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The natural history of asymptomatic adult moyamoya disease (MMD) is unclear, and the benefit of treatment remains controversial. This study aimed to investigate the natural history of asymptomatic MMD in a North American cohort and to evaluate risk factors associated with and the effects of treatment on disease progression.Medical records from 3 institutions of consecutive adult patients with MMD diagnosed between 1984 and 2018 were retrospectively reviewed. Patients with unilateral or bilateral asymptomatic MMD were evaluated for subsequent development of infarction or hemorrhage. Multivariate Cox proportional hazards regression assessed risk factors associated with infarction or hemorrhage, adjusting for age, sex, race, initial Suzuki grade, hypertension, hyperlipidemia, diabetes, obesity, presence of aneurysms, smoking status, aspirin, and statin use at diagnosis.We identified 106 hemispheres with asymptomatic MMD in 97 patients with mean 5.1 years (interquartile range, 1.0-7.9 years) of follow-up. Of 106 hemispheres, 59 were treated medically, and 47 were treated with revascularization with direct or indirect bypasses. The medical and surgical cohorts had a 1.9% and 1.3% annual rate of radiographic infarction or hemorrhage per hemisphere, respectively. Cox regression for radiographic events, including early postoperative events, showed no significant difference between the treatment groups (adjusted hazard ratio 0.34 [95% confidence interval 0.05-2.5]).We found an overall 1.7% annual rate of radiographic infarction or hemorrhage in asymptomatic MMD hemispheres. Although we did not find a benefit to surgical treatment within the study period, asymptomatic patients with expected long-term survival may benefit from surgery given the sustained long-term benefits after surgery despite an initial postoperative risk.

OBJECTIVE There is a reported elevated risk of cerebral aneurysms in patients with intracranial dural arteriovenous fistulas (dAVFs). However, the natural history, rate of spontaneous regression, and ideal treatment regimen are not well characterized. In this study, the authors aimed to describe the characteristics of patients with dAVFs and intracranial aneurysms and propose a classification system. METHODS The Consortium for Dural Arteriovenous Fistula Outcomes Research (CONDOR) database from 12 centers was retrospectively reviewed. Analysis was performed to compare dAVF patients with (dAVF+ cohort) and without (dAVF-only cohort) concomitant aneurysm. Aneurysms were categorized based on location as a dAVF flow-related aneurysm (FRA) or a dAVF non–flow-related aneurysm (NFRA), with further classification as extra- or intradural. Patients with traumatic pseudoaneurysms or aneurysms with associated arteriovenous malformations were excluded from the analysis. Patient demographics, dAVF anatomical information, aneurysm information, and follow-up data were collected. RESULTS Of the 1077 patients, 1043 were eligible for inclusion, comprising 978 (93.8%) and 65 (6.2%) in the dAVF-only and dAVF+ cohorts, respectively. There were 96 aneurysms in the dAVF+ cohort; 10 patients (1%) harbored 12 FRAs, and 55 patients (5.3%) harbored 84 NFRAs. Dural AVF+ patients had higher rates of smoking (59.3% vs 35.2%, p < 0.001) and illicit drug use (5.8% vs 1.5%, p = 0.02). Sixteen dAVF+ patients (24.6%) presented with aneurysm rupture, which represented 16.7% of the total aneurysms. One patient (1.5%) had aneurysm rupture during follow-up. Patients with dAVF+ were more likely to have a dAVF located in nonconventional locations, less likely to have arterial supply to the dAVF from external carotid artery branches, and more likely to have supply from pial branches. Rates of cortical venous drainage and Borden type distributions were comparable between cohorts. A minority (12.5%) of aneurysms were FRAs. The majority of the aneurysms underwent treatment via either endovascular (36.5%) or microsurgical (15.6%) technique. A small proportion of aneurysms managed conservatively either with or without dAVF treatment spontaneously regressed (6.2%). CONCLUSIONS Patients with dAVF have a similar risk of harboring a concomitant intracranial aneurysm unrelated to the dAVF (5.3%) compared with the general population (approximately 2%–5%) and a rare risk (0.9%) of harboring an FRA. Only 50% of FRAs are intradural. Dural AVF+ patients have differences in dAVF angioarchitecture. A subset of dAVF+ patients harbor FRAs that may regress after dAVF treatment.

Background and ObjectivesWhile somatic mutations have been well-studied in cancer, their roles in other complex traits are much less understood. Our goal is to identify somatic variants that may contribute to the formation of saccular cerebral aneurysms.MethodsWe performed whole-exome sequencing on aneurysm tissues and paired peripheral blood. RNA sequencing and the CRISPR/Cas9 system were then used to perform functional validation of our results.ResultsSomatic variants involved in supervillin (SVIL) or its regulation were found in 17% of aneurysm tissues. In the presence of a mutation in theSVILgene, the expression level of SVIL was downregulated in the aneurysm tissue compared with normal control vessels. Downstream signaling pathways that were induced by knockdown ofSVILvia the CRISPR/Cas9 system in vascular smooth muscle cells (vSMCs) were determined by evaluating changes in gene expression and protein kinase phosphorylation. We found thatSVILregulated the phenotypic modulation of vSMCs to the synthetic phenotype via Krüppel-like factor 4 and platelet-derived growth factor and affected cell migration of vSMCs via the RhoA/ROCK pathway.DiscussionWe propose that somatic variants form a novel mechanism for the development of cerebral aneurysms. Specifically, somatic variants inSVILresult in the phenotypic modulation of vSMCs, which increases the susceptibility to aneurysm formation. This finding suggests a new avenue for the therapeutic intervention and prevention of cerebral aneurysms.

Angiographic vasospasm after aneurysmal subarachnoid hemorrhage (aSAH) is associated with delayed cerebral ischemia (DCI)-related cerebral infarction (radiological DCI) and worsened neurological outcome. Transcranial Doppler (TCD) measurements of cerebral blood flow velocity are commonly used after aSAH to screen for vasospasm; however, their association with cerebral infarction is not well characterized. We sought to determine whether time-varying TCD-measured vasospasm severity is associated with cerebral infarction and investigate the performance characteristics of different time/severity cutoffs for predicting cerebral infarction. We conducted a retrospective single-center cohort study of consecutive adult patients with aSAH with at least one TCD study between 2011 and 2020. The primary outcome was radiological DCI, defined as a cerebral infarction developing at least 2 days after any surgical or endovascular intervention without an alternative cause. Cox proportional hazards models were used to examine associations between time-varying vasospasm severity and radiological DCI. Optimal TCD-based time/severity thresholds for predicting radiological DCI were then determined. Of 262 patients with aSAH who underwent TCD studies, 27 (10%) developed radiological DCI. Patients with radiological DCI had higher modified Fisher scale scores and trended toward earlier onset of vasospasm. Adjusted for age, Hunt and Hess scores, and modified Fisher scale scores, the worst-vessel vasospasm severity was associated with radiological DCI (adjusted hazard ratio 1.7 [95% confidence interval 1.1–2.4]). Vasospasm severity within a specific vessel was associated with risk of delayed infarction in the territory supplied by that vessel. Optimal discrimination of patients with radiological DCI was achieved with thresholds of mild vasospasm on days 4–5 or moderate vasospasm on days 6–9, with negative predictive values greater than 90% and positive predictive values near 20%. TCD-measured vasospasm severity is associated with radiological DCI after aSAH. An early, mild TCD-based vasospasm severity threshold had a high negative predictive value, supporting its role as a screening tool to identify at-risk patients.

Objective Spontaneous subarachnoid hemorrhage is often due to rupture of an intracranial aneurysm, but some patients present with no identifiable source. Increased incidence of nonaneurysmal subarachnoid hemorrhage (naSAH) has been reported over time. Methods We performed a retrospective analysis of naSAH from 2008−2017 to determine the rate of naSAH change over time and its association with cannabis use. Univariable and multivariable regression analyses were performed to study the trend over time, radiographic patterns of hemorrhage, and clinical outcome at the time of discharge. In addition, we compared the rate of naSAH with the rate of aneurysmal SAH (aSAH) to adjust for changes in hospital volume and prevalence/reporting of cannabis use in the population over time. Results A total of 86 naSAH and 328 aSAH patients were identified, with an increase in naSAH over time compared with aSAH (P = 0.0034). Increased cannabis use was associated with naSAH (odds ratio [OR] 2.1, 95% confidence interval 1.1, 4.1, P = 0.035) but not aSAH over time. Cannabis use was also associated with different subarachnoid hemorrhage patterns (P = 0.0065) in naSAH. Multivariable analysis demonstrated good neurologic outcome after naSAH to be inversely associated with cocaine use (OR 0.008 [0.002−0.4]), ventriculostomy placement (OR 0.004 [0.03−0.50]), and anticoagulant use (OR 0.016 [0.003−0.54]) but not with cannabis use. Conclusions As cannabis use becomes more prevalent with legalization, it is important to further investigate this association with spontaneous SAH.

Background: Cranial dural arteriovenous fistulas with cortical venous drainage are rare lesions that can present with hemorrhage. A high rate of rebleeding in the early period following hemorrhage has been reported, but published long-term rates are much lower. No study has examined how risk of rebleeding changes over time. Our objective was to quantify the relative incidence of rebleeding in the early and later periods following hemorrhage. Methods: Patients with dural arteriovenous fistula and cortical venous drainage presenting with hemorrhage were identified from the multinational CONDOR (Consortium for Dural Fistula Outcomes Research) database. Natural history follow-up was defined as time from hemorrhage to first treatment, rebleed, or last follow-up. Rebleeding in the first 2 weeks and first year were compared using incidence rate ratio and difference. Results: Of 1077 patients, 250 met the inclusion criteria and had 95 cumulative person-years natural history follow-up. The overall annualized rebleed rate was 7.3% (95% CI, 3.2–14.5). The incidence rate of rebleeding in the first 2 weeks was 0.0011 per person-day; an early rebleed risk of 1.6% in the first 14 days (95% CI, 0.3–5.1). For the remainder of the first year, the incidence rate was 0.00015 per person-day; a rebleed rate of 5.3% (CI, 1.7–12.4) over 1 year. The incidence rate ratio was 7.3 (95% CI, 1.4–37.7; P , 0.026). Conclusions: The risk of rebleeding of a dural arteriovenous fistula with cortical venous drainage presenting with hemorrhage is increased in the first 2 weeks justifying early treatment. However, the magnitude of this increase may be considerably lower than previously thought. Treatment within 5 days was associated with a low rate of rebleeding and appears an appropriate timeframe.

Background In adults with ischemic moyamoya disease (MMD), the efficacy of direct vs indirect revascularization procedures remains a matter of debate. Objective To investigate the outcomes of ischemic MMD in a North American cohort treated by direct and indirect revascularizations. Methods We retrospectively reviewed medical records of adult patients with MMD with ischemic presentation from 1984 to 2018 at the Brigham and Women's Hospital and Massachusetts General Hospital who underwent either direct or indirect bypasses. Early postoperative events and outcome at more than 6 mo postoperatively were evaluated using multivariable logistic regression analyses. Multivariable Cox proportional hazards regression analyses were used to evaluate delayed ischemic and hemorrhagic events. Analyses were performed per hemisphere. Results A total of 95 patients with MMD and 127 hemispheres were included in this study. A total of 3.5% and 8.6% of patients had early surgical complications in the direct and indirect bypass cohorts, respectively (P = .24). Hemispheres with direct bypasses had fewer long-term ischemic and hemorrhagic events at latest follow-up (adjusted hazard ratio [HR] 0.19, 95% confidence interval [CI] 0.058-0.63, P = .007; median follow-up 4.5 [interquartile range, IQR 1-8] yr). There was no difference between the direct and indirect bypass groups when the endpoint was limited to infarction and hemorrhage only (P = .12). There was no difference in outcome (modified Rankin Scale [mRS] ≥ 3) between the 2 cohorts (P = .92). Conclusion There was no difference in early postoperative events, long-term infarction or hemorrhage, or clinical outcome between direct and indirect revascularization. However, there was a significant decrease in all ischemic and hemorrhagic events combined in direct revascularizations compared to indirect revascularizations.

Background Acute strokes involving complete, isolated occlusion of the extracranial cervical internal carotid artery (EC-ICA) with no intracranial clot burden account for a minority of stroke cases that are managed variably. Here we present our two-decade experience and a systematic review of endovascular management of acute isolated EC-ICA strokes in the hyperacute phase (Methods Our prospectively maintained database was retrospectively searched for patients who presented between January 1, 2003 and December 31, 2022 with acute cervical ICA stroke confirmed on angiography. Only patients who had an isolated 100% occlusion of the cervical ICA segment and attempted acute stenting with/without angioplasty within the first 48 h of time since last known well were included. Demographics, procedural details, and outcomes were recorded. For the systematic review, a search of PubMed and Embase databases was conducted. Results Forty-six patients with acute, isolated EC-ICA occlusive stroke were included. Median presenting National Institutes of Health Stroke Scale (NIHSS) score was 8 (interquartile range 3–10) with a perfusion deficit in 78.3% of the 40 cases assessed with computed tomography perfusion imaging. Median time from symptom onset to intra-arterial puncture was 14.4 h. Immediate recanalization was achieved in 82.6% cases. Two cases (4.3%) of symptomatic intracranial hemorrhage (sICH) occurred postprocedure. Outcome measures were stable or improved discharge NIHSS score in 86.9% of cases, functional independence at 90 days (modified Rankin scale score ≤2) in 78.3%, and mortality in 6.5%. The systematic review included 167 patients from four articles. The estimated rate of immediate recanalization was 92.7% (95% confidence interval (CI), 88.77–96.77%), favorable outcome was 62.01% (95% CI, 55.04–69.87%), and sICH was 6.2% (95% CI, 3.41–11.32%). Conclusion Stenting and angioplasty for acute cervical ICA occlusive strokes during the hyperacute phase can be performed successfully with favorable clinical outcomes and an acceptable recanalization rate.

BackgroundTools predicting intracranial dural arteriovenous fistulas (dAVFs) treatment outcomes remain scarce. This study aimed to use a multicenter database comprising more than 1000 dAVFs to develop a practical scoring system that predicts treatment outcomes.MethodsPatients with angiographically confirmed dAVFs who underwent treatment within the Consortium for Dural Arteriovenous Fistula Outcomes Research-participating institutions were retrospectively reviewed. A subset comprising 80% of patients was randomly selected as training dataset, and the remaining 20% was used for validation. Univariable predictors of complete dAVF obliteration were entered into a stepwise multivariable regression model. The components of the proposed score (VEBAS) were weighted based on their ORs. Model performance was assessed using receiver operating curves (ROC) and areas under the ROC.ResultsA total of 880 dAVF patients were included. Venous stenosis (presence vs absence), elderly age (ConclusionThe VEBAS score is a practical grading system that can guide patient counseling when considering dAVF intervention by predicting the likelihood of treatment success, with higher scores portending a greater likelihood of complete obliteration.

OBJECTIVE Flow diverter devices have revolutionized the treatment of intracranial aneurysms (IAs) since their approval in 2011 and have continued to evolve. The devices have been widely adopted across institutions and centers over the past decade; however, long-term follow-up after treatment with the Pipeline embolization device (PED) is not well described in the literature. The authors’ institution was among the first to begin using PEDs, allowing them to report their series of patients treated with flow diverters ≥ 10 years ago. In this study, the authors aimed to evaluate the long-term angiographic and clinical outcomes of these patients and review lessons learned along the way. METHODS The authors performed a retrospective review of their institution’s IA database from January 2007 to July 2012. All patients with IAs treated with a PED prior to July 2012 were included. Clinical and angiographic characteristics were extracted. Available angiographic follow-up at 1, 3, 5, and 10 years was reported. RESULTS A total of 83 patients with 92 aneurysms treated with a PED ≥ 10 years ago were identified and included in the study. The mean aneurysm dome diameter was 9.2 (SD 5.7) mm, the mean aneurysm height was 10.4 (SD 6.8) mm, and the mean neck width was 4.1 (SD 2.4) mm. Only 1 (1.1%) aneurysm was ruptured at presentation. Eight (8.7%) aneurysms were recurrences of previous treatment modalities. The morphology was saccular in 77 (83.7%) aneurysms, fusiform in 14 (15.2%), and blister-like in 1 (1.1%). Among saccular aneurysms, 60 (77.9%) were wide-necked. Seventy-five (81.5%) aneurysms were in the internal carotid artery, 12 (13.0%) were vertebrobasilar, 3 (3.3%) were in the middle cerebral artery, and 2 (2.2%) were in the posterior cerebral artery. Angiographic follow-up at 1, 3, 5, and 10 years was available for 75, 59, 50, and 15 patients, respectively. The complete occlusion rates at 1, 3, 5, and 10 years were 94.7%, 96.6%, 96.0%, and 100%, respectively. The retreatment rates at 1, 3, 5, and 10 years were 8.0%, 6.8%, 8.0%, and 6.7%, respectively. CONCLUSIONS The authors provide their single-institution series of IA patients treated with a PED ≥ 10 years ago, with the first report of 10-year follow-up for the available patients.

BackgroundExtensive clot burden in tandem strokes accounts for poor mechanical thrombectomy (MT) outcomes. Several studies have shown the benefit of balloon guide catheters (BGCs) in MT and carotid artery stenting.ObjectiveIn view of this potential benefit, to investigate the safety and effectiveness of proximal flow arrest using a BGC during concurrent MT and carotid revascularization for tandem stroke treatment in a comparative, propensity score-matched (PSM) study.MethodsPatients with a tandem stroke identified from our endovascular database were dichotomized into groups treated with BGCs versus conventional guide catheters. One-to-one PSM adjustment for baseline demographics and treatment selection bias using nearest-neighbor matching was performed. Patient demographics, presentation characteristics, and procedural details were recorded. Outcomes assessed were final modified Thrombolysis in Cerebral Infarction (mTICI) grade, periprocedural symptomatic intracranial hemorrhage (sICH) rate, in-hospital mortality, and 90-day modified Rankin Scale (mRS) score. Mann-Whitney U test and multivariate logistic regression were performed to compare procedural parameters and clinical outcomes.ResultsConcurrent carotid revascularization (stenting with/without angioplasty) and MT was performed in 125 cases (BGC: 85; no BGC: 40). After PSM (40 patients/group), the BGC group had a significantly shorter procedure duration (77.9 vs 61.5 min; OR=0.996; P=0.006), lower discharge National Institutes of Health Stroke Scale score (8.0 vs 11.0; OR=0.987; P=0.042), and higher odds of 90-day mRS 0–2 score (52.3% vs 27.5%; OR=0.34; P=0.040). On multivariate regression, the BGC group had a significantly higher first pass effect rate (mTICI 2b or 3)(OR=1.115, 95% CI 1.015 to 1.432; P=0.013) and lower periprocedural sICH rate (OR=0.615, 95% CI 0.406 to 0.932; P=0.025). No difference in in-hospital mortality was observed (OR=1.591, 95% CI 0.976 to 2.593; P=0.067).ConclusionBGCs used for concurrent MT–carotid revascularization with flow arrest were safe and resulted in superior clinical and angiographic outcomes in patients with a tandem stroke.

Background Basilar artery occlusion (BAO) stroke is a catastrophic clinical event that results in significant morbidity and mortality. Whether MT is superior in improving outcomes remains largely inconclusive. We performed a meta-analysis of randomized controlled trials (RCTs) to better understand the efficacy and safety of MT in treating BAO compared to medical management (MM). Methods PubMed and EMBASE were searched to identify RCTs that directly compared the safety and efficacy of MT versus MM for patients with BAO. The primary outcome was modified Rankin scale (mRS) 0–3 at 3 months, and secondary outcome variables included National Institutes of Health Stroke Scale (NIHSS) at 24 hours, mRS 0–2 at 3 months, symptomatic intracranial hemorrhage (sICH), and 90-day mortality. Results Four RCTs with 988 patients (432 in the MM arm and 556 in the MT arm), were included. Patients receiving MT had significantly higher rate of mRS 0–2 (OR = 1.994, 95% CI: 1.319–3.012) and mRS 0–3 (OR = 2.259, 95% CI: 1.166–4.374) at 3 months in comparison to patients receiving MM. Mortality was also significantly reduced in the MT group (OR = 0.640, 95% CI: 0.493–0.831). However, increased odds of sICH were found in the MT group compared to the MM group (OR = 8.193, 95% CI: 2.451–27.389). No difference was observed in terms of NIHSS at 24 hours between the two arms. Conclusions Despite the higher risk of sICH, MT was associated with superior functional outcomes and reduced mortality compared to MM in BAO patients. A revision of current guidelines for treatment of acute ischemic stroke from basilar artery occlusion should be considered.

BackgroundHemodynamic stress, conditioned by the morphology of the surrounding vasculature, plays an important role in aneurysm formation. Our goal was to identify image-based location-specific parameters that are associated with posterior communicating artery (PCoA) aneurysms.MethodsThree-dimensional morphological parameters obtained from CT angiography or digital subtraction angiography from 187 patients with unilateral PCoA aneurysms, diagnosed at the Brigham and Women’s Hospital and Massachusetts General Hospital between 1990 and 2016, were evaluated. In order to control for genetic and clinical risk factors, we chose the contralateral unaffected PCoA as a control group. We examined diameters and angles of the surrounding parent and daughter vessels. Univariable and multivariable statistical analyses were performed to determine statistical significance. Sensitivity analyses with small aneurysms (≤5 mm) only and an unmatched analysis of 432 PCoA aneurysms and 197 control patients without PCoA aneurysms were also performed.ResultsIn a multivariable conditional logistic regression model we showed that smaller diameter size ratio (OR 1.45×10−5, 95% CI 1.12×10−7 to 1.88×10−3) and larger daughter-daughter angle (OR 1.04, 95% CI 1.02 to 1.07) were significantly associated with PCoA aneurysm presence after correcting for other variables. In subgroup analyses of small aneurysms (≤5 mm) and in an unmatched analysis the significance and direction of these results were preserved.ConclusionsLarger daughter-daughter angles and smaller diameter size ratio are significantly associated with the presence of PCoA aneurysms. These simple parameters can be utilized to guide the risk assessment for the formation of PCoA aneurysms in high risk patients.

OBJECTIVE Cranial dural arteriovenous fistulas (dAVFs) are often treated with endovascular therapy, but occasionally a multimodality approach including surgery and/or radiosurgery is utilized. Recurrence after an initial angiographic cure has been reported, with estimated rates ranging from 2% to 14.3%, but few risk factors have been identified. The objective of this study was to identify risk factors associated with recurrence of dAVF after putative cure. METHODS The Consortium for Dural Arteriovenous Fistula Outcomes Research (CONDOR) data were retrospectively reviewed. All patients with angiographic cure after treatment and subsequent angiographic follow-up were included. The primary outcome was recurrence, with risk factor analysis. Secondary outcomes included clinical outcomes, morbidity, and mortality associated with recurrence. Risk factor analysis was performed comparing the group of patients who experienced recurrence with those with durable cure (regardless of multiple recurrences). Time-to-event analysis was performed using all collective recurrence events (multiple per patients in some cases). RESULTS Of the 1077 patients included in the primary CONDOR data set, 457 met inclusion criteria. A total of 32 patients (7%) experienced 34 events of recurrence at a mean of 368.7 days (median 192 days). The recurrence rate was 4.5% overall. Kaplan-Meier analysis predicted long-term recurrence rates approaching 11% at 3 years. Grade III dAVFs treated with endovascular therapy were statistically significantly more likely to experience recurrence than those treated surgically (13.3% vs 0%, p = 0.0001). Tentorial location, cortical venous drainage, and deep cerebral venous drainage were all risk factors for recurrence. Endovascular intervention and radiosurgery were associated with recurrence. Six recurrences were symptomatic, including 2 with hemorrhage, 3 with nonhemorrhagic neurological deficit, and 1 with progressive flow-related symptoms (decreased vision). CONCLUSIONS Recurrence of dAVFs after putative cure can occur after endovascular treatment. Risk factors include tentorial location, cortical venous drainage, and deep cerebral drainage. Multimodality therapy can be used to achieve cure after recurrence. A delayed long-term angiographic evaluation (at least 1 year from cure) may be warranted, especially in cases with risk factors for recurrence.

OBJECTIVE Cranial dural arteriovenous fistulas (dAVFs) are rare lesions, hampering efforts to understand them and improve their care. To address this challenge, investigators with an established record of dAVF investigation formed an international, multicenter consortium aimed at better elucidating dAVF pathophysiology, imaging characteristics, natural history, and patient outcomes. This report describes the design of the Consortium for Dural Arteriovenous Fistula Outcomes Research (CONDOR) and includes characterization of the 1077-patient cohort. METHODS Potential collaborators with established interest in the field were identified via systematic review of the literature. To ensure uniformity of data collection, a quality control process was instituted. Data were retrospectively obtained. RESULTS CONDOR comprises 14 centers in the United States, the United Kingdom, the Netherlands, and Japan that have pooled their data from 1077 dAVF patients seen between 1990 and 2017. The cohort includes 359 patients (33%) with Borden type I dAVFs, 175 (16%) with Borden type II fistulas, and 529 (49%) with Borden type III fistulas. Overall, 852 patients (79%) presented with fistula-related symptoms: 427 (40%) presented with nonaggressive symptoms such as tinnitus or orbital phenomena, 258 (24%) presented with intracranial hemorrhage, and 167 (16%) presented with nonhemorrhagic neurological deficits. A smaller proportion (224 patients, 21%), whose dAVFs were discovered incidentally, were asymptomatic. Many patients (85%, 911/1077) underwent treatment via endovascular embolization (55%, 587/1077), surgery (10%, 103/1077), radiosurgery (3%, 36/1077), or multimodal therapy (17%, 184/1077). The overall angiographic cure rate was 83% (758/911 treated), and treatment-related permanent neurological morbidity was 2% (27/1467 total procedures). The median time from diagnosis to follow-up was 380 days (IQR 120–1038.5 days). CONCLUSIONS With more than 1000 patients, the CONDOR registry represents the largest registry of cranial dAVF patient data in the world. These unique, well-annotated data will enable multiple future analyses to be performed to better understand dAVFs and their management.

OBJECTIVE Current evidence suggests that intracranial dural arteriovenous fistulas (dAVFs) without cortical venous drainage (CVD) have a benign clinical course. However, no large study has evaluated the safety and efficacy of current treatments and their impact over the natural history of dAVFs without CVD. METHODS The authors conducted an analysis of the retrospectively collected multicenter Consortium for Dural Arteriovenous Fistula Outcomes Research (CONDOR) database. Patient demographics and presenting symptoms, angiographic features of the dAVFs, and treatment outcomes of patients with Borden type I dAVFs were reviewed. Clinical and radiological follow-up information was assessed to determine rates of new intracranial hemorrhage (ICH) or nonhemorrhagic neurological deficit (NHND), worsening of venous hyperdynamic symptoms (VHSs), angiographic recurrence, and progression or spontaneous regression of dAVFs over time. RESULTS A total of 342 patients/Borden type I dAVFs were identified. The mean patient age was 58.1 ± 15.6 years, and 62% were women. The mean follow-up time was 37.7 ± 54.3 months. Of 230 (67.3%) treated dAVFs, 178 (77%) underwent mainly endovascular embolization, 11 (4.7%) radiosurgery alone, and 4 (1.7%) open surgery as the primary modality. After the first embolization, most dAVFs (47.2%) achieved only partial reduction in early venous filling. Multiple complementary interventions increased complete obliteration rates from 37.9% after first embolization to 46.7% after two or more embolizations, and 55.2% after combined radiosurgery and open surgery. Immediate postprocedural complications occurred in 35 dAVFs (15.2%) and 6 (2.6%) with permanent sequelae. Of 127 completely obliterated dAVFs by any therapeutic modality, 2 (1.6%) showed angiographic recurrence/recanalization at a mean of 34.2 months after treatment. Progression to Borden-Shucart type II or III was documented in 2.2% of patients and subsequent development of a new dAVF in 1.6%. Partial spontaneous regression was found in 22 (21.4%) of 103 nontreated dAVFs. Multivariate Cox regression analysis demonstrated that older age, NHND, or severe venous-hyperdynamic symptoms at presentation and infratentorial location were associated with worse prognosis. Kaplan-Meier curves showed no significant difference for stable/improved symptoms survival probability in treated versus nontreated dAVFs. However, estimated survival times showed better trends for treated dAVFs compared with nontreated dAVFs (288.1 months vs 151.1 months, log-rank p = 0.28). This difference was statistically significant for treated dAVFs with 100% occlusion (394 months, log-rank p < 0.001). CONCLUSIONS Current therapeutic modalities for management of dAVFs without CVD may provide better symptom control when complete angiographic occlusion is achieved.

Objectives: The pathogenesis of intracranial aneurysms is multifactorial and includes genetic, environmental, and anatomic influences. We aimed to identify image-based morphological parameters that were associated with middle cerebral artery (MCA) bifurcation aneurysms. Materials and methods: We evaluated three-dimensional morphological parameters obtained from CT angiography (CTA) or digital subtraction angiography (DSA) from 317 patients with unilateral MCA bifurcation aneurysms diagnosed at the Brigham and Women's Hospital and Massachusetts General Hospital between 1990 and 2016. We chose the contralateral unaffected MCA bifurcation as the control group, in order to control for genetic and environmental risk factors. Diameters and angles of surrounding parent and daughter vessels of 634 MCAs were examined. Results: Univariable and multivariable statistical analyses were performed to determine statistical significance. Sensitivity analyses with smaller (≤ 3 mm) aneurysms only and with angles excluded, were also performed. In a multivariable conditional logistic regression model we showed that smaller diameter size ratio (OR 0.0004, 95% CI 0.0001–0.15), larger daughter-daughter angles (OR 1.08, 95% CI 1.06–1.11) and larger parent-daughter angle ratios (OR 4.24, 95% CI 1.77–10.16) were significantly associated with MCA aneurysm presence after correcting for other variables. In order to account for possible changes to the vasculature by the aneurysm, a subgroup analysis of small aneurysms (≤ 3 mm) was performed and showed that the results were similar. Conclusions: Easily measurable morphological parameters of the surrounding vasculature of the MCA may provide objective metrics to assess MCA aneurysm formation risk in high-risk patients.

We present a cohort of patients with anterior communicating artery (ACoA) aneurysms to investigate morphological characteristics and clinical factors associated with rupture of the aneurysms. 505 patients with ACoA aneurysms were identified at the Brigham and Women’s Hospital and Massachusetts General Hospital between 1990 and 2016, with available CT angiography (CTA). Three-dimensional (3D) reconstructions were performed to evaluate aneurysmal morphologic features, including location, projection, irregularity, the presence of daughter dome, height, height/width ratio, and relationships between surrounding vessels. Patient risk factors assessed included patient age, sex, tobacco use, alcohol use, and family history of aneurysms and aneurysmal subarachnoid hemorrhage. Logistic regression was used to build a predictive ACoA score for rupture. Morphologic features associated with ruptured ACoA aneurysms were the presence of a daughter dome (OR 21.4, 95% CI 10.6–43.1), smaller neck diameter (OR 0.55, 95% CI 0.42–0.71), larger aspect ratio (OR 3.57, 95% CI 2.05–6.24), larger flow angle (OR 1.03, 95% CI 1.02–1.05), and smaller ipsilateral A2-ACoA angle (OR 0.98, 95% CI 0.97–1.00). Tobacco use was predominantly associated with morphological factors intrinsic to the aneurysm that were associated with rupture while younger age was also associated with morphologic features extrinsic to the aneurysm that were associated with rupture. The ACoA score had good predictive capacity for rupture with AUC = 0.92 using the 0.632 bootstrap cross-validation for correction of overfitting bias. Ruptured ACoA aneurysms were associated with morphological features that are simple to assess using a simple scoring system. Tobacco use and younger age were predominantly associated with intrinsic and extrinsic morphological features characteristic of rupture, respectively.

Morphological factors of intracranial aneurysms and the surrounding vasculature could affect aneurysm rupture risk in a location specific manner. Our goal was to identify image-based morphological parameters that correlated with ruptured basilar tip aneurysms. Three-dimensional morphological parameters obtained from CT-angiography (CTA) or digital subtraction angiography (DSA) from 200 patients with basilar tip aneurysms diagnosed at the Brigham and Women’s Hospital and Massachusetts General Hospital between 1990 and 2016 were evaluated. We examined aneurysm wall irregularity, the presence of daughter domes, hypoplastic, aplastic or fetal PCoAs, vertebral dominance, maximum height, perpendicular height, width, neck diameter, aspect and size ratio, height/width ratio, and diameters and angles of surrounding parent and daughter vessels. Univariable and multivariable statistical analyses were performed to determine statistical significance. In multivariable analysis, presence of a daughter dome, aspect ratio, and larger flow angle were significantly associated with rupture status. We also introduced two new variables, diameter size ratio and parent-daughter angle ratio, which were both significantly inversely associated with ruptured basilar tip aneurysms. Notably, multivariable analyses also showed that larger diameter size ratio was associated with higher Hunt-Hess score while smaller flow angle was associated with higher Fisher grade. These easily measurable parameters, including a new parameter that is unlikely to be affected by the formation of the aneurysm, could aid in screening strategies in high-risk patients with basilar tip aneurysms. One should note, however, that the changes in parameters related to aneurysm morphology may be secondary to aneurysm rupture rather than causal.

Background and Objectives:Subarachnoid hemorrhage from cerebral aneurysm remains a devastating disease with high mortality and morbidity. Cerebral aneurysm and its rupture are more prevalent in post-menopausal women and have been postulated to be hormonally influenced. The goal of this study was to investigate the associations of female-specific factors, including reproductive life span, age at menarche, and age at menopause, with the incidence of aneurysmal subarachnoid hemorrhage (aSAH) in women.Methods:Participants in the Nurses’ Health Study were followed from 1980 or the time of reaching menopause until 2018, Only women with natural menopause or surgical menopause due to bilateral oophorectomy were included. Reproductive life span was defined by subtracting the age at menarche from the age at menopause. Multivariable stratified proportional hazards models were used to study reproductive life span, age at menarche and age at menopause with the incidence of aSAH. Multivariable models were adjusted for age, race, smoking, hysterectomy, hypertension, hyperlipidemia, body mass index, hormone therapy use, oral contraceptive use, and parity.Results:A total of 97,398 postmenopausal women with reproductive lifespan data were included, with 138 participants developed aneurysmal subarachnoid hemorrhage which was confirmed on medical record review by a physician. A shorter reproductive lifespan (≤35 years) was associated with a two-fold higher incidence of aSAH after multivariable adjustment (HR=2.0 [95%CI 1.4-2.8]). Early age at menopause (ageDiscussion:An earlier age at menopause, as well as a shorter reproductive life span duration (≤35 years), were associated with a higher risk of incident aSAH in women. No associations were noted for age at menarche, parity, oral contraceptive use or postmenopausal therapy use.

BACKGROUND: Low-grade intracranial dural arteriovenous fistulas (dAVF) have a benign natural history in the majority of cases. The benefit from treatment of these lesions is controversial.OBJECTIVE: To compare the outcomes of observation versus intervention for low-grade dAVFs.METHODS: We retrospectively reviewed dAVF patients from institutions participating in the CONsortium for Dural arteriovenous fistula Outcomes Research (CONDOR). Patients with low-grade (Borden type I) dAVFs were included and categorized into intervention or observation cohorts. The intervention and observation cohorts were matched in a 1:1 ratio using propensity scores. Primary outcome was modified Rankin Scale (mRS) at final follow-up. Secondary outcomes were excellent (mRS 0-1) and good (mRS 0-2) outcomes, symptomatic improvement, mortality, and obliteration at final follow-up.RESULTS: The intervention and observation cohorts comprised 230 and 125 patients, respectively. We found no differences in primary or secondary outcomes between the 2 unmatched cohorts at last follow-up (mean duration 36 mo), except obliteration rate was higher in the intervention cohort (78.5% vs 24.1%, P < .001). The matched intervention and observation cohorts each comprised 78 patients. We also found no differences in primary or secondary outcomes between the matched cohorts except obliteration was also more likely in the matched intervention cohort (P < .001). Procedural complication rates in the unmatched and matched intervention cohorts were 15.4% and 19.2%, respectively.CONCLUSION: Intervention for low-grade intracranial dAVFs achieves superior obliteration rates compared to conservative management, but it fails to improve neurological or functional outcomes. Our findings do not support the routine treatment of low-grade dAVFs.

Background Arteriovenous malformation (AVM) rupture is highly morbid. Outcomes after AVM rupture differ from other types of brain hemorrhage. There are no specific widely used grading systems designed to predict clinical outcome after AVM rupture. Objective To develop an all-comers scoring system to grade patients with AVM rupture and predict clinical outcome more accurately than grading systems currently in use. Methods We retrospectively reviewed patients who presented to our institution with a ruptured AVM. Using change in modified Rankin Score (mRS) as our response variable, we generated an ordinal logistic regression model to test for significant predictor variables. The full model was sequentially condensed until the simplest model with the highest area under the receiver operating curve (AUROC) was achieved. Results A total of 115 patients who presented with ruptured AVMs were included in the study, with a mean follow-up time of 4 yr. The Ruptured AVM Grading Scale (RAGS) consists of the Hunt and Hess (HH) score (1-5), patient age ( 70 = 2), deep venous drainage (1), and eloquence (1). The RAGS score outperformed other neurosurgical grading scales in predicting change in mRS, with an AUROC greater than 0.80 across all follow-up periods. Conclusion The RAGS score is a simple extension of the HH scale that predicts clinical outcome after AVM rupture more accurately than other grading systems.

BackgroundAnterior cranial fossa dural arteriovenous fistulas (ACF-dAVFs) are aggressive vascular lesions. The pattern of venous drainage is the most important determinant of symptoms. Due to the absence of a venous sinus in the anterior cranial fossa, most ACF-dAVFs have some degree of drainage through small cortical veins. We describe the natural history, angiographic presentation and outcomes of the largest cohort of ACF-dAVFs.MethodsThe CONDOR consortium includes data from 12 international centers. Patients included in the study were diagnosed with an arteriovenous fistula between 1990–2017. ACF-dAVFs were selected from a cohort of 1077 arteriovenous fistulas. The presentation, angioarchitecture and treatment outcomes of ACF-dAVF were extracted and analyzed.Results60 ACF-dAVFs were included in the analysis. Most ACF-dAVFs were symptomatic (38/60, 63%). The most common symptomatic presentation was intracranial hemorrhage (22/38, 57%). Most ACF-dAVFs drained through cortical veins (85%, 51/60), which in most instances drained into the superior sagittal sinus (63%, 32/51). The presence of cortical venous drainage predicted symptomatic presentation (OR 9.4, CI 1.98 to 69.1, p=0.01). Microsurgery was the most effective modality of treatment. 56% (19/34) of symptomatic patients who were treated had complete resolution of symptoms. Improvement of symptoms was not observed in untreated symptomatic ACF-dAVFs.ConclusionMost ACF-dAVFs have a symptomatic presentation. Drainage through cortical veins is a key angiographic feature of ACF-dAVFs that accounts for their malignant course. Microsurgery is the most effective treatment. Due to the high risk of bleeding, closure of ACF-dAVFs is indicated regardless of presentation.

BackgroundThe presence of angiographic vasospasm after aneurysmal subarachnoid hemorrhage (aSAH) is associated with delayed-cerebral ischemia (DCI)-related cerebral infarction and worsened neurological outcome. Transcranial doppler (TCD) measurements of cerebral blood velocity are commonly used after aSAH to screen for vasospasm. We sought to determine whether time-varying TCD measured vasospasm severity is associated with cerebral infarction and to investigate the performance characteristics of different time/severity cutoffs for predicting cerebral infarction.MethodsWe used a retrospective, single-center cohort of consecutive adult aSAH patients with angiographic vasospasm and at least one TCD study. Our primary outcome was DCI-related cerebral infarction, defined as an infarction developing at least 2 days after any surgical intervention without an alternative cause. Time-varying TCD vasospasm severity was defined ordinally (absent, mild, moderate, severe) by the most abnormal vessel on each post-admission hospital day. Cox proportional-hazards models were used to examine associations between time-varying vasospasm severity and infarction. The optimal TCD-based time/severity thresholds for predicting infarction were then identified using the Youden J statistic.ResultsOf 218 aSAH patients with angiographic vasospasm, 27 (12%) developed DCI-related infarction. As compared to those without infarction, patients with infarction had higher modified Fisher scale (mFS) scores, and an earlier onset of more-severe vasospasm. Adjusted for mFS, vasospasm severity was associated with infarction (aHR 1.9, 95% CI: 1.3-2.6). A threshold of at least mild vasospasm severity on hospital day 4 had a negative predictive value of 92% for the development of infarction, but a positive predictive value of 25%.ConclusionsIn aSAH, TCD-measured vasospasm severity is associated with DCI-related infarction. In a single-center dataset, a TCD-based threshold for predicting infarction had a high negative predictive value, supporting its role as an early screening tool to identify at-risk patients.

BackgroundAlthough the liquid embolic agent, Onyx, is often the preferred embolic treatment for cerebral dural arteriovenous fistulas (DAVFs), there have only been a limited number of single-center studies to evaluate its performance.ObjectiveTo carry out a multicenter study to determine the predictors of complications, obliteration, and functional outcomes associated with primary Onyx embolization of DAVFs.MethodsFrom the Consortium for Dural Arteriovenous Fistula Outcomes Research (CONDOR) database, we identified patients who were treated for DAVF with Onyx-only embolization as the primary treatment between 2000 and 2013. Obliteration rate after initial embolization was determined based on the final angiographic run. Factors predictive of complete obliteration, complications, and functional independence were evaluated with multivariate logistic regression models.ResultsA total 146 patients with DAVFs were primarily embolized with Onyx. Mean follow-up was 29 months (range 0–129 months). Complete obliteration was achieved in 80 (55%) patients after initial embolization. Major cerebral complications occurred in six patients (4.1%). At last follow-up, 84% patients were functionally independent. Presence of flow symptoms, age over 65, presence of an occipital artery feeder, and preprocedural home anticoagulation use were predictive of non-obliteration. The transverse-sigmoid sinus junction location was associated with fewer complications, whereas the tentorial location was predictive of poor functional outcomes.ConclusionsIn this multicenter study, we report satisfactory performance of Onyx as a primary DAVF embolic agent. The tentorium remains a more challenging location for DAVF embolization, whereas DAVFs located at the transverse-sigmoid sinus junction are associated with fewer complications.

Infectious intracranial aneurysms (IIAs), or mycotic aneurysms, are infectious inflammatory lesions that can cause devastating neurological damage or death. Recent systemic reviews have suggested endovascular treatment to be efficacious for IIA management.To compare the safety profile of different endovascular methods for treating ruptured and unruptured IIAs and factors associated with good clinical and radiographic outcomes.We conducted a retrospective single study of endovascularly treated ruptured and unruptured IIAs between 2003 and 2019. Univariate and multivariate analyses were used to study patient presentation, endovascular treatments used, and clinical and radiographic outcomes.Thirty-eight patients with ruptured (n = 20) and unruptured (n = 18) IIAs treated with endovascular methods were included. One patient required retreatment after aneurysm recanalization, and 2 patients demonstrated new infarcts after embolization. There was no postprocedural radiographic hemorrhage or infarct and no difference in clinical and radiographic outcomes comparing treatment modality. Hypertension was associated with ruptured IIA status and worse clinical outcome at 6 mo (odds ratio: 0.03 [95% confidence interval: 0.002-0.52]).In this study, the largest single-center series to date, we showed that endovascular intervention is a safe and effective strategy for both ruptured and unruptured IIAs. Hypertension was associated with ruptured status and worse clinical outcome. Procedures are generally well-tolerated and safe, with good outcomes for patients.

Acute myocardial infarction (AMI) is the rarest and least studied cardiac complication of aneurysmal subarachnoid hemorrhage (aSAH). Precise estimates of the incidence of AMI after aSAH are unavailable. Our goal was to estimate the incidence of registry-based AMI (rb-AMI) after aSAH and determine its association with clinical outcomes.Adult patients with aSAH in the National Inpatient Samples from 2002 to 2014 were included in the study. We evaluated risk factors for rb-AMI using univariate and multivariate regression models. Clinical outcomes that were assessed included functional status at discharge, in-patient mortality, length of stay, and total hospitalization cost, adjusting for patient demographics and cardiovascular risk factors through an inverse probability weighted analysis. Subgroup analyses were further performed stratified by rb-AMI type (ST-segment elevation myocardial infarction [STEMI] vs. non-STEMI [NSTEMI]).A total of 139,734 patients with aSAH were identified, 3.6% of whom had rb-AMI. NSTEMI was the most common type of rb-AMI occurring after aSAH (71% vs. 29% for NSTEMI vs. STEMI, respectively). Patient characteristics associated with higher odds of rb-AMI included age, female sex, poor aSAH grade, and various cardiovascular risk factors. Rb-AMI was also associated with poor functional status at discharge, higher in-hospital mortality, and a longer and more costly hospital stay.Rb-AMI occurs in 3.6% of patients with aSAH and is associated with poor functional status at discharge, higher in-patient mortality, and a longer and more costly hospitalization. Differentiating between different types of rb-AMI would be important in optimizing the management of patients with aSAH. Our definition of rb-AMI likely includes patients with neurogenic stress cardiomyopathy, which may confound the results.

Hemodynamic stress is thought to play an important role in the formation of intracranial aneurysms, which is conditioned by the geometry of the surrounding vasculature. Our goal was to identify image-based morphological parameters that were associated with basilar artery tip aneurysms (BTA) in a location-specific manner. Three-dimensional morphological parameters obtained from CT-angiography (CTA) or digital subtraction angiography (DSA) from 207 patients with BTAs and a control group of 106 patients with aneurysms elsewhere to control for non-morphological factors, who were diagnosed at the Brigham and Women’s Hospital and Massachusetts General Hospital between 1990 and 2016, were evaluated. We examined the presence of hypoplastic, aplastic or fetal PCoAs, vertebral dominance, and diameters and angles of surrounding parent and daughter vessels. Univariable and multivariable statistical analyses were performed to determine statistical significance. Sensitivity analyses with small (≤ 3 mm) aneurysms only and with angles excluded, were also performed. In multivariable analysis, daughter–daughter angle was directly, and parent artery diameter and diameter size ratio were inversely associated with BTAs. These results remained significant in the subgroup analysis of small aneurysms (width ≤ 3 mm) and when angles were excluded. These easily measurable and robust parameters that are unlikely to be affected by aneurysm formation could aid in risk stratification for the formation of BTAs in high-risk patients.