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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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 radiological evaluation, it is known that histopathological 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. 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 histological subtype of HS is critical for prognosis and treatment decision making, necessitating improved radiological classification of HS. The International League Against Epilepsy (ILAE) has issued a consensus classification scheme for subtyping HS histopathological changes. This review aims to explore how the ILAE subtypes of HS correlate with radiographic findings, introduce a grading system that integrates radiological and pathological reporting in HS, and outline an approach to detecting HS subtypes using MRI. This framework will not only benefit current clinical evaluations, but also enhance future studies involving high-resolution MRI in temporal lobe epilepsy.ABBREVIATIONS: CA = cornu ammonis; DG = dentate gyrus; HS = hippocampal sclerosis; ILAE = International League Against Epilepsy; SRLM = strata radiatum, lacunosum, and moleculare layers; TLE = temporal lobe epilepsy.

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.

Awake Craniotomy Program Implementation.

Importance: Implementing multidisciplinary teams for treatment of complex brain tumors needing awake craniotomies is associated with significant costs. To date, there is a paucity of analysis on the cost utility of introducing advanced multidisciplinary standardized teams to enable awake craniotomies. Objective: To assess the cost utility of introducing a standardized program of awake craniotomies. Design, Setting, and Participants: A retrospective economic evaluation was conducted at Mayo Clinic Florida. All patients with single, unilateral lesions who underwent elective awake craniotomies between January 2016 and December 2021 were considered eligible for inclusion. The economic perspective of the health care institution and a time horizon of 1 year were considered. Data were analyzed from October 2022 to May 2023. Exposure: Treatment with an awake craniotomy before standardization (2016-2018) compared with treatment with awake craniotomy after standardization (2018-2021). Main Outcomes and Measures: Patient demographics, perioperative, and postoperative outcomes, including length of stay, intensive care (ICU) admission, extent of resection, readmission rates, and 1-year mortality were compared between patients undergoing surgery before and after standardization. Direct medical costs were estimated from Medicare reimbursement rates for all billed procedures. A cost-utility analysis was performed considering differences in direct medical costs and in 1-year mortality within the periods before and after standardization of procedures. Uncertainty was explored in probability sensitivity analysis. Results: A total of 164 patients (mean [SD] age, 49.9 [15.7] years; 98 [60%] male patients) were included in the study. Of those, 56 underwent surgery before and 108 after implementation of procedure standardization. Procedure standardization was associated with reductions in length of stay from a mean (SD) of 3.34 (1.79) to 2.46 (1.61) days (difference, 0.88 days; 95% CI, 0.33-1.42 days; P = .002), length of stay in ICU from a mean (SD) of 1.32 (0.69) to 0.99 (0.90) nights (difference, 0.33 nights; 95% CI, 0.06-0.60 nights; P = .02), 30-day readmission rate from 14% (8 patients) in the prestandardization cohort to 5% (5 patients) (difference, 9%; 95% CI, 19.6%-0.3%; P = .03), while extent of resection and intraoperative complication rates were similar between both cohorts. The standardized protocol was associated with mean (SD) savings of $7088.80 ($12 389.50) and decreases in 1-year mortality (dominant intervention). This protocol was found to be cost saving in 75.5% of all simulations in probability sensitivity analysis. Conclusions and Relevance: In this economic evaluation of standardization of awake craniotomy, there was a generalized reduction in length of stay, ICU admission time, and direct medical costs with implementation of an optimized protocol. This was achieved without compromising patient outcomes and with similar extent of resection, complication rates, and reduced readmission rates.

Autologous cell immunotherapy (IGV-001) with IGF-1R antisense oligonucleotide in newly diagnosed glioblastoma patients.

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

Glioblastoma (GBM) is a fast-growing brain tumor that happens in about half of all gliomas. Surgery is the first treatment for patients with newly diagnosed GBM, followed by the usual radiation and chemotherapy pills named temozolomide. Temozolomide pills are then given as a long-term treatment. The outcome for the patient with newly diagnosed GBM remains poor. IGV-001 is specially made for each patient. The tumor cells are removed during surgery and mixed in the laboratory with a small DNA, IMV-001. This mix is the IGV-001 therapy that is designed to give antitumor immunity against GBM. IGV-001 is put into small biodiffusion chambers that are irradiated to stop the growth of any tumor cells in the chambers. In the phase IIb study, patients with newly diagnosed GBM are chosen and assigned to either the IGV-001 or the placebo group. A placebo does not contain any active ingredients. The small biodiffusion chambers containing either IGV-001 or placebo are surgically placed into the belly for 48 to 52 h and then removed. Patients then receive the usual radiation and chemotherapy treatment. Patients must be adults aged between 18 and 70 years. Patients also should be able to care for themselves overall, but may be unable to work or have lower ability to function. Patients with tumors on both sides of the brain are not eligible. The main point of this study is to see if IGV-001 helps patients live longer without making the illness worse compared with placebo. Clinical Trial Registration: NCT04485949 (ClinicalTrials.gov).

What Factors Predict the Development of Neurologic Deficits Following Resection of Intramedullary Spinal Cord Tumors: A Multi-Center Study.

BACKGROUND: Intramedullary spinal cord tumors are challenging to resect, and their postoperative neurological outcomes are often difficult to predict, with few studies assessing this outcome. METHODS: We reviewed the medical records of all patients surgically treated for Intramedullary spinal cord tumors at our multisite tertiary care institution (Mayo Clinic Arizona, Mayo Clinic Florida, Mayo Clinic Rochester) between June 2002 and May 2020. Variables that were significant in the univariate analyses were included in a multivariate logistic regression. "MissForest" operating on the Random Forest algorithm, was used for data imputation, and K-prototype was used for data clustering. Heatmaps were added to show correlations between postoperative neurological deficit and all other included variables. Shapley Additive exPlanations were implemented to understand each feature's importance. RESULTS: Our query resulted in 315 patients, with 160 meeting the inclusion criteria. There were 53 patients with astrocytoma, 66 with ependymoma, and 41 with hemangioblastoma. The mean age (standard deviation) was 42.3 (17.5), and 48.1% of patients were women (n = 77/160). Multivariate analysis revealed that pathologic grade >3 (OR = 1.55; CI = [0.67, 3.58], P = 0.046 predicted a new neurological deficit. Random Forest algorithm (supervised machine learning) found age, use of neuromonitoring, histology of the tumor, performing a midline myelotomy, and tumor location to be the most important predictors of new postoperative neurological deficits. CONCLUSIONS: Tumor grade/histology, age, use of neuromonitoring, and myelotomy type appeared to be most predictive of postoperative neurological deficits. These results can be used to better inform patients of perioperative risk.

Wireless Stimulation of Motor Cortex Through a Collagen Dura Substitute Using an Ultra-Thin Implant Fabricated on Parylene/PDMS.

We present the design, fabrication, and in vivo testing of an ultra-thin (100 µm) wireless and battery-free implant for stimulation of the brain's cortex. The implant is fabricated on a flexible and transparent parylene/PDMS substrate, and it is miniaturized to dimensions of 15.6 × 6.6 mm 2. The frequency and pulse width of the monophasic voltage pulses are determined through On-Off keying (OOK) modulation of a wireless transmission at 2.45 GHz. Furthermore, the implant triggered a motor response in vivo when tested in 6 rodents. Limb response was observed by wireless stimulation of the brain's motor cortex through an FDA-approved collagen dura substitute that was placed on the dura in the craniotomy site, with no direct contact between the implant's electrodes and the brain's cortical surface. Therefore, the wireless stimulation method reported herein enables the concept of an e-dura substitute, where wireless electronics can be integrated onto a conventional dura substitute to augment its therapeutic function and administer any desired stimulation protocol without the need for post-surgical intervention for battery replacement or reprogramming stimulation parameters.

Extent of Surgical Resection as a Predictor of Tumor Progression in Skull Base Chordomas: A Multicenter Volumetric Analysis.

INTRODUCTION: Skull-base chordomas are aggressive tumors with a propensity for recurrence/progression. Even with standard of care (SoC), 5-year recurrence rates are variable (19%-54%). This high recurrence/progression rate correlates with increased morbidity and mortality. We sought to analyze a multicenter cohort of skull base chordomas to identify predictors of progression in patients receiving SoC. METHODS: The [Blinded]-Neurosurgery data registry was queried for skull base chordomas treated from 2008-2020. Patients with the histopathologic diagnosis of chordoma were included. The cohort was composed of patients with preoperative and postoperative magnetic resonance imaging. Tumor volume and radiologic characteristics were obtained from axial T2 sequences using a Digital Imaging and Communications in Medicine viewer. Survival analysis was performed using Kaplan-Meier method, and time-to-event multivariate regression was performed to identify independent predictors of progression. RESULTS: The cohort included 195 patients, of which 66 patients met inclusion criteria; median age was 44, and 28 (42%) were females. Fifty-four (82%) received SoC, 7 (11%) resection only, and 5 (8%) radiotherapy only. Median preoperative and postoperative tumor volumes were 11.55 cm3 (0.33-54.89) and 0.34 cm3 (0-42.52), respectively. Recurrence rate with SoC was 37%. Postoperative tumor volume (P = 0.010) correlated with progression. A postoperative volume of >4.9 cm3 (P = 0.044), ≤81.3% of tumor resection (P = 0.02), and lower-clivus location (P < 0.005) correlated with decreased time to progression. CONCLUSIONS: Skull base chordomas can be challenging to resect. Even though maximal resection and radiotherapy improve rate of tumor progression, many of these lesions eventually recur. We have identified a postoperative tumor volume of ≥4.9 cm3 and extent of resection of ≤81.3% in this cohort as predictors of progression in patients receiving SoC.

Early Postoperative Seizures Following Awake Craniotomy and Functional Brain Mapping for Lesionectomy.

OBJECTIVE: Awake craniotomy with electrocorticography (ECoG) and direct electrical stimulation (DES) facilitates lesionectomy while avoiding adverse effects. Early postoperative seizures (EPS), occurring within 7 days following surgery, can lead to morbidity. However, risk factors for EPS after awake craniotomy including clinical and ECoG data are not well defined. METHODS: We retrospectively studied the incidence and risk factors of EPS following awake craniotomy for lesionectomy, and report short-term outcomes between January 1, 2020, and December 31, 2022. RESULTS: We included 138 patients (56 female) who underwent 142 awake craniotomies, average age was 50.78 ± 15.97 years. Eighty-eight (63.7%) patients had a preoperative history of tumor-related epilepsy treated with antiseizure medication (ASM), 12 (13.6%) with drug-resistance. All others (36.3%) received ASM prophylaxis with levetiracetam perioperatively and continued for 14 days. An equal number of cases (71) each utilized a novel circle grid or strip electrodes for ECoG. There were 31 (21.8%) cases of intraoperative seizures, 16 with EPS (11.3%). Acute abnormality on early postoperative neuroimaging (P = 0.01), subarachnoid hemorrhage (P = 0.01), young age (P = 0.01), and persistent postoperative neurologic deficits (P = 0.013) were associated with EPS. Acute abnormality on neuroimaging remained significant in multivariate analysis. Outcomes during hospitalization and early outpatient follow up were worse with EPS. CONCLUSIONS: We report novel findings using ECoG and clinical features to predict EPS, including acute perioperative brain injury, persistent postoperative deficits and young age. Given worse outcomes with EPS, clinical indicators for EPS should alert clinicians of potential need for early postoperative EEG monitoring and perioperative ASM adjustment.

Mesenchymal Stromal Cell Healing Outcomes in Clinical and Pre-Clinical Models to Treat Pressure Ulcers: A Systematic Review.

BACKGROUND: Despite numerous measures used to prevent pressure ulcers, their growing prevalence in recent years is expected to continue as the population ages. This review aims to report the outcomes of the regenerative potential of MSCs in treating pressure ulcers, assessing the effectiveness of MSCs in treating pressure ulcers. METHODS: A computerized search for articles on animal models that use MSCs as primary therapy to treat pressure ulcers, published from conception to present, was conducted using PubMed, MEDLINE, Embase, and CINAHL. Our search yielded 52 articles, narrowed to 44 after excluding duplicates. RESULTS: Out of 52 articles collected from four databases, 11 met the inclusion criteria. A total of 11 articles published between 2008 and 2020 met the inclusion criteria. Eight studies were observational descriptive papers in animal models, and three were prospective. Six studies used autologous MSCs, while five used allogenic MSCs. Three studies were conducted in humans, and the remaining eight were conducted in animals. The most common method of cell delivery was an intradermal injection in the margins of the ulcer. All studies reported positive results, including improved wound healing, reduced inflammation, and improved tissue regeneration. CONCLUSIONS: MSCs have shown promising results in treating pressure ulcers in animal and clinical trials. The combination of MSCs and scaffold materials has also been studied and found to be effective in wound healing. A standardized human wound model has been proposed further to investigate the efficacy of cell-based therapies for chronic wounds. However, more research is needed to determine the best quantity of cells to apply for pressure ulcers and to ensure the safety and efficacy of these treatments in clinical settings.

Systemic Therapy for Melanoma Brain and Leptomeningeal Metastases.

OPINION STATEMENT: Melanoma has a high propensity to metastasize to the brain which portends a poorer prognosis. With advanced radiation techniques and targeted therapies, outcomes however are improving. Melanoma brain metastases are best managed in a multi-disciplinary approach, including medical oncologists, neuro-oncologists, radiation oncologists, and neurosurgeons. The sequence of therapies is dependent on the number and size of brain metastases, status of systemic disease control, prior therapies, performance status, and neurological symptoms. The goal of treatment is to minimize neurologic morbidity and prolong both progression free and overall survival while maximizing quality of life. Surgery should be considered for solitary metastases, or large and/or symptomatic metastases with edema. Stereotactic radiosurgery offers a benefit over whole-brain radiation attributed to the relative radioresistance of melanoma and reduction in neurotoxicity. Thus far, data supports a more durable response with systemic therapy using combination immunotherapy of ipilimumab and nivolumab, though targeting the presence of BRAF mutations can also be utilized. BRAF inhibitor therapy is often used after immunotherapy failure, unless a more rapid initial response is needed and then can be done prior to initiating immunotherapy. Further trials are needed, particularly for leptomeningeal metastases which currently require the multi-disciplinary approach to determine best treatment plan.