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Magnetic resonance imaging-guided laser interstitial thermal therapy (LITT) is an ablative procedure using heat from a laser to provide cytoreduction in tissue. It is a minimally invasive procedure that has been used in intracranial pathologies such as high-grade gliomas, metastatic lesions, epilepsy, and other lesions. While LITT may offer a more acceptable complication profile compared to open surgery, the role of laser therapy for intracranial lesions in current treatment paradigms continues to evolve. This review will focus on the background and application of LITT, the current evidence for its use, and future directions for the technology.

Despite decades of clinical trials and surgical advances, the most common high-grade glioma, glioblastoma (GBM), remains an incurable disease with a dismal prognosis. Because of its infiltrative nature, GBM almost always recurs at the margin, or leading edge, where tumor cells invade the surrounding brain parenchyma. This region of GBMs is unique, or heterogeneous, with its own microenvironment that is different from the tumor bulk or core. The GBM microenvironment at the margin contains immunosuppressive constituents as well as invasive and therapy-resistant tumor cells that are difficult to treat. In addition, the blood-brain barrier remains essentially intact at the infiltrative margin of tumors; further limiting the effectiveness of therapies. The invasive margin creates the greatest challenge for neurosurgeons when managing these tumors. The current paradigm of resection of GBM tumors mainly focuses on resection of the contrast-enhancing component of tumors, while GBMs extend well beyond the contrast enhancement. The infiltrative margin represents a unique challenge and opportunity for solutions that may overcome current limitations in tumor treatments. In this review of the current literature, the authors discuss the current and developing advances focused on the detection and treatment of GBM at the infiltrative margin and how this could impact patient outcomes.

OBJECTIVE The importance of extent of resection (EOR) in glioblastoma (GBM) has been thoroughly demonstrated. However, few studies have explored the practices and benefits of early repeat resection (ERR) when residual tumor deemed resectable is unintentionally left after an initial resection, and the survival benefit of ERR is still unknown. Herein, the authors aimed to internationally survey current practices regarding ERR and to analyze differences based on geographic location and practice setting. METHODS The authors distributed a survey to the American Association of Neurological Surgeons and Congress of Neurological Surgeons Tumor Section, Society of British Neurological Surgeons, European Association of Neurosurgical Society, and Latin American Federation of Neurosurgical Societies. Neurosurgeons responded to questions about their training, practice setting, and current ERR practices. They also reported the EOR threshold below which they would pursue ERR and their likelihood of performing ERR using a Likert scale of 1–5 (5 being the most likely) in two sets of 5 cases, the first set for a patient’s initial hospitalization and the second for a referred patient who had undergone resection elsewhere. The resection likelihood index for each respondent was calculated as the mean Likert score across all cases. RESULTS Overall, 180 neurosurgeons from 25 countries responded to the survey. Neurosurgeons performed ERRs very rarely in their practices (< 1% of all GBM cases), with an EOR threshold of 80.2% (75%–95%). When presented with 10 cases, the case context (initial hospitalization vs referred patient) did not significantly change the surgeon ERR likelihood, although ERR likelihood did vary significantly on the basis of tumor location (p < 0.0001). Latin American neurosurgeons were more likely to pursue ERR in the provided cases. Neurosurgeons were more likely to pursue ERR when the tumor was MGMT methylated versus unmethylated, with a resection likelihood index of 3.78 and 3.21, respectively (p = 0.004); however, there was no significant difference between IDH mutant and IDH wild-type tumors. CONCLUSIONS Results of this survey reveal current practices regarding ERR, but they also demonstrate the variability in how neurosurgeons approach ERR. Standardized guidelines based on future studies incorporating tumor molecular characteristics are needed to guide neurosurgeons in their decision-making on this complicated issue.

To aid surgeons in more complete and safe resection of brain tumors, adjuvant technologies have been developed to improve visualization of target tissue. Fluorescence-guided surgery relies on the use of fluorophores and specific light wavelengths to better delineate tumor tissue, inflammation, and areas of blood–brain barrier breakdown. 5-aminolevulinic acid (5-ALA), the first fluorophore developed specifically for brain tumors, accumulates within tumor cells, improving visualization of tumors both at the core, and infiltrative margin. Here, we describe the background of how 5-ALA integrated into the modern neurosurgery practice, clinical evidence for the current use of 5-ALA, and future directions for its role in neurosurgical oncology. Maximal safe resection remains the standard of care for most brain tumors. Gross total resection of high-grade gliomas (HGGs) is associated with greater overall survival and progression-free survival (PFS) in comparison to subtotal resection or adjuvant treatment therapies alone.1–3 A major challenge neurosurgeons encounter when resecting infiltrative gliomas is identification of the glioma tumor margin to perform a radical resection while avoiding and preserving eloquent regions of the brain. 5-aminolevulinic acid (5-ALA) remains the only optical-imaging agent approved by the FDA for use in glioma surgery and identification of tumor tissue.4 A multicenter randomized, controlled trial revealed that 5-ALA fluorescence-guided surgery (FGS) almost doubled the extent of tumor resection and also improved 6-month PFS.5 In this review, we will highlight the current evidence for use of 5-ALA FGS in brain tumor surgery, as well as discuss the future directions for its use.

Tumor molecular characteristics

Chromogenic multiplex expression analysis of different biomarkers in formalin-fixed paraffin-embedded tissue of 34364, 34368, 34369, 34370, and 34371 tumors and quantitative analysis using Halo® Image Analysis Platform

Purpose:The treatment of glioblastoma (GBM) poses challenges. The use of immune checkpoint inhibition (ICI) has been disappointing as GBM is characterized by low mutational burden and low T-cell infiltration. The combination of ICI with other treatment modalities may improve efficacy.Patient and Methods:Patients with recurrent GBM were treated with avelumab, a human IgG1 antibody directed against PD-L1 (part A), or avelumab within a week after laser interstitial thermal therapy (LITT) and continuation of avelumab (part B). Bevacizumab was allowed to be combined with ICI to spare steroid use. The primary objective was to characterize the tolerability and safety of the regimens. The secondary objectives included overall survival, progression-free survival (PFS), signatures of plasma analytes, and immune cells.Results:A total of 12 patients (median age 64; range, 37–73) enrolled, five in part A and seven in part B. Two serious adverse events occurred in the same patient, LITT treated, not leading to death. The median survival from enrollment was 13 months [95% confidence interval (CI), 4–16 months] with no differences for part A or B. The median PFS was 3 months (95% CI, 1.5–4.5 months). The decrease in MICA/MICB, γδT cells, and CD4+ T cell EMRA correlated with prolonged survival.Conclusions:Avelumab was generally well tolerated. Adding bevacizumab to ICI may be beneficial by lowering cytokine and immune cell expression. The development of this combinatorial treatment warrants further investigation. Exploring the modulation of adaptive and innate immune cells and plasma analytes as biomarker signatures may instruct future studies in this dismal refractory disease.Significance:Our phase I of PD-L1 inhibition combined with LITT and using bevacizumab to spare steroids had a good safety profile for recurrent GBM. Developing combinatory treatment may help outcomes. In addition, we found significant immune modulation of cytokines and immune cells by bevacizumab, which may enhance the effect of ICI.

Neuro-imaging studies demonstrate simultaneous activation of the human precuneus and temporal pole, both in resting-state conditions and during a diverse array of higher-order functions. Despite remarkable advances in neuroscience research, the precise underlying structural connectivity remains unclear. Here, we investigate the connectivity of the precuneus and temporal pole through fiber micro-dissections in human hemispheres. We show the direct axonal connectivity between the posterior precuneus area POS2 and the areas 35 and TI of the temporal pole via the fifth subcomponent of the cingulum. This finding enhances the neuroanatomical knowledge regarding the connectivity of the posteromedial cortices, facilitates the detailed anatomo-functional integration in normal and pathological brain function, and suggests an axonal connectivity unique within the human brain supporting the differences in neural networks between species.

Background Glioblastoma (GBM) remains a largely incurable disease as current therapy fails to target the invasive nature of glioma growth in disease progression and recurrence. Here, we use the FDA-approved drug and small molecule Hippo inhibitor Verteporfin (VP) to target YAP-TEAD activity, known to mediate convergent aspects of tumor invasion/metastasis, and assess the drug’s efficacy and survival benefit in GBM models. Methods Up to 8 low-passage patient-derived GBM cell lines with distinct genomic drivers, including 3 primary/recurrent pairs, were treated with VP or vehicle (VEH) to assess in vitro effects on proliferation, migration, invasion, YAP-TEAD activity, and transcriptomics. Patient-derived orthotopic xenograft (PDX) models were used to assess VP’s brain penetrance and effects on tumor burden and survival. Results VP treatment disturbed YAP/TAZ-TEAD activity; disrupted transcriptome signatures related to invasion, epithelial-to-mesenchymal, and proneural-to-mesenchymal transition, phenocopying TEAD1-knockout effects; and impaired tumor migration/invasion dynamics across primary and recurrent GBM lines. In an aggressive orthotopic PDX GBM model, short-term VP treatment consistently diminished core and infiltrative tumor burden, which was associated with decreased tumor expression of Ki67, nuclear YAP, TEAD1, and TEAD-associated targets EGFR, CDH2, and ITGB1. Finally, long-term VP treatment appeared nontoxic and conferred survival benefit compared to VEH in 2 PDX models: as monotherapy in primary (de novo) GBM and in combination with Temozolomide chemoradiation in recurrent GBM, where VP treatment associated with increased MGMT methylation. Conclusions We demonstrate combined anti-invasive and anti-proliferative efficacy for VP with survival benefit in preclinical GBM models, indicating potential therapeutic value of this already FDA-approved drug if repurposed for GBM patients.

BACKGROUND Surgical resection is the primary treatment for cerebral metastases with safe complete resection as the goal. The robotically assisted digital surgical exoscope is a novel system with advanced visualization methods with recent applications in neurosurgery. OBJECTIVE To evaluate the outcomes for patients with cerebral metastases undergoing resection with the surgical exoscope. METHODS Data were retrospectively collected from patients with cerebral metastases where resection was achieved with using the surgical exoscope from 2016 to 2020. Demographics, clinical, imaging, and operative and outcome findings were collected. The relationship between perioperative data and discharge disposition as well as progression-free survival (PFS) and 12 mo overall survival (OS) was assessed. RESULTS A total of 31 patients (19 males) with a median patient age 63 yr (range 38-80) were included. Average pre- and postoperative volumes were 18.1 cc and 0.75 cc, respectively. Mean depth of the resected lesions was 0.6 cm (range 0-3.6 cm). Complete resection was achieved in 64.5% of patients. The mean extent of resection was 96.7%, with 71.0% achieving PFS at 6 mo. Overall PFS rate was 58.1% and the OS rate at 12 mo was 83.9%. Neurological complications included motor (35.5%) and sensory (12.9%) deficits, with 12 patients reporting no postoperative symptoms. CONCLUSION The surgical exoscope can delineate tumor tissues with high resolution, as shown by a gross total resection achieved for the majority of cases in our series. Postoperative complications and patient outcomes were similar to those reported with use of the operative microscope. Use of the exoscope can provide optimal visualization and delineation of cerebral metastases.

Objective To test the feasibility and efficacy of a 3D exoscope navigation-guided middle cranial fossa (MCF) approach to the internal auditory canal (IAC); to potentially obviate the need to use dissection landmarks and instead, use the navigation probe as a guide to find structures and drill down to the IAC. Patients Cadaveric dissection of six temporal bones. Intervention Computed tomography temporal bone was performed with fiducials on each specimen before the dissection to employ the navigation system. Using a 3D exoscope with navigation by Synaptive (Toronto, Ontario, Canada), the MCF approach was performed. Main outcome measures Navigation accuracy, ability to identify critical structures, and ability to drill out the IAC successfully. Results All six specimens had the IAC successfully drilled out using the 3D exoscope. All dissections were performed with navigation and did not require dissecting out the greater superficial petrosal nerve and superior semicircular canal. One specimen used landmark dissection to confirm the IAC after navigation had been used to locate the IAC first. Navigation accuracy mean was 1.86 mm (range, 1.56-2.05 mm). Conclusion A 3D exoscope navigation-guided MCF approach to the IAC is feasible without landmark dissection.

Patients with glioblastoma (GBM) need bold new approaches to their treatment, yet progress has been hindered by a relative inability to dynamically track treatment response, mechanisms of resistance, evolution of targetable mutations, and changes in mutational burden. We are writing on behalf of a multidisciplinary group of academic neuro-oncology professionals who met at the collaborative Christopher Davidson Forum at Washington University in St Louis in the fall of 2019. We propose a dramatic but necessary change to the routine management of patients with GBM to advance the field: to routinely biopsy recurrent GBM at the time of presumed recurrence. Data derived from these samples will identify true recurrence vs treatment effect, avoid treatments with little chance of success, enable clinical trial access, and aid in the scientific advancement of our understanding of GBM.

Purpose Glioblastoma (GBM) is the most aggressive malignant primary brain tumor. The unfavorable prognosis despite maximal therapy relates to high propensity for recurrence. Thus, overall survival (OS) is quite limited and local failure remains the fundamental problem. Here, we present a safety and feasibility trial after treating GBM intraoperatively by photodynamic therapy (PDT) after 5-aminolevulinic acid (5-ALA) administration and maximal resection. Methods Ten patients with newly diagnosed GBM were enrolled and treated between May 2017 and June 2018. The standardized therapeutic approach included maximal resection (near total or gross total tumor resection (GTR)) guided by 5-ALA fluorescence-guided surgery (FGS), followed by intraoperative PDT. Postoperatively, patients underwent adjuvant therapy (Stupp protocol). Follow-up included clinical examinations and brain MR imaging was performed every 3 months until tumor progression and/or death. Results There were no unacceptable or unexpected toxicities or serious adverse effects. At the time of the interim analysis, the actuarial 12-months progression-free survival (PFS) rate was 60% (median 17.1 months), and the actuarial 12-months OS rate was 80% (median 23.1 months). Conclusions This trial assessed the feasibility and the safety of intraoperative 5-ALA PDT as a novel approach for treating GBM after maximal tumor resection. The current standard of care remains microsurgical resection whenever feasible, followed by adjuvant therapy (Stupp protocol). We postulate that PDT delivered immediately after resection as an add-on therapy of this primary brain cancer is safe and may help to decrease the recurrence risk by targeting residual tumor cells in the resection cavity. Trial registration NCT number: NCT03048240. EudraCT number: 2016-002706-39. Graphic abstract

Evidence-based, clinical practice guidelines in the management of central nervous system tumors (CNS) continue to be developed and updated through the work of the Joint Section on Tumors of the Congress of Neurological Surgeons (CNS) and the American Association of Neurological Surgeons (AANS). The guidelines are created using the most current and clinically relevant evidence using systematic methodologies, which classify available data and provide recommendations for clinical practice. This update summarizes the Tumor Section Guidelines developed over the last five years for non-functioning pituitary adenomas, low grade gliomas, vestibular schwannomas, and metastatic brain tumors.

Resection of pituitary adenomas presents a number of unique challenges in neuro-oncology. The proximity of these lesions to key vascular and endocrine structures as well as the need to interpret neuronavigation in the context of shifting tumor position increases the complexity of the operation. More recently, substantial advances in fluorescence-guided surgery have been demonstrated to facilitate the identification of numerous tumor types and result in increased rates of complete resection and overall survival. A review of the literature was performed, and data regarding the mechanism of the fluorescence agents, their administration, and intraoperative tumor visualization were extracted. Both in vitro and in vivo studies were assessed. The application of these agents to pituitary tumors, their advantages and limitations, as well as future directions are presented here. Numerous laboratory and clinical studies have described the use of 5-ALA, fluorescein, indocyanine green, and OTL38 in pituitary lesions. All of these drugs have been demonstrated to accumulate in tumor cells. Several studies have reported the successful use of the majority of the agents in inducing intraoperative tumor fluorescence. However, their sensitivity and specificity varies across the literature and between functioning and non-functioning adenomas. At present, numerous studies have shown the feasibility and safety of these agents for pituitary adenomas. However, further research is needed to assess the applicability of fluorescence-guided surgery across different tumor subtypes as well as explore the relationship between their use and postoperative clinical outcomes.

Fluorescence-guided surgery provides surgeons with improved visualization of tumor tissue in the operating room to allow for maximal safe resection of brain tumors. Multiple fluorescent agents have been studied for fluorescence-guided surgery. Both nontargeted and targeted fluorescent agents are currently being used for glioblastoma multiforme visualization and resection. Fluorescence detection in the visible light or near infrared spectrum is possible. Visualization device advancements have permitted greater detection of fluorescence down to the cellular level, which may provide even greater ability for the neurosurgeon to resect tumors.

OBJECTIVESpinal cord injury (SCI) is an area of key interest in military medicine but has not been studied among the US Army Special Forces (SF), the most elite group of US soldiers. SF soldiers make up a disproportionate 60% of all Special Operations casualties. The objective of this study was to better understand SCI incidence in the SF, its mechanisms of acquisition, and potential areas for intervention by addressing key issues pertaining to protective equipment and body armor use.METHODSAn electronic survey questionnaire was formulated with the close collaboration of US board-certified neurosurgeons from the Mount Sinai Hospital and Cleveland Clinic Departments of Neurosurgery, retired military personnel of the SF, and operational staff of the Green Beret Foundation. The survey was sent to approximately 6000 SF soldiers to understand SCI diagnosis and its associations with various health and military variables.RESULTSThe response rate was 8.2%. Among the 492 respondents, 94 (19.1%) self-reported an SCI diagnosis. An airborne operation was the most commonly attributed cause (54.8%). Moreover, 87.1% of SF soldiers reported wearing headgear at the time of injury, but only 36.6% reported wearing body armor, even though body armor use has significantly increased in post-9/11 SF soldiers compared with that in their pre-9/11 counterparts. SCI was significantly associated with traumatic brain injury, arthritis, low sperm count, low testosterone, erectile dysfunction, tinnitus, hyperacusis, sleep apnea, posttraumatic stress disorder, major depressive disorder, and generalized anxiety disorder. Only 16.5% of SF soldiers diagnosed with SCI had been rescued via medical evacuation (medevac) for treatment.CONCLUSIONSA high number of SF soldiers self-reported an SCI diagnosis. Airborne operations landings were the leading cause of SCI, which coincided with warfare tactics employed during the Persian Gulf War, Operation Iraqi Freedom, and other conflicts. A majority of SCIs occurred while wearing headgear and no body armor, suggesting the need for improvements in protective equipment use and design. The low rate of medevac rescue for these injuries may suggest that medical rescue was not attainable at the time or that certain SCIs were deemed minor at the time of injury.

Background Third ventricle cavernous malformations (CMs) associated with ventriculomegaly and obstructive hydrocephalus are quite rare in patients. Preoperative surgical planning can be challenging due to the lesion's non-specific appearance on CT and magnetic resonance imaging that can mimic other intraventricular pathologies, such as a colloid cyst. Management of these lesions can be varied in the setting of obstructive hydrocephalus. Case Description The patient is a 78-year-old woman who first presented to her primary care provider with balance difficulties and inability to ambulate on her own. She also had bladder incontinence and progressive, severe headaches. Imaging of the brain demonstrated entrapment of the right lateral ventricle and obstructive hydrocephalus due to a lesion in the third ventricle obstructing the right foramen of Monro, thought to be a colloid cyst. A right frontal neuroendoscopic approach with direct visualization, however, confirmed a third ventricle CM. A septal pellucidum fenestration was performed to restore cerebrospinal fluid communication and no resection of the lesion was performed. The patient recovered well after the operation and at clinical follow-up reported no headaches and was walking well without a walker and with no neurological deficits. Conclusions A third ventricle CM was discovered after a neuroendoscopic approach for resection of a presumed colloid cyst in a patient with obstructive hydrocephalus. A neuroendoscopic septostomy was performed to treat the obstructive hydrocephalus and no resection was attempted. The patient suffered no complications and is at her neurologic baseline with no deficits.

BACKGROUND The supracerebellar infratentorial approach provides wide flexibility as a far-reaching corridor to the pineal region, posterior third ventricle, posterior medial temporal lobe, posterolateral mesencephalon, quadrigeminal cistern, and thalamus. Traditionally, the patient is placed in the sitting position, allowing gravity retraction on the cerebellum to widen the supracerebellar operative corridor beneath the tentorium. What this approach gains in anatomical orientation it lacks in surgeon ergonomics, as the sitting position presents technical challenges, forces the surgeon to adopt to an uncomfortable posture while performing the microsurgical dissection/tumor resection under the microscope, and is also associated with an increased risk of venous air embolism. OBSERVATIONS In this article, the authors present the use of the three-dimensional (3D) exoscope with a standard prone Concorde position as an alternative for the treatment of lesions requiring a supracerebellar infratentorial approach for lesions in the pineal region, posterior third ventricle, and the superior surface of the cerebellar vermis. The authors present four illustrative cases (one pineal cyst, one ependymoma, and two cerebellar metastases) in which this approach provided excellent intraoperative visualization and resulted in good postoperative results. A step-by-step description of our surgical technique is reviewed in detail. LESSONS The use of the 3D exoscope with the patient in the prone Concorde position is an effective and ergonomically favorable alternative to the traditional sitting position for the treatment of lesions requiring a supracerebellar infratentorial approach. This technique allows improved visualization of deep structures, with a possible decreased risk of potential complications.

Hyperthermia therapy (HT) of cancer is a well-known treatment approach. With the advent of new technologies, HT approaches are now important for the treatment of brain tumors. We review current clinical applications of HT in neuro-oncology and ongoing preclinical research aiming to advance HT approaches to clinical practice. Laser interstitial thermal therapy (LITT) is currently the most widely utilized thermal ablation approach in clinical practice mainly for the treatment of recurrent or deep-seated tumors in the brain. Magnetic hyperthermia therapy (MHT), which relies on the use of magnetic nanoparticles (MNPs) and alternating magnetic fields (AMFs), is a new quite promising HT treatment approach for brain tumors. Initial MHT clinical studies in combination with fractionated radiation therapy (RT) in patients have been completed in Europe with encouraging results. Another combination treatment with HT that warrants further investigation is immunotherapy. HT approaches for brain tumors will continue to a play an important role in neuro-oncology.

Maximal extent of resection (EOR) of glioblastoma (GBM) is associated with greater progression free survival (PFS) and improved patient outcomes. Recently, a novel surgical system has been developed that includes a 2D, robotically-controlled exoscope and brain tractography display. The purpose of this study was to assess outcomes in a series of patients with GBM undergoing resections using this surgical exoscope. A retrospective review was conducted for robotic exoscope assisted GBM resections between 2017 and 2019. EOR was computed from volumetric analyses of pre- and post-operative MRIs. Demographics, pathology/MGMT status, imaging, treatment, and outcomes data were collected. The relationship between these perioperative variables and discharge disposition as well as progression-free survival (PFS) was explored. A total of 26 patients with GBM (median age = 57 years) met inclusion criteria, comprising a total of 28 cases. Of these, 22 (79%) tumors were in eloquent regions, most commonly in the frontal lobe (14 cases, 50%). The median pre- and post-operative volumes were 24.0 cc and 1.3 cc, respectively. The median extent of resection for the cohort was 94.8%, with 86% achieving 6-month PFS. The most common neurological complication was a motor deficit followed by sensory loss, while 8 patients (29%) were symptom-free. The robotic exoscope is safe and effective for patients undergoing GBM surgery, with a majority achieving large-volume resections. These patients experienced complication profiles similar to those undergoing treatment with the traditional microscope. Further studies are needed to assess direct comparisons between exoscope and microscope-assisted GBM resection.

The challenges of neurosurgical patient management and surgical decision-making during the 2019-2020 COVID-19 worldwide pandemic are immense and never-before-seen in our generation of neurosurgeons. In this case-based formatted report, we present the Mount Sinai Hospital (New York, NY) Department of Neurosurgery institutional experience in the epicenter of the pandemic and the guiding principles for our current management of intracranial, skull base, and spine tumors. The detailed explanations of our surgical reasoning for each tumor case is tailored to assist neurosurgeons across the United States as they face these complex operative decisions put forth by the realities of the pandemic.

Patients treated with craniotomy for subdural hematoma (SDH) evacuation have a higher readmission incidence when compared to other neurosurgical patients. Factors predictive of readmission following craniotomy for SDH are incompletely understood. The National Surgical Quality Improvement (NSQIP) database was queried for all patients treated by craniotomy for SDH of any etiology (e.g. acute, chronic, spontaneous, traumatic) during the study period (2012–2014). Patients requiring repeat hospitalization within 30 days of surgery were identified and classified by reason for readmission. Binary logistic regression analysis was used to identify predictors of readmission. 1024 patients met inclusion criteria, among whom 109 (10.6%) were readmitted within 30 days. The most common causes of readmission were recurrent SDH (n = 27; 33.3%), seizure (n = 8; 9.9%), new neurological deficit (n = 6; 7.4%), stroke (n = 6; 7.4%), and altered mental status (AMS) (n = 6; 7.4%). Multivariable modeling identified hypertension requiring medication (OR = 2.78, P = 0.013) and abnormal INR (OR = 2.66, P = 0.035) as significantly associated with readmission following chronic SDH, while postoperative UTI (OR = 3.64, P = 0.01) and stroke (OR = 4.86, P = 0.018) were significant predictors of readmission following acute SDH. Readmission was associated with recurrent hemorrhage after chronic/spontaneous SDH, while seizures, AMS, and neurological deficits drove readmissions after acute/traumatic SDH. Careful management of anticoagulation and antihypertensive medications may be helpful in reducing the risk of readmission following craniotomy for chronic SDH.

BACKGROUND Laser Ablation of Abnormal Neurological Tissue using Robotic NeuroBlate System (LAANTERN) is an ongoing multicenter prospective NeuroBlate (Monteris Medical) LITT (laser interstitial thermal therapy) registry collecting real-world outcomes and quality-of-life (QoL) data. OBJECTIVE To compare 12-mo outcomes from all subjects undergoing LITT for intracranial tumors/neoplasms. METHODS Demographics, intraprocedural data, adverse events, QoL, hospitalizations, health economics, and survival data are collected; standard data management and monitoring occur. RESULTS A total of 14 centers enrolled 223 subjects; the median follow-up was 223 d. There were 119 (53.4%) females and 104 (46.6%) males. The median age was 54.3 yr (range 3-86) and 72.6% had at least 1 baseline comorbidity. The median baseline Karnofsky Performance Score (KPS) was 90. Of the ablated tumors, 131 were primary and 92 were metastatic. Most patients with primary tumors had high-grade gliomas (80.9%). Patients with metastatic cancer had recurrence (50.6%) or radiation necrosis (40%). The median postprocedure hospital stay was 33.4 h (12.7-733.4). The 1-yr estimated survival rate was 73%, and this was not impacted by disease etiology. Patient-reported QoL as assessed by the Functional Assessment of Cancer Therapy-Brain was stabilized postprocedure. KPS declined by an average of 5.7 to 10.5 points postprocedure; however, 50.5% had stabilized/improved KPS at 6 mo. There were no significant differences in KPS or QoL between patients with metastatic vs primary tumors. CONCLUSION Results from the ongoing LAANTERN registry demonstrate that LITT stabilizes and improves QoL from baseline levels in a malignant brain tumor patient population with high rates of comorbidities. Overall survival was better than anticipated for a real-world registry and comparative to published literature., Graphical Abstract Graphical Abstract

BACKGROUND The treatment of glioblastoma (GBM) poses many challenges. The use of immune checkpoint inhibition (ICI) has been disappointing as GBM is characterized by a low mutational burden and low infiltration by T cells. The combination of ICI with other treatment modalities may improve efficacy. METHODS Patients with recurrent GBM were treated with 800 mg avelumab, a human IgG1 antibody directed against PD-L1, either alone (in part A) or within a week after MRI-guided laser interstitial thermal therapy (LITT, in part B) and by-weekly thereafter (NCT03341806). To spare steroid use, bevacizumab was allowed to be combined with avelumab. The primary objective was to characterize the tolerability and safety of the regimen. The secondary objectives included overall survival, progression-free survival, and signature of plasma analytes. RESULTS A total of 12 patients (median age 64, range 37 - 73) enrolled from June 2018 to November 2019, 5 in part A and 7 in part B. Three serious adverse events (SAE) occurred in the same patient, not leading to death. There were 94 AEs reported, 5 grade 3, 28 grade 2, and 61 grade 1. The median PFS was 16.7 weeks (range 7.4-56.7) for patients in Part A and 30.9 weeks (range 8.5-77.7) for patients in Part B. The median survival for patients in part A was 11 months and 13.5 months for part B. The risk ratio of death by combining bevacizumab was 0.573 (p=0.258) with significantly decreased levels of peripheral blood plasma inflammatory markers such as EGF, CXCL5, VEGFA, LAP.TGβ1, ANGPT2 in women. CONCLUSIONS Avelumab was generally well-tolerated, and the combination with LITT had a manageable safety profile and increased survival in a subset of patients. The addition of bevacizumab may increase survival by lowering cytokine expression in a gender-dependent manner. These results warrant further investigation in the next phase study.

Diffuse midline gliomas (DMGs) are highly invasive, unresectable tumors in children. To date, there is no effective treatment for DMGs. Fractionated radiotherapy (RT), currently the standard of care, has provided limited disease control. Current obstacles to treatment include the blood brain barrier (BBB) that limits systemic drug delivery, tumor therapy resistance, and brainstem infiltration. Given the unmet need for more effective DMG treatments, photodynamic therapy (PDT), with the precursor photosensitizing agent 5-aminolevulinic acid (5-ALA), is an oncologic treatment that holds promise. 5-ALA PDT of tumors occurs by targeting tumor cells that accumulate the 5-ALA metabolite, protoporphyrin IX (PPIX), with 635 nm light to create deadly reactive oxygen species (ROS). We explore the synergism of 5-ALA PDT with the MEK inhibitor, trametinib, since the RAS/MEK signaling pathway regulates tumor cell proliferation and survival and has been shown to therapeutically enhance PDT in select tumor models. We demonstrated that sub-micromolar levels of 5-ALA PDT and nanomolar levels of trametinib successfully decrease cell proliferation and induce apoptosis in multiple DMG cell lines. Cell viability assays revealed that drug response differs based on the histone mutation (H3.1 or H3.3) of the line. Mechanisms of decreased cell survival involves the generation of reactive oxygen species that induces programmed cell death. Through the use of a DMG genetically engineered mouse model, we also found 5-ALA PDT to induce apoptosis in vivo. The synergistic effects of MEK inhibition and 5-ALA PDT in vitro and apoptotic effects of 5-ALA PDT in vivo, highlights the potential therapeutic efficacy of this treatment modality.

Surgical management strategies for glioblastoma (GBM) may differ among neurosurgeons with initial biopsy of suspected tumors and the need for early re-resection of tumors within 30 days of initial surgery. This study was initiated by the American Association of Neurological Surgeons (AANS) and Congress of Neurological Surgeons (CNS) Tumor Section’s interest in understanding the rates at which pre- and post-resection procedures, specifically biopsies prior to definitive resection and early re-resections, are performed by U.S. neurosurgeons in the management of GBM. A ten-question survey was distributed to members of the AANS/CNS Tumor Section. The survey response rate among AANS/CNS Tumor Section surgeons was approximately 16%. Results showed that a majority of respondents performed surgery on 11–25 GBM cases annually. Of those cases, most neurosurgeons claimed that biopsies are rarely performed prior to tumor resection, but in the

A retrospective review of prospectively collected data.The purpose of this study is to compare and validate several preoperative scores for predicting outcomes following spine tumor resection.Preoperative risk assessment for patients undergoing spinal tumor resection remains challenging. At present, few risk assessment tools have been validated in this high-risk population.The 2008 to 2014 National Surgical Quality Improvement database was used to identify all patients undergoing surgical resection of spinal tumors, stratified as extradural, intradural extramedullary, and intramedullary based on CPT codes. American Society of Anesthesiologists (ASA) score, modified Charlson Comorbidity Index (CCI), and modified Frailty Index (mFI) were computed. A binary logistic regression model was used to explore the relationship between these variables and postoperative outcomes, including mortality, major and minor adverse events, and hospital length of stay (LOS). Other significant variables such as demographics, operative time, and tumor location were controlled for in each model.Two thousand one hundred seventy patients met the inclusion criteria. Higher CCI scores were independent predictors of mortality (OR = 1.24, 95% CI: 1.14-1.36, P 0.001), major adverse events (OR = 1.07, 95% CI: 1.01-1.31, P = 0.018), minor adverse events (OR = 1.15, 95% CI: 1.10-1.20, P 0.001), and prolonged LOS (OR = 1.14, 95% CI: 1.09-1.19, P 0.001). Patients' mFI scores were significantly associated with mortality and LOS, but not major or minor adverse events. ASA scores were not associated with any outcome metric when controlling for other variables.The CCI demonstrated superior predictive capacity compared with mFI and ASA scores and may be valuable as a preoperative risk assessment tool for patients undergoing surgical resection of spinal tumors. The validation of assessment scores is important for preoperative risk stratification and improving outcomes in this high-risk group.3.

Background The presence of a caroticoclinoid bar (CCB) has been implicated in both transcranial and endonasal surgery. Its morphology reflects differences in the microsurgical anatomy of the parasellar area and its manipulation during anterior or middle clinoidectomy can result in internal carotid artery injury. Although adjustment of the surgical technique according to the CCB anatomic variants is required for safe surgical access to the paraclinoid region, a review indicated the lack of a systematic assortment of reported data regarding the prevalence of the CCB. Thus, our objective was to systematically review and document the prevalence of the CCB and its anatomic variations. Methods Three databases were systematically reviewed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement through August 2018 to identify relevant studies. Results A total of 27 reports (7521 subjects or specimens, 14,449 sides) were included in the present meta-analysis. The overall pooled prevalence of the CCB was 32.6% (95% confidence interval [CI], 26.6%–38.8%) when measured in the subjects or specimens and 23.6% (95% CI, 19.7%–27.6%) when measured in each side. The overall prevalence of the CCB reported from imaging studies was 23.1% (95% CI, 8.9%–41.4%) for the subjects/specimens and 18.7% (95% CI, 12.6%–25.7%) for each side. The presence of the CCB was slightly more prevalent (P = 0.050) on the right side. Conclusions Our results showed a considerable prevalence of the CCB, with lower prevalence rates found among imaging studies. Although meticulous preoperative investigation is mandatory, surgeons treating patients with parasellar pathologic entities should always be vigilant regarding the CCB.

We describe our experience using the extracorporeal video microscope, the "exoscope" for various applications within the field of lateral skull base surgery.A retrospective case series was performed investigating patient demographics, indications for surgery, procedure type, operative time, approach to the skull base, complications, adequacy of visualization, and surgeon comfortability.Six cases were performed with a three dimensional surgical exoscope, obviating the use of a traditional binocular microscope.Academic, tertiary referral center.Type of surgical approach, operative time, patient demographics, surgical complications, and surgeon comfortability.The following procedures were performed; four vestibular schwannoma resections via suboccipital craniotomy and two combined transmastoid and transtemporal approaches for temporal lobe encephalocele repairs. The average operative time was 227 and 577 minutes for temporal lobe encephalocele repairs and vestibular schwannoma cases, respectively. No intraoperative complications were encountered during these cases. None of the procedures required abandonment of the exoscope in favor of the microscope during the procedure. Advantages include high-resolution three-dimensional visualization, increased degrees of freedom for exoscope adjustment, and reduced surgeon fatigue in a fixed, unnatural posture. Limitations include decreased depth perception and increased operative time.The exoscope system is a safe and effective alternative or adjunct to the existing binocular operating microscope for lateral skull based procedures. The exoscope provides the surgeon with a comfortable, high-resolution visualization without compromising surgical exposure and patient safety.4.

Photodynamic therapy (PDT) is a two-step treatment involving the administration of a photosensitive agent followed by its activation at a specific light wavelength for targeting of tumor cells. A comprehensive review of the literature was performed to analyze the indications for PDT, mechanisms of action, use of different photosensitizers, the immunomodulatory effects of PDT, and both preclinical and clinical studies for use in high-grade gliomas (HGGs). PDT has been approved by the United States Food and Drug Administration (FDA) for the treatment of premalignant and malignant diseases, such as actinic keratoses, Barrett’s esophagus, esophageal cancers, and endobronchial non-small cell lung cancers, as well as for the treatment of choroidal neovascularization. In neuro-oncology, clinical trials are currently underway to demonstrate PDT efficacy against a number of malignancies that include HGGs and other brain tumors. Both photosensitizers and photosensitizing precursors have been used for PDT. 5-aminolevulinic acid (5-ALA), an intermediate in the heme synthesis pathway, is a photosensitizing precursor with FDA approval for PDT of actinic keratosis and as an intraoperative imaging agent for fluorescence-guided visualization of malignant tissue during glioma surgery. New trials are underway to utilize 5-ALA as a therapeutic agent for PDT of the intraoperative resection cavity and interstitial PDT for inoperable HGGs. PDT remains a promising therapeutic approach that requires further study in HGGs. Use of 5-ALA PDT permits selective tumor targeting due to the intracellular metabolism of 5-ALA. The immunomodulatory effects of PDT further strengthen its use for treatment of HGGs and requires a better understanding. The combination of PDT with adjuvant therapies for HGGs will need to be studied in randomized, controlled studies.

The US Food and Drug Administration (FDA) approved 5-aminolevulinic acid (5-ALA; Gleolan®; photonamic GmbH and Co. KG) for use as an intraoperative optical imaging agent in patients with suspected high-grade gliomas (HGGs) in 2017. This was the first ever optical imaging agent approved as an adjunct for the visualization of malignant tissue during surgery for brain tumors. The approval occurred a decade after European approval and a multicenter, phase III randomized trial which confirmed that surgeons using 5-ALA fluorescence-guided surgery as a surgical adjunct could achieve more complete resections of tumors in HGG patients and better patient outcomes than with conventional microsurgery. Much of the delay in the US FDA approval of 5-ALA stemmed from its conceptualization as a therapeutic and not as an intraoperative imaging tool. We chronicle the challenges encountered during the US FDA approval process to highlight a new standard for approval of intraoperative optical imaging agents in brain tumors.