Strategies to Improve Drug Delivery Across the Blood-Brain Barrier for Glioblastoma.

PURPOSE OF REVIEW: Glioblastoma remains resistant to most conventional treatments. Despite scientific advances in the past three decades, there has been a dearth of effective new treatments. New approaches to drug delivery and clinical trial design are needed. RECENT FINDINGS: We discuss how the blood-brain barrier and tumor microenvironment pose challenges for development of effective therapies for glioblastoma. Next, we discuss treatments in development that aim to overcome these barriers, including novel drug designs such as nanoparticles and antibody-drug conjugates, novel methods of drug delivery, including convection-enhanced and intra-arterial delivery, and novel methods to enhance drug penetration, such as blood-brain barrier disruption by focused ultrasound and laser interstitial thermal therapy. Lastly, we address future opportunities, positing combination therapy as the best strategy for effective treatment, neoadjuvant and window-of-opportunity approaches to simultaneously enhance therapeutic effectiveness with interrogation of on-treatment biologic endpoints, and adaptive platform and basket trials as imperative for future trial design. New approaches to GBM treatment should account for the blood-brain barrier and immunosuppression by improving drug delivery, combining treatments, and integrating novel clinical trial designs.

Arteriovenous shunts of the cervical spine: patient demographics, presentation, patterns of high-risk venous drainage, and updated classification.

BACKGROUND: Intracranial dural arteriovenous (AV) fistula classifications focus on presence/absence of retrograde flow in the cortical veins of the brain as this angiographic finding portends a worse prognosis. However, prior categorization systems of AV shunts in the spine do not incorporate these features. We propose an updated classification for spinal shunting lesions that terms any shunting lesion with retrograde flow in any cortical vein of the brain or spinal cord medullary vein as "high risk". To present this classification, we analyzed our center's most recent experience with cervical spine shunting lesions. METHODS: The electronic medical record at our institution was reviewed to identify shunting lesions of the cervical spine and patient demographics/presentation. Comprehensive craniospinal digital subtraction angiograms were evaluated to classify shunt location, type (arteriovenous malformation (AVM) vs arteriovenous fistula (AVF)), and presence of high-risk venous drainage. RESULTS: Some 52 lesions were identified and categorized as pial/dural/epidural/paravertebral AVFs and intramedullary/extraspinal AVMs. Lesions were classified as high risk or not depending on the presence of retrograde flow into at least one vein that directly drains the spinal cord or brain. All patients who presented with either hemorrhage or infarct had underlying high-risk lesions. Additionally, 50% (17/34) of symptomatic patients with high-risk lesions presented with neurological extremity symptoms (OR=10.0, p=0.037) most of which fit a myelopathic pattern. CONCLUSION: We present an updated classification system for shunting lesions of the spine that focuses on high-risk retrograde flow to the brain or spine in addition to anatomical location in order to better inform patient management.

Endovascular therapy for anterior circulation emergent large vessel occlusion stroke in patients with large ischemic cores: a report of the SNIS Standards and Guidelines Committee.

BACKGROUND: Early clinical trials validating endovascular therapy (EVT) for emergent large vessel occlusion (ELVO) ischemic stroke in the anterior circulation initially focused on patients with small or absent completed infarctions (ischemic cores) to maximize the probability of detecting a clinically meaningful and statistically significant benefit of EVT. Subsequently, real-world experience suggested that patients with large core ischemic strokes (LCS) at presentation may also benefit from EVT. Several large, retrospective, and prospective randomized clinical trials have recently been published that further validate this approach. These guidelines aim to provide an update for endovascular treatment of LCS. METHODS: A structured literature review of LCS studies available since 2019 and grading the strength and quality of the evidence was performed. Recommendations were made based on these new data by consensus of the authors, with additional input from the full SNIS Standards and Guidelines Committee and the SNIS Board of Directors. RESULTS: The management of ELVO strokes with large ischemic cores continues to evolve. The expert panel agreed on several recommendations: Recommendation 1: In patients with anterior circulation ELVO who present within 24 hours of last known normal with large infarct core (70-149 mL or ASPECTS 3-5) and meet other criteria of RESCUE-Japan LIMIT, SELECT2, ANGEL-ASPECT, TESLA, TENSION, or LASTE trials, thrombectomy is indicated (Class I, Level A). Recommendations 2-7 flow directly from recommendation 1. Recommendation 2: EVT in patients with LCS aged 18-85 years is beneficial (Class I, Level A). Recommendation 3: EVT in patients with LCS >85 years of age may be beneficial (Class I, Level B-R). Recommendation 4: Patients with LCS and NIHSS score 6-30 benefit from EVT in LCS (Class I, Level A). Recommendation 5: Patients with LCS and NIHSS score <6 and >30 may benefit from EVT in LCS (Class IIa, Level A). Recommendation 6: Patients with LCS and low baseline mRS (0-1) benefit from EVT (Class I, Level A). Recommendation 7: Patients with LCS and time of last known well 0-24 hours benefit from EVT (Class I, Level A). Recommendation 8: It is recommended that patients with ELVO LCS who also meet the criteria for on-label or guideline-directed use of IV thrombolysis receive IV thrombolysis, irrespective of whether endovascular treatments are being considered (Class I, Level B-NR). CONCLUSIONS: The indications for endovascular treatment of ELVO strokes continue to expand and now include patients with large ischemic cores on presentation. Further prospective randomized studies, including follow-up to assess the population-based efficacy of treating patients with LCS, are warranted.

MR Thermometry during Transcranial MR Imaging-Guided Focused Ultrasound Procedures: A Review.

Interest in transcranial MR imaging-guided focused ultrasound procedures has recently grown. These incisionless procedures enable precise focal ablation of brain tissue using real-time monitoring by MR thermometry. This article will provide an updated review on clinically applicable technical underpinnings and considerations of proton resonance frequency MR thermometry, the most common clinically used MR thermometry sequence.

Transvenous coil embolization of a Cognard V transverse-sigmoid sinus dural arteriovenous fistula.

Dural arteriovenous fistulas with drainage into the spinal veins, classified as Cognard type 5, can be challenging to diagnose and treat. Brainstem and cervical spinal cord signal abnormalities on magnetic resonance imaging result from venous congestion, and can mimic tumor, infection, or inflammation.1-3 Transarterial and transvenous embolization techniques can be used to treat dural arteriovenous fistulas endovascularly. Efficacious transvenous treatment relies on the ability to safely catheterize the draining vein at the dural arteriovenous fistula site. Transvenous access options may seem limited in the setting of occluded venous sinuses. This case highlights the technical aspects of the transvenous approach to embolization of a transverse-sigmoid sinus dural arteriovenous fistula within an isolated sinus,4,5 demonstrating traversal of the occluded venous sinus from a contralateral approach.6,7[Media: see text].

Robotic Diagnostic Cerebral Angiography: A Multicenter Experience of 113 Patients.

BACKGROUND: Neurointerventional robotic systems have potential to reduce occupational radiation, improve procedural precision, and allow for future remote teleoperation. A limited number of single institution case reports and series have been published outlining the safety and feasibility of robot-assisted diagnostic cerebral angiography. METHODS: This is a multicenter, retrospective case series of patients undergoing diagnostic cerebral angiography at three separate institutions - University of California, Davis (UCD); University of California, Los Angeles (UCLA); and University of California, San Francisco (UCSF). The equipment used was the CorPath GRX Robotic System (Corindus, Waltham, MA). RESULTS: A total of 113 cases were analyzed who underwent robot-assisted diagnostic cerebral angiography from September 28, 2020 to October 27, 2022. There were no significant complications related to use of the robotic system including stroke, arterial dissection, bleeding, or pseudoaneurysm formation at the access site. Using the robotic system, 88 of 113 (77.9%) cases were completed successfully without unplanned manual conversion. The principal causes for unplanned manual conversion included challenging anatomy, technical difficulty with the bedside robotic cassette, and hubbing out of the robotic system due to limited working length. For robotic operation, average fluoroscopy time was 13.2 min (interquartile range (IQR), 9.3 to 16.8 min) and average cumulative air kerma was 975.8 mGY (IQR, 350.8 to 1073.5 mGy). CONCLUSIONS: Robotic cerebral angiography with the CorPath GRX Robotic System is safe and easily learned by novice users without much prior manual experience. However, there are technical limitations such as a short working length and an inability to support 0.035" wires which may limit its widespread adoption in clinical practice.

Clinical evaluation of pulsatile tinnitus: history and physical examination techniques to predict vascular etiology.

BACKGROUND: Pulsatile tinnitus (PT) may be due to a spectrum of cerebrovascular etiologies, ranging from benign venous turbulence to life threatening dural arteriovenous fistulas. A focused clinical history and physical examination provide clues to the ultimate diagnosis; however, the predictive accuracy of these features in determining PT etiology remains uncertain. METHODS: Patients with clinical PT evaluation and DSA were included. The final etiology of PT after DSA was categorized as shunting, venous, arterial, or non-vascular. Clinical variables were compared between etiologies using multivariate logistic regression, and performance at predicting PT etiology was determined by area under the receiver operating curve (AUROC). RESULTS: 164 patients were included. On multivariate analysis, patient reported high pitch PT (relative risk (RR) 33.81; 95% CI 3.81 to 882.80) compared with exclusively low pitch PT and presence of a bruit on physical examination (9.95; 2.04 to 62.08; P=0.007) were associated with shunting PT. Hearing loss was associated with a lower risk of shunting PT (0.16; 0.03 to 0.79; P=0.029). Alleviation of PT with ipsilateral lateral neck pressure was associated with a higher risk of venous PT (5.24; 1.62 to 21.01; P=0.010). An AUROC of 0.882 was achieved for predicting the presence or absence of a shunt and 0.751 for venous PT. CONCLUSION: In patients with PT, clinical history and physical examination can achieve high performance at detecting a shunting lesion. Potentially treatable venous etiologies may also be suggested by relief with neck compression.

Evolving indications for pediatric neurointerventional radiology: A single institutional 25-year experience in infants less than one year of age and a brief historical review.

BACKGROUND AND PURPOSE: Pediatric neurointerventional radiology is an evolving subspecialty with growing indications and technological advancement such as miniaturization of devices and decreased radiation dose. The ability to perform these procedures is continuously balanced with necessity given the inherently higher risks of radiation and cerebrovascular injury in infants. The purpose of this study is to review our institution's neurointerventional experience in infants less than one year of age to elucidate trends in this patient population. METHODS: We retrospectively identified 132 patients from a neurointerventional database spanning 25 years (1997-2022) who underwent 226 procedures. Treatment type, indication, and location as well as patient demographics were extracted from the medical record. RESULTS: Neurointerventional procedures were performed as early as day of life 0 in a patient with an arteriovenous shunting malformation. Average age of intervention in the first year of life is 5.9 months. Thirty-eight of 226 procedures were completed in neonates. Intra-arterial chemotherapy (IAC) for the treatment of retinoblastoma comprised 36% of neurointerventional procedures completed in infants less than one year of age followed by low flow vascular malformations (21.2%), vein of Galen malformations (11.5%), and dural arteriovenous fistulas (AVF) (9.3%). Less frequent indications include non-Galenic pial AVF (4.4%) and tumor embolization (3.0%). The total number of interventions has increased secondary to the onset of retinoblastoma treatment in 2010 at our institution. CONCLUSION: The introduction of IAC for the treatment of retinoblastoma in the last decade is the primary driver for the increased trend in neurointerventional procedures completed in infants from 1997 to 2022.

Cerebrovascular pulsatile tinnitus: causes, treatments, and outcomes in 164 patients with neuroangiographic correlation.

BACKGROUND: Pulsatile tinnitus (PT) can cause significant detriment to quality of life and may herald a life-threatening condition. Endovascular evaluation is the gold standard for the definitive diagnosis of PT and facilitates treatment. However, no large study has determined the distribution of causes and treatment outcomes of PT evaluated endovascularly. METHODS: Consecutive patients evaluated at a multidisciplinary PT clinic from a single academic center were retrospectively reviewed. Patients with a suspected cerebrovascular etiology of PT based on clinical and/or non-invasive imaging, who were evaluated by endovascular techniques (arteriography, venography, manometry, and/or balloon test occlusion), were included in analysis. Baseline clinical features and treatment results by final etiology of PT were compared. RESULTS: Of 552 patients referred for PT evaluation, 164 patients (29.7%) who underwent endovascular evaluation of PT were included. Mean (±SD) age at first clinical evaluation was 54.3±14.1 years (range 25-89 years); 111 patients (67.7%) were female. PT causes were 75.6% vascular and 24.4% non-vascular. Arteriovenous shunting lesions caused 20.7% of cases, venous etiologies 48.2%, and arterial etiologies 6.7%. Of patients with a shunting lesion treated with endovascular embolization, 96.9% had lasting significant improvement or resolution in PT. Endovascular stenting for venous sinus stenosis gave 84.6% of patients lasting improvement or resolution in PT. Arterial and non-vascular PT had fewer patients treated endovascularly and less improvement in PT symptoms. CONCLUSION: PT with a suspected vascular cause is most often attributable to venous etiologies. PT caused by arteriovenous shunting or venous sinus stenosis may be effectively treated endovascularly.

Percutaneous sclerotherapy for head and neck lymphatic malformations in neonates and infants ≤12 months of age.

BACKGROUND: Percutaneous sclerotherapy is an effective treatment for lymphatic malformations (LM) of the head and neck in adults. The purpose of this study was to examine the indications and efficacy of sclerotherapy for head/neck LM in the neonate and infant population. METHODS: We retrospectively reviewed patients treated with percutaneous sclerotherapy for LM of the head/neck at age ≤12 months at a single vascular anomalies clinic. The clinical, anatomic, and technical aspects of each treatment, complications, and post-treatment clinical and imaging outcomes were analyzed. RESULTS: 22 patients underwent 36 treatments during the first year of life. Median age at first treatment was 6.2 months (range 2-320 days). Severe airway compromise was the most frequent indication for treatment (31.8%). Sclerosants included doxycycline (80.5%), sodium tetradecyl sulfate (55.5%), bleomycin (11.1%) and ethanol (2.8%). There were no immediate procedure-related complications; sclerosant-related laboratory complications included transient metabolic acidosis (8.3%) and hemolytic anemia (5.5%). Median follow-up was 3.7 years (IQR 0.6-4.8). 47.6% of patients showed >75% lesion size reduction and 19.0% showed minimal response (<25% improvement). At last follow-up, 71.4% of children were developmentally normal and asymptomatic, 23.8% had recurring symptoms, and 4.8% required permanent tracheostomy. Patients with ongoing symptoms or limited response to percutaneous sclerotherapy (33.3%) were treated with long-term sirolimus. CONCLUSIONS: Percutaneous sclerotherapy is a safe and effective treatment for symptomatic LM of the head and neck in neonates and infants. Treatment strategy and management of recurrent symptoms requires consensus from an experienced, multidisciplinary team.

MRI-guided endovascular intervention: current methods and future potential.

INTRODUCTION: Image-guided endovascular interventions, performed using the insertion and navigation of catheters through the vasculature, have been increasing in number over the years, as minimally invasive procedures continue to replace invasive surgical procedures. Such endovascular interventions are almost exclusively performed under x-ray fluoroscopy, which has the best spatial and temporal resolution of all clinical imaging modalities. Magnetic resonance imaging (MRI) offers unique advantages and could be an attractive alternative to conventional x-ray guidance, but also brings with it distinctive challenges. AREAS COVERED: In this review, the benefits and limitations of MRI-guided endovascular interventions are addressed, systems and devices for guiding such interventions are summarized, and clinical applications are discussed. EXPERT OPINION: MRI-guided endovascular interventions are still relatively new to the interventional radiology field, since significant technical hurdles remain to justify significant costs and demonstrate safety, design, and robustness. Clinical applications of MRI-guided interventions are promising but their full potential may not be realized until proper tools designed to function in the MRI environment are available. Translational research and further preclinical studies are needed before MRI-guided interventions will be practical in a clinical interventional setting.

Intraoperative Angiogram Using C-Arm Fluoroscopy and Direct Common Carotid Artery Puncture During Surgical Treatment of Paraclinoid Aneurysms.

BACKGROUND: Intraoperative angiography (IOA) has been shown to be a useful adjunct in surgical treatment of cerebral aneurysms. However, its use can be limited by hybrid operating room availability. On the other hand, the use of C-arm fluoroscopy can add challenges to IOA during navigation of the aortic arch and selection of the great vessels. We aimed to describe a simple method of IOA that can be applied during surgery of paraclinoid aneurysms and can be performed in a normal operating room without the need to navigate the aortic arch. METHODS: In patients undergoing surgery for paraclinoid aneurysms with need for cervical carotid artery exposure, IOA was performed using a single plane C-arm fluoroscopy unit after direct puncture of the carotid artery. RESULTS: Five patients were included: 2 with subarachnoid hemorrhage, 2 with unruptured aneurysm and history of subarachnoid hemorrhage, and 1 with unruptured aneurysm. There were 2 internal carotid blister aneurysms, 2 ophthalmic artery aneurysms, and 1 superior hypophyseal artery aneurysm. IOA was performed using direct carotid puncture through the neck incision required for proximal control. In all cases, intraoperative images were of sufficient quality to determine the completeness of aneurysm occlusion as well as parent and branching vessel patency. There were no postoperative infarctions and no complications related to IOA. CONCLUSIONS: IOA using direct carotid puncture can be performed in a standard operating room with the use of a C-arm, eliminating the need to catheterize the great vessels of the aortic arch.

Endovascular Therapy for Intracranial Giant Cell Arteritis : Systematic Review, Technical Considerations and the Effect of Intra-arterial Calcium Channel Blockers.

BACKGROUND: Giant cell arteritis (GCA) is a systemic vasculitis that may cause ischemic stroke. Rarely, GCA can present with aggressive intracranial stenoses, which are refractory to medical therapy. Endovascular treatment (EVT) is a possible rescue strategy to prevent ischemic complications in intracranial GCA but the safety and efficacy of EVT in this setting are not well-described. METHODS: A systematic literature review was performed to identify case reports and series with individual patient-level data describing EVT for intracranial GCA. The clinical course, therapeutic considerations, and technique of seven endovascular treatments in a single patient from the authors' experience are presented. RESULTS: The literature review identified 9 reports of 19 treatments, including percutaneous transluminal angioplasty (PTA) with or without stenting, in 14 patients (mean age 69.6 ± 6.3 years). Out of 12 patients 8 (66.7%) with sufficient data had > 1 pre-existing cardiovascular risk factor. All patients had infarction on MRI while on glucocorticoids and 7/14 (50%) progressed despite adjuvant immunosuppressive agents. Treatment was PTA alone in 15/19 (78.9%) cases and PTA + stent in 4/19 (21.1%). Repeat treatments were performed in 4/14 (28.6%) of patients (PTA-only). Non-flow limiting dissection was reported in 2/19 (10.5%) of treatments. The indications, technical details, and results of PTA are discussed in a single illustrative case. We report the novel use of intra-arterial calcium channel blocker infusion (verapamil) as adjuvant to PTA and as monotherapy, resulting in immediate improvement in cerebral blood flow. CONCLUSION: Endovascular treatment, including PTA with or without stenting or calcium channel blocker infusion, may be effective therapies in medically refractory GCA with intracranial stenosis.

Pharyngo-tympano-stapedial middle meningeal artery variant supply to a falcotentorial dural arteriovenous fistula.

The pharyngo-tympano-stapedial middle meningeal artery (PTS-MMA) variant has been described in one case report and never in the setting of arterial supply to a dural arteriovenous fistula, to our knowledge. We report the case of a middle-aged patient with severe, daily headache who presented to our institution for angiography and treatment. CT angiography and MRI demonstrated an enlarged left middle meningeal artery coursing to a large venous varix in the falcotentorial region. Dural arteriovenous fistula was confirmed by subsequent cerebral angiography. Endovascular treatment was performed but without complete obliteration of the fistula. Follow-up angiography demonstrated parasitized arterial supply from a right middle meningeal artery arising from the proximal cervical internal carotid artery coursing through the middle ear consistent with a PTS-MMA variant. The fistula was then treated surgically without recurrence at the 6-month follow-up.

Eptifibatide bridging therapy for staged carotid artery stenting and cardiac surgery: Safety and feasibility.

BACKGROUND: Prophylactic carotid artery stenting (CAS) is an effective strategy to reduce perioperative stroke in patients with severe carotid stenosis who require cardiothoracic surgery (CTS). Staging both procedures (CAS-CTS) during a single hospitalization presents conflicting demands for antiplatelet therapy and the optimal pharmacologic strategy between procedures is not established. The purpose of this study is to present our initial experience with a "bridging" protocol for staged CAS-CTS. METHODS: A retrospective review of staged CAS-CTS procedures at a single referral center was performed. All patients had multivessel coronary and/or valvular disease and severe carotid stenosis (>70%). Patients not previously on aspirin were also started on aspirin prior to surgery, followed by eptifibatide during CAS (intraprocedural bolus followed by post-procedural infusion which was continued until the morning of surgery). Pre- and perioperative (30 days) neurologic morbidity and mortality was the primary endpoint. RESULTS: 11 CAS procedures were performed in 10 patients using the protocol. The median duration of eptifibatide bridge therapy was 36 h (range 24-288 h). There was one minor bleeding complication (1/11, 9.1%) and no major bleeding complications during the bridging and post-operative period. There was one post-operative, non-neurologic death and zero perioperative ischemic strokes. CONCLUSIONS: For patients undergoing staged CAS-CTS, Eptifibatide bridging therapy is a viable temporary antiplatelet strategy with a favorable safety profile. This strategy enables a flexible range of time-intervals between procedures.

Management of vascular causes of pulsatile tinnitus.

Pulsatile tinnitus is a debilitating symptom affecting millions of Americans and can be a harbinger of hemorrhagic or ischemic stroke. Careful diagnostic evaluation of pulsatile tinnitus is critical in providing optimal care and guiding the appropriate treatment strategy. When a vascular cause of pulsatile tinnitus has been established, attention must be focused on the patient's risk of hemorrhagic stroke, ischemic stroke, or blindness, as well as the risks of the available treatment options, in order to guide decision-making. Herein we review our approach to management of the vascular causes of pulsatile tinnitus and provide a literature review while highlighting gaps in our current knowledge and evidence basis.

Diagnostic Approach to Pulsatile Tinnitus: A Narrative Review.

Importance: Pulsatile tinnitus is a debilitating symptom affecting millions of Americans and can be a harbinger of hemorrhagic or ischemic stroke. Careful diagnostic evaluation of pulsatile tinnitus is critical in providing optimal care and guiding the appropriate treatment strategy. Observations: An underlying cause of pulsatile tinnitus can be identified in more than 70% of patients with a thorough evaluation. We advocate categorizing the myriad causes of pulsatile tinnitus into structural, metabolic, and vascular groups. Structural causes of pulsatile tinnitus include neoplasms and temporal bone pathologic abnormalities. Metabolic causes of pulsatile tinnitus include ototoxic medications and systemic causes of high cardiac output. Vascular causes of pulsatile tinnitus include idiopathic intracranial hypertension and dural arteriovenous fistulas. This categorization facilitates a practical evaluation, referral, and treatment pattern. Conclusions and Relevance: Categorizing the underlying cause of pulsatile tinnitus ensures that dangerous causes of pulsatile tinnitus are not missed, and that patients receive the appropriate care from the proper specialist when needed.

Endovascular treatment strategy, technique, and outcomes for dural arteriovenous fistulas of the marginal sinus region.

BACKGROUND: Dural arteriovenous fistulas (AVF) of the foramen magnum region (FMR) are technically challenging lesions to treat. Transvenous (TV), transarterial (TA), and surgical approaches have been described, but the optimum treatment strategy is not defined. OBJECTIVE: To report treatment strategies and outcomes for FMR-AVF at a single, high-volume referral center. METHODS: A retrospective review from January 2010 to August 2020 identified patients with FMR-AVF at a single referral center. Angiographic features, treatment (observation, endovascular, surgical), and follow-up of angiographic and clinical results were recorded. The technical aspects of TV embolization are then presented in detail. RESULTS: 29 FMR-AVF were identified in 28 patients. Of these, 24/29 (82.8%) were treated and 5/29 (17.2%) were observed. Treatment was endovascular in 21/24 (87.5%), combined (endovascular+surgical) in 2/24 (8.3%), and surgical in 1/24 (4.2%). Endovascular treatments were 76.2% TV, 14.3% TA, and 9.5% combined TV/TA. Sufficient follow-up data were available for 20/28 (71.4%) with mean follow-up of 16.8 months. No AVF recurrence was seen for TA/TV, combined endovascular/surgical, or surgical groups, and there was one recurrence (7.1%) in the TV group. Symptomatic improvement was seen in all groups: TV (71.4% complete, 28.6% partial), TA (66.7% complete, 33.3% no follow-up), TV+TA (100% partial), endovascular/surgical (100% complete), and surgical (100% partial). Minor non-neurologic complications included 1/14 (7.1%) in the TV group and 1/3 (33.3%) in the TA/TV group. CONCLUSION: Endovascular treatment is safe and effective for most FMR-AVF. TV embolization has a high cure rate with few complications.

Robotics for neuroendovascular intervention: Background and primer.

The simultaneous growth of robotic-assisted surgery and telemedicine in recent years has only been accelerated by the recent coronavirus disease 2019 pandemic. Robotic assistance for neurovascular intervention has garnered significant interest due to opportunities for tele-stroke models of care for remote underserved areas. Lessons learned from medical robots in interventional cardiology and neurosurgery have contributed to incremental but vital advances in medical robotics despite important limitations. In this article, we discuss robot types and their clinical justification and ethics, as well as a general overview on available robots in thoracic/abdominal surgery, neurosurgery, and cardiac electrophysiology. We conclude with current clinical research in neuroendovascular intervention and a perspective on future directions.

Endovascular Biopsy of Vertebrobasilar Aneurysm in Patient With Polyarteritis Nodosa.

Background and Purpose: The management of unruptured intracranial aneurysms remains controversial. The decisions to treat are heavily informed by estimated risk of bleeding. However, these estimates are imprecise, and better methods for stratifying the risk or tailoring treatment strategy are badly needed. Here, we demonstrate an initial proof-of-principle concept for endovascular biopsy to identify the key molecular pathways and gene expression changes associated with aneurysm formation. We couple this technique with single cell RNA sequencing (scRNAseq) to develop a roadmap of the pathogenic changes of a dolichoectatic vertebrobasilar aneurysm in a patient with polyarteritis nodosa. Methods: Endovascular biopsy and fluorescence activated cell sorting was used to isolate the viable endothelial cells (ECs) using the established techniques. A single cell RNA sequencing (scRNAseq) was then performed on 24 aneurysmal ECs and 23 patient-matched non-aneurysmal ECs. An integrated panel of bioinformatic tools was applied to determine the differential gene expression, enriched signaling pathways, and cell subpopulations hypothesized to drive disease pathogenesis. Results: We identify a subset of 7 (29%) aneurysm-specific ECs with a distinct gene expression signature not found in the patient-matched control ECs. A gene set enrichment analysis identified these ECs to have increased the expression of genes regulating the leukocyte-endothelial cell adhesion, major histocompatibility complex (MHC) class I, T cell receptor recycling, tumor necrosis factor alpha (TNFα) response, and interferon gamma signaling. A histopathologic analysis of a different intracranial aneurysm that was later resected yielded a diagnosis of polyarteritis nodosa and positive staining for TNFα. Conclusions: We demonstrate feasibility of applying scRNAseq to the endovascular biopsy samples and identify a subpopulation of ECs associated with cerebral aneurysm in polyarteritis nodosa. Endovascular biopsy may be a safe method for deriving insight into the disease pathogenesis and tailoring the personalized treatment approaches to intracranial aneurysms.