Metabolic signatures derived from whole-brain MR-spectroscopy identify early tumor progression in high-grade gliomas using machine learning.

PURPOSE: Recurrence for high-grade gliomas is inevitable despite maximal safe resection and adjuvant chemoradiation, and current imaging techniques fall short in predicting future progression. However, we introduce a novel whole-brain magnetic resonance spectroscopy (WB-MRS) protocol that delves into the intricacies of tumor microenvironments, offering a comprehensive understanding of glioma progression to inform expectant surgical and adjuvant intervention. METHODS: We investigated five locoregional tumor metabolites in a post-treatment population and applied machine learning (ML) techniques to analyze key relationships within seven regions of interest: contralateral normal-appearing white matter (NAWM), fluid-attenuated inversion recovery (FLAIR), contrast-enhancing tumor at time of WB-MRS (Tumor), areas of future recurrence (AFR), whole-brain healthy (WBH), non-progressive FLAIR (NPF), and progressive FLAIR (PF). Five supervised ML classification models and a neural network were developed, optimized, trained, tested, and validated. Lastly, a web application was developed to host our novel calculator, the Miami Glioma Prediction Map (MGPM), for open-source interaction. RESULTS: Sixteen patients with histopathological confirmation of high-grade glioma prior to WB-MRS were included in this study, totaling 118,922 whole-brain voxels. ML models successfully differentiated normal-appearing white matter from tumor and future progression. Notably, the highest performing ML model predicted glioma progression within fluid-attenuated inversion recovery (FLAIR) signal in the post-treatment setting (mean AUC = 0.86), with Cho/Cr as the most important feature. CONCLUSIONS: This study marks a significant milestone as the first of its kind to unveil radiographic occult glioma progression in post-treatment gliomas within 8 months of discovery. These findings underscore the utility of ML-based WB-MRS growth predictions, presenting a promising avenue for the guidance of early treatment decision-making. This research represents a crucial advancement in predicting the timing and location of glioblastoma recurrence, which can inform treatment decisions to improve patient outcomes.

Outcomes of HSV-1 encephalitis infection in glioblastoma: An integrated systematic analysis.

INTRODUCTION: Herpes Simplex Virus-1 (HSV-1) is a neurotropic DNA virus with neural latency and stereotypic viral encephalitis. It has been reported to conceal underlying glioblastoma (GBM) due to similar radiographic imaging and clinical presentation. Limited data exist on the co-occurrence of GBM and HSV-1. To better describe the pathophysiology of HSV-1 superinfections in GBM, we performed a comprehensive review of GBM cases with superimposed HSV-1. METHODS: A comprehensive literature search of six electronic databases with apriori search criteria was performed to identify eligible cases of GBM with HSV-1. Relevant clinic-radiographic data were collected, Kaplan-Meier estimates, Fisher's exact test, and logistic regression analyses were used. RESULTS: We identified 20 cases of HSE in GBM with an overall survival (OS) of 8.0 months. The median age of presentation was 63 years (range: 24-78 years) and the median interval between GBM or HSE diagnosis was 2 months (range: 0.05-25 months). HSE diagnosis before GBM diagnosis was a predictor for improved survival (HR: 0.06; 95% CI: [0.01-0.54]; p < 0.01). There is a significant reduction in OS in patients with concomitant HSE and GBM compared to the cancer genome atlas (TCGA) cohort (median OS: 8 months vs. 14.2 months; p < 0.05). Finally, HSV does not directly infect GBM cells but indirectly activates a local immune response in the tumor microenvironment. CONCLUSIONS: Superimposed HSE in GBM may contribute to a significant reduction in OS compared to uninfected controls, potentially activating proto-oncogenes during active infection and latency. Preoperative HSE may induce an antiviral immune response, which may serve as a positive prognostic factor. Prompt antiviral treatment upon co-occurrence is necessary.

Nitric oxide synthase inhibitors as potential therapeutic agents for gliomas: A systematic review.

INTRODUCTION: Gliomas represent the most prevalent form of brain tumors, among which glioblastomas are the most malignant subtype. Despite advances in comprehending their biology and treatment strategies, median survival remains disappointingly low. Inflammatory processes involving nitric oxide (NO), critically contribute to glioma formation. The inducible isoform of NO synthase (iNOS) is highly overexpressed in gliomas and has been linked to resistance against temozolomide (TMZ) treatment, neoplastic transformation, and modulation of immune response. While both in vitro and in vivo studies showed the potential of iNOS inhibitors as effective treatments for gliomas, no clinical trials on gliomas have been published. This review aims to summarize the available evidence regarding iNOS as a target for glioma treatment, focusing on clinically relevant data. METHODS: Following PRISMA guidelines, we conducted a systematic review by searching PubMed/Medline, and Embase databases in May 2023. We included studies that investigated the impact of NOS inhibitors on glioma cells using L-NMMA, CM544, PBN, 1400W or l-NAME either alone or combined with TMZ. We extracted data on the NOS inhibitor used, subtype, study setting, animal model or cell lines employed, obtained results, and safety profile. Our inclusion criteria encompassed original articles in English or Spanish, studies with an untreated control group, and a primary outcome focused on the biological effects on glioma cells. RESULTS: Out of 871 articles screened from the aforementioned databases, 37 reports were assessed for eligibility. After excluding studies that did not utilize glioma cells or address the designated outcome, 11 original articles satisfied the inclusion and exclusion criteria. Although no NOS inhibitor has been tested in a published clinical trial, three inhibitors have been evaluated using in vivo models of intracranial gliomas. l-NAME, 1400W, and CM544 were tested in vitro. Co-administration of l-NAME, or CM544 with TMZ showed superior results in vitro compared to individual agent testing. CONCLUSION: Glioblastomas remain a challenging therapeutic target. iNOS inhibitors exhibit substantial potential as treatment options for oncologic lesions, and they have demonstrated a safe toxicity profile in humans for other pathological conditions. Research endeavors should be focused on investigating their potential effects on brain tumors.

Towards the definition of progressive disease in brain metastasis treated with laser ablation: an evidence-based study.

PURPOSE: The postoperative period after laser interstitial thermal therapy (LITT) is marked by a temporary increase in volume, which can impact the accuracy of radiographic assessment. The current criteria for progressive disease (PD) suggest that a 20% increase in size of brain metastasis (BM) assessed in 6-12 weeks intervals should be considered as local progression (LP). However, there is no agreement on how LP should be defined in this context. In this study, we aimed to statistically analyze which tumor volume variations were associated with LP. METHODS: We analyzed 40 BM that underwent LITT between 2013 and 2022. For this study, LP was defined following radiographic features. A ROC curve was generated to evaluate volume change as a predictor of LP and find the optimal cutoff point. A logistic regression analysis and Kaplan Meier curves were performed to assess the impact of various clinical variables on LP. RESULTS: Out of 40 lesions, 12 (30%) had LP. An increase in volume of 25.6% from baseline within 120-180 days after LITT presented a 70% sensitivity and 88.9% specificity for predicting LP (AUC: 0.78, p = 0.041). The multivariate analysis showed a 25% increase in volume between 120 and 180 days as a negative predictive factor (p = 0.02). Volumetric changes within 60-90 days after LITT did not predict LP (AUC: 0.57; p = 0.61). CONCLUSION: Volume changes within the first 120 days after the procedure are not independent indicators of LP of metastatic brain lesions treated with LITT.

Two-stage radiosurgery for large brain metastases: a systematic review and meta-analysis of clinical outcomes.

OBJECTIVE: Brain metastases (BMs) are the most common intracranial tumors. In several cases, they present as large masses, which are related to a worse prognosis and more complex therapeutic alternatives. Staged radiosurgery is reported to achieve local control with minimal radiation-related adverse events in BMs. However, no methodological consensus has been achieved in its use for large brain metastases (LBMs; > 2 cm). Therefore, the authors aimed to determine the effectiveness and safety of 2-stage Gamma Knife radiosurgery (GKRS) for LBMs, in order to optimize patients' postoperative course. METHODS: A systematic review of available literature was run in PubMed/MEDLINE, Scopus, Web of Science, Cochrane (OvidSP), and Google Scholar for works published up to December 14, 2022. Nonrandomized clinical trials, case series, and cohort studies were included. The risk of bias was assessed using the Risk of Bias in Nonrandomized Studies-of Interventions (ROBINS-I) and Joanna Briggs Institute tools. Pooled mean difference and rates estimates were calculated by a random-effects model meta-analysis. The degree of heterogeneity was expressed using the I2 statistic. A subgroup analysis was performed. Ultimately, the certainty of evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) assessment. RESULTS: Fourteen studies met the eligibility criteria (cohorts, case series, and nonrandomized clinical trials), including 958 patients. A total pooled mean volume reduction of 6.27 cm3 (95% CI 5.67-6.88 cm3) and 54.36% (95% CI 39.92%-68.79%) after 2-stage GKRS was reported. Pooled rates of complete response (44.63%; 95% CI 26.50%-64.31%), neurological mortality (16.19%; 95% CI 7.68%-30.98%), and all-cause mortality (47.92%; 95% CI 28.04%-68.49%) were calculated. Overall certainty of evidence ranged from very low to moderate. CONCLUSIONS: Two-stage GKRS is an effective and safe approach for the treatment of LBMs. Nevertheless, the lack of available literature and the weak methodological approaches used determine a low to very low certainty of evidence and cannot provide robust evidence to recommend this intervention. Therefore, it is necessary to conduct higher-quality primary studies.

Surgical management of brain metastasis from ovarian cancer: a systematic review and case series.

OBJECTIVE: Ovarian cancer is a rare origin of brain metastasis (BM), with an incidence of only 1%-3%. Consequently, the literature is sparse, and no treatment consensus guideline is available for ovarian BM. The authors conducted a systematic review of ovarian BM and performed a combined pooled cohort survival analysis with their case series. METHODS: A systematic review of PubMed, Scopus, and Web of Science consistent with PRISMA guidelines along with an institutional retrospective chart review was conducted. Inclusion criteria for the systematic review included patients with confirmed BM and primary ovarian cancer, reported perioperative complications and outcomes, differentiated histology, and explicitly reported individual patient data. Reviews, commentaries, technical notes, and articles without English-language translations were excluded. The Newcastle-Ottawa Quality Assessment Scale was used independently by the first and second authors to assess the quality of each article. The authors performed univariate and multivariate analyses of several survival prognostic factors. Kaplan-Meier curves were generated for significant prognostic factors in the univariate analysis. RESULTS: A total of 48 patients with individual data across 34 studies and 8 patients from the authors' institution were included. All patients (n = 56) underwent resection for BM; 83.9% received adjuvant radiotherapy following surgery and 41.1% of patients received adjuvant chemotherapy. The median progression-free survival was 12 months (range 2-43 months). The median overall survival was 9 months (range 1-49 months). On univariate analysis, a single BM and no extracranial metastasis conferred a survival benefit, while clear cell carcinoma as the primary histology corresponded to worsened OS. Multivariable analysis showed that age > 50 years (p = 0.002) and > 1 BM (p < 0.001) were risk factors for poor prognosis. Protective factors included the addition of the following multimodal adjuvant therapy with surgery: radiotherapy (p = 0.002), chemotherapy and radiotherapy (p = 0.005), and stereotactic radiosurgery (p = 0.002). CONCLUSIONS: Although the scarcity of published individual patient data hinders the determination of optimal management, the authors' analysis highlights that multimodal therapies, a single cranial lesion, and age < 50 years are associated with increased survival for patients with ovarian BMs.

Same-day discharge after craniotomy for brain tumor resection: enhancing patient selection through a prognostic scoring system.

OBJECTIVE: Neurosurgery, among other surgical fields, is amid a shift in patient management with enhanced recovery and same-day discharge (SDD) protocols slowly becoming more popular and feasible. While such protocols reduce the risk of nosocomial complications and improve patient satisfaction, appropriate patient selection remains an area of debate. The authors aimed to better quantify selection criteria through a prospective follow-up study of patients undergoing brain tumor resection with SDD. METHODS: Three arms of analysis were carried out. First, clinical data of SDD patients were prospectively collected between August 2021 and August 2022. In parallel, a retrospective analysis of patients who qualified for SDD but were excluded at surgeon clinical discretion over the same period was performed. Third, a comparative analysis of the pilot and follow-up studies was done from which a clinical scoring system for patient selection was derived. RESULTS: Over the duration of the study, 31 of 334 patients were selected for SDD while 59 qualified for SDD by previously defined criteria but were not selected at the surgeon's discretion. There was no difference in outcomes between the two groups, and there were no postoperative complications among the SDD group within 30 days of surgery. Preoperative clinical characteristics found to be significantly different between the two cohorts (left-sided lesion, extra-axial pathology, prior treatment of brain tumor, and tumor volume ≤ 11.75 cm3) were included in a predictive scoring system for successful SDD. The scoring system was found to significantly predict high or low likelihood for successful SDD when tested on the mixed prospective cohort. CONCLUSIONS: This study provides a straightforward clinical scoring system for appropriate selection of candidates for SDD after craniotomy for brain tumor resection. This clinical tool aims to aid clinicians in appropriate admission course selection and builds on the growing literature surrounding same-day and outpatient cranial neurosurgery.

Design-development of an at-home modular brain-computer interface (BCI) platform in a case study of cervical spinal cord injury.

OBJECTIVE: The objective of this study was to develop a portable and modular brain-computer interface (BCI) software platform independent of input and output devices. We implemented this platform in a case study of a subject with cervical spinal cord injury (C5 ASIA A). BACKGROUND: BCIs can restore independence for individuals with paralysis by using brain signals to control prosthetics or trigger functional electrical stimulation. Though several studies have successfully implemented this technology in the laboratory and the home, portability, device configuration, and caregiver setup remain challenges that limit deployment to the home environment. Portability is essential for transitioning BCI from the laboratory to the home. METHODS: The BCI platform implementation consisted of an Activa PC + S generator with two subdural four-contact electrodes implanted over the dominant left hand-arm region of the sensorimotor cortex, a minicomputer fixed to the back of the subject's wheelchair, a custom mobile phone application, and a mechanical glove as the end effector. To quantify the performance for this at-home implementation of the BCI, we quantified system setup time at home, chronic (14-month) decoding accuracy, hardware and software profiling, and Bluetooth communication latency between the App and the minicomputer. We created a dataset of motor-imagery labeled signals to train a binary motor imagery classifier on a remote computer for online, at-home use. RESULTS: Average bluetooth data transmission delay between the minicomputer and mobile App was 23 ± 0.014 ms. The average setup time for the subject's caregiver was 5.6 ± 0.83 min. The average times to acquire and decode neural signals and to send those decoded signals to the end-effector were respectively 404.1 ms and 1.02 ms. The 14-month median accuracy of the trained motor imagery classifier was 87.5 ± 4.71% without retraining. CONCLUSIONS: The study presents the feasibility of an at-home BCI system that subjects can seamlessly operate using a friendly mobile user interface, which does not require daily calibration nor the presence of a technical person for at-home setup. The study also describes the portability of the BCI system and the ability to plug-and-play multiple end effectors, providing the end-user the flexibility to choose the end effector to accomplish specific motor tasks for daily needs. Trial registration ClinicalTrials.gov: NCT02564419. First posted on 9/30/2015.

Safety and Efficacy of Balloon-Assisted Kyphoplasty Followed by Stereotactic Body Radiation Therapy for Pathological Fractures.

BACKGROUND AND OBJECTIVES: In patients experiencing pain secondary to pathological compression fractures, balloon-assisted kyphoplasty and subsequent stereotactic body radiation therapy (SBRT) may allow for restoration of vertebral height and irradiation of the underlying malignancy to control local disease progression. The aim of this study was to evaluate the safety and efficacy of kyphoplasty treatment before SBRT in patients with spinal metastases and benign tumors. METHODS: An analysis of a prospectively collected database of 70 patients and 75 metastatic and benign spinal lesions that underwent kyphoplasty before SBRT at a single institution (2002-2023) was conducted. Patient characteristics were recorded, including treatment history, dosimetry and fractionation schedule, pain outcomes, local control (LC), and overall survival. The Bilsky score and Spinal Instability Neoplastic Score were calculated to assess epidural involvement and spinal stability, respectively. RESULTS: The median time from kyphoplasty to SBRT was 29 days (range: 2-159). Seventy-two lesions (96%) were managed with single-fraction SBRT and 3 lesions (4%) with a multifraction regimen. The median single-fraction prescription dose was 20 Gy (range: 12-25) delivered to a median tumor volume of 35.1 cc (range: 2.2-160). After a median follow-up period of 9 months (range: 1-201), 6 lesions (8%) locally progressed. Pain was reported to improve or remain stable for most patients (88%). The LC rate was 88% at 6 months, 1 year, and 2 years. No prognostic factors were significantly associated with LC. The median overall survival was 11 months (range: 1-201) after radiosurgery. There were no reports of cement extravasation or radiation-induced neurological deficit. Two acute pain flares (3%) were reported 1 and 3 months after radiosurgery. CONCLUSION: The combined kyphoplasty and SBRT treatment paradigm can be used to treat patients with painful pathological compression fractures. Long-term LC and patient-reported improvement in pain were observed without the morbidity associated with open surgery.

Spine Stereotactic Radiosurgery Provides Long-Term Local Control and Overall Survival for Benign Intradural Tumors.

BACKGROUND AND OBJECTIVES: The role of radiosurgery in the treatment of benign intracranial tumors is well established. However, there are limited long-term follow-up studies on outcomes after stereotactic radiosurgery (SRS) for benign intradural spinal tumors. In this article, we report a large single-institution experience in using SRS to treat patients with benign intradural tumors of the spine. METHODS: Overall, 184 patients (55% female) and 207 benign intradural tumors were treated. The median patient age was 52 years (range: 19-93). Tumor histology included schwannoma (38%), meningioma (15%), neurofibroma (21%), hemangioma (9%), hemangioblastoma (8%), hemangiopericytoma (5%), and paraganglioma (4%). Thirty-four (16%) lesions underwent resection before radiosurgery. Twenty-three (11%) lesions were NF1-mutated. The median single-fraction margin dose was 14 Gy (range: 11-20), and the median multifraction margin dose was 21 Gy (range: 15-30). RESULTS: The median follow-up was 63 months (range: 1-258). At last follow-up, tumors volumetrically regressed (15%), remained stable (77%), or locally progressed (8%, median: 20 months [range: 3-161]) after SRS. The 1-, 5-, and 10-year local control rates were 97%, 92%, and 90%, respectively. On multivariable analysis, the absence of the NF1 mutation (P = .004, hazard ratio: 0.23, 95% CI: 0.08-0.63) and single-fraction SRS (P = .007, hazard ratio: 0.24, 95% CI: 0.08-0.68) correlated with improved local control. The median overall survival was 251 months (range: 1-258), and 1-, 5-, and 10-year overall survival rates were 95%, 85%, and 70%, respectively. For patients with pre-existing symptoms, tumor-associated pain and neurological deficits were noted to improve or remain stable in 85% and 87% of cases, respectively. Adverse radiation effects included delayed myelopathy (1%), acute pain flare (9%), dermatitis (0.5%), dysphagia (0.5%), and dysphonia (0.5%). CONCLUSION: With long-term follow-up, spine radiosurgery is a safe and effective treatment for benign intradural tumors. In carefully selected patients, even with an NF1 mutation, SRS is associated with a high likelihood of local tumor control.

Exploring the Landscape of Machine Learning Applications in Neurosurgery: A Bibliometric Analysis and Narrative Review of Trends and Future Directions.

BACKGROUND: The field of neurosurgery has consistently represented an area of innovation and integration of technology since its inception. As such, machine learning (ML) has found its way into applications within neurosurgery relatively rapidly. Through this bibliometric review and cluster analysis, we seek to identify trends and emerging applications of ML within neurosurgery. METHODS: A bibliometric analysis was carried out in the Web of Science database on publications from January 2000 to March 2023. The full data set of the 200 most cited publications including title, author information, journal, citation count, keywords, and abstracts for each publication was evaluated in CiteSpace. CiteSpace was used to elucidate publication characteristics, trends, and topic clusters via collaborate network analysis using the Kamada-Kawai algorithm. RESULTS: The 25 most cited titles were included in our analysis. Harvard University and its affiliates represented the top institution, contributing nearly 25% of publications in the literature. WORLD NEUROSURGERY was the journal with the highest net citation count of 747 (29%). Collaborative network analysis generated 12 unique clusters, the largest of which was machine learning, followed by feature importance and deep brain stimulation. CONCLUSION: This review highlights the most impactful articles pertaining to ML in the field of neurosurgery. ML has been applied into several sub-specialties within neurosurgery to optimize patient care, with special attention to outcome predictors, patient selection, and surgical decision making.

The Learning Curve and Clinical Outcomes With 250 Laser Ablations for Brain Tumors: A Pathway to Experience.

BACKGROUND AND OBJECTIVES: Laser interstitial thermal therapy (LITT) has gained popularity as a minimally invasive technique for treating brain tumors. Despite its proven safety profile, LITT is not yet widely available, and there is a lack of data on the learning curve required to achieve proficiency. This study analyzes a 250-patient cohort of laser-ablated tumors to describe changes in patient selection and clinical outcomes over time and experience, with the aim of providing insight into the learning curve for incorporating LITT into a neuro-oncology program and identifying a cutoff point that distinguishes novice from expert performance. METHODS: We retrospectively reviewed 250 patients with brain tumor who underwent LITT between 2013 and 2022. Demographic and clinical data were analyzed. Kaplan Meier curves were used for survival analysis. Operative time was evaluated using exponential curve-fit regression analysis to identify when consistent improvement began. RESULTS: The patients were divided into quartiles (Q) based on their date of surgery. Mean tumor volume increased over time (Q1 = 5.7 and Q4 = 11.9 cm 3 , P = .004), and newly diagnosed lesions were more frequently ablated ( P = .0001). Mean operative time (Q1 v Q4 = 322.3 v 204.6 min, P < .0001) and neurosurgical readmission rate (Q1 v Q4 = 7.8% v 0%, P = .03) were reduced over time. The exponential curve-fit analysis showed a sustained decay in operative time after case #74. The extent of ablation ( P = .69), the recurrence ( P = .11), and the postoperative complication rate ( P = .78) did not vary over time. CONCLUSION: After treating 74 patients, a downward trend in the operative time is observed. Patient selection is broadened as experience increases.

The Impact of Perilesional Heatsink Structures on Ablation Volumes in Laser Interstitial Thermal Therapy for Brain Metastases.

BACKGROUND AND OBJECTIVES: Laser interstitial thermal therapy (LITT) has demonstrated promise in surgical neuro-oncology because of its effectiveness in delivering precise thermal energy to lesions. The extent of ablation (EOA) is a prognostic factor in improving patient outcomes but is often affected by perilesional heatsink structures, which can lead to asymmetric ablations. The purpose of this study was to quantitatively evaluate the impact of various perilesional heatsink structures on the EOA in LITT for brain metastases. METHODS: Twenty-seven procedures for 22 unique patients with brain metastases fit the inclusion criteria. Intracranial heatsink structures were identified: sulci, meninges, cerebrospinal fluid (CSF) spaces, and vasculature. Asymmetric ablation was determined by measuring 3 pairs of orthogonal distances from the proximal, midpoint, and distal locations along the laser catheter to the farthest edge of the ablation zone bilaterally. Distances from the same points on the laser catheter to the nearest heatsink were also recorded. The Heatsink Effect Index was created to serve as a proxy for asymmetric ablation. Pearson correlations, t -tests, and analysis of variance were the statistical analyses performed. RESULTS: From the midpoint of the catheter, the 27 heatsinks were meninges (40.7%), sulci (22.2%), vasculature (22.2%), and CSF spaces (14.8%). Across all points along the catheter track, there was a significant generalized heatsink effect on asymmetric ablations ( P < .0001). There was a negative correlation observed between asymmetric ablations and EOA from the midpoint of the laser catheter (r = -0.445, P = .020). Compared with sulci, CSF spaces trended toward a greater effect on asymmetric ablation volumes ( P = .069). CONCLUSION: This novel quantitative analysis shows that perilesional heatsinks contribute to asymmetric ablations. CSF spaces trended toward higher degrees of asymmetric ablations. Importantly, neurosurgeons may anticipate asymmetric ablations preoperatively if heatsinks are located within 13.3 mm of the laser probe midpoint. These preliminary results may guide surgical decision-making in LITT for metastatic brain lesions.

Evaluation of the FLEXotendon glove-III through a human subject case study.

Cervical spinal cord injury (SCI) can significantly impair an individual's hand functionality due to the disruption of nerve signals from the brain to the upper extremity. Robotic assistive hand exoskeletons have been proposed as a potential technology to facilitate improved patient rehabilitation outcomes, but few exoskeleton studies utilize standardized hand function tests and questionnaires to produce quantitative data regarding exoskeleton performance. This work presents the human subject case study evaluation of the FLEXotendon Glove-III, a 5 degree-of-freedom voice-controlled, tendon-driven soft robotic assistive hand exoskeleton for individuals with SCI. The exoskeleton system was evaluated in a case study with two individuals with SCI through two standardized hand function tests namely, the Jebsen-Taylor Hand Function Test and the Toronto Rehabilitation Institute Hand Function Test and three questionnaires (Capabilities of Upper Extremities Questionnaire, Orthotics Prosthetics Users Survey, Quebec User Evaluation of Satisfaction with Assistive Technology). Minor design changes were made to the exoskeleton: integrated fingertip force sensors to sense excessive grasp force, a quick connect system to expedite the exoskeleton glove swapping process between users, compact tendon tension sensors to measure tendon force for admittance control, and a redesigned smartphone app to encompass all aspects of exoskeleton use.

Percutaneous Closure Device for the Carotid artery: An integrated review and design analysis.

Endovascular thrombectomies (EVTs) are the current standard of care therapy for treating acute ischemic strokes. While access through the femoral or radial arteries is routine, up to 20% of EVTs through these sites are unable to access the cerebral vasculature on the first pass. These shortcomings are commonly due to tortuous vasculature, atherosclerotic arteries, and type III aortic arch, seen especially in the elderly population. Recent studies have shown the benefits of accessing the cerebral vasculature through a percutaneous direct carotid puncture (DCP), which can reduce the time of the procedure by half. However, current vascular closure devices (VCDs) designed for the femoral artery are not suited to close the carotid artery due to the anatomical differences. This unmet clinical need further limits a DCP approach. Thus, to foster safe adoption of this potential approach, a VCD designed specifically for the carotid artery is needed. In this review, we outline the major biomechanical properties and shortcomings of current VCDs and propose the requirements necessary to effectively design and develop a carotid closure device.

Bilateral Laser Interstitial Thermal Therapy for Butterfly Gliomas Compared With Needle Biopsy: A Preliminary Survival Study.

BACKGROUND AND OBJECTIVES: Bilateral/butterfly glioblastoma (bGBM) has a poor prognosis. Resection of these tumors is limited due to severe comorbidities that arise from surgical procedures. Laser interstitial thermal therapy (LITT) offers a minimally invasive cytoreductive therapy for deep-seated tumors such as bGBM. The objective of this study was to evaluate the safety of bilateral LITT in patients with bGBM. METHODS: Medical records of all consecutive patients diagnosed with bGBM by a single surgeon at a single institution from January 2014 to August 2022 were reviewed. Clinical, safety, and radiographic volumetric data were obtained. In addition, an exploratory analysis of survival was performed. RESULTS: A total of 25 patients were included; 14 underwent biopsy only, and 11 underwent biopsy + LITT (7 underwent bilateral and 4 underwent unilateral LITT). No (0%) intraoperative or postoperative complications were recorded in the treatment group. Tumor volume negatively correlated with extent of treatment (r 2 = 0.44, P = .027). The median progression-free survival was 2.8 months in the biopsy-only group and 5.5 months in the biopsy + LITT group ( P = .026). The median overall survival was 4.3 months in the biopsy-only group and 10.3 months in the biopsy + LITT group ( P = .035). CONCLUSION: Bilateral LITT for bGBM can be safely performed and shows early improvement of the progression-free survival and long-term survival outcomes of these patients.

Surgical Approaches to Thalamic Gliomas: A Systematic Review.

BACKGROUND: Adult thalamic gliomas (ATGs) present a surgical challenge given their depth and proximity to eloquent brain regions. Choosing a surgical approach relies on different clinical variables such as anatomical location and size of the tumor. However, conclusive data regarding how these variables influence the balance between extent of resection and complications are lacking. We aim to systematically review the literature to describe the current surgical outcomes of ATG and to provide tools that may improve the decision-making process. METHODS: Literature regarding the surgical management of ATG patients was reviewed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Four databases were queried and a description of clinical characteristics and survival analysis were performed. An individual patient data analysis was conducted when feasible. RESULTS: A total of 462 patients were included from 13 studies. The mean age was 39.8 years with a median preoperative Karnofsky performance scale of 70. The lateral approaches were most frequently used (74.9%), followed by the interhemispheric (24.2%). Gross total and subtotal/partial resections were achieved in 81%, and 19% of all cases, respectively. New permanent neurological deficits were observed in 51/433 patients (11.8%). individual patient data was pooled from 5 studies (n = 71). In the multivariate analysis, tumors located within the posterior thalamus had worse median overall survival compared to anterior gliomas (14.5 vs. 27 months, P = 0.003). CONCLUSIONS: Surgical resection of ATGs can increase survival but at the risk of operative morbidity. Knowing which factors impact survival may allow neurosurgeons to propose a more evidence-based treatment to their patients.

Frontal lobe low-grade tumors seizure outcome: a pooled analysis of clinical predictors.

OBJECTIVE: Seizures present in 50-90 % of cases with low-grade brain tumors. Frontal lobe epilepsy is associated with dismal seizure outcomes compared to temporal lobe epilepsy. Our objective is to conduct a systematic review, report our case series, and perform a pooled analysis of clinical predictors of seizure outcomes in frontal lobe low-grade brain tumors. METHODS: Searches of five electronic databases from January 1990 to June 2022 were reviewed following PRISMA guidelines. Individual patient data was extracted from 22 articles that fit the inclusion criteria. A single-surgeon case series from our institution was also retrospectively reviewed and analyzed through a pooled cohort of 127 surgically treated patients with frontal lobe low-grade brain tumors. RESULTS: The mean age at surgery was 30.8 years, with 50.4 % of patients diagnosed as oligodendrogliomas. The majority of patients (81.1 %) were seizure-free after surgery (Engel I). On the multivariate analysis, gross total resection (GTR) (OR = 8.77, 95 % CI: 1.99-47.91, p = 0.006) and awake resection (OR = 9.94, 95 % CI: 1.93-87.81, p = 0.015) were associated with seizure-free outcome. A Kaplan-Meier curve showed that the probability of seizure freedom fell to 92.6 % at 3 months, and to 85.5 % at 27.3 months after surgery. CONCLUSION: Epilepsy from tumor origin demands a balance between oncological management and epilepsy cure. Our pooled analysis suggests that GTR and awake resections are positive predictive factors for an Engel I at more than 6 months follow-up. To validate these findings, a longer-term follow-up and larger cohorts are needed.

Surgically Treated Brain Metastases from Uterine Origin: A Case Series and Systematic Review.

OBJECTIVE: We aimed to describe our institutional case series of 9 surgically treated uterine brain metastases and perform a survival analysis through a systematic review and a pooled individual patient data study. METHODS: This study was divided into 2 sections: 1) a retrospective, single center patient series assessing outcomes of neurosurgical treatment modalities in patients with malignancy arising in the uterus with brain metastases and 2) a systematic review of the literature between 1980 and 2021 regarding treatment outcomes of individual patients with intracranial metastasis of uterine origin. Pooled cohort survival analysis was done via univariate and Cox regression multivariable analysis and Kaplan-Meier curves. RESULTS: Final statistical analysis included a total of 124 pooled cohort patients: one hundred fifteen patients from literature review studies plus 9 patients from our institution. Median age at the time of diagnosis was 54 years. Median time from diagnosis of the primary cancer to brain metastasis was 19 months (0-166 months). Surgery and radiotherapy resulted in the highest median OS of 11 months (P < 0.001). Multivariable analyses indicated that the presence of more than one central nervous systemlesion had an increased risk on OS (P = 0.003). Microsurgery, stereotactic radiosurgery, and whole brain radiotherapy remain the evidence-based mainstay applicable to the treatment of multiple brain metastases. CONCLUSIONS: Brain metastases of cancer arising in the uterus appear to result most often in multiple lesions with dismal prognosis. The seemingly most efficacious treatment modality is surgery and radiotherapy. However, this treatment is often not an option when more than 1 or 2 brain lesions are present.

Laser Interstitial Thermal Therapy Induces Robust Local Immune Response for Newly Diagnosed Glioblastoma With Long-term Survival and Disease Control.

Laser interstitial thermal therapy (LITT) is a minimally invasive neurosurgical technique used to ablate intra-axial brain tumors. The impact of LITT on the tumor microenvironment is scarcely reported. Nonablative LITT-induced hyperthermia (33-43˚C) increases intra-tumoral mutational burden and neoantigen production, promoting immunogenic cell death. To understand the local immune response post-LITT, we performed longitudinal molecular profiling in a newly diagnosed glioblastoma and conducted a systematic review of anti-tumoral immune responses after LITT. A 51-year-old male presented after a fall with progressive dizziness, ataxia, and worsening headaches with a small, frontal ring-enhancing lesion. After clinical and radiographic progression, the patient underwent stereotactic needle biopsy, confirming an IDH-WT World Health Organization Grade IV Glioblastoma, followed by LITT. The patient was subsequently started on adjuvant temozolomide, and 60 Gy fractionated radiotherapy to the post-LITT tumor volume. After 3 months, surgical debulking was conducted due to perilesional vasogenic edema and cognitive decline, with H&E staining demonstrating perivascular lymphocytic infiltration. Postoperative serial imaging over 3 years showed no evidence of tumor recurrence. The patient is currently alive 9 years after diagnosis. Multiplex immunofluorescence imaging of pre-LITT and post-LITT biopsies showed increased CD8 and activated macrophage infiltration and programmed death ligand 1 expression. This is the first depiction of the in-situ immune response to LITT and the first human clinical presentation of increased CD8 infiltration and programmed death ligand 1 expression in post-LITT tissue. Our findings point to LITT as a treatment approach with the potential for long-term delay of recurrence and improving response to immunotherapy.