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Purpose Flow diverting stents have revolutionized the treatment of intracranial aneurysms through endoluminal reconstruction of the parent vessel. Despite this, certain aneurysms require retreatment. The purpose of this study was to identify clinical and radiologic determinants of aneurysm retreatment following flow diversion. Methods A multicenter flow diversion database was evaluated to identify patients presenting with an unruptured, previously untreated aneurysm with a minimum of 12 months’ clinical and angiographic follow-up. Univariate and multivariate logistic regression modeling was performed to identify determinants of retreatment. Results We identified 189 aneurysms treated in 189 patients with a single flow-diverting stent. Mean age was 54 years, and 89% were female. Complete occlusion was achieved in 70.3% and 83.6% of patients at six and 12 months, respectively. Aneurysm retreatment with additional flow-diverting stents occurred in 5.8% of cases. Univariate analysis revealed that dome diameter [Formula: see text]10 mm ( p = 0.012), pre-clinoid internal carotid artery location ( p = 0.012), distal > proximal parent vessel diameter ( p = 0.042), and later dual antiplatelet therapy (DAPT) discontinuation ( p Conclusions Prolonged DAPT is the most important determinant of aneurysm retreatment following single-device flow diversion. Abbreviating DAPT duration to only six months should be a consideration in this population, especially for patients with a large aneurysm dome diameter.

BackgroundBleb presence in intracranial aneurysms (IAs) is a known indication of instability and vulnerability.ObjectiveTo develop and evaluate predictive models of bleb development in IAs based on hemodynamics, geometry, anatomical location, and patient population.MethodsCross-sectional data (one time point) of 2395 IAs were used for training bleb formation models using machine learning (random forest, support vector machine, logistic regression, k-nearest neighbor, and bagging). Aneurysm hemodynamics and geometry were characterized using image-based computational fluid dynamics. A separate dataset with 266 aneurysms was used for model evaluation. Model performance was quantified by the area under the receiving operating characteristic curve (AUC), true positive rate (TPR), false positive rate (FPR), precision, and balanced accuracy.ResultsThe final model retained 18 variables, including hemodynamic, geometrical, location, multiplicity, and morphology parameters, and patient population. Generally, strong and concentrated inflow jets, high speed, complex and unstable flow patterns, and concentrated, oscillatory, and heterogeneous wall shear stress patterns together with larger, more elongated, and more distorted shapes were associated with bleb formation. The best performance on the validation set was achieved by the random forest model (AUC=0.82, TPR=91%, FPR=36%, misclassification error=27%).ConclusionsBased on the premise that aneurysm characteristics prior to bleb formation resemble those derived from vascular reconstructions with their blebs virtually removed, machine learning models can identify aneurysms prone to bleb development with good accuracy. Pending further validation with longitudinal data, these models may prove valuable for assessing the propensity of IAs to progress to vulnerable states and potentially rupturing.

The Woven EndoBridge (WEB) can be used to treat wide-necked aneurysms without antiplatelet medications, suggesting it may have advantages in the setting of aneurysmal subarachnoid hemorrhage (aSAH). The goal was assessment of safety and efficacy of WEB in aSAH given the delayed nature of aneurysmal thrombosis. An international retrospective analysis of patients with aSAH treated with WEB was conducted at 7 tertiary centers from 2016 to 2020. Outcomes included rates of rebleeding, retreatment, complications, and complete occlusion. Furthermore, a systematic review and meta-analysis was conducted from 2011 to 2020 assessing the same outcomes. All pooled event rates were calculated using a random effect model. Consecutive patients with aSAH harbored 25 aneurysms that were treated with 29 WEB devices. The mean age was 53 years, and 65% were female. Zero experienced rebleeding, 2 were retreated, 2 experienced complications, 16 were completely occluded at 3 months, and 21 were completed occluded at 9–12 months. Meta-analysis of 309 WEB treatments for aSAH from 7 case series revealed 2.5% (95% CI 1–5%) had rebleeding, 9% (95% CI 4–17%) were retreated, 17% (95% CI 10–30%) had complications, and 61% (95% CI 51–71%) were completely occluded at 3–6 months. WEB embolization in the setting of aSAH provides similar protection against rebleeding with comparable retreatment rates to traditional approaches. However, there is a higher rate of incomplete radiographic occlusion and operative complications compared to WEB embolization of unruptured aneurysms. Long-term prospective studies are needed to fully delineate the role of WEB embolization in aSAH.

Background Transradial access for neurointerventional procedures was adopted and modified from cardiovascular intervention and is increasingly established as a safe and effective alternative to transfemoral catheterization. As social media influences public opinion on medical treatment, this study analyzes Twitter conversations to elucidate social media’s depiction of transradial access as a neurointerventional tool. Materials and methods Twitter hashtags #RadialFirst and #RadialForNeuro were evaluated using a mixed-method analysis of quantitative social media metrics and qualitative thematic analysis. Results Between January 2015 and April 2020, 104,146 tweets from 141 countries employed the hashtag #RadialFirst (2015 (1); 2016 (0); 2017 (22,804); 2018 (33,074); 2019 (38,352); 2020 (9,915 January-April)). These generated 226,909,374 impressions and were retweeted 80,120 times by 13,707 users. Media was present in 62.5% of tweets (e.g. wrist image, angiographic runs) but only 14.5% had a reference article. Physicians authored 70.8% of tweets; interventional cardiologists accounted for 83% of top 100 influencers. #RadialForNeuro is more nascent (6 posts in 2019; 323 posts January–April 2020), with 392,662 impressions, and 254 retweets by 177 users; physicians authored 35.6%. Compared to #RadialFirst, #RadialforNeuro tweets were more likely to include media (76%), less likely to include citations (9.7%), and more likely to discuss complications and troubleshooting techniques. Conclusion Twitter activity regarding transradial access permits information dissemination and discussion on approach benefits and challenges. However, many posts arise from non-physician sources and lack links to peer-reviewed publication. The public should be mindful that tweets may reflect opinions, rather than experience or scientific evidence.

Background Following non-traumatic subarachnoid hemorrhage (SAH), in-hospital delayed cerebral ischemia is predicted by two chief events on continuous EEG (cEEG): new or worsening epileptiform abnormalities (EAs) and deterioration of cEEG background frequencies. We evaluated the association between longitudinal outcomes and these cEEG biomarkers. We additionally evaluated the association between longitudinal outcomes and other in-hospital complications. Methods Patients with nontraumatic SAH undergoing ≥ 3 days of cEEG monitoring were enrolled in a prospective study evaluating longitudinal outcomes. Modified Rankin Scale (mRS) was assessed at discharge, and at 3- and 6-month follow-up time points. Adjusting for baseline severity in a cumulative proportional odds model, we modeled the mRS ordinally and measured the association between mRS and two forms of in-hospital cEEG deterioration: (1) cEEG evidence of new or worsening epileptiform abnormalities and (2) cEEG evidence of new background deterioration. We compared the magnitude of these associations at each time point with the association between mRS and other in-hospital complications: (1) delayed cerebral ischemia (DCI), (2) hospital-acquired infections (HAI), and (3) hydrocephalus. In a secondary analysis, we employed a linear mixed effects model to examine the association of mRS over time (dichotomized as 0–3 vs. 4–6) with both biomarkers of cEEG deterioration and with other in-hospital complications. Results In total, 175 mRS assessments were performed in 59 patients. New or worsening EAs developed in 23 (39%) patients, and new background deterioration developed in 24 (41%). Among cEEG biomarkers, new or worsening EAs were independently associated with mRS at discharge, 3, and 6 months, respectively (adjusted cumulative proportional odds 4.99, 95% CI 1.60–15.6; 3.28, 95% CI 1.14–9.5; and 2.71, 95% CI 0.95–7.76), but cEEG background deterioration lacked an association. Among hospital complications, DCI was associated with discharge, 3-, and 6-month outcomes (adjusted cumulative proportional odds 4.75, 95% CI 1.64–13.8; 3.4; 95% CI 1.24–9.01; and 2.45, 95% CI 0.94–6.6), but HAI and hydrocephalus lacked an association. The mixed effects model demonstrated that these associations were sustained over longitudinal assessments without an interaction with time. Conclusion Although new or worsening EAs and cEEG background deterioration have both been shown to predict DCI, only new or worsening EAs are associated with a sustained impairment in functional outcome. This novel finding raises the potential for identifying therapeutic targets that may also influence outcomes. Electronic supplementary material The online version of this article (10.1007/s12028-020-01177-x) contains supplementary material, which is available to authorized users.

BackgroundFlow diversion is a common endovascular treatment for cerebral aneurysms, but studies comparing different types of flow diverters are scarce.ObjectiveTo perform a propensity score matched cohort study comparing the Pipeline Embolization Device (PED) and Flow Redirection Intraluminal Device (FRED) for posterior circulation aneurysms.MethodsConsecutive aneurysms of the posterior circulation treated at 25 neurovascular centers with either PED or FRED were collected. Propensity score matching was used to control for age, duration of follow-up imaging, adjunctive coiling, and aneurysm location, size, and morphology; previously ruptured aneurysms were excluded. The two devices were compared for the following outcomes: procedural complications, aneurysm occlusion, and functional outcome.ResultsA total of 375 aneurysms of the posterior circulation were treated in 369 patients. The PED was used in 285 (77.2%) and FRED in 84 (22.8%) procedures. Aneurysms treated with the PED were more commonly fusiform and larger than those treated with FRED. To account for these important differences, propensity score matching was performed resulting in 33 PED and FRED unruptured aneurysm pairs. No differences were found in occlusion status and neurologic thromboembolic or hemorrhagic complications between the two devices. The proportion of patients with favorable functional outcome was higher with FRED (100% vs 87.9%, p=0.04).ConclusionComparative analysis of PED and FRED for the treatment of unruptured posterior circulation aneurysms did not identify significant differences in aneurysm occlusion or neurologic complications. Variations in functional outcomes warrant additional investigations.

OBJECTIVEDegenerative cerebral aneurysm walls are associated with aneurysm rupture and subarachnoid hemorrhage. Thin-walled regions (TWRs) represent fragile areas that may eventually lead to aneurysm rupture. Previous computational fluid dynamics (CFD) studies reported the correlation of maximum pressure (Pmax) areas and TWRs; however, the correlation with aneurysm rupture has not been established. This study aims to investigate this hemodynamic correlation.METHODSThe aneurysmal wall surface at the Pmax areas was intraoperatively evaluated using a fluid flow formula under pulsatile blood flow conditions in 23 patients with 23 saccular middle cerebral artery (MCA) bifurcation aneurysms (16 unruptured and 7 ruptured). The pressure difference (Pd) at the Pmax areas was calculated by subtracting the average pressure (Pave) from the Pmax and normalized by dividing this by the dynamic pressure at the aneurysm inlet side. The wall shear stress (WSS) was also calculated at the Pmax areas, aneurysm dome, and parent artery. These hemodynamic parameters were used to validate the correlation with TWRs in unruptured MCA aneurysms. The characteristic hemodynamic parameters at the rupture points in ruptured MCA aneurysms were then determined.RESULTSIn 13 of 16 unruptured aneurysms (81.2%), Pmax areas were identified that corresponded to TWRs. In 5 of the 7 ruptured cerebral aneurysms, the Pmax areas coincided with the rupture point. At these areas, the Pd values were not higher than those of the TWRs in unruptured cerebral aneurysms; however, minimum WSS, time-averaged WSS, and normalized WSS at the rupture point were significantly lower than those of the TWRs in unruptured aneurysms (p < 0.01).CONCLUSIONSAt the Pmax area of TWRs, decreased WSS appears to be the crucial hemodynamic parameter that indicates the risk of aneurysm rupture.

Flow diversion is a safe and effective treatment for many types of brain aneurysms. Even so, there remain some aneurysms that persist despite initial treatment. In studies with the longest follow-up (5 yr), at least 5% of aneurysms persist with this treatment modality. As the cumulative experience and clinical indications for flow diversion continue to expand, the anatomic and functional characteristics that are associated with aneurysm persistence are increasingly described. Identification of these factors preoperatively can help to guide initial treatment decisions, enhance monitoring protocols in the follow-up period, and establish best practices for re-treatment when necessary. Herein, we review published clinical series and provide examples to highlight variables implicated in aneurysm persistence after treatment with flow diversion.

Symptomatic cervical spinal stenosis and carotid artery stenosis are common neurosurgical diseases, but little is known about the management of their concurrent presentation. We present a 62 year-old woman with a precipitous decline in bilateral lower extremity strength, dexterity, and gait, and a 2-year history of amaurosis fugax. She was found to have cervical stenosis at C5-C7 with cord compression, lumbar stenosis at L3-L5 with a right L4-L5 synovial cyst, and moderate right internal carotid artery stenosis of 50–70%. The patient underwent a staged procedure. Stage 1 was a simultaneous right carotid endarterectomy and C6 corpectomy with C5-C7 anterior fusion. Stage 2 was a C3-T1 posterior decompression and fusion and L3-L5 decompression with synovial cyst removal. The presentation of concurrent cervical stenosis and CAS is likely underappreciated. Deciding between simultaneous or staged CEA and spinal decompression should be based on a careful risk-benefit assessment and tailored to the relative severity of symptoms, patient anatomy and comorbidities.

Background and Purpose: Dural arteriovenous fistulae can present with hemorrhage, but there remains a paucity of data regarding subsequent outcomes. We sought to use the CONDOR (Consortium for Dural Arteriovenous Fistula Outcomes Research), a multi-institutional registry, to characterize the morbidity and mortality of dural arteriovenous fistula–related hemorrhage. Methods: A retrospective review of patients in CONDOR who presented with dural arteriovenous fistula–related hemorrhage was performed. Patient characteristics, clinical follow-up, and radiographic details were analyzed for associations with poor outcome (defined as modified Rankin Scale score ≥3). Results: The CONDOR dataset yielded 262 patients with incident hemorrhage, with median follow-up of 1.4 years. Poor outcome was observed in 17.0% (95% CI, 12.3%–21.7%) at follow-up, including a 3.6% (95% CI, 1.3%–6.0%) mortality. Age and anticoagulant use were associated with poor outcome on multivariable analysis (odds ratio, 1.04, odds ratio, 5.1 respectively). Subtype of hemorrhage and venous shunting pattern of the lesion did not affect outcome significantly. Conclusions: Within the CONDOR registry, dural arteriovenous fistula–related hemorrhage was associated with a relatively lower morbidity and mortality than published outcomes from other arterialized cerebrovascular lesions but still at clinically consequential rates.

A 70-year-old gentleman with history of hypothyroidism, hyperlipidemia, hypertension, and right superior cerebellar aneurysm presented to the neurosurgery service in 2008 with vertigo. Diagnostic cerebral angiography performed that year demonstrated a vermian arteriovenous malformations (AVM). The patient underwent stereotactic proton beam radiosurgery, which resulted in a decrease in flow and size of the lesion, and the patient was lost to follow-up. Now at the age of 80, the patient presented with acute gait instability. Cerebral angiogram demonstrated his stable vermian AVM and a new 1.1 cm AVM nidus in the region of the left posterior thalamus. Although AVMs are often described as congenital lesions, there is a growing body of literature suggesting that AVMs can grow, spontaneously regress, and even arise de novo in response to some insult. Understanding what leads to the growth, remodeling, regression, and hemorrhage of AVMs is crucial in order to better direct therapeutic endeavors. We would argue that this patient's AVM is secondary to endothelial cell damage from radiation therapy. Radiation can cause endothelial cell injury and upregulation of factors, such as vascular endothelial growth factor and transforming growth factor beta expression, which are implicated in AVM development pathways. We believe that this patient's new AVM is secondary to entrance radiation dosing affecting the thalamus during radiation therapy for the original vermian AVM.

BACKGROUND: Recurrent atypical and malignant meningiomas have poor outcomes with surgical therapy alone. Neither adjuvant chemotherapy nor postoperative radiation therapy remedies this problem. OBJECTIVE: To evaluate our experience with the treatment of 15 patients treated with I-125 or Cs-131 brachytherapy radiation seeds as an adjuvant in these difficult cases. METHODS: Patients with high-grade recurrent meningioma who underwent resection and intraoperative placement of brachytherapy seeds at our institution from 2002 to 2014 were identified and studied by retrospective chart review. RESULTS: Fifteen patients with median age of 68.8 yr were treated with I-125 (n = 13) or Cs-131 (n = 2) brachytherapy seeds for cases of recurrent, grade II (n = 8), or grade III (n = 7) meningioma at our institution from 2002 to 2014. These lesions originated from a variety of locations including, convexity (3), falcine (3), frontal (2), occipital (1), parietal (2), 2 sphenoid wing (2), and temporal (2), based recurrent meningiomas. Patients had a median of 2 prior open surgical interventions and received local radiation therapy with a median dose of 55 Gy prior to brachytherapy. Survival at 2.5 yr was 56% for grade II and 17% for grade III lesions. Survival was significantly associated with patient age but not tumoral pathology. Forty percent of patients required reoperations for wound complications following brachytherapy. CONCLUSION: Brachytherapy with implantation of permanent radiation seeds provides a viable alternative treatment for recurrent meningioma while carrying a significant clinical risk of wound infection and need for reoperation.

Arteriovenous malformations (AVMs) of the central nervous system are dynamic lesions that can change with time. One of the most clinically important concerns is the development and potential rupture of AVM-associated aneurysms. In this report, we review pediatric cases of de novo development of AVM-associated aneurysms in 2 children and present the relevant clinical and radiographic records. These 2 cases, coupled with a review of the current literature, offer insight into the risks of AVMs in children and underline the importance of timely treatment of appropriate cases.

In this study, we derived and validated a composite EBI risk score. In addition to confirming the importance of EBI in determining long-term SAH recovery, the risk score could be used for patient selection or risk stratification in future clinical trials. The score was derived and validated in 2 independent cohorts, highlighting its ability to perform across separate patient populations. Future studies should focus on validating the application of EBI in clinical settings, examining other biomarkers in addition to sST2, and deepening our understanding of the pathophysiologic factors that lead to EBI and impact patient outcomes.

Background Recently, the American Academy of Otolaryngology-Head and Neck Surgery Foundation (AAO-HNSF) published evidence-based recommendations to improve the quality and management variation for patients who suffer from epistaxis, however, there were no clear guidelines on timing and techniques of endovascular management. Methods A systematic review and meta-analysis in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Our primary outcome was the proportion of patients who had immediate bleeding control after endovascular management. Secondary outcomes included percentage of major adverse events following embolization. Sensitivity analysis was conducted according to center protocol (materials used, unilateral vs. bilateral approach, and timing of treatment). Results Fourteen case series (with 719 patients) met our inclusion criteria for primary and secondary outcome. The pooled event rate for immediate control was 86% (95% confidence interval [CI], 82%-89%). Major adverse events (stroke, craniofacial skin necrosis, and retro-peritoneal hemorrhage) had an overall event rate of 2.4% (95% CI 1.4%-4%). Most embolizations were targeting distal portion of the internal maxillary (>95% of cases). Sensitivity analysis revealed that bilateral approaches were associated with less recurrence rates, however, higher rates of major adverse events were notes. Several factors were identified for heterogeneity between studies, including outcomes definitions, follow-up time, angiographic protocol, target vessels and embolization’s materials. Conclusions The best available evidence for endovascular management of epistaxis is based on retrospective observational studies. Deficiency of standardized reporting methods is a significant drawback to understand the exact role of endovascular treatment for epistaxis and whether it is superior to other operative methods. Disclosures N. Alotaibi: None. P. Harker: None. F. Robertson: None. J. Vranic: None. M. Koch: None. C. Stapleton: None. T. Leslie-Mazwi: None. A. Patel: None.

Background Compared to stent-assisted coiling the Woven EndoBridge (WEB) device offers the advantage of treatment of wide-necked aneurysms without antiplatelet medications. However, the safety and efficacy of WEB is yet to be fully defined in the setting of aneurysmal subarachnoid hemorrhage (aSAH), given concerns regarding the delayed nature of aneurysm thrombosis. Methods The search protocol was developed a priori according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A literature search using the OVID Medline, Embase, Web of Science, and Cochrane Library databases from inception to February 2020 was performed using relevant key words to identify cases of aSAH that were treated with WEB. The primary outcome measure was radiographic complete occlusion rates. Secondary outcomes included rebleeding and complications rates. All pooled event rates were calculated using random effect model. Results Six articles, all of which were observational case series, representing 261 ruptured aneurysms were included for analysis (average follow up time was 4 months). Most of these aneurysms were in the anterior circulation (>60%). The likelihood of a complete radiographic occlusion following WEB for ruptured aneurysms was 66.6% (95% CI 47–74%). Rebleeding rates were 2.8% (95% CI 1–6%). The pooled event rate for complications (procedural aneurysm rupture, thromboembolic, and device protrusion in the parent artery) across five studies was 17.9% (95% CI 9–32%). Overall retreatment rates were 10% (95% CI 4–22%) and the need for early or delayed stent placement was 5% (95% CI 1–12%). There was no significant heterogeneity between studies in rebleeding and stent placement outcomes (I2 Conclusion The WEB device in aSAH appears to provide similar protection against rebleeding and retreatment rates that are comparable to traditional approaches; however, there is a higher rate of incomplete radiographic occlusion and operative complications. Long-term prospective studies are needed to fully delineate the role of WEB embolization in aSAH. Disclosures N. Alotaibi: None. P. Harker: None. F. Robertson: None. J. Vranic: None. M. Koch: None. C. Stapleton: None. T. Leslie-Mazwi: None. A. Patel: None.

BACKGROUND: The Pipeline Embolization Device (PED; Medtronic) has been used off-label for the treatment of challenging posterior circulation aneurysms. Data on this modality are primarily limited to small retrospective single-center series. OBJECTIVE: To assess safety and efficacy of this treatment by establishing an international, multicenter collaboration. METHODS: Consecutive posterior circulation aneurysms treated with the PED from 2012 to 2019 across 11 neurovascular centers were retrospectively reviewed. Baseline demographics, aneurysm and treatment characteristics, complications, occlusion status, and functional outcome were assessed. RESULTS: There were 149 posterior circulation aneurysms treated with PED in 146 patients. A total of 24 (16.4) patients presented with subarachnoid hemorrhage. Most aneurysms were dissecting/blister (36.2) in morphology, followed by saccular (35.6) and fusiform (28.2). The most common locations were the vertebral (51.7) and basilar arteries (22.8). Complete or near-complete occlusion (>90) was achieved in 90.9 of aneurysms at a median follow-up of 12 mo. Dissecting/blister aneurysms were most likely to occlude (P =.06). Symptomatic neurologic complications occurred in 9.4 of aneurysms, associated with larger size, ruptured presentation, presentations with brain stem compression, cranial nerve palsy, or stroke. Favorable functional outcome (modified Rankin Score 0-2) was achieved in 86.2 of patients. There were 6 fatalities of which 4 occurred in aneurysmal subarachnoid hemorrhage patients. CONCLUSION: This multicenter study shows that PED for the treatment of posterior circulation is preferentially used for the treatment of fusiform and dissecting/blister aneurysm morphologies. Despite the challenges presented by these less-common morphologies, flow diversion may be performed with a neurologic complication rate of about 10 and favorable long-term aneurysm occlusion rates. © 2020 by the Congress of Neurological Surgeons

BACKGROUND Older age has been associated with worse outcomes in low-grade gliomas (LGGs). Given their rarity in the older population, determining optimal treatment plans and patient outcomes remains difficult. OBJECTIVE To retrospectively study LGG survival outcomes in an older population stratified by molecular genetic profiles. METHODS We included patients age ≥40 yr with pathologically confirmed World Health Organization grade II gliomas treated at a single institution between 1995 and 2015. We collected tumor genomic information when available. RESULTS Median overall survival for the entire group (n = 111, median age 51 yr, range 40-77 yr) was 15.75 yr with 5- and 10-yr survival rates of 84.3% and 67.7%, respectively. On univariate analysis, patients with isocitrate dehydrogenase (IDH) mutation had significantly increased survival compared to IDH wildtype (hazard ratio [HR] 0.17 [0.07-0.45], P

IntroductionThe LVIS Blue is an FDA-approved stent with 28% metallic coverage that is indicated for use in conjunction with coil embolization for the treatment of intracranial aneurysms. Given a porosity similar to approved flow diverters and higher than currently available intracranial stents, we sought to evaluate the effectiveness of this device for the treatment of intracranial aneurysms.MethodsWe performed an observational single-center study to evaluate initial occlusion and occlusion at 6-month follow-up for patients treated with the LVIS Blue in conjunction with coil embolization at our institution using the modified Raymond–Roy classification (mRRC), where mRRC 1 indicates complete embolization, mRRC 2 persistent opacification of the aneurysm neck, mRRC 3a filling of the aneurysm dome within coil interstices, and mRRC 3b filling of the aneurysm dome.ResultsSixteen aneurysms were treated with the LVIS Blue device in conjunction with coil embolization with 6-month angiographic follow-up. Aneurysms were treated throughout the intracranial circulation: five proximal internal carotid artery (ICA) (ophthalmic or communicating segments), two superior cerebellar artery, two ICA terminus, two anterior communicating artery, two distal middle cerebral artery, one posterior inferior cerebellar artery, and two basilar tip aneurysms. Post-procedurally, there was one mRRC 1 closure, five mRRC 2 closures, and 10 mRRC 3a or 3b occlusion. At follow-up, all the mRRC 1 and mRRC 3a closures, 85% of the mRRC 3b closures and 75% of the mRRC 2 closures were stable or improved to an mRRC 1 or 2 at follow-up.ConclusionsThe LVIS Blue represents a safe option as a coil adjunct for endovascular embolization within both the proximal and distal anterior and posterior circulation.

Background Aneurysmal subarachnoid hemorrhage (aSAH) is associated with a high mortality and poor neurologic outcomes. The biologic underpinnings of the morbidity and mortality associated with aSAH remain poorly understood. Objective To ascertain potential insights into pathological mechanisms of injury after aSAH using an approach of metabolomics coupled with machine learning methods. Methods Using cerebrospinal fluid (CSF) samples from 81 aSAH enrolled in a retrospective cohort biorepository, samples collected during the peak of delayed cerebral ischemia were analyzed using liquid chromatography-tandem mass spectrometry. A total of 138 metabolites were measured and quantified in each sample. Data were analyzed using elastic net (EN) machine learning and orthogonal partial least squares-discriminant analysis (OPLS-DA) to identify the leading CSF metabolites associated with poor outcome, as determined by the modified Rankin Scale (mRS) at discharge and at 90 d. Repeated measures analysis determined the effect size for each metabolite on poor outcome. Results EN machine learning and OPLS-DA analysis identified 8 and 10 metabolites, respectively, that predicted poor mRS (mRS 3-6) at discharge and at 90 d. Of these candidates, symmetric dimethylarginine (SDMA), dimethylguanidine valeric acid (DMGV), and ornithine were consistent markers, with an association with poor mRS at discharge (P = .0005, .002, and .0001, respectively) and at 90 d (P = .0036, .0001, and .004, respectively). SDMA also demonstrated a significantly elevated CSF concentration compared with nonaneurysmal subarachnoid hemorrhage controls (P = .0087). Conclusion SDMA, DMGV, and ornithine are vasoactive molecules linked to the nitric oxide pathway that predicts poor outcome after severe aSAH. Further study of dimethylarginine metabolites in brain injury after aSAH is warranted.

The aim of the present paper is to report undiagnosed sporadic neurofibromatosis type 2 presenting with symptomatic compressive spinal tumors following pregnancy. A 36-year-old woman experienced progressive, severe lumbar radicular pain in the second trimester of pregnancy which became intractable soon after delivery. Magnetic resonance imaging revealed a complex heterogeneous hypointense mass lesion around the conus. There were two small punctate lesions in the cauda equina suggestive of myxopapillary ependymoma with ‘drop metastases.’ The patient underwent surgical resection of two cystic compressive conus masses. Her low back pain improved after surgery. The masses were consistent with cystic/cellular schwannomas. An incidental finding was of a small, low-grade spinal ependymoma which lacked the characteristic histologic features of myxopapillary ependymoma. Multiple, large cystic schwannomas are not uncommon in schwannomatosis, however, the co-occurrence of low-grade ependymoma strongly suggests a clinical diagnosis of new, sporadic neurofibromatosis type 2. Although cranial nerve schwannomas (orbital, auditory) have been reported to enlarge during pregnancy, to our knowledge, this is the first report of multiple cystic/cellular schwannomas causing severe pain (due to conus compression) during and immediately after pregnancy. Keywords: Segmental schwannomatosis, Neurofibromatosis type 2, Pregnancy, Ependymoma

OBJECTIVE: To investigate whether soluble growth stimulation expressed gene 2 (sST2), a prognostic marker in cardiovascular and inflammatory disorders, is associated with neurological injury after aneurysmal subarachnoid hemorrhage (SAH).METHODS: We studied SAH patients from 2 independent cohorts. Outcome assessments included functional status at 90 days using the modified Rankin Scale (mRS), mortality, and delayed cerebral ischemia (DCI). The relationships between sST2 plasma level and outcome measures were assessed in both cross-sectional and longitudinal analysis. Primary blood mononuclear cells from SAH patients and elective aneurysm controls were analyzed by multiparameter flow cytometry.RESULTS: In the discovery cohort, sST2 predicted 90-day mRS 3-6 (C index = 0.724, p INTERPRETATION: Plasma sST2 predicts DCI, functional outcome, and mortality after SAH, independent of clinical and radiographic markers. Elevated sST2 is also associated with changes in CD14+ CD16+ monocytes. ANN NEUROL 2019;86:384-394.

OBJECTIVES: Endovascular thrombectomy (EVT) has revolutionized stroke care for large vessel occlusions (LVOs). However, over half treated remain functionally disabled or die. Patients with tandem lesions, or severe stenosis/occlusion of the cervical internal carotid artery (ICA) with intracranial LVO, may have technical EVT challenges and worse outcomes. We sought to compare treatments and outcomes for patients with anterior circulation tandem lesions versus isolated LVOs. MATERIALS AND METHODS: Consecutive tandem lesion and isolated LVO patients were identified at a single center. Demographics, medical history, presentations, treatments, and outcomes were collected and analyzed. RESULTS: From 381 EVT patients, 62 had tandem lesions related to atherosclerosis (74%) or dissection (26%). Compared to isolated intracranial LVOs, they were younger (63 vs 70, p=0.003), less atrial fibrillation (13% vs 40%, p

Cerebral arteriovenous malformations (AVM) are traditionally considered primary congenital lesions that result from embryological aberrations in vasculogenesis. Recent insights, however, suggest that these lesions may be secondary to a vascular insult such as ischemia or trauma. Herein, the authors present a rare case of a secondary cerebral AVM, occurring in a young girl who received prior cranial radiation therapy. At age 3years, she underwent surgical resection, chemotherapy, and photon radiation therapy for treatment of a fourth ventricular ependymoma. At age 19years, she developed new onset seizures and was found to have a left medial temporal lobe AVM. Her seizures were managed successfully with anti-epileptic medications and the AVM was treated with proton radiation therapy. This case highlights a rare but possible vascular sequela of radiation therapy and adds to the growing body of evidence that cerebral AVM may arise as secondary lesions.

Flow diversion for treatment of intracranial aneurysms frequently necessitates covering adjacent branch vessels. Although branch vessel occlusion is common, associated clinical deficits are rare. It has been hypothesized that clinically silent branch vessel occlusion is due to underlying collateral circulation. To study the role of collateral circulation in covered branch vessel occlusion, we assessed collateral vessels and altered branch vessel flow on transfemoral catheter angiography in patients undergoing flow diversion of intracranial aneurysms.Angiograms obtained before treatment, immediately after treatment, and during follow-up were evaluated for branch vessel flow patterns and associated collateral circulation in a consecutive retrospective cohort of 84 patients from 2011 to 2017 with branch vessel coverage related to aneurysm flow diversion using the Pipeline embolization device.We identified 142 branch vessels covered by the Pipeline device construct for treatment of 89 aneurysms, predominately in the anterior circulation (90%). Collateral circulation was observed in approximately one third of these vessels and was associated with diminished (P0.001) or absent (P0.001) flow on follow-up angiography. Only 2 of 80 terminal branch vessels (no collaterals) were occluded, and these occurred in a patient with Pipeline device construct thrombosis. Altered branch vessel flow was not associated with vascular risk factors, treatment technique, or outcome measures, including new or worsening neurologic deficit.Altered flow in branch vessels covered during flow diversion reflects underlying collateral circulation and is not associated with downstream ischemic deficits.

Tumor-to-tumor metastasis is an uncommon phenomenon, and a metastasis from an extracranial donor tumor to an intracranial recipient tumor is extremely rare. In particular, there are only 14 cases reported in the literature that describe a tumor-to-tumor metastasis involving a glioma. We present a rare case of an 83-year-old man with an 11-year history of lentigo maligna melanoma who presented with impaired balance and cognitive slowing and was found to have rapid progression of a previously known indolent right frontal brain mass. Pathologic examination of the tumor after resection revealed the presence of both malignant melanoma and an oligodendroglioma WHO grade II. To the best of our knowledge, this is the first reported case of malignant melanoma metastasizing to an oligodendroglioma that has been confirmed by immunohistochemistry and genetic analysis.

Background and purposeBRANCH (wide-neck bifurcation aneurysms of the middle cerebral artery and basilar apex treated by endovascular techniques) is a multicentre, retrospective study comparing core lab evaluation of angiographic outcomes with self-reported outcomes.Materials and methodsConsecutive patients were enrolled from 10 US centres, aged between 18 and 85 with unruptured wide-neck middle cerebral artery (MCA) or basilar apex aneurysms treated endovascularly. Patient demographics, aneurysm morphology, procedural information, mortality and morbidity data and core lab and self-reported modified Raymond Roy (RR) outcomes were obtained.Results115 patients met inclusion criteria. Intervention-related mortality and significant morbidity rates were 1.7% (2/115) and 5.8% (6/103) respectively. Core lab adjudicated RR1 and 2 occlusion rates at follow-up were 30.6% and 32.4% respectively. The retreatment rate within the follow-up window was 10/115 (8.7%) and in stent stenosis at follow-up was 5/63 (7.9%). Self-reporting shows a statistically significant direction to angiographic RR one outcomes at follow-up compared with core lab evaluation, with OR 1.75 (95% CI 1.08 to 2.83).ConclusionEndovascular treatment of wide-neck MCA and basilar apex aneurysms resulted in a core lab adjudicated RR1 occlusion rate of 30.6%. Self-reported results at follow-up favour better angiographic outcomes, with OR 1.75 (95% CI 1.08 to 2.83). These data demonstrate the need for novel endovascular devices specifically designed to treat complex intracranial aneurysms, as well as the importance of core lab adjudication in assessing outcomes in such a trial.

Introduction: Soluble ST2 (sST2) is a member of the Toll-like receptor superfamily implicated in pro-inflammatory signaling. We investigated whether sST2 predicts delayed cerebral ischemia (DCI) and 90-day clinical outcome in patients with aneurysmal subarachnoid hemorrhage (SAH). Methods: Soluble ST2 was measured in plasma samples from 182 patients who presented to a single institution with SAH. Blood samples were collected between days 1 and 5 after onset of SAH, and prior to the onset of DCI. Functional outcome was assessed at 3 months using the modified Rankin Scale (mRS) with good and poor outcome defined as mRS 0-2 and 3-6, respectively. Using a consensus definition, DCI was defined as a 2-point drop in GCS over a sustained period in patients whose clinical deterioration could not be explained by another cause. The relationships between sST2 level, DCI and outcome were assessed in univariable analysis. Multivariable logistic regression, Kaplan-Meier survival analysis, and receiver operating characteristic curves were used to determine the ability of sST2 to predict outcome and mortality. These findings were tested for replication in an independent cohort of 51 SAH patients recruited from a separate institution. Results: The discovery cohort consisted of 182 subjects (mean age 56±12 years, 61% women). Elevated plasma sST2 predicted the development of DCI (OR 2.10, 95% 1.06-4.18 CI, P=0.0295), which remained an independent predictor after adjustment for age, World Federation of Neurological Surgeons (WFNS) grading score, modified Fisher score, intra-arterial vasodilator therapy and hydrocephalus (OR 2.78, 95% CI 1.00-7.97, p=0.0453). Elevated sST2 was also independently associated with poor 90-day functional outcome (OR 2.65, 95%CI 1.07-6.59, P =0.0304), and mortality (OR 5.36, 95% CI 1.48-19.39, p=0.0039) when adjusted for age, WFNS score, modified Fisher score and hydrocephalus. In the replication cohort (N=51, 88% women), sST2 level was an independent predictor of DCI (OR 5.02, 95% CI 1.46-17.20, p=0.0034) and outcome at 90 days (OR 4.24, 95% CI 1.31-13.74, p=0.0072). Conclusion: Plasma sST2 level predicted risk of DCI, outcome, and mortality after SAH. Further study of the potential link between sST2 and brain injury after SAH is warranted.

Endoscopic third ventriculostomy (ETV) is a common treatment for noncommunicating hydrocephalus. Although rare, vascular injury and traumatic pseudoaneurysm development during ETV have been reported. The authors present the case of a 13-year-old boy who underwent repeat ETV (rETV) for shunt and ETV failure, and who suffered an intraoperative subarachnoid hemorrhage due to iatrogenic injury to the basilar tip, with subsequent development of a pseudoaneurysm. Despite initial primary coil embolization, the aneurysm recurred and was definitively treated with flow diversion. In this report, the authors review complication rates associated with ETV and rETV as well as the emerging use of flow diversion and its applications in vessel reconstruction within the pediatric population.

Introduction/Purpose Flow diversion with the Pipeline Embolization Device (PED) often necessitates covering branch vessels. A number of studies suggest a low rate of branch vessel occlusion with only rare clinical complications from these occlusions. We and others hypothesize that branch vessel occlusion is generally clinically silent due to collateral circulation from ECA to ICA anastomoses (e.g. in the case of the ophthalmic artery) or via the circle of Willis. Materials and Methods We reviewed a consecutive retrospective cohort of 64 patients from 2011–2016, who had branch vessel coverage associated with aneurysm flow diversion. Immediate post-treatment angiography and interval follow-up angiography was evaluated for branch vessel opacification. Branch vessels demonstrated either normal, slow, or absent contrast opacification. Collateral circulation was assessed for all branch vessels with slow or absent flow when selective angiography was available. Results In our cohort, we identified 106 branch vessels covered by the PED construct in 64 patients. These were primarily anterior circulation branches (99 of 106) and of those, most were ophthalmic arteries (56 of 99). Slow flow was seen in 11 of 106 branches (10%), only 1 of which progressed on follow up to full occlusion. Angiographic occlusion was seen in 11 vessels (10%). Seven patients had new or worsening neurologic deficits, two of which were associated with stent thrombosis. Three patients had new visual deficits although the covered ophthalmic artery remained patent; two patients had new or worsening 6th nerve palsy related to mass effect from coils and/or the thrombosed aneurysm. The majority of branch vessels with altered flow (slow or absent) had angiographic evidence of collateral circulation (15 of 22, 68%). Altered branch vessel flow was not associated with new or worsening neurologic deficit. In the subset of branch vessels with altered flow, lack of collateral circulation was associated with new or worsening neurologic deficit (p Conclusion Branch vessel occlusion is a well-known ramification from flow diversion, but rarely results in clinical deficits. Most patients with altered branch vessel flow (either slow or absent) have distal supply via collateral circulation. In our cohort with altered branch vessel flow, new or worsening neurologic symptoms were associated with absent collateral circulation. Disclosures S. Raymond: None. M. Koch: None. C. Stapleton: None. C. Torok: None. A. Patel: 2; C; Medtronic, Penumbra.

OBJECTIVE Vascular malformations of the spine represent rare clinical entities with profound neurological implications. Previously reported studies on management strategies for spinal dural arteriovenous fistulas (sDAVFs) appeared before the advent of modern liquid embolic agents. Authors of the present study review their institutional experience with endovascularly and surgically treated sDAVFs. METHODS The authors performed a retrospective, observational, single-center case series on sDAVFs treated with endovascular embolization, microsurgical occlusion, or both between 2004 and 2013. The mode, efficacy, and clinical effect of treatment were evaluated. RESULTS Forty-seven patients with spinal arteriovenous malformations were evaluated using spinal angiography, which demonstrated 34 Type I sDAVFs (thoracic 20, lumbar 12, and cervical 2). Twenty-nine of the patients (85%) were male, and the median patient age was 63.3 years. Twenty patients underwent primary endovascular embolization (16 Onyx, 4 N-butyl cyanoacrylate [NBCA]), and 14 underwent primary surgical clipping. At a mean follow-up of 36 weeks, according to angiography or MR angiography, 5 patients treated with endovascular embolization demonstrated persistent arteriovenous shunting, whereas none of the surgically treated patients showed lesion persistence (p = 0.0237). Thirty patients (88%) experienced some resolution of their presenting symptoms (embolization 17 [85%], surgery 13 [93%], p = 1.00). CONCLUSIONS Microsurgical occlusion remains the most definitive treatment modality for sDAVFs, though modern endovascular techniques remain a viable option for the initial treatment of anatomically amenable lesions. Treatment of these lesions usually results in some clinical improvement.

Aneurysmal rupture leading to subarachnoid hemorrhage (SAH) represents a dire clinical entity with profound neurologic and systemic manifestations. Despite several advances in microsurgical and endovascular technology, mortality rates remain high, and survivors often suffer substantial neurologic morbidity. In these patients, presentation can range from a moderate acute onset headache to a near-comatose state. Optimal care relies on accurate and prompt diagnosis to minimize the deleterious effects of the subarachnoid blood on the central nervous system (CNS) and to eliminate the risk of rerupture. The acute care of these patients focuses on the prevention of a rerupture with either open surgical or endovascular intervention. Subsequent intensive care of these patients is driven by the prevention of vasospasm, hydrocephalus, and management of acute medical issues associated with SAH. The care of SAH requires a concerted effort of multispecialty physicians for the prompt recognition, treatment, and management of this profound disease entity.

Flow diversion is a novel treatment for brain aneurysms that works by redirecting blood flow away from the aneurysm. Immediately after placement of the stent, blood flow stagnates within the aneurysm dome and it undergoes thrombosis. Over time, a new endothelium develops across the neck, thereby reconstructing the parent vessel and curing the aneurysm. The use of this treatment method for ruptured aneurysms has two specific concerns: 1) risk of hemorrhage from the aneurysm after treatment because of potential delayed aneurysm occlusion; and 2) hemorrhagic complications from antiplatelet use, which is required to prevent thromboembolic complications from the device. In this review, we explore these two concerns based on the emerging published literature. Optimal peri-procedural management of these issues in the neurocritical care setting is vital to improving outcomes. We also identify ongoing clinical trials of flow diversion for the treatment of ruptured aneurysms. Flow diversion is an alternative to clipping or coiling for many ruptured aneurysms and may be potentially more efficacious in certain aneurysm subtypes.

Objectives Ischemic stroke due to large-vessel occlusion (LVO) is a complication after cardiothoracic surgery (CTS). Recently published endovascular stroke trials have major implications for treating LVO strokes; we evaluated our experience in patients undergoing CTS. Methods Our prospective institutional CTS database was reviewed between July 2013 and April 2018 for ischemic strokes. Patients with LVO were identified and their course and outcomes analyzed. Results A total of 5947 patients were reviewed; 148 (2.48%) had a cerebrovascular complication; 92.5% were ischemic. Of these 10.9% had an LVO. Prolonged aortic crossclamp was associated with LVO (odds ratio, 1.012 for every minute of prolonged aortic crossclamp time; confidence interval, 1.001-1.023) and remained significant in patients with ejection fraction >45%; prolonged cardiac bypass time was only associated with LVO in patients with ejection fraction >45% (odds ratio, 1.012 for every minute of prolonged cardiac bypass time; confidence interval, 1.003-1.021). Patients fell into 2 categories: detection of neurologic deficit in the stable postoperative patient or detection of deficit on emergence from anesthesia. Seven patients met criteria for emergent revascularization, with median National Institutes of Health Stroke Scale score 15, and shorter times from last seen well to deficit detection compared with patients not meeting criteria (P = .032). Median National Institutes of Health Stroke Scale day 7 score improved to 5. There was a trend toward better modified Rankin Scale scores at 3 months in patients who underwent thrombectomy. Conclusions LVO complicates a small proportion of patients after CTS and may be more likely with prolonged aortic crossclamp and cardiac bypass times. Both early and late window endovascular stroke treatment has the potential to positively modify the complication profile of CTS. Greater awareness of this treatment option is needed.

Background: Vertebral artery (VA) dissection causing acute stroke is commonly treated with anticoagulation and rarely requires stenting. While stenting for atherosclerotic stenosis of VA is an established and efficient treatment option, the safety of stenting for VA dissection has not been studied. Case information: We report the technical challenges associated with stenting of a proximal VA dissection in a 74 year-old male with NIHSSS > 20 outside of the time window for thrombolytic therapy presenting with acute basilar artery thrombus and a hypoplastic contralateral VA. Methods: A coronary Drug-Eluting Stent (DES) was implemented in right VA following balloon angioplasty and basilar artery thrombolysis to maintain the patency of the dissected area in proximal VA. Results: The procedure was completed without complication. Postoperative Digital Subtraction Angiography (DSA) confirmed the patency of the vertebrobasilar system. There was no evidence of significant residual stenosis in the right vertebral artery on the follow up Computed Tomography Angiography (CTA) 2 months after the stent placement. Conclusion: Endovascular stenting of proximal VA dissection in the setting of acute ischemic stroke is relatively safe and feasible. It could be particularly considered in patients ineligible for IV thrombolysis with a hypoplastic contralateral VA. Further studies are needed to evaluate the long-term safety and efficacy of stenting for VA dissection.

Flow diversion is an endovascular technique for embolization of intracranial aneurysms using a semi-porous stent to that redirects blood flow away from the aneurysm and is a scaffold for vessel remodeling. With flow diversion, aneurysms close slowly over 6-12 months as endothelial growth into the stent covers the neck of the aneurysm. Flow diversion is the preferred treatment for unruptured, large, paraclinoid aneurysms, which are otherwise challenging to treat with conventional open surgical or endovascular techniques. Post-embolization perianeurysmal edema (PAE) is an uncommon complication that occurs weeks to months after embolization and manifests as brain parenchymal edema surrounding the treated aneurysm. The clinical presentation is varied and includes headache, seizure or focal neurologic deficit. Frequently, PAE is misdiagnosed as an embolic stroke, which is a more common post-embolization complication and has some clinical and imaging overlap. PAE can be differentiated from ischemia by the absence of restricted diffusion and aneurysm wall enhancement on post-contrast Magnetic Resonance Imaging (MRI). PAE was initially described following coil embolization, but has subsequently been observed after flow diversion alone or with adjunctive coiling. Post-embolization PAE presumably results from rapid aneurysm thrombosis, endothelial cell necrosis, and the ensuing inflammatory reaction, which spreads to the adjacent brain parenchyma. Early recognition of PAE is critical to initiate appropriate therapy.

Progression of anaplastic glioma (World Health Organization [WHO] grade III) is typically determined radiographically, and transformation to glioblastoma (GB) (WHO grade IV) is often presumed at that time. However, the frequency of actual histopathologic transformation of anaplastic glioma and the subsequent clinical impact is unclear. To determine these associations, we retrospectively reviewed all anaplastic glioma patients who underwent surgery at our center at first radiographic progression, and we examined the effects of histological diagnosis, clinical history, and molecular factors on transformation rate and survival. We identified 85 anaplastic glioma (39 astrocytoma, 24 oligodendroglioma, 22 oligoastrocytoma), of which 38.8% transformed to GB. Transformation was associated with shorter overall survival (OS) from the time of diagnosis (3.4 vs. 10.9 years, p = 0.0005) and second surgery (1.0 vs. 3.5 years, p < 0.0001). Original histologic subtype did not significantly impact the risk of transformation or OS. No other factors, including surgery, adjuvant therapy or molecular markers, significantly affected the risk of transformation. However, mutations in isocitrate dehydrogenase 1 (IDH1) was associated with longer time to progression (median 4.6 vs. 1.4 years, p = 0.008) and OS (median 10.0 vs. 4.2 years, p = 0.046). At radiographic progression, tissue diagnosis may be warranted as histologic grade may provide valuable prognostic information and affect therapeutic clinical trial selection criteria for this patient population.

Vein of Galen aneurysmal malformations (VGAMs) are rare vascular malformations involving the median prosencephalic vein of Markowski, the precursor of the vein of Galen and the embryonic drainage of the choroid plexus. Although reported to comprise 30 % of pediatric vascular and 1 % of pediatric congenital anomalies [1], the exact incidence of VGAMs is difficult to quantify given the array of vascular pathology causing dilation of the median prosencephalic vein of Markowski or the vein of Galen [2]. In this chapter, we review relevant VGAM vascular anatomy and embryology, classifications schemes, clinical features and pathophysiology, and treatment strategies.

BackgroundArterial bifurcations are common locations for aneurysm development given the altered hemodynamic forces and shear stress variations present at these locations. Recent reports indicate that a wide basilar artery bifurcation angle is an independent predictor of aneurysm development, growth, and subsequent rupture.MethodsTo determine the effect of basilar artery bifurcation angle on rates of initial occlusion, recanalization, and retreatment of basilar artery apex aneurysms following coil embolization, the records of 46 patients with basilar artery apex aneurysms treated with endovascular coil embolization from 2007 to 2013 were analyzed.ResultsA wide basilar artery bifurcation angle was associated with a Raymond–Roy Occlusion Classification (RROC) III occlusion in univariate analysis, but was not a statistically significant factor in multivariate modeling. An increasing basilar artery bifurcation angle was not associated with aneurysm recanalization or retreatment following coil embolization. Increasing packing density ( p ConclusionBasilar artery bifurcation angle fails to predict rates of initial occlusion, recanalization, and retreatment on multivariate modeling in our series. Basilar artery apex aneurysm neck size independently correlates with basilar artery bifurcation angle.

Brain arteriovenous malformations (AVMs) are abnormal connections between arteries and veins that can result in hemorrhagic stroke. A genetic basis for AVMs is suspected, and we investigated potential mutations in a 14-year-old girl who developed a recurrent brain AVM. Whole-exome sequencing (WES) of AVM lesion tissue and blood was performed accompanied by in silico modeling, protein expression observation in lesion tissue and zebrafish modeling. A stop-gain mutation (c.C739T:p.R247X) in the gene SMAD family member 9 (SMAD9) was discovered. In the human brain tissue, immunofluorescent staining demonstrated a vascular predominance of SMAD9 at the protein level. Vascular SMAD9 was markedly reduced in AVM peri-nidal blood vessels, which was accompanied by a decrease in phosphorylated SMAD4, a downstream effector protein of the bone morphogenic protein signaling pathway. Zebrafish modeling (Tg kdrl:eGFP) of the morpholino splice site and translation-blocking knockdown of SMAD9 resulted in abnormal cerebral artery-to-vein connections with morphologic similarities to human AVMs. Orthogonal trajectories of evidence established a relationship between the candidate mutation discovered in SMAD9 via WES and the clinical phenotype. Replication in similar rare cases of recurrent AVM, or even more broadly sporadic AVM, may be informative in building a more comprehensive understanding of AVM pathogenesis.

A 1-year, single-center, randomized trial demonstrated that the calcineurin inhibitor or adjuvant immunosuppression, independently, does not affect BK-viruria or viremia and that monitoring and pre-emptive withdrawal of immunosuppression was associated with resolution of BK-viremia and absence of clinical BK-nephropathy without acute rejection or graft loss. A retrospective 5-year review of this trial was conducted. In cases of BK viremia, the antimetabolite was withdrawn and for sustained viremia, the calcineurin inhibitor was minimized. Five-year follow-up was available on 97% of patients. Overall 5-year patient survival was 91% and graft survival was 84%. There were no differences in patient-survival by immunosuppressive regimen or presence of BK-viremia. Immunosuppression and viremia did not influence graft survival. Acute rejection occurred in 12% by 5-years after transplant, was less common with tacrolimus versus cyclosporine (9% vs. 18%; p = 0.082), and was lowest with the tacrolimus-azathioprine regimen (5%, p = 0.127). Tacrolimus was associated with better renal function at 5-years (eGFR 63 FK vs. 52 CsA mL/min, p = 0.001). Minimization of immunosuppression upon detection of BK-viremia was associated with excellent graft survival at 5-years, low rejection rates and excellent renal function. It is a safe, short and long-term strategy that resulted in freedom from clinically evident BK-virus nephropathy.

Diffuse peritubular capillary C4d deposition in renal allograft biopsies is associated with donor-specific antibodies (DSA) and graft failure. The significance of focal C4d+ is unclear. We reviewed 368 biopsies from 301 patients performed for renal dysfunction or proteinuria over 5 years. Diffuse C4d+, focal C4d+ and C4d- detected by immunofluorescence occurred in 9.5%, 20.9% and 69.4% of biopsies, respectively. Patients were similar in gender, age, cause of renal disease, donor source, HLA mismatch, serum creatinine at baseline and interval from transplantation to biopsy. Diffuse and focal C4d+ were associated with acute cellular rejection (p < 0.001). Transplant glomerulopathy was associated with diffuse C4d+. DSA at the time of biopsy, were positive in 79.3% of diffusely C4d+ patients, 68.8% of those with focal C4d+ (p = 0.27) and 9.9% of patients with C4d- (p < 0.001, compared to either the focal or diffuse groups, respectively). Allograft survival at 40 months was lower in diffuse C4d+ compared to the C4d- group (p = 0.014), but not when compared to the focal C4d+ group. There was a clear trend toward worse graft survival in patients with focal C4d+ in this time interval, but focal C4d+ compared to both diffuse C4d+ and C4d-groups was not statistically significant (p = 0.08).

Prophylaxis reduces cytomegalovirus (CMV) disease, but is associated with increased costs and risks for side effects, viral resistance and late onset CMV disease. Preemptive therapy avoids drug costs but requires frequent monitoring and may not prevent complications of asymptomatic CMV replication. Kidney transplant recipients at risk for CMV (D+/R-, D+/R+, D-/R+) were randomized to prophylaxis (valganciclovir 900 mg q.d. for 100 days, n=49) or preemptive therapy (900 mg b.i.d. for 21 days, n=49) for CMV DNAemia (CMV DNA level>2000 copies/mL in >or=1 whole blood specimens by quantitative PCR) assessed weekly for 16 weeks and at 5, 6, 9 and 12 months. More patients in the preemptive group, 29 (59%) than in the prophylaxis group, 14 (29%) developed CMV DNAemia, p=0.004. Late onset of CMV DNAemia (>100 days after transplant) occurred in 11 (24%) randomized to prophylaxis, and none randomized to preemptive therapy. Symptomatic infection occurred in five patients, four (3 D+/R- and 1 D+/R+) in the prophylactic group and one (D+/R-) in the preemptive group. Peak CMV levels were highest in the D+/R- patients. Both strategies were effective in preventing symptomatic CMV. Overall costs were similar and insensitive to wide fluctuations in costs of either monitoring or drug.

BACKGROUND The relative benefit versus safety of induction therapy in live-donor renal transplant recipients is controversial. This paper presents observational data of live-donor recipients who received Thymoglobulin induction and standard maintenance immunosuppressive therapy. METHODS Review and analysis of clinic records and electronic databases of live-donor renal transplants that received Thymoglobulin induction from May 1996 through 2003. RESULTS Data analysis included 214 live-donor recipients (146 related, 68 unrelated) with a mean follow-up of 3.0+/-1.9 years. The average age of recipients was 44+/-13 years, with a majority being Caucasian (86%) and male (64%). Nineteen (9%) received previous transplants. No patients experienced delayed graft function and 10 (5%) developed acute rejection. Overall, predicted five-year patient survival was 96% and graft survival was 82%. The rates of CMV infection (5%), malignancy (3%), and lymphoproliferative disorder (0.5%) were low. When compared to live-donor kidney transplant recipients nationwide, the center cohort demonstrated improved five year patient (96% center versus 90% national, P=0.0326) and graft survival (82% center versus 79% national, P=0.0901), and a lower one-year acute rejection rate (2% center versus 21 % national, P

Background Nonaneurysmal subarachnoid hemorrhage (SAH) has been historically associated with a benign clinical course. However, recent studies have suggested that nonaneurysmal SAH can present with different hemorrhage patterns that may be associated with differential rates of morbidity. Herein, we analyze a retrospective consecutive cohort of patients with nonaneurysmal SAH to determine outcomes. We also seek to evaluate a validated radiographic grading scale to determine its utility in predicting vasospasm in the setting of different hemorrhage patterns. Methods After institutional review board approval, the records of 563 consecutive patients admitted with spontaneous SAH between January 2007 and 2014 were retrospectively reviewed. A total of 138 of these patients had no identifiable source of hemorrhage and were further divided into 2 groups depending on their pattern of hemorrhage: perimesencephalic or diffuse. Clinical characteristics and outcomes were assessed. Results In nonaneurysmal SAH, 70 patients (50.7%) had a perimesencephalic pattern of hemorrhage, whereas 68 (49.3%) experienced diffuse SAH. Radiographic vasospasm developed in 6 patients (8.6%) with perimesencephalic SAH and in 14 patients (20.6%) with a diffuse SAH pattern. When comparing historical rates of vasospasm based on the Barrow Neurological Institute (BNI) scale and rates in the nonaneurysmal diffuse pattern in this series, there was no significant difference in distribution (chi-square; P = .149), compared with a difference seen with the perimesencephalic group ( P Conclusions Nonaneurysmal SAH is associated with the potential for vasospasm, with higher rates in the diffuse versus perimesencephalic SAH patterns. The BNI grading scale for aneurysmal SAH can be used to predict the risk of vasospasm in diffuse, nonaneurysmal SAH.

Chordomas and chondrosarcomas are rare skull base tumors, with similar radiographic and clinical presentations. We investigated factors influencing long-term survival in these 2 tumors using the Surveillance Epidemiology and End Results (SEER) database.Patients with chordoma (n = 416) and chondrosarcoma (n = 269) within the skull base from 1983 to 2009 were identified within the SEER database. Kaplan-Meier curves and Cox proportional hazards models were used to test associations with survival. t tests and χ(2) tests were used to compare groups.Chordoma and chondrosarcoma patients were similar demographically. Survival at 5 years was 65% for chordomas and 81.8% (P0.0001) for chondrosarcomas and at 10 years was 32.3% and 49.5% (P = 0.004). Multivariate analysis demonstrated chordomas had a worse prognosis even when we controlled for age and tumor size (hazard ratio 3.0, 95% confidence interval 1.9-4.7, P0.0001). For chordomas, multivariate analysis demonstrated increasing age and tumor size were significantly associated with reduced survival. For chondrosarcomas, multivariate analysis demonstrated older age, earlier decade of diagnosis, and mesenchymal subtype were significantly associated with reduced survival. Postoperative radiation was given to 42% and 41% of patients with chordomas and chondrosarcomas, respectively. The addition of radiation did not improve survival.Consistent with previous case series, skull base chordomas have significantly worse prognosis than chondrosarcomas. Patients in the SEER database had worse survival overall compared with existing case series for both chordomas and chondrosarcomas, suggesting selection bias in the existing literature.