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Neural stem cells (NSCs) are capable of tremendous migratory potential to areas of pathology in the central nervous system. When implanted into a diseased or injured nervous system, NSCs can travel through great distances to and engraft within areas of discrete as well as diffuse abnormalities. Engraftment is often followed by integration into the local neural milieu, accompanied by stable gene expression from the NSCs. In addition, the pluripotency of NSCs endows them with the capability to replace diseased tissues in an appropriate manner. Recent evidence has also suggested that engrafted exogenous NSCs may have effects on the surrounding microenvironment, such as promoting protection and/or regeneration of host neural pathways. These characteristics of NSCs would seem to make them ideal agents for the treatment of various central nervous system pathologies, especially brain tumors. Brain tumors are generally difficult to treat because of the unique location of the lesions. In primary gliomas, the extensive infiltrative nature of the tumor cells presents a challenge for their effective and total eradication, hence the high rate of treatment failure and disease recurrence. In addition, normal brain structures are distorted and are often destroyed by the growing neoplasm. Even with effective therapy to surgically resect and destroy the neoplastic tissues, the brain is still injured, which often leaves the patient in a debilitated state. The unique ability of NSCs to "home in" on tumor cells followed by the delivery of a desired gene product makes the NSC a very promising agent in brain tumor therapy. Cytolytic viruses and genes coding for anti-tumor cytokines, pro-drug converting enzymes, and various neurotrophic factors have all been engineered into engraftable NSCs for delivery to tumors. When they are specially tagged, such injected NSCs can be visualized with the use of novel imaging techniques and tracked in vivo within living animals over real time. If the NSCs were also capable of participating in the subsequent repair and regeneration of the tumor-afflicted brain-at present a potential but as-yet-unproven aspect of this intervention-then its role in abetting anti-tumor therapy would be complete. It is important to emphasize, however, that the use of NSCs is adjunctive and is not a replacement for other therapies that should be used in parallel. [ABSTRACT FROM AUTHOR]

Background: Prostate-specific membrane antigen (PSMA) is a membrane-bound metallopeptidase highly expressed in the neovasculature of many solid tumors including gliomas. It is a particularly enticing therapeutic target due to its ability to internalize, thereby delivering radioligands or pharmaceuticals to the intracellular compartment. Targeting the neovasculature of gliomas using PSMA for diagnosis and management has been a recent area of increased study and promise. The purpose of this review is to synthesize the current state and future directions of PSMA use in the histopathologic study, imaging, and treatment of gliomas., Methods: PubMed and Scopus databases were used to conduct a literature review on PSMA use in gliomas in June 2023. Terms searched included "PSMA," "Prostate-Specific Membrane Antigen" OR "PSMA" OR "PSMA PET" AND "glioma" OR "high grade glioma" OR "glioblastoma" OR "GBM.", Results: Ninety-four publications were screened for relevance with 61 studies, case reports, and reviews being read to provide comprehensive context for the historical, contemporary, and prospective use of PSMA in glioma management., Conclusions: PSMA PET imaging is currently a promising and accurate radiographic tool for the diagnosis and management of gliomas. PSMA histopathology likely represents a viable tool for helping predict glioma behavior. More studies are needed to investigate the role of PSMA-targeted therapeutics in glioma management, but preliminary reports have indicated its potential usefulness in treatment., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Recent studies have investigated if the sodium fluorescein-guided (SFg) improves the extent of resection of BMs when compared to standard white light (sWL). Therefore, we aimed to assess the comparative efficacy and safety of SFg and sWL for resection of BMs., Methods: We searched Medline, Embase, and Cochrane Library databases following Cochrane and PRISMA guidelines for studies reporting comparative data of SFg and WL resection of BMs. We pooled odds ratios (OR) with 95% confidence intervals under random effects and applied I² statistics and leave-one-out sensitivity analysis to assess heterogeneity. I² > 40% was considered significant for heterogeneity., Results: Five studies involving 816 patients were included, of whom 390 underwent BMs resection with SFg and 426 with sWL, and ages ranging between 26 and 86.2 years old. Analysis revealed a statistically significant higher likelihood of complete resection in the SFg group when compared to the sWL group (OR = 2.15, 95%CI: 1.18-3.92, p = 0.01; I² = 47%). Sensitivity analysis revealed a consistent result in all five scenarios, with low heterogeneity in two of the five scenarios. Three studies reported significant improvement in OS in the SFg group, and the qualitative assessment of complications and procedure-related mortality did not provide sufficient information for conclusions., Conclusion: This systematic review and meta-analysis identified a higher likelihood of complete resection in the SFg group when compared to the standard sWL group. This study is the first to directly compare the impact of SFg and sWL on resection outcomes for BMs., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Brain metastases pose a significant therapeutic challenge in the field of oncology, necessitating treatments that effectively control disease progression while preserving neurological and cognitive functions. Among various interventions, brachytherapy, which involves the direct placement of radioactive sources into or near tumors or into the resected cavity, can play an important role in treatment. Current literature describes brachytherapy's capacity to deliver targeted, high-dose radiation while minimizing damage to adjacent healthy tissues-a crucial consideration in the choice of treatment modality. Furthermore, advancements in implantation techniques as well as in the development of different isotopes have expanded its efficacy and safety profile. This review delineates the contemporary applications of brachytherapy in managing brain metastases, examining its advantages, constraints, and associated clinical outcomes, and provides a comprehensive understanding of advances in the use of brachytherapy for brain metastasis treatment, with implications for improved patient outcomes and enhanced quality of life.

Background: Ependymal cysts (EC) typically present supra-tentorially near the lateral ventricle, juxta ventricular, or temporoparietal regions. Previous cases have also identified infratentorial EC of the brainstem, cerebellum, and subarachnoid spaces. They are mostly asymptomatic. In this paper, we present the first-ever case of a symptomatic medullary ependymal cyst treated with surgery, along with a comprehensive review of the literature on EC of other parts of the brain stem., Case Description: This 51-year-old female presented with hearing loss, dizziness, diplopia, and ataxia. Radiographic imaging indicated the presence of a non-enhancing lesion in the medulla with a mass effect on the brainstem. Pathological examination confirmed its characterization as an ependymal cyst. The patient underwent a suboccipital craniotomy for the fenestration of the medullary ependymal cyst under neuro-navigation, Intra-op ultrasound and intra-operative neuro-monitoring. Histopathological examination confirmed the diagnosis of an ependymal cyst. At one month follow-up, her KPS is 90, ECOG PS 1, and her ataxia has improved with complete resolution of diplopia., Conclusion: Due to their rarity and potential similarity to other cystic structures, EC may be overlooked or incorrectly diagnosed resulting in mismanagement and surgical disaster. Therefore, a comprehensive understanding and awareness of their distinct characteristics are essential for accurate diagnosis and appropriate management., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Purpose: The efficacy of systemic therapies for glioblastoma (GBM) remains limited due to the constraints of systemic toxicity and blood-brain barrier (BBB) permeability. Temporoparietal fascial flaps (TPFFs) and vascularized peri cranial flaps (PCF) are not restricted by the blood-brain barrier (BBB), as they derive their vascular supply from branches of the external carotid artery. Transposition of a vascularized TPFF or PCF along a GBM resection cavity may bring autologous tissue not restricted by the BBB in close vicinity to the tumor bed microenvironment, permit ingrowth of vascular channels fed by the external circulation, and offer a mechanism of bypassing the BBB. In addition, circulating immune cells in the vascularized flap may have better access to tumor-associated antigens (TAA) within the tumor microenvironment. We conducted a first-in-human Phase I trial assessing the safety of lining the resection cavity with autologous TPFF/PCF of newly diagnosed patients with GBM., Methods: 12 patients underwent safe, maximal surgical resection of newly diagnosed GBMs, followed by lining of the resection cavity with a pedicled, autologous TPFF or PCF. Safety was assessed by monitoring adverse events. Secondary analysis of efficacy was examined as the proportion of patients experiencing progression-free disease (PFS) as indicated by response assessment in neuro-oncology (RANO) criteria and overall survival (OS). The study was powered to determine whether a Phase II study was warranted based on these early results. For this analysis, subjects who were alive and had not progressed as of the date of the last follow-up were considered censored and all living patients who were alive as of the date of last follow-up were considered censored for overall survival. For simplicity, we assumed that a 70% PFS rate at 6 months would be considered an encouraging response and would make an argument for further investigation of the procedure., Results: Median age of included patients was 57 years (range 46-69 years). All patients were Isocitrate dehydrogenase (IDH) wildtype. Average tumor volume was 56.6 cm 3 (range 14-145 cm 3 ). Resection was qualified as gross total resection (GTR) of all of the enhancing diseases in all patients. Grade III or above adverse events were encountered in 3 patients. No Grade IV or V serious adverse events occurred in the immediate post-operative period including seizure, infection, stroke, or tumor growing along the flap. Disease progression at the site of the original tumor was identified in only 4 (33%) patients (median 23 months, range 8-25 months), 3 of whom underwent re-operation. Histopathological analyses of those implanted flaps and tumor bed biopsy at repeat surgery demonstrated robust immune infiltrates within the transplanted flap. Importantly, no patient demonstrated evidence of tumor infiltration into the implanted flap. At the time of this manuscript preparation, only 4/12 (33%) of patients have died. Based on the statistical considerations above and including all 12 patients 10/12 (83.3%) had 6-month PFS. The median PFS was 9.10 months, and the OS was 17.6 months. 4/12 (33%) of patients have been alive for more than two years and our longest surviving patient currently is alive at 60 months., Conclusions: This pilot study suggests that insertion of pedicled autologous TPFF/PCF along a GBM resection cavity is safe and feasible. Based on the encouraging response rate in 6-month PFS and OS, larger phase II studies are warranted to assess and reproduce safety, feasibility, and efficacy. TRIAL REGISTRATION NUMBER AND DATE OF REGISTRATION FOR PROSPECTIVELY REGISTERED TRIALS: ClinicalTrials.gov ID NCT03630289, dated: 08/02/2018., (© 2024. The Author(s).)

Standard-of-care first-line therapy for patients with newly diagnosed glioblastoma (ndGBM) is maximal safe surgical resection, then concurrent radiotherapy and temozolomide, followed by maintenance temozolomide. IGV-001, the first product of the Goldspire™ platform, is a first-in-class autologous immunotherapeutic product that combines personalized whole tumor-derived cells with an antisense oligonucleotide (IMV-001) in implantable biodiffusion chambers, with the intent to induce a tumor-specific immune response in patients with ndGBM. Here, we describe the design and rationale of a randomized, double-blind, phase IIb trial evaluating IGV-001 compared with placebo, both followed by standard-of-care treatment in patients with ndGBM. The primary end point is progression-free survival, and key secondary end points include overall survival and safety.

The nasoseptal flap is a workhorse reconstructive option for anterior skull base defects during endonasal surgery. This paper highlights the versatility of the nasoseptal flap. After providing a brief historical perspective, this review will focus on the relevant primary literature published in the last ten years. We will touch upon new applications of the flap, how the flap has been modified to expand its reach and robustness, and some of the current limitations. We will conclude by discussing what the future holds for improving upon the design and use of the nasoseptal flap in anterior skull base reconstruction.

Background: Rarely, Pituitary adenomas (PA) can co-occur with intrasellar or intracavernous aneurysms. There is currently no clear guidance for the management of this dual pathology. We attempt to provide an algorithm to help guide clinical decision making for treatment of PAs co-occurring with adjacent cerebral aneurysms., Methods: A comprehensive literature search was conducted following PRISMA guidelines using various databases. Search terms included "(Pituitary Adenoma OR Prolactinoma OR Macroadenoma OR Adenoma) AND (ICA OR Internal Carotid Artery OR paracliniod OR clinoid) Aneurysm AND (Intra-cavernous OR intracavernous OR intrasellar OR Cavernous).", Results: A total of 24 studies with 24 patients were included. Twelve (50%) patients experienced visual symptoms. Ten patients (42%) had an aneurysm embedded within the adenoma. Fourteen patients (58%) had an aneurysm adjacent to the adenoma. Embedded aneurysms were significantly associated with rupture events., Conclusion: Vision loss is the most pressing determinant of treatment. In the absence of visual symptoms, the aneurysm should be treated first by coil embolization. If not amenable to coiling, place flow diverting stent followed by six months of anticoagulation and antiplatelet therapy. If visual loss is apparent, the adenoma-aneurysm spatial relationship becomes critical. In cases of an adjacent aneurysm, the adenoma should be removed transsphenoidally with extreme care and aneurysm rupture protocols in place. If the aneurysm is embedded within the adenoma, then a BTO is favored with permanent ICA occlusion followed by transsphenoidal resection if adequate collateral supply is demonstrated. If there is inadequate collateral supply, then an open-approach for amenable aneurysms with transcranial adenoma debulking should be performed., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Purpose: To outline the dose rationale for the first in-human intrathecal delivery of bevacizumab for LMS of GBM., Methods: A 19-year-old female patient presented to Lenox Hill Hospital following thalamic GBM recurrence. She subsequently underwent two infusions of intra-arterial BEV (NCT01269853) and experienced a period of relative disease stability until progression in 2022. One month later, MRI disclosed diffuse enhancement representative of LMS of GBM. The patient subsequently underwent five cycles of IT BEV in mid-2022 (IND 162119). Doses of 25 mg, 37.5 mg, 50 mg, 50 mg, and 37.8 mg were delivered at two-week intervals between doses 1-4. The final 37.8 mg dose was given one day following her fourth dose, given that the patient was to be discharged, traveled several hours to our center, and was tolerating therapy well. Dosage was decreased due to the short interval between the final two treatments. Shortly after IT BEV completion, she received a third dose of IA BEV., Results: Our patient did not show any signs of serious adverse effects or dose limiting toxicities following any of the treatments. It is difficult to determine PFS due to the rapid progression associated with LMS of GBM and rapid timeframe of treatment., Conclusion: LMS continues to be a devastating progression in many types of cancer, including GBM, and novel ways to deliver therapeutics may offer patients symptomatic and therapeutic benefits., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: We systematically reviewed visual outcomes over the last three decades in patients undergoing treatment for base of skull (BOS) meningiomas and provide recommendations to preserve vision., Methods: In accordance with the PRISMA guidelines for systematic reviews, a search was conducted from 6/1/2022-9/1/2022 using PubMed and Web of Science. Inclusion criteria included (1) patients treated for BOS meningiomas (2) treatment modality specified (3) specifics of surgical techniques and/or dose/fractions of radiotherapy (4) individual patient outcomes of treatment. Each study was assessed for bias based on study design and heterogeneity of results., Results: A total of 50 studies were included (N = 2911). When comparing improved vision versus unchanged or worsened vision, studies investigating surgery alone published from 2006 and onward had significantly better visual outcomes compared to pre-2006 studies (p = 0.02). When comparing improved vision versus unchanged or worsened vision, studies investigating combined therapy with surgery and radiation published from 2008 and onward had significantly better visual outcomes compared to pre-2008 studies (p < 0.01). Combined modality therapy was less likely to worsen vision compared to either surgery or radiation monotherapy (p < 0.01). However, surgery and radiation monotherapy were more likely to actually improve outcomes compared to combination therapy (p < 0.01)., Conclusion: For over a decade we have observed improvement in visual outcomes in patients managed for meningioma of BOS, likely attributing the innovation in microsurgical and more targeted and conformal radiation techniques. Combination therapy may be the safest option for preventing worsening of vision, but the highest rates of improving visual function are achieved through monotherapy when indicated., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: We systematically reviewed the current landscape of hippocampal-avoidance radiotherapy, focusing specifically on rates of hippocampal tumor recurrence and changes in neurocognitive function., Methods: PubMed was queried for studies involving hippocampal-avoidance radiation therapy and results were screened using PRISMA guidelines. Results were analyzed for median overall survival, progression-free survival, hippocampal relapse rates, and neurocognitive function testing., Results: Of 3709 search results, 19 articles were included and a total of 1611 patients analyzed. Of these studies, 7 were randomized controlled trials, 4 prospective cohort studies, and 8 retrospective cohort studies. All studies evaluated hippocampal-avoidance whole brain radiation treatment (WBRT) and/or prophylactic cranial irradiation (PCI) in patients with brain metastases. Hippocampal relapse rates were low (overall effect size = 0.04; 95% confidence interval [0.03, 0.05]) and there was no significant difference in risk of relapse between the five studies that compared HA-WBRT/HA-PCI and WBRT/PCI groups (risk difference = 0.01; 95% confidence interval [- 0.02, 0.03]; p = 0.63). 11 out of 19 studies included neurocognitive function testing. Significant differences were reported in overall cognitive function and memory and verbal learning 3-24 months post-RT. Differences in executive function were reported by one study, Brown et al., at 4 months. No studies reported differences in verbal fluency, visual learning, concentration, processing speed, and psychomotor speed at any timepoint., Conclusion: Current studies in HA-WBRT/HA-PCI showed low hippocampal relapse or metastasis rates. Significant differences in neurocognitive testing were most prominent in overall cognitive function, memory, and verbal learning. Studies were hampered by loss to follow-up., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Adjuvant radiotherapy is often necessary following surgical resection of brain metastases to improve local tumor control and survival. Brachytherapy using cesium-131 offers a novel method for loco-regional radiotherapy. We reviewed the current literature reporting the use of cesium-131 brachytherapy for the treatment of brain metastases. Published studies and ongoing trials were reviewed to identify treatment protocols and clinical outcomes of cesium-131 brachytherapy for brain metastases. Cesium-131 brachytherapy was further compared to current outcomes for iodine-125 brachytherapy and stereotactic radiosurgery. Intraoperative brachytherapy allows patients to receive two treatment modalities in one setting while minimizing tumor cell repopulation. After initial interest, the use of iodine-125 brachytherapy has declined due to unfavorable rates of radiation necrosis without survival improvement. Recent data on intracavitary cesium-131 brachytherapy in brain metastases have demonstrated improved locoregional tumor control with low risks of radiation necrosis, with associated improvements in patients compliance and satisfaction. Cesium-131 isotope has a short half-life, delivers 90% of its dose within a month, shortens the time to initiation of systemic therapy compared to iodine-125 or external radiotherapy, and has an excellent radiation safety profile. Further analyses have demonstrated superior cost-effectiveness and quality-of-life improvement ratios of cesium-131 brachytherapy than adjuvant stereotactic radiosurgery. Cesium-131 brachytherapy is a safe and effective post-surgical treatment option for brain metastases with associated clinical and cost-effectiveness benefits in appropriately selected patients., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Purpose: Operative guidelines and use optimization for new surgical exoscopes are not well described in the literature. In this study, we evaluated use of the ORBEYE (Olympus) surgical exoscope system during 5-ALA fluorescence-guided resection of GBMs to optimize workflow and exoscope settings., Methods: The ORBEYE exoscope system was fitted with a blue light filter for 5-ALA mediated fluorescence-guided surgery (FGS). Intraoperative images were obtained during 5-ALA FGS in 9 patients with primary or recurrent GBM. The exoscope was set up at constant, increasing focal distances from the target tissue, and light source intensity varied. High-resolution 4 K images were captured and analyzed. Comparisons of fluorescence to background were then generated for use optimization., Results: Light intensity did not significantly influence tumor fluorescence (P = 0.878). However, focal distance significantly impacted relative fluorescent intensity (P = 0.007). Maximum average fluorescence was seen consistently at a focal length of 220 mm and a light intensity of approximately 75% maximum. Decreasing focal distance from 400 mm to 220 mm significantly increased visualized fluorescence (P = 0.0038)., Conclusions: The ORBEYE surgical exoscope system with blue light filter is a powerful imaging tool for 5-ALA FGS in GBM. The ORBEYE blue filter performs optimally at shorter focal distance with moderate light intensity. Similar to microscope systems, decreasing focal distance significantly influences visualized fluorescence., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Brain and spinal tumors affect 1 in 1000 people by 25 years of age, and have diverse histological, biological, anatomical and dissemination characteristics. A mortality of 30-40% means the majority are cured, although two-thirds have life-long disability, linked to accumulated brain injury that is acquired prior to diagnosis, and after surgery or chemo-radiotherapy. Only four drugs have been licensed globally for brain tumors in 40 years and only one for children. Most new cancer drugs in clinical trials do not cross the blood-brain barrier (BBB). Techniques to enhance brain tumor drug delivery are explored in this review, and cover those that augment penetration of the BBB, and those that bypass the BBB. Developing appropriate delivery techniques could improve patient outcomes by ensuring efficacious drug exposure to tumors (including those that are drug-resistant), reducing systemic toxicities and targeting leptomeningeal metastases. Together, this drug delivery strategy seeks to enhance the efficacy of new drugs and enable re-evaluation of existing drugs that might have previously failed because of inadequate delivery. A literature review of repurposed drugs is reported, and a range of preclinical brain tumor models available for translational development are explored.

Flash visual evoked potentials (fVEPs) provide a means to interrogate visual system functioning intraoperatively during tumor resection in which the optic pathway is at risk for injury. Due to technical limitations, fVEPs have remained underutilized in the armamentarium of intraoperative neurophysiological monitoring (IONM) techniques. Here we review the evolution of fVEPs as an IONM technique with emphasis on the enabling technological and intraoperative improvements. A combined approach with electroretinography (ERG) has enhanced feasibility of fVEP neuromonitoring as a practical application to increase safety and reduce error during tumor resection near the prechiasmal optic pathway. The major advance has been towards differentiating true cases of damage from false findings. We use two illustrative neurosurgical cases in which fVEPs were monitored with and without ERG to discuss limitations and demonstrate how ERG data can clarify false-positive findings in the operating room. Standardization measures have focused on uniformity of photostimulation parameters for fVEP recordings between neurosurgical groups., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: Iatrogenic neurologic deficits adversely affect patient outcomes following brain tumor resection. Motor evoked potential (MEP) monitoring allows surgeons to assess the integrity of motor-eloquent areas in real-time during tumor resection to lessen the risk of iatrogenic insult. We retrospectively associate intraoperative transcranial and direct cortical MEPs (TC-MEPs, DC-MEPs) to early and late post-operative motor function to prognosticate short- and long-term motor recovery in brain tumor patients undergoing surgical resection in peri-eloquent regions., Methods: We reviewed 121 brain tumor patients undergoing craniotomies with DC-MEP and/or TC-MEP monitoring. Motor function scores were recorded at multiple time-points up to 1 year postoperatively. Sensitivity, specificity, and positive and negative predictive values (PPV, NPV) were calculated at each time point., Results: The sensitivity, specificity, PPV, and NPV of TC-MEP in the immediate postoperative period was 17.5%, 100%, 100%, and 69.4%, respectively. For DC-MEP monitoring, the respective values were 25.0%, 100%, 100%, and 68.8%. By discharge, sensitivity had increased for both TC-MEP and DC MEPs to 43.8%, and 50.0% respectively. Subset analysis on patients without tumor recurrence/progression at long term follow-up (n = 62 pts, 51.2%) found that all patients with stable monitoring maintained or improved from preoperative status. One patient with transient intraoperative TC-MEP loss and permanent DC-MEP loss suffered a permanent deficit., Conclusion: Brain tumor patients who undergo surgery with intact MEP monitoring and experience new postoperative deficits likely suffer transient deficits that will improve over the postoperative course in the absence of disease progression., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Webinars offer novel educational opportunities beyond those of traditional, in-person experiences. BRAINterns is an open-access webinar-based education platform created to replace opportunities lost during the coronavirus disease 2019 pandemic. This program previously showed the efficacy of webinars to expand access to careers in medicine, and in particular, neurosurgery. BRAINterns 2.0 was established to assess the durability of Web-based learning., Methods: A modified 4-week webinar series was held during July 2021. A retrospective exit survey was distributed to participants and responses analyzed., Results: A total of 16,045 people registered for BRAINterns 2.0, representing 103 countries. Survey responses were received from 3765 participants (23% response rate). New, first-time registrants comprised 66% of participants, with the rest being returning participants. A total of 342 students participated in a dedicated module delivered entirely in Spanish. Females represented 81% of respondents. Participants identified that desirable elements of the program were opportunities to hear from women (53%) and people of color (44%) in health care. Participants heard about the series through TikTok (n = 1251; 33%), Instagram (n = 1109; 29%), Facebook (n = 637; 17%), and word of mouth (n = 708; 19%) with assistance from an ambassador program., Conclusions: Webinar-based education programs continue to be of interest to students in an increasingly digital world. Social media, and specifically the use of educational ambassadors, are effective to improve visibility of educational programs across a diverse population of students. Understanding the desires of participants is critical to building a successful online education platform., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objectives: TikTok is a social media platform that has gained popularity and become a powerful engine to disseminate public health and medical information. To date, no study has characterized the qualities of popular TikTok videos related to neurosurgery, or assessed biases in the content of these videos., Methods: The TikTok web browser application was queried using "#neurosurgery" to identify neurosurgery-related videos. The top 100 videos meeting inclusion criteria were analyzed and video characteristics determined. Bias was assessed by the DISCERN scoring system using 3 independent reviewers. A Kruskal-Wallis H test was used to correlate video popularity with video characteristics and to correlate bias with creator and video type., Results: The 100 videos evaluated totaled 8.8 million likes, 104,718 comments, and 100,856 shares. The oldest video was posted February 2020 and the most recent March 2022. Videos were most commonly entertaining ( n  = 64, 64%), and educational ( n  = 46, 46%). Video popularity was associated with videos that aimed to entertain, and least associated with videos depicting neurosurgery lifestyle. Low DISCERN scores, indicating more biased content, were seen across the neurosurgical content with the entertaining video category demonstrating the highest bias., Conclusions: Neurosurgical content on TikTok contains a high degree of bias across all creator and video types. Entertaining videos are associated with the highest numbers of likes but also the greatest bias. These data may be used to guide institutions and neurosurgeons to grow interest in the field of neurosurgery and disseminate unbiased information while expanding their social media presence., (© 2022 The Author(s).)

Objective: Stimulated Raman histology (SRH) offers efficient and accurate intraoperative neuropathological tissue analysis without procedural alteration to the diagnostic specimen. However, there are limited data demonstrating one-to-one tissue comparisons between SRH and traditional frozen sectioning. This study explores the non-inferiority of SRH as compared to frozen section on the same piece of tissue in neurosurgical patients., Methods: Tissue was collected over a 1-month period from 18 patients who underwent resection of central nervous system lesions. SRH and frozen section analyses were compared for diagnostic capabilities as well as assessed for quality and condition of tissue via a survey completed by pathologists., Results: SRH was sufficient for diagnosis in 78% of specimens as compared to 94% of specimens by frozen section of the same specimen. A Fisher's exact test determined there was no significant difference in diagnostic capability between the two groups. Additionally, both quality of SRH and condition of tissue after SRH were deemed to be non-inferior to frozen section., Conclusions: This study provides further evidence for the non-inferiority of SRH techniques. It is also the first study to demonstrate SRH accuracy using one-to-one tissue analysis in neuropathological specimens., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: There has been a paradigm shift in the management of hypothalamic hamartoma (HH) from traditional microsurgical techniques to less invasive alternatives. However, large and extensive HH may fail to respond to these therapies, necessitating craniotomies., Methods: All patients who underwent microsurgical resection of a complex HH by the 2 senior authors from 2011 to 2021 were included. Charts were retrospectively reviewed and demographic, clinical, imaging, and outcome data were recorded., Results: Eight patients (mean age, 7 years) were included. Two had failed previous treatments. All 7 presented with gelastic seizures and cognitive dysfunction, 6 showed central precocious puberty, and 3 had behavioral problems. The mean lesion size was 21.6 mm and all had interpeduncular extension, 5 had intraventricular extension (Delalande type I, 3; type III, 4; type IV, 1). A frontotemporal orbitozygomatic approach with optic nerve decompression was used in all patients, supplemented by another approach in 3 (endoscopic transventricular, 3; transcallosal, 1). Gross total resection was achieved in 6 patients and subtotal resection in 2. Transient complications occurred in 3 patients (37.5%): self-limited sodium imbalance (n = 3), subdural hygroma (n = 2). Permanent complications occurred in 2 patients (25%): perforator infarct (n = 1) and short-term memory loss (n = 1). All patients experienced seizure resolution with preserved hypothalamic-pituitary axis function. After a mean follow-up of 41 months (range, 2-66 months), 7 patients remained seizure free, and 1 had rare seizures. Cognitive and behavioral symptoms improved in all patients., Conclusions: For large HH with interpeduncular extension, microsurgery via the frontotemporal orbitozygomatic approach is a safe and highly effective treatment modality., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose: Pre-clinical evidence suggests bevacizumab (BV) depletes the GBM peri-vascular cancer-stem cell niche. This phase I/II study assesses the safety and efficacy of repeated doses of superselective intra-arterial cerebral infusion (SIACI) of BV after blood-brain barrier disruption (BBBD)., Methods: Date of surgery was day 0. Evaluated patients received repeated SIACI bevacizumab (15 mg/kg) with BBBD at days 30 ± 7, 120 ± 7, and 210 ± 7 along with 6 weeks of standard chemoradiation. Response assessment in neuro-oncology criteria and the Kaplan-Meier product-limit method was used to evaluate progression free and overall survival (PFS and OS, respectively)., Results: Twenty-three patients with a median age of 60.5 years (SD = 12.6; 24.7-78.3) were included. Isocitrate dehydrogenase mutation was found in 1/23 (4%) patients. MGMT status was available for 11/23 patients (7 unmethylated; 3 methylated; 1 inconclusive). Median tumor volume was 24.0 cm3 (SD = 31.1, 1.7-48.3 cm 3 ). Median PFS was 11.5 months (95% CI 7.7-25.9) with 6, 12, 24 and 60 month PFS estimated to be 91.3% (95% CI 69.5-97.8), 47.4% (26.3-65.9), 32.5% (14.4-52.2) and 5.4% (0.4-21.8), respectively. Median OS was 23.1 months (95% CI 12.2-36.9) with 12, 24, and 36 month OS as 77.3% (95% CI 53.6-89.9), 45.0% (22.3-65.3) and 32.1% (12.5-53.8), respectively., Conclusions: Repeated dosing of IA BV after BBBD offers an encouraging outcome in terms of PFS and OS. Phase III trials are warranted to determine whether repeated IA BV combined with Stupp protocol is superior to Stupp protocol alone for newly diagnosed GBM., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: Delivery of drugs intraarterially to brain tumors has been demonstrated in adults. In this study, the authors initiated a phase I trial of superselective intraarterial cerebral infusion (SIACI) of bevacizumab and cetuximab in pediatric patients with refractory high-grade glioma (diffuse intrinsic pontine glioma [DIPG] and glioblastoma) to determine the safety and efficacy in this population., Methods: SIACI was used to deliver mannitol (12.5 ml of 20% mannitol) to disrupt the blood-brain barrier (BBB), followed by bevacizumab (15 mg/kg) and cetuximab (200 mg/m2) to target VEGF and EGFR, respectively. Patients with brainstem tumors had a balloon inflated in the distal basilar artery during mannitol infusion., Results: Thirteen patients were treated (10 with DIPG and 3 with high-grade glioma). Toxicities included grade I epistaxis (2 patients) and grade I rash (2 patients). There were no dose-limiting toxicities. Of the 10 symptomatic patients, 6 exhibited subjective improvement; 92% showed decreased enhancement on day 1 posttreatment MRI. Of 10 patients who underwent MRI at 1 month, 5 had progressive disease and 5 had stable disease on FLAIR, whereas contrast-enhanced scans demonstrated progressive disease in 4 patients, stable disease in 2, partial response in 2, and complete response in 1. The mean overall survival for the 10 DIPG patients was 519 days (17.3 months), with a mean posttreatment survival of 214.8 days (7.2 months)., Conclusions: SIACI of bevacizumab and cetuximab was well tolerated in all 13 children. The authors' results demonstrate safety of this method and warrant further study to determine efficacy. As molecular targets are clarified, novel means of bypassing the BBB, such as intraarterial therapy and convection-enhanced delivery, become more critical. Clinical trial registration no.: NCT01884740 (clinicaltrials.gov).

Objective: To replace educational opportunities lost during the coronavirus disease 2019 (COVID-19) pandemic, the Department of Neurosurgery at Lenox Hill Hospital produced an open-access webinar series ("BRAINterns") that covered a broad range of health care topics with a focus on neurosurgery., Methods: This 8-week webinar series ran from July 1 to August 28, 2020. An optional exit survey was distributed to participants. Data were analyzed to characterize and better understand trends among a global cohort of participants., Results: A total of 16,484 people registered for BRAINterns, and 6675 took the survey (40.5% response rate). Responders represented 87 countries, of which the majority were from the United States and Canada (90.48%, n = 6039). Responders were primarily female (82.9%, n = 5521). Racial and ethnic representation was majority Asian (42%, n = 2798), followed by White (22.7%, n = 1514), Hispanic/Latino (16.2%, n = 1080), and Black and African American (7.7%, n = 516). Participants reported hearing about BRAINterns through various social media platforms (72.18%, n = 4818)-the most popular was TikTok (33.4%, n = 2232). Overall, 93.4% of participants reported that the course was a good use of their time during the pandemic, and 86.7% reported that the course helped replace lost opportunities., Conclusions: These data demonstrate that webinar-based education is an effective method of expanding access to careers in medicine and in particular, neurosurgery, to traditionally underrepresented populations. Social media can be a powerful tool to combat barriers to early exposure and vastly improve diversity within the field., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Deep learning represents end-to-end machine learning in which feature selection from images and classification happen concurrently. This articles provides updates on how deep learning is being applied to the study of glioma and its genetic heterogeneity. Deep learning algorithms can detect patterns in routine and advanced MR imaging that elude the eyes of neuroradiologists and make predictions about glioma genetics, which impact diagnosis, treatment response, patient management, and long-term survival. The success of these deep learning initiatives may enhance the performance of neuroradiologists and add greater value to patient care by expediting treatment., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: The coronavirus disease 2019 (COVID-19) pandemic has infected more than 13 million people on a global scale and claimed more than half million deaths across 213 countries and territories. While the focus is currently on recovery from the pandemic, the disease has significantly changed the way we practice medicine and neurosurgery in New York City and the United States. Apart from the emergency cases, several health systems across the country have similarly started to perform elective surgeries. Although COVID-19 screening and testing guidelines have been proposed and adopted by many hospitals, these may not adequately protect the operating room personnel who are in proximity to the patient for prolonged periods. There are concerning reports of especially high transmission rates of COVID-19 in transmucosal head and neck procedures conducted by otolaryngologists and neurosurgeons, despite attempts at wearing what constitutes appropriate personal protective equipment., Methods: Here, we describe a simple technique of additional draping that can be used for all cranial, endonasal, spinal, and neurointerventional cases to limit the transmission of coronavirus., Results: The proposed technique offers a simple, commonly available, cost-effective alternative that avoids the use of additional retractor systems. Moreover, this technique can be used in all neurosurgical procedures., Conclusions: With the rising concerns regarding airborne spread of the virus, we expect that these precautions will prove highly useful as we enter the recovery phase of this pandemic and hospitals attempt to prevent a return to widespread infection. In addition, its availability and cost effectiveness make this technique especially attractive to practical use in centers with limited resources., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Neuro-oncological research is at the forefront of the rising cancer therapy market, as evidenced by its growing revenue and the multitude of clinical trials investigating innovative treatment approaches. The Feinstein Institute for Medical Research, in conjunction with the Department of Neurosurgery at Lenox Hill Hospital and the Zucker School of Medicine at Hofstra / Northwell, sponsored The Brain Tumor Biotech Summit in New York City in June 2019. The aim of the Summit was to provide a forum that encourages collaboration between cancer specialists, biotechnology and pharmaceutical industry leaders, and the investment community in order to promote innovation and advance emerging therapies for brain tumors. Areas highlighted during the Summit included immunotherapy, precision medicine, and novel applications and experimental treatments such as receptor targeting, methods for improved drug delivery, and innovative intraoperative techniques and technologies. This review synthesizes the recent breakthroughs in brain tumor research as presented at The Brain Tumor Biotech Summit., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: The Coronavirus disease 2019 (COVID-19) outbreak has left a lasting mark on medicine globally., Methods: Here we outline the steps that the Lenox Hill Hospital/Northwell Health Neurosurgery Department-located within the epicenter of the pandemic in New York City-is currently taking to recover our neurosurgical efforts in the age of COVID-19., Results: We outline measurable milestones to identify the transition to the recovery period and hope these recommendations may serve as a framework for an effective path forward., Conclusions: We believe that recovery following the COVID-19 pandemic offers unique opportunities to disrupt and rebuild the historical patient and office experience as we evolve with modern medicine in a post-COVID-19 world., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: The advent of the operating microscope (OM) revolutionized the field of neurosurgery. It allowed surgeons to operate on and effectively treat diseases previously inaccessible with conventional eyesight because of magnification and illumination. Improvements in the essential methods of visualization and the quality of the optics have plateaued. Another main limitation of the OM remains its ergonomics because of the need of the surgeon and assistant to directly interface with the OM objective. Recently, exoscopes have been introduced to overcome some shortcomings of the conventional OM., Objective: To subjectively review the individual authors experience with the current exoscope platforms in an attempt to provide a resource to the neurosurgeon when considering imaging options., Methods: Experts with previous use of each individual platform were contacted and asked to contribute their experiences., Results: In total, 4 systems are discussed. They include the VITOM (Karl Storz, Tuttlingen, Germany), the Olympus ORBEYE (Olympus, Tokyo, Japan), the Synaptive Modus V (Synaptive Medical, Toronto, Canada), and the Zeiss KINEVO (Carl Zeiss AG, Oberkochen, Germany)., Conclusion: The advent of exoscopes has the potential to begin to allow surgeons to move beyond solely the microscope for intraoperative visualization while improving upon its ergonomic disadvantages., (Copyright © 2019 by the Congress of Neurological Surgeons.)

Introduction: Intra-arterial (IA) delivery of therapeutic agents across the blood-brain barrier (BBB) is an evolving strategy which enables the distribution of high concentration therapeutics through a targeted vascular territory, while potentially limiting systemic toxicity. Studies have demonstrated IA methods to be safe and efficacious for a variety of therapeutics. However, further characterization of the clinical efficacy of IA therapy for the treatment of brain tumors and refinement of its potential applications are necessary., Methods: We have reviewed the preclinical and clinical evidence supporting superselective intraarterial cerebral infusion (SSIACI) with BBB disruption for the treatment of brain tumors. In addition, we review ongoing clinical trials expanding the applicability and investigating the efficacy of IA therapy for the treatment of brain tumors., Results: Trends in recent studies have embraced the use of SSIACI and less neurotoxic chemotherapies. The majority of trials continue to use mannitol as the preferred method of hyperosmolar BBB disruption. Recent preclinical and preliminary human investigations into the IA delivery of Bevacizumab have demonstrated its safety and efficacy as an anti-tumor agent both alone and in combination with chemotherapy., Conclusion: IA drug delivery may significantly affect the way treatments are delivered to patients with brain tumors, and in particular GBM. With refinement and standardization of the techniques of IA drug delivery, improved drug selection and formulations, and the development of methods to minimize treatment-related neurological injury, IA therapy may offer significant benefits for the treatment of brain tumors.

This manuscript will review emerging applications of artificial intelligence, specifically deep learning, and its application to glioblastoma multiforme (GBM), the most common primary malignant brain tumor. Current deep learning approaches, commonly convolutional neural networks (CNNs), that take input data from MR images to grade gliomas (high grade from low grade) and predict overall survival will be shown. There will be more in-depth review of recent articles that have applied different CNNs to predict the genetics of glioma on pre-operative MR images, specifically 1p19q codeletion, MGMT promoter, and IDH mutations, which are important criteria for the diagnosis, treatment management, and prognostication of patients with GBM. Finally, there will be a brief mention of current challenges with DL techniques and their application to image analysis in GBM.

The name of author Jason A. Ellis was missing in the intial online publication, and there was a typo in the sixth author's first name. The original article has been corrected.

Background: High-dose bevacizumab delivered via super selective intra-arterial cerebral infusion (SIACI) is one promising clinical trial combination for patients with glioblastoma (GBM). Although both continuous intravenous and intra-arterial administration of bevacizumab, and rechallenge with intravenous bevacizumab, have demonstrated improved survival, this is the first description of rechallenging GBM with SIACI of bevacizumab., Case Description: We report a case of a 43-year-old woman with recurrent GBM who had received treatment from 3 clinical trials, including a rechallenge with SIACI of bevacizumab. First, she enrolled into a phase I/II trial for patients newly diagnosed with GBM (NCT01811498) and received 3 doses of SIACI bevacizumab over 180 days in addition to standard of care chemotherapy and radiation. Following progression, as indicated on her magnetic resonance imaging scan, she consented for a separate clinical trial for her disease and received 2 cycles of temozolomide with an investigational agent. The patient was removed from the study on tumor progression. Subsequently, she was rechallenged with SIACI of bevacizumab via a third clinical trial (NCT01269853) and then completed 3 intravenous infusions. After completing the third trial, her magnetic resonance imaging scan demonstrated improvement based on Response Assessment In Neuro-Oncology criteria., Conclusions: This is the first report to highlight the effect of rechallenging a patient with SIACI of bevacizumab following disease progression after initial bevacizumab treatment and subsequent alternate clinical trial failure. There is a need to conduct further clinical trials to evaluate the benefits of rechallenge with SIACI versus intravenous bevacizumab for GBM and further explore theories of bevacizumab resistance., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Cerebral bypass operation is a technically challenging operation that requires excellent surgical visibility and efficient ergonomics to minimize complications and maximize successful revascularization. Despite the operative microscope's utilization for the past two generations, there remains a need for continued improvement in operative visualization and surgical ergonomics., Objective: To report the positives and negatives of our initial experience using a novel 4 K high-definition (4K-HD) 3-dimensional (3D) exoscope (EX) for cranial bypass surgery., Methods: A retrospective review over 6 mo was performed of all patients who have undergone cerebral bypass surgery at a single institution using the 4K-HD 3D EX. Advantages and disadvantages of the EX and clinical outcome of the patients were assessed., Results: A total of 5 patients underwent cerebral EC-IC bypass surgery with no EX-related complications and successful revascularization. The lightweight design of the EX allowed for easy instrument maneuverability as well as uncomplicated surgical set up in the operating room. The assistance of the cosurgeon was significantly more efficient compared to that of the operating microscope. The large monitor allowed for an immersive, collaborative, and valuable educational surgical experience., Conclusion: Using the EX for cerebral bypass surgery, with 3D ultra-high-definition optics, enhancements of ergonomics, and improved training, we believe that the 3D 4K-HD EX may represent the next generation of operative scopes in microneurosurgery., (Copyright © 2018 by the Congress of Neurological Surgeons.)