicled graft [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e] Common indirect revascularization techniques involve the dura mater (encephalodurosynangiosis, EDS), the temporalis muscle (encephalomyosynangiosis, EMS) or further variants thereof such as encephalao-duro-arterio-synangiosis (EDAS) and encephalo-duro-arterio-myo-synangiosis (EDAMS) [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eStudies examining the efficacy of combined revascularization procedures have provided evidence of improved angiographic revascularization when EMS [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e], EDAMS [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e] and EDAS [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e] are used in combination with STA-MCA direct bypass. Radiological studies have also shown increased cortical perfusion in patients treated with indirect revascularization techniques such as EDAS [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. To date, the use of EDS as a further indirect revascularization technique in combination with STA-MCA direct bypass has not been angiographically characterized as to whether or not vessel growth occurs, possibly due to the simplicity of the technique as well as the small surface contact between dura and brain surface. In our institution, EDS is performed via a mini-craniotomy which is significantly less invasive than other indirect techniques requiring greater exposure. We therefore aimed to characterize the angiographic bypass development of both minimally invasive indirect EDS and direct STA-MCA bypass over time as well as possible predictors of EDS development.\u003c/p\u003e"},{"header":"2. Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1 Study Design\u003c/h2\u003e \u003cp\u003eWe retrospectively identified all Moyamoya patients who were treated using a minimally invasive EDS as an indirect bypass strategy combined with an STA-MCA direct bypass on at least one hemisphere in our department between January 2007 and December 2019. All patients with unilateral moyamoya and moyamoya syndrome using the ICD code 167.5 (moyamoya) were included. Moyamoya disease (MMD), moyamoya syndrome and unilateral MMV were defined based on the guidelines established by the Research Committee for Moyamoya Disease and patients with possible associated diseases were classified as moyamoya syndrome [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].\u003c/p\u003e \u003cp\u003e \u003cb\u003eVariables\u003c/b\u003e \u003c/p\u003e \u003cp\u003eElectronic medical records were used to gather data on patient demographics, time of surgery, follow-up time, angiographic follow-up, history of complications and MRI and hemodynamic diagnostics (obtained either by xenon-computerized tomography or acetazolamide-stimulated single-photon emission computed tomography).\u003c/p\u003e \u003cp\u003eSeverity of the MMV was classified using the Suzuki and Berlin Gradings [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]Preoperative CVRC was included in the calculation of the Berlin Grading. The qualitative assessment of the CVRC was performed as described before [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Briefly, CVRC was assessed qualitatively by visual interpretation with a standardized side-by-side display of anatomically normalized resting and acetazolamide images together with the rCVRC map. Impaired cerebrovascular reserve capacity (CVRC) was defined as a missing signal increase after acetazolamide stimulation. If stimulation with acetazolamide leaded to an increase of the signal, CVRC was considered sustained.\u003c/p\u003e \u003cp\u003e \u003cb\u003eAngiographic Evaluation\u003c/b\u003e \u003c/p\u003e \u003cp\u003eQualitative angiographic analysis of direct bypass development was performed as previously described by Czabanka et al [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e] with the exception that we implemented a three-grade classification instead of four in which the Czabanka grades 1 and 2 were combined to better allow for uniform comparison of diverse angiographic image sets. Accordingly, angiographic filling of STA-MCA bypasses were classified either as \u0026ldquo;poor\u0026rdquo; (no filling of the MCA territory), \u0026ldquo;moderate\u0026rdquo; (antegrade filing of one or two MCA branches) or \u0026ldquo;high\u0026rdquo; (complete filling of the MCA territory) [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Angiographic filling of EDS was classified in adaptation to previously described methods either as \u0026ldquo;poor\u0026rdquo; (no filling), moderate (opacification of cortical vessels) or \u0026ldquo;high\u0026rdquo; (any filling of the MCA territory)[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. \u003cb\u003e(\u003c/b\u003eFig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e\u003cb\u003e).\u003c/b\u003e\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eIn our department, the EDS was performed without changing the exposure strategy for direct revascularization perfomed via a mini-craniotomy of 3 centimeters in diameter [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. At the end of the direct revascularization procedure, the dural flap was inverted and pushed beneath the bone \u003cb\u003e(\u003c/b\u003eFig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e\u003cb\u003e).\u003c/b\u003e\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.2 Statistical analysis\u003c/h2\u003e \u003cp\u003eQuantitative values are presented as median values with range. Univariate Cox regression analysis was performed among all cases of surgically treated MMV using \u0026ldquo;high\u0026rdquo; of bypass filling (\u0026ldquo;poor\u0026rdquo;, \u0026ldquo;moderate\u0026rdquo;, and \u0026ldquo;high\u0026rdquo;) as dependent variables. Multivariate analysis was performed on those variables which reached a p-value of \u0026lt;\u0026thinsp;0.150. All analyses were performed independently for time periods of 3\u0026ndash;6 months, 6\u0026ndash;12 months, 12\u0026ndash;24 months and \u0026gt;\u0026thinsp;24 months following initial revascularization. P-values of less than 0.05 were considered statistically significant. All analyses were performed in SPSS (version 24; IBM Corp.).\u003c/p\u003e \u003c/div\u003e"},{"header":"3 Results","content":"\u003cp\u003e\u003cstrong\u003e3.1 Patient characteristics\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe analyzed a total of 139 surgically treated hemispheres in 81 MMV patients. All patients were operated in a single institution between 2007 and 2019 by the senior author. Of these patients, 65 (80%) \u0026nbsp;had Moyamoya Disease (MMD), 4 (5%) had unilateral MMD (uMMD) and \u0026nbsp;12 (15%) had Moyamoya syndrome. The median age at first surgical intervention was 44 years old (range: 6-65 years old and 4 (5%) patients were under 18 years of age. Regarding gender distribution, 58 (72%) of patients were female and 28% were male. The majority of our cohort was of Caucasian background (92%), 6% were of Asian and 2% were of Middle Eastern descent (\u003cstrong\u003eTable 1).\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 1: Patient demographics and disease characteristics.\u0026nbsp;\u003c/strong\u003eAge is reported as median and range. All other parameters as absolute number of patients or hemispheres with percent of total in parentheses.\u003c/p\u003e\n\u003ctable border=\"0\" cellpadding=\"0\" cellspacing=\"0\" width=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"48.01980198019802%\"\u003e\n \u003cp\u003e\u003cstrong\u003eParameter\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.564356435643564%\"\u003e\n \u003cp\u003eN (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.415841584158414%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"48.01980198019802%\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.564356435643564%\"\u003e\n \u003cp\u003e44 (6-65)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.415841584158414%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"48.01980198019802%\"\u003e\n \u003cp\u003e\u003cstrong\u003eGender\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.564356435643564%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"33.415841584158414%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"48.01980198019802%\"\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.564356435643564%\"\u003e\n \u003cp\u003e23 (28%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.415841584158414%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"48.01980198019802%\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.564356435643564%\"\u003e\n \u003cp\u003e58 (72%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.415841584158414%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"48.01980198019802%\"\u003e\n \u003cp\u003e\u003cstrong\u003eDiagnosis\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.564356435643564%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"33.415841584158414%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"48.13895781637717%\"\u003e\n \u003cp\u003eMMD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" width=\"51.86104218362283%\"\u003e\n \u003cp\u003e65 (80%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"48.13895781637717%\"\u003e\n \u003cp\u003eMMS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" width=\"51.86104218362283%\"\u003e\n \u003cp\u003e12 (15%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"48.13895781637717%\"\u003e\n \u003cp\u003euMMD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" width=\"51.86104218362283%\"\u003e\n \u003cp\u003e4 (5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"48.13895781637717%\"\u003e\n \u003cp\u003e\u003cstrong\u003eOnset\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" width=\"51.86104218362283%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"48.13895781637717%\"\u003e\n \u003cp\u003eIschemic\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" width=\"51.86104218362283%\"\u003e\n \u003cp\u003e72 (89%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"48.13895781637717%\"\u003e\n \u003cp\u003eHemorrhagic\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" width=\"51.86104218362283%\"\u003e\n \u003cp\u003e9 (11%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"48.13895781637717%\"\u003e\n \u003cp\u003e\u003cstrong\u003eSuzuki Grade\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" width=\"51.86104218362283%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"48.13895781637717%\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" width=\"51.86104218362283%\"\u003e\n \u003cp\u003e14 (10%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"48.13895781637717%\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" width=\"51.86104218362283%\"\u003e\n \u003cp\u003e50 (36%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"48.13895781637717%\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" width=\"51.86104218362283%\"\u003e\n \u003cp\u003e49 (35%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"48.13895781637717%\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" width=\"51.86104218362283%\"\u003e\n \u003cp\u003e12 (9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"48.13895781637717%\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" width=\"51.86104218362283%\"\u003e\n \u003cp\u003e12 (9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"48.13895781637717%\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" width=\"51.86104218362283%\"\u003e\n \u003cp\u003e2 (1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"48.13895781637717%\"\u003e\n \u003cp\u003e\u003cstrong\u003eBerlin Grade\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" width=\"51.86104218362283%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"48.13895781637717%\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" width=\"51.86104218362283%\"\u003e\n \u003cp\u003e35 (25%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"48.13895781637717%\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" width=\"51.86104218362283%\"\u003e\n \u003cp\u003e83 (60%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"48.13895781637717%\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" width=\"51.86104218362283%\"\u003e\n \u003cp\u003e21 (15%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"48.13895781637717%\"\u003e\n \u003cp\u003e\u003cstrong\u003eFollow Up\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" width=\"51.86104218362283%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"48.13895781637717%\"\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"bottom\" width=\"51.86104218362283%\"\u003e\n \u003cp\u003e1.6 years (2.5 months-6.7 years)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"48.13895781637717%\"\u003e\n \u003cp\u003e\u003cstrong\u003eComplications\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" width=\"51.86104218362283%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"48.13895781637717%\"\u003e\n \u003cp\u003eWound Healing disorder\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" width=\"51.86104218362283%\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"48.13895781637717%\"\u003e\n \u003cp\u003eNew Ischemia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" width=\"51.86104218362283%\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eThe majority of our cohort (89%) presented with ischemic events leading to diagnosis of MMV with only 9 patients (11%) suffering from hemorrhagic lesions. Berlin grading of all hemispheres revealed \u0026nbsp;35 (25%) grade 1, 83 (60%) grade 2, \u0026nbsp;21 (15%) \u0026nbsp;grade 3. Suzuki classification showed 14 stage 1 (10%), 50 stage 2 (36%), 49 stage 3 (35%), 12 stage 4 (9%), 12 stage 5 (9%), 2 stage 6 (1%) hemispheres.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.2 Angiographic evaluation\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe median follow-up period for all patients was 1.6 years (range 2.5 months \u0026ndash; 6.7 years). For the timepoints 3-6 months postoperative data was available from all 139 hemispheres, at 6-12 months from 78 hemispheres (56%), at 12-24 months for 42 hemispheres (30%) and timepoints beyond 24 months from 14 hemispheres (10%).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eEDS and STA-MCA bypass filling\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eAt 3-6 months following combined revascularization rates of poor bypass filling were seen more frequently (55%) in EDS than STA-MCA (47%). Accordingly, higher rates of moderate bypass filling were 46% of STA-MCA compared to 40% in EDS. The rate of high bypass filling was similar between EDS (5%) and STA-MCA (7%) at this early time point (\u003cstrong\u003eFigure 3).\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAt 6-12 months following combined revascularization poor bypass filling rates were stable compared to the first six months following surgery with 47% of STA-MCA and 39% of EDS hemispheres. \u0026nbsp;The rate of moderate bypass filling increased among EDS to 57% (from 40%) of hemispheres with the rate in STA-MCA bypass remaining similar to the earlier time point at 45% (versus 46% at 0-6 months). The rates of high bypass filling rose slightly in STA-MCA from 7% to 9% of hemispheres at this time point while EDS remained similar at 4% (versus 5% at 3-6 months) (\u003cstrong\u003eFigure 3).\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAt 12-24 months following combined revascularization poor filling rates remained stable compared to the earlier timepoints among STA-MCA (49%) with EDS at 39% of hemispheres. At this point, an increase in the rate of high bypass filling could be seen in 14% of STA-MCA and EDS cases. Moderate bypass filling remained similar in both groups at 51% (STA-MCA) and 47% (EDS) of hemispheres. (\u003cstrong\u003eFigure 3).\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAt time points longer than 24 months following combined revascularization, the rates of poor and moderate bypass filling remained stable for STA-MCA (poor: 42%, moderate: 49% of hemispheres) with lower rates of high bypass filling compared to earlier timepoints of 12-24 months (9% versus 14%). EDS showed a further increase in high bypass filling to 23% from 14% of hemispheres at 12-24 months. months. Accordingly, rates of poor bypass filling decreased by 6% and moderate filling by 3% (\u003cstrong\u003eFigure 3).\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eComparing STA-MCA function over all time points showed that 3% of bypasses showed a regression of function with 52% remaining stable and 45% showing an increase of angiographic illing. In contrast, a higher proportion of EDS showed a regression of bypass filling over time (18%) with 34% remaining stable and 48% improving over time. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cu\u003eBypass occlusion and postoperative complications\u003c/u\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFour patients (4.9%) experienced a postoperative complication following revascularization surgery. Of these, two were wound healing disorders and two were ischemic events related to surgery. \u0026nbsp;The majority of patients undergoing bypass surgery had no bypass occlusion over the period of observation (90,1%). Four patients in our cohort experienced STA-MCA bypass occlusion of one hemisphere within 1 year of surgery, two cases of bypass occlusion occurred 3.5 years following surgery and two patients experienced bypass occlusion at 5.5 and 6.1 years. Of these, one case of neurological deterioration (recurrent TIAs) was reported resulting in repeat revascularization surgery using a frontal branch of the STA. This case of bypass occlusion occurred within 6 months following initial surgery and the development of EDS filling was rated as \u0026ldquo;poor\u0026rdquo;. In the remaining eight hemispheres which demonstrated asymptomatic STA-MCA occlusion, angiographic filling of EDS was rated \u0026ldquo;moderate\u0026rdquo; or \u0026ldquo;high\u0026rdquo;.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cu\u003ePredictors of EDS development\u0026nbsp;\u003c/u\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFinally, we examined the relationship between several demographic and angiographic factors and the development of EDS function over time. Using univariate cox regression analysis with good EDS outcome defined as a dependent variable, we found that at all time points only the degree of STA-MCA bypass filling was significantly associated with poor EDS bypass filling \u003cstrong\u003e(Table 2a-d).\u0026nbsp;\u003c/strong\u003eMultivariate regression analysis performed on the variables preoperative deficit, history of TIA (3-6 months postoperatively), Berlin Grade, STA-MCA grades, Suzuki stage and age (6-12 months postoperatively) revealed no new significant predictors of EDS development, while STA-MCA bypass filling remained significant\u003cstrong\u003e\u0026nbsp;(Table 2e).\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2: \u0026nbsp;Model summary of regression analysis.\u0026nbsp;\u003c/strong\u003eModel summary of regression analysis on moderators analyzed with \u0026ldquo;good bypass function\u0026rdquo; being defined as the dependent variable. P\u0026lt;0.05. Tables 2a-2d show univariate regression analysis models. Table 2e displays results of multivariate regression analysis using variables from the univariate analysis which gave a p-value of \u0026lt;0.15. No variables meeting this criteria were available in the time periods 12-24 months and \u0026gt;24 months, therefore no results are depicted for these times. STA-MCA bypass development was classified as \u0026ldquo;poor\u0026rdquo; (no filling of the MCA territory), \u0026ldquo;moderate\u0026rdquo; (antegrade filing of one or two MCA branches) or \u0026ldquo;high\u0026rdquo; (complete filling of the MCA territory) {Czabanka, 2011 #9. EDS development was classified as \u0026ldquo;poor\u0026rdquo; (no filling), moderate (opacification of cortical vessels) or \u0026ldquo;high\u0026rdquo; (filling of the MCA territory)\u0026nbsp;[15]. Good leptomeningeal collateralization was determined based on the presence of anastomoses in the watershed zones of the posterior cerebral artery to the anterior and/or to the middle cerebreal artery and poor collateralization was determined in absence of the above anastomoses\u0026nbsp;[16]. Intra-extracranial collateralization was examined based on the presence and degree (none, moderate, extensive) of transdural collaterals arising from the middle meningeal artery\u0026nbsp;[17, 18]. Development of MMV was classified as either absent, faint and localized or abundant\u0026nbsp;[15]\u0026nbsp;as either absent, faint and localized or abundant.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ea)\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellpadding=\"0\" cellspacing=\"0\" width=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"39.96569468267582%\"\u003e\n \u003cp\u003e\u003cstrong\u003e3-6 Months\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"18.69639794168096%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"13.20754716981132%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"15.95197255574614%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" width=\"2.9159519725557463%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"9.262435677530018%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"39.96569468267582%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"18.69639794168096%\"\u003e\n \u003cp\u003e\u003cstrong\u003eHazard Ratio\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"13.20754716981132%\"\u003e\n \u003cp\u003e\u003cstrong\u003eP\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" valign=\"top\" width=\"28.130360205831902%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;CI\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"39.96569468267582%\"\u003e\n \u003cp\u003eBerlin Grade\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"18.69639794168096%\"\u003e\n \u003cp\u003e-0.165\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"13.20754716981132%\"\u003e\n \u003cp\u003e0.471\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"15.95197255574614%\"\u003e\n \u003cp\u003e-0.222\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"2.9159519725557463%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"9.262435677530018%\"\u003e\n \u003cp\u003e0.104\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"39.96569468267582%\"\u003e\n \u003cp\u003eSuzuki Stage\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"18.69639794168096%\"\u003e\n \u003cp\u003e0.262\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"13.20754716981132%\"\u003e\n \u003cp\u003e0.266\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"15.95197255574614%\"\u003e\n \u003cp\u003e-0.068\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"2.9159519725557463%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"9.262435677530018%\"\u003e\n \u003cp\u003e0.241\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"39.96569468267582%\"\u003e\n \u003cp\u003eAge\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"18.69639794168096%\"\u003e\n \u003cp\u003e0.037\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"13.20754716981132%\"\u003e\n \u003cp\u003e0.787\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"15.95197255574614%\"\u003e\n \u003cp\u003e-0.010\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"2.9159519725557463%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"9.262435677530018%\"\u003e\n \u003cp\u003e0.013\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"39.96569468267582%\"\u003e\n \u003cp\u003ePreoperative Deficit\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"18.69639794168096%\"\u003e\n \u003cp\u003e0.239\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"13.20754716981132%\"\u003e\n \u003cp\u003e0.115\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"15.95197255574614%\"\u003e\n \u003cp\u003e-0.067\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"2.9159519725557463%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"9.262435677530018%\"\u003e\n \u003cp\u003e0.602\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"39.96569468267582%\"\u003e\n \u003cp\u003eHistory of Stroke\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"18.69639794168096%\"\u003e\n \u003cp\u003e-0.031\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"13.20754716981132%\"\u003e\n \u003cp\u003e0.822\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"15.95197255574614%\"\u003e\n \u003cp\u003e-0.331\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"2.9159519725557463%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"9.262435677530018%\"\u003e\n \u003cp\u003e0.264\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"39.96569468267582%\"\u003e\n \u003cp\u003eHistory of TIA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"18.69639794168096%\"\u003e\n \u003cp\u003e0.225\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"13.20754716981132%\"\u003e\n \u003cp\u003e0.143\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"15.95197255574614%\"\u003e\n \u003cp\u003e-0.098\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"2.9159519725557463%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"9.262435677530018%\"\u003e\n \u003cp\u003e0.660\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"39.96569468267582%\"\u003e\n \u003cp\u003eHistory of Hemorrhage\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"18.69639794168096%\"\u003e\n \u003cp\u003e-0.025\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"13.20754716981132%\"\u003e\n \u003cp\u003e0.867\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"15.95197255574614%\"\u003e\n \u003cp\u003e-0.557\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"2.9159519725557463%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"9.262435677530018%\"\u003e\n \u003cp\u003e0.470\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"39.96569468267582%\"\u003e\n \u003cp\u003eLeptomeningeal Collaterals\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"18.69639794168096%\"\u003e\n \u003cp\u003e0.057\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"13.20754716981132%\"\u003e\n \u003cp\u003e0.670\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"15.95197255574614%\"\u003e\n \u003cp\u003e-0.493\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"2.9159519725557463%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"9.262435677530018%\"\u003e\n \u003cp\u003e0.761\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"39.96569468267582%\"\u003e\n \u003cp\u003eIntra-Extracranial Collaterals\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"18.69639794168096%\"\u003e\n \u003cp\u003e-0.153\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"13.20754716981132%\"\u003e\n \u003cp\u003e0.222\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"15.95197255574614%\"\u003e\n \u003cp\u003e-0.713\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"2.9159519725557463%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"9.262435677530018%\"\u003e\n \u003cp\u003e0.169\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"39.96569468267582%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eSTA Bypass\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"18.69639794168096%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e0.334\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"13.20754716981132%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e0.016\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"15.95197255574614%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e0.062\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"2.9159519725557463%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"9.262435677530018%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e0.566\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"39.96569468267582%\"\u003e\n \u003cp\u003eMMV decreased\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"18.69639794168096%\"\u003e\n \u003cp\u003e0.015\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"13.20754716981132%\"\u003e\n \u003cp\u003e0.91\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"15.95197255574614%\"\u003e\n \u003cp\u003e-0.482\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"2.9159519725557463%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"9.262435677530018%\"\u003e\n \u003cp\u003e0.540\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eb)\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellpadding=\"0\" cellspacing=\"0\" width=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"38.813559322033896%\"\u003e\n \u003cp\u003e\u003cstrong\u003e6-12 Months\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"20.338983050847457%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"14.23728813559322%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"14.23728813559322%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" width=\"3.0508474576271185%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"9.322033898305085%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"38.813559322033896%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"20.338983050847457%\"\u003e\n \u003cp\u003e\u003cstrong\u003eHazard Ratio\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"14.23728813559322%\"\u003e\n \u003cp\u003e\u003cstrong\u003eP\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" valign=\"top\" width=\"26.610169491525422%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; CI\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"38.813559322033896%\"\u003e\n \u003cp\u003eBerlin Grade\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"20.338983050847457%\"\u003e\n \u003cp\u003e0.422\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"14.23728813559322%\"\u003e\n \u003cp\u003e0.061\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"14.23728813559322%\"\u003e\n \u003cp\u003e-0.009\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"3.0508474576271185%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"9.322033898305085%\"\u003e\n \u003cp\u003e0.370\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"38.813559322033896%\"\u003e\n \u003cp\u003eSuzuki Stage\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"20.338983050847457%\"\u003e\n \u003cp\u003e-0.334\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"14.23728813559322%\"\u003e\n \u003cp\u003e0.143\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"14.23728813559322%\"\u003e\n \u003cp\u003e-0.286\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"3.0508474576271185%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"9.322033898305085%\"\u003e\n \u003cp\u003e0.043\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"38.813559322033896%\"\u003e\n \u003cp\u003eAge\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"20.338983050847457%\"\u003e\n \u003cp\u003e-0.245\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"14.23728813559322%\"\u003e\n \u003cp\u003e0.139\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"14.23728813559322%\"\u003e\n \u003cp\u003e-0.027\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"3.0508474576271185%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"9.322033898305085%\"\u003e\n \u003cp\u003e0.004\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"38.813559322033896%\"\u003e\n \u003cp\u003ePreoperative Deficit\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"20.338983050847457%\"\u003e\n \u003cp\u003e-0.180\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"14.23728813559322%\"\u003e\n \u003cp\u003e0.253\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"14.23728813559322%\"\u003e\n \u003cp\u003e-0.577\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"3.0508474576271185%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"9.322033898305085%\"\u003e\n \u003cp\u003e0.157\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"38.813559322033896%\"\u003e\n \u003cp\u003eHistory of Stroke\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"20.338983050847457%\"\u003e\n \u003cp\u003e0.073\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"14.23728813559322%\"\u003e\n \u003cp\u003e0.633\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"14.23728813559322%\"\u003e\n \u003cp\u003e-0.273\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"3.0508474576271185%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"9.322033898305085%\"\u003e\n \u003cp\u003e0.442\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"38.813559322033896%\"\u003e\n \u003cp\u003eHistory of TIA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"20.338983050847457%\"\u003e\n \u003cp\u003e-0.079\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"14.23728813559322%\"\u003e\n \u003cp\u003e0.634\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"14.23728813559322%\"\u003e\n \u003cp\u003e-0.584\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"3.0508474576271185%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"9.322033898305085%\"\u003e\n \u003cp\u003e0.361\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"38.813559322033896%\"\u003e\n \u003cp\u003eHistory of Hemorrhage\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"20.338983050847457%\"\u003e\n \u003cp\u003e-0.056\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"14.23728813559322%\"\u003e\n \u003cp\u003e0.723\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"14.23728813559322%\"\u003e\n \u003cp\u003e-0.766\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"3.0508474576271185%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"9.322033898305085%\"\u003e\n \u003cp\u003e0.537\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"38.813559322033896%\"\u003e\n \u003cp\u003eLeptomeningeal Collaterals\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"20.338983050847457%\"\u003e\n \u003cp\u003e-0.220\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"14.23728813559322%\"\u003e\n \u003cp\u003e0.186\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"14.23728813559322%\"\u003e\n \u003cp\u003e-0.614\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"3.0508474576271185%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"9.322033898305085%\"\u003e\n \u003cp\u003e0.124\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"38.813559322033896%\"\u003e\n \u003cp\u003eIntra-Extracranial Collaterals\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"20.338983050847457%\"\u003e\n \u003cp\u003e0.218\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"14.23728813559322%\"\u003e\n \u003cp\u003e0.169\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"14.23728813559322%\"\u003e\n \u003cp\u003e-0.090\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"3.0508474576271185%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"9.322033898305085%\"\u003e\n \u003cp\u003e0.491\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"38.813559322033896%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eSTA Bypass\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"20.338983050847457%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e0.491\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"14.23728813559322%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e0.004\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"14.23728813559322%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e0.150\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"3.0508474576271185%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"9.322033898305085%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e0.726\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"38.813559322033896%\"\u003e\n \u003cp\u003eMMV decreased\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"20.338983050847457%\"\u003e\n \u003cp\u003e-0.007\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"14.23728813559322%\"\u003e\n \u003cp\u003e0.964\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"14.23728813559322%\"\u003e\n \u003cp\u003e-0.260\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"3.0508474576271185%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"9.322033898305085%\"\u003e\n \u003cp\u003e0.559\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003ec)\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellpadding=\"0\" cellspacing=\"0\" width=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"36.277602523659304%\"\u003e\n \u003cp\u003e\u003cstrong\u003e12-24 Months\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"19.085173501577287%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"12.145110410094638%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"14.984227129337539%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"11.514195583596214%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"5.993690851735016%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"36.277602523659304%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"19.085173501577287%\"\u003e\n \u003cp\u003e\u003cstrong\u003eHazard Ratio\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"12.145110410094638%\"\u003e\n \u003cp\u003e\u003cstrong\u003eP\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" valign=\"top\" width=\"26.498422712933753%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; CI\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.993690851735016%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"36.277602523659304%\"\u003e\n \u003cp\u003eBerlin Grade\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"19.085173501577287%\"\u003e\n \u003cp\u003e-0.034\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"12.145110410094638%\"\u003e\n \u003cp\u003e0.922\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"14.984227129337539%\"\u003e\n \u003cp\u003e-1.371\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"2.8391167192429023%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"8.675078864353312%\"\u003e\n \u003cp\u003e0.906\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.993690851735016%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"36.277602523659304%\"\u003e\n \u003cp\u003eSuzuki Stage\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"19.085173501577287%\"\u003e\n \u003cp\u003e-0.120\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"12.145110410094638%\"\u003e\n \u003cp\u003e0.743\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"14.984227129337539%\"\u003e\n \u003cp\u003e-1.740\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"2.8391167192429023%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"8.675078864353312%\"\u003e\n \u003cp\u003e2.069\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.993690851735016%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"36.277602523659304%\"\u003e\n \u003cp\u003eAge\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"19.085173501577287%\"\u003e\n \u003cp\u003e-0.051\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"12.145110410094638%\"\u003e\n \u003cp\u003e0.850\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"14.984227129337539%\"\u003e\n \u003cp\u003e-0.077\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"2.8391167192429023%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"8.675078864353312%\"\u003e\n \u003cp\u003e0.079\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.993690851735016%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"36.277602523659304%\"\u003e\n \u003cp\u003ePreoperative Deficit\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"19.085173501577287%\"\u003e\n \u003cp\u003e-0.024\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"12.145110410094638%\"\u003e\n \u003cp\u003e0.904\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"14.984227129337539%\"\u003e\n \u003cp\u003e-1.939\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"2.8391167192429023%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"8.675078864353312%\"\u003e\n \u003cp\u003e1.410\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.993690851735016%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"36.277602523659304%\"\u003e\n \u003cp\u003eHistory of Stroke\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"19.085173501577287%\"\u003e\n \u003cp\u003e0.021\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"12.145110410094638%\"\u003e\n \u003cp\u003e0.913\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"14.984227129337539%\"\u003e\n \u003cp\u003e-1.986\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"2.8391167192429023%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"8.675078864353312%\"\u003e\n \u003cp\u003e1.853\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.993690851735016%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"36.277602523659304%\"\u003e\n \u003cp\u003eHistory of TIA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"19.085173501577287%\"\u003e\n \u003cp\u003e-0.079\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"12.145110410094638%\"\u003e\n \u003cp\u003e0.768\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"14.984227129337539%\"\u003e\n \u003cp\u003e-3.955\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"2.8391167192429023%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"8.675078864353312%\"\u003e\n \u003cp\u003e4.241\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.993690851735016%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"36.277602523659304%\"\u003e\n \u003cp\u003eHistory of Hemorrhage\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"19.085173501577287%\"\u003e\n \u003cp\u003e-0.297\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"12.145110410094638%\"\u003e\n \u003cp\u003e0.214\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"14.984227129337539%\"\u003e\n \u003cp\u003e-0.141\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"2.8391167192429023%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"8.675078864353312%\"\u003e\n \u003cp\u003e0.702\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.993690851735016%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"36.277602523659304%\"\u003e\n \u003cp\u003eLeptomeningeal Collaterals\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"19.085173501577287%\"\u003e\n \u003cp\u003e-0.249\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"12.145110410094638%\"\u003e\n \u003cp\u003e0.318\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"14.984227129337539%\"\u003e\n \u003cp\u003e-0.619\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"2.8391167192429023%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"8.675078864353312%\"\u003e\n \u003cp\u003e0.838\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.993690851735016%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"36.277602523659304%\"\u003e\n \u003cp\u003eIntra-Extracranial Collaterals\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"19.085173501577287%\"\u003e\n \u003cp\u003e-0.363\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"12.145110410094638%\"\u003e\n \u003cp\u003e0.159\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"14.984227129337539%\"\u003e\n \u003cp\u003e-0.859\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"2.8391167192429023%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"8.675078864353312%\"\u003e\n \u003cp\u003e0.154\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.993690851735016%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"36.277602523659304%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eSTA Bypass\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.085173501577287%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e0.481\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"12.145110410094638%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e0.006\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.984227129337539%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e0.214\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"2.8391167192429023%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.675078864353312%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e0.969\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.993690851735016%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"36.277602523659304%\"\u003e\n \u003cp\u003eMMV decreased\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"19.085173501577287%\"\u003e\n \u003cp\u003e0.075\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"12.145110410094638%\"\u003e\n \u003cp\u003e0.753\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"14.984227129337539%\"\u003e\n \u003cp\u003e-2.543\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"2.8391167192429023%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"8.675078864353312%\"\u003e\n \u003cp\u003e3.215\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.993690851735016%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003ed).\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellpadding=\"0\" cellspacing=\"0\" width=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"30.4%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026gt;24 Months\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"28.64%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"11.04%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.76%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"bottom\" width=\"16.16%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"30.4%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"28.64%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"11.04%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.76%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"bottom\" width=\"16.16%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"30.4%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"28.64%\"\u003e\n \u003cp\u003e\u003cstrong\u003eHazard Ratio\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"11.04%\"\u003e\n \u003cp\u003e\u003cstrong\u003eP\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"13.76%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"bottom\" width=\"16.16%\"\u003e\n \u003cp\u003e\u003cstrong\u003eCI\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"30.44871794871795%\"\u003e\n \u003cp\u003eBerlin Grade\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"28.685897435897434%\"\u003e\n \u003cp\u003e-0.219\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"11.057692307692308%\"\u003e\n \u003cp\u003e0.455\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"13.782051282051283%\"\u003e\n \u003cp\u003e- 0.367\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"2.7243589743589745%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"13.301282051282051%\"\u003e\n \u003cp\u003e0.172\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"30.44871794871795%\"\u003e\n \u003cp\u003eSuzuki Stage\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"28.685897435897434%\"\u003e\n \u003cp\u003e0.075\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"11.057692307692308%\"\u003e\n \u003cp\u003e0.817\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"13.782051282051283%\"\u003e\n \u003cp\u003e-0.222\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"2.7243589743589745%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"13.301282051282051%\"\u003e\n \u003cp\u003e0.277\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"30.44871794871795%\"\u003e\n \u003cp\u003eAge\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"28.685897435897434%\"\u003e\n \u003cp\u003e0.005\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"11.057692307692308%\"\u003e\n \u003cp\u003e0.981\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"13.782051282051283%\"\u003e\n \u003cp\u003e-0.020\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"2.7243589743589745%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"13.301282051282051%\"\u003e\n \u003cp\u003e0.020\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"30.44871794871795%\"\u003e\n \u003cp\u003ePreoperative Deficit\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"28.685897435897434%\"\u003e\n \u003cp\u003e0.135\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"11.057692307692308%\"\u003e\n \u003cp\u003e0.422\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"13.782051282051283%\"\u003e\n \u003cp\u003e-0.251\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"2.7243589743589745%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"13.301282051282051%\"\u003e\n \u003cp\u003e0.571\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"30.44871794871795%\"\u003e\n \u003cp\u003eHistory of Stroke\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"28.685897435897434%\"\u003e\n \u003cp\u003e0.074\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"11.057692307692308%\"\u003e\n \u003cp\u003e0.675\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"13.782051282051283%\"\u003e\n \u003cp\u003e-0.359\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"2.7243589743589745%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"13.301282051282051%\"\u003e\n \u003cp\u003e0.540\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"30.44871794871795%\"\u003e\n \u003cp\u003eHistory of TIA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"28.685897435897434%\"\u003e\n \u003cp\u003e-0.058\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"11.057692307692308%\"\u003e\n \u003cp\u003e0.771\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"13.782051282051283%\"\u003e\n \u003cp\u003e-0.814\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"2.7243589743589745%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"13.301282051282051%\"\u003e\n \u003cp\u003e0.614\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"30.44871794871795%\"\u003e\n \u003cp\u003eHistory of Hemorrhage\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"28.685897435897434%\"\u003e\n \u003cp\u003e-0.063\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"11.057692307692308%\"\u003e\n \u003cp\u003e0.740\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"13.782051282051283%\"\u003e\n \u003cp\u003e-1.079\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"2.7243589743589745%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"13.301282051282051%\"\u003e\n \u003cp\u003e0.782\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"30.44871794871795%\"\u003e\n \u003cp\u003eLeptomeningeal Collaterals\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"28.685897435897434%\"\u003e\n \u003cp\u003e-0.155\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"11.057692307692308%\"\u003e\n \u003cp\u003e0.442\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"13.782051282051283%\"\u003e\n \u003cp\u003e-0.843\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"2.7243589743589745%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"13.301282051282051%\"\u003e\n \u003cp\u003e0.386\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"30.44871794871795%\"\u003e\n \u003cp\u003eIntra-Extracranial Collaterals\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"28.685897435897434%\"\u003e\n \u003cp\u003e-0.339\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"11.057692307692308%\"\u003e\n \u003cp\u003e0.168\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"13.782051282051283%\"\u003e\n \u003cp\u003e-0.989\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"2.7243589743589745%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"13.301282051282051%\"\u003e\n \u003cp\u003e0.187\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"30.44871794871795%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eSTA Bypass\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"28.685897435897434%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e0.636\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"11.057692307692308%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e0.002\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"13.782051282051283%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e0.336\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"2.7243589743589745%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"13.301282051282051%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e1.227\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"30.44871794871795%\"\u003e\n \u003cp\u003eMMV decreased\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"28.685897435897434%\"\u003e\n \u003cp\u003e-0.095\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"11.057692307692308%\"\u003e\n \u003cp\u003e0.631\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"13.782051282051283%\"\u003e\n \u003cp\u003e-0.741\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"2.7243589743589745%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"13.301282051282051%\"\u003e\n \u003cp\u003e0.462\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\n\u003cp\u003e\u003cstrong\u003ee).\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"0\" cellpadding=\"0\" cellspacing=\"0\" width=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"38.52889667250438%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"20.31523642732049%\"\u003e\n \u003cp\u003e\u003cstrong\u003eHazard Ratio\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"12.959719789842381%\"\u003e\n \u003cp\u003e\u003cstrong\u003eP\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" valign=\"top\" width=\"28.19614711033275%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; CI\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"38.52889667250438%\"\u003e\n \u003cp\u003e\u003cstrong\u003e3-6 Months\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"20.31523642732049%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"12.959719789842381%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"15.936952714535902%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"2.9772329246935203%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"9.281961471103328%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"38.52889667250438%\"\u003e\n \u003cp\u003ePreoperative Deficit\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"20.31523642732049%\"\u003e\n \u003cp\u003e-0.115\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"12.959719789842381%\"\u003e\n \u003cp\u003e0.477\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"15.936952714535902%\"\u003e\n \u003cp\u003e-0.511\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"2.9772329246935203%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"9.281961471103328%\"\u003e\n \u003cp\u003e0.243\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"38.52889667250438%\"\u003e\n \u003cp\u003eHistory of TIA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"20.31523642732049%\"\u003e\n \u003cp\u003e0.119\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"12.959719789842381%\"\u003e\n \u003cp\u003e0.396\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"15.936952714535902%\"\u003e\n \u003cp\u003e-0.204\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"2.9772329246935203%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"9.281961471103328%\"\u003e\n \u003cp\u003e0.510\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"38.52889667250438%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eSTA Bypass\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"20.31523642732049%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e0.461\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"12.959719789842381%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e0.003\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"15.936952714535902%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e0.151\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"2.9772329246935203%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e-\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"9.281961471103328%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e0.673\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"38.52889667250438%\"\u003e\n \u003cp\u003e\u003cstrong\u003e6-12 Months\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"20.31523642732049%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"12.959719789842381%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"15.936952714535902%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"2.9772329246935203%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"9.281961471103328%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"38.52889667250438%\"\u003e\n \u003cp\u003eBerlin Grade\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"20.31523642732049%\"\u003e\n \u003cp\u003e0.439\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"12.959719789842381%\"\u003e\n \u003cp\u003e0.272\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"15.936952714535902%\"\u003e\n \u003cp\u003e-0.218\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"2.9772329246935203%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"9.281961471103328%\"\u003e\n \u003cp\u003e0.662\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"38.52889667250438%\"\u003e\n \u003cp\u003eSuzuki Stage\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"20.31523642732049%\"\u003e\n \u003cp\u003e-0.833\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"12.959719789842381%\"\u003e\n \u003cp\u003e0.201\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"15.936952714535902%\"\u003e\n \u003cp\u003e-0.990\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"2.9772329246935203%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"9.281961471103328%\"\u003e\n \u003cp\u003e0.250\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"38.52889667250438%\"\u003e\n \u003cp\u003eAge\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"20.31523642732049%\"\u003e\n \u003cp\u003e-0.193\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"12.959719789842381%\"\u003e\n \u003cp\u003e0.204\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"15.936952714535902%\"\u003e\n \u003cp\u003e-0.023\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"2.9772329246935203%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"9.281961471103328%\"\u003e\n \u003cp\u003e0.005\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"38.52889667250438%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eSTA-Bypass\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"20.31523642732049%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e0.469\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"12.959719789842381%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e0.022\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"15.936952714535902%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e0.096\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"2.9772329246935203%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e-\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"9.281961471103328%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e1.122\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"38.52889667250438%\"\u003e\n \u003cp\u003e\u003cstrong\u003e12-24 Months\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"20.31523642732049%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"12.959719789842381%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"15.936952714535902%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"2.9772329246935203%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"9.281961471103328%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"38.52889667250438%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"20.31523642732049%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"12.959719789842381%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"15.936952714535902%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"2.9772329246935203%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"9.281961471103328%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"38.52889667250438%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026gt;24 Months\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"20.31523642732049%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"12.959719789842381%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"15.936952714535902%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"2.9772329246935203%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"9.281961471103328%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"38.52889667250438%\"\u003e\n \u003cp\u003e\u003cstrong\u003e-\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"20.31523642732049%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"12.959719789842381%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"15.936952714535902%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"2.9772329246935203%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" width=\"9.281961471103328%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e"},{"header":"4 Discussion","content":"\u003cp\u003eAlthough the use of combined bypass strategies in the treatment of both hemorrhagic and ischemic MMV is supported by studies demonstrating positive angiographic, hemodynamic and clinical results\u0026nbsp;[\u003ca href=\"#_ENREF_6\" title=\"Miyamoto, 2014 #300\"\u003e6\u003c/a\u003e,\u0026nbsp;\u003ca href=\"#_ENREF_9\" title=\"Czabanka, 2011 #307\"\u003e9\u003c/a\u003e,\u0026nbsp;\u003ca href=\"#_ENREF_18\" title=\"Kim, 2016 #306\"\u003e18-21\u003c/a\u003e], the use of EDS as a method of indirect revascularization combined with STA-MCA bypass has remained uncharacterized despite its simplicity and ability to perform in a minimally invasive fashion.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eSeveral studies on \u0026nbsp;of EDAS\u0026nbsp;[\u003ca href=\"#_ENREF_13\" title=\"Guo, 2021 #662\"\u003e13\u003c/a\u003e,\u0026nbsp;\u003ca href=\"#_ENREF_22\" title=\"Zhang, 2020 #584\"\u003e22\u003c/a\u003e]\u0026nbsp;and EMS\u0026nbsp;[\u003ca href=\"#_ENREF_9\" title=\"Czabanka, 2011 #307\"\u003e9\u003c/a\u003e,\u0026nbsp;\u003ca href=\"#_ENREF_23\" title=\"Imai, 2015 #568\"\u003e23\u003c/a\u003e]\u0026nbsp;alone or in combination with STA-MCA bypass have demonstrated increased vessel growth on angiography. However, specific evaluation of EDS has rarely been performed. One study in hemorrhagic-onset MMV patients has analyzed angiographic outcome in a subset of patients (24 hemispheres) receiving combined revascularization using EDS compared to EDAS (30 hemispheres)\u0026nbsp;[\u003ca href=\"#_ENREF_24\" title=\"Zhao, 2018 #693\"\u003e24\u003c/a\u003e]. In this series, angiographic development as measured by the Matsushima revascularization level showed no statistically significant difference between the EDS and EDAS groups. As EDS requires less surgical exposure than the above mentioned techniques, these results suggest that its use may allow for comparable angiographic outcome with less invasiveness.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eDespite initial evidence that EDS may provide angiographic outcome compared to more invasive techniques, our study is to the best of our knowledge, the first to characterize the outcome of EDS in combination with direct bypass in a large cohort of hemorrhagic and ischemic onset MMV. In particular, we describe the use of a minimally invasive EDS via a small craniotomy approximately 3 centimeters in diameter which even further reduces the invasiveness of the overall procedure .\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eOur cohort consisting of 139 hemispheres with 89% ischemic onset and median age of 44 years was representative in comparison to other Caucasian MMV series\u0026nbsp;[\u003ca href=\"#_ENREF_3\" title=\"Acker, 2015 #309\"\u003e3,\u003c/a\u003e,\u0026nbsp;\u003ca href=\"#_ENREF_25\" title=\"Kraemer, 2019 #547\"\u003e25\u003c/a\u003e]. Here, we did indeed observe that STA-MCA direct bypass showed better angiographic filling at an earlier timepoint than EDS. STA-MCA function was found to be highest at earlier timepoints following initial revascularization and then stagnates at this level after 12 months following surgery. \u0026nbsp;At time points after 12 months following combined revascularization surgery EDS bypass filling began to improve whereas STA-MCA stagnated. These results differ slightly from previous angiographic analysis of an Asian cohort consisting of 25 hemispheres receiving combined bypass surgery using EDAS alone and follow-up at 6 and 12 months\u0026nbsp;[\u003ca href=\"#_ENREF_26\" title=\"Zhao, 2020 #569\"\u003e26\u003c/a\u003e]. In these patients maximal neoangiogenesis from indirect bypass was found already at 6 months. This difference to our results may have several reasons, including the use of indirect bypass alone, smaller sample size and follow-up conducted only up to 12 months following surgery in the Asian cohort. \u0026nbsp;A previous analysis from our institution on EMS bypass development alone and in combination with STA-MCA at 6 and 12 months following revascularization demonstrated similar dynamics of bypass function when compared to our results for EDS\u0026nbsp;[\u003ca href=\"#_ENREF_9\" title=\"Czabanka, 2011 #307\"\u003e9\u003c/a\u003e]. In particular, EDS and EMS both show an increase in the proportion of high bypass filling at later time periods (12 versus 6 months) whereas STA-MCA bypass function shows good function earlier. These findings support the recommendation of aiming for direct revascularization whenever possible in order to provide immediate support for insufficient reserve capacity\u0026nbsp;[\u003ca href=\"#_ENREF_7\" title=\"Acker, 2018 #266\"\u003e7\u003c/a\u003e].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn our study, Cox-regression analysis showed that the grade of STA-MCA bypass development was significantly associated with EDS bypass development, with better STA-MCA bypass filling predicting poor EDS angiographic filling. Functional adaptation of direct anastomoses is hypothesized to rely mainly on pressure gradients from donor to recipient arteries, whereas development of indirect anastomoses involves several precluding steps of angiogenesis and arteriogenesis\u0026nbsp;[\u003ca href=\"#_ENREF_23\" title=\"Imai, 2015 #568\"\u003e23\u003c/a\u003e]. Accordingly, angiographic evidence of bypass perfusion and development of vascular networks may be expected to arise sooner in direct bypasses than indirect\u0026nbsp;[\u003ca href=\"#_ENREF_7\" title=\"Acker, 2018 #266\"\u003e7\u003c/a\u003e], therefore possibly mitigating the angiogenic signals which would otherwise promote EDS development in compensation for insufficient direct bypass function. This question of predictive factors for bypass neoangiogenesis has been addressed in previous studies which have focused on hemorrhagic onset MMV. First, a multicenteric analysis of 231 hemispheres from patients undergoing various indirect revascularization procedures found that \u0026nbsp;hemorrhagic disease onset positively predicts poor neovascularization and that abundant moyamoya vessels were positively associated with good postoperative neovascularization resulting from indirect bypass\u0026nbsp;[\u003ca href=\"#_ENREF_12\" title=\"Zhao, 2019 #570\"\u003e12\u003c/a\u003e]. We observed no statistically significant relationship between angiographic grading Suzuki or Berlin grading and the development of EDS, which is concurrent with a recent report on the development of EDAMS in an Indian population\u0026nbsp;[\u003ca href=\"#_ENREF_27\" title=\"Furtado, 2021 #661\"\u003e27\u003c/a\u003e]. Secondly, neoangiogenesis and good bypass function have also been previously described to occur more frequently in pediatric than adult patients\u0026nbsp;[\u003ca href=\"#_ENREF_28\" title=\"Liu, 2020 #582\"\u003e28\u003c/a\u003e]. In contrast to this study, our analysis revealed no statistically significant relationship between age and degree of indirect bypass development which may be due to the fact that our pediatric patients in were teenagers closer to 18 years of age rather than younger children. Children also made up only a very small part of our total collective with 4/81 patients being under the age of 18. \u0026nbsp;A further study on a smaller cohort consisting of 64 operated hemispheres found that only the location of initial hemorrhage in the anterior territory was predictive of good postoperative collateral formation\u0026nbsp;[\u003ca href=\"#_ENREF_29\" title=\"Ge, 2020 #571\"\u003e29\u003c/a\u003e]. The use of different grading systems of postoperative neoangiogenesis between these two analyses may have contributed to their varying conclusions. As our study included only a minority of hemorrhagic onset cases a direct comparison of results is challenging.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAlthough angiographic bypass performance is not a guaranteed indicator of clinical stability good angiographic revascularization from indirect bypass (EDAS) has been shown to positively associate with lower incidence of hemorrhage and improvement of neurological symptoms in patients with hemorrhagic onset MMD\u0026nbsp;[\u003ca href=\"#_ENREF_12\" title=\"Zhao, 2019 #570\"\u003e12\u003c/a\u003e]\u0026nbsp;In patients undergoing direct STA-MCA revascularization there is also evidence for reduced secondary stroke in cases with good angiographic revascularization\u0026nbsp;[\u003ca href=\"#_ENREF_30\" title=\"Qian, 2015 #304\"\u003e30\u003c/a\u003e]. n our cohort angiographic direct bypass occlusion was found in a total of eight hemispheres, one of which required repeat revascularization using a frontal STA branch due to persisting neurological symptoms. This patient also showed poor EDS development. In the remaining seven hemispheres there was \u0026nbsp;STA-MCA occlusion with good or moderate angiographic filling of EDS. These observations support the hypothesis that combined revascularization with EDS may provide a second line of protection against ischemic insult in case of direct bypass failure similar to EMS\u0026nbsp;[\u003ca href=\"#_ENREF_9\" title=\"Czabanka, 2011 #307\"\u003e9\u003c/a\u003e]. As the here described EDS does not require any additional invasiveness during the direct revascularization surgery, it can easily be transferred to the clinical routine. The postoperative complication rate was lower than that of EMS reported previously\u0026nbsp;[\u003ca href=\"#_ENREF_9\" title=\"Czabanka, 2011 #307\"\u003e9\u003c/a\u003e], which could be attributed to the minimally invasive approach via a mini-craniotomy. Nevertheless, due to the relatively small surface of the EDS through the mini craniotomy (performed as a minimally invasive or, MIS-EDS), the hemodynamic functionality in addition to angiographic development should be further assessed in the future.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eLimitations of the current study include its retrospective design with the majority of adult patients which may skew interpretation of factors affecting bypass development in terms of children versus adults. As this analysis focused on angiographic outcome, data on the development of cerebrovascular reserve capacity over time was not included as this is not regularly performed following surgery in asymptomatic patients, also due to the possible side effects of repetitive acetazolamide and radionuclide application. Thus, the functional contribution of EDS in addition to STA-MCA remains unquantified. Although such analysis may provide more insight into the functional consequences of good or poor bypass development over time, the clinical outcome of patients remains the most important factor in daily neurosurgical practice. As EDS is a procedure which is not performed alone, but only in combination with direct bypass we do not have control group in which only EDS can be compared to. In this regard, a further limitation of our study is that we have no patients which were treated with EDS alone in order to elucidate the development and clinical effect of EDS without the contribution of STA-MCA vascularization. This however lies in the nature of the procedure which is not a stand-alone technique. Nonetheless, EDS merits evaluation as it continues to be implemented in the clinical routine and as our study shows, can be performed in a miminally invasive fashion with angiographic benefit.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eTo the best of our knowledge this study represents the largest cohort in which long-term angiographic characterization of combined revascularization with EDS and STA-MCA direct bypass development has been performed. While there are currently no randomized control trials regarding the benefit of different bypass strategies, in our experience EDS is a safe technique of indirect revascularization for MMV and can be used in a standardized fashion through a small craniotomy for both pediatric and adult patients. Despite the use \u0026nbsp;of EDS in clinical practice, until now it has remained unclear whether there is an angiographic benefit. Our results demonstrate that EDS may offer a reasonable option to perform combined revascularization in patients with moyamoya disease and serves as a second line of protection with angiographic evidence of vascularization resulting from EDS. Prospective comparative studies are warranted to address the efficacy of this combined technique in comparison to direct bypass only.\u003c/p\u003e\n"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthical Approval and Consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis retrospective analysis was approved by the local ethics committee and was conducted in accordance with the Declaration of Helsinki\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eHuman and Animal Ethics\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis retrospective analysis was approved by the local ethics committee and was conducted in accordance with the Declaration of Helsinki\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors consent to publication of this article\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e- Availability of supporting data\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAvailable upon reasonable written request\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e- Competing interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e- Funding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo funding was received for this work\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e- Authors\u0026apos; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eK.L wrote the main manuscript text, prepared figures and tables and performed statistical anaylsis. G.A supervised manuscript writing and correction. D.B and F.M aquired data from patient records. P.V, G.A and K.L designed the study. All authors reviewed the manuscript prior to submission.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e- Acknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors thank Kimberly Ohm for her generous contribution of the illustrations in Figure 2.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e- Authors\u0026apos; information\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCorresponding author:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eProf. Peter Vajkoczy\u003c/p\u003e\n\u003cp\u003eDepartment of Neurosurgery\u003c/p\u003e\n\u003cp\u003eCharit\u0026eacute;\u0026ndash;Universit\u0026auml;tsmedizin Berlin, Germany\u003c/p\u003e\n\u003cp\[email protected]\u003c/p\u003e\n\u003cp\u003eTel:030450660002\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003e\u003cspan\u003eSuzuki, J. and A. 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Stroke, 2014. \u003cstrong\u003e45\u003c/strong\u003e(10): p.\u0026nbsp;3025\u0026ndash;31.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eLee, S.B., et al., \u003cem\u003eLong-term follow-up results in 142 adult patients with moyamoya disease according to management modality\u003c/em\u003e. Acta Neurochir (Wien), 2012. \u003cstrong\u003e154\u003c/strong\u003e(7): p.\u0026nbsp;1179\u0026ndash;87.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eBang, J.S., et al., \u003cem\u003eQuantitative angiographic comparison with the OSIRIS program between the direct and indirect revascularization modalities in adult moyamoya disease\u003c/em\u003e. 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BMC Neurol, 2020. \u003cstrong\u003e20\u003c/strong\u003e(1): p.\u0026nbsp;28.\u003c/span\u003e\u003c/li\u003e\n \u003cli\u003e\u003cspan\u003eQian, C., et al., \u003cem\u003eThe Efficacy of Surgical Treatment for the Secondary Prevention of Stroke in Symptomatic Moyamoya Disease: A Meta-Analysis\u003c/em\u003e. Medicine (Baltimore), 2015. \u003cstrong\u003e94\u003c/strong\u003e(49): p. e2218.\u003c/span\u003e\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"neurosurgical-review","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"nrev","sideBox":"Learn more about [Neurosurgical Review](https://www.springer.com/journal/10143)","snPcode":"10143","submissionUrl":"https://submission.nature.com/new-submission/10143/3","title":"Neurosurgical Review","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Moyamoya, Encephalodurosynangiosis, Bypass, Angiogenesis, Angiography","lastPublishedDoi":"10.21203/rs.3.rs-1720929/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-1720929/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground: \u003c/strong\u003e\u003c/p\u003e\u003cp\u003eMoyamoya Vasculopathy (MMV) can be treated using direct, indirect, or combined revascularization procedures. We perform combined revascularization using the STA-MCA bypass and minimally invasive encephalodurosynangiosis (EDS). Due to lack of systematic analyses to date it remains unclear whether and to which extent this limited EDS serves as a growth source for extracerebral blood vessels into the brain. The objective of the current study is to characterize the extent of angiographic filling of EDS and STA-MCA bypass development over time and to determine possible predictors of EDS development in adult MMV patients. \u003c/p\u003e\u003cp\u003e\u003cstrong\u003eMethods: \u003c/strong\u003e\u003c/p\u003e\u003cp\u003eSingle-center retrospective analysis of 81 MMV patients (139 hemispheres) treated with a minimally invasive EDS and STA-MCA bypass. Angiographic images, clinical/operative data were reviewed and scored. Uni-/ and multivariate COX-regression analyses identified preoperative predictors of good EDS vascularization. \u003c/p\u003e\u003cp\u003e\u003cstrong\u003eResults: \u003c/strong\u003e\u003c/p\u003e\u003cp\u003eAt 3-6 months after surgery EDS showed moderate and high angiographic filling in 40% and 5% of hemispheres, respectively. After 12 months moderate and high filling was in 57% and 4% of hemispheres, respectively. STA-MCA bypass filling was moderate in 47% and high in 7% of hemispheres at 3-6 months and 45% moderate and 9% high after 12 months. High STA-MCA bypass filling on angiography was a negative predictor of EDS development.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eConclusions:\u003c/strong\u003e\u003c/p\u003e\u003cp\u003eMinimally invasive EDS is a simple technique and serves as a source of vessel growth into the brain. EDS development lags behind that of STA-MCA bypass and can be recommended as an additive revascularization source when combined with a direct bypass.\u003c/p\u003e","manuscriptTitle":"Longitudinal angiographic characterization of the efficacy of combined cerebral revascularization using encephalodurosynangiosis in patients with Moyamoya Disease","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2022-06-08 15:05:04","doi":"10.21203/rs.3.rs-1720929/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Major revision","date":"2022-07-28T08:44:11+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2022-06-21T13:43:55+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"a0443cc7-0d4b-4bd8-a73f-620364a64174","date":"2022-06-16T22:53:29+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2022-06-16T18:21:25+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2022-06-07T05:21:03+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2022-06-06T04:59:32+00:00","index":"","fulltext":""},{"type":"submitted","content":"Neurosurgical Review","date":"2022-06-02T23:43:44+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"neurosurgical-review","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"nrev","sideBox":"Learn more about [Neurosurgical Review](https://www.springer.com/journal/10143)","snPcode":"10143","submissionUrl":"https://submission.nature.com/new-submission/10143/3","title":"Neurosurgical Review","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"51c52eb2-a0f9-41de-a478-2801f0bb6aea","owner":[],"postedDate":"June 8th, 2022","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2022-09-11T17:44:10+00:00","versionOfRecord":[],"versionCreatedAt":"2022-06-08 15:05:04","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-1720929","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-1720929","identity":"rs-1720929","version":["v1"]},"buildId":"7rjqhiLT3MXkJMwkYKINL","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}