Awake Robotic Minimally-Invasive Transforaminal Lumbar Interbody Fusion under Spinal Anesthesia: a Prospective Study with 1-year Follow-up.

BACKGROUND: We describe our protocol and outcomes of awake robotic minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) under spinal anesthesia. METHODS: We conducted a prospective study of 10 consecutive patients undergoing awake robotic single-level MIS-TLIF with the Mazor X robot. We prospectively collected patient-reported outcomes (back and leg pain VAS, and Oswestry Disability Index) pre-operatively, at the 1-month, and 1-year follow-up, and assessed fusion and screw placement accuracy with the 1-year CT scan. RESULTS: Median age was 61 years (IQR=57.7-66); median BMI 27kg/m2. No intraoperative complications reported. 9/10 patients were discharged home, 50% discharged on the day of surgery. Median length of stay was 16.5h (IQR=5-35.5); median follow-up 12.5 months (IQR=12-13.5), with 9 patients having at least 12-month follow-up, with CT scans documenting good screw placement (Gertzbein-Robbins Grade A) and solid bony fusion. Median pre-op back pain VAS was 7.8 (IQR=6.9-8) versus 1.5 (IQR=0-3.2) at 1-month post-op, p<0.01, and 0 (IQR=0-1) at 1-year follow-up, p<0.01; median preop leg pain 8 (IQR=7.4-8) versus 0 (IQR=0-1.2) at 1-month post-op, p<0.01, and 0 (IQR=0-2) at 1-year follow-up, p<0.01; median preop ODI 47.5 (IQR=27.8-57.5) versus 4 (IQR=0-16) at 1-month post-op, p<0.01, and 0 (IQR=0-7) at 1-year follow-up, p<0.01. Median preoperative disc high of the index level 8mm (IQR=2.4-9.5), versus 11.4mm (IQR=9.2-11.2) postoperatively, p< 0.01. Median preoperative lordosis of the index level 5 degrees (IQR=3.4-8.5), versus 10.1 degrees (7.3-12.2) postoperatively, p< 0.01. CONCLUSIONS: Our study showed significant improvement in PROs at 1-month and 1-year follow-up after awake robotic MIS-TLIF, as well as solid bony fusion on CT scans.

International Hackathon as a Tool to Augment Education, Collaboration, and Innovation in Global Neurosurgery.

BACKGROUND AND OBJECTIVES: Health care providers' exposure to global surgical disparities is limited in current nursing and/or medical school curricula. For instance, global health is often associated with infectious diseases or maternal health without acknowledging the growing need for surgical care in low- and middle-income countries (LMICs). We propose an international virtual hackathon based on neurosurgical patient cases in under-resourced settings as an educational tool to bring awareness to global surgical disparities and develop relationships among trainees in different countries. METHODS: Participants were recruited through email listservs, a social media campaign, and prize offerings. A 3-day virtual hackathon event was administered, which included workshops, mentorship, keynote panels, and pitch presentations to judges. Participants were presented with real patient cases and directed to solve a barrier to their care. Surveys assessed participants' backgrounds and event experience. The hackathon was executed through Zoom at Harvard Innovation Lab in Boston, MA, on March 25 to 27, 2022. Participants included medical students, with additional participants from business, engineering, or current health care workers. RESULTS: Three hundred seven applications were submitted for 100 spots. Participants included medical students, physicians, nurses, engineers, entrepreneurs, and undergraduates representing 25 countries and 82 cities. Fifty-one participants previously met a neurosurgeon, while 39 previously met a global health expert, with no difference between LMIC and high-income countries' respondents. Teams spent an average of 2.75 hours working with mentors, and 88% of postevent respondents said the event was "very" or "extremely conducive" to networking. Projects fell into 4 categories: access, language barriers, education and training, and resources. The winning team, which was interdisciplinary and international, developed an application that analyzes patient anatomy while performing physical therapy to facilitate remote care and clinical decision-making. CONCLUSION: An international virtual hackathon can be an educational tool to increase innovative ideas to address surgical disparities in LMICs and establish early collaborative relationships with medical trainees from different countries.

Effects of PreOperative radiotherapy in a preclinical glioblastoma model: a paradigm-shift approach.

PURPOSE: PreOperative radiotherapy (RT) is commonly used in the treatment of brain metastasis and different cancer types but has never been used in primary glioblastoma (GBM). Here, we aim to establish, describe, and validate the use of PreOperative RT for the treatment of GBM in a preclinical model. METHODS: Rat brains were locally irradiated with 30-Gy, hypofractionated in five doses 2 weeks before or after the resection of intracranial GBM. Kaplan-Meier analysis determined survival. Hematoxylin-eosin staining was performed, and nuclei size and p21 senescence marker were measured in both resected and recurrent rodent tumors. Immunohistochemistry assessed microglia/macrophage markers, and RNAseq analyzed gene expression changes in recurrent tumors. Akoya Multiplex Staining on two human patients from our ongoing Phase I/IIa trial served as proof of principle. RESULTS: PreOperative RT group median survival was significantly higher than PostOperative RT (p < 0.05). Radiation enlarged cytoplasm and nuclei in PreOperative RT resected tumors (p < 0.001) and induced senescence in PostOperative RT recurrent tumors (p < 0.05). Gene Set Enrichment Analysis (GSEA) suggested a more proliferative profile in PreOperative RT group. PreOperative RT showed lower macrophage/microglia recruitment in recurrent tumors (p < 0.01) compared to PostOperative RT. Akoya Multiplex results indicated TGF-ß accumulation in the cytoplasm of TAMs and CD4 + lymphocyte predominance in PostOperative group. CONCLUSIONS: This is the first preclinical study showing feasibility and longer overall survival using neoadjuvant radiotherapy before GBM resection in a mammalian model. This suggests strong superiority for new clinical radiation strategies. Further studies and trials are required to confirm our results.

Transcriptional determinism and stochasticity contribute to the complexity of autism-associated SHANK family genes.

Precision of transcription is critical because transcriptional dysregulation is disease causing. Traditional methods of transcriptional profiling are inadequate to elucidate the full spectrum of the transcriptome, particularly for longer and less abundant mRNAs. SHANK3 is one of the most common autism causative genes. Twenty-four Shank3-mutant animal lines have been developed for autism modeling. However, their preclinical validity has been questioned due to incomplete Shank3 transcript structure. We apply an integrative approach combining cDNA-capture and long-read sequencing to profile the SHANK3 transcriptome in humans and mice. We unexpectedly discover an extremely complex SHANK3 transcriptome. Specific SHANK3 transcripts are altered in Shank3-mutant mice and postmortem brain tissues from individuals with autism spectrum disorder. The enhanced SHANK3 transcriptome significantly improves the detection rate for potential deleterious variants from genomics studies of neuropsychiatric disorders. Our findings suggest that both deterministic and stochastic transcription of the genome is associated with SHANK family genes.

International Hackathon as a Tool to Augment Education, Collaboration, and Innovation in Global Neurosurgery.

BACKGROUND AND OBJECTIVES: Health care providers' exposure to global surgical disparities is limited in current nursing and/or medical school curricula. For instance, global health is often associated with infectious diseases or maternal health without acknowledging the growing need for surgical care in low- and middle-income countries (LMICs). We propose an international virtual hackathon based on neurosurgical patient cases in under-resourced settings as an educational tool to bring awareness to global surgical disparities and develop relationships among trainees in different countries. METHODS: Participants were recruited through email listservs, a social media campaign, and prize offerings. A 3-day virtual hackathon event was administered, which included workshops, mentorship, keynote panels, and pitch presentations to judges. Participants were presented with real patient cases and directed to solve a barrier to their care. Surveys assessed participants' backgrounds and event experience. The hackathon was executed through Zoom at Harvard Innovation Lab in Boston, MA, on March 25 to 27, 2022. Participants included medical students, with additional participants from business, engineering, or current health care workers. RESULTS: Three hundred seven applications were submitted for 100 spots. Participants included medical students, physicians, nurses, engineers, entrepreneurs, and undergraduates representing 25 countries and 82 cities. Fifty-one participants previously met a neurosurgeon, while 39 previously met a global health expert, with no difference between LMIC and high-income countries' respondents. Teams spent an average of 2.75 hours working with mentors, and 88% of postevent respondents said the event was "very" or "extremely conducive" to networking. Projects fell into 4 categories: access, language barriers, education and training, and resources. The winning team, which was interdisciplinary and international, developed an application that analyzes patient anatomy while performing physical therapy to facilitate remote care and clinical decision-making. CONCLUSION: An international virtual hackathon can be an educational tool to increase innovative ideas to address surgical disparities in LMICs and establish early collaborative relationships with medical trainees from different countries.

A Wireless Battery-Free Implant With Optical Telemetry for In Vivo Cortical Stimulation.

We present a 100 µm-thick, wireless, and battery-free implant for brain stimulation through a U.S. Food and Drug Administration-approved collagen dura substitute without contact with the brain's surface, while providing visible-light spectrum telemetry to track the onset of stimulation. The device is fabricated on a 16 × 6.67 mm2 biocompatible parylene/PDMS substrate and is encapsulated with a 2 µm-thick transparent parylene layer that enables the relay of the LED brightness. The in vivo rodent testing confirmed the implant's ability to trigger motor response while generating observable brightness through the skin. The results reveal the prospect of wireless stimulation with enhanced safety by eliminating contact between the implant and the brain, with optical telemetry for facilitated tracking.

Rapid detection of IDH mutations in gliomas by intraoperative mass spectrometry.

The development and performance of two mass spectrometry (MS) workflows for the intraoperative diagnosis of isocitrate dehydrogenase (IDH) mutations in glioma is implemented by independent teams at Mayo Clinic, Jacksonville, and Huashan Hospital, Shanghai. The infiltrative nature of gliomas makes rapid diagnosis necessary to guide the extent of surgical resection of central nervous system (CNS) tumors. The combination of tissue biopsy and MS analysis used here satisfies this requirement. The key feature of both described methods is the use of tandem MS to measure the oncometabolite 2-hydroxyglutarate (2HG) relative to endogenous glutamate (Glu) to characterize the presence of mutant tumor. The experiments i) provide IDH mutation status for individual patients and ii) demonstrate a strong correlation of 2HG signals with tumor infiltration. The measured ratio of 2HG to Glu correlates with IDH-mutant (IDH-mut) glioma (P < 0.0001) in the tumor core data of both teams. Despite using different ionization methods and different mass spectrometers, comparable performance in determining IDH mutations from core tumor biopsies was achieved with sensitivities, specificities, and accuracies all at 100%. None of the 31 patients at Mayo Clinic or the 74 patients at Huashan Hospital were misclassified when analyzing tumor core biopsies. Robustness of the methodology was evaluated by postoperative re-examination of samples. Both teams noted the presence of high concentrations of 2HG at surgical margins, supporting future use of intraoperative MS to monitor for clean surgical margins. The power of MS diagnostics is shown in resolving contradictory clinical features, e.g., in distinguishing gliosis from IDH-mut glioma.

Transcriptional Determinism and Stochasticity Contribute to the Complexity of Autism Associated SHANK Family Genes.

Precision of transcription is critical because transcriptional dysregulation is disease causing. Traditional methods of transcriptional profiling are inadequate to elucidate the full spectrum of the transcriptome, particularly for longer and less abundant mRNAs. SHANK3 is one of the most common autism causative genes. Twenty-four Shank3 mutant animal lines have been developed for autism modeling. However, their preclinical validity has been questioned due to incomplete Shank3 transcript structure. We applied an integrative approach combining cDNA-capture and long-read sequencing to profile the SHANK3 transcriptome in human and mice. We unexpectedly discovered an extremely complex SHANK3 transcriptome. Specific SHANK3 transcripts were altered in Shank3 mutant mice and postmortem brains tissues from individuals with ASD. The enhanced SHANK3 transcriptome significantly improved the detection rate for potential deleterious variants from genomics studies of neuropsychiatric disorders. Our findings suggest the stochastic transcription of genome associated with SHANK family genes.

Preoperative Risk Assessment Before Elective Craniotomy: Are Aspirin, Arrhythmias, Deep Venous Thromboses, and Hyperglycemia Contraindications to Surgery?

OBJECTIVE: Perioperative risk assessment and stratification before craniotomy is necessary to identify and optimize modifiable risk factors. Due to the high costs of diagnostic testing and concerns for delaying surgery, some have questioned whether and when surgery delays are warranted and supported by the current body of literature. The objective of this scoping review was to evaluate the available evidence on the prognostic value of preoperative risk assessment before anesthesia for elective craniotomy. METHODS: In this scoping review, we reviewed 156 papers that assess preoperative risk assessment before elective craniotomy, of which 27 papers were included in the final analysis. RESULTS: There is little high-quality evidence to suggest significant risk reduction when 4 common preexisting abnormalities are present: preoperative chronic aspirin therapy, cardiac arrhythmias, deep vein thrombosis, or hyperglycemia. CONCLUSIONS: The risk of delaying craniotomy should ultimately be weighed against the perceived risks associated the patient's comorbid conditions and should be considered on an individualized basis.

Alfred Washington Adson: Perspectives on Intracranial Neurosurgery and the Responsibilities of the Neurosurgeon.

In a period when the budding field of neurosurgery was believed to have little promise, Dr Alfred Washington Adson founded and led the first neurosurgical department at Mayo Clinic. He was not without reservations-surgical intervention for neurological conditions was rarely pursued because of poor outcomes and high complication rates, and Dr Adson acknowledged his early concerns about the future of neurosurgery in his memoirs. However, his education, mentorship, his training, and his first neurosurgical cases helped to shape the impact he ultimately had on the field and his legacy as a neurosurgeon. Dr Adson trained with several renowned Mayo general surgeons, notably his mentor Dr Emil Beckman, whose desire for operative precision shaped Dr Adson's drive to develop his own skills as a surgeon. Two years into his residency, he became the youngest staff surgeon and was tasked with managing the neurosurgical cases at Mayo. The five neurosurgical cases overseen by Dr Adson in the next year illuminated the opportunity for neurosurgery to drastically improve the lives of patients. Dr Adson, given the option of continuing as either a general surgeon or a neurosurgeon, ultimately chose to pursue neurosurgery. This article seeks to provide a historical perspective on the neurosurgeon Dr Alfred Washington Adson using primary and secondary accounts from the Mayo archives, highlighting his contributions to the early understanding of intracranial pathology and how his early experiences as a trainee developed into a personal passion for self-improvement, education, and advocacy for health care in America.

In Vitro Enhanced Osteogenic Potential of Human Mesenchymal Stem Cells Seeded in a Poly (Lactic-co-Glycolic) Acid Scaffold: A Systematic Review.

Study Design: Human bone marrow stem cells (hBMSCs) and human adipose-derived stem cells (hADSCs) have demonstrated the capability to regenerate bone once they have differentiated into osteoblasts. Objective: This systematic review aimed to evaluate the in vitro osteogenic differentiation potential of these cells when seeded in a poly (lactic-co-glycolic) acid (PLGA) scaffold. Methods: A literature search of 4 databases following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was conducted in January 2021 for studies evaluating the osteogenic differentiation potential of hBMSCs and hADSCs seeded in a PLGA scaffold. Only in vitro models were included. Studies in languages other than English were excluded. Results: A total of 257 studies were identified after the removal of duplicates. Seven articles fulfilled our inclusion and exclusion criteria. Four of these reviews used hADSCs and three used hBMSCs in the scaffold. Upregulation in osteogenic gene expression was seen in all the cells seeded in a 3-dimensional scaffold compared with 2-dimensional films. High angiogenic gene expression was found in hADSCs. Addition of inorganic material to the scaffold material affected cell performance. Conclusions: Viability, proliferation, and differentiation of cells strongly depend on the environment where they grow. There are several factors that can enhance the differentiation capacity of stem cells. A PLGA scaffold proved to be a biocompatible material capable of boosting the osteogenic differentiation potential and mineralization capacity in hBMSCs and hADSCs.

Patient-derived organoids recapitulate glioma-intrinsic immune program and progenitor populations of glioblastoma.

Glioblastoma multiforme (GBM) is a highly lethal human cancer thought to originate from a self-renewing and therapeutically-resistant population of glioblastoma stem cells (GSCs). The intrinsic mechanisms enacted by GSCs during 3D tumor formation, however, remain unclear, especially in the stages prior to angiogenic/immunological infiltration. In this study, we performed a deep characterization of the genetic, immune, and metabolic profiles of GBM organoids from several patient-derived GSCs (GBMO). Despite being devoid of immune cells, transcriptomic analysis across GBMO revealed a surprising immune-like molecular program, enriched in cytokine, antigen presentation and processing, T-cell receptor inhibitors, and interferon genes. We find two important cell populations thought to drive GBM progression, Special AT-rich sequence-binding protein 2 (SATB2+) and homeodomain-only protein homeobox (HOPX+) progenitors, contribute to this immune landscape in GBMO and GBM in vivo. These progenitors, but not other cell types in GBMO, are resistant to conventional GBM therapies, temozolomide and irradiation. Our work defines a novel intrinsic immune-like landscape in GBMO driven, in part, by SATB2+ and HOPX+ progenitors and deepens our understanding of the intrinsic mechanisms utilized by GSCs in early GBM formation.

Spontaneous rhinorrhea and idiopathic intracranial hypertension: a complex and challenging association.

INTRODUCTION: Spontaneous CSF leak is a known complication of idiopathic intracranial hypertension (IIH). Patients with CSF rhinorrhea present a unique challenge within the IIH population, as the occurrence of a leak can mask the typical IIH symptoms and signs, complicating the diagnosis. Treatment of leaks in this population can also be challenging, with the risk of rhinorrhea recurrence if intracranial hypertension is not adequately treated. OBJECTIVE: The aim of this narrative review was to examine current literature on the association between spontaneous CSF rhinorrhea leaks and IIH, focusing on key clinical features, diagnostic approaches, management strategies, and outcomes. MATERIAL AND METHODS: A literature search was executed using the PubMed and Scopus databases. The search was confined to articles published between January 1985 and August 2023; extracted data was then analysed to form the foundation of the narrative review. RESULTS: This search yielded 26 articles, comprising 943 patients. Average age was 46.8 ± 6.5 years, and average body mass index was 35.8 ± 4.8. Most of the patients were female (74.33%). Presenting symptoms were rhinorrhea, headaches and meningitis. The most common imaging findings were empty sella and encephalocele. The standard treatment approach was endoscopic endonasal approach for correction of CSF rhinorrhea leak, and shunt placement was also performed in 128 (13%) patients. Recurrences were observed in 10% of cases. CONCLUSIONS: The complex relationship between spontaneous CSF leaks and IIH is a challenge that benefits from multidisciplinary evaluation and management for successful treatment. Treatments such as endoscopic repair, acetazolamide, and VP/ /LP shunts reduce complications and recurrence. Personalised plans addressing elevated intracranial pressure are crucial for successful outcomes.

From the Operating Room to the Laboratory: Role of the Neuroscience Tissue Biorepository in the Clinical, Translational, and Basic Science Research Pipeline.

OBJECTIVE: To establish a neurologic disorder-driven biospecimen repository to bridge the operating room with the basic science laboratory and to generate a feedback cycle of increased institutional and national collaborations, federal funding, and human clinical trials. METHODS: Patients were prospectively enrolled from April 2017 to July 2022. Tissue, blood, cerebrospinal fluid, bone marrow aspirate, and adipose tissue were collected whenever surgically safe. Detailed clinical, imaging, and surgical information was collected. Neoplastic and nonneoplastic samples were categorized and diagnosed in accordance with current World Health Organization classifications and current standard practices for surgical pathology at the time of surgery. RESULTS: A total of 11,700 different specimens from 813 unique patients have been collected, with 14.2% and 8.5% of patients representing ethnic and racial minorities, respectively. These include samples from a total of 463 unique patients with a primary central nervous system tumor, 88 with metastasis to the central nervous system, and 262 with nonneoplastic diagnoses. Cerebrospinal fluid and adipose tissue dedicated banks with samples from 130 and 16 unique patients, respectively, have also been established. Translational efforts have led to 42 new active basic research projects; 4 completed and 6 active National Institutes of Health-funded projects; and 2 investigational new drug and 5 potential Food and Drug Administration-approved phase 0/1 human clinical trials, including 2 investigator initiated and 3 industry sponsored. CONCLUSION: We established a comprehensive biobank with detailed notation with broad potential that has helped us to transform our practice of research and patient care and allowed us to grow in research and clinical trials in addition to providing a source of tissue for new discoveries.

Awake brain mapping paradigms for nondominant hemisphere gliomas.

OBJECTIVE: Traditionally, resection of nondominant hemisphere brain tumors was performed under general anesthesia. An improved understanding of right-lateralized neural networks has led to a paradigm shift in recent decades, where the right or nondominant hemisphere is no longer perceived as "functionally silent." There is an increasing interest in awake brain mapping for nondominant hemisphere resections. The objective of this study was to perform a comprehensive review of the existing brain mapping paradigms for patients with nondominant hemisphere gliomas undergoing awake craniotomies. METHODS: In accordance with PRISMA guidelines, systematic searches of the Medline, Embase, and American Psychological Association PsycInfo databases were undertaken from database inception to July 1, 2023. Studies providing a description of the intraoperative mapping paradigm used to assess cognition during an awake craniotomy for resection of a nondominant hemisphere glioma were included. RESULTS: The search yielded 1084 potentially eligible articles. Thirty-nine unique studies reporting on 788 patients were included in the systematic review. The most frequently tested cognitive domains in patients with nondominant hemisphere tumors were spatial attention/neglect (17/39 studies, 43.6%), speech-motor/language (17/39 studies, 43.6%), and social cognition (9/39 studies, 23.1%). Within the frontal lobe, the highest number of positive mapping sites was identified for speech-motor/language, spatial attention/neglect, dual tasking assessing motor and language function, working memory, and social cognition. Within the parietal lobe, eloquence was most frequently found upon testing spatial attention/neglect, speech-motor/language, and calculation. Within the temporal lobe, the assessment of spatial attention/neglect yielded the highest number of positive mapping sites. CONCLUSIONS: Cognitive testing in the nondominant hemisphere is predominantly focused on evaluating two domains: spatial attention/neglect and the motor aspects of speech/language. Multidisciplinary teams involved in awake brain mapping should consider testing an extended range of functions to minimize the risk of postoperative deficits and provide valuable information about anatomo-functional organization of cognitive networks.

Radiologic Classification of Hippocampal Sclerosis in Epilepsy.

Temporal lobe epilepsy is a common form of epilepsy that is often associated with hippocampal sclerosis (HS). Although HS is commonly considered a binary assessment in radiologic evaluation, it is known that histopathologic changes occur in distinct clusters. Some subtypes of HS only affect certain subfields, resulting in minimal changes to the overall volume of the hippocampus. This is likely a major reason why whole hippocampal volumetrics have underperformed versus expert readers in the diagnosis of HS. With recent advancements in MRI technology, it is now possible to characterize the substructure of the hippocampus more accurately. However, this is not consistently addressed in radiographic evaluations. The histologic subtype of HS is critical for prognosis and treatment decision-making, necessitating improved radiologic classification of HS. The International League Against Epilepsy (ILAE) has issued a consensus classification scheme for subtyping HS histopathologic changes. This review aims to explore how the ILAE subtypes of HS correlate with radiographic findings, introduce a grading system that integrates radiologic and pathologic reporting in HS, and outline an approach to detecting HS subtypes by using MRI. This framework will not only benefit current clinical evaluations, but also enhance future studies involving high-resolution MRI in temporal lobe epilepsy.

Enhancing outcomes in deep brain stimulation: a comparative study of direct targeting using 7T versus 3T MRI.

OBJECTIVE: The aim of this study was to compare outcomes of direct targeting in deep brain stimulation (DBS) for essential tremor using 7T MRI versus 3T MRI. The authors hypothesized that 7T MRI direct targeting would be noninferior to 3T MRI in early tremor outcomes. METHODS: A retrospective study was conducted on patients undergoing unilateral thalamic DBS for essential tremor between 2021 and 2023. Two matched cohorts were assessed, one using 7T MRI and the other using 3T MRI for surgical planning. The primary endpoint was the percentage improvement in the Fahn-Tolosa-Marin Tremor Rating Scale (TRS) scores. Additionally, the authors assessed optimized programming settings and variance in electrode position on postoperative imaging. Demographic and clinical data were compared using the nonparametric Mann-Whitney U-test. The squared Euclidean distance of each contact from the group mean centroid was calculated and averaged across the entire cohort to provide the variance (i.e., the mean squared distance) of electrode contact position. RESULTS: A total of 34 patients were analyzed, with 17 in each cohort. There were no significant differences in demographic information or mean surgical dates between the groups. There were no differences in intraoperative target repositioning or adverse events. The 7T group had a significantly greater TRS improvement than the 3T group (64.9% ± 11.4% vs 50.9% ± 16.4%, p = 0.004). Patients in the 7T cohort also had a lower mean stimulation current compared with those in the 3T cohort (2.0 ± 0.8 mA vs 2.7 ± 0.9 mA, p = 0.01). Image evaluation revealed that although the mean electrode position was comparable between 7T and 3T, the 7T electrode positioning was more clustered, indicating a lower variance in the final electrode location. The mean Euclidean distance between the individual electrode tips and the group centroid was significantly less at 7T than at 3T (1.82 ± 0.68 mm vs 2.75 ± 0.81 mm, p = 0.001). CONCLUSIONS: Despite concerns for increased artifacts and distortions at 7T, the authors show that these effects can be mitigated with an appropriate workflow, leading to improved surgical outcomes with direct targeting using 7T MRI. Their results suggest similar accuracy but greater precision in targeting with 7T MRI compared with 3T MRI, resulting in lower stimulation currents and improved tremor reduction. Future studies are needed to assess outcomes related to 7T MRI in targeting other subcortical structures.

Repeated surgical resections for management of high-grade glioma and its impact on quality of life.

PURPOSE: High-grade gliomas (HGG) are aggressive cancers, and their recurrence is inevitable, despite advances in treatment options. While repeated tumor resection has been shown to increase survival rate, its impact on quality of life is not clearly defined. To address this gap, we compared quality of life (QoL) changes in HGG patients who underwent first-time (FTR) versus repeat surgical resections (RSR) for management of recurrence. METHODS: Forty-four adults with HGG who underwent tumor resection were included in this study and classified into either the FTR group (n = 23) or the RSR group (n = 21). All patients completed comprehensive neuropsychological evaluations that included the Functional Assessment of Cancer Therapy-General (FACT-G) and Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog) scales, pre-operatively and at two weeks post-operatively. RESULTS: There was no difference between the FTR and RSR groups in any of the QoL indices (all p > .05), except for improved emotional well-being and worsened social well-being, suggesting minimal detrimental effects of repeat surgeries on QoL in comparison to first time surgery. CONCLUSIONS: These results suggest that repeated resection is a viable strategy in certain cases for management of HGG recurrence, with similar impact on QoL as observed in patients undergoing first time surgery. These encouraging outcomes provide useful insight to guide treatment strategies and patient and clinician decision making to optimize surgical and functional outcomes.

EZH2 Inhibition Sensitizes IDH1R132H-Mutant Gliomas to Histone Deacetylase Inhibitor.

Isocitrate Dehydrogenase-1 (IDH1) is commonly mutated in lower-grade diffuse gliomas. The IDH1R132H mutation is an important diagnostic tool for tumor diagnosis and prognosis; however, its role in glioma development, and its impact on response to therapy, is not fully understood. We developed a murine model of proneural IDH1R132H-mutated glioma that shows elevated production of 2-hydroxyglutarate (2-HG) and increased trimethylation of lysine residue K27 on histone H3 (H3K27me3) compared to IDH1 wild-type tumors. We found that using Tazemetostat to inhibit the methyltransferase for H3K27, Enhancer of Zeste 2 (EZH2), reduced H3K27me3 levels and increased acetylation on H3K27. We also found that, although the histone deacetylase inhibitor (HDACi) Panobinostat was less cytotoxic in IDH1R132H-mutated cells (either isolated from murine glioma or oligodendrocyte progenitor cells infected in vitro with a retrovirus expressing IDH1R132H) compared to IDH1-wild-type cells, combination treatment with Tazemetostat is synergistic in both mutant and wild-type models. These findings indicate a novel therapeutic strategy for IDH1-mutated gliomas that targets the specific epigenetic alteration in these tumors.