The circle of Willis predicts the antihypertensive effects of carotid artery stenting.

OBJECTIVE Carotid artery stenting (CAS) has antihypertensive effects, but the durability and degree of this response remain variable. The authors propose that this clinical variability is a function of the presence or absence of a complete circle of Willis (COW). Incomplete COWs perfuse through a higher-resistance pial collateral pathway, and therefore patients may require a higher mean arterial pressure (MAP). Carotid artery revascularization in these patients would reduce the end-organ collateral demand that has been hypothesized to drive the MAP response. METHODS Using a retrospective, nonrandomized within-subject case-control design, the authors compared the postoperative effects of CAS in patients with and without a complete COW by using changes in MAP and antihypertensive medication as end points. They recorded MAP and antihypertensive medications 3 months prior to surgery, preoperatively, immediately postoperatively, and at the 3-month follow-up. RESULTS Data were collected from 64 consecutive patients undergoing CAS. Patients without a complete COW (25%) were more likely to demonstrate a decrease in BP response to stenting (i.e., a drop in MAP of 10 mm Hg and/or a reduction or cessation of BP medications at 3 months postoperatively). Of the patients in the incomplete COW cohort, 75% had this outcome, whereas of those in the complete COW cohort, only 41% had it (p < 0.041). These findings remained statistically significant in a logistic regression analysis for possible confounders (p < 0.024). A receiver operating curve analysis of preoperative data indicated that a MAP > 96.3 mm Hg was 55.5% sensitive and 57.4% specific for predicting a complete COW and that patients with a MAP > 96.3 mm Hg were more likely to demonstrate a good MAP decrease following CAS (p < 0.0092). CONCLUSIONS CAS is associated with a significant decrease in MAP and/or a reduction/cessation in BP medications in patients in whom a complete COW is absent.

The Cancer Genome Atlas expression profiles of low-grade gliomas.

Differentiating between low-grade gliomas (LGGs) of astrocytic and oligodendroglial origin remains a major challenge in neurooncology. Here the authors analyzed The Cancer Genome Atlas (TCGA) profiles of LGGs with the goal of identifying distinct molecular characteristics that would afford accurate and reliable discrimination of astrocytic and oligodendroglial tumors. They found that 1) oligodendrogliomas are more likely to exhibit the glioma-CpG island methylator phenotype (G-CIMP), relative to low-grade astrocytomas; 2) relative to oligodendrogliomas, low-grade astrocytomas exhibit a higher expression of genes related to mitosis, replication, and inflammation; and 3) low-grade astrocytic tumors harbor microRNA profiles similar to those previously described for glioblastoma tumors. Orthogonal intersection of these molecular characteristics with existing molecular markers, such as IDH1 mutation, TP53 mutation, and 1p19q status, should facilitate accurate and reliable pathological diagnosis of LGGs.

Rate-controlled intraventricular endoscopic irrigation via bipolar foot pedal activation: technical note.

Irrigation during intraventricular endoscopic surgery is critical for visualization, with normal intracranial pressure maintained by balancing fluid ingress and egress. Although irrigation is typically achieved through manual manipulation of inexact stopcocks, the authors have developed a rate-controlled, foot pedal-activated system for precise intraventricular irrigation by using a standard irrigating bipolar electrocautery machine.This study is a retrospective review of patients who underwent endoscopic intraventricular surgery between January 1, 2018, and September 25, 2019, in which this irrigation system was used. Important components of this system include a bipolar module irrigation regulator that is set to a desired rate, a secure connection of the bipolar irrigation tubing to the endoscope, and one or more open egress ports on the endoscope for passive fluid drainage. Nineteen consecutive patients were identified on review (average age ± SD, 4.3 ± 4.1 years). Procedures performed included third ventriculostomies (n = 10); arachnoid/choroid cyst fenestrations/resections (n = 3); biopsy/tumor resection (n = 1); and combined procedures (n = 5). Foot pedal-controlled irrigation provided visualization of all intraventricular structures. A single operator was able to control the endoscope, endoscopic instruments, and irrigation, with assistance as indicated for more complex maneuvers. There were no perioperative complications. Because this setup is easily constructed from a standard irrigating bipolar machine, delivers precise irrigation flow rates, and facilitates a single-surgeon bimanual technique, these data support the utility of foot-controlled irrigation for endoscopic intraventricular surgery.

Extracellular Vesicles as a Platform for Glioma Therapeutic Development.

Normal and pathologic cells secrete extracellular vesicles (EV), which are defined as 30-2,000 nm spherical organelles. It has been found that EV mediate various biological functions including cellular remodeling and export of biomolecules, extracellular communication, immune stimulation and suppression, and modulation of the cellular microenvironment. EV secreted by human glioma cells contain a wealth of tumor-specific proteins and nucleic acids that can be isolated from patients with these neoplasms. Thus, EV contribute to the development of biomarkers, and additionally have certain therapeutic potential for possible use in neuro-oncology and neurosurgery.

Balloon Bridge: Novel Technique for Reaccessing Carotid Artery Stent.

BACKGROUND: Crossing a nascently deployed carotid artery stent (CAS) is required to perform angioplasty and filter recapture. If the traversing balloon or filter recapture catheters are eccentric or tangentially angled to the vertical axis of the CAS, they can ensnare on the ledge of the proximal CAS step-off, potentially causing life-threatening complications secondary to deformation, displacement, or mechanical occlusion of the stent. We report a novel "balloon bridge" technique that facilitates safe entry and passage across the CAS with both a balloon catheter and a large-bore guide catheter (LBGC). METHODS: We used the balloon bridge technique for 2 patients with >90% carotid artery stenosis and steep carotid artery angles of origin who underwent routine CAS, balloon angioplasty, and distal embolic protection. During filter recapture, the balloon was inflated across the junction of the distal LBGC tip and proximal CAS, centering the LBGC within the vessel lumen and CAS. During balloon deflation, the LBGC was sequentially advanced, successfully navigating the LBGC across the proximal stent construct without resistance or complication. RESULTS: The balloon bridge technique was completed without complications. We believe that the mechanism of action is secondary to balloon-facilitated LBGC alignment with the true axis of the stent. CONCLUSIONS: Traversing a CAS with an LBGC or balloon catheter can be tedious and fraught with the potential of neurologic peril should mechanical deformation and occlusion occur. The balloon bridge technique is safe and highly effective for navigating a catheter that is eccentric or tangentially angled to the long axis of a CAS.

Improving Door to Groin Puncture Time for Mechanical Thrombectomy via Iterative Quality Protocol Interventions.

INTRODUCTION: Delays in door to groin puncture time (DGPT) for patients with ischemic stroke caused by acute large vessel occlusions (LVO) are associated with worse clinical outcomes. We present the results of a quality improvement protocol for endovascular stroke treatment at the University of California, San Diego (UCSD) that aimed to minimize DGPT. MATERIALS AND METHODS: Our stroke team implemented a series of quality improvement measures to decrease DGPT, with a target of 90 minutes or less. Sixty-three patients treated at our center were retrospectively divided into three groups based on the date of their intervention as a proxy for the implementation of process improvement protocols: 23 patients treated from July to December 2015, 24 patients treated from January to July 2016, and 16 patients treated from July 2016 to December 2016. Multivariate log-linear and logistic regression analyses were used to assess the predictors of prolonged DGPT and compliance with target DGPT (<90 min), respectively. RESULTS: Date of intervention-a proxy for the implementation of process improvement protocols-was predictive of compliance with target DGPT. Patients treated from July 2016 to December 2016-after the full implementation of process improvements-were 3.2 times more likely to meet or exceed the target DGPT compared to patients treated from July 2015 to December 2015 (p=0.011). When adjusting for potential confounders in a multivariate analysis, patients in the final cohort were associated with shorter DGPT (Exp(B)=0.61, p=0.013) and remained significantly more likely to achieve the DGPT goal (OR=14.2, p=0.007). CONCLUSION: An iterative quality improvement process can significantly improve DGPT. This analysis demonstrates the utility of a formal quality improvement system at an academic comprehensive stroke center.

Comprehensive Endovascular and Open Surgical Management of Cerebral Arteriovenous Malformations.

Arteriovenious malformations (AVMs) are associated with significant morbidity and mortality, and have a rupture risk of ~3% per year. Treatment of AVMs must be tailored specifically to the lesion, with surgical resection being the gold standard for small, accessible lesions. Pre-operative embolization of AVMs can reduce nidal blood flow and remove high-risk AVM features such as intranidal or venous aneurysms, thereby simplifying a challenging neurosurgical procedure. Herein, we describe our approach for the staged endovascular embolization and open resection of AVMs, and highlight the advantages of having a comprehensively trained neurovascular surgeon leading a multi-disciplinary clinical team. This includes planning the craniotomy and resection to immediately follow the final embolization stage, thereby using a single session of anesthesia for aggressive embolization, and rapid resection. Finally, we provide a representative case of a 22-year-old female with an unruptured right frontal AVM diagnosed during a seizure workup, who was successfully treated via staged embolizations followed by open surgical resection.

Low-profile Visualized Intraluminal Support Junior Device for the Treatment of Intracranial Aneurysms.

OBJECTIVE: Early case series suggest that the recently introduced Low-profile Visualized Intraluminal Support Junior (LVIS Jr.) device (MicroVention-Terumo, Inc., Tustin, CA) may be used to treat wide-necked aneurysms that would otherwise require treatment with intrasaccular devices or open surgery. We report our single-center experience utilizing LVIS Jr. to treat intracranial aneurysms involving 1.8-2.5 mm parent arteries. METHODS: We retrospectively reviewed records of patients treated with the LVIS Jr. device for intracranial aneurysms at a single center. A total of 21 aneurysms were treated in 18 patients. Aneurysms were 2-25 mm in diameter; one was ruptured, while three had recurred after previous rupture and treatment. Lesions were distributed across the anterior (n=12) and posterior (n=9) circulations. Three were fusiform morphology. RESULTS: Stent deployment was successful in 100% of cases with no immediate complications. Seventeen aneurysms were treated with stent-assisted coil embolization resulting in immediate complete occlusion in 94% of cases. Two fusiform aneurysms arising from the posterior circulation were further treated with elective clip ligation after delayed expansion and recurrence; no lesions required further endovascular treatment. Four aneurysms were treated by flow diversion with stand-alone LVIS Jr. stent, and complete occlusion was achieved in three cases. Small foci of delayed ischemic injury were noted in two patients in the setting of antiplatelet medication noncompliance. No in-stent stenosis, migration, hemorrhage, or permanent deficits were observed. Good functional outcome based on the modified Rankin Scale score (mRS ≤ 2) was achieved in 100% of cases. CONCLUSION: Our midterm results suggest that the LVIS Jr. stent may be used for a variety of intracranial aneurysms involving small parent arteries (1.8-2.5 mm) with complete angiographic occlusion, parent vessel preservation, and functional clinical outcomes. This off-label expansion would increase the number of aneurysms amenable to endovascular treatment. Future studies may build upon our experiences with flow diversion and treatment of complex or multiple lesions.

Hypoplastic Internal Carotid Artery Co-Presenting with Neurofibromatosis and Intracranial Masses.

Neurofibromatosis type 1 (NF1) is associated with systemic vascular disease, and it can also affect intracranial vasculature in a small percentage of patients. Very rarely, NF1 may co-present with hypoplasia of the internal carotid artery (ICA). Prior reports have documented NF1 with bilateral optic gliomas and a unilateral hypoplastic internal carotid artery; however, we report a case with the aforementioned findings in addition to a right-sided lentiform mass. This case report further suggests a common congenital pathway related to neurofibromin loss of function resulting in both nerve sheath tumors and cerebrovascular anomalies.

Simulator-Based Angiography and Endovascular Neurosurgery Curriculum: A Longitudinal Evaluation of Performance Following Simulator-Based Angiography Training.

This study establishes performance metrics for angiography and neuroendovascular surgery procedures based on longitudinal improvement in individual trainees with differing levels of training and experience. Over the course of 30 days, five trainees performed 10 diagnostic angiograms, coiled 10 carotid terminus aneurysms in the setting of subarachnoid hemorrhage, and performed 10 left middle cerebral artery embolectomies on a Simbionix Angio Mentor™ simulator. All procedures were nonconsecutive. Total procedure time, fluoroscopy time, contrast dose, heart rate, blood pressures, medications administered, packing densities, the number of coils used, and the number of stent-retriever passes were recorded. Image quality was rated, and the absolute value of technically unsafe events was recorded. The trainees' device selection, macrovascular access, microvascular access, clinical management, and the overall performance of the trainee was rated during each procedure based on a traditional Likert scale score of 1=fail, 2=poor, 3=satisfactory, 4=good, and 5=excellent. These ordinal values correspond with published assessment scales on surgical technique. After performing five diagnostic angiograms and five embolectomies, all participants demonstrated marked decreases in procedure time, fluoroscopy doses, contrast doses, and adverse technical events; marked improvements in image quality, device selection, access scores, and overall technical performance were additionally observed (p < 0.05). Similarly, trainees demonstrated marked improvement in technical performance and clinical management after five coiling procedures (p < 0.05). However, trainees with less prior experience deploying coils continued to experience intra-procedural ruptures up to the eighth embolization procedure; this observation likely corresponded with less tactile procedural experience to an exertion of greater force than appropriate for coil placement. Trainees across all levels of training and prior experience demonstrated a significant performance improvement after completion of our simulator curriculum consisting of five diagnostic angiograms, five embolectomy cases, and 10 aneurysm coil embolizations.

Extracellular vesicles as a platform for 'liquid biopsy' in glioblastoma patients.

Extracellular vesicles (EVs) are cell-secreted vesicles that range from 30-2000 nm in size. These vesicles are secreted by both normal and neoplastic cells. Physiologically, EVs serve multiple critical biologic functions, including cellular remodeling, intracellular communication, modulation of the tumor microenvironment and regulation of immune function. Because EVs contain genetic and proteomic contents that reflect the cell of origin, it is possible to detect tumor-specific material in EVs secreted by cancer cells. Importantly, EVs secreted by cancer cells transgress anatomic compartments and can be detected in the blood, cerebrospinal fluid, and other biofluids of cancer patients. In this context, there is a growing interest in analyzing EVs from the biofluid of cancer patients as a means of disease diagnosis and therapeutic monitoring. In this article, we review the development of EVs as a diagnostic platform for the most common form of brain cancer, glioblastoma, discuss potential clinical translational opportunities and identify the central challenges associated with future clinical applications.

Epidemiology of metastatic brain tumors.

Metastatic tumors are the most common brain tumors in adults, and their incidence is increasing. An accurate understanding of the epidemiology of metastatic brain tumors is useful for health care professionals to allocate appropriate clinical, diagnostic, therapeutic, and research resources. Reported incidences in the literature are derived from epidemiologic population-based studies; clinical studies from surgical, radiological, and autopsy series; and reviews of hospital and clinical medical records. Despite these various sources of information, an accurate incidence of metastatic brain tumors is difficult, and current figures are estimates at best. Here, we review the available data regarding the epidemiology of metastatic brain tumors.