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Despite some success in secondary brain metastases, targeted or immune-based therapies have shown limited efficacy against primary brain malignancies such as glioblastoma (GBM). Although the intratumoral heterogeneity of GBM is implicated in treatment resistance, it remains unclear whether this diversity is observed within brain metastases and to what extent cancer cell–intrinsic heterogeneity sculpts the local immune microenvironment. Here, we profiled the immunogenomic state of 93 spatially distinct regions from 30 malignant brain tumors through whole-exome, RNA, and T-cell receptor sequencing. Our analyses identified differences between primary and secondary malignancies, with gliomas displaying more spatial heterogeneity at the genomic and neoantigen levels. In addition, this spatial diversity was recapitulated in the distribution of T-cell clones in which some gliomas harbored highly expanded but spatially restricted clonotypes. This study defines the immunogenomic landscape across a cohort of malignant brain tumors and contains implications for the design of targeted and immune-based therapies against intracranial malignancies. Significance: This study describes the impact of spatial heterogeneity on genomic and immunologic characteristics of gliomas and brain metastases. The results suggest that gliomas harbor significantly greater intratumoral heterogeneity of genomic alterations, neoantigens, and T-cell clones than brain metastases, indicating the importance of multisector analysis for clinical or translational studies. This article is highlighted in the In This Issue feature, p. 1

Background The benefit of intravenous thrombolysis (IVT) before mechanical thrombectomy (MT) in patients with large vessel occlusion (LVO) stroke is uncertain. Conventional metrics of final modified thrombolysis in cerebral ischemia (mTICI) score and 90-d modified Rankin Scale may be insensitive to IVT effects on procedural complexity and duration. Objective To study the effect of IVT prior to MT on clot survival. Methods We performed a single-center retrospective analysis of 257 acute stroke patients with LVO undergoing MT and analyzed the effect of IVT prior to MT using a novel, pass-by-pass clot survival methodology. Results The use of IVT was associated with a significantly lower number of passes to attain mTICI 2B or greater (P = .002) or mTICI 3 (P = .039) reperfusion. The number of patients who achieved mTICI 2B or greater after the first pass was significantly higher in the IVT group (P = .003). This increased rate of reperfusion persisted into subsequent passes. Conclusion IVT prior to MT reduces the number of thrombectomy passes required to achieve mTICI 2B or mTICI 3 reperfusion. This information should be considered as the merits of IVT prior to MT are debated.

Background Mechanical thrombectomy (MT) is the standard of care for the treatment of proximal anterior circulation large vessel occlusions. However, little is known about its efficacy and safety in the treatment of distal intracranial occlusions. Methods This is a multicenter retrospective study of patients treated with MT at 15 comprehensive centers between January 2015 and December 2018. The study cohort was divided into 2 groups based on the location of occlusion (proximal vs. distal). Distal occlusion was defined as occlusion of M3 segment of the middle cerebral artery, any segment of the anterior cerebral artery, or any segment of the posterior cerebral artery. Only isolated distal occlusion was included. Good outcome was defined as 90-day modified Rankin scale score 0–2. Results A total of 4710 patients were included in this study, of whom 189 (4%) had MT for distal occlusions. Compared with the proximal occlusion group, distal occlusion group had a higher rate of good outcome (45% vs. 36%; P = 0.03) and a lower rate of successful reperfusion (78% vs. 84%; P = 0.04). However, the differences did not retain significance in adjusted models. Otherwise there was no difference in the rate of hemorrhagic complications, mortality, or procedure-related complications between the 2 groups. Successful reperfusion, age, and admission stroke severity emerged as predictors of good functional outcome in the distal occlusion group. Conclusions Thrombectomies of distal vessels achieve high rate of successful reperfusion with similar safety profile to those in more proximal locations.

Background and purpose Flow diversion of aneurysms located in the M1 segment and middle cerebral artery bifurcation with Pipeline embolization device is sometimes performed, but further study is needed to support its regular use in aneurysm treatment. Here, we report measures of safety and efficacy for Pipeline embolization in the proximal middle cerebral artery in a multi-center cohort. Materials and methods Clinical and angiographic data of eligible patients were retrospectively obtained from participating centers and assessed for key clinical and angiographic outcomes. Additional details were extracted for patients with complications. Results In our multi-center cohort, complete aneurysm occlusion was achieved in 71% (17/24) of treated aneurysms. There were no deaths or disabling strokes, but non-disabling ischemic strokes occurred in 8% (2/24) of patients. For aneurysms in the M1 segment, complete aneurysm occlusion was observed in 75% (12/16) of aneurysms, aneurysm volume reduction was observed in 100% (16/16) of aneurysms, and non-disabling ischemic strokes occurred in 13% (2/16) of patients. For aneurysms at the middle cerebral artery bifurcation, complete aneurysm occlusion was observed in 63% (5/8) of aneurysms, aneurysm volume reduction occurred in 88% (7/8) of aneurysms, and ischemic or hemorrhagic complications occurred in 0% (0/8) of patients. Conclusion Pipeline embolization of cerebral aneurysms in the M1 segment and middle cerebral artery bifurcation demonstrated a 71% rate of complete aneurysm occlusion. There were no deaths or disabling strokes, but there was an 8% rate of non-disabling ischemic strokes.

Background and purpose Flow diversion is commonly used to treat intracranial aneurysms in various regions of the cerebral vasculature, but is only approved for use in the internal carotid arteries. Treatment of distal PICA aneurysms with PED is sometimes performed but has not been well studied. Here, we report our experience with flow diversion of distal PICA aneurysms with PED. Materials and methods Clinical and angiographic data of eligible patients was retrospectively obtained and assessed for key demographic characteristics and clinical and angiographic outcomes. Principal outcomes included rates of aneurysm occlusion, ischemic or hemorrhagic complication, technical complication, and in-stent stenosis. Results Three female and 2 male patients underwent placement of PED in the PICA for treatment of 5 distal PICA aneurysms. Clinical and angiographic follow-up was obtained for all patients. Complete aneurysm occlusion was observed in 100% (5/5) of treated aneurysms at 6 month and longest angiographic follow-up. While there were no ischemic or device-related complications, delayed hemorrhagic complications occurred in 20% (1/5) of patients. Conclusion Pipeline embolization of distal PICA aneurysms can be performed in select patients. Further study is necessary in larger cohorts to better define clinical scenarios in which flow diversion in the distal PICA should be considered.

Background and Purpose:Early brain injury may be a more significant contributor to poor outcome after aneurysmal subarachnoid hemorrhage (aSAH) than vasospasm and delayed cerebral ischemia. However, studying this process has been hampered by lack of a means of quantifying the spectrum of injury. Global cerebral edema (GCE) is the most widely accepted manifestation of early brain injury but is currently assessed only through subjective, qualitative or semi-quantitative means. Selective sulcal volume (SSV), the CSF volume above the lateral ventricles, has been proposed as a quantitative biomarker of GCE, but is time-consuming to measure manually. Here we implement an automated algorithm to extract SSV and evaluate the age-dependent relationship of reduced SSV on early outcomes after aSAH.Methods:We selected all adults with aSAH admitted to a single institution with imaging within 72 hours of ictus. Scans were assessed for qualitative presence of GCE. SSV was automatically segmented from serial CTs using a deep learning-based approach. Early SSV was the lowest SSV from all early scans. Modified Rankin Scale score of 4 to 6 at hospital discharge was classified as a poor outcome.Results:Two hundred forty-four patients with aSAH were included. Sixty-five (27%) had GCE on admission while 24 developed it subsequently within 72 hours. Median SSV on admission was 10.7 mL but frequently decreased, with minimum early SSV being 3.0 mL (interquartile range, 0.3–11.9). Early SSV below 5 mL was highly predictive of qualitative GCE (area under receiver-operating-characteristic curve, 0.90). Reduced early SSV was an independent predictor of poor outcome, with a stronger effect in younger patients.Conclusions:Automated assessment of SSV provides an objective biomarker of GCE that can be leveraged to quantify early brain injury and dissect its impact on outcomes after aSAH. Such quantitative analysis suggests that GCE may be more impactful to younger patients with SAH.

OBJECTIVEDelayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (SAH) is characterized by large-artery vasospasm, distal autoregulatory dysfunction, cortical spreading depression, and microvessel thrombi. Large-artery vasospasm has been identified as an independent predictor of poor outcome in numerous studies. Recently, several animal studies have identified a strong protective role for inhalational anesthetics against secondary brain injury after SAH including DCI—a phenomenon referred to as anesthetic conditioning. The aim of the present study was to assess the potential role of inhalational anesthetics against cerebral vasospasm and DCI in patients suffering from an SAH.METHODSAfter IRB approval, data were collected retrospectively for all SAH patients admitted to the authors’ hospital between January 1, 2010, and December 31, 2013, who received general anesthesia with either inhalational anesthetics only (sevoflurane or desflurane) or combined inhalational (sevoflurane or desflurane) and intravenous (propofol) anesthetics during aneurysm treatment. The primary outcomes were development of angiographic vasospasm and development of DCI during hospitalization. Univariate and logistic regression analyses were performed to identify independent predictors of these endpoints.RESULTSThe cohort included 157 SAH patients whose mean age was 56 ± 14 (± SD). An inhalational anesthetic–only technique was employed in 119 patients (76%), while a combination of inhalational and intravenous anesthetics was employed in 34 patients (22%). As expected, patients in the inhalational anesthetic–only group were exposed to significantly more inhalational agent than patients in the combination anesthetic group (p < 0.05). Multivariate logistic regression analysis identified inhalational anesthetic–only technique (OR 0.35, 95% CI 0.14–0.89), Hunt and Hess grade (OR 1.51, 95% CI 1.03–2.22), and diabetes (OR 0.19, 95% CI 0.06–0.55) as significant predictors of angiographic vasospasm. In contradistinction, the inhalational anesthetic–only technique had no significant impact on the incidence of DCI or functional outcome at discharge, though greater exposure to desflurane (as measured by end-tidal concentration) was associated with a lower incidence of DCI.CONCLUSIONSThese data represent the first evidence in humans that inhalational anesthetics may exert a conditioning protective effect against angiographic vasospasm in SAH patients. Future studies will be needed to determine whether optimized inhalational anesthetic paradigms produce definitive protection against angiographic vasospasm; whether they protect against other events leading to secondary brain injury after SAH, including microvascular thrombi, autoregulatory dysfunction, blood-brain barrier breakdown, neuroinflammation, and neuronal cell death; and, if so, whether this protection ultimately improves patient outcome.

Endoscopic transsphenoidal surgery (ETSS) is a well-established treatment for patients with nonfunctioning pituitary adenomas (NFPAs). Data on the rates of pituitary dysfunction and recovery in a large cohort of NFPA patients undergoing ETSS and the predictors of endocrine function before and after ETSS are scarce. This study is purposed to analyze the comprehensive changes in hormonal function and identify factors that predict recovery or worsening of hormonal axes following ETSS for NFPA. A retrospective review of 601 consecutive patients who underwent ETSS between 2010 and 2018 at one institution was performed. Recovery or development of new hypopituitarism was analyzed in 209 NFPA patients who underwent ETSS. Patients with preoperative endocrine deficits (59.8%) in one or more pituitary axes had larger tumor volumes (P = 0.001) than those without preoperative deficits. Recovery of preoperative pituitary deficit occurred in all four axes, with overall mean recovery of 29.7%. The cortisol axis showed the highest recovery whereas the thyroid axis showed the lowest, with 1-year cumulative recovery rates of 44.3% and 6.1%, respectively. Postoperative hypopituitarism occurred overall in 17.2%, most frequently in the thyroid axis (24.3%, 27/111) and least frequently in the cortisol axis (9.7%, 16/165). Axis-specific predictors of post-operative recovery and deficiency were identified. Dynamic alterations in pituitary hormones were observed in a proportion of patients following ETSS in NFPA patients. Postoperative endocrine vulnerability, recovery, and factors that predicted recovery or loss of endocrine function depended on the hormonal system, necessitating an axis-specific surveillance strategy postoperatively.

Background Standard treatment of idiopathic intracranial hypertension (IIH) involves reduction of intracranial pressure (ICP) to normal range, often via a ventriculoperitoneal shunt (VPS). We describe a case of a middle-aged man who presented with symptoms consistent with IIH. After ICP was normalized with a VPS, the patient had neurologic deterioration into a coma. He completely recovered after a month when his ICP was allowed to increase and remain above the normal range. Case Description A 50-year-old man presented with daily headaches, visual loss (right > left), and increased lumbar opening pressure consistent with IIH. A VPS was inserted using a Strata II valve with a pressure setting of 1.5, lowering ICP into the normal range. The patient initially had a normal postoperative course, but then became comatose and developed imaging signs consistent with intracranial hypotension. A Codman Certas valve was placed at a setting of 7 and a distal slit-cut peritoneal catheter was used (as opposed to standard open output). This custom system drained at pressure >26 mm Hg based on intraoperative manometry. The patient tolerated this well and is currently planned for a gradual reduction in ICP with valve setting adjustments as an outpatient. Conclusions In patients with chronic IIH, reduction to normal ICP may unexpectedly lead to encephalopathic changes. Personalized shunts may facilitate reduction of ICP to still elevated but tolerable levels in these patients.

BackgroundThe transradial approach (TRA) has gained increasing popularity for neuroendovascular procedures. However, the experience with TRA in neuroangiography is still in early stages in most centers, and the safety and feasibility of this approach have not been well established. The purpose of this study is to report the safety and feasibility of TRA for neuroendovascular procedures.MethodsWe reviewed charts from six institutions in the USA to include consecutive patients who underwent diagnostic or interventional neuroendovascular procedures through TRA from July 2018 to July 2019. Collected data included baseline characteristics, procedural variables, complications, and whether there was a crossover to transfemoral access.ResultsA total of 2203 patients were included in the study (age 56.1±15.2, 60.8% women). Of these, 1697 (77%) patients underwent diagnostic procedures and 506 (23%) underwent interventional procedures. Successfully completed procedures included aneurysm coiling (n=97), flow diversion (n=89), stent-assisted coiling (n=57), balloon-assisted coiling (n=19), and stroke thrombectomy (n=76). Crossover to femoral access was required in 114 (5.2%). There were no major complications related to the radial access site. Minor complications related to access site were seen in 14 (0.6%) patients.ConclusionIn this early stage of transforming to the ‘radial-first’ approach for neuroendovascular procedures, TRA was safe with low complication rates for both diagnostic and interventional procedures. A wide range of procedures were completed successfully using TRA.

Purpose: Most World Health Organization (WHO) grade I meningiomas carry a favorable prognosis. Some become clinically aggressive with recurrence, invasion, and resistance to conventional therapies (grade 1.5; recurrent/progressive WHO grade I tumors requiring further treatment within 10 years). We aimed to identify biomarker signatures in grade 1.5 meningiomas where histopathology and genetic evaluation has fallen short. Experimental Design: Mass spectrometry (MS)–based phosphoproteomics and peptide chip array kinomics were used to compare grade I and 1.5 tumors. Ingenuity Pathway Analysis (IPA) identified alterations in signaling pathways with validation by Western blot analysis. The selected biomarker was evaluated in an independent cohort of 140 samples (79/140 genotyped for meningioma mutations) by tissue microarray and correlated with clinical variables. Results: The MS-based phosphoproteomics revealed differential Ser/Thr phosphorylation in 32 phosphopeptides. The kinomic profiling by peptide chip array identified 10 phosphopeptides, including a 360% increase in phosphorylation of RB1, in the 1.5 group. IPA of the combined datasets and Western blot validation revealed regulation of AKT and cell-cycle checkpoint cascades. RB1 hyperphosphorylation at the S780 site distinguished grade 1.5 meningiomas in an independent cohort of 140 samples and was associated with decreased progression/recurrence-free survival. Mutations in NF2, TRAF7, SMO, KLF4, and AKT1 E17K did not predict RB1 S780 staining or progression in grade 1.5 meningiomas. Conclusions: RB1 S780 staining distinguishes grade 1.5 meningiomas, independent of histology, subtype, WHO grade, or genotype. This promising biomarker for risk stratification of histologically bland WHO grade I meningiomas provides insight into the pathways of oncogenesis driving these outlying clinically aggressive tumors.

Recent investigation of the meninges, specifically the dura layer, has highlighted its importance in CNS immune surveillance beyond a purely structural role. However, most of our understanding of the meninges stems from the use of pre-clinical models rather than human samples. In this study, we use single cell RNA-sequencing to perform the first characterization of both non-tumor-associated human dura and meningioma samples. First, we reveal a complex immune microenvironment in human dura that is transcriptionally distinct from that of meningioma. In addition, through T cell receptor sequencing, we show significant TCR overlap between matched dura and meningioma samples. We also identify a functionally heterogeneous population of non-immune cell types and report copy-number variant heterogeneity within our meningioma samples. Our comprehensive investigation of both the immune and non-immune cell landscapes of human dura and meningioma at a single cell resolution provide new insight into previously uncharacterized roles of human dura.

Introduction/Purpose Flow diversion of aneurysms located in the M1 segment and middle cerebral artery bifurcation with Pipeline embolization device is sometimes performed, but further study is needed to support its regular use in aneurysm treatment. Here, we report measures of safety and efficacy for Pipeline embolization in the proximal middle cerebral artery in a multi-center cohort. Materials and Methods Clinical and angiographic data of eligible patients undergoing Pipeline embolization of aneurysms located in the M1 segment and middle cerebral artery bifurcation were retrospectively obtained from participating centers and assessed for key clinical, angiographic, and cross-sectional imaging outcomes. Additional details were extracted for patients with complications. Results In our multi-center cohort, complete aneurysm occlusion was achieved in 71% (17/24) of treated aneurysms. There were no deaths or disabling strokes, but non-disabling ischemic strokes occurred in 8% (2/24) of patients. For aneurysms in the M1 segment, complete aneurysm occlusion was observed in 75% (12/16) of aneurysms, aneurysm volume reduction was observed in 100% (16/16) of aneurysms, and non-disabling ischemic strokes occurred in 13% (2/16) of patients. An illustrative example of an M1 aneurysm treated with PED is provided in figure 1. For aneurysms at the middle cerebral artery bifurcation, complete aneurysm occlusion was observed in 63% (5/8) of aneurysms, aneurysm volume reduction occurred in 88% (7/8) of aneurysms, and ischemic or hemorrhagic complications occurred in 0% (0/8) of patients. 19% (3/16) of patients that remained asymptomatic in the follow-up period and underwent cross-sectional imaging had clinically silent basal ganglia infarcts identified. Conclusion Pipeline embolization of cerebral aneurysms in the M1 segment and middle cerebral artery bifurcation demonstrated a 71% rate of complete aneurysm occlusion. There were no deaths or disabling strokes, but there was an 8% rate of non-disabling ischemic strokes. Further work is necessary to describe the long-term effects of silent basal ganglia infarcts caused by PED. Disclosures D. Lauzier: None. B. Root: None. Y. Kayan: 2; C; Microvention, Penumbra, Medtronic. J. Delgado Almandoz: 2; C; Medtronic, Microvention. J. Osbun: 2; C; Medtronic, Microvention. A. Chatterjee: None. K. Whaley: None. M. Tipps: None. C. Moran: 2; C; Medtronic, Cerenovus. A. Kansagra: 2; C; Penumbra, Microvention, iSchemaView.

Introduction Limited data is available about the outcomes of mechanical thrombectomy (MT) in stroke patients presenting with a large core infarct. We aim to investigate the safety and efficacy of MT in patients with large vessel occlusion and Alberta Stroke Program Early CT Score (ASPECTS) of 2-5. Methods Data from Stroke Thrombectomy and Aneurysm Registry (STAR), which combined the prospectively maintained databases of 28 thrombectomy-capable stroke centers in the US, Europe, and Asia, was interrogated. We identified thrombectomy patients presenting with an occlusion in the Internal carotid artery (ICA) or M1 segment of the middle cerebral artery (MCA). Multivariable regression analysis was performed to assess factors associated with favorable 90-day outcome (modified Rankin scale 0-3), including interaction terms between ASPECTS 2-5 and receiving MT in the extended window (≥ 6 hours from symptom-onset). Results Among MT patients who presented with ICA or M1 occlusion, 2132 had ASPECTS≥6 and 213 patients had ASPECTS 2-5. Patients in the low ASPECTS group were younger (70 vs. 72 years old, P=0.003) and more likely to present with an ICA occlusion (47.9% vs. 28.8%, P Conclusion More than one in three patients presenting with ASPECTS (2-5) may achieve favorable 90-day functional outcome following MT. Favorable outcome was 4 times higher in low ASPECTS patients who had successful recanalization. The effect of low ASPECTS on 90-day outcome did not differ in patients presenting in the early versus extended MT window. Disclosures E. Almallouhi: None. S. Al Kasab: None. Z. Hubbard: None. G. Porto: None. A. Alawieh: None. R. Chalhoub: None. E. Bass: None. P. Jabbour: None. R. Starke: None. S. Wolfe: None. A. Arthur: None. I. Maier: None. J. Grossberg: None. A. Rai: None. M. Park: None. J. Mascitelli: None. M. Psychogios: None. R. De Leacy: None. D. Raper: None. T. Dumont: None. M. Levitt: None. A. Polifka: None. J. Osbun: None. R. Crosa: None. J. Kim: None. W. Casagrande: None. M. Mokin: None. C. Matouk: None. A. Shaban: None. I. Fragata: None. A. Yoo: None. A. Spiotta: 1; C; Stryker, Penumbra, and Medtronic. 2; C; Penumbra, Stryker, Cerenovus, Terumo.

IntroductionTransradial access is increasingly used among neurointerventionalists as an alternative to the transfemoral route. Currently available data, building on the interventional cardiology experience, primarily focus on right radial access. However, there are clinical scenarios when left-sided access may be indicated. The purpose of this study was to evaluate the technical feasibility of left transradial access to cerebral angiography across three institutions.MethodsA retrospective chart review was performed for patients who underwent cerebral angiography accessed via the left radial artery at three institutions between January 2018 and July 2019. The outcome variables studied were successful catheterization, vascular complications, and fluoroscopic time.ResultsNineteen patients underwent a total of 25 cerebral angiograms via left transradial access for cerebral aneurysms (n=15), basilar occlusion (n=1), carotid stenosis (n=1), arteriovenous malformation (n=1), and cervical neurofibroma (n=1). There were 12 diagnostic angiograms and 13 interventional angiograms. The left transradial approach was chosen due to left vertebrobasilar pathology (n=22), right subclavian stenosis (n=2), and previous right arm amputation (n=1). There was one instance of radial artery spasm, which resolved after catheter removal, and one conversion to transfemoral access in an interventional case due to lack of distal catheter support. There were no procedural complications.ConclusionsLeft transradial access in diagnostic and interventional cerebral angiography is a technically feasible, safe, and an effective alternative when indicated, and may be preferable for situations in which pathology locations or anatomic limitations preclude right-sided radial access.

BackgroundUse of the radial artery as an access site for neurointerventional procedures is gaining popularity after several studies in interventional cardiology have demonstrated superior patient safety, decreased length of stay, and patient preference compared with femoral artery access. The transradial approach has yet to be characterized for intraoperative cerebral angiography.ObjectiveTo report a multicenter experience on the use of radial artery access in intraoperative cerebral angiography, including case series and discussion of technical nuances.Methods27 patients underwent attempted transradial cerebral angiography betweenMay 2017 and May 2019. Data were collected regarding technique, patient positioning, vessels selected, technical success rate, and access site complications.Results24 of the 27 patients (88.8%) underwent successful transradial intraoperative cerebral angiography. 18 patients (66.7%) were positioned supine, 6 patients (22.2%) were positioned prone, 1 patient (3.7%) was positioned lateral, and 2 patients (7.4%) were positioned three-quarters prone. A total of 31 vessels were selected including 13 right carotid arteries (8 common, 1 external, 4 internal), 11 left carotid arteries (9 common and 2 internal), and 6 vertebral arteries (5 right and 1 left). Two patients (7.4%) required conversion to femoral access in order to complete the intraoperative angiogram (1 due to arterial vasospasm and 1 due to inadvertent venous catheterization). One procedure (3.7%) was aborted because of inability to obtain the appropriate fluoroscopic views due to patient positioning. No patient experienced stroke, arterial dissection, or access site complication.ConclusionsTransradial intraoperative cerebral angiography is safe and feasible with potential for improved operating room workflow ergonomics, faster patient mobility in the postoperative period, and reduced costs.

Background The Pipeline Embolization Device (PED) has been increasingly used for the treatment of posterior circulation aneurysms. The purpose of the present study was to examine the clinical and angiographic outcomes of patients with vertebrobasilar aneurysms treated with the PED. Methods We performed a retrospective review of vertebrobasilar aneurysms treated with the PED at 4 high-volume neurovascular centers. Patient, aneurysm, and procedural data were collected, including perioperative and delayed complications. Aneurysm occlusion on follow-up imaging studies was defined as complete (100%), near-complete (>90%), or incomplete ( Results The cohort included 35 patients with 37 vertebrobasilar aneurysms who underwent 36 treatment sessions. Of the 35 patients, 10 were men (29%), and the mean patient age was 54.1 years (range, 32–75). Eight patients (23%) underwent urgent treatment because of a ruptured aneurysm (n = 6), brainstem perforator stroke (n = 1), or post-traumatic pseudoaneurysm (n = 1). Of the 37 aneurysms, 22 arose from the vertebral artery (59%) and 15 from the basilar artery (41%). Also, 19 were saccular aneurysms (51%), with a mean size of 7.7 mm (range, 1.7–38.0); 17 were fusiform aneurysms (46%), with a mean size of 11.0 mm (range, 4.3–34); and 1 was a 2.9-mm blister aneurysm. The overall procedural complication rate was 14% (5 of 36), including 3 neurologically symptomatic complications. At a mean follow-up period of 14 months (range, 3–59), 24 of 34 aneurysms (71%) were completely occluded and 29 of 34 (85%) were completely or near-completely occluded. Conclusion Our results show that Pipeline embolization of vertebrobasilar aneurysms is associated with acceptable occlusion and complication rates.

BackgroundThe transradial approach (TRA) to endovascular procedures decreases access site morbidity and mortality in comparison with the traditional transfemoral technique (TFA). Despite its improved safety profile, there is a concern that TRA is less favorable for neurointerventional procedures that require large coaxial systems to manage the small tortuous cerebral vessels.ObjectiveTo report our experience with TRA for flow diverter placement for treatment of unruptured cerebral aneurysms.MethodsWe performed a retrospective review of prospective institutional databases at two high-volume centers to identify 49 patients who underwent flow diversion for aneurysm treatment via primary TRA between November 2016 and November 2018. Patient demographics, procedural techniques, and clinical data were recorded.ResultsOf the 49 patients, 39 underwent successful flow diversion placement by TRA. Ten patients were converted to TFA after attempted TRA. There were no procedural complications. Reasons for failure included tortuosity in eight patients and severe radial artery spasm in two.ConclusionsIn the largest reported series to date of flow diverter deployment via TRA for aneurysm treatment, we demonstrate the technical feasibility and safety of the method. The most common reason for failure of TRA was an acute angle of left common carotid artery origin or left internal carotid artery tortuosity. Overall, our data suggest that increasing adoption of TRA is merited given its apparent equivalence to the current TFA technique and its documented reduction in access site complications.

OBJECTIVE Brain arteriovenous malformations (AVMs) carry a risk of rupture and subsequent morbidity or mortality unless fully treated. AVMs in pediatric patients are known to occasionally recur after obliteration. The objective of this study was to characterize the risk of AVM recurrence following angiographically confirmed obliteration in children. METHODS Consecutive pediatric AVMs treated at a single center were identified from a prospective database. Patients with angiographically confirmed AVM obliteration following treatment were included in this study. Associations between AVM recurrence and patient or procedural factors were characterized using the two-tailed Fisher exact test or Mann-Whitney U-test. A literature search was conducted using PubMed, Scopus, Embase, and the Clarivate Web of Science with defined search criteria, and eligible studies were included alongside this study cohort in a meta-analysis. Rates of AVM recurrence following obliteration were pooled across studies with a random-effects model and reported with 95% confidence intervals (CIs). RESULTS Recurrence after angiographic confirmation of AVM obliteration was observed in 10.4% (7/67) of pediatric AVMs treated at the authors’ center. Patients with recurrent AVMs were significantly younger than those without recurrence (p = 0.002). In the meta-analysis, which included 1134 patients across 24 studies, the rate of recurrence was 4.8% (95% CI 3.0%–6.7%). The rate of AVM recurrence following radiosurgery was 0.7% (95% CI 0%–1.6%), which was significantly lower than the 8.5% rate (95% CI 5.0%–12.0%) following microsurgery. CONCLUSIONS Recurrence of obliterated brain AVMs is common in children. Recurrence is more common in young children and following microsurgery.

Introduction: Previous studies have reported that Hispanic stroke patients have limited access to mechanical thrombectomy (MT) compared to other ethnic groups. This has resulted in worse stroke outcomes in this group. However, limited data is available about the outcomes of MT in Hispanic patients. Methods: We used data from the Stroke Thrombectomy and Aneurysm Registry (STAR) that combined the prospectively maintained databases of 28 thrombectomy-capable stroke centers in the US, Europe, and Asia. Consecutive patients who underwent MT were included in these analyses and patients were divided into 2 groups (Hispanics vs. non-Hispanics). Baseline features, time from symptom onset, thrombolysis receipt, final thrombolysis in cerebral infarction (TICI) score, symptomatic hemorrhage, and 90-day functional outcomes (measured by modified Rankin scale-mRS) were compared between Hispanic and non-Hispanics patients. A generalized linear model with logit link was used to assess the relationship between ethnicity and favorable outcomes at 90-day (mRS 0-2) controlling for confounders. Results: We included 2015 patients in these analyses. Of those, 285 (14.1%) were Hispanic. As shown in table 1, Hispanic patients were older (72 vs. 70, p=0.007), more likely to have diabetes (41.1% vs. 26.5%, p Conclusion: Hispanic patients receiving MT have higher rate of stroke risk factors including diabetes and hypertension. Moreover, Hispanic ethnicity was independently associated with lower probability of favorable 90-day outcome.

Introduction: Recent trials have proven safety and efficacy of mechanical thrombectomy for patients presenting with emergent large vessel occlusion beyond 6 hours of symptom onset. While evidence supports using baseline CT scan to evaluate the candidacy for mechanical thrombectomy for patients presenting in the early window, late window trials have used advanced imaging such as CT and MR perfusion. We aim to assess outcomes of MT stratified by admission Alberta Stroke Program Early CT Score (ASPECTS). Methods: We used data from the prospectively maintained registries of 28 stroke centers in the Stroke Thrombectomy and Aneurysm (STAR) collaboration. Demographics, comorbidities, LVO site, ASPECTS, MT technique, radiographic and clinical outcome data were collected. Patients with M1 or ICA occlusion were included in these analyses. Multivariable analysis was performed using a generalized linear model with logit link to assess for variables associated with favorable outcomes. Results: 3356 patients in the STAR database were reviewed and 347 (10.3%) of those underwent MT in the late window (table). Median age was 69, 189 (54.5%) were female, and 181 (52.2%) were white. 295 patients ASPECTS ≥6. In this group, 200 (68.8%) had M1 occlusion, and the remaining had ICA occlusion. Aspiration thrombectomy was used in 139 (47.1%) of patients. Successful reperfusion was achieved (mTICI≥2b) in 264 (76.1%). sICH was observed in 15 (5.1%). Excellent functional outcome (mRS 0-2) was observed in 124 (42%) patients. ASPECTS score was independently associated with favorable outcomes (aOR 1.2, 95% CI 1.1-1.4, P=0.006). Conclusion: Excellent outcomes are observed in patients with good ASPECT score presenting in the late window irrespective of perfusion criteria. Admission CT scan could be used to triage patients presenting with emergent large vessel occlusion beyond 6 hours of symptom onset.

Background The demand of thrombectomy treatment for acute ischemic stroke increased dramatically in the United States after the publication of 5 pivotal trials in 2015. The impact of call burden on career satisfaction and burnout in neurointerventionalists has not been explored. Methods A qualitative approach was chosen to obtain rich, detailed accounts of physician experiences. From July 2018 to July 2019, we conducted in-depth, semistructured interviews (mean duration, 43 minutes) with 16 academic neurointerventionalists from various institutions in the United States. Participants were chosen from the Society of Neurointerventional Surgery to include multiple specialties, career stages, and geographic locations. Key themes/subthemes were organized into a conceptual model and shown by exemplary quotes. Results Participants report a diverse range of previously uncharacterized ways in which stroke call responsibilities affect their lives. Unrealistic performance expectations, discipline-based inequalities, poor organizational workflow, limited opportunities for growth and advancement, and lack of control over call conditions are some of the key themes identified. Participants describe a need for interventions that address both the issues of workload stress (i.e., resources for stroke call and administrative work) and their ability to accomplish professional goals (i.e., flexible work arrangements, leadership autonomy support, and organizational value congruence). Conclusions The burden of stroke call has strong implications for career satisfaction and burnout in neurointerventionalists. This model can be used by hospitals, departments, and physician groups to better conceptualize conditions that facilitate burnout and attrition. Changes to hospital management practices and culture may be the most productive focal areas for intervention.

BACKGROUND Although endoscopic transsphenoidal surgery (ETSS) is an established treatment for patients with nonfunctioning pituitary adenomas (NFPAs), data are limited regarding the rates and predictors of pituitary dysfunction and recovery in a large cohort of NFPA patients undergoing ETSS. OBJECTIVE To analyze the comprehensive changes in hormonal function and identify factors that predict recovery or worsening of hormonal axes following ETSS for NFPA. METHODS Among a cohort of 601 consecutive patients who underwent ETSS for NFPA between 2010 and 2018 at Washington University in Saint Louis, recovery or development of new hypopituitarism was retrospectively analyzed in 209 patients. RESULTS Preoperative endocrine deficits were observed in 59.8% of patients (125/209), and the deficit rates were 76.8% for male gonadal axis (86/112), 42.5% for thyroid axis, 25.8% for growth hormone axis, and 15.8% for cortisol axis. Recovery of preoperative pituitary deficit was noted in all four axes, with highest recovery in the cortisol axis with a 1-year cumulative recovery rate of 44.3%. New-onset postoperative hypopituitarism occurred most frequently in the thyroid axis (24.3%, 27/111) and least frequently in the cortisol axis (9.7%, 16/165). Multivariate analyses revealed axis-specific predictors of postoperative recovery and de novo deficiency. Older age was a negative predictor for recovery of both male hypogonadism (P= 0.04) and adrenal insufficiency (P=0.046), and a larger tumor volume was a negative predictor for recovery of hypothyroidism (P=0.043). Although higher body mass index was generally associated with any new postoperative pituitary deficit (P=0.03), most predictors of new onset deficits also differed by hormone axis. CONCLUSIONS Dynamic changes in pituitary hormonal levels were observed in a significant fraction of patients following ETSS in NFPA patients. The specific hormonal axis dictated postoperative endocrine vulnerability, recovery, and predictors of recovery or loss of endocrine function.

BackgroundCurrently, there are no large-scale studies in the neurointerventional literature comparing safety between transradial (TRA) and transfemoral (TFA) approaches for flow diversion procedures. This study aims to assess complication rates in a large multicenter registry for TRA versus TFA flow diversion.MethodsWe retrospectively analyzed flow diversion cases for cerebral aneurysms from 14 institutions from 2010 to 2019. Pooled analysis of proportions was calculated using weighted analysis with 95% CI to account for results from multiple centers. Access site complication rate and overall complication rate were compared between the two approaches.ResultsA total of 2,285 patients who underwent flow diversion were analyzed, with 134 (5.86%) treated with TRA and 2151 (94.14%) via TFA. The two groups shared similar patient and aneurysm characteristics. Crossover from TRA to TFA was documented in 12 (8.63%) patients. There were no access site complications in the TRA group. There was a significantly higher access site complication rate in the TFA cohort as compared with TRA (2.48%, 95% CI 2.40% to 2.57%, vs 0%; p=0.039). One death resulted from a femoral access site complication. The overall complications rate was also higher in the TFA group (9.02%, 95% CI 8.15% to 9.89%) compared with the TRA group (3.73%, 95% CI 3.13% to 4.28%; p=0.035).ConclusionTRA may be a safer approach for flow diversion to treat cerebral aneurysms at a wide range of locations. Both access site complication rate and overall complication rate were lower for TRA flow diversion compared with TFA in this large series.

BackgroundDiagnostic cerebral angiograms are increasingly being performed by transradial access (TRA) in adults, following data from the coronary literature supporting fewer access-site complications. Despite this ongoing trend in neuroangiography, there has been no discussion of its use in the pediatric population. Pediatric TRA has scarcely been described even for coronary or other applications. This is the first dedicated large study of transradial access for neuroangiography in pediatric patients.MethodsA multi-institutional series of consecutively performed pediatric transradial angiograms and interventions was collected. This included demographic, procedural, outcomes, and safety data. Data was prospectively recorded and retrospectively analyzed.ResultsThirty-seven diagnostic angiograms and 24 interventions were performed in 47 pediatric patients. Mean age, height, and weight was 14.1 years, 158.6 cm, and 57.1 kg, respectively. The radial artery measured 2.09+/-0.54 mm distally, and 2.09+/-0.44 mm proximally. Proximal and distal angiography were performed for both diagnostic and interventional application (17 distal angiograms, two distal interventions). Clinically significant vasospasm occurred in eight patients (13.1%). Re-access was successfully performed 11 times in seven patients. Conversion to femoral access occurred in five cases (8.2%). The only access-related complication was a small asymptomatic wrist hematoma after TR band removal.ConclusionsTransradial access in pediatric patients is safe and feasible. It can be performed successfully in many cases but carries some unique challenges compared with the adult population. Despite the challenge of higher rates of vasospasm and conversion to femoral access, it is worth exploring further, given the potential benefits.

BackgroundThere are limited outcome data to guide the choice of treatment in pediatric patients with cerebral aneurysms.ObjectiveTo describe our institutional experience treating pediatric patients with cerebral aneurysms and to conduct a meta-analysis of available studies to provide the best current evidence on treatment related outcomes.MethodsWe identified pediatric patients with cerebral aneurysms evaluated or treated at our institution using a comprehensive case log. We also identified studies to include in a meta-analysis through a systematic search of Pubmed, SCOPUS, EMBASE, and the Cochrane Database of Systematic Reviews. As part of both the local analysis and meta-analysis, we recorded patient characteristics, aneurysm characteristics, management, and outcomes. Statistical analysis was performed using Fisher’s exact test and the two tailed Student’s t test, as appropriate.Results42 pediatric patients with 57 aneurysms were evaluated at our institution, and treatment specific outcome data were available in 560 patients as part of our meta-analysis. Endovascular and surgical treatments yielded comparable rates of favorable outcome in all children (88.3% vs 82.7%, respectively, P=0.097), in children with ruptured aneurysms (75% vs 83%, respectively, P=0.357), and in children with unruptured aneurysms (96% vs 97%, respectively, P=1.000).ConclusionEndovascular and surgical treatment yield comparable long term clinical outcomes in pediatric patients with cerebral aneurysms.

Flow diversion is a viable alternative for treatment of wide-neck and fusiform aneurysms originating from the posterior inferior cerebellar artery (PICA), but coverage of the PICA and vertebral perforating arteries may be a concern. The aim of this study was to examine procedural, clinical, and angiographic outcomes of patients with PICA aneurysms treated with the Pipeline Embolization Device.Retrospective review was performed of PICA aneurysms treated with the Pipeline device at 3 neurovascular centers, including periprocedural complications and clinical and angiographic outcomes.In 16 procedures, 14 PICA aneurysms were treated with the Pipeline device. These included 11 saccular aneurysms with a mean size of 7.4 mm (range, 2.0-11.1 mm) and 3 fusiform aneurysms with a mean diameter of 6.1 mm (range, 5.0-8.0 mm) and mean length of 10.3 mm (range, 6.0-15.0 mm). One patient developed a PICA territory infarct with mild leg weakness that resolved in7 days. Overall complication rate was 7% (1/14) per patient and 6% (1/16) per procedure. Mean duration of clinical follow-up was 13.5 months (range, 3 weeks to 61.7 months), with all patients returning to baseline functional status. Complete or near-complete aneurysm occlusion was achieved in 58% (7/12) of cases with angiographic follow-up (mean, 15 months; range, 4-61 months). All covered PICAs remained patent.Flow diversion of PICA aneurysms is a safe and viable treatment option when traditional endovascular options are unlikely to preserve parent vessel patency.

Background Flow diversion of posterior cerebral artery (PCA) aneurysms has not been widely reported, possibly owing to concerns regarding parent vessel size and branch vessel coverage. Objective To examine the safety and effectiveness of PCA aneurysm flow diverter treatment. Methods Retrospective review of PCA aneurysms treated with the Pipeline Embolization Device (PED; Medtronic Inc, Dublin, Ireland) at 3 neurovascular centers, including periprocedural complications and clinical and angiographic outcomes. Systematic review of the literature identified published reports of PCA aneurysms treated with flow diversion. Rates of aneurysm occlusion and complications were calculated, and outcomes of saccular and fusiform aneurysm treatments were compared. Results Ten PCA aneurysms in 9 patients were treated with the PED. There were 2 intraprocedural thromboembolic events (20%), including 1 symptomatic infarction and 1 delayed PED thrombosis. Eight of 10 patients returned to or improved from their baseline functional status. Complete aneurysm occlusion with parent vessel preservation was achieved in 75% (6/8) of cases at mean follow-up of 16.7 mo. Eleven of 12 (92%) major branch vessels covered by a PED remained patent. Including the present study, systematic review of 15 studies found a complete aneurysm occlusion rate of 88% (30/34) and complication rate of 26% (10/38), including 5 symptomatic ischemic strokes (13%; 5/38). Fusiform aneurysms more frequently completely occluded compared with saccular aneurysms (100% vs 70%; P = .03) but were associated with a higher complication rate (43% vs 9%; P = .06). Conclusion The safety and effectiveness profile of flow diverter treatment of PCA aneurysms may be acceptable in select cases.

BackgroundFlow diversion of intracranial aneurysms with the Pipeline Embolization Device (PED) is commonly performed, but the value of long-term angiographic follow-up has not been rigorously evaluated. Here we examine the prevalence of actionable findings of aneurysm recurrence and development of in-stent stenosis in a cohort of patients that underwent long-term angiographic follow-up at multiple time points.MethodsAngiographic data from eligible patients were retrospectively assessed for aneurysm occlusion, in-stent stenosis, and aneurysm regrowth or recurrence. Patients were included in this study if they underwent angiographic imaging at 6 months post-treatment and at least one later time point.Results100% (132/132) of aneurysms occluded at 6 months remained occluded at final follow-up. 85.7% (6/7), 56.3% (27/48), and 25% (6/24) of aneurysms with entry remnant, subtotal filling, and total filling, respectively, at 6 months were completely occluded at final follow-up. 98.7% (147/149) of PED constructs that demonstrated no stenosis at 6 months demonstrated no stenosis at final angiography, while 44.4% (8/18) of PED constructs demonstrating in-stent stenosis at 6 months had resolution of stenosis on final angiography.ConclusionsAmong patients who undergo treatment of intracranial aneurysms with PED, the value of long-term angiography in patients demonstrating complete aneurysm occlusion and no in-stent stenosis on 6 month post-treatment angiography is low.

Background and purpose Flow diversion may have advantages in the treatment of posterior communicating artery (PComA) aneurysms associated with a fetal origin posterior cerebral artery (PCA), which can be challenging to treat with conventional techniques. However, a PComA incorporated into the aneurysm may prevent or delay aneurysm occlusion. Also, coverage of a fetal origin PCA risks infarction of a large vascular territory. The purpose of this study was to examine the safety and effectiveness of using the Pipeline Embolization Device (PED) to treat PComA aneurysms associated with a fetal origin PCA. Patients and methods Retrospective review of PComA aneurysms associated with a fetal origin PCA treated with the PED at two neurovascular centers was performed. Periprocedural complications and clinical and angiographic outcomes were reviewed. Results Seven female patients underwent a total of seven PED procedures to treat seven PcomA aneurysms associated with a fetal origin PCA. The symptomatic complication rate was 14% (1/7) per patient and 13% (1/8) per procedure. Angiographic follow up was obtained for 6 of 7 aneurysms. Follow-up DSA at 5–7 months after treatment demonstrated complete occlusion of 17% (1/6) of aneurysms. One aneurysm was retreated with a second PED and occlusion was demonstrated 36 months after the second treatment, yielding an overall complete occlusion rate of 33% (2/6). Conclusions PED treatment was largely ineffective at treating PComA aneurysms associated with a fetal origin PCA, and should only be considered when conventional treatment options, including microsurgical clipping, are not feasible.

Background Aneurysms at the origin of the posterior communicating artery (PcommA) have been demonstrated to be effectively treated with the pipeline embolization device (PED). Much less is known about the efficacy of the PED for aneurysms associated with a fetal posterior cerebral artery (fPCA) variant. Objective To study PED treatment efficacy of PcommA aneurysms, including fPCA aneurysms. Methods A prospectively maintained university database of aneurysm patients treated with the PED was retrospectively reviewed. Demographics, treatment details, and imaging were reviewed for all PcommA and fPCA aneurysms. Results Out of a total of 285 patients treated with PED, 50 patients (mean age 57.5 ± 12.2 yr, 42 females) with unruptured PcommA (9 fPCA) aneurysms were identified. Mean follow-up duration was 14.0 ± 11.6 mo (48 patients). Roy-Raymond class I occlusion on follow-up magnetic resonance or catheter angiography (mean time 11.7 ± 6.8 mo) was achieved in 30 patients (62.5%), class II occlusion in 11 patients (22.9%) and class III occlusion in 7 patients (14.5%). The PcommA was occluded in 56% of patients without any clinical symptoms. No deaths or permanent neurological complications occurred. In fPCA aneurysms, class I occlusion was seen in 1 patient, class 2 occlusion in 2 patients, and class III occlusion in 6 patients. Multivariate analysis revealed an independent association between incomplete occlusion and fPCA configuration (OR 73.65; 95% CI: 5.84-929.13; P = .001). Conclusion The PED is a safe and effective treatment for PcommA aneurysms, although fetal anatomy should increase consideration of traditional endovascular techniques or surgical clipping.

IntroductionEndovascular embolization of intracranial meningiomas is commonly used as an adjunct to surgical resection. We sought to describe the anatomic locations and vascular supplies of meningiomas to identify characteristics predictive of successful preoperative endovascular embolization.MethodsWe conducted a retrospective review of 139 meningioma cases receiving cerebral angiograms for possible preoperative endovascular embolization at our institution between December 2000 and March 2017. The extent of embolization, arterial supply, anatomic location, and procedural complications were recorded for each case. Univariate and multivariate analyses were performed to identify tumor characteristics that predicted successful embolization.ResultsOf the total meningioma patients undergoing preoperative angiography, 78% (108/139) were successfully embolized, with a 2.8% periprocedural complication rate (3/108). Within the subset of patients with successful embolization, 31% (33/108) achieved complete angiographic embolization. Significant multivariate predictors of embolization (either partial or complete) were convexity/parasagittal locations (OR 5.15, 95% CI 0.93 to 28.54, p=0.060), meningohypophyseal trunk (MHT, OR 4.65, 95% CI 1.63 to 13.23, p=0.004), middle meningeal artery (MMA, OR 10.89, 95% CI 3.43 to 34.64, pConclusionsTumor characteristics can be used to predict the likelihood of preoperative meningioma embolization. Parasagittal and convexity meningiomas, and those with APA supply, are most likely to achieve complete angiographic embolization.

The role of somatic genetic variants in the pathogenesis of intracranial-aneurysm formation is unknown. We identified a 23-year-old man with progressive, right-sided intracranial aneurysms, ipsilateral to an impressive cutaneous phenotype. The index individual underwent a series of genetic evaluations for known connective-tissue disorders, but the evaluations were unrevealing. Paired-sample exome sequencing between blood and fibroblasts derived from the diseased areas detected a single novel variant predicted to cause a p.Tyr562Cys (g.149505130T>C [GRCh37/hg19]; c.1685A>G) change within the platelet-derived growth factor receptor β gene (PDGFRB), a juxtamembrane-coding region. Variant-allele fractions ranged from 18.75% to 53.33% within histologically abnormal tissue, suggesting post-zygotic or somatic mosaicism. In an independent cohort of aneurysm specimens, we detected somatic-activating PDGFRB variants in the juxtamembrane domain or the kinase activation loop in 4/6 fusiform aneurysms (and 0/38 saccular aneurysms; Fisher’s exact test, p < 0.001). PDGFRB-variant, but not wild-type, patient cells were found to have overactive auto-phosphorylation with downstream activation of ERK, SRC, and AKT. The expression of discovered variants demonstrated non-ligand-dependent auto-phosphorylation, responsive to the kinase inhibitor sunitinib. Somatic gain-of-function variants in PDGFRB are a novel mechanism in the pathophysiology of fusiform cerebral aneurysms and suggest a potential role for targeted therapy with kinase inhibitors.

This report illustrates the case of a 23-year-old woman with fulminant acute disseminated encephalomyelitis (ADEM) in the setting of hepatic epithelial hemangioendothelioma (EHE) requiring urgent decompressive hemicraniectomy. There were no findings suggestive of infection, angionecrotic vasculitis, or neoplasm. She had no antecedent viral infection and no other signs or symptoms of previously described paraneoplastic processes. While previous cases of ADEM requiring hemicraniectomy have been reported, this is the first without antecedent viral infection or prolonged fever at onset and in the setting of this rare liver malignancy. This case supports the inclusion of ADEM in the differential diagnosis of acute neurologic decline in the absence of malignancies associated with known paraneoplastic syndromes. EHE may be associated with paraneoplastic processes requiring urgent neurosurgical intervention.

Introduction The Pipeline Embolization Device (PED) has greatly expanded the range of aneurysms amenable to endovascular treatment, including those with wide necks that incorporate branch vessels. Published occlusion rates of anterior circulation aneurysms treated with the PED typically exceed 85%1–7 with morbidity rates of less than 7%.7 8 Prompted by this success, the PED is being increasingly utilized for the off-label treatment of posterior circulation aneurysms with widely varying results.9 10 The purpose of this study was to examine the procedural, clinical, and angiographic outcomes of patients with vertebrobasilar aneurysms treated with the PED. Methods Retrospective review of the neurointerventional databases of three high-volume neurovascular centers was approved by respective institutional review boards to identify patients with vertebrobasilar aneurysms treated with the PED between 2012 and December 2016. Demographic, clinical, and angiographic data were collected from electronic medical records. Procedural details, including devices used and peri-procedural complications, were collected from operative reports. Preoperative digital subtraction angiography was reviewed to determine the morphological characteristics of treated aneurysms, including largest diameter in any dimension, location, shape, and incorporated branch vessels. Follow-up angiographic images were also reviewed for intra-PED stenosis and patency of branch vessels covered by the PED. Results During the study period, 27 patients with 29 vertebrobasilar aneurysms underwent 28 treatments with the PED. The patients were 37% (10/27) men and 63% (17/27) women with a mean age of 53.3 years (range, 32–75 years), 44% (12/27) of whom were previous or current smokers. 74% (20/27) of patients were asymptomatic at presentation. Six of the remaining patients presented with subarachnoid hemorrhage (SAH; 22%, 6/27) and one patient presented with stroke related to thrombosis of brainstem perforators incorporated into the aneurysm (3.7%, 1/27). Aneurysm locations included the basilar trunk (41%, 12/29), basilar tip (7%, 2/29), vertebral artery (VA) proximal to the posterior inferior cerebellar artery (PICA; 10%, 3/29), VA at the PICA origin (10%, 3/29), and post-PICA VA (17%, 5/29). There were 15 saccular aneurysms (50%) with a mean size of 8.1 mm (range, 1.7–38 mm), 13 fusiform aneurysms (47%) with mean size of 11.8 mm (range, 4.3–34 mm) and length of 11.4 mm (range, 3.4–33), and one 2.9 mm blister aneurysm. The overall procedural complication rate was 18% (5/28), and the neurologic morbidity and mortality rate was 11% (3/28). Excluding aneurysms in patients who died, angiographic follow up was available for 96% (26/27) of patients. Mean duration of follow up was 12 months (range, 3–59 months). At last angiographic follow up, 67% (18/27) of aneurysms were completely occluded and 81% (22/27) were completely or near-completely occluded. A total of 36 branch vessels in 21 patients were covered by at least one PED. At last angiographic follow up, 8% (3/36) of covered branch vessels were occluded, none of which were symptomatic. Conclusion Pipeline embolization of vertebrobasilar aneurysms is associated with a higher complication rate and lower occlusion rate compared with anterior circulation aneurysms, but may be a viable treatment option in select cases. Disclosures A. Wallace: None. M. Kamran: None. T. Madaelil: None. Y. Kayan: 2; C; Medtronic, Penumbra, MicroVention. A. Kansagra: None. J. Grossberg: None. J. Delgado Almandoz: 2; C; Medtronic, Penumbra, Microvention, Accriva Diagnostics. C. Moran: 2; C; Medtronic. A. Roy: None. D. Cross: None. B. Howard: None. C. Cawley: None. J. Dion: None. T. CreveCoeur: None. J. Osbun: 1; C; MicroVention.

We report a case of renal cell carcinoma (RCC) metastasis to the calvarium and describe a strategy for percutaneous embolization of hypervascular calvarial tumors with intracranial extension. An elderly patient with history of RCC presented with left-sided weakness. Imaging studies showed a large right frontoparietal calvarial mass with intra- and extracranial extension. The tumor was devascularized by direct puncture tumor embolization using Onyx 18, allowing subsequent operative resection without significant blood loss or the need for flap reconstruction of the scalp. Compared to more common endovascular approaches, direct-needle puncture embolization of transcalvarial masses may offer lower risk of injury to scalp vessels and underlying brain parenchyma.

BACKGROUND: Chordomas and chondrosarcomas can occur in the skull base. Currently, 45% of chordomas and 56% of chondrosarcomas recur within 5 years of surgery. The role of adjuvant therapy is highly debated. No pharmacotherapies have been approved by the U.S. Food and Drug Administration for chordomas or chondrosarcomas. High propensity for recurrence and lack of definitive adjuvant therapy necessitate additional basic science research to identify molecular anomalies associated with recurrent disease.METHODS: We pooled tumor lysates from patients based on clinical criteria into 4 groups: primary chordomas, primary chordomas that recurred, primary chondrosarcomas, and primary chondrosarcomas that recurred. We used a peptide labeling method, isobaric tags for relative and absolute quantitation, to uniquely identify each tumor group. Phosphorylated peptides were identified and quantified via mass spectroscopy to determine and predict active kinases. -RESULTS: Six groups of phosphorylated peptides were associated with primary tumors that later recurred. Specific kinases associated with primary chordomas that recurred were FES and FER. Specific kinases associated with primary chondrosarcomas that recurred were FES, FER, SRC family kinases, PKC, ROCK, and mitogen-activated protein kinase signaling (JNK, ERK1, p38).CONCLUSIONS: These data provide clinicians with a means to screen skull base chordomas and chondrosarcomas to help identify tumors with a propensity to recur. Many of these kinases can be efficaciously inhibited by Food and Drug Administrationeapproved drugs that have not yet been used in clinical trials for treatment of skull base chordomas or chondrosarcomas. Validation of kinases identified in this study may advance treatment options for patients with these tumors.

Background and Purpose The Pipeline Embolization Device (PED; Covidien, Irvine, CA) is being increasingly utilized for off-label indications, but has not been widely utilized to treat posterior cerebral artery (PCA) aneurysms. Potential concerns regarding placement of the PED in the PCA include the relatively small parent vessel diameter and coverage of major branch vessels and P1 thalamic perforators. Herein, we report our experience using the PED for the treatment of PCA aneurysms. Materials and Methods Institutional review board approval was obtained to retrospectively review the neurointerventional databases of three high-volume neurovascular centers for PCA aneurysms treated with the PED between January 2012 and January 2016. Demographic information, clinical history, and outcomes were collected from electronic medical records. Procedural details and periprocedural complications were collected from operative reports. Preoperative digital subtraction angiography (DSA) was reviewed to determine aneurysm characteristics and anatomy of surrounding branch vessels. Follow up MR and DSA were reviewed for aneurysm occlusion, stenosis within the PED, and the status of branch vessels covered by the PED. Results The study included 10 PCA aneurysms in 9 patients (3 men, 6 women) with a mean age of 56 years (range, 18–74 years). There were 6 saccular aneurysms with a mean aneurysm size of 12.3 mm (range, 7–16 mm), and 4 fusiform aneurysms with mean size of 6.2 mm (range, 3.9–11.0 mm) and mean length of 18.8 mm (range, 5–45 mm). Eight aneurysms were treated with a single PED, and two aneurysms were treated with two PEDs. The PEDs ranged from 2.5–4.25 mm in diameter and 12–35 mm in length. Six of 10 PEDs were deployed entirely within the PCA. In two patients, the PED extended from the PCA into the basilar artery, covering the contralateral PCA and both superior cerebellar arteries. There were no deaths. There were two intraprocedural thromboembolic events (20%; 2/10), one of which resulted in symptomatic infarction (10%; 1/10), and one case of delayed PED thrombosis (10%; 1/10). Angiographic follow up was obtained for 9 of 10 aneurysms, including MRA for two patients, DSA for five patients, and DSA at 6 months and CTA at 24 months for one patient. The mean duration of angiographic follow up was 16.7 months (range, 2–33 months). Excluding the case of delayed parent vessel thrombosis, complete aneurysm occlusion was achieved in 75% (6/8) of cases at longest follow up during the study period. There were no instances of in-stent stenosis. All major branch vessels covered by a PED were patent at last angiographic follow. Conclusions PED embolization may be a viable treatment option for select PCA aneurysms that may be considered under appropriate clinical circumstances. Disclosures A. Wallace: None. J. Grossberg: None. J. Delgado Almandoz: None. M. Kamran: None. A. Roy: None. Y. Kayan: None. M. Austin: None. B. Howard: None. C. Moran: 2; C; Medtronic Neurovascular, Microvention. M. Cawley: None. D. Cross: None. J. Dion: None. A. Kansagra: None. J. Osbun: None.

Background Endovascular treatment of lesions associated with the cerebellar arteries is ideally performed with preservation of cerebellar artery flow, but cerebellar artery sacrifice may sometimes be necessary. Clinical outcomes and complication rates of cerebellar artery sacrifice not well defined. Methods We retrospectively reviewed cases of endovascular sacrifice of the superior cerebellar artery (SCA), posterior inferior cerebellar artery (PICA), and anterior inferior cerebellar artery (AICA) in patients with aneurysms, arteriovenous malformations (AVM), or tumors supplied by the corresponding artery. Baseline modified Rankin Scale (mRS) and pre-procedure acute intracranial hemorrhage hydrocephalus, and/or ventriculostomy were recorded along with diameter of the sacrificed cerebellar artery. Outcomes included new clinical neurological deficits, imaging evidence of cerebellar infarction, worsening hydrocephalus, new EVD placement, and craniectomy within 4 weeks of the procedure. Modified Rankin Scale at discharge and at 3 months was also recorded. Results Of the 28 patients treated with endovascular cerebellar artery sacrifice, 22 had aneurysms, 5 had AVMs, and 1 had a tumor (hemangioblastoma) fed by the sacrificed cerebellar artery. Overall, 16 PICAs, 8 SCAs, and 4 AICAs were sacrificed. The mean vessel diameter was 1.45 mm. Twelve patients (42.9%) developed clinical neurological deficits within 4 weeks of the procedure that could be attributed to the occluded vessel. Of these patients, 8 developed imaging evidence of infarction in the corresponding arterial territory within 4 weeks of the procedure. Separately, there were 3 patients that developed imaging evidence of infarction without associated clinical neurological deficits. The mean vessel diameter of patients who developed imaging evidence of infarction was 1.2 mm, and the mean vessel diameter of patients who did not develop imaging evidence of infarction was 1.5 mm. Ten patients (35.7%) developed worsening hydrocephalus within 4 weeks of the procedure; 6 of these patients required placement of a new EVD. A single patient without worsening hydrocephalus required a new EVD electively after several unsuccessful attempts at weaning the indwelling contralateral EVD. Two patients required craniotomy within 4 weeks of the procedure, one which was planned pre-procedure and the other which was for evacuation of a new acute hematoma secondary to AVM hemorrhage. Six patients (21.4%) died prior to hospital discharge. Sixteen patients (57.1%) made a good recovery at 3 months (mRS ≤2). Mean angiographic follow-up period was 137.7 days (range 0–1169 days). Conclusions Similar to open surgical cerebellar artery sacrifice, endovascular cerebellar artery sacrifice is associated with a high risk of infarction, hydrocephalus, and death. Disclosures M. Austin: None. R. Rimer: None. C. Chou: None. A. Wallace: None. M. Kamran: None. C. Moran: 2; C; Medtronic, Microvention. D. Cross: None. J. Osbun: None. G. Zipfel: 1; C; NIH, AHA. R. Dacey: None. A. Kansagra: None.

Introduction Aneurysms at the origin of the posterior communicating artery (PcommA) have been demonstrated to be effectively treated with the Pipeline Embolization Device (PED). Much less is known about the efficacy of the PED for aneurysms associated with a fetal posterior cerebral artery (fPCA) variant. Herein, the largest series of patients with ICA aneurysms at the origin of the PcommA or fPCA treated with the PED is presented. Methods A prospectively maintained university database of aneurysm patients treated with the PED was retrospectively reviewed. Demographics, treatment details, and imaging were reviewed for all PcommA and fPCA aneurysms. Results Out of a total of 285 patients treated with PED, 50 patients (mean age 57.5±12.2 years, 42 females) with unruptured PcommA (9 fPCA) aneurysms were identified. Mean follow-up duration was 14.0±11.6 months (48 patients). Roy-Raymond Class I occlusion on follow up Magnetic Resonance or catheter angiography (mean time 11.7±6.8 months) was achieved in 30 patients (62.5%), Class II occlusion in 11 patients (22.9%) and Class III occlusion in 7 patients (14.5%). The PcommA was occluded in 56% of patients without any clinical symptoms. No deaths or permanent neurological complications occurred. In fPCA aneurysms, Class I occlusion was seen in 1 patient, Class II occlusion in 2 patients, and Class III occlusion in 6 patients (figure 1). Multivariate analysis revealed an independent association between incomplete occlusion and fPCA configuration (OR 73.65; 95% CI [5.84–929.13]; p=0.001). The current literature on flow diversion treatment of fPCA aneurysms was reviewed and added to the current series and found to be associated with a low rate of aneurysm occlusion (5/23 or 22%; table 1). Conclusion PEDs are a safe and effective choice in the treatment of PcommA aneurysms. The presence of fetal anatomy, however, should increase consideration of traditional intra-saccular endovascular techniques or surgical clipping. Longer follow-up is needed to determine the ultimate efficacy of PED treatment for these aneurysms. Disclosures A. Roy: None. B. Howard: None. D. Haussen: None. J. Osbun: None. S. Halani: None. S. Skukalek: None. F. Tong: None. R. Nogueira: None. J. Dion: None. C. Cawley: None. J. Grossberg: None.

Background and Purpose Endovascular vertebral artery sacrifice is performed to facilitate surgical resection of cervical spine tumors that encase or are in close proximity the vertebral artery, other surgeries that necessitate vertebral artery transection active extravasation or delayed pseudoaneurysm secondary to penetrating trauma or deceleration injury. Herein, we report our experience with this procedure. Materials and Methods Institutional review board approval was obtained to retrospectively review the neurointerventional databases of a tertiary medical center for all cases of endovascular vertebral artery sacrifice performed between January 2003 and December 2016. Demographic information, clinical history, and outcomes were collected from electronic medical records. Procedural details and periprocedural complications were collected from operative reports. Preoperative digital subtraction angiography (DSA) was reviewed for details of vertebral artery anatomy. Results During the study period, 15 unilateral endovascular vertebral artery occlusions were performed. The cohort included 10 men and 5 women with a mean age of 55 years (range, 18–82 years). Indications for the procedure included preoperative vertebral artery sacrifice prior to cervical tumor resection (80%; 12/15), surgical fixation of a C4-C5 fracture subluxation associated with an occlusive vertebral artery dissection, surgical removal of a misplaced central line, and delayed pseudoaneurysm after gunshot trauma. The vertebral arteries were codominant in 73% (11/15) of cases. The non-dominant vertebral artery was occluded in 20% (3/15) of cases. The dominant vertebral artery was occluded in one case in which the contralateral vertebral artery measured 3 mm in maximum diameter. Prior to endovascular occlusion, the vertebral arteries were patent and normal caliber (47%; 7/15), patent but narrowed (47%; 7/15), and occluded in 1 case. Successful endovascular occlusion was achieved in 93% (13/14) of cases performed prior to surgical transection of the target artery. The mean diameter of the occluded vertebral artery segment was 3.3 mm (range, 1.7–5.7 mm). The vertebral arteries were most commonly occluded using coils (53%; 8/15) or a combination of coils and Micro Vascular Plugs (33%; 5/15; Medtronic; Plymouth, MN). One vertebral artery was occluded with a combination of coils and an Amplatzer Vascular Plug (Medtronic; Plymouth, MN) and 42 coils (patient 11), and one was occluded with 5 Micro Vascular Plugs (patient 13). The mean numbers of coils used without and with vascular plugs were 23 (range, 6–33) and 9 (range, 4–13), respectively. The mean number of Micro Vascular Plugs used in combination with coils was 2.9 (range, 1–5). Antecedent temporary balloon occlusion testing to confirm filling of the basilar artery and ipsilateral posterior inferior cerebellar artery from the contralateral vertebral artery was performed in four cases using a 7 × 7 mm (3 cases) or 4 × 7 mm (1 case) HyperForm balloon. In each of these cases the balloon was also used to arrest antegrade flow during occlusion. Five patients (33%; 5/15) received aspirin postoperatively. There were no procedure-related complications. Conclusion Endovascular vertebral artery sacrifice is a safe and effective treatment for minimizing blood loss during surgeries that involve transection of the vertebral artery. Disclosures A. Wallace: None. M. Austin: None. M. Kamran: None. A. Kansagra: None. J. Osbun: None. D. Cross: None. C. Moran: 2; C; Medtronic Neurovascular, Microvention.

There is a need to better understand meningioma oncogenesis for biomarker discovery and development of targeted therapies. Histological or genetic criteria do not accurately predict aggressiveness. Post-translational studies in meningioma progression are lacking. In the present work, we introduce a combination of mass spectrometry-based phosphoproteomics and peptide array kinomics to profile atypical and anaplastic (high-grade) meningiomas. In the discovery set of fresh-frozen tissue specimens (14), the A-kinase anchor protein 12 (AKAP12) protein was found downregulated across the grades. AKAP12 knockdown in benign meningioma cells SF4433 increases proliferation, cell cycle, migration, invasion, and confers an anaplastic profile. Differentially regulated pathways were characteristic of high-grade meningiomas. Low AKAP12 expression in a larger cohort of patients (75) characterized tumor invasiveness, recurrence, and progression, indicating its potential as a prognostic biomarker. These results demonstrate AKAP12 as a central regulator of meningioma aggressiveness with a possible role in progression.

Isolated internal carotid artery (ICA) thrombus in the absence of underlying atherosclerotic disease is a rare entity. We report a case of a patient presenting with right arm weakness, slurred speech, and altered mental status in the setting of acute on chronic pancreatitis. The patient was found to have scattered left cerebral hemisphere cortical infarctions, and catheter angiography confirmed the presence of intraluminal left ICA thrombus, with no evidence of atherosclerotic disease in the cervical or intracranial vasculature. Further workup also demonstrated the presence of anemia of chronic disease. The patient was initiated on anticoagulation, and follow-up imaging demonstrated a complete resolution of the left ICA thrombus. In the reported case, coagulopathy in the setting of acute on chronic pancreatitis was presumably the primary etiology. Anemia of chronic disease, related to a proinflammatory state, may also play a contributory role.

Brain arteriovenous malformations (AVMs) represent an uncommon disease of the central nervous system characterized by an arteriovenous shunt in which one or multiple arterial pedicles feed into a vascular nidus, creating early drainage into a venous outflow channel. These lesions are considered to be congenital and can come to clinical attention in a variety of ways such as seizure, intracranial hemorrhage, chronic headache or progressive neurological deficit. We focus on the epidemiology, clinical presentation and diagnostic evaluation in this chapter.

Background In the endovascular treatment of wide-necked unruptured aneurysms, there is controversy over which adjunctive device (stent vs balloon) is appropriate. At the payer level it has been posited that stents and balloons treat the same aneurysms, and, as such, the more expensive stents should not be reimbursed. Objective We challenge this assertion, and instead hypothesize that aneurysms treated with stent assistance are morphologically different than those selected for balloon assistance. Methods Retrospective review of unruptured aneurysms treated with an adjunctive device between 2008 and 2010. Morphological analysis was performed on the pretreatment 2-D catheter angiogram. The immediate posttreatment Raymond score was compared with that seen on the 12-month follow-up angiogram. Results One hundred six unruptured aneurysms were treated with an adjunctive device and followed for a mean of 24.5 months. Morphological analysis revealed a lower dome-to-neck ratio (1.5 vs 1.2) and aspect ratio (1.44 vs 1.16) in the aneurysms treated with stent assistance vs balloon assistance. Of the 15.3% that were worse on follow-up angiography, there was no statistical difference between those treated with a stent vs a balloon (17.1% vs 14.2%). The overall re-treatment rate was 10.2% and was not statistically different between the 2 groups (12.7% vs 5.7%). Conclusion We found that unruptured aneurysms selected for treatment with stent-assisted coiling are morphologically different from those selected for treatment with balloon assistance. Despite the more challenging morphology, Raymond scores and re-treatment rates at 1 year were not statistically different between the 2 groups, suggesting an important role for stents in the treatment of unruptured aneurysms.

Background Blood blister type aneurysms (BBAs) and pseudoaneurysms create a unique treatment challenge. Despite many advances in open surgical and endovascular techniques, this subset of patients retains relatively high rates of morbidity and mortality. Recently, BBAs have been treated with flow-diverting stents such as the Pipeline Embolization Device (PED) with overall positive results. Methods Four patients presented with dissecting internal carotid artery (ICA) aneurysms treated with the PED (two BBAs presenting with subarachnoid hemorrhage (SAH), two pseudoaneurysms after injury during endoscopic trans-sphenoidal tumor surgery). Results Three patients had a successful angiographic and neurological outcome. One patient with a BBA re-ruptured during initial PED placement, again in the postoperative period, and later died. Primary PED treatment involved telescoping stents in two patients and coil embolization supplementation in one patient. Conclusions The PED should be used selectively in the setting of acute SAH. Dual antiplatelet therapy can complicate hydrocephalus management, and the lack of immediate aneurysm occlusion creates the risk of short-term re-rupture. PED treatment for iatrogenic ICA pseudoaneurysms can provide a good angiographic and neurological outcome.

ObjectiveCarotid cavernous fistula (CCF) development after Pipeline Embolization Device (PED) treatment of cavernous carotid aneurysms (CCA) can be a challenging pathology to treat for the neurointerventionalist.MethodsA database of all patients whose aneurysms were treated with the PED since its approval by the Food and Drug Administration in 2011 was retrospectively reviewed. Demographic information, aneurysm characteristics, treatment technique, antiplatelet regimen, and follow-up data were collected. A literature review of all papers that describe PED treatment of CCA was then completed.ResultsA total of 44 patients with 45 CCAs were identified (38 women, 6 men). The mean age was 59.9±9.0 years. The mean maximal aneurysm diameter was 15.9±6.9 mm (mean neck 7.1±3.6 mm). A single PED was deployed in 32 patients, with two PEDs deployed in 10 patients and three PEDs in 3 patients. Adjunctive coiling was performed in 3 patients. Mean follow-up duration based on final imaging (MR angiography or digital subtraction angiography) was 14.1±12.2 months. Five patients (11.4%) developed CCFs in the post-procedural period after PED treatment, all within 2 weeks of device placement. These CCFs were treated with a balloon test occlusion followed by parent artery sacrifice. Our literature review yielded only three reports of CCFs after PED placement, with the largest series having a CCF rate of 2.3%.ConclusionsCCF formation is a known risk of PED treatment of CCA. Although transvenous embolization can be used for treating CCFs, parent artery sacrifice remains a viable option on the basis of these data. Studies support the view that adjunctive coiling may have a protective effect against post-PED CCF formation. None of the coiled aneurysms in our database or in the literature have ruptured. Follow-up data will lead to a better understanding of the safety profile of the PED for CCA.

Self-injection of household cleaning detergents (more specifically, commercial toilet bowl cleaner) into the reservoir of a ventriculoperitoneal shunt (VPS) has never been reported in the neurosurgical literature. A right-handed 41-year-old female with a past medical history significant for bipolar depression (with multiple prior hospital admissions for suicide attempts) and pseudotumor cerebri (status-post VPS placement from a right frontal approach) successfully injected ∼5 ml of toilet bowl cleaner into her ventricular shunt reservoir during a suicide attempt. She was found unresponsive by a family member 48 h after this event and presented to our hospital in moribund neurological condition (bilaterally fixed and dilated pupils with decerebrate posturing). Head computed tomography (CT) demonstrated marked ventriculomegaly. She was taken emergently to the operating room for placement of a left frontal ventriculostomy. Cerebrospinal fluid (CSF) sampled intraoperatively showed numerous Gram-positive cocci (later determined to be Staphylococcus epidermidis). For this reason, her right-sided shunt system was also removed in its entirety. She was treated with broad-spectrum intravenous and intraventricular antibiotics for her bacterial ventriculitis and her CSF was aggressively drained to treat her hydrocephalus. Once her infection had resolved, the shunt was replaced (using a right parietal approach) and she went on to make an excellent neurological recovery. Here, the authors present the case of a patient who self-injected household cleaning detergents into her VPS reservoir—and, likely, the ventricular system—during a suicide attempt and subsequently developed hydrocephalus and ventriculitis. Following this infrequent clinical scenario, consideration should be given to temporary ventriculostomy placement and shunt removal. Moreover, in patients with a known history of psychiatric co-morbidities—and particularly those patients with prior suicide attempts—the neurosurgeon should give serious consideration to placing the shunt system in an anatomical region which is difficult for the patient to self-access based upon their handedness.

Incisional cerebrospinal fluid (CSF) leakage after cranial surgery is a significant cause of morbidity due to poor wound healing and infection, meningitis, and pseudomeningocele formation. Many common dural closure techniques, such as sutures, autologous grafts, gelatin or collagen sponges, and fibrin glues, are used to achieve watertight closure, although none are US Food and Drug Administration approved for this use. DuraSeal Dural Sealant System is a polyethylene glycol (PEG) hydrogel approved by the U.S. Food and Drug Administration for obtaining watertight dural closure when applied after standard dural suturing. This multicenter, prospective randomized study further evaluated the safety of a PEG hydrogel compared with common dural sealing techniques.A total of 237 patients undergoing elective cranial surgery at 17 institutions were randomized to dural closure augmented with the PEG hydrogel or a control "standard of care" dural sealing technique after Valsalva maneuver demonstrated an intraoperative nonwatertight dural closure. Data were collected on complications resulting in unplanned postoperative interventions or reoperations, surgical site infections, CSF leaks, and other neurological complications within 30 days. Surgeons also provided data on the ease of use of the dural sealing techniques, as well as preparation and application times.The incidences of neurosurgical complications, surgical site infections, and CSF leaks were similar between treatment and control groups, with no statistically significant difference between the measures. In the PEG hydrogel group (n = 120), the incidence of neurosurgical complications was 5.8% (n = 7), the incidence of surgical site infections was 1.7% (n = 2), and the incidence of CSF leak was 0.8% (n = 1). In the control group (n = 117), the incidence of neurosurgical complications was 7.7% (n = 9), the incidence of surgical site infection was 2.6% (n = 3), and the incidence of CSF leak was 1.7% (n = 2). Sealant preparation time was less than 5 minutes in 96.6% of the PEG hydrogel group compared with 66.4% of controls (P

Background Meningomas represent the most common primary intracranial tumor. The majority are benign World Health Organization (WHO) Grade I lesions, but a subset of these behave in an aggressive manner. Protein biomarkers are needed to distinguish aggressive from benign Grade I lesions. Materials and Methods Pooled protein lysates were derived from five clinically aggressive Grade I and five typically benign WHO Grade I tumors snap frozen at the time of surgery. Proteins were separated in each group using two-dimensional gel electrophoresis (2DGE) and protein spots of interest were identified using liquid chromatography–mass spectrometry (LC-MS). Potential biomarker candidates were validated using western blot assays in individual tumor samples and by tissue microarray (TMA). Results Seven candidate biomarkers were obtained from the 2DGE and validated via western blot and TMA. Biomarker validation data allowed for the creation of predictive models using binary logistical regression that correctly identified 85.9% of aggressive tumors within the larger cohort of Grade I meningioma. Conclusion Simple protein separation by 2DGE and identification of candidate biomarkers by LC-MS allowed for the identification of seven candidate biomarkers that when used in predictive models accurately distinguish aggressive from benign behavior in WHO Grade I meningioma.